Refine
Year of publication
Document Type
- Doctoral Thesis (8964)
- Journal article (8586)
- Complete part of issue (703)
- Book article / Book chapter (479)
- Book (218)
- Conference Proceeding (202)
- Preprint (130)
- Review (115)
- Master Thesis (105)
- Working Paper (105)
Language
- English (11113)
- German (8628)
- French (58)
- Multiple languages (22)
- Spanish (22)
- Russian (6)
- Italian (2)
- Portuguese (2)
Keywords
- Würzburg (739)
- Universität (668)
- Wuerzburg (668)
- Wurzburg (660)
- University (608)
- Organische Chemie (135)
- Psychologie (128)
- Anorganische Chemie (124)
- Maus (124)
- Toxikologie (123)
- Medizin (111)
- inflammation (108)
- apoptosis (105)
- Signaltransduktion (104)
- Deutschland (100)
- Genexpression (99)
- Taufliege (93)
- cancer (89)
- Biochemie (87)
- gene expression (81)
- Apoptosis (79)
- MRI (77)
- T-Lymphozyt (76)
- depression (75)
- Chemie (74)
- Tissue Engineering (73)
- Drosophila (72)
- Jahresbericht (71)
- Herzinsuffizienz (67)
- children (66)
- HIV (65)
- boron (64)
- Depression (62)
- Thrombozyt (62)
- therapy (62)
- Apoptose (60)
- COVID-19 (60)
- NMR-Tomographie (60)
- Biologie (59)
- Dendritische Zelle (58)
- Infektionsbiologie (58)
- Molekularbiologie (57)
- expression (57)
- oxidative stress (57)
- Bericht (56)
- Kernspintomografie (56)
- Kind (55)
- Escherichia coli (54)
- ADHD (53)
- Neurobiologie (53)
- breast cancer (53)
- machine learning (53)
- multiple myeloma (53)
- Diabetes mellitus (52)
- Molekulargenetik (52)
- Physiologische Chemie (51)
- Rezension (51)
- Candida albicans (50)
- Drosophila melanogaster (50)
- Krebs <Medizin> (50)
- Lebensqualität (50)
- Melanom (50)
- Annual Report (49)
- Immunologie (49)
- Neisseria meningitidis (49)
- infection (49)
- Bor (48)
- Hadron-Hadron scattering (experiments) (48)
- melanoma (48)
- virtual reality (48)
- Aspergillus fumigatus (47)
- Herzinfarkt (47)
- Schizophrenie (47)
- Staphylococcus aureus (47)
- Therapie (47)
- heart failure (47)
- Entzündung (46)
- Simulation (46)
- Transkriptionsfaktor (46)
- Tumor (46)
- anxiety (46)
- metabolism (46)
- stroke (46)
- Geschichte (45)
- Topologischer Isolator (45)
- cytokines (45)
- myocardial infarction (45)
- Ackerschmalwand (44)
- Schlaganfall (44)
- T cells (44)
- Universitätsbibliothek (44)
- remote sensing (44)
- Biomarker (43)
- Brustkrebs (43)
- Germany (43)
- Zeitschrift (43)
- biomarker (43)
- magnetic resonance imaging (43)
- mice (43)
- multiple sclerosis (43)
- Genregulation (42)
- Plasmozytom (42)
- Ratte (42)
- dendritic cells (42)
- platelets (42)
- EEG (41)
- Oxidativer Stress (41)
- PET (41)
- signal transduction (41)
- DNA damage (40)
- Report (40)
- Rezeptor (40)
- prostate cancer (40)
- quality of life (40)
- Fluoreszenz (39)
- Multiples Myelom (39)
- SARS-CoV-2 (39)
- University Library (39)
- Virologie (39)
- Zellkultur (39)
- evolution (39)
- in vitro (39)
- ischemic stroke (39)
- Calcium (38)
- Evolution (38)
- Multiple Sklerose (38)
- Stammzelle (38)
- Angst (37)
- Serotonin (37)
- Strahlentherapie (37)
- climate change (37)
- fluorescence (37)
- Chemische Synthese (36)
- China (36)
- Entwicklung (36)
- Fabry disease (36)
- Immuntherapie (36)
- Spektroskopie (36)
- biodiversity (36)
- Biene (35)
- Chirurgie (35)
- Immunsystem (35)
- MRT (35)
- Zelldifferenzierung (35)
- brain (35)
- differentiation (35)
- macrophages (35)
- mouse (35)
- obesity (35)
- Antikörper (34)
- Arteriosklerose (34)
- Endothel (34)
- Jugend (34)
- genetics (34)
- prognosis (34)
- schizophrenia (34)
- tissue engineering (34)
- Arabidopsis thaliana (33)
- Blut-Hirn-Schranke (33)
- DNA (33)
- Einzelhandel (33)
- Nanopartikel (33)
- Quantenpunkt (33)
- Stress (33)
- Supramolekulare Chemie (33)
- deep learning (33)
- pain (33)
- phosphorylation (33)
- Bayern (32)
- Deutsch (32)
- Lernen (32)
- Molekularstrahlepitaxie (32)
- Regulation (32)
- Schmerz (32)
- Selbstorganisation (32)
- diagnosis (32)
- gene (32)
- rat (32)
- Modellierung (31)
- Proliferation (31)
- Zellzyklus (31)
- heart (31)
- mortality (31)
- Adipositas (30)
- CXCR4 (30)
- Herz (30)
- Inhibitor (30)
- Kinder (30)
- Maschinelles Lernen (30)
- Universität Würzburg (30)
- immunotherapy (30)
- protein (30)
- survival (30)
- ADHS (29)
- Aufmerksamkeit (29)
- B cells (29)
- Fernerkundung (29)
- Fluoreszenzmikroskopie (29)
- Genetik (29)
- Leistungsbewertung (29)
- Masernvirus (29)
- Photoelektronenspektroskopie (29)
- Positronen-Emissions-Tomografie (29)
- Proteine (29)
- Silicium (29)
- Virulenz (29)
- radiotherapy (29)
- regulatory T cells (29)
- stem cells (29)
- DNS-Reparatur (28)
- Elektrophysiologie (28)
- Epigenetik (28)
- Exziton (28)
- Immunsuppression (28)
- Malaria (28)
- Microarray (28)
- Parkinson-Krankheit (28)
- Polymere (28)
- Trypanosoma brucei (28)
- atherosclerosis (28)
- mouse model (28)
- surgery (28)
- Angiogenese (27)
- DNA methylation (27)
- Gehirn (27)
- Mensch (27)
- Sprachentwicklung (27)
- Stickstoffmonoxid (27)
- identification (27)
- mitochondria (27)
- positron emission tomography (27)
- proliferation (27)
- Archäologie (26)
- Bioinformatik (26)
- Cytokine (26)
- High energy physics (26)
- Human-Animal Studies (26)
- Immunreaktion (26)
- Infektion (26)
- Inhibition (26)
- Klimaänderung (26)
- MAP-Kinase (26)
- Makrophage (26)
- Migration (26)
- Myc (26)
- Myokardinfarkt (26)
- Parkinson's disease (26)
- RNA (26)
- Raman-Spektroskopie (26)
- autophagy (26)
- bone (26)
- chronic kidney disease (26)
- dSTORM (26)
- endothelial cells (26)
- learning (26)
- microRNA (26)
- physics (26)
- virulence (26)
- 3D printing (25)
- Bakterien (25)
- DNS-Schädigung (25)
- Environmental Humanities (25)
- Kognition (25)
- Literary Studies (25)
- Mikroskopie (25)
- Organischer Halbleiter (25)
- Parton Distributions (25)
- Polymorphismus (25)
- Prognose (25)
- Rezidiv (25)
- Schwertkärpfling (25)
- Verhalten (25)
- artificial intelligence (25)
- blood (25)
- epidemiology (25)
- medicine (25)
- mesenchymal stem cells (25)
- migration (25)
- regulation (25)
- resistance (25)
- Aminosäuren (24)
- Animal Studies (24)
- Atherosklerose (24)
- Aufsatzsammlung (24)
- BMP (24)
- Biofilm (24)
- Cultural Animal Studies (24)
- Cultural Studies (24)
- Ecocriticism (24)
- Fettsucht (24)
- Halbleiter (24)
- Knochenzement (24)
- Literatur (24)
- Pharmakokinetik (24)
- Tiermodell (24)
- Vaccinia-Virus (24)
- Virtuelle Realität (24)
- behavior (24)
- development (24)
- immunohistochemistry (24)
- miRNS (24)
- neuroinflammation (24)
- self-assembly (24)
- 3D-Druck (23)
- Autoantikörper (23)
- BDNF (23)
- Cancer (23)
- Glioblastom (23)
- Inflammation (23)
- Knockout <Molekulargenetik> (23)
- Listeria monocytogenes (23)
- Motoneuron (23)
- NMR-Bildgebung (23)
- Parkinson’s disease (23)
- Zytokine (23)
- activation (23)
- attention (23)
- classification (23)
- colorectal cancer (23)
- cytotoxicity (23)
- disease (23)
- human (23)
- measles virus (23)
- recurrence (23)
- transcription (23)
- treatment (23)
- Diagnostik (22)
- Differenzierung (22)
- Expression (22)
- GPCR (22)
- Gedächtnis (22)
- Genanalyse (22)
- Hydrogel (22)
- Optimierung (22)
- P300 (22)
- Pflanzen (22)
- Screening (22)
- antibodies (22)
- cAMP (22)
- calcium (22)
- chemotherapy (22)
- emotion (22)
- extracellular matrix (22)
- follow-up (22)
- hippocampus (22)
- imaging (22)
- memory (22)
- osteoporosis (22)
- perception (22)
- physical activity (22)
- toxicity (22)
- validation (22)
- Angststörung (21)
- Chemotherapie (21)
- Dickdarmkrebs (21)
- Evaluation (21)
- Fabry-Krankheit (21)
- Gefühl (21)
- Glaukom (21)
- HPLC (21)
- In vitro (21)
- Knochen-Morphogenese-Proteine (21)
- Kollagen (21)
- LHC (21)
- Organische Synthese (21)
- Osteoporose (21)
- Synapse (21)
- T-Zellen (21)
- TRAIL (21)
- adrenocortical carcinoma (21)
- blood-brain barrier (21)
- cytoskeleton (21)
- deep brain stimulation (21)
- neuropathic pain (21)
- receptor (21)
- serotonin (21)
- stress (21)
- transcriptome (21)
- Übergangsmetallkomplexe (21)
- ATLAS detector (20)
- Apis mellifera (20)
- Aufmerksamkeits-Defizit-Syndrom (20)
- Borylene (20)
- Computersimulation (20)
- Erziehung (20)
- Hippocampus (20)
- Insulin (20)
- Legionella pneumophila (20)
- Lunge (20)
- Mausmodell (20)
- NFATc1 (20)
- NMR-Spektroskopie (20)
- Synthese (20)
- angiogenesis (20)
- binding (20)
- flow cytometry (20)
- honeybee (20)
- metastasis (20)
- mutation (20)
- risk factors (20)
- topological insulators (20)
- transcription factors (20)
- Ameisen (19)
- Antibiotikum (19)
- Cytologie (19)
- Fragebogen (19)
- Genmutation (19)
- HIV-Infektion (19)
- Herzmuskel (19)
- Julius-Maximilians-Universität Würzburg (19)
- Metabolismus (19)
- Palliativmedizin (19)
- Prostatakrebs (19)
- Quecksilbertellurid (19)
- Rezeption (19)
- Sonderpädagogik (19)
- Stoffwechsel (19)
- TNF (19)
- annual report (19)
- antibiotics (19)
- biology (19)
- cell death (19)
- dopamine (19)
- echocardiography (19)
- epigenetics (19)
- fMRI (19)
- foraging (19)
- immune response (19)
- land use (19)
- lymphoma (19)
- management (19)
- mass spectrometry (19)
- miRNA (19)
- mouse models (19)
- p53 (19)
- pregnancy (19)
- psychology (19)
- sepsis (19)
- theranostics (19)
- transplantation (19)
- Actin (18)
- Autoimmunität (18)
- B-Lymphozyt (18)
- Bildgebendes Verfahren (18)
- Biomechanik (18)
- Boron (18)
- DNS (18)
- EAE (18)
- Europäische Union (18)
- Farbstoff (18)
- G-Protein gekoppelte Rezeptoren (18)
- Herzfrequenzvariabilität (18)
- Herzhypertrophie (18)
- Kaliumkanal (18)
- Krebs (18)
- MRSA (18)
- Neisseria gonorrhoeae (18)
- Netzwerk (18)
- Neurodegeneration (18)
- Niere (18)
- Optische Spektroskopie (18)
- Prävention (18)
- Resistenz (18)
- Ultraschall (18)
- Virulenzfaktor (18)
- active zone (18)
- aging (18)
- ants (18)
- autoimmunity (18)
- bacteria (18)
- crystal structure (18)
- diabetes (18)
- in vivo (18)
- kidney (18)
- luminescence (18)
- neuroprotection (18)
- outcome (18)
- platelet (18)
- polymorphism (18)
- proteins (18)
- spectroscopy (18)
- time series (18)
- ARPES (17)
- Arzneimitteldesign (17)
- Biodiversität (17)
- Biomaterial (17)
- DFT (17)
- DNA repair (17)
- Endothelzelle (17)
- Fluoreszenz-Resonanz-Energie-Transfer (17)
- Fremdsprachenunterricht (17)
- Fuchsbandwurm (17)
- Helicobacter pylori (17)
- Immunmodulation (17)
- Interaktion (17)
- MODIS (17)
- MYC (17)
- Makrophagen (17)
- Masern (17)
- Merkel cell carcinoma (17)
- Methylierung (17)
- Molekulardynamik (17)
- Motivation (17)
- Mutation (17)
- NIR-Spektroskopie (17)
- Nachhaltigkeit (17)
- Naphthylisochinolinalkaloide (17)
- Neurogenese (17)
- PET/CT (17)
- Photolumineszenz (17)
- Plattenepithelcarcinom (17)
- Polyneuropathie (17)
- Pädiatrie (17)
- Regulatorischer T-Lymphozyt (17)
- Rheumatoide Arthritis (17)
- Sepsis (17)
- Sol-Gel-Verfahren (17)
- Spinale Muskelatrophie (17)
- Tanzania (17)
- Wirkstoff (17)
- Zellmigration (17)
- Zellskelett (17)
- bees (17)
- biomarkers (17)
- bipolar disorder (17)
- blood pressure (17)
- diabetes mellitus (17)
- epithelial cells (17)
- event-related potentials (17)
- fibrosis (17)
- gene regulation (17)
- genotoxicity (17)
- immunosuppression (17)
- innate immunity (17)
- ischemia (17)
- lung cancer (17)
- mental health (17)
- messenger RNA (17)
- metagenomics (17)
- nitric oxide (17)
- simulation (17)
- structure elucidation (17)
- tumor (17)
- B-Zell-Lymphom (16)
- Bavaria (16)
- Decay (16)
- Dendritische Zellen (16)
- Digitalisierung (16)
- Embryonalentwicklung (16)
- Emotion (16)
- Festkörperphysik (16)
- Fremdsprachenlernen (16)
- Galliumarsenid (16)
- Heart failure (16)
- Hypertonie (16)
- Konditionierung (16)
- Kongress (16)
- Künstliche Intelligenz (16)
- Ligand <Biochemie> (16)
- Magnetresonanztomographie (16)
- Monte-Carlo-Simulation (16)
- Muscarinrezeptor (16)
- Namibia (16)
- RNS (16)
- ROS (16)
- Spintronik (16)
- Stammzelltransplantation (16)
- T-cells (16)
- Thrombose (16)
- Ultrakurzzeitspektroskopie (16)
- actin (16)
- additive manufacturing (16)
- asthma (16)
- cells (16)
- diborenes (16)
- enzyme replacement therapy (16)
- hemodialysis (16)
- insects (16)
- mRNA (16)
- malaria (16)
- metabolomics (16)
- model (16)
- monocytes (16)
- neurodegeneration (16)
- neurons (16)
- nutrition (16)
- olfaction (16)
- ovarian cancer (16)
- prevalence (16)
- prevention (16)
- supramolecular chemistry (16)
- vision (16)
- Ökologie (16)
- 1 (15)
- Abscisinsäure (15)
- Aldosteron (15)
- Allergie (15)
- Bestrahlung (15)
- Colonkrebs (15)
- Cyclo-AMP (15)
- Dichtefunktionalformalismus (15)
- Diffusion (15)
- Drei-Fünf-Halbleiter (15)
- Dünne Schicht (15)
- Echinococcus (15)
- Extension (15)
- Femtosekundenspektroskopie (15)
- Halbleiterlaser (15)
- Impfung (15)
- Implantat (15)
- Ischämie (15)
- Kernspintomographie (15)
- Kontrastmittel (15)
- Maligne Hyperthermie (15)
- Massenspektrometrie (15)
- Medicine (15)
- Merocyanine (15)
- Mitochondrium (15)
- NMR (15)
- Nanostruktur (15)
- Nebenniere (15)
- Onkologie (15)
- Optimale Kontrolle (15)
- Organische Solarzelle (15)
- Phosphorylierung (15)
- Polymerase-Kettenreaktion (15)
- Prostatakarzinom (15)
- Rastertunnelmikroskopie (15)
- Romanistik (15)
- Sentinel-2 (15)
- Supersymmetry (15)
- Säugling (15)
- Therapeutisches Drug Monitoring (15)
- Transcription (15)
- Transforming Growth Factor beta (15)
- Transkription (15)
- Tumor-Nekrose-Faktor (15)
- Unterfranken (15)
- Wundheilung (15)
- Xiphophorus (15)
- association (15)
- cardiac hypertrophy (15)
- conservation (15)
- dendritic cell (15)
- diversity (15)
- ecology (15)
- escherichia coli (15)
- exercise (15)
- fracture (15)
- glaucoma (15)
- growth (15)
- hadron-hadron scattering (15)
- hypertension (15)
- inhibition (15)
- microscopy (15)
- mushroom body (15)
- optogenetics (15)
- pancreatic cancer (15)
- performance (15)
- prediction (15)
- prefrontal cortex (15)
- proton-proton collision (15)
- rheumatoid arthritis (15)
- synthesis (15)
- Übergangsmetall (15)
- Activation (14)
- Aggregation (14)
- Alter Orient (14)
- Alzheimer-Krankheit (14)
- Arzneimittel (14)
- Aufmerksamkeitsdefizit-Syndrom (14)
- Calciumphosphat (14)
- Chemokine (14)
- Chlamydia trachomatis (14)
- Chronische Herzinsuffizienz (14)
- Datennetz (14)
- Diabetes (14)
- Einzelmolekülmikroskopie (14)
- Elektroencephalogramm (14)
- Europarecht (14)
- Extrazelluläre Matrix (14)
- Fanconi-Anämie (14)
- Furcht (14)
- Guanylatcyclase (14)
- HNSCC (14)
- Herzchirurgie (14)
- HgTe (14)
- Higgs boson (14)
- Hämodialyse (14)
- Informationsverarbeitung (14)
- Invasion (14)
- Ionenkanal (14)
- Katalyse (14)
- Kernhülle (14)
- Kolonkarzinom (14)
- Koronare Herzkrankheit (14)
- Kulturanthropologie (14)
- Lehrerbildung (14)
- Lungenkrebs (14)
- Lymphozyt (14)
- MSC (14)
- Mammakarzinom (14)
- Meiose (14)
- Mitose (14)
- Monoklonaler Antikörper (14)
- NHC (14)
- Natürliche Killerzelle (14)
- Nervenzelle (14)
- Optischer Resonator (14)
- PSMA (14)
- Parkinson (14)
- Perylenderivate (14)
- Plasmodium falciparum (14)
- Reaktivität (14)
- Real time quantitative PCR (14)
- Rehabilitation (14)
- Remodeling (14)
- Robotik (14)
- SPECT (14)
- Sekundärmetabolit (14)
- Spumaviren (14)
- Strukturaufklärung (14)
- Tansania (14)
- Theoretische Chemie (14)
- Topologie (14)
- Transkription <Genetik> (14)
- Transplantation (14)
- West Africa (14)
- Zelle (14)
- Zwei-Sechs-Halbleiter (14)
- biofabrication (14)
- borylation (14)
- case report (14)
- cell cycle (14)
- chemistry (14)
- circadian clock (14)
- cultural studies (14)
- ecosystem services (14)
- evaluation (14)
- fNIRS (14)
- glioblastoma (14)
- guidelines (14)
- honey bees (14)
- in-vitro (14)
- in-vivo (14)
- inorganic chemistry (14)
- insulin (14)
- lymphocytes (14)
- mechanisms (14)
- melt electrowriting (14)
- nanoparticles (14)
- neutrophils (14)
- pharmacokinetics (14)
- photoelectron spectroscopy (14)
- quantum dot (14)
- reconstruction (14)
- rehabilitation (14)
- risk (14)
- sphingolipids (14)
- super-resolution microscopy (14)
- symbiosis (14)
- vaccinia virus (14)
- AIDS (13)
- ARDS (13)
- Alter (13)
- Alzheimerkrankheit (13)
- Angiotensin II (13)
- Arbeitsgedächtnis (13)
- Aspergillose (13)
- Aspergillus (13)
- Asthma (13)
- Bibliographie (13)
- CRISPR/Cas-Methode (13)
- Candida (13)
- Computertomographie (13)
- Cytotoxizität (13)
- Elektronischer Transport (13)
- Genotoxizität (13)
- Geographie (13)
- Globalisierung (13)
- Glucocorticosteroide (13)
- Heterocyclische Carbene <-N> (13)
- Heterostruktur (13)
- Hitzeschock-Proteine (13)
- Immunbiologie (13)
- Immunhistochemie (13)
- Insekten (13)
- Interferon (13)
- Komposit (13)
- Konfokale Mikroskopie (13)
- Lippen-Kiefer-Gaumenspalte (13)
- Literaturwissenschaft (13)
- Microscopy (13)
- Mittelalter (13)
- Morbus Fabry (13)
- NK cells (13)
- Neuronale Plastizität (13)
- Osteoarthritis (13)
- Perfusion (13)
- Physics (13)
- Physik (13)
- Psychiatrie (13)
- Quantifizierung (13)
- RNS-Interferenz (13)
- Risikofaktor (13)
- Schwangerschaft (13)
- Sphingolipide (13)
- Sprachwissenschaft (13)
- Stabilität (13)
- Supersymmetrie (13)
- Tumorzelle (13)
- VASP (13)
- VEGF (13)
- adolescents (13)
- age (13)
- amygdala (13)
- animal model (13)
- autoantibodies (13)
- cGMP (13)
- cardiomyopathy (13)
- cartilage (13)
- cell staining (13)
- cytokine (13)
- diet (13)
- fear conditioning (13)
- fungi (13)
- gender (13)
- humans (13)
- hypoxia (13)
- invasion (13)
- liver (13)
- meiosis (13)
- metaanalysis (13)
- micronuclei (13)
- molecular docking (13)
- mutations (13)
- neurology (13)
- osteoarthritis (13)
- panic disorder (13)
- perylene bisimide (13)
- preterm infants (13)
- proteomics (13)
- reliability (13)
- replication (13)
- safety (13)
- therapeutic drug monitoring (13)
- translation (13)
- traumatic brain injury (13)
- ubiquitin (13)
- vitamin D (13)
- vorsprachliche Entwicklung (13)
- working memory (13)
- zebrafish (13)
- Überleben (13)
- ALS (12)
- Adenosinrezeptor (12)
- Adhäsion (12)
- Altern (12)
- Arzneimittelüberwachung (12)
- Brain-derived neurotrophic factor (12)
- Click-Chemie (12)
- Comet Assay (12)
- Computer Center University of Wuerzburg (12)
- Dialyse (12)
- Diboren (12)
- Dopamin (12)
- Durchflusscytometrie (12)
- EGFR (12)
- ERP (12)
- Enzym (12)
- FRET (12)
- Fibrose (12)
- Fluorescence (12)
- Gen (12)
- Grundschule (12)
- Hirntumor (12)
- Immunotherapy (12)
- Kinderheilkunde (12)
- Klima (12)
- Klimawandel (12)
- Kohlenstoff-Nanoröhre (12)
- Komplikationen (12)
- Kulturwissenschaften (12)
- Kutikula (12)
- Lymphom (12)
- Magnetische Kernresonanz (12)
- Medienkompetenz (12)
- Metastase (12)
- Modell (12)
- Monitoring (12)
- NFAT (12)
- Nanostrukturiertes Material (12)
- Netzhaut (12)
- Nigeria (12)
- Non-Hodgkin-Lymphom (12)
- Onkogen (12)
- PCR (12)
- PRRT (12)
- Pharmakologie (12)
- Pilzkörper (12)
- Polytrauma (12)
- Quality of Experience (12)
- Quantenchemie (12)
- Rekonstruktion (12)
- Religion (12)
- Replikation (12)
- Rotatorenmanschette (12)
- Ruthenium (12)
- SMN (12)
- SNP (12)
- Schule (12)
- Siliciumorganische Verbindungen (12)
- Spracherwerb (12)
- Supraleitung (12)
- Toll-like-Rezeptoren (12)
- Tumor-Nekrose-Faktor <alpha> (12)
- Ubiquitin (12)
- Ultrakurzer Lichtimpuls (12)
- Validierung (12)
- Westafrika (12)
- Zelladhäsion (12)
- adhesion (12)
- antibody (12)
- blood–brain barrier (12)
- carbenes (12)
- catalysis (12)
- colorectal carcinoma (12)
- complications (12)
- database (12)
- dementia (12)
- drug delivery (12)
- dynamics (12)
- electronic properties and materials (12)
- emotions (12)
- endothelium (12)
- genome (12)
- genomics (12)
- head and neck cancer (12)
- heart rate (12)
- interaction (12)
- malignant hyperthermia (12)
- measles (12)
- mechanism (12)
- microarray (12)
- microbiome (12)
- molecular beam epitaxy (12)
- molecular biology (12)
- monoclonal antibodies (12)
- neuropathy (12)
- nuclear envelope (12)
- oncology (12)
- optimization (12)
- plasticity (12)
- pollen (12)
- pollination (12)
- polymers (12)
- rats (12)
- recombination (12)
- review (12)
- screening (12)
- synaptic plasticity (12)
- systematic review (12)
- thrombosis (12)
- tinnitus (12)
- topological insulator (12)
- total knee arthroplasty (12)
- trabeculectomy (12)
- tumor microenvironment (12)
- ultrasound (12)
- water oxidation (12)
- ++ (11)
- 3D (11)
- Alzheimer's disease (11)
- Alzheimer’s disease (11)
- Anorexia nervosa (11)
- Antigen CD8 (11)
- Arabidopsis (11)
- Atherosclerosis (11)
- B-Zelle (11)
- Bakterielle Infektion (11)
- Bioisosterie (11)
- Biosynthese (11)
- Bioverfügbarkeit (11)
- Blazar (11)
- Bruchpilot (11)
- CRISPR/Cas9 (11)
- Chromatin (11)
- Computertomografie (11)
- Dynamik (11)
- Elektronentransfer (11)
- Epidemiologie (11)
- Epidermaler Wachstumsfaktor-Rezeptor (11)
- Flavonoide (11)
- Fließverhalten (11)
- Fotovoltaik (11)
- Genom (11)
- Geschlecht (11)
- Handlungsorientierung (11)
- Hypoxie (11)
- Immuncytochemie (11)
- Immunology (11)
- Japankärpfling (11)
- Knochen (11)
- Knochenersatz (11)
- Kolorektales Karzinom (11)
- LASP1 (11)
- LPS (11)
- Laser (11)
- Längsschnittuntersuchung (11)
- MS (11)
- Mais (11)
- Mathematik (11)
- Megakaryozyt (11)
- Mensch-Maschine-Kommunikation (11)
- Mesenchymale Stammzellen (11)
- Mesenchymzelle (11)
- Model (11)
- Multiple Myeloma (11)
- Mutagenität (11)
- NIRS (11)
- Nanodiamant (11)
- Neuropathie (11)
- Niereninsuffizienz (11)
- Operation (11)
- Osteoinduktion (11)
- Parasit (11)
- Parathormon (11)
- Perylenbisimid (11)
- Phylogenie (11)
- Proteaseinhibitor (11)
- Proteasen (11)
- Psychotherapie (11)
- Pulmonale Hypertonie (11)
- Quality of life (11)
- Quanten-Hall-Effekt (11)
- Reperfusion (11)
- Risikofaktoren (11)
- Salmonella (11)
- Schizophrenia (11)
- Schlafapnoe (11)
- Schließzelle (11)
- Schultergelenk (11)
- Schädel-Hirn-Trauma (11)
- Silicate (11)
- Skala (11)
- Small RNA (11)
- Sprache (11)
- Squark (11)
- Stammzellen (11)
- Sterblichkeit (11)
- Symbiose (11)
- T cell (11)
- TWEAK (11)
- Training (11)
- Transplantat-Wirt-Reaktion (11)
- Tuberkelbakterium (11)
- USA (11)
- Vasodilatator-stimuliertes Phosphoprotein (11)
- Wahrnehmung (11)
- X-ray crystallography (11)
- Zebrabärbling (11)
- Zelltod (11)
- allergy (11)
- atrial fibrillation (11)
- biocompatibility (11)
- biofilm (11)
- cancer treatment (11)
- cell adhesion (11)
- clinical trial (11)
- cochlear implant (11)
- communication (11)
- coping (11)
- dosimetry (11)
- emotion regulation (11)
- fatigue (11)
- fear (11)
- fluorescence microscopy (11)
- glioblastoma multiforme (11)
- hydrogels (11)
- immunology (11)
- kinetics (11)
- lung (11)
- membrane proteins (11)
- microglia (11)
- molecular dynamics (11)
- molecular imaging (11)
- nervous system (11)
- neural networks (11)
- neuroendocrine tumor (11)
- next generation sequencing (11)
- oncolytic virus (11)
- periodontitis (11)
- phenotype (11)
- psychiatric disorders (11)
- randomized controlled trial (11)
- reactive oxygen species (11)
- relapse (11)
- signaling (11)
- tight junctions (11)
- transport (11)
- university (11)
- Alkohol (10)
- Antigen CD28 (10)
- BERA (10)
- BMP-2 (10)
- Bacteria (10)
- Bauchspeicheldrüsenkrebs (10)
- Beschichtung (10)
- Bildverarbeitung (10)
- Bioinformatics (10)
- Biokompatibilität (10)
- Borole (10)
- Cadherine (10)
- Calciumphosphate (10)
- Carbene (10)
- Children (10)
- Chronische Niereninsuffizienz (10)
- Churritisch (10)
- Cochlear-Implantat (10)
- Computational chemistry (10)
- Coronaviren (10)
- Covid-19 (10)
- Cyclo-GMP (10)
- Depressivität (10)
- Diamant (10)
- Digital Humanities (10)
- Dimerisierung (10)
- Dotierung (10)
- Echokardiographie (10)
- Eierstockkrebs (10)
- Elektrochemie (10)
- Elektronenkorrelation (10)
- Englisch (10)
- Enzyminhibitor (10)
- Erbkrankheit (10)
- Ereigniskorreliertes Potenzial (10)
- Erwachsener (10)
- Franken (10)
- Frau (10)
- Funktionalisierung <Chemie> (10)
- Funktionelle Kernspintomografie (10)
- Förderung (10)
- Geldpolitik (10)
- Glatter Krallenfrosch (10)
- Grenzfläche (10)
- HSM-Satztest (10)
- Herzmuskelzelle (10)
- Honigbiene (10)
- Hypophosphatasie (10)
- IL-4 (10)
- Immunfluoreszenz (10)
- Impfstoff (10)
- Induzierte pluripotente Stammzelle (10)
- Interleukin 4 (10)
- Interview (10)
- JNK (10)
- Klassifikation (10)
- Kleinsatellit (10)
- Kniegelenk (10)
- Kohlenstoff (10)
- Kommunikation (10)
- Komplikation (10)
- Kooperation (10)
- Kultur (10)
- LC-MS (10)
- Ladungstransfer (10)
- Ligand (10)
- Lokalisation (10)
- Magnesiumphosphate (10)
- Magnetismus (10)
- Mathematikunterricht (10)
- Mathematisches Modell (10)
- Medulloblastom (10)
- Metakognition (10)
- Metallocene (10)
- Methylphenidat (10)
- Mikrokerne (10)
- Musik (10)
- NAFLD (10)
- Nahrungserwerb (10)
- Nebennierenrindenkarzinom (10)
- Neolithikum (10)
- Neuropathischer Schmerz (10)
- Niger (10)
- Osteosynthese (10)
- PD-1 (10)
- PD-L1 (10)
- Pain (10)
- Panikstörung (10)
- Parodontitis (10)
- Pathogenität (10)
- Platelets (10)
- Plattenepithelkarzinom (10)
- Prevalence (10)
- Prostaglandine (10)
- Präfrontaler Cortex (10)
- Pädagogik (10)
- Qualitätskontrolle (10)
- RNA interference (10)
- RNA-seq (10)
- RNS-Spleißen (10)
- Radiotherapy (10)
- Remote Sensing (10)
- Rhodium (10)
- Rituximab (10)
- SAR (10)
- Schilddrüse (10)
- Sentinel-1 (10)
- Silaanaloga (10)
- Silber (10)
- Silicon (10)
- South Africa (10)
- Sprachverstehen (10)
- Staphylococcus (10)
- Starke Kopplung (10)
- Stickstoffmonoxid-Synthase (10)
- Stressreaktion (10)
- Stroke (10)
- Struktur (10)
- T-Lymphozyten (10)
- T-Lymphozyten-Rezeptor (10)
- Tagesrhythmus (10)
- Theologie (10)
- Totalsynthese (10)
- Toxizität (10)
- Transthorakale Echokardiographie (10)
- Treg (10)
- Trypanosomen (10)
- Verwaltungsrecht (10)
- Vitamin D (10)
- Vor- und Frühgeschichte (10)
- Vorschulkind (10)
- Wachstum (10)
- agriculture (10)
- aldosterone (10)
- amino acids (10)
- antimicrobial resistance (10)
- bariatric surgery (10)
- bioinformatics (10)
- biosynthesis (10)
- body size (10)
- boranes (10)
- cancer therapy (10)
- chemokines (10)
- chronic heart failure (10)
- circadian rhythms (10)
- cognitive impairment (10)
- collagen (10)
- comparison (10)
- complex (10)
- coronary artery disease (10)
- cortisol (10)
- decision-making (10)
- density functional calculations (10)
- eNOS (10)
- education (10)
- gene therapy (10)
- genome-wide association (10)
- glioma (10)
- global change (10)
- glycine receptor (10)
- human behaviour (10)
- immunomodulation (10)
- induced pluripotent stem cells (10)
- injury (10)
- insect (10)
- knockout (10)
- leaf-cutting ants (10)
- leukemia (10)
- lymph nodes (10)
- mapping (10)
- membrane potential (10)
- motivation (10)
- near-infrared spectroscopy (10)
- neuroscience (10)
- oncolytic virotherapy (10)
- oxidativer Stress (10)
- quality assurance (10)
- quantification (10)
- regulatorische T-Zellen (10)
- remodeling (10)
- senescence (10)
- silicon (10)
- social interaction (10)
- stem cell transplantation (10)
- subthalamic nucleus (10)
- synapse (10)
- tDCS (10)
- transcriptomics (10)
- tumors (10)
- vaccination (10)
- vertigo (10)
- walking (10)
- Östrogene (10)
- 3 (9)
- Adenosin (9)
- Adenosine receptors (9)
- Affekt (9)
- Afrika (9)
- Alps (9)
- Analyse (9)
- Angeregter Zustand (9)
- Anxiety (9)
- Aorta (9)
- Aortenstenose (9)
- Autophagie (9)
- Beyond Standard Model (9)
- Biotransformation (9)
- Bordetella pertussis (9)
- Borylierung (9)
- Boğazkale (9)
- Butyrat (9)
- CT (9)
- Carcinogenese (9)
- Catalysis (9)
- Chiralität <Chemie> (9)
- Cloud Computing (9)
- Deep learning (9)
- Dendritic cells (9)
- Diagnose (9)
- Diborane (9)
- Diskursanalyse (9)
- Dünndarm (9)
- Einzelphotonenemission (9)
- Elektroencephalographie (9)
- Elektronenmikroskopie (9)
- Elektronenstruktur (9)
- Elementarteilchenphysik (9)
- Epithel (9)
- Ernährung (9)
- Experimentelle Psychologie (9)
- Extremwertstatistik (9)
- Familie (9)
- Fanconi Anämie (9)
- Fettgewebe (9)
- Fibroblastenwachstumsfaktor (9)
- Fibromyalgie (9)
- Finite-Elemente-Methode (9)
- Frühgeborene (9)
- GIS (9)
- Geistigbehindertenpädagogik (9)
- Gentherapie (9)
- Geoinformationssystem (9)
- Geruchswahrnehmung (9)
- Glioblastoma (9)
- Google Earth Engine (9)
- Grammatik (9)
- Haut (9)
- Herzmuskelkrankheit (9)
- Hethiter (9)
- Hyaluronsäure (9)
- Immunisierung (9)
- Impulsivität (9)
- Innovation (9)
- Instrumentelle Analytik (9)
- Integrine (9)
- Iran (9)
- Isolierung <Chemie> (9)
- Jugendliche (9)
- Juvenile chronische Arthritis (9)
- Kapillarelektrophorese (9)
- Knorpel (9)
- Konflikt (9)
- Koordinationslehre (9)
- Korpus <Linguistik> (9)
- LC-MS/MS (9)
- Landsat (9)
- Leber (9)
- Linguistik (9)
- Löslichkeit (9)
- MAPK (9)
- Macrophage (9)
- Magnetische Resonanz (9)
- Mehrfachbindung (9)
- Mehrsprachigkeit (9)
- Messenger-RNS (9)
- Mice (9)
- Molekulare Erkennung (9)
- Monozyt (9)
- Morphologie (9)
- Mukoviszidose (9)
- Myokardprotektion (9)
- NO (9)
- NSCLC (9)
- Nebennierenrindenkrebs (9)
- Neuroinflammation (9)
- Nierentransplantation (9)
- Oberfläche (9)
- Oberflächenphysik (9)
- Optoelektronik (9)
- Pathogenese (9)
- Persönlichkeit (9)
- Pharmakotherapie (9)
- Photolumineszenzspektroskopie (9)
- Physiologie (9)
- Plasmamembran (9)
- Protein (9)
- Pseudomonas syringae (9)
- Psychoonkologie (9)
- Quantenmechanik (9)
- Rechenzentrum (9)
- Rechtsvergleich (9)
- Regeneration (9)
- Regionalentwicklung (9)
- Revision (9)
- Sarkoidose (9)
- Satellit (9)
- Schmalwand <Arabidopsis> (9)
- Schwindel (9)
- Schüttgut (9)
- Spin-Bahn-Wechselwirkung (9)
- Squaraine (9)
- Stathmin (9)
- Stereoselektive Synthese (9)
- Supply Chain Management (9)
- Syntax (9)
- Systembiologie (9)
- Südafrika (9)
- TDM (9)
- Textverstehen (9)
- Therapy (9)
- Tourismus (9)
- Trabekulektomie (9)
- Transplantat (9)
- Transport (9)
- Trypanosoma (9)
- Tumorantigen (9)
- Vakuole (9)
- Vergleich (9)
- Visuelle Aufmerksamkeit (9)
- Wurzel (9)
- Zellkern (9)
- Zentralnervensystem (9)
- Zinkselenid (9)
- actin cytoskeleton (9)
- adolescence (9)
- aggregation (9)
- amyotrophic lateral sclerosis (9)
- antennal lobe (9)
- anxiety disorders (9)
- aromaticity (9)
- astrocytes (9)
- biomechanics (9)
- blood brain barrier (9)
- bone cement (9)
- bone marrow (9)
- cardiac surgery (9)
- cardiovascular disease (9)
- cell culture (9)
- cell migration (9)
- cell wall (9)
- central nervous system (9)
- cerebrospinal fluid (9)
- chromatin (9)
- computed tomography (9)
- coronary heart disease (9)
- cuticular hydrocarbons (9)
- cystic fibrosis (9)
- cytotoxic T cells (9)
- decision making (9)
- dendritische Zellen (9)
- dialysis (9)
- dispersal (9)
- earth observation (9)
- electroencephalography (9)
- electron microscopy (9)
- electrophysiology (9)
- energy (9)
- experimental autoimmune encephalomyelitis (9)
- family (9)
- foamy virus (9)
- forest (9)
- gephyrin (9)
- glucose (9)
- high energy physics (9)
- hip (9)
- hyaluronic acid (9)
- hydrogel (9)
- impact (9)
- incidence (9)
- inhibitor (9)
- interferon (9)
- latency (9)
- macrophage (9)
- major depression (9)
- mechanotransduction (9)
- mesenchymale Stammzellen (9)
- metapopulation (9)
- methylation (9)
- mitosis (9)
- monitoring (9)
- monoklonale Antikörper (9)
- myocardium (9)
- navigation (9)
- neurogenesis (9)
- optical spectroscopy (9)
- organic chemistry (9)
- organic semiconductors (9)
- pathogens (9)
- pathway (9)
- perfusion (9)
- peripheral nervous system (9)
- permeability (9)
- personality (9)
- pharmacology (9)
- photocatalysis (9)
- platelet activation (9)
- platelet aggregation (9)
- prognostic factors (9)
- quantum dots (9)
- radiation (9)
- rectal cancer (9)
- reveals (9)
- selection (9)
- serum (9)
- sleep (9)
- spinal muscular atrophy (9)
- systematic uncertainty (9)
- temperature (9)
- tolerance (9)
- transcription factor (9)
- transient absorption (9)
- transmission (9)
- type 2 diabetes (9)
- vaccine (9)
- water (9)
- wound healing (9)
- Übersetzung (9)
- ATLAS (8)
- AdS-CFT-Korrespondenz (8)
- Adhärenz (8)
- Aggregat <Chemie> (8)
- Akt (8)
- Aktiver galaktischer Kern (8)
- Algorithmus (8)
- Alltagskultur (8)
- Ancistrocladaceae (8)
- Anthocyane (8)
- Antibiotika (8)
- Antigen (8)
- Antigen CD40 (8)
- Aortenklappenersatz (8)
- Arthrose (8)
- Arthroskopie (8)
- Arzneimittelforschung (8)
- Astrophysik (8)
- Asymmetrie (8)
- Asymmetrische Synthese (8)
- Auge (8)
- Autoaggressionskrankheit (8)
- Autonomer Roboter (8)
- Bauchspeicheldrüse (8)
- Biradikal (8)
- Blimp-1 (8)
- Blutdruck (8)
- Blutstammzelle (8)
- Botanik (8)
- Brain (8)
- Burkina Faso (8)
- CD28 (8)
- CD40 (8)
- CD95 (8)
- COMT (8)
- Caenorhabditis elegans (8)
- Camponotus floridanus (8)
- Chlamydia (8)
- Compressed Sensing (8)
- Cross-Section (8)
- Cysteinproteasen (8)
- Cytomegalie-Virus (8)
- DLBCL (8)
- Darm (8)
- Data Mining (8)
- Datenbank (8)
- Degradation (8)
- Demenz (8)
- Deutschunterricht (8)
- Diborene (8)
- ELISA (8)
- ERK (8)
- Elektronenspin (8)
- Elektronenspinresonanz (8)
- Emotionsregulation (8)
- Endothelzellen (8)
- Engagement (8)
- Erbrechen (8)
- Europa (8)
- Europe (8)
- Exziton-Polariton (8)
- Fachdidaktik (8)
- Femtosekundenbereich (8)
- Fibroblasten (8)
- Fitness (8)
- Fluoreszenzspektroskopie (8)
- Forschung (8)
- Fußball (8)
- GABA (8)
- Gammastrahlung (8)
- Gedächtnisleistung (8)
- Genotoxicity (8)
- Geschlechtsunterschied (8)
- Gewebe (8)
- Gliom (8)
- Graphen (8)
- HPLC-MS (8)
- Habichtskraut (8)
- Haemophilus influenzae (8)
- Harnwegsinfektion (8)
- Hernie (8)
- Hochbegabung (8)
- Hubbard-Modell (8)
- Humangenetik (8)
- Hymenoptera (8)
- Hypertrophie (8)
- Hüftgelenk (8)
- IL-10 (8)
- Immunantwort (8)
- In vivo (8)
- India (8)
- Indien (8)
- Inklusion (8)
- Keilschrifttext (8)
- Kephalometrie (8)
- Kieferorthopädie (8)
- Kinetik (8)
- Knochenersatzmaterial (8)
- Knockout (8)
- Komposit <Zahnmedizin> (8)
- Kondo-Effekt (8)
- Korrelation (8)
- Kreuzband (8)
- Kristallstruktur (8)
- Landwirtschaft (8)
- Langerhans-Inseln (8)
- Lanthanoide (8)
- Lehre (8)
- Leishmania (8)
- Lernautonomie (8)
- Lower Franconia (8)
- Lumineszenz (8)
- Lungenfibrose (8)
- Machine Learning (8)
- Magenbypass (8)
- Makuladegeneration (8)
- Mass (8)
- Meeresschwämme (8)
- Meiosis (8)
- Meningitis (8)
- Meningokokken (8)
- Metaanalyse (8)
- Methode (8)
- Mikroglia (8)
- Mikrokerntest (8)
- Mikrostruktur (8)
- Mitochondrien (8)
- Mobiler Roboter (8)
- Molekül (8)
- Monozyten (8)
- Multiple myeloma (8)
- Myokarditis (8)
- N-heterocyclic carbenes (8)
- Nachsorge (8)
- Nanodraht (8)
- Naturstoff (8)
- Neugeborenes (8)
- Neutrino (8)
- Notfallmedizin (8)
- Obesity (8)
- Onkolyse (8)
- Optogenetik (8)
- Organisches Molekül (8)
- Oxylipine (8)
- PONV (8)
- Pankreaskarzinom (8)
- Parton distributions (8)
- Pemphigus (8)
- Peptide (8)
- Periphere arterielle Verschlusskrankheit (8)
- Permeabilität (8)
- Pharmakodynamik (8)
- Photodissoziation (8)
- Photovoltaik (8)
- Platin (8)
- Pollen (8)
- Polycyclische Aromaten (8)
- Protein p53 (8)
- Protein-Tyrosin-Kinasen (8)
- Proteinbindung (8)
- Protonen-NMR-Spektroskopie (8)
- Präkonditionierung (8)
- Psychische Störung (8)
- Pump-Probe-Technik (8)
- Quantendynamik (8)
- Quelle (8)
- Quran (8)
- RNA sequencing (8)
- Radikal <Chemie> (8)
- Raf <Biochemie> (8)
- Raf-Kinasen (8)
- Raman spectroscopy (8)
- Rastertunnelmikroskop (8)
- Rechenzentrum Universität Würzburg (8)
- Rechnungslegung (8)
- Regenerative Medizin (8)
- Rekombination (8)
- Retroviren (8)
- Ringöffnungspolymerisation (8)
- Roman (8)
- Röntgen-Photoelektronenspektroskopie (8)
- Salmonella typhimurium (8)
- Schmerzforschung (8)
- Schwämme (8)
- Semimagnetischer Halbleiter (8)
- Siliciumcarbid (8)
- Sozialpsychologie (8)
- Sprachaudiometrie (8)
- Statistik (8)
- Stent (8)
- Stofftransport <Biologie> (8)
- Survival (8)
- Synthesis (8)
- T cell activation (8)
- T lymphocytes (8)
- T-Zelle (8)
- Tabak (8)
- Tagung (8)
- Text Mining (8)
- Textanalyse (8)
- Thrombosis (8)
- Thrombozyten (8)
- Thymus (8)
- Tight junction (8)
- Titan (8)
- Transkriptomanalyse (8)
- Trauma (8)
- Trypanosomiase (8)
- Tumorimmunologie (8)
- UAV (8)
- Ultraschalldiagnostik (8)
- Unterricht (8)
- Vascular endothelial Growth Factor (8)
- Virusinfektion (8)
- Visualisierung (8)
- Vulnerabilität (8)
- Wirkstofffreisetzung (8)
- Zahnmedizin (8)
- Zeitreihenanalyse (8)
- absorption (8)
- acute kidney injury (8)
- adaptation (8)
- adherence (8)
- adipose tissue (8)
- adults (8)
- ageing (8)
- aggression (8)
- allogeneic stem cell transplantation (8)
- analysis of variance (8)
- animal models (8)
- antigen (8)
- behaviour (8)
- bladder cancer (8)
- body mass index (8)
- borylene (8)
- calcium phosphate (8)
- cell biology (8)
- central complex (8)
- ceramide (8)
- charge transfer (8)
- chronic pain (8)
- classical conditioning (8)
- cleft lip and palate (8)
- coagulation (8)
- coherence (8)
- copper (8)
- crystallization (8)
- decay (8)
- distribution (8)
- division of labor (8)
- domain (8)
- dystonia (8)
- efficacy (8)
- electronic structure (8)
- embodiment (8)
- endocytosis (8)
- energy transfer (8)
- extinction (8)
- flavonoids (8)
- forest management (8)
- gastric cancer (8)
- genes (8)
- health-related quality of life (8)
- hearing (8)
- histology (8)
- immune evasion (8)
- implant (8)
- in vivo imaging (8)
- integrins (8)
- iron (8)
- jet energy scale (8)
- juvenile idiopathic arthritis (8)
- kinematic alignment (8)
- knee (8)
- learning and memory (8)
- lithium (8)
- mHealth (8)
- melt electrospinning writing (8)
- meta-analysis (8)
- methylphenidate (8)
- microbiology (8)
- microenvironment (8)
- microstructure (8)
- monocyte (8)
- morphology (8)
- mutualism (8)
- optimal control (8)
- organic solar cells (8)
- organoids (8)
- pancreas (8)
- pediatrics (8)
- permafrost (8)
- phylogeny (8)
- polycyclic aromatic hydrocarbons (8)
- preconditioning (8)
- presence (8)
- primary care (8)
- progression (8)
- protease (8)
- psoriasis (8)
- pulmonary hypertension (8)
- questionnaire (8)
- radicals (8)
- radioligand therapy (8)
- receptors (8)
- recovery (8)
- regenerative medicine (8)
- scaffold (8)
- secondary structure (8)
- secretion (8)
- semiconductor (8)
- shoulder (8)
- skin biopsy (8)
- smoking (8)
- social cognition (8)
- social insects (8)
- sodium (8)
- software (8)
- species richness (8)
- spintronics (8)
- staphylococcus aureus (8)
- structure (8)
- susceptibility (8)
- targeted therapy (8)
- technology (8)
- thymus (8)
- tool (8)
- transcriptional regulation (8)
- vestibular schwannoma (8)
- 3D tissue model (7)
- 53BP1 (7)
- Adsorption (7)
- Adulte Stammzelle (7)
- Africa (7)
- Aktin (7)
- Aktivierung (7)
- Aktivierung <Physiologie> (7)
- Akute myeloische Leukämie (7)
- Akutes Nierenversagen (7)
- Alzheimer disease (7)
- Anpassung (7)
- Antagonist (7)
- Anämie (7)
- Anästhesie (7)
- Audiologie (7)
- Audiometrie (7)
- Augmentation (7)
- Ausbreitung (7)
- Autoimmunity (7)
- B-Zellen (7)
- Behandlung (7)
- Behinderung (7)
- Bindungsaktivierung (7)
- Biographie (7)
- Blattschneiderameisen (7)
- Blut (7)
- Blutgerinnung (7)
- Bordetella (7)
- Borylenkomplexe (7)
- CMV (7)
- CNS (7)
- Calciumkanal (7)
- Candida auris (7)
- Catecholmethyltransferase <Catechol-0-Methyltransferase> (7)
- Charakterisierung (7)
- Charcot-Marie-Tooth (7)
- Chronobiologie (7)
- Chrysomelidae (7)
- Cisplatin (7)
- Coronavirus (7)
- Cytoskeleton (7)
- DHEA (7)
- DNS-Doppelstrangbruch (7)
- Deutsch als Fremdsprache (7)
- Didaktik (7)
- Differentielle Genexpression (7)
- Dopamine (7)
- Durchblutung (7)
- Durchflusszytometrie (7)
- Dysgnathie (7)
- E-Learning (7)
- ELISPOT (7)
- EMG (7)
- ERK1/2 (7)
- ERN (7)
- Echinococcus multilocularis (7)
- Einwandige Kohlenstoff-Nanoröhre (7)
- Eisen (7)
- Elektrokardiogramm (7)
- Embryo (7)
- Endoprothetik (7)
- Ethik (7)
- FISH (7)
- Fahrsimulator (7)
- Fanconi anemia (7)
- Festkörperoberfläche (7)
- Fibroblast (7)
- Fluoreszenz-in-situ-Hybridisierung (7)
- Flüssigkristall (7)
- Fortpflanzung (7)
- Fraktur (7)
- Freundschaft (7)
- Gallium (7)
- Gehirn-Computer-Schnittstelle (7)
- Geistige Behinderung (7)
- Gelenkknorpel (7)
- Genetics (7)
- Geochemie (7)
- Geologie (7)
- Geomorphologie (7)
- Geriatrie (7)
- Germanium (7)
- Geruch (7)
- Geruchssinn (7)
- Geschlechterforschung (7)
- Gesellschaftsrecht (7)
- Gewalt (7)
- Graft-versus-host-disease (7)
- Guillain-Barré-Syndrom (7)
- HIV-1 (7)
- HUVEC (7)
- Heart (7)
- Herzfrequenz (7)
- Hfq (7)
- High throughput screening (7)
- Histologie (7)
- Honeybee (7)
- Hyaliner Knorpel (7)
- Hypervalentes Molekül (7)
- Hämostase (7)
- Immunglobuline (7)
- Innenstadt (7)
- Integrin (7)
- Interleukin 6 (7)
- Internet (7)
- Jasmonate (7)
- KHK (7)
- Kandidatengen (7)
- Kardiologie (7)
- Kardiomyopathie (7)
- Karriere (7)
- Keramik (7)
- Keratinozyten (7)
- Kindheit (7)
- Kniegelenkprothese (7)
- Knieprothese (7)
- Knochenregeneration (7)
- Kohlenwasserstoffe (7)
- Komplement <Immunologie> (7)
- Komplexe (7)
- Koordinationspolymere (7)
- Koran (7)
- Kutikularwachs (7)
- LEED (7)
- Landnutzung (7)
- Langzeitergebnisse (7)
- Learning (7)
- Learning autonomy (7)
- Leishmaniose (7)
- Lernerautonomie (7)
- Lithium-Ionen-Akkumulator (7)
- Lungenfunktion (7)
- MBE (7)
- MYCN (7)
- Macht (7)
- Mangan (7)
- Manganarsenide (7)
- Mehragentensystem (7)
- Membranproteine (7)
- Metapopulation (7)
- Micronuclei (7)
- Mimik (7)
- Molekularbewegung (7)
- Monte Carlo (7)
- Monte-Carlo (7)
- Mortalität (7)
- Motilität (7)
- Motorisches Lernen (7)
- Mundschleimhaut (7)
- Museum (7)
- N-Myc (7)
- NDVI (7)
- Nash-Gleichgewicht (7)
- Naturstoffe (7)
- Neolithic (7)
- Nervendegeneration (7)
- Neuralgie (7)
- Neuroblastom (7)
- Neuroethologie (7)
- Neurootologie (7)
- Newton-Verfahren (7)
- Nicht-kleinzelliges Bronchialkarzinom (7)
- Nierenfunktion (7)
- Nierenversagen (7)
- Nierenzellkarzinom (7)
- Nuklearmedizin (7)
- Numerisches Verfahren (7)
- Ontogenie (7)
- Operations Management (7)
- Organisation (7)
- Outcome (7)
- Oxidation (7)
- Paniksyndrom (7)
- Parkinson disease (7)
- Performance Evaluation (7)
- Phagozytose (7)
- Pheromon (7)
- Photochemie (7)
- Photoionisation (7)
- Plasma (7)
- Promotor (7)
- Propofol (7)
- Proteinkinase C (7)
- Proteomanalyse (7)
- Pulsformung (7)
- Qualität (7)
- Qualitätssicherung (7)
- Quantenwell (7)
- REMPI (7)
- RNA-binding proteins (7)
- Radioastronomie (7)
- Raman (7)
- Ranvier-Schnürring (7)
- Rat (7)
- Rechtschreibung (7)
- Regulierung (7)
- Rheumatoid arthritis (7)
- Röntgenspektroskopie (7)
- SARS (7)
- SERS (7)
- SGLT1 (7)
- SMA (7)
- STAT3 (7)
- Saccharomyces cerevisiae (7)
- Sandwich-Verbindungen (7)
- Schilddrüsenkrebs (7)
- Schistosomiasis (7)
- Schmerztherapie (7)
- Schulleistung (7)
- Schulter (7)
- Siliciumdioxid (7)
- Soziale Insekten (7)
- Spanisch (7)
- Spin (7)
- Spintronics (7)
- Spiroergometrie (7)
- Stadtplanung (7)
- Steuerrecht (7)
- Strategisches Management (7)
- Struvit (7)
- Studie (7)
- Störlärm (7)
- Subarachnoidalblutung (7)
- Synchrotronstrahlung (7)
- Systematik (7)
- Säugetiere (7)
- T cell receptor (7)
- TRAF2 (7)
- Tissue engineering (7)
- Toxoplasma gondii (7)
- Transcriptome (7)
- Transfektion (7)
- TrkB (7)
- Ubiquitinierung (7)
- Umfrage (7)
- United States (7)
- Unternehmen (7)
- Unternehmensbewertung (7)
- Vagus (7)
- Vaskularisation (7)
- Vegetation (7)
- Venusfliegenfalle (7)
- Verbraucherverhalten (7)
- Verkehrspsychologie (7)
- Verunreinigung (7)
- Vestibularisschwannom (7)
- Wilms tumor (7)
- Wolfram (7)
- Wundinfektion (7)
- X-ray (7)
- Zellwand (7)
- Zoologie (7)
- Zytoskelett (7)
- Zytotoxizität (7)
- acute ischemic stroke (7)
- acute myeloid leukemia (7)
- adolescent (7)
- adsorption (7)
- adult neurogenesis (7)
- algorithm (7)
- altitudinal gradient (7)
- anemia (7)
- animal behavior (7)
- animal behaviour (7)
- antibacterial activity (7)
- antibiotic resistance (7)
- antidepressant (7)
- arabidopsis thaliana (7)
- aspergillosis (7)
- automation (7)
- autonomic nervous system (7)
- basal ganglia (7)
- biomaterials (7)
- bioprinting (7)
- blood flow (7)
- bone mineral density (7)
- bone regeneration (7)
- brain development (7)
- brain-computer interface (7)
- butyrate (7)
- caffeine (7)
- capillary electrophoresis (7)
- carbon dioxide (7)
- carcinoma (7)
- catecholamines (7)
- cell membranes (7)
- cerebellum (7)
- change detection (7)
- chemokine receptor (7)
- click chemistry (7)
- co-culture (7)
- cognition (7)
- cognitive control (7)
- cognitive decline (7)
- comparative genomics (7)
- complexes (7)
- complexity (7)
- cytokinesis (7)
- degeneration (7)
- degradation (7)
- design (7)
- developmental biology (7)
- diagnostics (7)
- diborynes (7)
- diffusion (7)
- drought (7)
- drug (7)
- drug design (7)
- dyes (7)
- endurance (7)
- enzyme (7)
- enzymes (7)
- exciton (7)
- extracellular vesicles (7)
- facial expression (7)
- facial expressions (7)
- feedback (7)
- femtosecond spectroscopy (7)
- fibromyalgia syndrome (7)
- fluorescence imaging (7)
- fluorescent probes (7)
- fungal infection (7)
- gastrointestinal tract (7)
- genomic damage (7)
- glucocorticoid receptor (7)
- guard cell (7)
- heterocycles (7)
- honey bee (7)
- hymenoptera (7)
- hypophosphatasia (7)
- immersion (7)
- immune system (7)
- immunofluorescence (7)
- immunoprecipitation (7)
- infections (7)
- inflammatory bowel disease (7)
- isolation (7)
- kinase (7)
- knockout mice (7)
- kolorektales Karzinom (7)
- localization (7)
- locomotion (7)
- luciferase (7)
- marine sponges (7)
- medulloblastoma (7)
- megakaryocytes (7)
- membrane (7)
- meningitis (7)
- methionine (7)
- minimally invasive (7)
- modeling (7)
- monoclonal antibody (7)
- motility (7)
- motoneuron (7)
- motor learning (7)
- mri (7)
- multicenter (7)
- myelin (7)
- myocarditis (7)
- nanodiamond (7)
- neuroblastoma (7)
- neuromuscular junction (7)
- neurotrophins (7)
- noise (7)
- nucleus (7)
- oxidation (7)
- pH (7)
- pathogenesis (7)
- pediatric (7)
- pemphigus (7)
- personalized medicine (7)
- photoinduced electron transfer (7)
- plasmodium falciparum (7)
- polycaprolactone (7)
- population (7)
- potassium (7)
- pre-speech development (7)
- precision medicine (7)
- prospective (7)
- public health (7)
- pulse shaping (7)
- quantum dynamics (7)
- radioiodine therapy (7)
- random forest (7)
- recognition (7)
- recruitment (7)
- reperfusion (7)
- resilience (7)
- responses (7)
- retina (7)
- risk factor (7)
- rotator cuff (7)
- sRNA (7)
- salt stress (7)
- secondary prevention (7)
- segmentation (7)
- semiconductors (7)
- serotonin transporter (7)
- sex chromosomes (7)
- sex differences (7)
- shear stress (7)
- signaltransduction (7)
- silver (7)
- small RNA (7)
- small fiber neuropathy (7)
- social anxiety (7)
- speech audiometry (7)
- superconductivity (7)
- survey (7)
- systems biology (7)
- target (7)
- taxonomy (7)
- telomeres (7)
- thermodynamics (7)
- thrombo-inflammation (7)
- total hip arthroplasty (7)
- translational research (7)
- translocation (7)
- trial (7)
- two-dimensional materials (7)
- variability (7)
- virus (7)
- visual system (7)
- wearable (7)
- Übergangsmetalloxide (7)
- Übergewicht (7)
- - (6)
- 18F-FDG (6)
- 19. Jahrhundert (6)
- 2 (6)
- ABA (6)
- ACC (6)
- AMPK (6)
- ANP (6)
- ATLAS <Teilchendetektor> (6)
- Abwehrreaktion (6)
- Akustikusneurinom (6)
- Akute Leukämie (6)
- Allergy (6)
- Alpen (6)
- Amino acids (6)
- Amygdala (6)
- Analoga (6)
- Anatolische Sprachen (6)
- Angeborene Immunität (6)
- Angsterkrankungen (6)
- Anionentranslokator (6)
- Antibody (6)
- Antizipation (6)
- Aortenaneurysma (6)
- Aortenklappenstenose (6)
- Arbeitsteilung (6)
- Assoziatives Gedächtnis (6)
- Atriales natriuretisches Hormon (6)
- Aufsichtsrat (6)
- Automation (6)
- B-cell lymphoma (6)
- B7-H1 (6)
- BCI (6)
- BRAF (6)
- BRCA1 (6)
- Beta-Rezeptor (6)
- Bildgebung (6)
- Bildung (6)
- Bilharziose (6)
- Biologische Uhr (6)
- Biology (6)
- Blutstillung (6)
- Borheterocyclen (6)
- Boğazköy (6)
- Bronchialasthma (6)
- C-reactive protein (6)
- CD1d (6)
- CML (6)
- CNTF (6)
- COPD (6)
- CRPS (6)
- Calcineurin (6)
- Campylobacter jejuni (6)
- Carcinogen (6)
- Cataglyphis (6)
- Chemische Bindung (6)
- Chemotaxis (6)
- Chromatographie (6)
- Chromophor (6)
- Chronophin (6)
- Ciliary neurotrophic factor (6)
- Computational Chemistry (6)
- Cycloaddition (6)
- Cyclodextrine (6)
- DFB-Laser (6)
- DNA binding (6)
- DNA-Methylierung (6)
- Datenanalyse (6)
- Dehydroepiandrosteron (6)
- Desfluran (6)
- Domäne <Biochemie> (6)
- Dreidimensionale Rekonstruktion (6)
- Drugs (6)
- Dünnschichtsolarzelle (6)
- EBV (6)
- ECM (6)
- EHEC (6)
- EKP (6)
- Earth observation (6)
- Ecology (6)
- Ehrenamtliche Tätigkeit (6)
- Einkaufszentrum (6)
- Elektroporation (6)
- Enantioselektivität (6)
- Endocytose (6)
- Endodontie (6)
- Endozytose (6)
- Enterobacteriaceae (6)
- Entscheidungsunterstützungssystem (6)
- Entwicklungsländer (6)
- Entwicklungspsychologie (6)
- Fabry (6)
- Fahrerverhalten (6)
- Fanconi Anemia (6)
- Fas-Ligand (6)
- Fatigue (6)
- Finanzmathematik (6)
- Fn14 (6)
- Formicidae (6)
- Fotoionisation (6)
- Fotophysik (6)
- Fourier-Spektroskopie (6)
- Fragmentation (6)
- Frankreich (6)
- Französisch (6)
- Funktion (6)
- Funktionelle NMR-Tomographie (6)
- GC-MS (6)
- GPVI (6)
- GaAs (6)
- Gammaastronomie (6)
- Gender (6)
- Gentoxizität (6)
- Geobotanik (6)
- Gerste (6)
- Geschlechtsbestimmung (6)
- Gesicht (6)
- Glucose (6)
- Glucosetransportproteine (6)
- Gluino Production (6)
- Glykoproteine (6)
- Glykosylierung (6)
- Gold (6)
- Growth (6)
- Grundschulkind (6)
- HAART (6)
- HBMEC (6)
- HGF (6)
- Hadron colliders (6)
- Halbleiteroberfläche (6)
- Hautbiopsie (6)
- HeLa cells (6)
- Heparin (6)
- Hepatitis C (6)
- Hepatozyten-Wachstumsfaktor (6)
- Herzkatheter (6)
- Heterocyclische Verbindungen (6)
- Higgs bosons (6)
- Higgs physics (6)
- Hochtemperatursupraleiter (6)
- Hubbard model (6)
- Humanismus (6)
- Hydrogeologie (6)
- Hypertension (6)
- Hypothalamus (6)
- Hypoxia (6)
- Hörgerät (6)
- Hörverlust (6)
- Hüftgelenkprothese (6)
- ICD-10 (6)
- ITS2 (6)
- Imaging (6)
- Immun-Checkpoint (6)
- Immunaktivierung (6)
- Immunoblot (6)
- Immuntoleranz (6)
- Infrarotspektroskopie (6)
- Integration (6)
- Intensivstation (6)
- Interferon <gamma-> (6)
- Interleukin-4 (6)
- IoT (6)
- Juvenile idiopathische Arthritis (6)
- Kation (6)
- Keratinozyt (6)
- Kiefergelenk (6)
- Kinasen (6)
- Kleinkern (6)
- Knochendichte (6)
- Knochenmark (6)
- Kohlenhydrate (6)
- Komplexität (6)
- Komplexitätstheorie (6)
- Konjugierte Polymere (6)
- Koordinationschemie (6)
- Kostimulation (6)
- Kraniosynostose (6)
- Körperliche Aktivität (6)
- LASP-1 (6)
- LOH (6)
- Ladungstransport (6)
- Large Hadron Collider (6)
- Laserspektroskopie (6)
- Latrophilin (6)
- Legionella (6)
- Leistung (6)
- Leonhard classification (6)
- Leonhard-Klassifikation (6)
- Lipide (6)
- Lymphome (6)
- Lymphozyten (6)
- MASS (6)
- MHC (6)
- Magenchirurgie (6)
- Magnetic Resonance Imaging (6)
- Magnetic resonance imaging (6)
- Magnetowiderstand (6)
- Makroökonomie (6)
- Manisch-depressive Krankheit (6)
- Mechanisms (6)
- Medien (6)
- Melanin (6)
- Melanoma (6)
- Membran (6)
- Memory (6)
- Mensch-Maschine-Schnittstelle (6)
- Metabolism (6)
- Metabolomics (6)
- Metagedächtnis (6)
- Metalloproteinasen (6)
- Methylation (6)
- Mikrobiologie (6)
- Mikroresonator (6)
- Mitochondria (6)
- Molekulardesign (6)
- Monoklonaler bispezifischer Antikörper (6)
- Montessori (6)
- Morbus Crohn (6)
- Multidrug-Resistenz (6)
- Multiple sclerosis (6)
- Mutationsanalyse (6)
- Myatrophische Lateralsklerose (6)
- Mykenische Kultur (6)
- Myocardial infarction (6)
- Myokard (6)
- NLO Computations (6)
- NLRP3 (6)
- NMR spectroscopy (6)
- NRF2 (6)
- Nachhaltigkeitsrecht (6)
- Nachuntersuchung (6)
- Nahrung (6)
- Nanoparticles (6)
- Nasenschleimhaut (6)
- Nationalsozialismus (6)
- Nebennierenkarzinom (6)
- Nebennierenrindeninsuffizienz (6)
- Nebennierentumor (6)
- Nephroblastom (6)
- Neue Medien (6)
- Neugeborene (6)
- Neuroanatomie (6)
- Neurofascin (6)
- Neurologie (6)
- Neuromonitoring (6)
- Nichtlineare Optimierung (6)
- Nickel (6)
- Nickelkomplexe (6)
- Non-coding RNA (6)
- Notfall (6)
- Nucleinsäuren (6)
- Nuklearfaktor Kappa B (6)
- OLED (6)
- Olfaction (6)
- Oncology (6)
- Oozyte (6)
- Opioide (6)
- Optik (6)
- Optogenetics (6)
- PCI (6)
- Paracetamol (6)
- Pathologie (6)
- Peptidsynthese (6)
- Perowskit (6)
- Pflanzengeographie (6)
- Phonologische Bewusstheit (6)
- Phosphane (6)
- Photophysik (6)
- Physikalische Chemie (6)
- Phänotyp (6)
- Plastizität (6)
- Platelet (6)
- Platinkomplexe (6)
- Plattenosteosynthese (6)
- Politik (6)
- Polymerisation (6)
- Polymerkomplexe (6)
- Porin (6)
- Probiotikum (6)
- Proteasom (6)
- Proteom (6)
- Prothetik (6)
- Pulver (6)
- QM/MM (6)
- Quanteninformation (6)
- RNA polymerase II (6)
- RNAi (6)
- RT-PCR (6)
- Rac1 (6)
- Raf (6)
- Rashba-Effekt (6)
- Reaktive Sauerstoffspezies (6)
- Rechnernetz (6)
- Rechtsprechung (6)
- Regulatory T cells (6)
- Rektumkarzinom (6)
- Religionsunterricht (6)
- Renin-Angiotensin-System (6)
- Resektion (6)
- Resilienz (6)
- Retina (6)
- Rheologie (6)
- RhoA (6)
- Rhodopsin (6)
- Ribosom (6)
- Risiko (6)
- Routing (6)
- SDN (6)
- SSTR (6)
- Salmonella enterica (6)
- Schrei (6)
- Selbsteinschätzung (6)
- Selen (6)
- Self-assembly (6)
- Semiconductor (6)
- Sensitivität (6)
- Sensor (6)
- Signalkette (6)
- Siliciumkomplexe (6)
- Siloxane (6)
- Skalierung (6)
- Smad (6)
- Small nuclear RNP (6)
- Software (6)
- Sol-Gel (6)
- Solarzelle (6)
- Soziologie (6)
- Sprachentwicklungsstörung (6)
- Sprachtest (6)
- Stickstoffoxidsynthase (6)
- Strahlensensibilität (6)
- Streptococcus pneumoniae (6)
- Streptomyces (6)
- Stroma (6)
- Supramolecular Chemistry (6)
- T-lymphocytes (6)
- TAVI (6)
- TGF-beta (6)
- TNF-alpha (6)
- TNFR2 (6)
- Targeted drug delivery (6)
- Temperatur (6)
- Therapeutic Drug Monitoring (6)
- Therapieerfolg (6)
- Thermodynamik (6)
- Thermoregulation (6)
- Tinnitus (6)
- Toleranz (6)
- Tomate (6)
- Top physics (6)
- Transgene Tiere (6)
- Transiente Absorption (6)
- Transkriptom (6)
- Transporter (6)
- Transposon (6)
- Treatment (6)
- Troponin (6)
- Tuberkulose (6)
- Tumortherapie (6)
- UV-VIS-Spektroskopie (6)
- Ultrafast spectroscopy (6)
- Umweltschutz (6)
- Ungleichheit (6)
- Universitätsbibliothek Würzburg (6)
- VSG (6)
- Vaccination (6)
- Valenz <Linguistik> (6)
- Vergleichende politische Wissenschaft (6)
- Verteiltes System (6)
- Virtual Reality (6)
- Virtualisierung (6)
- Virus (6)
- Viskosität (6)
- Wechselwirkung (6)
- Wissen (6)
- Wortschatz (6)
- Wärmeleitfähigkeit (6)
- XPS (6)
- Xenopus laevis (6)
- Zelllinie (6)
- Zellteilung (6)
- Zirkulardichroismus (6)
- acid sphingomyelinase (6)
- actinomycetes (6)
- adenosine (6)
- alignment (6)
- alkaloids (6)
- alternative splicing (6)
- anatomy (6)
- anorexia nervosa (6)
- anthocyanins (6)
- antidepressants (6)
- antimicrobial peptides (6)
- antioxidants (6)
- arthroscopy (6)
- aspergillus fumigatus (6)
- astrocytoma (6)
- auditory (6)
- autoantibody (6)
- autoimmune disease (6)
- bacterial pathogens (6)
- bee (6)
- behavioral conditioning (6)
- biophysics (6)
- biopsy (6)
- bioreactor (6)
- body weight (6)
- boronate esters (6)
- brain tumor (6)
- cancer immunotherapy (6)
- cancer metabolism (6)
- cancer stem cells (6)
- cardiomyocytes (6)
- cardiovascular diseases (6)
- cell (6)
- cell proliferation (6)
- cement (6)
- childhood (6)
- chlamydia (6)
- chondrocytes (6)
- circadian rhythm (6)
- circular dichroism (6)
- climate (6)
- clinical study (6)
- colon cancer (6)
- comet assay (6)
- comorbidity (6)
- competition (6)
- cosmology (6)
- cyclodextrin (6)
- cytokinins (6)
- damage (6)
- deadwood (6)
- democracy (6)
- density functional theory (6)
- dental education (6)
- detoxification (6)
- disability (6)
- down regulation (6)
- drosophila melanogaster (6)
- drug discovery (6)
- drugs (6)
- eHealth (6)
- eating disorders (6)
- efficiency (6)
- ejection fraction (6)
- encephalitis (6)
- endovascular (6)
- energy metabolism (6)
- engagement (6)
- estrogens (6)
- ethanol (6)
- experience (6)
- exposure (6)
- eye movements (6)
- eye tracking (6)
- eyes (6)
- factor XII (6)
- fear generalization (6)
- fibromyalgia (6)
- fish (6)
- fluorescence resonance energy transfer (6)
- fluorine (6)
- follicular lymphoma (6)
- functional magnetic resonance imaging (6)
- gas phase (6)
- geomorphology (6)
- germinal center (6)
- glaucoma surgery (6)
- global warming (6)
- glucocorticoids (6)
- glutamate (6)
- glycoprotein VI (6)
- grazing (6)
- guard cells (6)
- guideline adherence (6)
- heterochromatin (6)
- homeostasis (6)
- homogeneous catalysis (6)
- honeybees (6)
- host-pathogen interaction (6)
- hydroboration (6)
- hyperexpression techniques (6)
- ideomotor theory (6)
- immune cells (6)
- immunity (6)
- impulsivity (6)
- in vitro selection (6)
- incisional hernia (6)
- infarction (6)
- infectious diseases (6)
- influenza (6)
- information (6)
- infrared spectroscopy (6)
- inhibitors (6)
- intraocular pressure (6)
- kidneys (6)
- language (6)
- leishmaniasis (6)
- lesions (6)
- lipids (6)
- localization microscopy (6)
- lung fibrosis (6)
- lysosome (6)
- magnetic properties and materials (6)
- magnetic resonance (6)
- mechanical thrombectomy (6)
- medaka (6)
- medical education (6)
- meningococcal disease (6)
- metabolic syndrome (6)
- miR-21 (6)
- microbiota (6)
- microdialysis (6)
- modelling (6)
- models (6)
- molecular neuroscience (6)
- motor control (6)
- movement disorders (6)
- murine (6)
- muscarinic receptors (6)
- muscle (6)
- mushroom bodies (6)
- myeloma (6)
- naphthylisoquinoline alkaloids (6)
- natural disturbance (6)
- natural products (6)
- nephrotoxicity (6)
- neurobiology (6)
- neurodevelopment (6)
- neuronal differentiation (6)
- nuclear medicine (6)
- octopamine (6)
- oilseed rape (6)
- organization (6)
- osteogenic differentiation (6)
- osteoinduction (6)
- osteosynthesis (6)
- outcomes (6)
- pathways (6)
- periprosthetic infection (6)
- persistence (6)
- phagocytosis (6)
- phenology (6)
- photoluminescence (6)
- phylogenetic trees (6)
- physiology (6)
- plasma membrane (6)
- polarization (6)
- polymerase chain reaction (6)
- polyneuropathy (6)
- polyphenols (6)
- predictors (6)
- protease inhibitors (6)
- protein binding (6)
- protein kinase (6)
- quantum optics (6)
- radical (6)
- radiosensitivity (6)
- repair (6)
- response inhibition (6)
- retinal pigment epithelium (6)
- reward (6)
- risk stratification (6)
- ruthenium (6)
- scale (6)
- school (6)
- semiconductor laser (6)
- semiconductor lasers (6)
- sensitivity (6)
- sensor (6)
- sequence (6)
- sequence alignment (6)
- siRNA (6)
- signaling pathway (6)
- signalling (6)
- skeletal muscle (6)
- skin (6)
- sleeping sickness (6)
- small interfering RNAs (6)
- social attention (6)
- sol-gel (6)
- solar cells (6)
- solubility (6)
- somatic mutations (6)
- spacer (6)
- spectral karyotyping (6)
- sponges (6)
- stability (6)
- states (6)
- stomata (6)
- structural biology (6)
- supersymmetry (6)
- surface (6)
- sustainability (6)
- symptoms (6)
- system (6)
- thermoregulation (6)
- thrombin (6)
- thymoma (6)
- thyroid cancer (6)
- time-resolved spectroscopy (6)
- tissue (6)
- titanium (6)
- tomography (6)
- total synthesis (6)
- training (6)
- transfection (6)
- transition metal (6)
- tumor immunology (6)
- tumor necrosis factor (6)
- uveal melanoma (6)
- valence (6)
- vascularization (6)
- viral infection (6)
- volatile anesthetics (6)
- weight loss (6)
- wild bees (6)
- Überlebenszeit (6)
- 3D cell culture (5)
- 3D-Pulverdruck (5)
- 5-HTTLPR (5)
- ABC-Transporter (5)
- ACE-Hemmer (5)
- ACTH (5)
- AFM (5)
- AI (5)
- AMD (5)
- ATP (5)
- Absorptionsspektroskopie (5)
- Abstimmbarer Laser (5)
- Actin-bindende Proteine (5)
- Adenokarzinom (5)
- Adoleszenz (5)
- Adult (5)
- Aggression (5)
- Agonist (5)
- Aktivierung <Chemie> (5)
- Akustikustumor (5)
- Akzeptanz (5)
- Alkine (5)
- Alkoholismus (5)
- Altersversorgung (5)
- Alzheimer (5)
- Angstsensitivität (5)
- Antigenpräsentation (5)
- Antimikrobieller Wirkstoff (5)
- Antioxidantien (5)
- Aquaporin (5)
- Arbeitsmarkt (5)
- Archaeology (5)
- Arthrodese (5)
- Assoziationsstudie (5)
- Augenheilkunde (5)
- Aurora-A (5)
- Ausstellungskatalog (5)
- Autoantigen (5)
- Autoimmunerkrankung (5)
- Automatisierung (5)
- Axon (5)
- B cell (5)
- B-MYB (5)
- B-cells (5)
- Bcl-2 (5)
- Begabung (5)
- Belastung (5)
- Berechnung (5)
- Beta-1-Rezeptor (5)
- Betriebliche Altersversorgung (5)
- Bewusstsein (5)
- Biofabrication (5)
- Biogenese (5)
- Biologischer Abbau (5)
- Biopsie (5)
- Blei (5)
- Boden (5)
- Bone regeneration (5)
- Borane (5)
- Borate (5)
- Breaking (5)
- Bronzezeit (5)
- Bruschit (5)
- Bruxismus (5)
- C. elegans (5)
- CD-Spektroskopie (5)
- CD8 (5)
- CEACAM1 (5)
- CIDP (5)
- CSF (5)
- CVID (5)
- CYR61 (5)
- Cadmiumselenid (5)
- Camponotus (5)
- Caspasen (5)
- Ceramide (5)
- Channelrhodopsin (5)
- Chemotherapy (5)
- Chiralität (5)
- Cholesterin (5)
- Chronisch thromboembolische pulmonale Hypertonie (5)
- Chronischer Schmerz (5)
- Churriter (5)
- Climate change (5)
- Cochlea (5)
- Cognitive control (5)
- Coherent Multidimensional Spectroscopy (5)
- Colitis ulcerosa (5)
- Computer Center (5)
- Crohn-Krankheit (5)
- CubeSat (5)
- Cuneiform text (5)
- Cystein (5)
- Cytokines (5)
- DNA replication (5)
- DNA-Reparatur (5)
- Dark Matter (5)
- Degeneration (5)
- Deletion (5)
- Demökologie (5)
- Development (5)
- Diabetes mellitus Typ 1 (5)
- Diels-Alder reactions (5)
- Differentialgleichung (5)
- Dimension 3 (5)
- Distale Radiusfraktur (5)
- Drahtloses Sensorsystem (5)
- Dystonie (5)
- Earth Observation (5)
- Electron microscopy (5)
- Electrospinning (5)
- Elektronendichte (5)
- Elektronengas (5)
- Embryonale Stammzelle (5)
- Emotionen (5)
- Encephalitis (5)
- Energietransfer (5)
- Energy (5)
- Entscheidung (5)
- Entscheidungsunterstützung (5)
- Entwicklungsbiologie (5)
- Enzyme replacement therapy (5)
- Epigenetic (5)
- Erythropoietin (5)
- Essverhalten (5)
- European Union (5)
- Expositionstherapie (5)
- Extinktion (5)
- FACS (5)
- FGF (5)
- FGFR (5)
- Fahrerassistenzsystem (5)
- Fermionensystem (5)
- Festkörpertheorie (5)
- Film (5)
- Fließregulierung (5)
- Fluoreszenzkorrelationsspektroskopie (5)
- Foamyviren (5)
- Fragmentierung (5)
- Frühdiagnostik (5)
- Funde (5)
- Furchtgeneralisierung (5)
- Furchtkonditionierung (5)
- G-protein (5)
- GDNF (5)
- GFAP (5)
- GWAS (5)
- Gastrointestinaltrakt (5)
- Geburtshilfe (5)
- Gefäßprothese (5)
- Gemeinde (5)
- Gen notch (5)
- Gene (5)
- Gene-expression (5)
- Gentransfer (5)
- Gephyrin (5)
- German as a foreign language (5)
- Gewebedoppler (5)
- Gewebekultur (5)
- Glas (5)
- Glutamattransporter (5)
- Glycinrezeptor (5)
- Governance (5)
- Graph (5)
- Graphenzeichnen (5)
- GvHD (5)
- HLA-G (5)
- HMG-Proteine (5)
- HRV (5)
- HUWE1 (5)
- Halbleiterschicht (5)
- Halbsandwich-Verbindungen (5)
- Hals-Nasen-Ohren-Tumor (5)
- Handelsforschung (5)
- Handlung (5)
- Heilpflanzen (5)
- Hepatitis B (5)
- Herzschrittmacher (5)
- Hittites (5)
- Hochauflösendes Verfahren (5)
- Homogene Katalyse (5)
- Hormone (5)
- Humorale Immunität (5)
- Hydroxylapatit (5)
- Hämatopoese (5)
- Hörscreening (5)
- ICD (5)
- IL-2 (5)
- IMRT (5)
- Imatinib (5)
- Immunität <Medizin> (5)
- Immunoassay (5)
- Immunobiologie (5)
- Impurity Profiling (5)
- In-vitro-Kultur (5)
- In-vivo (5)
- InSAR (5)
- Influenza (5)
- Insulin-like Growth Factor I (5)
- Interleukin 2 (5)
- Internationalisierung (5)
- Invasive Aspergillose (5)
- Jasmonsäure (5)
- Judit <Buch> (5)
- Kardiovaskuläres System (5)
- Karl Leonhard (5)
- Kartierung (5)
- Keimzentrum (5)
- Kernproteine (5)
- Kerntransport (5)
- Kidney (5)
- Kinase (5)
- Kinder und Jugendliche (5)
- Kinder- und Jugendpsychiatrie (5)
- Kinematik (5)
- Kirche (5)
- Klassische Konditionierung (5)
- Klinisches Experiment (5)
- Knorpelzelle (5)
- Kombinationstherapie (5)
- Kombinatorische Synthese (5)
- Komorbidität (5)
- Komorbiditäten (5)
- Komplement (5)
- Komödie (5)
- Kondensierte Materie (5)
- Konsumentenverhalten (5)
- Kontrollierte Wirkstofffreisetzung (5)
- Kontrollierte klinische Studie (5)
- Kosmologie (5)
- Krankheit (5)
- Krebsforschung (5)
- Kunsterziehung (5)
- Käfer (5)
- Körperliche Leistungsfähigkeit (5)
- LL-37 (5)
- Laktat (5)
- Latenz (5)
- Lautheit (5)
- Learner autonomy (5)
- Lebensmittel (5)
- Leberzellkrebs (5)
- Leberzirrhose (5)
- Lehrerfortbildung (5)
- Lehrmittel (5)
- Leishmania major (5)
- Leistungsdiagnostik (5)
- Lesen (5)
- Lewis-Base (5)
- Linienbandkeramik (5)
- Listeria (5)
- Lung (5)
- Lymphknoten (5)
- MAGIC-Teleskop (5)
- Macaranga (5)
- Magenkrebs (5)
- Magnetischer Halbleiter (5)
- Malaria tropica (5)
- Management (5)
- Manganverbindungen (5)
- Mangelernährung (5)
- Mathematische Modellierung (5)
- Medizingeschichte (5)
- Medulloblastoma (5)
- Meerschweinchen (5)
- Membrantransport (5)
- Messung (5)
- Metabolom (5)
- Metabolomik (5)
- Metagenom (5)
- Metallocenophane (5)
- Metallorganische Polymere (5)
- Metallorganische Verbindungen (5)
- Metallorganisches Netzwerk (5)
- Microtubules (5)
- Migräne (5)
- Mikrokern (5)
- Mikroorganismus (5)
- Mikrotubulus (5)
- Minimal-invasive Chirurgie (5)
- Minoische Kultur (5)
- Mitomycin C (5)
- Monetary Policy (5)
- Monoschicht (5)
- Morphology (5)
- Mouse (5)
- Mozart (5)
- Multiple Sclerosis (5)
- Multiproteinkomplex (5)
- Muskeldystrophie (5)
- Muskelzelle (5)
- Mutationen (5)
- Mutualismus (5)
- Myelom (5)
- Mädchen (5)
- NASH (5)
- NEXAFS (5)
- NF-AT (5)
- NF-KAPPA-B (5)
- NF-kappaB (5)
- NFκB (5)
- NGA (5)
- NLO computations (5)
- NPY (5)
- Nachkriegszeit (5)
- Nahfeldoptik (5)
- Nahinfrarotspektroskopie (5)
- Namibia <Nordwest> (5)
- Nanometerbereich (5)
- Nanooptik (5)
- Nanoröhre (5)
- Narbenhernie (5)
- Narkose (5)
- Natriumkanal (5)
- Natural Products (5)
- Naturschutz (5)
- Nebennierenrinde (5)
- Nebenschilddrüse (5)
- Neisseria (5)
- Nekrose (5)
- Nervenfaser (5)
- Neurogenetik (5)
- Neuronales Netz (5)
- Neuropathy (5)
- Neuropeptide (5)
- Neurophysiologie (5)
- Neuroprotektion (5)
- Neurowissenschaften (5)
- Nichtlineare Spektroskopie (5)
- Niederdimensionaler Halbleiter (5)
- Niederschlag (5)
- Notenbank (5)
- OCD (5)
- OCT (5)
- Oberflächenfunktionalisierung (5)
- Oberflächenverstärkter Raman-Effekt (5)
- Occludin (5)
- Oligomerisation (5)
- Opiatrezeptor (5)
- Optimization (5)
- Optische Fernerkundung (5)
- Orientierung (5)
- Ovarialkarzinom (5)
- P4 (5)
- PALM (5)
- PDE (5)
- PDXP (5)
- PMMA (5)
- Pandemie (5)
- Pankreas (5)
- Parallele Bildgebung (5)
- Patientenverfügung (5)
- Patientenzufriedenheit (5)
- Pentakoordination (5)
- Periphere Stammzellentransplantation (5)
- Permeation (5)
- Perovskite (5)
- Perylenbisdicarboximide <Perylen-3,4:9,10-bis(dicarboximide)> (5)
- Perylendianhydrid (5)
- Pflanzenfressende Insekten (5)
- Pharmazie (5)
- Phasenvariation (5)
- Philosophie (5)
- Phosphatase (5)
- Phosphatasen (5)
- Phosphine (5)
- Photochemische Reaktion (5)
- Photochemistry (5)
- Photoemission (5)
- Phytoprostane (5)
- Pilze (5)
- Piperidinderivate (5)
- PolSAR (5)
- Polymer (5)
- Polyphenole (5)
- Polysomnographie (5)
- Portugiesisch (5)
- Positronen-Emissions-Tomographie (5)
- Posttranskriptionelle Regulation (5)
- Prednisolon (5)
- PrfA (5)
- Primaten (5)
- Projektarbeit (5)
- Propaganda (5)
- Protease (5)
- Protein-Protein-Wechselwirkung (5)
- Proteinkinase A (5)
- Proteinkinasen (5)
- Prothese (5)
- Prädiktor (5)
- Prädiktoren (5)
- Prävalenz (5)
- Punktmutation (5)
- Pyrolyse (5)
- Pädagogische Psychologie (5)
- Qualitative Inhaltsanalyse (5)
- Qualitätsmanagement (5)
- Quantenkontrolle (5)
- Quantenspinsystem (5)
- Quantitative anatomy (5)
- RADS (5)
- RFID (5)
- RS-Virus (5)
- RS1 (5)
- RYGB (5)
- Radioiodtherapie (5)
- Randschluss (5)
- Rapid Prototyping (5)
- RapidEye (5)
- Rauchen (5)
- Raumordnung (5)
- Reaktionskinetik (5)
- Reaktionsmechanismus (5)
- Regression (5)
- Regulatorische T-Zellen (5)
- Reinheitsanalytik (5)
- Reproduktionsmedizin (5)
- Reverse Transkriptase-Polymerase-Kettenreaktion (5)
- Ribavirin (5)
- Risikoanalyse (5)
- Risk (5)
- Roboter (5)
- Rutheniumkomplexe (5)
- Röntgenbeugung (5)
- Röntgenstrahlung (5)
- SLAC1 (5)
- STEC (5)
- Sagittalnahtsynostose (5)
- Salzstress (5)
- Savanne (5)
- Scaffold (5)
- Schlafkrankheit (5)
- Schreiben (5)
- Schulbuch (5)
- Schwamm (5)
- Sekundarstufe (5)
- Selbst (5)
- Selektivität (5)
- Semitistik (5)
- Senile Makuladegeneration (5)
- Septuaginta (5)
- Sequenzanalyse (5)
- Signal transduction (5)
- Silylen (5)
- Skelettmuskel (5)
- Skin (5)
- Software Defined Networking (5)
- Software Engineering (5)
- Sonderpädagogik / Wörterbuch (5)
- Sonderpädagogik / Zeitschrift (5)
- Sonographie (5)
- Spaltöffnung (5)
- Spectroscopy (5)
- Speichel (5)
- Spermatogenese (5)
- Spezifität (5)
- Spin flip (5)
- Sport (5)
- Spred-Proteine (5)
- Stability (5)
- Stadtentwicklung (5)
- Standardmodell <Elementarteilchenphysik> (5)
- Standortplanung (5)
- Standortpolitik (5)
- Staphylococcus epidermidis (5)
- Startle (5)
- Stem cells (5)
- Stereochemie (5)
- Sterilität (5)
- Stimulation (5)
- Strahlungstransport (5)
- Strain (5)
- Structural Biology (5)
- Struktur-Aktivitäts-Beziehung (5)
- Studium (5)
- Supraleiter (5)
- Symmetrie (5)
- Synapsin (5)
- Synaptonemalkomplex (5)
- Synthesediamant (5)
- Systemtheorie (5)
- T-cell (5)
- TKI (5)
- TLR4 (5)
- TMJ (5)
- TNF-α (5)
- TP53 (5)
- Taxonomie (5)
- TerraSAR-X (5)
- Textlinguistik (5)
- Theoretical Chemistry (5)
- Theoretische Informatik (5)
- Theoretische Physik (5)
- Thrombozytenaggregation (5)
- Titandioxid (5)
- Top quark (5)
- Totalendoprothese (5)
- Toxin (5)
- Tragödie (5)
- Transformation (5)
- Transportprozess (5)
- Triarylamine (5)
- Tumorsuppressorgen (5)
- Ugarit (5)
- Ultraschallkardiographie (5)
- Umwelt (5)
- Unterkiefer (5)
- Urämie (5)
- VE-Cadherin (5)
- Vaccine (5)
- Vaccinia virus (5)
- Validation (5)
- Vaskularisierung (5)
- Venlafaxin (5)
- Ventilation (5)
- Verarbeitungsflüssigkeit (5)
- Verbundfestigkeit (5)
- Visualization (5)
- Visuelle Wahrnehmung (5)
- Wachstumsfaktor (5)
- Wasser (5)
- Wasserstoffbrückenbindung (5)
- Wettbewerb (5)
- Wirtschaft (5)
- Wortbildung (5)
- Würzburger Hörfeld (5)
- XMCD (5)
- XRD (5)
- Yersinia enterocolitica (5)
- Zea mays (5)
- Zebrafisch (5)
- Zebrafish (5)
- Zink (5)
- Zucker (5)
- accuracy (5)
- acoustic neuroma (5)
- acute heart failure (5)
- adalimumab (5)
- adenocarcinoma (5)
- adipocytes (5)
- adrenal (5)
- adrenal insufficiency (5)
- akute Herzinsuffizienz (5)
- alcohol (5)
- algorithms (5)
- allosteric modulation (5)
- amino acid (5)
- amplification (5)
- angiography (5)
- ankle (5)
- annotation (5)
- antibiotic (5)
- anticipation (5)
- anticoagulation (5)
- antigenic variation (5)
- antimicrobial stewardship (5)
- antimicrobials (5)
- aorta (5)
- arousal (5)
- arrhythmia (5)
- arthritis (5)
- augmented reality (5)
- autism (5)
- back pain (5)
- balance (5)
- bioink (5)
- bioisosterism (5)
- biokinetics (5)
- biological locomotion (5)
- bismuth (5)
- blood plasma (5)
- blood-brain-barrier (5)
- bond activation (5)
- brain computer interface (5)
- bronchopulmonary dysplasia (5)
- burden (5)
- caloric restriction (5)
- candidate gene (5)
- carcinomas (5)
- cardiac (5)
- cardioprotection (5)
- cardiovascular (5)
- cardiovascular events (5)
- cardiovascular risk factors (5)
- cartilage regeneration (5)
- cell cultures (5)
- cell cycle and cell division (5)
- cell differentiation (5)
- ceramides (5)
- cerebral ischemia (5)
- chemical communication (5)
- chemical ecology (5)
- chemokine (5)
- child (5)
- chirality (5)
- ciliary neurotrophic factor (5)
- cisplatin (5)
- clinical trials (5)
- cloning (5)
- collagens (5)
- complement (5)
- condensed matter physics (5)
- congestive heart failure (5)
- contrast agent (5)
- coronavirus (5)
- correction (5)
- correlation (5)
- costimulation (5)
- creatine kinase (5)
- critical illness (5)
- cross-coupling (5)
- demyelination (5)
- dendritische Zelle (5)
- dentate gyrus (5)
- dexamethasone (5)
- diagnostic markers (5)
- diborene (5)
- discourse analysis (5)
- docking (5)
- driving simulation (5)
- drug repurposing (5)
- dyes/pigments (5)
- ecological momentary assessment (5)
- elderly (5)
- electrochemistry (5)
- electrospinning (5)
- embryo (5)
- emission (5)
- empathy (5)
- encapsulation (5)
- end-stage renal disease (5)
- endoscopy (5)
- endothelial dysfunction (5)
- endothelial progenitor cells (5)
- endurance training (5)
- environment (5)
- enzyme-linked immunoassays (5)
- epithelial-mesenchymal transition (5)
- erythropoietin (5)
- estrogen (5)
- excitons (5)
- experimental design (5)
- eye-tracking (5)
- fatty acids (5)
- fibroblasts (5)
- flagella (5)
- food security (5)
- food-cues (5)
- forensic neuropathology (5)
- fusion (5)
- gait (5)
- galactomannan (5)
- gametogenesis (5)
- gender differences (5)
- gene targeting (5)
- gene-expression (5)
- generation (5)
- genotype (5)
- giant cell arteritis (5)
- glycolysis (5)
- gp130 (5)
- graph drawing (5)
- hearing loss (5)
- heart rate variability (5)
- heat transfer (5)
- hematopoietic stem cells (5)
- history (5)
- hospitalization (5)
- human-computer interaction (5)
- hyperekplexia (5)
- hypertrophy (5)
- immunization (5)
- implementation (5)
- in situ hybridization (5)
- in vitro model (5)
- inflammasome (5)
- inflammatory pain (5)
- innovation (5)
- insulin resistance (5)
- integration (5)
- integrin (5)
- intestinal epithelial barrier (5)
- intestine (5)
- ion channel (5)
- iron oxide nanoparticles (5)
- irradiation (5)
- jasmonates (5)
- keratinocytes (5)
- kinematics (5)
- knee arthroplasty (5)
- lactate (5)
- land cover (5)
- language acquisition (5)
- larvae (5)
- late enhancement (5)
- lipid rafts (5)
- liquid crystals (5)
- long-term outcome (5)
- longitudinal study (5)
- loss of heterozygosity (5)
- loudness (5)
- magnesium phosphate cement (5)
- magnetism (5)
- masked priming (5)
- mast cells (5)
- matrix metalloproteinases (5)
- medical rehabilitation (5)
- megakaryocyte (5)
- mental disorders (5)
- mesenchymal stem cell (5)
- metabarcoding (5)
- microglomeruli (5)
- microsatellite instability (5)
- middle cerebral artery occlusion (5)
- migraine (5)
- migrants (5)
- mineralization (5)
- minimal invasiv (5)
- mobility (5)
- molecular medicine (5)
- morbidity (5)
- motoneurons (5)
- movement ecology (5)
- music (5)
- mycotoxin (5)
- nano (5)
- nanostructures (5)
- natural killer cells (5)
- nature conservation (5)
- neisseria meningitidis (5)
- nephroblastoma (5)
- network (5)
- neuroanatomy (5)
- neuroethology (5)
- neuromelanin (5)
- neuronal plasticity (5)
- neuropeptides (5)
- neuropsychiatric disorders (5)
- neurotrophic factor (5)
- neutrophil (5)
- newborn hearing screening (5)
- nickel (5)
- nitric oxide synthase (5)
- norepinephrine (5)
- nucleolus (5)
- nutrients (5)
- object detection (5)
- oncogenes (5)
- oncolysis (5)
- opioid receptors (5)
- organic semiconductor (5)
- organic synthesis (5)
- organische Halbleiter (5)
- osteoblasts (5)
- osteogenesis (5)
- paraganglioma (5)
- parasitic diseases (5)
- parathyroid hormone (5)
- patch-clamp (5)
- pathogenicity (5)
- peptide (5)
- perception and action (5)
- pharmacokinetic (5)
- phase variation (5)
- phenotypic plasticity (5)
- pheochromocytoma (5)
- photophysics (5)
- phylogenetic analysis (5)
- plant-insect interactions (5)
- plants (5)
- plasma cells (5)
- polyomavirus (5)
- population pharmacokinetics (5)
- porin (5)
- power (5)
- preclinical research (5)
- preterm (5)
- prognostic marker (5)
- promoter (5)
- prostate-specific membrane antigen (5)
- protein domains (5)
- protein expression (5)
- psychiatry (5)
- psychological distress (5)
- pulmonary embolism (5)
- pyrolysis (5)
- quality (5)
- qubit (5)
- radial (5)
- reactive intermediates (5)
- receptor tyrosine kinase (5)
- recombinant proteins (5)
- refractory (5)
- regeneration (5)
- regression analysis (5)
- renal cell carcinoma (5)
- renal function (5)
- replacement (5)
- resin (5)
- resolution (5)
- resveratrol (5)
- retinoic acid (5)
- retrospective (5)
- revision (5)
- ring-opening polymerization (5)
- rotator cuff tear (5)
- saliva (5)
- sarcopenia (5)
- seasonality (5)
- self (5)
- self-organization (5)
- sevoflurane (5)
- sexual selection (5)
- shock (5)
- single-crystal X-ray study (5)
- skin punch biopsy (5)
- soil (5)
- somatostatin receptor (5)
- soziale Insekten (5)
- soziale Kompetenz (5)
- specificity (5)
- spider phobia (5)
- spiders (5)
- spin (5)
- spinal cord (5)
- splicing (5)
- startle disease (5)
- stem-cell transplantation (5)
- strain (5)
- stromal cells (5)
- structural elucidation (5)
- structure-activity relationships (5)
- subarachnoid hemorrhage (5)
- subtypes (5)
- sucrose (5)
- sudden cardiac death (5)
- super-resolution (5)
- surfactants (5)
- sympathetic nervous system (5)
- synaptic proteins (5)
- synaptic vesicles (5)
- synchrotron radiation (5)
- systematic literature review (5)
- teaching (5)
- teeth (5)
- telemedicine (5)
- testosterone (5)
- text comprehension (5)
- thrombolysis (5)
- tight junction (5)
- transcranial direct current stimulation (5)
- transformation (5)
- transgenic mice (5)
- transporter (5)
- transverse momentum (5)
- tremor (5)
- tsetse fly (5)
- tuberculosis (5)
- tumour (5)
- ubiquitination (5)
- uremic toxins (5)
- urine (5)
- vancomycin (5)
- variants (5)
- vasculitis (5)
- ventilation (5)
- violence (5)
- virtual screening (5)
- virulence factors (5)
- visualization (5)
- voluntary service (5)
- well-being (5)
- winter wheat (5)
- wissenschaftlicher Nachwuchs (5)
- women (5)
- xx (5)
- zwitterionic (5)
- Ägäische Kultur (5)
- Ökonometrie (5)
- Überlebensrate (5)
- γ-H2AX (5)
- --- (4)
- 3D Printing (4)
- 3D reconstruction (4)
- 5-Fluorouracil (4)
- ACL (4)
- AGN (4)
- ANCA (4)
- APOBEC3G (4)
- ASSR (4)
- AVHRR (4)
- Ablösung (4)
- Abschlussprüfer (4)
- Abwehr (4)
- Accounting (4)
- Acyrthosiphon pisum (4)
- AdS-CFT Correspondence (4)
- AdS/CFT (4)
- AdS/CFT correspondence (4)
- Addukt (4)
- Adenoviren (4)
- Adenylate cyclase (4)
- Adjuvans (4)
- Adrenocortical Carcinoma (4)
- Adsorbat (4)
- Aerogel (4)
- Ag(111) (4)
- Agoraphobie (4)
- Agrobacterium tumefaciens (4)
- Akromioklavikulargelenk (4)
- Aktionsforschung (4)
- Aktive Zone (4)
- Alkalische Phosphatase (4)
- Alkoholabhängigkeit (4)
- Alternative Medizin (4)
- Alterung (4)
- Altes Testament (4)
- Aluminiumarsenid (4)
- Alveoläre Echinokokkose (4)
- Alzheimers disease (4)
- Ameise (4)
- Amplifikation (4)
- Analgesie (4)
- Analysis (4)
- Anandamid (4)
- Anaphylaxis (4)
- Ancistrocladus (4)
- Aneuploidie (4)
- Aneurysma (4)
- Anfangsunterricht (4)
- Angewandte Psychologie (4)
- Angiogenesis (4)
- Animal model (4)
- Anionenkanal (4)
- Annotation (4)
- Antarctica (4)
- Antennallobus (4)
- Anthropogene Klimaänderung (4)
- Anthropogener Einfluss (4)
- Antiangiogenese (4)
- Antidepressiva (4)
- Antigen CD4 (4)
- Antigen CD44 (4)
- Antigen CD95 (4)
- Antike (4)
- Antimykotikum (4)
- Antioxidans (4)
- Ants (4)
- Anura (4)
- Appendizitis (4)
- Approximationsalgorithmus (4)
- Aroma (4)
- Assoziation (4)
- Astrozytom (4)
- Atemwegsinfektion (4)
- Atlas detector (4)
- Audit Quality (4)
- Augmented Reality (4)
- Autonomie (4)
- Autophagy (4)
- Avidität (4)
- Aziridine (4)
- B chromosomes (4)
- B lymphocytes (4)
- B-Lymphozyten (4)
- B-lymphocytes (4)
- BCG (4)
- BERAphon® (4)
- BMD (4)
- BRET (4)
- Bacillus subtilis (4)
- Bank (4)
- Barth syndrome (4)
- Basaliom (4)
- Bauchfellentzündung (4)
- Begrenzte Staatlichkeit (4)
- Behavior (4)
- Beschaffung (4)
- Bestäubung (4)
- Betriebswirtschaftslehre (4)
- Bevacizumab (4)
- Bewegungssteuerung (4)
- Bienen <Familie> (4)
- Bilanzpolitik (4)
- Bildanalyse (4)
- Bilderzeugung (4)
- Biofilmbildung (4)
- Biophysik (4)
- Bioreaktor (4)
- Bipolar disorder (4)
- Biradikale (4)
- Bismut (4)
- Bisphosphonate (4)
- Blasenkrebs (4)
- Blattkäfer (4)
- Blutgefäß (4)
- Blutspiegel (4)
- Bodenerosion (4)
- Borneo (4)
- Borrelia (4)
- Bortezomib (4)
- Borylation (4)
- Borylen (4)
- Borylgruppe (4)
- Borylkomplexe (4)
- Boson (4)
- Breast cancer (4)
- Brief (4)
- Burkholderia pseudomallei (4)
- Bypass (4)
- Bypassoperation (4)
- C-C coupling (4)
- C-MYC (4)
- CAPM (4)
- CCI (4)
- CD150 (4)
- CD28 Superagonist (4)
- CD44 (4)
- CMR (4)
- CNV (4)
- CPT (4)
- CRP (4)
- CT angiography (4)
- CTLA-4 (4)
- Cancer genetics (4)
- Cannabinoide (4)
- Capital-Asset-Pricing-Modell (4)
- Carben (4)
- Carcinogenesis (4)
- Carotisstenose (4)
- Catecholamine (4)
- Cell culture (4)
- Central Asia (4)
- Cephalometry (4)
- Channelrhodopsin-2 (4)
- Charcot-Marie-Syndrom (4)
- Charged Aerosol Detection (4)
- Chemische Reinheit (4)
- Chemische Ökologie (4)
- Chemistry (4)
- Chemometrie (4)
- Chirality (4)
- Chloroquin (4)
- Chorioamnionitis (4)
- Chromosomenaberration (4)
- Climate Change (4)
- Clopidogrel (4)
- Cluster-Analyse (4)
- Cognition (4)
- Computerunterstütztes Lernen (4)
- Conditioning (4)
- Corporate Governance (4)
- Corpus amygdaloideum (4)
- Costa Rica (4)
- Craniosynostosis (4)
- Crowdsourcing (4)
- Cushing-Syndrom (4)
- Cushing’s syndrome (4)
- Cyanoborate (4)
- Cyclodextrin (4)
- Cyclophane (4)
- Cyclovoltammetrie (4)
- DCF (4)
- DCM (4)
- DFT calculations (4)
- DHEAS (4)
- DNA damage response (4)
- DNA transcription (4)
- DNA-Replikation (4)
- DNA-Schaden (4)
- DNA-binding proteins (4)
- DNS-Bindung (4)
- DRG (4)
- Darmflora (4)
- Darmkrebs (4)
- Dasatinib (4)
- Demokratie (4)
- Dendritic cell (4)
- Dentalkeramik (4)
- Design (4)
- Desmosom (4)
- Dexamethason (4)
- Diabetische Polyneuropathie (4)
- Diagnosis (4)
- Diborane(4) (4)
- Dictyostelium discoideum (4)
- Dienstgüte (4)
- Differentiation (4)
- Diffusions-MRT (4)
- Diffusionsverfahren <Halbleitertechnologie> (4)
- Digital Storytelling (4)
- Dimension 2 (4)
- Dimere (4)
- Dionaea muscipula (4)
- Dipolare Cycloaddition (4)
- Distributions (4)
- Diversity (4)
- Docetaxel (4)
- Doppelbindung (4)
- Drama (4)
- Duftstoff (4)
- Dunkle Materie (4)
- Duplikation (4)
- Dynamics (4)
- E. coli Nissle 1917 (4)
- ECG (4)
- EGF (4)
- EKG (4)
- EPR (4)
- Echtzeit (4)
- Effizienz (4)
- Eisenkomplexe (4)
- Eisenoxide (4)
- Electronic Commerce (4)
- Electroweak interaction (4)
- Elektrocochleographie (4)
- Elektromyographie (4)
- Elektronenspektroskopie (4)
- Elektronentransport (4)
- Elektrospinnen (4)
- Elliptische Differentialgleichung (4)
- Emotionserkennung (4)
- Endoprothese (4)
- Endosymbiont (4)
- Endothelbarriere (4)
- Endotheldysfunktion (4)
- Endothelium (4)
- Enrichement (4)
- Entstehung (4)
- Enzymersatztherapie (4)
- Ependymom (4)
- Epigenetics (4)
- Epitaxie (4)
- Epitaxy (4)
- Ereigniskorrelierte Potentiale (4)
- Erfahrung (4)
- Erhebungsinstrumente (4)
- Erneuerbare Energien (4)
- Erratum (4)
- Erwachsenenbildung (4)
- Erzählen (4)
- Essgewohnheit (4)
- Estradiol (4)
- Ethanol (4)
- Ethnografie (4)
- Euler equations (4)
- Europäische Zentralbank (4)
- Excitons (4)
- Expansion Microscopy (4)
- Extrakt (4)
- Extremwerttheorie (4)
- FDG (4)
- FKBP5 (4)
- FMRI (4)
- FSHD (4)
- Fahren (4)
- Fahrsimulation (4)
- Fake News (4)
- Fazialisparese (4)
- Fear (4)
- Feldeffekttransistor (4)
- Feminismus (4)
- Fertilität (4)
- Fettleber (4)
- Fettsäurestoffwechsel (4)
- Fettzelle (4)
- Fibroblasts (4)
- Finanzkrise (4)
- First Responder (4)
- Fließregulierungsmittel (4)
- Fluorescence Microscopy (4)
- Foamyvirus (4)
- Follikuläres Lymphom (4)
- Fortpflanzungsverhalten (4)
- Fotokatalyse (4)
- Foxp3 (4)
- Friedrich (4)
- Frühe Neuzeit (4)
- Fullerene (4)
- Funktionswerkstoff (4)
- G protein-coupled receptors (4)
- G proteins (4)
- G-Protein gekoppelte Rezeptor (4)
- G-Protein gekoppelter Rezeptor (4)
- GC-A (4)
- GVHD (4)
- Galliumarsenid-Bauelement (4)
- Galliumarsenidlaser (4)
- Gasionisationsdetektor (4)
- Gedächtnisbildung (4)
- Geflüchtete (4)
- Geisteswissenschaften (4)
- Geißel <Biologie> (4)
- Gelatine (4)
- Gelingensbedingungen (4)
- Gene regulation (4)
- Generalisierung (4)
- Genomschaden (4)
- Geobotanik ; Pflanzengeographie (4)
- Geophysik (4)
- Gesichtsschmerz (4)
- Gesprochene Sprache (4)
- Gesundheitsförderung (4)
- Gesundheitswesen (4)
- Glatte Muskulatur (4)
- Glioma (4)
- Glucocorticosteroidrezeptor (4)
- Glucosestoffwechsel (4)
- Glutamatrezeptor (4)
- Glutamin (4)
- Glutathion (4)
- Gram-positive bacteria (4)
- Graphene (4)
- Griechenland <Altertum> (4)
- Grundwasserneubildung (4)
- Grün fluoreszierendes Protein (4)
- Guanidinderivate (4)
- Gynäkologie (4)
- HFmrEF (4)
- HFpEF (4)
- HSM-sentence-test (4)
- Haftung (4)
- Halbleiterphysik (4)
- Hall, Stuart (4)
- Halothan (4)
- Handchirurgie (4)
- Handgelenk (4)
- Harnblasenkarzinom (4)
- Hautkrebs (4)
- Helicasen (4)
- Helicobacter (4)
- Hepatozelluläres Karzinom (4)
- Herstellung (4)
- Herzfunktion (4)
- Heterocyclen (4)
- Heubacillus (4)
- Hieracium (4)
- Hierarchy (4)
- Higgs (4)
- Hirnödem (4)
- Histone (4)
- Histopathologie (4)
- Hitzestress (4)
- Hochschule (4)
- Hochtemperatursupraleitung (4)
- Hornhaut (4)
- Hospitalismus <Hygiene> (4)
- Hsp90 (4)
- Hybridpolymer (4)
- Hybridpolymere (4)
- Hydrodynamik (4)
- Hydrolyse (4)
- Hyperaldosteronismus (4)
- Hypertrophische Herzmuskelkrankheit (4)
- Hyponatriämie (4)
- Hypoparathyreoidismus (4)
- Hypophosphatasia (4)
- Hämodynamik (4)
- Hämophilie A (4)
- Höhengradient (4)
- Höherkoordination (4)
- Hörstörung (4)
- Hörtest (4)
- Hüfte (4)
- Hüftendoprothetik (4)
- ICSI (4)
- IL-6 (4)
- Identifizierung (4)
- Illustration (4)
- Image Processing (4)
- Immunohistochemistry (4)
- Immunstimulation (4)
- Implantierbarer Kardioverter-Defibrillator (4)
- Inanspruchnahme (4)
- Infektionskrankheit (4)
- Informationskompetenz (4)
- Infrarot (4)
- Inhalation (4)
- Innate immunity (4)
- Insekt (4)
- Instabilität (4)
- Interaktionen (4)
- Interkulturelles Lernen (4)
- Interleukin 1-beta (4)
- Interleukin 13 (4)
- Interleukin 17 (4)
- Interleukin 8 (4)
- Internationalität (4)
- Internet der Dinge (4)
- Internet of Things (4)
- Invertase (4)
- Ionic Liquids (4)
- Ionisierende Strahlung (4)
- Iridiumkomplexe (4)
- Ischämische Präkonditionierung (4)
- Isolation (4)
- JIA (4)
- Japan (4)
- Judith <Book> (4)
- Jura (4)
- Jura <Geologie> (4)
- Kalium (4)
- Kalorimetrie (4)
- Karoo (4)
- Karst (4)
- KasA (4)
- Katalog (4)
- Kaufverhalten (4)
- Kilimandscharo (4)
- Kindergarten (4)
- Kinderpsychiatrie (4)
- Kindesalter (4)
- Klausur (4)
- Klonierung (4)
- Knie (4)
- Knochenbildung (4)
- Knochenkleber (4)
- Knochenzemente (4)
- Knorpelregeneration (4)
- Kognitive Entwicklung (4)
- Kohlenmonoxid (4)
- Kohärente Kontrolle (4)
- Kombinatorik (4)
- Kongestive Herzmuskelkrankheit (4)
- Kontinentales Tiefbohrprogramm (4)
- Koordinationsverbindungen (4)
- Koordinativ ungesättigte Verbindungen (4)
- Korrosion (4)
- Kosten (4)
- Kraftmikroskopie (4)
- Kraniometrie (4)
- Krankheitsverarbeitung (4)
- Krebstherapie (4)
- Kreuzreaktion (4)
- Kristallisation (4)
- Kristallwachstum (4)
- Kupfer (4)
- LC/MS (4)
- LINC complex (4)
- Lactate (4)
- Lagerungsplagiozephalus (4)
- Lamina (4)
- Lamine (4)
- Laminin (4)
- Langerhans cells (4)
- Langfristige Prognose (4)
- Laparoskopie (4)
- Laufzeit (4)
- Lebensalter (4)
- Leberresektion (4)
- Legionärskrankheit (4)
- Leistungssport (4)
- Lenalidomid (4)
- Lepidoptera (4)
- Leptin (4)
- Lernerfolg (4)
- Lernpsychologie (4)
- Lernverhalten (4)
- Leukozyt (4)
- Leukämie (4)
- Lewis acids (4)
- Lewis-Säure (4)
- LiDAR (4)
- Localization (4)
- Lopinavir (4)
- Loss of heterozygosity (4)
- Low-density-Lipoproteine (4)
- Lung cancer (4)
- Lungenembolie (4)
- Lymphogranulomatose (4)
- Lysosom (4)
- MALDI-MS (4)
- MALT (4)
- MCP-1 (4)
- MIBG (4)
- MIZ1 (4)
- MMB (4)
- MMP (4)
- MOLLI (4)
- MPEC (4)
- MPFL (4)
- MR (4)
- MR-Spektroskopie (4)
- MSCs (4)
- MTUS1 (4)
- Macrophages (4)
- Magnetoelektronik (4)
- Magnetohydrodynamik (4)
- Magnetpartikelbildgebung (4)
- Maisstärke (4)
- Malignes Lymphom (4)
- Mammographie (4)
- Massenmedien (4)
- Mechanismus (4)
- Medaka (4)
- Mediendidaktik (4)
- Medienkritik (4)
- Medienpädagogik (4)
- Medizinische Ausbildung (4)
- Mehrkriterielle Optimierung (4)
- Melodie (4)
- Meningococci (4)
- Mensch-Maschine-Interaktion (4)
- Menschenrechte (4)
- Mergers and Acquisitions (4)
- Mesenchymale Stammzelle (4)
- Mesopotamien (4)
- Metabolisches Syndrom (4)
- Metabolit (4)
- Metallkomplexe (4)
- Metallosupramolekulare Chemie (4)
- Metamorphose <Geologie> (4)
- Metformin (4)
- Mexiko (4)
- Microglia (4)
- Mikroarray (4)
- Mikrodialyse (4)
- Mikropartikel (4)
- Mikrosatelliteninstabilität (4)
- Mitotane (4)
- Mittelohr (4)
- Mixed Reality (4)
- Mixed-Methods (4)
- Miz1 (4)
- Mobilität (4)
- Modeling (4)
- Modelling (4)
- Models (4)
- Molekulare Bildgebung (4)
- Molekülphysik (4)
- Molybdän (4)
- Morbidität (4)
- Morbus Alzheimer (4)
- Mortality (4)
- Motorische Endplatte (4)
- Mund-Kiefer-Gesichts-Chirurgie (4)
- Mundhöhlenkarzinom (4)
- Muskel (4)
- Muskelatrophie (4)
- Mustererkennung (4)
- Mutagenese (4)
- Myasthenia gravis (4)
- Mycobacterium tuberculosis (4)
- Myelin (4)
- Mykobakterien (4)
- Mykose (4)
- Mäuse (4)
- NAD (4)
- NET (4)
- NF-kappa-B (4)
- NF-κB (4)
- NFkB (4)
- NFkappaB (4)
- NGF (4)
- NGS (4)
- NMDA-Rezeptor (4)
- NSSI (4)
- NT-proBNP (4)
- NaV1.9 (4)
- Naphthylisochinolin-Alkaloide (4)
- Natur (4)
- Natural products (4)
- Nausea (4)
- Navigation (4)
- Nebenniereninsuffizienz (4)
- Nebenwirkung (4)
- Nebenwirkungen (4)
- Nephrotoxizität (4)
- Nervennetz (4)
- Nestbau (4)
- Netzwerkanalyse (4)
- Neugeborenenhörscreening (4)
- Neurochirurgie (4)
- Neuromelanin (4)
- Neurons (4)
- Neurospora crassa (4)
- Neurotrophic factors (4)
- Neutrophiler Granulozyt (4)
- Nibelungenlied (4)
- Nichtglatte Optimierung (4)
- Nickelverbindungen (4)
- Nicotiana tabacum (4)
- Nitratreduktase (4)
- Nonlinear Dynamics (4)
- Numerisches Modell (4)
- Oberflächenzustand (4)
- Oligomere (4)
- Omarthrose (4)
- Oncostatin M (4)
- Online-Handel (4)
- Onlinehandel (4)
- OpenSpaceAlps (4)
- Operationstechnik (4)
- Optical spectroscopy (4)
- Organic Chemistry (4)
- Organischer Feldeffekttransistor (4)
- Organoid (4)
- Ormocer (4)
- Orthopädie (4)
- Osteoblasten (4)
- Osteoinduction (4)
- Osteopontin (4)
- Osteotomie (4)
- Overlay-Netz (4)
- Oxidative Stress (4)
- Oxidative stress (4)
- PAK (4)
- PBMC (4)
- PEG (4)
- PER (4)
- PI3K (4)
- PKA (4)
- PSA (4)
- PSMA-RADS (4)
- PTCA (4)
- PTCDA (4)
- PTEN (4)
- PTH (4)
- Paläoklima (4)
- Palökologie (4)
- Parallelkorpus (4)
- Partielle Differentialgleichung (4)
- Pathogenitätsinsel (4)
- Pathogens (4)
- Pathway (4)
- Patient (4)
- Patienten (4)
- Patientenschulung (4)
- Pe (4)
- Perception (4)
- Performance (4)
- Peripheres Nervensystem (4)
- Perylene Bisimide (4)
- Pflanzeninhaltsstoff (4)
- Pharmacokinetics (4)
- Phasenumwandlung (4)
- Phenomenology (4)
- Pheromone (4)
- Phobie (4)
- Phosphatidylinositolkinase <Phosphatidylinositol-3-Kinase> (4)
- Phosphoglykolatphosphatase (4)
- Phospholipide (4)
- Phosphor (4)
- Photorezeptor (4)
- Photostrom (4)
- Phthalocyanin (4)
- Physikalische Eigenschaft (4)
- Phänologie (4)
- Phäochromozytom (4)
- Placebo (4)
- Plants (4)
- Plasmon (4)
- Pleuraempyem (4)
- Pollination (4)
- Polyadenylierung (4)
- Polyethylenglykole (4)
- Pontryagin maximum principle (4)
- Prehistory (4)
- Prescriptive Analytics (4)
- Priming (4)
- Prion (4)
- Private Altersversorgung (4)
- Professionalisierung (4)
- Promotor <Genetik> (4)
- Propriozeption (4)
- Prosodie (4)
- Prostaglandin E2 (4)
- Prostata (4)
- Protein-Protein-Interaktion (4)
- Proteinfaltung (4)
- Proteininteraktion (4)
- Proteinkinase B (4)
- Proteinsynthese (4)
- Proteintyrosinphosphatase (4)
- Präparation (4)
- Pseudomonas (4)
- Psychische Gesundheit (4)
- Psychobiologie (4)
- Pulswellengeschwindigkeit (4)
- Punktion (4)
- Punktwolke (4)
- Puppenhandillusion (4)
- Purkinje cells (4)
- Pyridoxalphosphat (4)
- Pyrrolizidinalkaloide (4)
- QSAR (4)
- QoE (4)
- Quadrocopter (4)
- Quality of Life (4)
- Quantendraht (4)
- Quantenfeldtheorie (4)
- Quantenkaskadenlaser (4)
- Quantum information (4)
- RCT (4)
- RIXS (4)
- RNA modification (4)
- RNA-Seq (4)
- RNS-Bindungsproteine (4)
- RSK (4)
- RZUW (4)
- Rachitis (4)
- Radioonkologie (4)
- Randqualität (4)
- Rashba effect (4)
- Raumwahrnehmung (4)
- Recht (4)
- Rechtsmedizin (4)
- Regelung (4)
- Regenwald (4)
- Register (4)
- Registrierung <Bildverarbeitung> (4)
- Regressionsanalyse (4)
- Reifung (4)
- Rekombinantes Protein (4)
- Rekrutierung (4)
- Relaxation (4)
- Relaxationszeit (4)
- Reliabilität (4)
- Remote sensing (4)
- Renormierungsgruppe (4)
- Repräsentation (4)
- Ressourcenmanagement (4)
- Restaurative Zahnmedizin (4)
- Reverse Transkriptase (4)
- Rhabdomyosarkom (4)
- Rheumatismus (4)
- Rheumatologie (4)
- Rho-Proteine (4)
- Robotics (4)
- Romanische Sprachen (4)
- Rotatorenmanschettenruptur (4)
- Roux-en-Y gastric bypass surgery (4)
- Ruthenium complexes (4)
- Röntgen-Kleinwinkelstreuung (4)
- Röntgendiffraktometrie (4)
- SAS <Programm> (4)
- SLC2A3 (4)
- SOAT1 (4)
- SOX9 (4)
- SPRED2 (4)
- SQH method (4)
- Saccharose (4)
- Sahara (4)
- Sahel (4)
- Salmonella Typhimurium (4)
- Salzhydratschmelze (4)
- Sap47 (4)
- Sauerstoff (4)
- Schaf (4)
- Schlaf (4)
- Schnarchen (4)
- Schulklasse (4)
- Schulterendoprothetik (4)
- Schwein (4)
- Schweiz (4)
- Schwere-Fermionen-System (4)
- Schüler (4)
- Score (4)
- Sekundärkrankheit (4)
- Sekundärprävention (4)
- Sekundärstruktur (4)
- Selbstassemblierung (4)
- Selenoproteine (4)
- Sensitivity (4)
- Serotoninstoffwechsel (4)
- Serum (4)
- Sevofluran (4)
- Sex determination (4)
- Signaling (4)
- Silanole (4)
- Silicone (4)
- Silikon (4)
- Simulator (4)
- Sintern (4)
- SnRK1 (4)
- Social Media (4)
- Softwareentwicklung (4)
- Soziale Wahrnehmung (4)
- Sozialphilosophie (4)
- Speicheldrüse (4)
- Spessart (4)
- Sphingolipidstoffwechsel (4)
- Sphingomyelinphosphodiesterase (4)
- Sponges (4)
- Sprachverständnistest (4)
- Staatliche Museen zu Berlin. Antikensammlung (4)
- Stabilisierung (4)
- Standortfaktor (4)
- Staphylococcus epidermis (4)
- Statine (4)
- Stereoselektivität (4)
- Stereotyp (4)
- Steuern (4)
- Stickstoff (4)
- Stimme (4)
- Strategie (4)
- Stratigraphie (4)
- Straßenverkehr (4)
- Stressinkontinenz (4)
- Strukturanalyse (4)
- Störgeräusch (4)
- Supramolekulare Struktur (4)
- Surgery (4)
- Synapsine (4)
- Synaptonemal complex (4)
- Synuclein <alpha-> (4)
- System (4)
- Systematische Übersichtsarbeit (4)
- T Zellen (4)
- T-Zell-Aktivierung (4)
- T-Zell-Lymphom (4)
- TFIIH (4)
- TNAP (4)
- TNF receptor superfamily (4)
- TNFR1 (4)
- Tandem-Massenspektrometrie (4)
- Tandem-Reaktion (4)
- Telekommunikationsnetz (4)
- Temperaturabhängigkeit (4)
- Textsorte (4)
- Th17 (4)
- Theoretische Ökologie (4)
- Theorie (4)
- Theory of Mind (4)
- Thymom (4)
- Tiere (4)
- Transfer (4)
- Transforming Growth Factor (4)
- Transgenic mice (4)
- Transkriptionsfaktoren (4)
- Translation <Genetik> (4)
- Translokation (4)
- Transpiration <Pflanzen> (4)
- Transplantatabstoßung (4)
- Triarylborane (4)
- Trypanosomiasis (4)
- Tubulin (4)
- Tumorerkrankungen (4)
- Typ 1 (4)
- USP28 (4)
- UV/Vis spectroscopy (4)
- Ultraschnelle Photochemie (4)
- Ultraviolett-Photoelektronenspektroskopie (4)
- Umweltrecht (4)
- Unabhängigkeit (4)
- Unlauterer Wettbewerb (4)
- Unternehmenstheorie (4)
- Ureaplasma parvum (4)
- Urheberrecht (4)
- Urin (4)
- Urämietoxine (4)
- VEP (4)
- VMAT (4)
- Vaccinia Virus (4)
- Validität (4)
- Vektor <Genetik> (4)
- Velocity-Map-Imaging (4)
- Verfassungsrecht (4)
- Verhaltensstörung (4)
- Verkapselung (4)
- Verkehrssicherheit (4)
- Verlauf (4)
- Verletzung (4)
- Versorgungsqualität (4)
- Verzeichnis (4)
- Viren (4)
- Vitamin D3 (4)
- Vitamin-D-Mangel (4)
- Volkskunde (4)
- Vorhofflimmern (4)
- Vorläuferzelle (4)
- Völkerrecht (4)
- Wachstumsfaktoren (4)
- Wald (4)
- Wasserhaushalt (4)
- Wasseroxidation (4)
- Wasserstoffperoxid (4)
- Wassertransport (4)
- Weimarer Republik (4)
- Wellenpaket (4)
- Wide-gap-Halbleiter (4)
- William (4)
- Williams, Raymond (4)
- Wirbelsäulenverletzung (4)
- Wirkmechanismus (4)
- Wirkstoff-Rezeptor-Bindung (4)
- Wirkstoffe (4)
- Wirkung (4)
- Wirt (4)
- Wirtschaftsinformatik (4)
- Wirtszelle (4)
- Wissenschaftlicher Nachwuchs (4)
- Wissenschaftssprache (4)
- Wissensrepräsentation (4)
- Wittig-Reaktion (4)
- Wnt (4)
- Wnt-Proteine (4)
- Wolfgang Amadeus (4)
- Wolframkomplexe (4)
- XML (4)
- Xmrk (4)
- Yoga (4)
- Z boson (4)
- Zahnimplantat (4)
- Zeitaufgelöste Spektroskopie (4)
- Zeitauflösung (4)
- Zeitreihe (4)
- Zellkontakt (4)
- Zement (4)
- Zinkoxid (4)
- Zufriedenheit (4)
- Zwangsstörung (4)
- Zweisprachigkeit (4)
- Zwitterion (4)
- abscisic acid (4)
- accumulation (4)
- action (4)
- active galactic nuclei (4)
- acute respiratory distress syndrome (4)
- adhesion molecules (4)
- adjuvant treatment (4)
- adrenal gland (4)
- adulte Neurogenese (4)
- adulthood (4)
- affect (4)
- age-related macular degeneration (4)
- agency (4)
- agroecology (4)
- albumin (4)
- alkaline phosphatase (4)
- allogene Stammzelltransplantation (4)
- allogeneic hematopoietic stem cell transplantation (4)
- alpha-synuclein (4)
- amyotrophic-lateral-sclerosis (4)
- analgesia (4)
- aneurysm (4)
- angeborenes Immunsystem (4)
- animals (4)
- anion channel (4)
- antagonist (4)
- antagonists (4)
- antibacterial (4)
- antifungal susceptibility (4)
- antifungals (4)
- antimicrobial (4)
- antioxidant (4)
- antiretroviral therapy (4)
- antisense RNA (4)
- apis mellifera (4)
- appendicitis (4)
- aquaporin (4)
- arteriosclerosis (4)
- arthroplasty (4)
- arthropods (4)
- associative learning (4)
- athletes (4)
- atopic dermatitis (4)
- attention-deficit/hyperactivity disorder (ADHD) (4)
- attentional bias (4)
- auditory pathway (4)
- autoantigen (4)
- autoimmune (4)
- auxin (4)
- avatars (4)
- awareness (4)
- axonal damage (4)
- bee decline (4)
- beta diversity (4)
- bevacizumab (4)
- bilingualism (4)
- binding analysis (4)
- biochemistry (4)
- biodiversity conservation (4)
- biofilm formation (4)
- biofilms (4)
- biological models (4)
- biologics (4)
- biomass (4)
- birds (4)
- bisphosphonates (4)
- blazar (4)
- bleeding (4)
- body composition (4)
- bone adhesive (4)
- bone metastases (4)
- bone substitute (4)
- bone-mineral density (4)
- borylenes (4)
- brain edema (4)
- bridging (4)
- cAAC (4)
- calcium phosphate cement (4)
- cancer genomics (4)
- cancer patients (4)
- candida albicans (4)
- capsaicin (4)
- carbanion (4)
- carbohydrates (4)
- carbon (4)
- carborane (4)
- cardiac magnetic resonance imaging (4)
- cardiac metabolism (4)
- cardiorespiratory fitness (4)
- cardiovascular genetics (4)
- care (4)
- cell-cycle arrest (4)
- cervical dystonia (4)
- characterization (4)
- chemotaxis (4)
- chiral separation (4)
- chlamydia trachomatis (4)
- chondrogenesis (4)
- chondrogenic differentiation (4)
- cirrhosis (4)
- cluster analysis (4)
- cochlea (4)
- colon (4)
- colony-stimulating factor (4)
- combination therapy (4)
- comparative genomic hybridization (4)
- compensation (4)
- complement system (4)
- complication (4)
- computational chemistry (4)
- consciousness (4)
- consortium (4)
- context (4)
- convolutional neural network (4)
- convolutional neural networks (4)
- cooperation (4)
- copy number variation (4)
- corneal confocal microscopy (4)
- corporate assessment (4)
- corporate law (4)
- corpus linguistics (4)
- costs (4)
- critical care (4)
- crosstalk (4)
- crowdsensing (4)
- crystallography (4)
- culture (4)
- cycloaddition (4)
- cysteine protease (4)
- deadwood enrichment (4)
- deafness (4)
- death receptors (4)
- decellularization (4)
- decoherence (4)
- deficiency (4)
- definition (4)
- dehydrocoupling (4)
- dental implants (4)
- dermatology (4)
- desflurane (4)
- desmosome (4)
- desmosomes (4)
- detrended fluctuation analysis (4)
- diabetic nephropathy (4)
- diborane (4)
- diboranes (4)
- diboration (4)
- diffuse large B-cell lymphoma (4)
- diffusion tensor imaging (4)
- dimerization (4)
- disease severity (4)
- drosophila (4)
- drug metabolism (4)
- dynamic (4)
- dysgnathia (4)
- dyslexia (4)
- ecological intensification (4)
- economic growth (4)
- economics (4)
- ecosystem function (4)
- ecosystem service (4)
- editorial (4)
- electrocardiography (4)
- electroencephalogram (4)
- electrohydrodynamic (4)
- electron (4)
- electron tomography (4)
- electron transfer (4)
- emotional regulation (4)
- emotionale Kompetenz (4)
- endurance exercise (4)
- entanglement (4)
- epithelium (4)
- essential genes (4)
- estrogen receptor (4)
- evolutionary genetics (4)
- excited states (4)
- exciton coupling (4)
- exciton dynamics (4)
- experimental stroke (4)
- exposure therapy (4)
- extracorporeal membrane oxygenation (4)
- extrazelluläre Matrix (4)
- face perception (4)
- face processing (4)
- failure (4)
- feminism (4)
- ferroptosis (4)
- fertility (4)
- fibrin (4)
- fibroblast (4)
- fibronectin (4)
- fish model (4)
- fitness (4)
- flagellum (4)
- flow (4)
- fluorescent protein (4)
- fluoroarene (4)
- follow up (4)
- foot (4)
- forensic neurotraumatology (4)
- forest ecology (4)
- fullerenes (4)
- functional analysis (4)
- functional characterization (4)
- functional diversity (4)
- functionalization (4)
- fungal structure (4)
- gait analysis (4)
- gait initiation (4)
- games (4)
- genetic loci (4)
- genome annotation (4)
- geoarchaeology (4)
- geography (4)
- gingivitis (4)
- globalization (4)
- glucose transporter (4)
- glutamine (4)
- gynecology (4)
- habitats (4)
- halothane (4)
- head (4)
- healthy volunteers (4)
- hematology (4)
- hepatitis C virus (4)
- hernia (4)
- hip fracture (4)
- homologous recombination (4)
- host cells (4)
- humanized mice (4)
- hybrid materials (4)
- hydrocarbons (4)
- hydrodynamics (4)
- hydrogen bonding (4)
- hydrolysis (4)
- hydroxyapatite (4)
- hypercortisolism (4)
- hypofractionation (4)
- iNOS (4)
- iPSC (4)
- image processing (4)
- imaging techniques (4)
- immune checkpoint blockade (4)
- immunohistochemistry techniques (4)
- immunosenescence (4)
- individual-based model (4)
- induction (4)
- infant (4)
- influenza A virus (4)
- innate immune response (4)
- inpatient rehabilitation (4)
- insect brain (4)
- insulin receptor (4)
- intellectual disability (4)
- intensive care (4)
- interoception (4)
- intervention (4)
- interview (4)
- intestinal barrier (4)
- invasive aspergillosis (4)
- invasive fungal infection (4)
- invasive pulmonary aspergillosis (4)
- ion channels (4)
- ionic liquids (4)
- jet energy resolution (4)
- kardiale Hypertrophie (4)
- kidney function (4)
- language development (4)
- learning curve (4)
- left ventricular hypertrophy (4)
- lenalidomide (4)
- leukemic cells (4)
- ligands (4)
- lines (4)
- linguistics (4)
- linkage (4)
- lipid bilayer (4)
- lipidomics (4)
- literature (4)
- living cells (4)
- locus coeruleus (4)
- lokale Selbstregelungen (4)
- loneliness (4)
- mRNA expression (4)
- macrocycles (4)
- macular degeneration (4)
- maize (4)
- major depressive disorder (4)
- malignant melanoma (4)
- mammalian cells (4)
- man-computer interface (4)
- mandible (4)
- manganese (4)
- marine sponge (4)
- mass (4)
- mathematics (4)
- matrix metalloproteinase (4)
- measurement (4)
- medical research (4)
- medical students (4)
- medullary thyroid carcinoma (4)
- melatonin (4)
- melody (4)
- melt electrowriting (MEW) (4)
- memory B cells (4)
- men (4)
- meningioma (4)
- meningococci (4)
- mesenchymal stromal cells (4)
- metabolic adaptation (4)
- metabolic test (4)
- miRNAs (4)
- microRNAs (4)
- microarrays (4)
- microcavity (4)
- micronucleus test (4)
- middle ear (4)
- mindfulness (4)
- minimally invasive surgery (4)
- mitochondrial DNA (4)
- modulation (4)
- molecular modeling (4)
- molecular modelling (4)
- molecular recognition (4)
- molybdenum (4)
- mood (4)
- morality (4)
- morphometry (4)
- mtDNA (4)
- multi-fluid mixture (4)
- multisensory integration (4)
- multisensory processing (4)
- musculoskeletal system (4)
- mutagenesis (4)
- mutagenicity (4)
- myasthenia gravis (4)
- myelination (4)
- myocardial perfusion (4)
- myofibroblast (4)
- n-Halbleiter (4)
- nNOS (4)
- natural enemies (4)
- natural language processing (4)
- networks (4)
- neural stem cell (4)
- neural stem cells (4)
- neuroimaging (4)
- neuroimmunology (4)
- neurotrophic factors (4)
- new species (4)
- nociception (4)
- non-covalent interactions (4)
- noradrenaline (4)
- norepinephrine transporter (4)
- nuclear magnetic resonance (4)
- oligodendrocytes (4)
- oligomerization (4)
- ontology (4)
- opioids (4)
- optical coherence tomography (4)
- organic (4)
- organic photovoltaics (4)
- organoid (4)
- orientation (4)
- osteoblast (4)
- osteotomy (4)
- outbreak (4)
- oxidative addition (4)
- oxygenation (4)
- p38 (4)
- paediatrics (4)
- palliative care (4)
- parallel corpus (4)
- parasite (4)
- parasitology (4)
- parathyroid (4)
- particle physics (4)
- pathology (4)
- patient (4)
- patient blood management (4)
- pentacoordinate (4)
- peptides (4)
- performance monitoring (4)
- periodic catatonia (4)
- perioperative management (4)
- periprothetische Infektion (4)
- personality traits (4)
- pharmacogenetics (4)
- pharmacotherapy (4)
- phase transition (4)
- phase transitions and critical phenomena (4)
- pheromone (4)
- phosphate (4)
- phosphoantigen (4)
- phosphorescence (4)
- photodissociation (4)
- photodynamic therapy (4)
- photonic devices (4)
- phytic acid (4)
- phytoprostanes (4)
- plant cuticle (4)
- plasma (4)
- plasmonics (4)
- platinum (4)
- pluripotency (4)
- political discourse (4)
- pollution (4)
- polycycles (4)
- polygenic risk score (4)
- polymer (4)
- polymerization (4)
- population genetics (4)
- positron-emission-tomography (4)
- post-traumatic stress disorder (4)
- postoperative Komplikationen (4)
- principal component analysis (4)
- prognostic factor (4)
- prognostic value (4)
- propofol (4)
- protease inhibitor (4)
- protein structure (4)
- protein synthesis (4)
- protein-protein interaction (4)
- proteome (4)
- psychische Belastung (4)
- psycho-oncology (4)
- psychophysics (4)
- punishment (4)
- purification (4)
- quality control (4)
- quality indicators (4)
- quantum control (4)
- radar (4)
- radiation therapy (4)
- radiochemotherapy (4)
- radiology (4)
- radionuclide therapy (4)
- rainforest (4)
- reaction mechanisms (4)
- reaction time (4)
- reactivity (4)
- reading (4)
- real-time (4)
- recommendations (4)
- red blood cells (4)
- regulator (4)
- regulator genes (4)
- regulatorische T Zellen (4)
- regulatory T-cells (4)
- religion (4)
- renal failure (4)
- reoperation (4)
- reporter gene (4)
- reproduction (4)
- resonant tunneling diode (4)
- response regulator (4)
- results (4)
- retrospektiv (4)
- reverse transcriptase (4)
- rheology (4)
- rhodium (4)
- rhodopsin (4)
- ribosomal RNA (4)
- ribosome biogenesis (4)
- risk assessment (4)
- root (4)
- rotation (4)
- ruthenium complexes (4)
- saccades (4)
- salivary gland (4)
- saproxylic beetles (4)
- scaling (4)
- scanning tunneling microscopy (4)
- schistosomiasis (4)
- score (4)
- secondary metabolites (4)
- selenium (4)
- self-regulation (4)
- sequence analysis (4)
- sequence motif analysis (4)
- sex (4)
- sex determination (4)
- shRNA (4)
- shape (4)
- signalling pathways (4)
- singlet oxygen (4)
- skin cancer (4)
- sleep bruxism (4)
- small intestine (4)
- smartwatch (4)
- soccer (4)
- social media (4)
- social systems (4)
- specialization (4)
- speciation (4)
- speech (4)
- sperm (4)
- spermatogenesis (4)
- spermiogenesis (4)
- sphingomyelinase (4)
- spillover (4)
- spin injection (4)
- spleen (4)
- spoken language (4)
- standardization (4)
- startle reflex (4)
- statins (4)
- stemness (4)
- stent (4)
- stereogen (4)
- stereogenic (4)
- stereoselektive Synthese (4)
- stimulation (4)
- strain rate (4)
- streptomyces (4)
- streptozotocin (4)
- stress response (4)
- strong coupling (4)
- struvite (4)
- substantia nigra (4)
- sulfur (4)
- supramolekulare Chemie (4)
- surface water (4)
- surgical and invasive medical procedures (4)
- surgical oncology (4)
- surveillance (4)
- survival analysis (4)
- sustained fear (4)
- synapses (4)
- synaptonemal complex (4)
- synthetic biology (4)
- systemic sclerosis (4)
- systems (4)
- task switching (4)
- theory of mind (4)
- thermal conductivity (4)
- thiol-ene (4)
- thromboembolism (4)
- thrombopoiesis (4)
- thymic carcinoma (4)
- thyroid (4)
- time series analysis (4)
- toe (4)
- toll-like receptors (4)
- tomato (4)
- top quark mass (4)
- topology (4)
- total knee replacement (4)
- toxicology (4)
- trabecular meshwork (4)
- transactivation (4)
- transcranial magnetic stimulation (4)
- transcriptome analysis (4)
- transient absorption spectroscopy (4)
- transient ischemic attack (4)
- transition metal complex (4)
- transition metal complexes (4)
- transposable elements (4)
- triarylamine (4)
- triarylborane (4)
- troponin (4)
- trypanosoma (4)
- tryptophan (4)
- tumor heterogeneity (4)
- tumor suppressor gene (4)
- tumorigenesis (4)
- tungsten (4)
- tyrosine kinase (4)
- ultimatum game (4)
- ultrafast photochemistry (4)
- ultrastructure (4)
- unconscious processing (4)
- urinary tract infection (4)
- user experience (4)
- validity (4)
- valuation of a company (4)
- vasculogenesis (4)
- velocity (4)
- vertical transmission (4)
- vesicles (4)
- viability (4)
- virotherapy (4)
- viruses (4)
- visual attention (4)
- visual perception (4)
- vitamin B6 (4)
- vitamin C (4)
- wall shear stress (4)
- wax (4)
- x (4)
- xxx (4)
- youth (4)
- zinc (4)
- zinc oxide (4)
- zinc oxide nanoparticles (4)
- Ästhetik (4)
- Östrogenrezeptor (4)
- Übelkeit (4)
- Überexpression (4)
- 16S rRNA (3)
- 18F-DCFPyL (3)
- 18F-FDG PET/CT (3)
- 18F-LMI1195 (3)
- 3 D bioprinting (3)
- 3D models (3)
- 3D powder printing (3)
- 3D scaffolds (3)
- 3D-Stereophotogrammetrie (3)
- 3D-Zellkultur (3)
- 4-0xadiazin-6-ones (3)
- 5-HT1A (3)
- 5-HT2C (3)
- 5-HTT (3)
- 5-Methylcytosine (3)
- 5-fluorouracil (3)
- A-priori-Wissen (3)
- A1 (3)
- ABR (3)
- ACE (3)
- ADP (3)
- AKT (3)
- AML (3)
- ARIA (3)
- ASC (3)
- Abschirmung (3)
- Absolute Configuration (3)
- Acetylcholinesterase (3)
- Acetylcholinrezeptor (3)
- Acetylsalicylsäure (3)
- Acne inversa (3)
- Actinoide (3)
- Actinomycetes (3)
- Adaptation (3)
- Adaptive Optics (3)
- Adaptive Optik (3)
- Adaptivregelung (3)
- Adaptorproteine (3)
- Additive Fertigung (3)
- Adenom-Karzinom-Sequenz (3)
- Adhesion (3)
- Adhäsine (3)
- Adrenalin (3)
- Adrenerger Rezeptor (3)
- Advanced Analytics (3)
- Advanced Glycation Endproducts (3)
- Adventitia (3)
- Affenimmundefizienzvirus (3)
- Age (3)
- Agency (3)
- Aging (3)
- Aktiengesellschaft (3)
- Aktienrecht (3)
- Aktin-Zytoskelett (3)
- Aktionspotenzial (3)
- Aktivität (3)
- Akupunktur (3)
- Akute lymphatische Leukämie (3)
- AlGaAs (3)
- Albino rats (3)
- Albumin (3)
- Aldehyde (3)
- Aldosteronantagonist (3)
- Algorithmische Geometrie (3)
- Alkaloid (3)
- Alkaloide (3)
- Allgemeine Entzündungsreaktion (3)
- Allgemeine atmosphärische Zirkulation (3)
- Allogeneic stem cell transplantation (3)
- Alopecia areata (3)
- Altersbestimmung (3)
- Alterssicherung (3)
- Altertum (3)
- Aluminium (3)
- Ambulante Behandlung (3)
- Ameisenstaat (3)
- Aminosäure (3)
- Amisulprid (3)
- Amphibian oocytes (3)
- Amphiphile Verbindungen (3)
- Amplitude (3)
- Amyloid <beta-> (3)
- Amyloidose (3)
- Anastomose (3)
- Anastomoseninsuffizienz (3)
- Anatomie (3)
- Andrea (Komponist) (3)
- Angewandte Mathematik (3)
- Angewandte Psychologie / Zeitschrift / Experimentelle Psychologie (3)
- Angiographie (3)
- Angiotensin (3)
- Angola (3)
- Anion (3)
- Anisotropie (3)
- Anthracenderivate (3)
- Anthropocene (3)
- Antibiotikatherapie (3)
- Antibodies (3)
- Antiferromagnetismus (3)
- Antigen CD22 (3)
- Antimalariamittel (3)
- Antimikrobielle Peptide (3)
- Antimykotika (3)
- Antimykotikaresistenz (3)
- Antipsychotika (3)
- Antworthemmung (3)
- Antwortverhalten (3)
- Anästhetikum (3)
- Apherese (3)
- Aplysina aerophoba (3)
- Apobec (3)
- Araneae (3)
- Arbeit (3)
- Arbeitsplatz (3)
- Arctic (3)
- Arginin (3)
- Aromastoff (3)
- Aromaten (3)
- Aromatically annulated triquinacenes (3)
- Aromatisch anellierte Triquinacene (3)
- Array (3)
- Arrhythmie (3)
- Art (3)
- Arthroplasty (3)
- Artificial Intelligence (3)
- Aseptische Lockerung (3)
- Association study (3)
- Assyriologie (3)
- Asteraceae (3)
- Atemwege (3)
- Atorvastatin (3)
- Atta vollenweideri (3)
- Attika (3)
- Attraktivität (3)
- Aufklärungsgespräch (3)
- Aufmerksamkeitsprozesse (3)
- Augendruck (3)
- Ausgrabung (3)
- Auslauftrichter (3)
- Ausländer (3)
- Ausstellung (3)
- Auswertung (3)
- Authentizität (3)
- Autismus (3)
- Autoantibodies (3)
- Automatische Klassifikation (3)
- Automatisiertes Fahren (3)
- Autonomes Fahrzeug (3)
- Autonomous UAV (3)
- Autophagie <Physiologie> (3)
- Autoradiography (3)
- Außenhandel (3)
- Avatar <Informatik> (3)
- B-cell (3)
- BIS (3)
- BL-Lacertae-Objekt (3)
- BN compounds (3)
- BP180 (3)
- BRAF mutation (3)
- Bacillus anthracis (3)
- Bacterial infection (3)
- Baden (3)
- Bakteriophagen (3)
- Bandwürmer (3)
- Bariatrische Chirurgie (3)
- Basalganglien (3)
- Basilarmembran (3)
- Basketball (3)
- Batterie (3)
- Bauchwandhernie (3)
- Bayesian classifier (3)
- Bcl-2-Proteinfamilie (3)
- Bedeutung (3)
- Bedürfnis (3)
- Befestigungskomposit (3)
- Behaviour (3)
- Benchmarking (3)
- Benn, Gottfried (3)
- Berechnungskomplexität (3)
- Bernasconi (3)
- Beruf (3)
- Beryllium (3)
- Beschleunigungssensor (3)
- Bestandsmanagement (3)
- Bestärkendes Lernen <Künstliche Intelligenz> (3)
- Bewegung (3)
- Bewegungssehen (3)
- Bewegungsstörung (3)
- Bewertung (3)
- Bewältigung (3)
- Bias (3)
- Biene <Gattung> (3)
- Bienenwolf (3)
- Big Data (3)
- Bild (3)
- Bilderbuch (3)
- Bildqualität (3)
- Bildrekonstruktion (3)
- Bindegewebe (3)
- Biodistribution (3)
- Biofabrikation (3)
- Biografie (3)
- Biographieforschung (3)
- Bioinks (3)
- Biokinetics (3)
- Biologische Aktivität (3)
- Biologisches Material (3)
- Biomarkers (3)
- Biomedical engineering (3)
- Biomedicine (3)
- Bioprinting (3)
- Biosensor (3)
- Biosphärenreservat (3)
- Biotechnologie (3)
- Bipolare Störung (3)
- Biradicals (3)
- Blickbewegung (3)
- Blochmannia (3)
- Blockchain (3)
- Blood-brain barrier (3)
- Bluthochdruck (3)
- Blutverlust (3)
- Bone marrow transplantation (3)
- Bone morphogenetic protein-2 (3)
- Bordetella bronchiseptica (3)
- Borirene (3)
- Borkomplexe (3)
- Borreliose (3)
- Borylentransfer (3)
- Bosons (3)
- Brachytherapie (3)
- Brackets (3)
- Brain-computer interface (3)
- Bridging (3)
- Brombeere (3)
- Brownsche Bewegung (3)
- Bruchfläche (3)
- Buchdruck (3)
- Bundeswehr (3)
- Bupivacain (3)
- Burkholderia (3)
- Business Intelligence (3)
- Butyrate (3)
- C/EBP (3)
- C5aR1 (3)
- CA3 (3)
- CAAC (3)
- CAD/CAM (3)
- CAR T cell (3)
- CAR T cells (3)
- CCL2 (3)
- CCR2 (3)
- CCR7 (3)
- CD22 (3)
- CD23 (3)
- CD27 (3)
- CD39 (3)
- CD4(+) (3)
- CD4+ T cells (3)
- CD40L (3)
- CD73 (3)
- CD8 T cell (3)
- CD8+ T cells (3)
- CD8+ T-Zellen (3)
- CD9 (3)
- CDH13 (3)
- CEA (3)
- CGH (3)
- CMT (3)
- CNO (3)
- CO2 (3)
- COVID-19 pandemic (3)
- COVID‐19 (3)
- CRISPR Cas9 (3)
- CRMO (3)
- CTGF (3)
- CVD (3)
- CYP11B2 (3)
- Calcium Imaging (3)
- Calcium-bindende Proteine (3)
- Calciumhydroxid (3)
- Calciumphosphatzemente (3)
- Calciumtransport (3)
- Calibration (3)
- Camerloher (3)
- Capsaicin (3)
- Carbenoide (3)
- Carcino-embryonales Antigen (3)
- Carcinogenicity (3)
- Carcinogens (3)
- Cardiomyopathy (3)
- Carrier-Proteine (3)
- Cas9 (3)
- CaseTrain (3)
- Caspase (3)
- Caspr (3)
- Cathepsin (3)
- CdSe (3)
- CdTe (3)
- CePt5 (3)
- Cell cycle (3)
- Cells (3)
- Central nervous system (3)
- Ceramid (3)
- Cerebellar cortex (3)
- Cerebrospinal fluid (3)
- Chaos (3)
- Chaostheorie (3)
- Chaperone (3)
- Chemieunterricht (3)
- Chemische Kommunikation (3)
- Chemokin CXCL10 (3)
- Chemokinrezeptor (3)
- Chimärismus (3)
- Chirp (3)
- Cholesterinstoffwechsel (3)
- Cholinesteraseinhibitor (3)
- Chondrozyten (3)
- Chromosomes (3)
- Chronisch-myeloische Leukämie (3)
- Circadian Rhythms (3)
- Circular Dichroism (3)
- Circular dichroism (3)
- Classification (3)
- Cluster (3)
- Co-culture (3)
- Cochlea-Implantat (3)
- Coexpression (3)
- Coffein (3)
- Coherent control (3)
- Coleoptera (3)
- Collagen (3)
- Colorectal Cancer (3)
- Comorbidity (3)
- Complexity (3)
- Computer Vision (3)
- Computerspiel (3)
- Conference (3)
- Coping (3)
- Copula (3)
- Coulomb-Blockade (3)
- Cranio-Corpo-Graphie (3)
- Creation (3)
- Crohn's disease (3)
- Cu(111) (3)
- Cyanobacteria (3)
- Cycloadditionen (3)
- Cycloadditions (3)
- Cystic fibrosis (3)
- Cytogenetik (3)
- Cytostatikum (3)
- DAT (3)
- DBH (3)
- DFB laser (3)
- DMD (3)
- DNA double strand breaks (3)
- DNA double-strand breaks (3)
- DNS-Schaden (3)
- DNS-Sequenz (3)
- DSG2 (3)
- DTI (3)
- DUB (3)
- DW-MRI (3)
- DWI (3)
- DYT1 (3)
- DaTscan (3)
- Data Fusion (3)
- Data Warehouse (3)
- Dauerfrostboden (3)
- Deeskalation (3)
- Definition (3)
- Deformation (3)
- Demethylierung (3)
- Deoxyribozymes (3)
- Dermatologie (3)
- Desmogleine (3)
- Detektion (3)
- Devisenmarkt (3)
- Diabetes Mellitus (3)
- Diboran(4) (3)
- Diborin (3)
- Dictyostelium (3)
- Dienstleistung (3)
- Differentialdiagnose (3)
- Differentialgeometrie (3)
- Diffusionsgewichtete Magnetresonanztomographie (3)
- Digital Religions (3)
- Diindenoperylen (3)
- Dilatation (3)
- Dimorphismus (3)
- Discounter (3)
- Dispersion (3)
- Dissertation (3)
- Distributed Control (3)
- Diversität (3)
- Docking (3)
- Doppler-Echokardiographie (3)
- Dosimetrie (3)
- Dosis-Wirkungs-Beziehung (3)
- Down syndrome (3)
- Drahtloses lokales Netz (3)
- Dreiecksgitter (3)
- Druckmessung (3)
- Drug resistance (3)
- Duchenne muscular dystrophy (3)
- Duchenne-Syndrom (3)
- Durchflußzytometrie (3)
- Durchstrahlungselektronenmikroskopie (3)
- Dynamisches System (3)
- Düne (3)
- Dünndarmtransplantation (3)
- Dünnschichttransistor (3)
- E-cadherin (3)
- ECMO (3)
- EDA (3)
- ELBWI (3)
- EMT (3)
- EPC (3)
- EPR spectroscopy (3)
- ESS (3)
- Echtzeitsystem (3)
- Ecosystem services (3)
- Effektivität (3)
- Efficiency (3)
- Egypt (3)
- Ehescheidung (3)
- Eiablage (3)
- Eigenwert (3)
- Einfluss (3)
- Einflussfaktoren (3)
- Einkommensverteilung (3)
- Einsilbiges Wort (3)
- Einstellung (3)
- Einzelhandelsbetrieb (3)
- Einzelhandelsentwicklung (3)
- Einzelmolekülspektroskopie (3)
- Einzelzellanalyse (3)
- Eisenmangel (3)
- Elastizität (3)
- Elastizitätsmodul (3)
- Electroencephalographie (3)
- Electron Microscopy (3)
- Electropermeabilization (3)
- Electrophysiology (3)
- Elektrochromie (3)
- Elektrofusion (3)
- Elektron-Phonon-Wechselwirkung (3)
- Elektronenspinresonanzspektroskopie (3)
- Elektronensprayionisations-Massenspektrometrie (3)
- Elektronische Eigenschaft (3)
- Elektrorheologie (3)
- Ellenbogen (3)
- Eltern (3)
- Embodiment (3)
- Emerin (3)
- Emotionsverarbeitung (3)
- Empfängnisverhütung (3)
- Empowerment (3)
- Encephalomyelitis (3)
- Endobrachyösophagus (3)
- Endokrinologie (3)
- Endotheliale Dysfunktion (3)
- Energieeffizienz (3)
- Energy Efficiency (3)
- Energy Transfer (3)
- Enoyl-acyl-carrier-protein-Reductase <Enoyl-[acyl-carrier-protein]-Reductase> (3)
- Entgeltumwandlung (3)
- Entmarkung (3)
- Entnahmemorbidität (3)
- Entscheidungsfindung (3)
- Environment (3)
- Enzephalitis (3)
- Enzyme (3)
- Enzyme induction (3)
- Enzyme-linked immunosorbent assay (3)
- Enzymes (3)
- Enzymkinetik (3)
- Epac (3)
- Ephedrin (3)
- Epichloë (3)
- Epidermaler Wachstumsfaktor (3)
- Epidermis (3)
- Ereignisdatenanalyse (3)
- Ergospirometrie (3)
- Erregbarkeit (3)
- Erreger (3)
- Erste Hilfe (3)
- Ertaubung (3)
- Erwachsene (3)
- Erweiterte Realität <Informatik> (3)
- Erythrozyt (3)
- Erzähltechnik (3)
- Erzählung (3)
- Escitalopram (3)
- Essstörungen (3)
- Estrogene (3)
- Etomidat (3)
- European beech (3)
- Europäische Ethnologie (3)
- Event (3)
- Event-related potential (3)
- Events (3)
- Evoziertes Potenzial (3)
- Exciton (3)
- Exekutive Funktionen (3)
- Expansion microscopy (3)
- Experimentelle autoimmune Enzephalomyelitis (3)
- Extrazellulärraum (3)
- Exzitonenkopplung (3)
- FAEP (3)
- FAP (3)
- FIR-Spektroskopie (3)
- FRAP (3)
- FSME (3)
- FT-IR-Spektroskopie (3)
- FTY720 (3)
- FabI (3)
- Fabry-associated pain (3)
- Fahrerassistenz (3)
- Faktorenanalyse (3)
- Fallstudie (3)
- Fanconi Anaemia (3)
- Femtochemie (3)
- Femtosekunden (3)
- Femtosekundenlaser (3)
- Fernröntgenseitenbild (3)
- Ferrocen (3)
- Ferromagnetic Semiconductors (3)
- Ferromagnetische Schicht (3)
- Fettsäurebiosynthese (3)
- Fettsäuren (3)
- Fibrin (3)
- Fibromyalgia syndrome (3)
- Fibronektin (3)
- Fingolimod (3)
- Finite Elemente (3)
- Finite-Volumen-Methode (3)
- Fisch (3)
- Fische (3)
- Flavour <Elementarteilchen> (3)
- Flavourmischung (3)
- Fließfähigkeit (3)
- Flora (3)
- Fluid (3)
- Fluor-19 (3)
- Fluorescence spectroscopy (3)
- Fluoxetin (3)
- Fluss (3)
- Fokker-Planck-Gleichung (3)
- Foldamers (3)
- Follow-up (3)
- Forecasting (3)
- Formulierung (3)
- Formulierungsentwicklung (3)
- Fossile Muscheln (3)
- Fotochemie (3)
- FoxP3 (3)
- Fragmentbefestigung (3)
- Frailty (3)
- Franconia (3)
- Frauenarbeit (3)
- Freiburger Sprachverständnistest (3)
- Freie-Elektronen-Laser (3)
- Fremdsprache (3)
- Frequenzvervielfachung (3)
- Fries (3)
- Frosch (3)
- Frühgeborenes (3)
- Frühgeburt (3)
- Frühneuhochdeutsch (3)
- Fulleren (3)
- Fundusautofluoreszenz (3)
- Fusarium (3)
- Fusion (3)
- G-Protein (3)
- G-Proteine (3)
- G-protein-coupled receptors (3)
- GABAA receptors (3)
- GAS2L3 (3)
- GDF-15 (3)
- GDF-5 (3)
- GFP (3)
- GLUT3 (3)
- GM-CSF (3)
- GMP (3)
- Galectine (3)
- Galerkin-Methode (3)
- Gamma-Burst (3)
- Ganztagsschule (3)
- Gasgemisch (3)
- Gasphase (3)
- Gastric-banding (3)
- Gastrointestinaler Tumor (3)
- Gauge-gravity correspondence (3)
- Gaussian approximation (3)
- Gebrechlichkeit (3)
- Gebärmutterhalskrebs (3)
- Gefahr (3)
- Gefäßpflanzen (3)
- Gelernte Hilflosigkeit (3)
- Gemcitabin (3)
- Gen-Knockout (3)
- Gender Studies (3)
- Gene therapy (3)
- Genome (3)
- Genomics (3)
- Genotyp (3)
- Gentamicin (3)
- Geoarchäologie (3)
- Geografie (3)
- Geomorphogenese (3)
- Geomorphology (3)
- Gerechtigkeit (3)
- Gerinnungsfaktor XII (3)
- German (3)
- Germanen (3)
- Geschichte 1800-1900 (3)
- Geschlechtschromosomen (3)
- Geschmack (3)
- Gesellschaften ohne Zentralgewalt (3)
- Gestationsdiabetes (3)
- Gesundheitssystem (3)
- Gesundheitsverhalten (3)
- Gewebekleber (3)
- Gewebemodell (3)
- Gibbs free energy of binding (3)
- Gingivitis (3)
- Gitterbaufehler (3)
- Glaskeramik (3)
- Gletscher (3)
- Glia (3)
- Glioblastoma multiforme (3)
- Glucocorticoide (3)
- Glucosetransport (3)
- Glucosinolate (3)
- Glukose (3)
- Glutamat (3)
- Glutamat-Decarboxylase (3)
- Glutathione (3)
- Glycin (3)
- Golgi (3)
- Grad-seq (3)
- Grading (3)
- Graft-versus-host disease (3)
- Griechenland (3)
- Griechisch (3)
- Grimmelshausen (3)
- Grippe (3)
- Grundfrequenz (3)
- Grundwasser (3)
- Grundwasserbildung (3)
- Guillain-Barré syndrome (3)
- HFOV (3)
- HFrEF (3)
- HHV-6 (3)
- HSM (3)
- Hadron Colliders (3)
- Halogene (3)
- Hamburg (3)
- Hand (3)
- Handschrift (3)
- Haplotypanalyse (3)
- Harmonic Imaging (3)
- Harnableitung (3)
- Harninkontinenz (3)
- Harnwegsinfektionen (3)
- Hauptgruppenelementverbindungen (3)
- Hausarzt (3)
- Hautflügler (3)
- Hautmodell (3)
- Hearing loss (3)
- Hefeartige Pilze (3)
- Helferzelle (3)
- Heliosphäre (3)
- Hepatotoxizität (3)
- Herbivory (3)
- Hereditäres Angioödem (3)
- Hermeneutik (3)
- Herrschaft (3)
- Herz-Lungen-Maschine (3)
- Herzoperation (3)
- Herzrhythmusstörung (3)
- Herzstoffwechsel (3)
- Herztransplantation (3)
- Heteroepitaxie (3)
- Heterostruktur-Bauelement (3)
- Hexacoordination (3)
- Hexakoordination (3)
- Hey (3)
- Hill numbers (3)
- Hip (3)
- Hirnendothelzellen (3)
- Hirnforschung (3)
- Hirnhautentzündung (3)
- Hirninfarkt (3)
- Hirnmetastase (3)
- Hirnmetastasen (3)
- Hirnstimulation (3)
- Hirschsprung disease (3)
- Histon-Deacetylase (3)
- Historische Aufnahme (3)
- Hitzeschockprotein (3)
- Hitzeschockproteine (3)
- Hitzeschocktranskriptionsfaktor (3)
- Hochdosischemotherapie (3)
- Hochschullehrende (3)
- Hochschulschrift (3)
- Hodgkin lymphoma (3)
- Hofkomponist (3)
- Holozän (3)
- Homerus (3)
- Human-Computer Interaction (3)
- Humans (3)
- Hummel (3)
- Hummeln (3)
- Hydroborierung (3)
- Hydroxyethylstärke (3)
- Hyperalgesie (3)
- Hyperekplexie (3)
- Hyperglykämie (3)
- Hypernephrom (3)
- Hyperthermie (3)
- Hämodiafiltration (3)
- Härte (3)
- Höranstrengung (3)
- Hörprüfung (3)
- Hüftprothese (3)
- Hüfttotalendoprothese (3)
- ICU (3)
- IGF-1 (3)
- IGF-I (3)
- IGRT (3)
- IL-12 (3)
- IL-1β (3)
- IS256 (3)
- ISS (3)
- IT-Sicherheit (3)
- IVF (3)
- Identität (3)
- Identitätsentwicklung (3)
- Ideomotorik (3)
- IgE (3)
- IgG (3)
- IgM (3)
- Iminoborane (3)
- Immundefekt (3)
- Immunglobulin (3)
- Immunglobulin M (3)
- Immunoseneszenz (3)
- Immunosuppression (3)
- Impedanzspektroskopie (3)
- Impfstatus (3)
- Implantate (3)
- Implantation (3)
- In-vitro (3)
- Index (3)
- Indiumarsenid (3)
- Indiumphosphid (3)
- Individuationsprozess (3)
- Industrie 4.0 (3)
- Infarkt (3)
- Inflation Targeting (3)
- Information (3)
- Information Extraction (3)
- Information Retrieval (3)
- Inhaltsanalyse (3)
- Inhibitorische Synapse (3)
- Initiation (3)
- Inklusion <Soziologie> (3)
- Inklusiver Unterricht (3)
- Innere Uhr (3)
- Insects (3)
- Insulinresistenz (3)
- Intensivmedizin (3)
- Intensivtransport (3)
- Interleukin (3)
- Interleukin 5 (3)
- Interleukin-1 (3)
- Interleukin-5 (3)
- Interleukin-6 (3)
- Intermedialität (3)
- Internationale Politik (3)
- Internationales Gesellschaftsrecht (3)
- Intervention (3)
- Interventionsradiologie (3)
- Intraokularer Druck (3)
- Intrazellulärraum (3)
- Inzidentalom (3)
- Inzidenz (3)
- Inzidenz <Medizin> (3)
- Iod (3)
- Ionische Flüssigkeiten (3)
- Irradiation (3)
- Ischemia (3)
- Ischemic stroke (3)
- Ischämischer Schlaganfall (3)
- Isolierung (3)
- Isomer (3)
- Italien (3)
- Italienisch (3)
- J- and H-Aggregate (3)
- J- and H-Aggregates (3)
- Jurassic (3)
- Kafka (3)
- Kaiserschnitt (3)
- Kalzium (3)
- Kaninchen (3)
- Kannenpflanze (3)
- Kanzerogenese (3)
- Kardiomyozyt (3)
- Kardiomyozyten (3)
- Kardioprotektion (3)
- Kardiovaskuläre Krankheit (3)
- Karyotyp (3)
- Karzinom (3)
- Karzinomzellen (3)
- Katarakt (3)
- Katatonie (3)
- Katecholamine (3)
- Kausalmodell (3)
- Kehlkopf (3)
- Kenyon cells (3)
- Keramikfaser (3)
- Kernspinrelaxation (3)
- Ketogene Kost (3)
- Ketonkörper (3)
- Ki-67 (3)
- Ki67 (3)
- Kiefer- und Gesichtschirurgie (3)
- Kiefernrindenextrakt (3)
- Kinderchirurgie (3)
- Kleinkinderziehung (3)
- Klimamodell (3)
- Klimaschutz (3)
- Klinische Psychotherapie (3)
- Klinische Studie (3)
- Klonalität (3)
- Knee (3)
- Kniegelenkarthrose (3)
- Knochenmarktransplantation (3)
- Knochennekrose (3)
- Knochenstoffwechsel (3)
- Knochentumor (3)
- Knockdown (3)
- Knockout-Maus (3)
- Knorpelintegration (3)
- Koffein (3)
- Kognitive Psychologie (3)
- Kognitive Verhaltenstherapie (3)
- Kognitiver Prozess (3)
- Kohlendioxid (3)
- Kokultur (3)
- Kolon (3)
- Kolonialismus (3)
- Komfortlaut (3)
- Kommune (3)
- Kommunikationstraining (3)
- Komplexes regionales Schmerzsyndrom (3)
- Kompressionstherapie (3)
- Komprimierte Abtastung (3)
- Kondensation (3)
- Kondo-Modell (3)
- Kondo-System (3)
- Konfidenzintervall (3)
- Konjugate (3)
- Konjugation (3)
- Kontamination (3)
- Kontinenz (3)
- Kontrolle (3)
- Kontrolltheorie (3)
- Konvergenz (3)
- Konversationsanalyse (3)
- Kopforthesentherapie (3)
- Korbblütler (3)
- Koronarchirurgie (3)
- Koronarperfusion (3)
- Korpuslinguistik (3)
- Korrektur (3)
- Korrelative Mikroskopie (3)
- Kosmische Strahlung (3)
- Kraftmessung (3)
- Kraniopharyngeom (3)
- Kraniopharyngiom (3)
- Krankenhaus (3)
- Krankheitsverlauf (3)
- Kreatinkinase (3)
- Kreditmarkt (3)
- Krieg (3)
- Kristallographie (3)
- Kulturkontakt (3)
- Kulturtheorie (3)
- Kunst (3)
- Kurfürst (3)
- Kurzzeitphysik (3)
- Körper (3)
- Körperwahrnehmung (3)
- L929 (3)
- LAD (3)
- LC-HRESIMS (3)
- LIF (3)
- LNCaP (3)
- LTD (3)
- Lactatdehydrogenase (3)
- Laminopathie (3)
- Landschaft (3)
- Landschaftsentwicklung (3)
- Landshuter Gesangbuch (3)
- Langzeitdepression (3)
- Langzeitprognose (3)
- Larve (3)
- Laryngeale Konstriktion (3)
- Larynx (3)
- Larynxkarzinom (3)
- Laserchemie (3)
- Laserdiode (3)
- Laserstrahlung (3)
- Late Enhancement (3)
- Learning and memory (3)
- Lebendgebärende Zahnkarpfen (3)
- Lebensdauer (3)
- Lebensmitteleinzelhandel (3)
- Lebermetastase (3)
- Legasthenie (3)
- Legionellen (3)
- Lehr-Lern-Labor (3)
- Lehramtsstudium (3)
- Lehrerhandreichung (3)
- Lehrkräftebildung (3)
- Leistenhernie (3)
- Lepra (3)
- Lepton (3)
- Lernstrategien (3)
- Lerntechnik (3)
- Letalität (3)
- Leukoplakie (3)
- Lewis acid (3)
- Lewis-Addukt (3)
- Lexikographie (3)
- Licht (3)
- Lichtstreuung (3)
- Lidschlag (3)
- Ligamentum cruciatum anterius (3)
- Linear Pottery (3)
- Linienbreite (3)
- Lipidmembran (3)
- Lipidstoffwechsel (3)
- Lipopolysaccharid (3)
- Lipopolysaccharide (3)
- Lipoprotein (3)
- Lipoxygenase (3)
- Lipoxygenase <5-> (3)
- Literaturunterricht (3)
- Ljapunov-Funktion (3)
- LoRaWAN (3)
- Lolium perenne (3)
- Luminescence (3)
- Lungenentzündung (3)
- Lungenmetastase (3)
- Lungenperfusionsmodell (3)
- Lungentumor (3)
- Lurche (3)
- Luttinger-Flüssigkeit (3)
- Lycopersicon esculentum (3)
- Lyme-Krankheit (3)
- Lymphocytes (3)
- Lymphoma (3)
- Lysosomale Speicherkrankheit (3)
- Lysozym (3)
- Ländlicher Raum (3)
- Längsschnittstudie (3)
- MALT-Lymphom (3)
- MALT1 (3)
- MAP kinase (3)
- MC simulation (3)
- MDD (3)
- MDR (3)
- MDSC (3)
- MEK (3)
- MGMT (3)
- MHC Klasse II (3)
- MLC1 (3)
- MLST (3)
- MMN (3)
- MMP-9 (3)
- MOF (3)
- MOFs (3)
- MPI (3)
- MSCT (3)
- MSSM (3)
- Magma (3)
- Magnesiumphosphat (3)
- Magnetic Anisotropy (3)
- Magnetische Eigenschaft (3)
- Magnetischer Röntgenzirkulardichroismus (3)
- Magnetoelastizität (3)
- Magnetresonanz (3)
- Magnetresonanztomografie (3)
- Makrocyclische Verbindungen (3)
- Malariamücke (3)
- Malaysia (3)
- Malignant Hyperthermia (3)
- Malignant hyperthermia (3)
- Malignant melanoma (3)
- Malnutrition (3)
- Mamma (3)
- Manganate (3)
- Manganselenide (3)
- Mangansilicide (3)
- Mannheim (3)
- Mantelzell-Lymphom (3)
- Mantle cell lymphoma (3)
- Mapping (3)
- Marker (3)
- Markteintrittsstrategie (3)
- Mastdarmkrebs (3)
- Materielle Kultur (3)
- Matrixmetalloproteinasen (3)
- Maximilian <Bayern> (3)
- Mc4r (3)
- Measurement (3)
- Measuring Masses (3)
- Mechanische Eigenschaft (3)
- Mechanorezeptor (3)
- Mechanotransduktion (3)
- Medien-/Kulturwissenschaft (3)
- Medienanalyse (3)
- Medienkonsum (3)
- Medizinische Rehabilitation (3)
- Medizinstudent (3)
- Medizinstudium (3)
- Megakaryocyte (3)
- Megakaryopoese (3)
- Mehrschichtsystem (3)
- Melatonin (3)
- Melt Electrowriting (3)
- Melt electrowriting (3)
- Memantin (3)
- Membranpotential (3)
- Membranrezeptor (3)
- Memristor (3)
- Meniskus (3)
- Merkel cell polyomavirus (3)
- Merkel-Zellkarzinom (3)
- Merocyanin (3)
- Mesenchymal Stem Cells (3)
- Mesenchymale Stromazellen (3)
- Mesophyll (3)
- Mesoskopisches System (3)
- Metall-Isolator-Phasenumwandlung (3)
- Metallcarbonyle (3)
- Metalloarenophane (3)
- Metalloberfläche (3)
- Metalloprotease (3)
- Metallorganische Chemie (3)
- Metapher (3)
- Metastasierung (3)
- Methodenentwicklung (3)
- Methohexital (3)
- Methotrexate (3)
- Methyltransferase (3)
- Metoprolol (3)
- Microdialyse (3)
- Migrationshintergrund (3)
- Mikrokavität (3)
- Mikroklima (3)
- Mikrooptik (3)
- Mikroporosität (3)
- Mikrosatelliten (3)
- Mikrotubuli (3)
- Mikroverkapselung (3)
- Mineralisation (3)
- Mineralokortikoidrezeptor (3)
- Mip (3)
- Mismatch (3)
- Mittelhochdeutsch (3)
- Mittelmeerraum (3)
- Modifizierung (3)
- Molecular Beam Epitaxy (3)
- Molecular biology (3)
- Molecular dynamics (3)
- Monoaminoxidase (3)
- Monodromie (3)
- Monte Carlo simulation (3)
- Morphogenese (3)
- Mosaik (3)
- Motorische Entwicklung (3)
- Mott-Übergang (3)
- Mouse model (3)
- Mucorales (3)
- Multiagentensystem (3)
- Multimedia (3)
- Multiple bonds (3)
- Multispecies Studies (3)
- Mundart (3)
- Mundhöhle (3)
- Mundhöhlenkrebs (3)
- Mundhöhlentumor (3)
- Muscarin (3)
- Muscarinic receptor subtypes (3)
- Muscarinic receptors (3)
- Museumspädagogik (3)
- Musikwahrnehmung (3)
- Muskelkraft (3)
- Muster (3)
- Mutante (3)
- Mutationsrate (3)
- Mycobacterium (3)
- Myelin oligodendrocyte glycoprotein antibodies (MOG-IgG) (3)
- Myeloma (3)
- Mythos (3)
- Mädchenfußball (3)
- Münchner Hof (3)
- N-Heterocyclic Carbenes (3)
- N-heterocyclic carbene (3)
- N170 (3)
- NADPH-Oxidase (3)
- NIR (3)
- NK cell (3)
- NK-Zellen (3)
- NLS (3)
- NMR-spectroscopy (3)
- NOS1AP (3)
- NSG (3)
- NVP-BEZ235 (3)
- Nabelhernie (3)
- Nachruf (3)
- Nahtmaterial (3)
- Nanoelektronik (3)
- Nanomaterialien (3)
- Naphthalinderivate (3)
- Naphthylisochinoline (3)
- Narrative (3)
- Narratologie (3)
- Natalizumab (3)
- Nationalpark (3)
- Natrium (3)
- Natrium-Calcium-Austauscher (3)
- NaturenKulturen (3)
- Nebennierenkrise (3)
- Nepenthes (3)
- Nervenstimulation (3)
- Nervensystem (3)
- Nestin (3)
- Networks (3)
- Netzwerkmanagement (3)
- Neumarkt <Oberpfalz> (3)
- Neuroblast (3)
- Neuroendokrines System (3)
- Neuromyelitis optica spectrum disorders (NMOSD) (3)
- Neuronale Netze (3)
- Neuropeptid Y (3)
- Neuroprotection (3)
- Neuropsychologie (3)
- Neuroscience (3)
- Neurotizismus (3)
- Neurotransmitter (3)
- Neurotrophe Faktoren (3)
- Neurotrophine (3)
- Neutrophil (3)
- Neutrophils (3)
- New Zealand (3)
- Nichtadiabatischer Prozess (3)
- Nichtionisierende Strahlung (3)
- Nichtkonvexe Optimierung (3)
- Nichtlineares System (3)
- Nicotin (3)
- Nicotine (3)
- Nicotinischer Acetylcholinrezeptor (3)
- Niederdimensionales Elektronengas (3)
- Niederdimensionales System (3)
- Nierenkrebs (3)
- Nitric oxide (3)
- Nociceptor (3)
- Noradrenalin (3)
- Norm (3)
- Nozizeption (3)
- Nozizeptor (3)
- Nrf2 (3)
- Nucleolus (3)
- Nude-mice (3)
- Numerische Strömungssimulation (3)
- ODMR-Spektroskopie (3)
- OSAS (3)
- OST1 (3)
- Oberflächenplasmonresonanz (3)
- Octopamin (3)
- Octopamine (3)
- Olfaktion (3)
- Olfaktorik (3)
- Oligonucleotide (3)
- Omega-3-Fettsäuren (3)
- Omp85 (3)
- Oogenese (3)
- Open Access (3)
- Operante Konditionierung (3)
- Optic neuritis (3)
- Optical Spectroscopy (3)
- Optische Eigenschaft (3)
- Optische Zeichenerkennung (3)
- Organic Semiconductors (3)
- Organisationskultur (3)
- Organische Halbleiter (3)
- Orient (3)
- Orientalistik (3)
- Oropharynx (3)
- Osmolarität (3)
- Osseointegration (3)
- Osteoarthrose (3)
- Osteoblast (3)
- Osteoklast (3)
- Osteoporosis (3)
- Outcome survey (3)
- OxLDL (3)
- Oxygen (3)
- P-glycoprotein (3)
- PDGF (3)
- PDZ-Domain (3)
- PDZ-Domäne (3)
- PFC (3)
- PKB (3)
- PKC (3)
- PLC (3)
- PMCA (3)
- PNP (3)
- PROM (3)
- PTSD (3)
- PZT (3)
- Paclitaxel (3)
- Pair Production (3)
- Pakistan (3)
- Palliative Care (3)
- Palliativversorgung (3)
- Pappel (3)
- Paracyclophane (3)
- Paraffin (3)
- Parallel Imaging (3)
- Pareto-Verteilung (3)
- Parkinson Disease (3)
- Parkinsons disease (3)
- Particle Physics (3)
- Particle data analysis (3)
- Passionsspiel (3)
- Passivrauchen (3)
- Patella (3)
- Patellaluxation (3)
- Pathogener Mikroorganismus (3)
- Pathogenitätsinseln (3)
- Pathology (3)
- Pathophysiologie (3)
- Patient education (3)
- Patterns (3)
- Peer-to-Peer-Netz (3)
- Pentacoordination (3)
- Peristaltik (3)
- Peritonitis (3)
- Permafrost (3)
- Peroxisom (3)
- Persönlichkeitsmerkmale (3)
- Persönlichkeitsstörung (3)
- Perylen (3)
- Pest (3)
- Peyer's patch (3)
- Phagosom (3)
- Pharmaceutical Analysis (3)
- Pharmazeutischer Hilfsstoff (3)
- Phonologie (3)
- Phosphate (3)
- Phosphorylation (3)
- Photoinduzierter Elektronentransfer (3)
- Photoluminescence (3)
- Photolyse (3)
- Photolysis (3)
- Photonische Kristalle (3)
- Photonischer Kristall (3)
- Photopolymerisation (3)
- Photosensibilisator (3)
- Physical activity (3)
- Physik jenseits des Standardmodells (3)
- Physikunterricht (3)
- Physiologische Psychologie (3)
- Phytohormone (3)
- Piperidinalkaloide (3)
- Plaque (3)
- Plasmodium (3)
- Plastik (3)
- Plattform (3)
- Platy (3)
- Pleuraerguss (3)
- Plexus brachialis (3)
- Pluripotenz (3)
- Plättchen (3)
- Pneumolysin (3)
- Poetik (3)
- Poetologie (3)
- Polycomb (3)
- Polycyclic Aromatic Hydrocarbons (3)
- Polyglycidol (3)
- Polymerase chain reaction (3)
- Polymers (3)
- Polymorphismen (3)
- Polyomaviren (3)
- Populationsgenetik (3)
- Poribacteria (3)
- Porphyrin (3)
- Porphyrine (3)
- Poröser Stoff (3)
- Positron Emission Tomography (3)
- Positron emission tomography (3)
- Postmoderne (3)
- Posttranslationale Änderung (3)
- Predictors (3)
- Pregnancy (3)
- Preisbindung (3)
- Prionprotein (3)
- Procyanidine (3)
- Prognosefaktor (3)
- Prognosefaktoren (3)
- Promoter (3)
- Prophylaxe (3)
- Prostate Cancer (3)
- Prostatektomie (3)
- Protection (3)
- Protein p8 (3)
- Protein-Serin-Threonin-Kinasen (3)
- Proteinkinase CK2 (3)
- Proteinkinase D (3)
- Proteintransport (3)
- Proteinurie (3)
- Proteomics (3)
- Proton-Proton Collisions (3)
- Protonenpumpe (3)
- Protozoen (3)
- Präfrontaler Kortex (3)
- Prüfungshonorare (3)
- Prüfungsqualität (3)
- Pseudarthrose (3)
- Pseudomonas aeruginosa (3)
- Psychology (3)
- Psychoneuroimmunologie (3)
- Psychopathologie (3)
- Psychophysik (3)
- Psychotherapeutischer Prozess (3)
- Psychotherapy (3)
- Pulswelle (3)
- Pycnogenol (3)
- Pyrene (3)
- QCD (3)
- QST (3)
- Quadrotor (3)
- Quantenelektrodynamik (3)
- Quantitative Analyse (3)
- Quantum Information (3)
- Quantum Monte Carlo (3)
- Quantum dots (3)
- Quantum dynamics (3)
- Quantum many-body systems (3)
- Quartär (3)
- Quercetin (3)
- R package (3)
- RHO (3)
- RIM101 (3)
- RKIP (3)
- RNA metabolism (3)
- RNA splicing (3)
- RNA structure (3)
- RNA-SEQ (3)
- RNA-sequencing (3)
- RNAseq (3)
- RNS-Viren (3)
- RPE (3)
- RSK2 (3)
- RT-qPCR (3)
- Rac (3)
- Radarsat-2 (3)
- Radiation (3)
- Radikal (3)
- Radiochemotherapie (3)
- Radiologie (3)
- Radiosurgery (3)
- Radius (3)
- Raman Spektroskopie (3)
- Ranunculus auricomus (3)
- Rassismus (3)
- Rastertunnelspektroskopie (3)
- Rating (3)
- Rats (3)
- Raucher (3)
- Raumfahrt (3)
- Raumverhalten (3)
- Rauschen (3)
- Real-time PCR (3)
- Reanimation (3)
- Rechnungswesen (3)
- Rechtschreibschwäche (3)
- Recovery (3)
- Recurrence (3)
- Recurrensparese (3)
- Reduction (3)
- Reform (3)
- Reformpädagogik (3)
- Regionalanästhesie (3)
- Regionalwirtschaft (3)
- Regularisierung (3)
- Relapse (3)
- Relaxometry (3)
- Religious Education (3)
- Religiöse Bildung (3)
- Remifentanil (3)
- Remineralisation (3)
- Remission (3)
- Renaissance (3)
- Renal cell carcinoma (3)
- Renin-Angiotensin-Aldosteron-System (3)
- Replikationsursprung (3)
- Repression <Genetik> (3)
- Reproduktion (3)
- Resistance (3)
- Resonanz (3)
- Resonanz-Raman-Effekt (3)
- Resonanz-Tunneldiode (3)
- Resonanz-Tunneleffekt (3)
- Ressourcenallokation (3)
- Restenose (3)
- Retinoic acid (3)
- Retinsäure (3)
- Rezeptortyrosinkinase (3)
- Rezidivrate (3)
- Rho (3)
- Rho GTPase (3)
- Rhodiumkomplexe (3)
- Riester-Rente (3)
- Ringspannung (3)
- Risikomanagement (3)
- Risk Assessment (3)
- Risk factors (3)
- Ritual (3)
- Rossameise (3)
- Rubus (3)
- Ruthenium Komplexe (3)
- Räumliche Verteilung (3)
- Römisches Reich (3)
- Röntgenabsorptionsspektroskopie (3)
- Röntgenastronomie (3)
- Röntgenkristallographie (3)
- Röntgenmikroskopie (3)
- Röntgenstrukturanalyse (3)
- SBRT (3)
- SEM (3)
- SF-36 (3)
- SGLT (3)
- SIRS (3)
- SIV (3)
- SLAM (3)
- SLOOP (3)
- SM background (3)
- SMARD1 (3)
- SOCE (3)
- SPECT/CT (3)
- SRT (3)
- STAT (3)
- STAT6 (3)
- STIM2 (3)
- STM (3)
- STR (3)
- SWOT (3)
- Salmonella typhi (3)
- Salz (3)
- Samenpflanzen (3)
- Sammeln (3)
- Sarkopenie (3)
- Satellitenfernerkundung (3)
- Satzglied (3)
- Scarabaeidae (3)
- Scattering (3)
- Scheibe-Aggregat (3)
- Scherfestigkeit (3)
- Scherstress (3)
- Schichttechnik (3)
- Schilddrüsenkarzinom (3)
- Schleimhaut (3)
- Schleswig-Holstein (3)
- Schließzellen (3)
- Schockraumalgorithmus (3)
- Schreckreaktion (3)
- Schreimelodie (3)
- Schuppenflechte (3)
- Schwann cells (3)
- Schwingungsspektroskopie (3)
- Search (3)
- Secretion (3)
- Sectio caesarea (3)
- Sedimentologie (3)
- Segmentierung (3)
- Sekundarstufe 1 (3)
- Selbstgesteuertes Lernen (3)
- Selbstmord (3)
- Selenoprotein P (3)
- Self-Assembly (3)
- Semantik (3)
- Semiconductors (3)
- Seneca (3)
- Senescence (3)
- Seneszenz (3)
- Sensors (3)
- Sequenzierung (3)
- Serotonin-Reuptake-Hemmer (3)
- Serotonintransporter (3)
- Service Learning (3)
- Sexualität (3)
- Shigella (3)
- Shigella flexneri (3)
- Sicherheit (3)
- Sicherheitspolitik (3)
- Siedlungsarchäologie (3)
- Signaltransduction (3)
- Silanderivate (3)
- Siloran (3)
- Simulationstraining (3)
- Singlet Oxygen (3)
- Singulettsauerstoff (3)
- Sinnesphysiologie (3)
- Situationsbewusstsein (3)
- Skalierbarkeit (3)
- Skiverletzung (3)
- Skorpion (3)
- Social Cognition (3)
- Social interaction (3)
- Socrates (3)
- Software-defined networking (3)
- Softwarearchitektur (3)
- Solubilisation (3)
- Sonnenwind (3)
- Sozialangst (3)
- Sozialgeschichte (3)
- Sozialisation (3)
- Sozialität (3)
- Soziologie des Dritten (3)
- Species richness (3)
- Speckle tracking (3)
- Speiseröhre (3)
- Spektroelektrochemie (3)
- Spermatogenesis (3)
- Spezialisierung (3)
- Spieltheorie (3)
- Spin-Gitter-Relaxation (3)
- Spinal Muscular Atrophy (3)
- Spinalanästhesie (3)
- Spinalganglion (3)
- Spinchemie (3)
- Spinnenseide (3)
- Spironolacton (3)
- Spleißen (3)
- Spleißosom (3)
- Splicing (3)
- Sprachverständlichkeit (3)
- Spred Protein (3)
- Src-Proteine (3)
- Staat (3)
- Stachellose Biene (3)
- Staging (3)
- Stakeholder (3)
- Standardisierung (3)
- Staphylokokken (3)
- Stat3 (3)
- Sterbebegleitung (3)
- Stereophotogrammetrie (3)
- Stereophotogrammetry (3)
- Stereoselectivity (3)
- Sternpolymere (3)
- Steroide (3)
- Steroidhormon (3)
- Steuer (3)
- Stickstoffoxide (3)
- Stochastische Resonanz (3)
- Stochastischer Prozess (3)
- Stomata (3)
- Stoßwelle (3)
- Strafrecht (3)
- Straftat (3)
- Strafvollzug (3)
- Strahlung (3)
- Strainrate (3)
- Strandkiefer (3)
- Structural elucidation (3)
- Strukturbasiertes Wirkstoffdesign (3)
- Strömung (3)
- Suberin (3)
- Substantia nigra (3)
- Substratspezifität (3)
- Succinylcholine (3)
- Sucht (3)
- Suizidalität (3)
- Sulforaphan (3)
- Super-resolution microscopy (3)
- Superparamagnetismus (3)
- Supersymmetric models (3)
- Supply Chain (3)
- Surface modification (3)
- Surface plasmons (3)
- Switzerland (3)
- Symmetry (3)
- Synaptische Transmission (3)
- Synaptische Vesikel (3)
- Synchronisierung (3)
- Synchronization (3)
- Systemisches Risiko (3)
- Süddeutsche Zeitung (3)
- Südkorea (3)
- Südostasien (3)
- T cell development (3)
- T cell receptors (3)
- T lymphocyte (3)
- T-Zell-Rezeptor (3)
- T-Zellaktivierung (3)
- T-Zellrezeptor (3)
- T-cadherin (3)
- T-cell lymphoma (3)
- T1 (3)
- TCR (3)
- TD-DFT (3)
- TEM (3)
- TGF-ß (3)
- TGN1412 (3)
- THA (3)
- TLR3 (3)
- TLR8 (3)
- TNF superfamily (3)
- TRAF1 (3)
- TRH (3)
- TRPA1 (3)
- TTFields (3)
- Taiwan (3)
- Talentförderung (3)
- Tantal (3)
- Targeted therapy (3)
- Taxol (3)
- Teaching (3)
- Testament (3)
- Testbatterie (3)
- Testosteron (3)
- Text (3)
- Textvergleich (3)
- Therapieergebnisse (3)
- Therapieresistenz (3)
- Thermoelektrizität (3)
- Thiazolidindione (3)
- Thigmotaxis (3)
- Thioaldehyde (3)
- Thiophen (3)
- Thioredoxin (3)
- Thrombozytenaktivierung (3)
- Thrombozytopenie (3)
- Thrombus (3)
- Thyroid cancer (3)
- Tibiakopfbruch (3)
- Tibiakopfimpressionsfraktur (3)
- Tiergesellschaft (3)
- Tierversuch (3)
- Tierökologie (3)
- Titanium (3)
- Tolerance (3)
- Tomografie (3)
- Topoisomerase I (3)
- Topological Insulator (3)
- Topological insulators (3)
- Topologische Phase (3)
- Topologische Supraleitung (3)
- Topology (3)
- Tourette syndrome (3)
- Tourism (3)
- Trachea (3)
- Tragik (3)
- Transaktivierung (3)
- Transforming Growth Factor beta 1 (3)
- Transiente Absorptionsspektroskopie (3)
- Transistor (3)
- Transparent-leitendes Oxid (3)
- Transportspektroskopie (3)
- Tricalciumphosphat (3)
- Triphyophyllum peltatum (3)
- Triquinacenderivate (3)
- Trockenstress (3)
- Trypanosoma brucei brucei (3)
- Trypanosomes (3)
- Tuberculosis (3)
- Tuff (3)
- Tumor-necrosis-factor (3)
- Tumormodell (3)
- Tumorstammzellen (3)
- Tumorstoffwechsel (3)
- Tumorsuppressor-Gen (3)
- Tumortherapiefelder (3)
- Tumorwachstum (3)
- Tumorzellen (3)
- Turbulenz (3)
- Tyrosinkinaseinhibitor (3)
- UPEC (3)
- USP8 (3)
- Ubiquitin-Protein-Ligase (3)
- Ulcerative colitis (3)
- Ultrafiltration (3)
- Ultraschallkontrastmittel (3)
- Umbilikalhernie (3)
- Umweltfaktor (3)
- Umweltpolitik (3)
- Unterrichtsmethode (3)
- Ureaplasma urealyticum (3)
- Urothelkarzinom (3)
- Uzbekistan (3)
- VKORC1 (3)
- VLBWI (3)
- VMD2 (3)
- VSOP (3)
- Variant surface glycoprotein (3)
- Variants (3)
- Varianzanalyse (3)
- Variationsrechnung (3)
- Vasopressin (3)
- Vegetatives Nervensystem (3)
- Verbraucherschutz (3)
- Verbreitung (3)
- Vereinte Nationen (3)
- Vernetzung <Chemie> (3)
- Versorgung (3)
- Verstärkung (3)
- Verteilung (3)
- Vertigo (3)
- Vertrauen (3)
- Verwaltung (3)
- Verwundbarkeit (3)
- Vesikel (3)
- Viabilität (3)
- Vibrio cholerae (3)
- Video Streaming (3)
- Videolaryngoskopie (3)
- Videoübertragung (3)
- Vielfalt (3)
- Vietnam (3)
- Vif (3)
- Vigilanz (3)
- Virulenzfaktoren (3)
- Visuelles System (3)
- Visus (3)
- Viszeralchirurgie (3)
- Vitamin K (3)
- Volatile Anästhetika (3)
- Volumenregulation (3)
- Volumentomographie (3)
- Vorhofohramputation (3)
- Vorkommen (3)
- Vorlesung (3)
- Vorsprachliche Entwicklung (3)
- Vulgata (3)
- Vulkanologie (3)
- Vulneranz (3)
- W boson (3)
- WNT (3)
- Wachs (3)
- Warburg effect (3)
- Warnung (3)
- Wasserlöslichkeit (3)
- Weak (3)
- Wechselkurspolitik (3)
- Weiterbildung (3)
- Wellenleiter (3)
- Werbung (3)
- Wert (3)
- Wertigkeit (3)
- Wertschöpfungskette (3)
- Wespen (3)
- Western Cape (3)
- Weyarn / Stift (3)
- Wiederbelebung (3)
- Wilms Tumor (3)
- Wilms' tumor (3)
- Wirkstoff-Träger-System (3)
- Wirkstoffdesign (3)
- Wirtschaftsentwicklung (3)
- Wirtschaftsprüfer (3)
- Wirtschaftsprüfung (3)
- Wirtschaftswachstum (3)
- Wissenschaft (3)
- Wissenserwerb (3)
- Wissensmanagement (3)
- Working memory (3)
- Wurzelhalsgalle (3)
- Wurzelkanalbehandlung (3)
- Währungsunion (3)
- Wärmeübertragung (3)
- Würzburg / Institut für Humangenetik (3)
- Würzburg / Sonderforschungsbereich II-VI-Halbleiter (3)
- Würzburg / Universität / Lehrstuhl für Bioinformatik (3)
- Xenobiotikum (3)
- Xenophon (3)
- Xenopus oocytes (3)
- Xenotransplantation (3)
- Xylem (3)
- Y chromosome (3)
- YAP (3)
- YB-1 (3)
- Zahnersatz (3)
- Zahnprothetik (3)
- Zelloberfläche (3)
- Zentralasien (3)
- Zerfall (3)
- Zetafunktion (3)
- Zinn (3)
- Zivilgesellschaft (3)
- Zugspannung (3)
- Zweidimensionales Material (3)
- Zweiphotonenabsorption (3)
- Zwischenmolekulare Kraft (3)
- ab initio calculations (3)
- abandonment (3)
- abiotic stress (3)
- abnormalities (3)
- absolute configuration (3)
- accelerometer (3)
- acceptance (3)
- acetylcholine (3)
- acetylsalicylic acid (3)
- acquisition (3)
- acrophobia (3)
- actins (3)
- action effects (3)
- action potential (3)
- activity (3)
- acupuncture (3)
- acute graft-versus-host disease (3)
- acute lymphoblastic leukemia (3)
- acute myeloid leukaemia (3)
- acute renal failure (3)
- adaption (3)
- adaptive immune system (3)
- adaptive immunity (3)
- addiction (3)
- adduct (3)
- adenocarcinoma of the lung (3)
- adenoma (3)
- adiponectin (3)
- adipose (3)
- adipose-derived stromal cells (3)
- adjuvant (3)
- adrenal crisis (3)
- adrenocortical cancer (3)
- adult ADHD (3)
- adverse events (3)
- aerobic fitness (3)
- affinity (3)
- african trypanosomes (3)
- agalsidase alfa (3)
- agalsidase beta (3)
- age groups (3)
- agonist (3)
- agr (3)
- airway management (3)
- akutes Koronarsyndrom (3)
- aldehydes (3)
- allometric scaling (3)
- alpha (3)
- altitudinal gradients (3)
- alveolar echinococcosis (3)
- ambulant (3)
- amplicon sequencing (3)
- amyloidosis (3)
- anaemia (3)
- analysis (3)
- anandamide (3)
- anastomotic leakage (3)
- angiotensin II (3)
- animal sociality (3)
- anisotropy (3)
- annulation (3)
- ansa-Komplexe (3)
- anterior insula (3)
- anthropogenic disturbance (3)
- antibakteriell (3)
- anticoagulants (3)
- antigen presentation (3)
- antigen testing (3)
- antimikrobielle Peptide (3)
- antimony (3)
- aortic aneurysm (3)
- aortic stenosis (3)
- applied physics (3)
- approach (3)
- approximation algorithm (3)
- arabidopsis (3)
- architecture (3)
- arctic (3)
- arrhythmogenic cardiomyopathy (3)
- artemisinin (3)
- arthrography (3)
- articulation (3)
- artificial photosynthesis (3)
- aspirin (3)
- assay (3)
- assistierte Reproduktion (3)
- assistive technology (3)
- association study (3)
- asymmetry (3)
- attention deficit/hyperactivity disorder (3)
- attentional control (3)
- auditory cortex (3)
- auditory evoked potentials (3)
- autism spectrum disorder (3)
- autograft (3)
- autologous stem cell transplantation (3)
- autonomes Nervensystem (3)
- avidity (3)
- axonal transport (3)
- axons (3)
- azobenzenes (3)
- bZIP (3)
- bacillus subtilis (3)
- bacterial (3)
- bacterial infection (3)
- bacterial meningitis (3)
- bacteriophage (3)
- bark beetles (3)
- barrier (3)
- beta-D-glucan (3)
- beta-oxidation (3)
- binding protein (3)
- bioactivity (3)
- biocatalysis (3)
- bioconjugation (3)
- biogenic amines (3)
- bioinformatic (3)
- biological activity (3)
- biological pest control (3)
- biological techniques (3)
- bioluminescence imaging (3)
- biomedical engineering (3)
- biomedical materials (3)
- biosensor (3)
- biosensors (3)
- biotechnology (3)
- biotransformation (3)
- birth cohort (3)
- black holes (3)
- blended learning (3)
- blood coagulation (3)
- blood vessel (3)
- body ownership (3)
- bonding agent (3)
- bone defect (3)
- bone density (3)
- bone disease (3)
- bone metabolism (3)
- bone morphogenetic protein (3)
- bone morphogenetic proteins (3)
- bone-marrow (3)
- boroles (3)
- boronate (3)
- brain cancer (3)
- brain derived neurotrophic factor (3)
- breast-tumors (3)
- bruxism (3)
- bullous pemphigoid (3)
- bumblebees (3)
- burn severity (3)
- butterflies (3)
- c-Fos (3)
- c-Myc (3)
- c-myc (3)
- cFLIP (3)
- calcification (3)
- calcium signaling (3)
- calorimetry (3)
- calpain (3)
- cancer cells (3)
- cancer microenvironment (3)
- candida (3)
- canine (3)
- canine cancer therapy (3)
- canola (3)
- capecitabine (3)
- carabid beetles (3)
- carbene ligands (3)
- carbon nanotubes (3)
- carcinogenesis (3)
- carcinogenicity (3)
- carcinoma cells (3)
- cardiac MRI (3)
- cardiac imaging (3)
- cardiac rehabilitation (3)
- cardiolipin (3)
- cardiology (3)
- cardiovascular magnetic resonance (3)
- caspase-3 (3)
- caspases (3)
- cathepsin (3)
- cationic species (3)
- cations (3)
- causality (3)
- cell binding (3)
- cell fusion (3)
- cell growth (3)
- cell imaging (3)
- cell labeling (3)
- cell signalling (3)
- cell therapy (3)
- central-nervous-system (3)
- ceramics (3)
- cerebEND (3)
- cerebellar tDCS (3)
- cerebrovascular disorders (3)
- cestode (3)
- chalcogens (3)
- channel (3)
- channelrhodopsin (3)
- chaperone (3)
- chaperones (3)
- charge separation (3)
- charged aerosol detector (3)
- chemische Kommunikation (3)
- chimeric antigen receptor (3)
- chlamydia infection (3)
- cholesterol (3)
- chromophore (3)
- chronic stress (3)
- chronophin (3)
- citrus (3)
- claudin-1 (3)
- clinical genetics (3)
- clinical outcome (3)
- clinical practice (3)
- clonality (3)
- closed head injury (3)
- cluster (3)
- coating (3)
- coatings (3)
- cochlear implantation (3)
- coexistence (3)
- cohort studies (3)
- cohort study (3)
- colonoscopy (3)
- community (3)
- community ecology (3)
- complexation (3)
- compliance (3)
- composite (3)
- conditioned response (3)
- confocal microscopy (3)
- conjugation (3)
- consolidation (3)
- contrast (3)
- contrast media (3)
- control (3)
- conversion (3)
- coordination polymer (3)
- coordination polymers (3)
- coreceptor (3)
- cornea (3)
- coronary artery bypass grafting (3)
- corticosteroids (3)
- count time series (3)
- criteria (3)
- critically ill (3)
- crossing minimization (3)
- crowdsourcing (3)
- cryptochrome (3)
- curriculum (3)
- curved hydrocarbons (3)
- cycloid psychosis (3)
- cyclophanes (3)
- cytogenetics (3)
- cytosol (3)
- data acquisition (3)
- data analysis (3)
- data fusion (3)
- data mining (3)
- death (3)
- decomposition (3)
- defects (3)
- deficient mice (3)
- deformation (3)
- deformation quantization (3)
- deletion (3)
- density (3)
- deoxyribozymes (3)
- depressive disorder (3)
- derivation (3)
- derivatives (3)
- desmin (3)
- detection (3)
- developmental differentiation (3)
- diabetic cardiomyopathy (3)
- diagnostic (3)
- diagnostic medicine (3)
- diastolic dysfunction (3)
- diazepam (3)
- differential diagnosis (3)
- differentiation potential (3)
- dilated cardiomyopathy (3)
- disease progression (3)
- diseases (3)
- disorder (3)
- distraction (3)
- diversity gradients (3)
- dizziness (3)
- doctoral graduates (3)
- dogs (3)
- double-blind (3)
- driving (3)
- drought stress (3)
- drug adverse reaction (3)
- drug allergy (3)
- drug development (3)
- drug hypersensitivity (3)
- drug release (3)
- drug resistance (3)
- drug therapy (3)
- duchenne muscular dystrophy (3)
- dunce (3)
- dynamic programming (3)
- dyspnea (3)
- early detection (3)
- early diagnosis (3)
- early intervention (3)
- early-life stress (3)
- eating behavior (3)
- edge states (3)
- electrical and electronic engineering (3)
- electrical impedance tomography (3)
- electrocatalysis (3)
- electrochromic device (3)
- electrohydrodynamics (3)
- electromyography (3)
- electron density (3)
- electroporation (3)
- elevated plus-maze (3)
- elevation (3)
- elevational gradient (3)
- elongation (3)
- embodied cognition (3)
- embryonic stem cell (3)
- embryonic stem cells (3)
- embryos (3)
- emerin (3)
- emotion processing (3)
- emotion recognition (3)
- emotional processing (3)
- emphysema (3)
- empowerment (3)
- endophenotype (3)
- endophyte (3)
- endoradiotherapy (3)
- endothelial barrier (3)
- endothelial cell (3)
- endotheliale Vorläuferzellen (3)
- engineering (3)
- entomology (3)
- entrepreneurship (3)
- entropy (3)
- entropy production (3)
- environmental health (3)
- environmental justice (3)
- ependymoma (3)
- epidermis (3)
- ereigniskorrelierte Potentiale (3)
- esophagus (3)
- essential tremor (3)
- ethics (3)
- etiology (3)
- etomidate (3)
- evidence-based medicine (3)
- evoked potentials (3)
- evozierte Potentiale (3)
- ex vivo (3)
- executive functions (3)
- exercise intensity (3)
- exome sequencing (3)
- exosomes (3)
- expression analysis (3)
- extreme value theory (3)
- fMRT (3)
- fabry disease (3)
- face (3)
- fanconi anemia (3)
- fatty acid (3)
- fatty liver disease (3)
- fear of progression (3)
- feasibility (3)
- feeding (3)
- female (3)
- fermentation (3)
- ferroelectricity (3)
- ferromagnetism (3)
- fiber (3)
- fibroblast activation protein (3)
- finite element method (3)
- fire (3)
- fixation (3)
- flexibility (3)
- flow regulation (3)
- flow regulator (3)
- flowability (3)
- flowers (3)
- fluorescence correlation spectroscopy (3)
- fluorescence spectroscopy (3)
- fluoroquinolones (3)
- flux (3)
- foamy viruses (3)
- foamyvirus (3)
- food safety (3)
- force (3)
- forestry (3)
- formicidae (3)
- fpVCT (3)
- fragment reattachment (3)
- fragmentation (3)
- frailty (3)
- framing (3)
- free electron laser (3)
- frontotemporal dementia (3)
- fully convolutional neural networks (3)
- functional imaging (3)
- functional neuroimaging (3)
- functional training (3)
- fungal infections (3)
- fungal pathogens (3)
- fungal rhodopsins (3)
- furan (3)
- gametocyte (3)
- gamma astronomy (3)
- gamma radiation (3)
- gamma rays (3)
- gas (3)
- gastric bypass (3)
- gastroenterology (3)
- gastrointestinale Tumore (3)
- gefitinib (3)
- gekrümmte Kohlenwasserstoffe (3)
- gene expression profiling (3)
- generalization (3)
- genetic engineering (3)
- genetic modifiers (3)
- genetic testing (3)
- genetic variation (3)
- genome assembly (3)
- genome integrity (3)
- genome sequence (3)
- genotyping (3)
- geometry (3)
- geophysics (3)
- gestaltungsorientierte Bildungsforschung (3)
- girls (3)
- glaciers (3)
- glial fibrillary acidic protein (3)
- global convergence (3)
- glomerular filtration rate (3)
- glomeruli (3)
- glutamate transporters (3)
- glutathione (3)
- glycoproteins (3)
- gold (3)
- grading (3)
- graft (3)
- grammar (3)
- granzyme B (3)
- graphene (3)
- growth cone (3)
- growth factor (3)
- growth hormone deficiency (3)
- guanylyl cyclase (3)
- guided bone regeneration (3)
- guinea pig (3)
- gynogenesis (3)
- haemodialysis (3)
- haemostasis (3)
- handlungs- und entwicklungsorientierte Didaktik (3)
- hands (3)
- hangover (3)
- hardness (3)
- head and neck (3)
- healing (3)
- healthcare (3)
- hearing aid (3)
- hearing screening (3)
- heart transplantation (3)
- heat shock protein (3)
- heat shock response (3)
- helicase (3)
- helminths (3)
- hematopoiesis (3)
- hemodiafiltration (3)
- hemoglobin (3)
- hemolysin (3)
- hepatitis B virus (3)
- hepatocellular carcinoma (3)
- hepatotoxicity (3)
- herbivores (3)
- herbivory (3)
- heritability (3)
- herpesvirus (3)
- heterogeneity (3)
- hiPSC-CM (3)
- high-intensity interval training (3)
- hip arthroplasty (3)
- histone H2AX (3)
- histones (3)
- histopathology (3)
- historical document analysis (3)
- history of medicine (3)
- homology modeling (3)
- honeycomb lattice (3)
- hormones (3)
- hospital (3)
- host-pathogen interactions (3)
- human brain (3)
- human brain microvascular endothelial cells (3)
- human genetics (3)
- human immunodeficiency virus (3)
- human learning (3)
- human rights (3)
- humane mesenchymale Stammzellen (3)
- humidity (3)
- hydrological modelling (3)
- hydrology (3)
- hyperalgesia (3)
- hypercholesterolemia (3)
- hypertrophic cardiomyopathy (3)
- idiopathic pulmonary fibrosis (3)
- illness (3)
- image analysis (3)
- image quality (3)
- image segmentation (3)
- imaging the immune system (3)
- immediate early genes (3)
- immersive technologies (3)
- immune activation (3)
- immune escape (3)
- immune reconstitution (3)
- immune suppression (3)
- immunisation (3)
- immunoassay (3)
- immunocytochemistry (3)
- immunodeficiency (3)
- immunoglobulin (3)
- immunoreactive neurons (3)
- impedance spectroscopy (3)
- impurities (3)
- impurity profiling (3)
- inclusion (3)
- indication for surgery (3)
- individual differences (3)
- individual-based simulation (3)
- infant cry (3)
- infants (3)
- infectious disease (3)
- inflammatory diseases (3)
- inflammatory response (3)
- information extraction (3)
- informed consent (3)
- infrared (3)
- innate immune system (3)
- instrument (3)
- insulator (3)
- intelligence (3)
- intensity distribution (3)
- intentional binding (3)
- interaction networks (3)
- interactome (3)
- interface (3)
- interleukin 4 (3)
- interleukin-4 (3)
- interleukin-6 (3)
- interleukins (3)
- intermanual transfer (3)
- intuition (3)
- inventory (3)
- investigators (3)
- involvement (3)
- iodine (3)
- iron deficiency (3)
- irrigation (3)
- ischemia reperfusion injury (3)
- ischemia/reperfusion injury (3)
- islet transplantation (3)
- islets of Langerhans (3)
- isoliert (3)
- isomerization (3)
- isotopes (3)
- jasmonic acid (3)
- jet energy scale uncertainty (3)
- jets (3)
- juvenile hormone (3)
- kardiovaskuläre Risikofaktoren (3)
- ketogenic diet (3)
- kinase inhibitor (3)
- kinesin (3)
- kinetic model (3)
- knee joint (3)
- knee replacement (3)
- knock-out (3)
- kutikuläre Kohlenwasserstoffe (3)
- lamina (3)
- laminopathy (3)
- land-use change (3)
- landscape ecology (3)
- laparoscopic ventral hernia repair (3)
- larynx (3)
- laser (3)
- leaf beetle (3)
- learning strategies (3)
- leaves (3)
- left ventricular ejection fraction (3)
- leishmania major (3)
- length of stenosis (3)
- leptin (3)
- leukocytes (3)
- levodopa (3)
- library screening (3)
- life events (3)
- life history (3)
- ligand (3)
- ligand binding (3)
- light quark jet (3)
- linkage analysis (3)
- lipid metabolism (3)
- liraglutide (3)
- literature review (3)
- lithium-ion battery (3)
- liver metastasis (3)
- local field potentials (3)
- locomotor activity (3)
- low back pain (3)
- low-grade glioma (3)
- low-valent compounds (3)
- lower extremity (3)
- lung and intrathoracic tumors (3)
- lung injury (3)
- lymph node dissection (3)
- mCRP (3)
- mTOR (3)
- macrocycle (3)
- magnesium phosphate (3)
- magnetic susceptibility (3)
- main group elements (3)
- major histocompatibility complex (3)
- malignancy (3)
- malignant tumors (3)
- malnutrition (3)
- mammography (3)
- marine natural products (3)
- masculinity (3)
- mastocytosis (3)
- materials for optics (3)
- mathematical modelling (3)
- maturation (3)
- mechanical properties (3)
- mechanics (3)
- mechanosensing (3)
- media literacy (3)
- medical (3)
- megakaryopoiesis (3)
- melanogaster (3)
- melanoma cells (3)
- memory formation (3)
- mercury (3)
- merocyanines (3)
- mesencephalic locomotor region (3)
- mesoscopic (3)
- mesoscopics (3)
- messenger-RNA (3)
- metabolic modeling (3)
- metabolischer Test (3)
- metabolites (3)
- metabonomics (3)
- metacognition (3)
- metacomprehension (3)
- metallocenophanes (3)
- metallosupramolecular chemistry (3)
- metals (3)
- methionine restriction (3)
- methods (3)
- miR (3)
- miR-26 (3)
- micelles (3)
- microRNA-221 (3)
- microbial ecology (3)
- microbial rhodopsins (3)
- microclimate (3)
- microfluidics (3)
- microsatellites (3)
- microtubules (3)
- microvascular endothelial cells (3)
- midazolam (3)
- mild cognitive impairment (3)
- mimicry (3)
- mineralocorticoid receptor (3)
- minimal-invasiv (3)
- mitotane (3)
- mixed methods (3)
- mobile health (3)
- modular (3)
- molecular characterization (3)
- molecular cloning (3)
- molecular diagnostics (3)
- molecular epidemiology (3)
- molecular phylogeny (3)
- molecular structure (3)
- monoamine oxidase (3)
- morphogenesis (3)
- mosaicism (3)
- mothers (3)
- multi-unit recording (3)
- multijet background (3)
- multilocularis (3)
- multiple bonds (3)
- multiple linear regression (3)
- multiple system atrophy (3)
- multivariate analysis (3)
- muscarinic antagonists (3)
- muscarinic receptor subtypes (3)
- muscle strength (3)
- mutants (3)
- mutation analysis (3)
- mycotoxins (3)
- myopathy (3)
- nanoparticle (3)
- nanophotonics and plasmonics (3)
- nanotechnology (3)
- nanotube (3)
- naphthalene diimide (3)
- national park (3)
- national parks (3)
- natural history (3)
- natural variation (3)
- necroptosis (3)
- necrosis-factor-alpha (3)
- negative affect (3)
- neoadjuvant (3)
- neonate (3)
- nerve fibers (3)
- nest climate (3)
- network analysis (3)
- networking (3)
- neural circuits (3)
- neural crest (3)
- neurofascin (3)
- neurofilament light chain (3)
- neurological disorders (3)
- neuromodulation (3)
- neuromonitoring (3)
- neuronal (3)
- neuronal network (3)
- neuronal nitric oxide synthase (3)
- neuropathischer Schmerz (3)
- neuropathology (3)
- neuropeptide (3)
- neuroplasticity (3)
- neuropsychology (3)
- neutropenia (3)
- new media (3)
- newborn (3)
- next-generation sequencing (3)
- niche (3)
- nicht-kovalente Wechselwirkungen (3)
- nicotine addiction (3)
- non-prompt lepton (3)
- non-verbal communication (3)
- nonsmooth optimization (3)
- nuclear export (3)
- nuclear lamina (3)
- nucleotide excision repair (3)
- numerical cognition (3)
- nystagmus (3)
- obstructive pulmonary disease (3)
- occlusion (3)
- older adults (3)
- olfactory learning (3)
- olfactory memory (3)
- oligomers (3)
- oncolytic viruses (3)
- onkolytische Virotherapie (3)
- open abdomen (3)
- operant conditioning (3)
- optical (3)
- optoelectronics (3)
- oral anticancer drugs (3)
- oral bioavailability (3)
- ordinary differential equations (3)
- organic light emitting diodes (3)
- organic molecule (3)
- organic photodiodes (3)
- organic solar cell (3)
- organische Photovoltaik (3)
- organische Solarzelle (3)
- origin (3)
- orofacial clefts (3)
- oropharynx (3)
- orthodontics (3)
- oscillation (3)
- oscillations (3)
- osteogene Differenzierung (3)
- outcomes research (3)
- outpatient (3)
- output elasticities (3)
- ovarian carcinoma (3)
- oxygen/glucose deprivation (3)
- p38 MAPK (3)
- p97 (3)
- pICln (3)
- paclitaxel (3)
- paediatric cancer (3)
- paleoecology (3)
- palliativ (3)
- pandemic (3)
- parallel imaging (3)
- parastomal hernia (3)
- parents (3)
- pars plana vitrectomy (3)
- particles (3)
- pasture (3)
- patellar tendon (3)
- pathogen (3)
- pathogenicity island (3)
- pathogenicity islands (3)
- pathophysiology (3)
- patient education (3)
- patients (3)
- pattern (3)
- pemphigus vulgaris (3)
- pentacene (3)
- peptide receptor radionuclide therapy (3)
- performance evaluation (3)
- periodische Katatonie (3)
- peripheral nerve (3)
- peripheral neuropathy (3)
- peristalsis (3)
- peritonitis (3)
- permeation (3)
- peroxisome (3)
- perylene dyes (3)
- phage (3)
- phage display (3)
- pharmacodynamics (3)
- pharmacovigilance (3)
- phenomenology (3)
- pheromones (3)
- phonological awareness (3)
- phosphatase (3)
- phosphorus (3)
- photoemission (3)
- photoionization (3)
- photolysis (3)
- photoperiodism (3)
- photosynthesis (3)
- photothrombotic stroke (3)
- phylogenetics (3)
- physical fitness (3)
- phytohormones (3)
- pigmentation (3)
- piperidines (3)
- plant (3)
- plant extract (3)
- plaque (3)
- pleural empyema (3)
- point-of-care (3)
- polarized training (3)
- politics (3)
- pollen foraging (3)
- pollen tube (3)
- pollinator (3)
- poly(2-ethyl-2-oxazoline) (3)
- poly(2-oxazine) (3)
- poly(2-oxazoline) (3)
- poly(2-oxazoline)s (3)
- polymer processing (3)
- polymorphisms (3)
- polyploidy (3)
- poor prognosis (3)
- positive selection (3)
- postoperative nausea and vomiting (3)
- posttranslational modifications (3)
- posture (3)
- potassium channels (3)
- preschool (3)
- preschool children (3)
- preterm birth (3)
- primary cells (3)
- primary hyperparathyroidism (3)
- primary school (3)
- priming (3)
- primärer Hyperaldosteronismus (3)
- prion protein (3)
- pro-inflammatory cytokines (3)
- process mining (3)
- processing fluency (3)
- progenitor cells (3)
- progenitors (3)
- progeria (3)
- programmed cell death (3)
- promoter polymorphism (3)
- prosocial behavior (3)
- prospective study (3)
- prostaglandins (3)
- prostate-specific membrane antigen (PSMA) (3)
- prosthesis (3)
- proteasome (3)
- protected areas (3)
- protein adsorption (3)
- protein crystallography (3)
- protein folding (3)
- protein kinases (3)
- protein phosphorylation (3)
- protein purification (3)
- proteinuria (3)
- proximal gradient method (3)
- psychometrics (3)
- psychopathology (3)
- psychosocial stress (3)
- psychotherapy (3)
- pulse wave velocity (3)
- pyrene (3)
- qPCR (3)
- quality of democracy (3)
- quality of experience (3)
- quantitative analysis (3)
- quantum chemistry (3)
- quantum mechanics (3)
- quantum physics (3)
- quantum well (3)
- quantum wells (3)
- qubits (3)
- quercetin (3)
- rOCT1 (3)
- radical reactions (3)
- radiography (3)
- radiomics (3)
- radius (3)
- randomized controlled-trial (3)
- randomized trial (3)
- rapid prototyping (3)
- rare diseases (3)
- reactivation (3)
- reaktive Intermediate (3)
- real time PCR (3)
- real-time PCR (3)
- rearrangement (3)
- receptor tyrosine kinases (3)
- reference values (3)
- reflection (3)
- regulatory RNA (3)
- regulatory T cell (3)
- reinforcement learning (3)
- rejection (3)
- relaxation (3)
- relief (3)
- remineralization (3)
- remodelling (3)
- renal (3)
- renal cancer (3)
- reporter genes (3)
- reporting and data system (3)
- reproductive success (3)
- research (3)
- restriction (3)
- resuscitation (3)
- retrospective analysis (3)
- retroviral vectors (3)
- rhinitis (3)
- rhodesain (3)
- ribosome (3)
- riboswitch (3)
- rice (3)
- rickets (3)
- robustness (3)
- root growth (3)
- rubber hand illusion (3)
- safety behavior (3)
- salt (3)
- salthydratic melt (3)
- salvage radiotherapy (3)
- sample (3)
- sarcoidosis (3)
- satellite data (3)
- satellite remote sensing (3)
- scFv (3)
- scanning electron microscopy (3)
- scleroderma (3)
- secondary lung tumors (3)
- sedimentology (3)
- selectivity (3)
- selenoproteins (3)
- self-assessment (3)
- self-efficacy (3)
- semantic segmentation (3)
- semi-natural habitats (3)
- semiotics (3)
- sense of agency (3)
- sensor fusion (3)
- sensory cues (3)
- sensory neurons (3)
- sentinel (3)
- septic (3)
- sequence databases (3)
- sequestration (3)
- seroprevalence (3)
- serotonergic system (3)
- serotonin transporter gene (3)
- serum concentration (3)
- serum resistance (3)
- service (3)
- shear bond strength (3)
- shoulder arthroplasty (3)
- sialic acid (3)
- side effects (3)
- signal peptides (3)
- signal to noise ratio (3)
- silicon compounds (3)
- single photon emission (3)
- single top production (3)
- single top quark (3)
- single-molecule biophysics (3)
- single-sided deafness (3)
- situation awareness (3)
- sleeve gastrectomy (3)
- small RNAs (3)
- small-molecule activation (3)
- smooth muscle (3)
- snRNP (3)
- social (3)
- sodium channel (3)
- spatial attention (3)
- speckle tracking (3)
- speech perception (3)
- speech recognition (3)
- speech recognition test (3)
- sphingolipid (3)
- sphingosine-1-phosphate (3)
- spin polarization (3)
- spin-orbit coupling (3)
- spine (3)
- spiroergometry (3)
- squamous cell carcinoma (3)
- standard model (3)
- startle (3)
- statistical data (3)
- statistics (3)
- stem (3)
- stem cell therapy (3)
- stenosis (3)
- stereoselective synthesis (3)
- stereotactic body radiation therapy (3)
- stereotactic body radiotherapy (3)
- stereotactic irradiation (3)
- stiffness (3)
- stingless bees (3)
- stochastic processes (3)
- stomach (3)
- strains (3)
- strategies (3)
- strategy (3)
- stress resistance (3)
- striatum (3)
- stroke unit (3)
- stroma (3)
- structure-activity relationship (3)
- structured illumination microscopy (3)
- study (3)
- substituent (3)
- subunit (3)
- subventricular zone (3)
- sucrose responsiveness (3)
- superparamagnetism (3)
- superresolution (3)
- suppressor cells (3)
- surface modification (3)
- surface science (3)
- surgical site infection (3)
- survival rate (3)
- survival rates (3)
- susceptibility loci (3)
- swarming (3)
- swine (3)
- synaptic inhibition (3)
- synaptic transmission (3)
- syndrome (3)
- syntaktische Funktion (3)
- syntaktische Struktur (3)
- synthetic methods (3)
- tMCAO (3)
- tapeworm (3)
- targeting (3)
- taxation (3)
- teacher education (3)
- team sport (3)
- temozolomide (3)
- temperate forests (3)
- temporal binding (3)
- temporal bone (3)
- tendon (3)
- theology (3)
- theoretical chemistry (3)
- therapeutic strategy (3)
- thermogenesis (3)
- thin film (3)
- thin films (3)
- threat (3)
- three-dimensional imaging (3)
- thyroid gland (3)
- time perception (3)
- time-resolved photoelectron spectroscopy (3)
- timing (3)
- tooth extraction (3)
- top quark (3)
- top quark pair (3)
- topography (3)
- topological matter (3)
- topologische Isolatoren (3)
- toxins (3)
- trabectome (3)
- trade-offs (3)
- trafficking (3)
- tranexamic acid (3)
- trans-splicing (3)
- transcriptional control (3)
- transfer (3)
- transgen (3)
- transiente Absorption (3)
- transition (3)
- transkranielle Gleichstromstimulation (3)
- transmission electron microscopy (3)
- transportation (3)
- transtemporal (3)
- trap (3)
- trauma (3)
- treatment outcome (3)
- treatment response (3)
- triglycerides (3)
- tropical ecology (3)
- tumor cells (3)
- tundra (3)
- turbulence (3)
- two-photon absorption (3)
- ulcerative colitis (3)
- ultrafiltration (3)
- umbilical hernia (3)
- university library (3)
- upper extremity (3)
- urban (3)
- urbanization (3)
- uremic toxin (3)
- urinary tract infections (3)
- usability (3)
- use (3)
- user-centered design (3)
- vaccines (3)
- vacuole (3)
- vandetanib (3)
- vascular (3)
- vascular plants (3)
- vegetation (3)
- vesicle trafficking (3)
- vibration (3)
- video analysis (3)
- viral load (3)
- viral replication (3)
- virology (3)
- virtual environments (3)
- virtuelle Realität (3)
- virtuelles Screening (3)
- visual acuity (3)
- visual orientation (3)
- von Willebrand factor (3)
- vulnerability curve (3)
- waggle dance (3)
- water purification (3)
- weight gain (3)
- whole exome sequencing (3)
- whole-exome sequencing (3)
- wrist (3)
- xenotransplantation (3)
- xerostomia (3)
- yoga (3)
- zeitaufgelöste Spektroskopie (3)
- Ägypten <Altertum> (3)
- Ängstliche Depression (3)
- Ästhetische Bildung (3)
- Ätiologie (3)
- Ökosystem (3)
- Österreich (3)
- Übergangsmetallverbindungen (3)
- Übung (3)
- α-synuclein (3)
- γδ T cells (3)
- "-omics" (2)
- (Ga (2)
- (Ga,Mn)As (2)
- 1,2-Azaborinine (2)
- 10-bis(dicarboximide)> (2)
- 11C-HED (2)
- 123I-mIBG (2)
- 123I-metaiodobenzylguanidine (2)
- 177Lu (2)
- 18F-FDS (2)
- 19th century (2)
- 2"-> (2)
- 2':6' (2)
- 2-APB (2)
- 2015 (2)
- 2B (2)
- 2D (2)
- 2Dimensionale Spektroskopie (2)
- 3 Tesla (2)
- 3-DPG (2)
- 31P-MRS (2)
- 3D - rapid prototyping (2)
- 3D Bioprinting (2)
- 3D Modell (2)
- 3D Pulverdruck (2)
- 3D Tumormodell (2)
- 3D analysis (2)
- 3D fluoroscopy (2)
- 3D in vitro model (2)
- 3D model generation (2)
- 3D tumour model (2)
- 3D-Bildgebung (2)
- 3D-Gewebemodell (2)
- 3D-Kultur (2)
- 3D-Modell (2)
- 3D-Rekonstruktion (2)
- 3D-Ultraschall (2)
- 3D-conformal radiotherapy (2)
- 3D-printed tooth (2)
- 4 (2)
- 4-0xadiazine-2-carboxylate (2)
- 4-Aminobiphenyl (2)
- 4-HNE (2)
- 4-aminobiphenyl (2)
- 4:9 (2)
- 4D flow (2)
- 5-Azacytidine (2)
- 5-Azadeoxycytidin (2)
- 5-FU (2)
- 5-HT transporter (2)
- 5-HT1A receptor (2)
- 5-azadeoxycytidine micronucleus (2)
- 5G (2)
- 6 (2)
- 68Ga-DOTATATE (2)
- 7 T (2)
- 7T (2)
- 8p22 (2)
- A1 adenosine receptors (2)
- A20 (2)
- AAA (2)
- AAA-Knochen (2)
- ABCG2 (2)
- ACID (2)
- ADAM9 (2)
- ADC (2)
- ADMA (2)
- ADST (2)
- AFLP (2)
- AICD (2)
- AKT1 (2)
- ALCL (2)
- ALMT (2)
- AMACR (2)
- AMADEUS (2)
- AMSOL (2)
- ANOVA (2)
- AP-1 (2)
- AP1 (2)
- APC (2)
- AQP4 (2)
- ARONJ (2)
- ASCA (2)
- ASCs (2)
- ASM (2)
- ATF4 (2)
- ATF5 (2)
- ATM (2)
- ATRT (2)
- Ab interno trabeculectomy (2)
- Ab-initio-Rechnung (2)
- Abelsche Gruppe (2)
- Ablenkung (2)
- Abrieb (2)
- Abschlussprüfung (2)
- Abscisic Acid (2)
- Abscisic acid (2)
- Absolute Konfiguration (2)
- Absolutquantifizierung (2)
- Absorption (2)
- Abstoßung (2)
- Abszess (2)
- Abtreibung (2)
- Acetaminophen (2)
- Acetylation (2)
- Acetylcystein (2)
- Acetylierung (2)
- Achilles (2)
- Achtsamkeit (2)
- Achtsamkeitsbasiertes Training (2)
- Ackerbohne (2)
- Acromyrmex fracticornis (2)
- Actin nucleation (2)
- Actinomyceten (2)
- Active Galactic Nuclei (2)
- Active galactic nucleus (2)
- Activity (2)
- Acute Kidney Injury (2)
- Acute lymphocytic leukaemia (2)
- Acute myeloid leukemia (2)
- Acute myeloid leukemia (AML) (2)
- Adamov (2)
- Additive Manufacturing (2)
- Adenocarcinom (2)
- Adenosine receptor (2)
- Adenylatcyclase (2)
- Aderhaut (2)
- Aderhautmelanom (2)
- Adhesion GPCR (2)
- Adhesion-GPCR (2)
- Adhäsionsmoleküle (2)
- Adhäsivbrücke (2)
- Adhäsive Restauration (2)
- Adhäsivfraktur (2)
- Adipogenesis (2)
- Adipokine (2)
- Adiponektin (2)
- Adipositaschirurgie (2)
- Adjuvant (2)
- Adjuvante Therapie (2)
- Adolescence (2)
- Adrenostatika (2)
- Adulte Neurogenese (2)
- Adults (2)
- Advanced glycosylation end products (2)
- Aequos G1 (2)
- Aerosol (2)
- Aflatoxin (2)
- African Trypanosomes (2)
- African trypanosomes (2)
- Afrikanische Union (2)
- Agalsidase beta (2)
- Agent (2)
- Agent <Informatik> (2)
- Agent <Künstliche Intelligenz> (2)
- Agoraphobia (2)
- Agrobacterium (2)
- Akademisierung (2)
- Akkadisch (2)
- Akkulturation (2)
- Aktiv (2)
- Akustisch evoziertes Potenzial (2)
- Akute Extremitätenischämie (2)
- Akutes ischämisches Nierenversagen (2)
- Akzeptor <Chemie> (2)
- Alain ; Boudjedra (2)
- Alcohol (2)
- Aldosterone (2)
- Aldosteronismus (2)
- Aldosteronsynthaseinhibitor (2)
- Algen (2)
- Algerien (2)
- Algorithm (2)
- Alignment (2)
- Alkoholkonsum (2)
- Alkoxysilane (2)
- Allelische Verlustanalyse (2)
- Allgemeines Gleichgewichtsmodell (2)
- Allgemeinmedizin (2)
- Alloantigen (2)
- Allogene Stammzelltransplantation (2)
- Allograft rejection (2)
- Allosterie (2)
- Allosterischer Effektor (2)
- Allotransplantation (2)
- Alltag (2)
- Alpha-2-Rezeptor (2)
- Alternans (2)
- Alternative (2)
- Altersdepression (2)
- Altersvorsorge (2)
- Altfranzösisch (2)
- Aluminafluorene (2)
- Aluminiumnitrid (2)
- Aluminiumverbindungen (2)
- Alveolarmakrophagen (2)
- Alzheimer's Disease (2)
- Amazon Molly (2)
- Ames test (2)
- Amino Acids (2)
- Aminobisphosphonate (2)
- Aminobuttersäure <gamma-> (2)
- Aminoglykoside (2)
- Ammoniten (2)
- Ammonshorn (2)
- Amphotericin B (2)
- Amplification (2)
- Amputation (2)
- Amyotrophe Lateralsklerose (2)
- Analfistel (2)
- Anaplastisches Schilddrüsenkarzinom (2)
- Anastomosenheilung (2)
- Anatolien (2)
- Androgene (2)
- Aneuploidy (2)
- Angabe (2)
- Angewandte Mikrobiologie (2)
- Angiotensin-II-Blocker (2)
- Angstsyndrom (2)
- Anidulafungin (2)
- Animal models (2)
- Anisotrope Diffusion (2)
- Anode (2)
- Anoplolepis gracilipes (2)
- Antarctic ice sheet (2)
- Antarktis (2)
- Antenne (2)
- Anthracen (2)
- Anthropometrie (2)
- Anthropozän (2)
- Anti-k Jet (2)
- Antiaromatizität (2)
- Antibiotic (2)
- Antibiotics (2)
- Antibiotikafreisetzung (2)
- Antibiotikaprophylaxe (2)
- Antibiotikaresistenz (2)
- Antibiotikaresistenzen (2)
- Antidepressivum (2)
- Antiepileptika (2)
- Antigen CD14 (2)
- Antigen CD19 (2)
- Antigen CD25 (2)
- Antikenrezeption (2)
- Antikoagulation (2)
- Antikonvulsiva (2)
- Antikörper-Fusionsproteine (2)
- Antimon (2)
- Antimonide (2)
- Antimonverbindungen (2)
- Antipsychotics (2)
- Antisense (2)
- Antisense RNA (2)
- Antisepsis (2)
- Anton Ulrich, Braunschweig-Lüneburg, Herzog (2)
- Anwendung (2)
- Anwendungssoftware (2)
- Anxiety disorder (2)
- Anxiety sensitivity (2)
- Anästhesiologie (2)
- Anästhetika-induzierte Postkonditionierung (2)
- Anästhetika-induzierte Präkonditionierung (2)
- Aortendissektion (2)
- Aortenklappe (2)
- Aortic valve stenosis (2)
- Aortokoronarer Bypass (2)
- Apolipoprotein (2)
- Apolipoprotein E (2)
- Apologie (2)
- Apology (2)
- Apoplast (2)
- Appetitlosigkeit (2)
- Approach-Avoidance-Task (2)
- Approximation (2)
- Aptamer (2)
- Aquaporine (2)
- Arabismus (2)
- Arachidonsäure (2)
- Arbeitsbelastung (2)
- Arbeitsrecht (2)
- Archaea (2)
- Architekt (2)
- Argentina (2)
- Arginine (2)
- Argumentation (2)
- Aristeas (2)
- Aristeas-Brief (2)
- Arno Schmidt (2)
- Aromaticity (2)
- Aromatizität (2)
- Arrestine (2)
- Arten-Energy-Theory (2)
- Artenreichtum (2)
- Arteria carotis interna (2)
- Arterielle Gefäßsteifigkeit (2)
- Arterielle Verschlusskrankheit (2)
- Arteriosclerosis (2)
- Arthroplastik (2)
- Arthur (2)
- Arzneibuch (2)
- Arzt (2)
- Asien (2)
- Aspartatproteasen (2)
- Aspergillosis (2)
- Aspirin (2)
- Assemblage (2)
- Assembly (2)
- Association (2)
- Associative learning (2)
- Assoziatives Lernen (2)
- Astronomie (2)
- Astrozyt (2)
- Astrozyten (2)
- Asylrecht (2)
- AtSUC4 (2)
- Ataciguat (2)
- Atemstörung (2)
- Atharvaveda (2)
- Atomic and molecular interactions with photons (2)
- Atrophie (2)
- Attention (2)
- Attention-deficit/hyperactivity disorder (2)
- Attenuierung (2)
- Audiovisuelle Medien (2)
- Audit sampling (2)
- Auditor Independence (2)
- Auditory brainstem responses AER (2)
- Auditory steady-state responses ASSR (2)
- Aufführung (2)
- Aufgabenorientierung (2)
- Aufgabenwechsel (2)
- Aufmerksamkeitsdefizit-/Hyperaktivitätsstörung (2)
- Aufmerksamkeitskontrolle (2)
- Aufmerksamkeitslenkung (2)
- Aufmerksamkeitsverzerrung (2)
- Augenbewegung (2)
- Augenfolgebewegung (2)
- Augenhintergrund (2)
- Augenkrankheit (2)
- Augenlid (2)
- Ausfallsicheres System (2)
- Ausfallsicherheit (2)
- Ausgrabungen (2)
- Aushärtung (2)
- Auskunftsdienst (2)
- Ausländerstudium (2)
- Austauschreaktion (2)
- Autism spectrum disorders (2)
- Autismus-Spektrum-Störung (2)
- Auto-Scaling (2)
- Autobiographie ; Robbe-Grillet (2)
- Autogene Transplantation (2)
- Autologous hematopoietic stem cell transplantation (2)
- Autoradiographie (2)
- Autorenlesung (2)
- Autorotation (2)
- Autotransporterprotein (2)
- Außenpolitik (2)
- Außerschulische Bildung (2)
- Avemar (2)
- Aversive Konditionierung (2)
- Avicenna (2)
- Awareness (2)
- Axion (2)
- Axon degeneration (2)
- Axonal degeneration (2)
- Azaborinine (2)
- Azide (2)
- Azoalkene (2)
- B cell differentiation (2)
- B cell receptors (2)
- B-Lymphozyten-Rezeptor (2)
- B-N-Kupplung (2)
- B-Zelldifferenzierung (2)
- B-scan-Ultraschallkardiographie (2)
- BAD (2)
- BALF (2)
- BAV-Förderbetrag (2)
- BBCH (2)
- BCL6 (2)
- BCMA (2)
- BDG (2)
- BDNF stimulation (2)
- BERAphon (2)
- BGK approximation (2)
- BH3-only proteins (2)
- BK-Kanal (2)
- BMI (2)
- BMP signaling (2)
- BMP variants (2)
- BMPR-IA (2)
- BNIP3 (2)
- BNP (2)
- BOLD signal (2)
- BPD (2)
- BRCA2 (2)
- BRENDA (2)
- BTN3 (2)
- Bacillus (2)
- Bacillus megaterium (2)
- Bacterial meningitis (2)
- Bacterial pathogens (2)
- Bakterielle Hirnhautentzündung (2)
- Bakteriengift (2)
- Balanced lethal System (2)
- Balanced lethal Systeme (2)
- Ballistischer Transport (2)
- Bandstruktur (2)
- Barbaricum (2)
- Bariatric surgery (2)
- Bariumtitanat (2)
- Barrett's esophagus (2)
- Barrett-Ösophagus (2)
- Barrettösophagus (2)
- Barrieren (2)
- Basalmembran (2)
- Base text (2)
- Basilius, Caesariensis (2)
- Bauchaorta (2)
- Bauchwand (2)
- Baum (2)
- Baumkrone (2)
- Baumwollratte (2)
- Bcl-2 Familie (2)
- Bcl-2 family (2)
- Beamtenrecht (2)
- Beatmung (2)
- Bedürfnisse (2)
- Bee abundance (2)
- Bees (2)
- Befestigungszement (2)
- Befindlichkeit (2)
- Befragung (2)
- Begabtenförderung (2)
- Begriff (2)
- Behindertenbeauftragte (2)
- Belastungselektrokardiogramm (2)
- Beliefs (2)
- Belyi map (2)
- Benchmark (2)
- Benfotiamin (2)
- Benin (2)
- Benutzeroberfläche (2)
- Benutzerschnittstelle (2)
- Benzene (2)
- Benzochinone (2)
- Benzvalen (2)
- Beobachter (2)
- Berchtesgaden (2)
- Berichterstattung (2)
- Berlin (2)
- Berufsanfang (2)
- Beschneidung (2)
- Beschäftigung (2)
- Besteuerung (2)
- Bestimmung (2)
- Bestäuber (2)
- Bestäubungsökologie (2)
- Besucherverhalten (2)
- Beta-2-Rezeptor (2)
- Beta-Hydroxybutyrat (2)
- Beta-catenin (2)
- Betablocker (2)
- Betreuungsrecht (2)
- Betrieb (2)
- Betriebsformenwandel (2)
- Betriebsrente (2)
- Betriebssystem (2)
- Bewegungsapparat (2)
- Bi2Se3 (2)
- Biaxiale Biegefestigkeit (2)
- Bibel (2)
- Bibel. Judit (2)
- Bibliografie (2)
- Biegefestigkeit (2)
- Bienenbrut (2)
- Big Five (2)
- Biholomorphe Abbildung (2)
- Bilanzierung (2)
- Bildbetrachtung (2)
- Bildhauer (2)
- Bildnerisches Gestalten (2)
- Bindeproteine (2)
- Bindestelle (2)
- Binomialverteilung (2)
- BioGlue (2)
- BioID (2)
- BioVaSc (2)
- Bioaktive Verbindungen (2)
- Bioaktivität (2)
- Bioassay (2)
- Bioavailability (2)
- Biochemistry (2)
- Biodiversity (2)
- Biodruck (2)
- Bioengineering (2)
- Biographisches Interview (2)
- Bioink (2)
- Biokatalyse (2)
- Biokompatibel (2)
- Biologika (2)
- Biologische Schädlingsbekämpfung (2)
- Biologisches System (2)
- Biomechanics (2)
- Biomembran (2)
- Biometrie (2)
- Biomolekül (2)
- Bioorganik (2)
- Bioorganische Chemie (2)
- Bioreactor (2)
- Biosphärenreservat Rhön (2)
- Biostatistik (2)
- Biosynthesis (2)
- Biotechnologische Industrie (2)
- Bismuthene (2)
- Bismutselenide (2)
- Bismutverbindungen (2)
- Bisphenol A (2)
- Bisphosphonates (2)
- Bispidinderivate (2)
- Bitopische Liganden (2)
- Bivalves (2)
- Blake (2)
- Blastozyste (2)
- Bleiakkumulator (2)
- Blinddarmentzündung (2)
- Blood pressure (2)
- Blumeria graminis (2)
- Blut-Nerven-Barriere (2)
- Blut-Nerven-Schranke (2)
- Blutalkohol (2)
- Blutkontakt (2)
- Blutplättchen (2)
- Blutung (2)
- Bmi1 (2)
- Board of directors (2)
- Bocca (2)
- Bodenfeuchte (2)
- Bodengeografie (2)
- Bodenwasser (2)
- Body weight (2)
- Body-Mass-Index (2)
- Bodyplethysmographie (2)
- Bombus (2)
- Bombus terrestris (2)
- Bond Activation (2)
- Bone marrow (2)
- Bone morphogenetic protein (2)
- Bone-Lock-System (2)
- Bone-marrow-transplantation (2)
- Bor-Stickstoff-Verbindungen (2)
- Bor-Übergangsmetallkomplexe (2)
- Boranes (2)
- Bordetella petrii (2)
- Borkenkäfer (2)
- Borolderivate (2)
- Borrelia burgdorferi (2)
- Borrelien (2)
- Borverbindungen (2)
- Borylanion (2)
- Borylenkomplex (2)
- Borylradikale (2)
- Bose-Einstein-Kondensation (2)
- Box-Jenkins-Verfahren (2)
- Box–Jenkins Program (2)
- Bradykinin (2)
- Brain endothelial cells (2)
- Brain natriuretic Peptide (2)
- Brainstem-Evoked-Response-Audiometry BERA (2)
- Brassica napus (2)
- Brazil (2)
- Breast-cancer (2)
- Breast-tumors (2)
- Breastcancer (2)
- Bronchialkarzinom (2)
- Bruchfestigkeit (2)
- Bruchverhalten (2)
- Brushite (2)
- Brust (2)
- Brustaorta (2)
- Brustbein (2)
- Brutbiologie (2)
- Buchpreis (2)
- Bulimia nervosa (2)
- Bullöses Pemphigoid (2)
- Bundesverfassungsgericht (2)
- Burst (2)
- Business Improvement District (2)
- Business Improvement Districts (2)
- Butyrylcholinesterase (2)
- BvgAS-System (2)
- Bärtierchen (2)
- Bürgertum (2)
- Bū-Ǧadra, Rašīd (2)
- C-60 fullerene (2)
- C-F bond activation (2)
- C-H activation (2)
- C-RAF (2)
- C-X-C motif chemokine receptor 4 (2)
- C-coupled naphthylisoquinoline alkaloids (2)
- C-reaktives Protein (2)
- C. callunae (2)
- C. efficiens (2)
- C. glutamicum (2)
- C/Si-Austausch (2)
- C/Si-Bioisosteric Investigations (2)
- C/Si-Bioisostric Investigations (2)
- C1-Inhibitor (2)
- C1-inhibitor (2)
- C3 (2)
- C57BL/6 mice (2)
- C5a (2)
- C6 (2)
- C60 (2)
- CA19-9 (2)
- CABG (2)
- CAD-CAM (2)
- CAD/CAM restoration material (2)
- CADe (2)
- CAIPIRINHA (2)
- CARS-Spektroskopie (2)
- CBCT (2)
- CCL4 (2)
- CCN1 (2)
- CCR4 (2)
- CD117 (2)
- CD147 (2)
- CD20 (2)
- CD274 (2)
- CD28 superagonist (2)
- CD28-Superagonist (2)
- CD28-superagonist (2)
- CD30 (2)
- CD38 (2)
- CD4(+) T-cells (2)
- CD4+ (2)
- CD46 (2)
- CD70 (2)
- CD8 T-Zellen (2)
- CD83mRNA (2)
- CD84 (2)
- CDC42 (2)
- CDI (2)
- CDL (2)
- CHO-Zelle (2)
- CHO-Zellen (2)
- CI (2)
- CIP2A (2)
- CK2 (2)
- CKD (2)
- CLL (2)
- CLN3 (2)
- CNN (2)
- CNS cancer (2)
- CNS disease (2)
- CNS disorders (2)
- CORDEX Africa (2)
- CORM (2)
- COVID-19-Pandemie (2)
- CP-Parität (2)
- CRC (2)
- CRE (2)
- CREB (2)
- CRISPR (2)
- CSF-1 (2)
- CSI (2)
- CSS (2)
- CSVD (2)
- CTEPH (2)
- CVD-Verfahren (2)
- CX3CR1 (2)
- CXCL10 (2)
- CXCL12 (2)
- CXCL13 (2)
- CXCR2 (2)
- CXCR7 (2)
- CYP11B1 (2)
- CYP24A1 (2)
- CYP2W1 (2)
- CaMKII (2)
- Ca\(^{2+}\) signalling (2)
- Caco2 cells (2)
- Cadherin (2)
- Cadherin-13 (2)
- Cadherin-13 (CDH13) (2)
- Cadmiumsulfid (2)
- Cadmiumtellurid (2)
- Calcitonin (2)
- Calciumion (2)
- Calearo (2)
- Calpain (2)
- Cambrian (2)
- Canada (2)
- Cancer immunotherapy (2)
- Cancer treatment (2)
- Capacity Management (2)
- Capecitabin (2)
- Capillary Electrophoresis (2)
- Carbamate (2)
- Carbazolderivate (2)
- Carbenkomplexe (2)
- Carbocations (2)
- Carborane (2)
- Carcinogenität (2)
- Cardiac (2)
- Cardiac Surgery (2)
- Cardiac hypertrophy (2)
- Cardiomyocyte (2)
- Cardiovascular disease (2)
- Cardiovascular diseases (2)
- Cardiovascular risk factors (2)
- Carfilzomib (2)
- Carnica-Biene (2)
- Cartilage (2)
- Cartilage Tissue Engineering (2)
- Cartilage regeneration (2)
- Cascading Style Sheets (2)
- Caspase-1 (2)
- Caspases (2)
- Catechine (2)
- Catechol-0-Methyltransferase (2)
- Caveolae (2)
- Cayley graph (2)
- Cdc42 (2)
- Cdu1 (2)
- Cefotaxim (2)
- Cell (2)
- Cell adhesion (2)
- Cell migration (2)
- Cell therapy (2)
- Cellculture (2)
- Cement (2)
- Cephalometric (2)
- Cephalosporine (2)
- Cerebellum (2)
- Cerlegierung (2)
- ChIP-sequencing (2)
- ChR2 (2)
- Chagas disease (2)
- Chaotisches System (2)
- Charcot-Marie-Tooth disease (2)
- Checkpoint-Inhibitor (2)
- Chelatbildner (2)
- Chemical Synthesis (2)
- Chemische Analyse (2)
- Chemische Reaktion (2)
- Chemisorption (2)
- Chemokinrezpetor (2)
- Chemoresistenz (2)
- Chemotherapieresistenz (2)
- Childhood (2)
- Childhood medulloblastoma (2)
- Chili RNA Aptamer (2)
- Chimerism (2)
- Chirale Verbindungen (2)
- Chirp-Reiz (2)
- Chirurgiegeschichte (2)
- ChlaDUB1 (2)
- Chlamydia pneumoniae (2)
- Chlorinderivate (2)
- Cholesterol (2)
- Cholinesterase (2)
- Chondrogenese (2)
- Chondrogenesis (2)
- Chondrogenic Differentiation (2)
- Chorasan (2)
- Christentum (2)
- Christianity (2)
- Chromatin structure (2)
- Chromosom 8 (2)
- Chromosomenanalyse (2)
- Chromosomenverlust (2)
- Chronic heart failure (2)
- Chronic kidney disease (2)
- Chronische Nierenerkrankung (2)
- Chronotrope Inkompetenz (2)
- Chrysididae (2)
- Chrétien <de Troyes> (2)
- Ciclosporin (2)
- Circadian clock (2)
- Circadianer Rhythmus (2)
- Circular-Dichroismus (2)
- Cirl (2)
- Citalopram (2)
- Cl Lowe limit (2)
- Claudin (2)
- Claudin-1 (2)
- Claudine <Biologie> (2)
- Cleft (2)
- Clinical Neuroradiology (2)
- Clinical trial (2)
- Clostridium-difficile-Infektion (2)
- Cloud Gaming (2)
- Cluster <Wirtschaft> (2)
- Cluster C Persönlichkeitsstörungen (2)
- Clusteranalyse (2)
- Co-Kultur (2)
- Cobalt (2)
- Cochlea Implantat (2)
- Code examples (2)
- Codierung (2)
- Coffin-Lowry syndrome (2)
- Cofilin (2)
- Cognitive conflict (2)
- Colombia (2)
- Colonization (2)
- Colorectal carcinoma (2)
- Columnare Phase (2)
- Combination (2)
- Comet assay (2)
- Comet-Assay (2)
- Compliance (2)
- Compliance <Patient> (2)
- Composite international diagnostic interview (2)
- Computed tomography (2)
- Computerphysik (2)
- Concealed Information Test (2)
- Conductivity (2)
- Confidence interval (2)
- Conformal field theory (2)
- Congo (2)
- Conical Intersections (2)
- Conjugation (2)
- Connexin (2)
- Conservation (2)
- Consistent partial least squares (2)
- Constant Score (2)
- Constant score (2)
- Constant-Score (2)
- Constraints (2)
- Contactin-1 (2)
- Contaminants (2)
- Content Management (2)
- Continuous Performance Test (2)
- Controllability (2)
- Controlling (2)
- Convolutional Neural Network (2)
- Coordination Chemistry (2)
- Copeptin (2)
- Copolymerisation (2)
- Copyright (2)
- Corannulene (2)
- Corporate Social Responsibility (2)
- Corpus (Linguistics) (2)
- Corpus striatum (2)
- Correlated Fermions (2)
- Correlative microscopy (2)
- Cortactin (2)
- Cortex (2)
- Corti-Organ (2)
- Corticosteroide (2)
- Cortison (2)
- Corynebacterium callunae (2)
- Corynebacterium efficiens (2)
- Corynebacterium glutamicum (2)
- Cosmology (2)
- Coupled Cluster (2)
- Covid-19 Pandemie (2)
- CpG (2)
- CpG-ODN (2)
- Crab-Nebel (2)
- Craniomandibuläre Dysfunktion (2)
- Craniopharyngioma (2)
- Craving (2)
- Crohn´s disease (2)
- Crohn’s disease (2)
- Cross-section (2)
- Crosslinking (2)
- Crosstalk (2)
- Crouzon (2)
- Crush (2)
- Cryo-EM (2)
- Cryptochrom (2)
- Crystal Structure (2)
- CsrA (2)
- CuPc (2)
- Cue-Reaktivität (2)
- Cuprate (2)
- Curriculum (2)
- Cushing’s disease (2)
- Cuticle (2)
- Cuticular waxes (2)
- Cyaninfarbstoff (2)
- Cyclische Verbindungen (2)
- Cyclization (2)
- Cyclo-GMP-Derivate (2)
- Cyclonucleotide (2)
- Cyclopentadienderivate (2)
- Cyclophosphamid (2)
- Cyclophosphamide (2)
- Cymantren (2)
- Cys-loop receptor (2)
- Cysteinderivate (2)
- Cytochrom C (2)
- Cytochrom P-450 (2)
- Cytochrome C (2)
- Cytokeratin (2)
- Cytokeratine (2)
- Cytoplasma (2)
- Cytotoxicity (2)
- Césaire, Aimé (2)
- D-Norm (2)
- D665 (2)
- DAPI staining (2)
- DASH (2)
- DCIS (2)
- DHAP (2)
- DIRA (2)
- DM-domain gene (2)
- DM2 (2)
- DMS (2)
- DNA Binding (2)
- DNA Methylation (2)
- DNA Repair (2)
- DNA Reparatur (2)
- DNA Schaden (2)
- DNA antibodies (2)
- DNA barcoding (2)
- DNA delivery (2)
- DNA double-strand break (2)
- DNA fingerprinting (2)
- DNA helicase (2)
- DNA methyltransferases (2)
- DNA sequencing (2)
- DNA storage (2)
- DNA-Binding (2)
- DNA-PK (2)
- DNA-Repair (2)
- DNA-Reparaturgene (2)
- DNA-Schäden (2)
- DNA-Typisierung (2)
- DNA-repair (2)
- DNA-typing (2)
- DNA/RNA sensors (2)
- DNMT3A (2)
- DNMT3B (2)
- DNS-Strangbruch (2)
- DNS-Topoisomerasen (2)
- DOT1 (2)
- DOTATOC (2)
- DRD4 (2)
- DREAM (2)
- DROSHA (2)
- DSM-IV (2)
- Dacron (2)
- Damage (2)
- Dante, Alighieri (2)
- Dark-Matter (2)
- Darmepithel (2)
- Darmwandnervensystem (2)
- Darstellungsmatrix (2)
- Data-Warehouse-Konzept (2)
- Data-driven Operations Management (2)
- Database (2)
- Datenfusion (2)
- Datenschutz (2)
- Dativ (2)
- Debonding (2)
- Decision Support Systems (2)
- Dectin-1 (2)
- Deep Learning (2)
- Deep sequencing (2)
- Deep sternal wound infection (2)
- Deformationsquantisierung (2)
- Deformität (2)
- Defäkographie (2)
- Dehydrokupplung (2)
- Delay Discounting (2)
- Deletion <Genetik> (2)
- Delta-Valve (2)
- Demokratische Republik Kongo (2)
- Demyelination (2)
- Demyelinisierung (2)
- Dentale Implantate (2)
- Dentalwerkstoff (2)
- Dentin (2)
- Dentinadhäsivsysteme (2)
- Dentinhaftvermittler (2)
- Dependenz (2)
- Depolarisation (2)
- Deregulierung (2)
- Derivation (2)
- Derivatisierung (2)
- Desertifikation (2)
- Desmoglein (2)
- DeuCze-Korpus (2)
- Deutsche Sprachwissenschaft (2)
- Deutsches Sprachgebiet (2)
- Deutschland (Bundesrepublik) (2)
- Deutschland / Stammzellgesetz (2)
- Dezentrale Regelung (2)
- Dezentralisierung (2)
- Diabetes mellitus Typ 2 (2)
- Diabetic polyneuropathy (2)
- Diagnosesystem (2)
- Diagnostic medicine (2)
- Dialekt (2)
- Dialektologie (2)
- Dialysepatienten (2)
- Dialysis (2)
- Diamiktit (2)
- Diborabenzol (2)
- Diboran (2)
- Diboret (2)
- Diborierung (2)
- Dichtegewichtung (2)
- Dickenmessung (2)
- Diels-Alder-Reaktion (2)
- Diethylstilbestrol (2)
- Difenidol (2)
- Differential effects of stressors (2)
- Differenziertes Schilddrüsenkarzinom (2)
- Differenzierungspotential (2)
- Diffusion Tensor Imaging (2)
- Diffusion coefficient (2)
- Diffusionsgewichtete Magnetresonanztomografie (2)
- Digital Elevation Model (2)
- Digital Religions Education (2)
- Digitale Signalverarbeitung (2)
- Digitalization (2)
- Dihydroborane (2)
- Dihydrooxazole (2)
- Dilatative Kardiomyopathie (2)
- Dioncophyllaceae (2)
- Diphosphonate (2)
- Direkte Demokratie (2)
- Dirichlet-Reihe (2)
- Disease (2)
- Diseases (2)
- Diskriminanzanalyse (2)
- Diskriminierung (2)
- Diskursmarker (2)
- Disney (2)
- Dispergierung (2)
- Distress (2)
- Distributed computing (2)
- Disulfidbrücken (2)
- Djebar, Assia (2)
- Dobutamin-Stressechokardiographie (2)
- Docking <Chemie> (2)
- Dodecaborane (2)
- Dominanz (2)
- Domäne (2)
- Donator <Chemie> (2)
- Dopaminerge Nervenzelle (2)
- Dopaminrezeptor (2)
- Dopaminstoffwechsel (2)
- Dopamintransporter (2)
- Doppelbesteuerung (2)
- Doppelkronen (2)
- Doppelverbeitragung (2)
- Dorsal Root Ganglion (2)
- Dorsal root ganglion (2)
- Dose response (2)
- Dose-response relationship (2)
- Dosimetry (2)
- Dosisreduktion (2)
- Dot-Depth Problem (2)
- Down-Syndrom (2)
- Dreidimensionale Bildverarbeitung (2)
- Dreidimensionales Bild (2)
- Dreidimensionales Modell (2)
- Dreifachbindung (2)
- Drogen (2)
- Drug design (2)
- Drug development (2)
- Drylands (2)
- Dsg2 (2)
- Dual-Source-Computertomographie (2)
- Duchenne (2)
- Duodenopankreatektomie (2)
- Durchblutungsmessung (2)
- Dwyka (2)
- Dyade (2)
- Dyes (2)
- Dystonia (2)
- Dämpfung (2)
- Dämpfungseigenschaften (2)
- Dünen (2)
- Dünndarmmotilität (2)
- Dünndarmtransplantat (2)
- E-Commerce (2)
- E-Government (2)
- E-learning (2)
- E. coli (2)
- E. coli Nissle (2)
- E. coli serotype 06 (2)
- EAA (2)
- EAAC1 (2)
- EBRA (2)
- ECMO-Therapie (2)
- EDA-NOCV (2)
- EEA (2)
- EF (2)
- EF-1A (2)
- EGF-Rezeptor (2)
- EGF-receptor (2)
- EGFP (2)
- EORTC (2)
- ERI (2)
- ERK signaling (2)
- ERT (2)
- ETiCS (2)
- EU (2)
- EUROASPIRE (2)
- EW (2)
- EXKK (2)
- EZH2 (2)
- Early Basso Continuo (2)
- Early Music (2)
- Early Neolithic (2)
- Early-onset (2)
- Earnings Quality (2)
- Echinococcosis (2)
- Ecological Momentary Assessment (2)
- Edelmetall (2)
- Edition (2)
- Efavirenz (2)
- Effektive Theorie (2)
- Effizienter Algorithmus (2)
- Effizienzsteigerung (2)
- Effluxpumpen (2)
- Ehrenamt (2)
- Eierstocktumor (2)
- Eindringerkennung (2)
- Einführung (2)
- Eingeweidewürmer (2)
- Einkauf (2)
- Einmodenlaser (2)
- Einsamkeit (2)
- Einsatzfahrten (2)
- Einsilbersprachverständnistest (2)
- Einwanderung (2)
- Einzelphotonenquelle (2)
- Eiparasitismus (2)
- Eisenoxid-Nanopartikel (2)
- Ekel (2)
- Elderly (2)
- Electroencephalography (2)
- Electromagnon (2)
- Electron Transfer (2)
- Electronic commerce (2)
- Electronic spectroscopy (2)
- Elektrische Leitfähigkeit (2)
- Elektrizitätsverbrauch (2)
- Elektroakupunktur (2)
- Elektroimpedanztomographie (2)
- Elektromagnon (2)
- Elektromobilität (2)
- Elektron-Elektron-Streuung (2)
- Elektronendichteverteilung (2)
- Elektronenflüssigkeit (2)
- Elektronenstrahllithographie (2)
- Elektronenzustand (2)
- Elektronische Anregung (2)
- Elektronische Spektroskopie (2)
- Elektronisches Publizieren (2)
- Elektrophysiologische Untersuchung (2)
- Elektrospinning (2)
- Elektrostimulation (2)
- Elementarteilchen (2)
- Elfenbeinküste (2)
- Elite Controller (2)
- Elmex (2)
- Elternarbeit (2)
- Elterntraining (2)
- Embolisation (2)
- Emotion regulation (2)
- Emotional processing (2)
- Empathie (2)
- Empirical Analysis (2)
- Empirische Forschung (2)
- Emulsion (2)
- Enantiomere (2)
- Enantiomerentrennung (2)
- Enantioselectivity (2)
- Encephalopathia hepatica (2)
- End-of-Life Care (2)
- End-zu-End-Anastomose (2)
- Endocannabinoide (2)
- Endocytosis (2)
- Endodermis (2)
- Endophytische Pilze (2)
- Endophänotyp (2)
- Endoplasmatisches Retikulum (2)
- Endoribonuklease P (2)
- Endoskopie (2)
- Endosom (2)
- Endosonographie (2)
- Endothelial cells (2)
- Endothelial dysfunction (2)
- Endothelin (2)
- Endotracheale Intubation (2)
- Energie (2)
- Energierecht (2)
- Energiereiches Teilchen (2)
- Energiespeicher (2)
- Energiestoffwechsel (2)
- Engadin (2)
- England (2)
- Englischunterricht (2)
- Enol Iactones (2)
- Enoxaparin (2)
- Enoyl-ACP-Reduktase (2)
- Enoyl-acyl-carrier-protein-Reductase (2)
- Entamoeba histolytica (2)
- Entanglement (2)
- Enterococcus faecium (2)
- Enterprise-Resource-Planning (2)
- Entropie (2)
- Entscheidbarkeit (2)
- Entscheidungen (2)
- Entscheidungsneutralität (2)
- Entscheidungsprozess (2)
- Entscheidungssammlung (2)
- Entscheidungsverhalten (2)
- Entstehungsgeschichte (2)
- Entzündungsparameter (2)
- Entzündungsreaktion (2)
- Entzündungsschmerz (2)
- Epidemiology (2)
- Epigenese (2)
- Epik (2)
- Epiphyten (2)
- Epitaxieschicht (2)
- Epithelial-mesenchymale Transition (2)
- Epithelkörperchen (2)
- Epithelzelle (2)
- Epitop (2)
- Epitope (2)
- Epitranscriptomics (2)
- Eplerenone (2)
- Epoxidation (2)
- Epoxidierung (2)
- Epstein-Barr-Virus (2)
- Erbrecht (2)
- Erdbeere (2)
- Erdbeobachtung (2)
- Erfahrungsverankerte Rezeption (2)
- Ergebnisse (2)
- Ergänzung (2)
- Erinnerung (2)
- Erk (2)
- Erlotinib (2)
- Erneuerbare-Energien-Gesetz (2)
- Ernteertrag (2)
- Ernährungstherapie (2)
- Ersatzstoff (2)
- Erwachsenenalter (2)
- Erysiphe graminis (2)
- Erythropoetin (2)
- Erythrozyten (2)
- Eschatologie (2)
- Eschatology (2)
- Escherichia coli K1 (2)
- Eskalation (2)
- Essstörung (2)
- Esterasen (2)
- Estimation (2)
- Estrogen (2)
- Etacrynsäure (2)
- Ethernet (2)
- Ethnizität (2)
- Ethnographie (2)
- Ethnologie (2)
- Etrusker (2)
- EuGH (2)
- Eukaryoten (2)
- Euphronios (2)
- European Central Bank (2)
- European Organization for Nuclear Research. ATLAS Collaboration (2)
- Europäische Aktiengesellschaft (2)
- Europäische Integration (2)
- Europäisches Arzneibuch (2)
- Euthanasie (2)
- Event-related potentials (2)
- Everolimus (2)
- Evolutionspsychologie (2)
- Evolutionärer Algorithmus (2)
- Ewing-Sarkom (2)
- Exacerbation (2)
- Examensklausur (2)
- Exciton coupling (2)
- Exegese (2)
- Exercise capacity (2)
- Exercise testing (2)
- Exomsequenzierung (2)
- Exosom <Vesikel> (2)
- Exotics (2)
- Expansion (2)
- Expansionsmikroskopie (2)
- Experiment (2)
- Experimental autoimmune encephalomyelitis (2)
- Experimental physics (2)
- Experteninterviews (2)
- Expertensystem (2)
- Expertise (2)
- Explainable AI (2)
- Explainable Artificial Intelligence (2)
- Explorative Datenanalyse (2)
- Explosion (2)
- Export (2)
- Expressionsanalyse (2)
- Extended Reality (2)
- Extensions of gauge sector (2)
- Extracellular Vesicles (2)
- Extracellular matrix (2)
- Extracorporeal Membrane Oxygenation (2)
- Extrakorporale Dialyse (2)
- Extrakorporale Membranoxygenierung (2)
- Extraterrestrische Forschung (2)
- Extraversion (2)
- Extrazellulärmatrix (2)
- Extreme Value Theory (2)
- Extremereignisse (2)
- Extremwert (2)
- Exziton-Exziton-Annihilierung (2)
- Exzitotoxizität (2)
- Eye-Tracking (2)
- Eyelid (2)
- Ezetimib (2)
- F-actin (2)
- F8 fimbriae (2)
- FAAH (2)
- FAS (2)
- FCS (2)
- FDG PET/CT (2)
- FDG-PET/CT (2)
- FFPE (2)
- FGF-pathway (2)
- FGFR1 (2)
- FIB-4 (2)
- FKBP52 (2)
- FOSL1 (2)
- FRET sensors (2)
- FTIR spectroscopy (2)
- Fabry genotype (2)
- Fabry nephropathy (2)
- Fabry phenotype (2)
- Fachsprache (2)
- Factor receptor (2)
- Fagus sylvatica (2)
- Fahrertraining (2)
- Fahrradergometer (2)
- Falle (2)
- Fallsammlung (2)
- Familienuntersuchung (2)
- Family-Investigation (2)
- FarR (2)
- Farbensehen (2)
- Farbwahrnehmung (2)
- FasL (2)
- Faser (2)
- Fatty acids (2)
- Fbw7 (2)
- Fc-receptor (2)
- FcγR (2)
- Fear conditioning (2)
- Feedback (2)
- Fehlertoleranz (2)
- Fehlerverarbeitung (2)
- Fehlstellung (2)
- Feldforschung (2)
- Feldstärkemessung (2)
- Feldtheorie (2)
- Female (2)
- Femtochemistry (2)
- Fermentation (2)
- Fernsehmaske (2)
- Fernwartung (2)
- Ferroelektrikum (2)
- Ferromagnete (2)
- Ferromagnetikum (2)
- Ferromagnetische Halbleiter (2)
- Ferromagnetismus (2)
- Ferroptosis (2)
- Fersenbeinbruch (2)
- Festkörper (2)
- Festkörper-NMR (2)
- Fett (2)
- Fettgewebsstammzellen (2)
- Fettleibigkeit (2)
- Fettsäure (2)
- Fibrinogen (2)
- Fibromyalgia (2)
- Fibromyalgiesyndrom (2)
- Fibronectin (2)
- Ficaria calthifolia (2)
- Ficaria verna (2)
- Fieber (2)
- Field programmable gate array (2)
- Figur (2)
- Figurenrede (2)
- Fingerprint-Verfahren (2)
- Fish (2)
- Fixateur interne (2)
- Flagelle (2)
- Flagellen (2)
- Flagelline (2)
- Flash-Speicher (2)
- Flavonoids (2)
- Flexibilität (2)
- Fließeigenschaften (2)
- Flow cytometry (2)
- Fluconazol (2)
- Fluconazole (2)
- Fluency (2)
- Flugkörper (2)
- Flugzeitmassenspektrometrie (2)
- Fluid-Feststoff-System (2)
- Fluktuation (2)
- Fluorchinolone (2)
- Fluorescence in situ hybridization (2)
- Fluorescence microscopy (2)
- Fluoreszenzaktivierter Zellsortierer (2)
- Fluoreszenzlöschung (2)
- Fluoreszenzmarkierung (2)
- Fluoreszenzsonde (2)
- Fluoreszenzspektrometer (2)
- Fluorierung (2)
- Fluoxetine (2)
- Flussufer (2)
- Flächenbedarf (2)
- Flüchtlingskrise (2)
- Flüssiger Zustand (2)
- Flüssigkristalle (2)
- Foamy virus (2)
- Fokker–Planck equation (2)
- Foldamere (2)
- Formaldehyd (2)
- Formation Flight (2)
- Formulation development (2)
- Forschungsparadigma (2)
- Fossil (2)
- FoxO3 (2)
- Fractalkin (2)
- Framework <Informatik> (2)
- Framework for Information Literacy for Higher Education (2)
- France (2)
- Frankfurter Allgemeine (2)
- Franz (2)
- Frauen (2)
- Freedom House (2)
- Freies Molekül (2)
- Freizügigkeit (2)
- Frequency (2)
- Frequency Domain (2)
- Frequenzanalyse (2)
- Freud (2)
- Friedreich-Ataxie (2)
- Front National (2)
- Frucht (2)
- Frustrated Lewis Pairs (2)
- Frustration (2)
- Frömmigkeit (2)
- Frühe akustisch evozierte Potentiale FAEP (2)
- Frühförderung (2)
- Frühjahr-Sommer-Encephalitis (2)
- Frühphase (2)
- Fullerenderivate (2)
- Fumonisine (2)
- Functional analyses (2)
- Fundoplikatio (2)
- Funktionelle Bildgebung (2)
- Funktionelle Kernspintomographie (2)
- Funktionelle Störung (2)
- Funktionentheorie (2)
- Funktionstest (2)
- Furan (2)
- Furanderivate (2)
- Furaneol (2)
- Furylborane (2)
- Fusion proteins (2)
- Fusobacterium nucleatum (2)
- Future Internet (2)
- Fußballverein (2)
- Fähigkeit (2)
- Förderschule (2)
- Förderschwerpunkt geistige Entwicklung (2)
- Förster Resonance Energy Transfer (2)
- Förster Resonanz Energie Transfer (2)
- Führung (2)
- G Protein (2)
- G protein coupled receptor (2)
- G protein-coupled receptor (2)
- G-Protein-gekoppelte Rezeptoren (2)
- G-Protein-gekoppelter Rezeptor (2)
- G-protein coupled receptor (2)
- G-protein coupled receptors (2)
- G-protein-coupled receptor (2)
- G-quadruplexes (2)
- GABA-Rezeptor (2)
- GABP (2)
- GAD1 (2)
- GAD65 (2)
- GAP (2)
- GATA-3 (2)
- GEF (2)
- GERD (2)
- GIRK (2)
- GLAST (2)
- GLP-1 (2)
- GLT1 (2)
- GLUT1 (2)
- GLUT2 (2)
- GLV-1H68 (2)
- GLaD-Studie (2)
- GLaD-study (2)
- GPS (2)
- GRAPPA (2)
- GRP78 (2)
- GSK3 (2)
- GTP-bindende Proteine (2)
- GUT (2)
- GaMnAs (2)
- Gadolinium (2)
- Galaxienentwicklung (2)
- Galaxienhaufen (2)
- Galeruca tanaceti (2)
- Galle (2)
- Galliumantimonid (2)
- Galliumnitrid (2)
- Galois-Theorie (2)
- Galvanische Abscheidung (2)
- Gamet (2)
- Gametogenese (2)
- Gamma (2)
- Gamma-Konvergenz (2)
- Ganganalyse (2)
- Ganzkörperbestrahlung (2)
- Gas (2)
- Gas chromatography (2)
- Gastroenterologische Endoskopie (2)
- Gastroschisis (2)
- Gastroösophageale Refluxkrankheit (2)
- Gastroösophagealer Reflux (2)
- Gastrulation (2)
- Gauge/Gravity Duality (2)
- Gaumen (2)
- Gaumenplatte (2)
- Gaumenspalte (2)
- Gedächtnisentwicklung (2)
- Gedächtniszellen (2)
- Gefahrenabwehr (2)
- Gefitinib (2)
- Gefrierstrukturierung (2)
- Gefäßchirurgie (2)
- Gefäßverschluss (2)
- Gefäßwand (2)
- Gefüge (2)
- Gegenwartssprache (2)
- Geistiges Eigentum (2)
- Geld (2)
- Geldtheorie (2)
- Gelelektrophorese (2)
- Gelenkpositionierung (2)
- Gemeinnützigkeit (2)
- Gemeinschaftsunterkunft (2)
- Gemeinschaftsökologie (2)
- Gen BRCA 1 (2)
- Gender studies (2)
- Gene Regulation (2)
- Gene cloning (2)
- Gene duplication (2)
- Generalized Nash Equilibrium Problem (2)
- Genes (2)
- Genetic instability (2)
- Genetics research (2)
- Genitiv (2)
- Genklonierung (2)
- Genomik (2)
- Genomvariabilität (2)
- Gentechnologie (2)
- Geophysics (2)
- Geriatrics (2)
- Gerichtete Erstarrung (2)
- Gerichtshof (2)
- Geringverdiener (2)
- German Hepatitis C-Registry (2)
- German people (2)
- Germanistik (2)
- Geschichte 1100-1600 (2)
- Geschichte 1605-1687 (2)
- Geschichte 1900-2000 (2)
- Geschichte 1919-1945 (2)
- Geschichte 2014 (2)
- Geschichte der Zahnheilkunde (2)
- Geschlechtsdifferenzierung (2)
- Gesetzliche Krankenversicherung (2)
- Gestaltungsorientierte Bildungsforschung (2)
- Gesteinsbildung (2)
- Gesteinskunde (2)
- Gesundheit (2)
- Gewalttätigkeit (2)
- Geweberegeneration (2)
- Gewicht (2)
- Gewichtsabnahme (2)
- Gewürz (2)
- Glasfaserstift (2)
- Glatiramer acetate (2)
- Gleason score (2)
- Gleichberechtigung (2)
- Gleichverteilung (2)
- Gletscherschwankung (2)
- Gliederfüßer (2)
- Gliedergürtelmuskeldystrophie (2)
- Global Governance (2)
- Globale Optimierung (2)
- Globaler Süden (2)
- Glomeruli (2)
- Glucocorticoids (2)
- Glucose metabolism (2)
- Glucosetransporter (2)
- Gluino production (2)
- Glukokortikoide (2)
- Glutamate (2)
- Glycerin (2)
- Glycoengineering (2)
- Glykane (2)
- Glykolyse (2)
- Gold Nanoparticles (2)
- Golf von Akaba (2)
- Golgi apparatus (2)
- Golgi-Apparat (2)
- Gondwana (2)
- Gothenburg model (2)
- Gott <Motiv> (2)
- Graft versus host disease (2)
- Graft-versus-leukemia (2)
- Gram-negative Bakterien (2)
- Granulieren (2)
- Granulit (2)
- Granulozyt (2)
- Gravitation (2)
- Grenze (2)
- Grenzwert (2)
- Grimmelshausen, Hans Jakob Christoffel von / Simplizissimus (2)
- Group B Streptococcus (2)
- Growth-differentiation Factor 15 (2)
- Großbritannien (2)
- Grundrechte (2)
- Grundstücksübertragung (2)
- Grundsubstanz (2)
- Grundvorstellung (2)
- Grundwortschatz (2)
- Guanidiniocarbonylpyrrol (2)
- Guanylylcyclase (2)
- Guidelines (2)
- Guillain-Barre-Syndrome (2)
- Guinea-pig uterus (2)
- Gymnasium (2)
- Gyrasehemmer (2)
- H-1-NMR spectroscopy (2)
- H2O2 (2)
- HADS-D (2)
- HAE (2)
- HAND (2)
- HBV (2)
- HCC (2)
- HCM (2)
- HD (2)
- HDAC (2)
- HDBSCAN (2)
- HDGF (2)
- HEMT (2)
- HERV-K (2)
- HES (2)
- HFQ (2)
- HIF-1 (2)
- HIF-1α (2)
- HIV-Demenz (2)
- HIV-Infection (2)
- HIV-infection (2)
- HIVDR (2)
- HKT transporter (2)
- HLA-E (2)
- HMG (2)
- HPA axis (2)
- HPK1 (2)
- HPLC-CD-Kopplung (2)
- HPP (2)
- HPV (2)
- HRQOL (2)
- HRXRD (2)
- HSC (2)
- HSM-sentence test (2)
- HSM-test (2)
- HSP90 inhibitor (2)
- HT-29 (2)
- HaCaT (2)
- Habitat (2)
- Habitat fragmentation (2)
- Haemostasis (2)
Institute
- Theodor-Boveri-Institut für Biowissenschaften (2306)
- Graduate School of Life Sciences (1034)
- Physikalisches Institut (811)
- Institut für Anorganische Chemie (678)
- Medizinische Klinik und Poliklinik I (667)
- Institut für Psychologie (604)
- Medizinische Klinik und Poliklinik II (579)
- Institut für Organische Chemie (562)
- Neurologische Klinik und Poliklinik (527)
- Klinik und Poliklinik für Allgemein-, Viszeral-, Gefäß- und Kinderchirurgie (Chirurgische Klinik I) (508)
Schriftenreihe
- Cultural Animal Studies, Band 3 (24)
- Spezielle Didaktik der Sportarten (2)
- Aesthetische Eigenzeiten, 17 (1)
- Akten des ... Symposiums des Mediävistenverbandes; 13,2 (1)
- Alter Orient und Altes Testament : Sonderreihe Veröffentlichungen zur Kultur und Geschichte des Alten Orients ; 3 (1)
- Aventiuren; 13 (1)
- Berichte aus der Informatik (1)
- Deuterocanonical and Cognate Literature Studies (1)
- Deuterocanonical and Cognate Literature Yearbook (1)
- Epistemata. Reihe Literaturwissenschaft ; 483 (1)
Sonstige beteiligte Institutionen
- VolkswagenStiftung (24)
- Johns Hopkins School of Medicine (18)
- Fraunhofer-Institut für Silicatforschung ISC (8)
- Helmholtz Institute for RNA-based Infection Research (HIRI) (7)
- IZKF Nachwuchsgruppe Geweberegeneration für muskuloskelettale Erkrankungen (7)
- Akademie der Wissenschaften und der Literatur, Mainz (6)
- DFG Forschungsgruppe 2757 / Lokale Selbstregelungen im Kontext schwacher Staatlichkeit in Antike und Moderne (LoSAM) (6)
- Clinical Trial Center (CTC) / Zentrale für Klinische Studien Würzburg (ZKSW) (5)
- Johns Hopkins University School of Medicine (5)
- Universität Leipzig (5)
ResearcherID
- B-1911-2015 (1)
- B-4606-2017 (1)
- C-2593-2016 (1)
- D-1221-2009 (1)
- D-1250-2010 (1)
- D-3057-2014 (1)
- I-5818-2014 (1)
- J-8841-2015 (1)
- M-1240-2017 (1)
- N-2030-2015 (1)
In a world of constant change, uncertainty has become a daily challenge for businesses. Rapidly shifting market conditions highlight the need for flexible responses to unforeseen events. Operations Management (OM) is crucial for optimizing business processes, including site planning, production control, and inventory management. Traditionally, companies have relied on theoretical models from microeconomics, game theory, optimization, and simulation. However, advancements in machine learning and mathematical optimization have led to a new research field: data-driven OM.
Data-driven OM uses real data, especially time series data, to create more realistic models that better capture decision-making complexities. Despite the promise of this new research area, a significant challenge remains: the availability of extensive historical training data. Synthetic data, which mimics real data, has been used to address this issue in other machine learning applications.
Therefore, this dissertation explores how synthetic data can be leveraged to improve decisions for data-driven inventory management, focusing on the single-period newsvendor problem, a classic stochastic optimization problem in inventory management.
The first article, "A Meta Analysis of Data-Driven Newsvendor Approaches", presents a standardized evaluation framework for data-driven prescriptive approaches, tested through a numerical study. Findings suggest model performance is not robust, emphasizing the need for a standardized evaluation process.
The second article, "Application of Generative Adversarial Networks in Inventory Management", examines using synthetic data generated by Generative Adversarial Networks (GANs) for the newsvendor problem. This study shows GANs can model complex demand relationships, offering a promising alternative to traditional methods.
The third article, "Combining Synthetic Data and Transfer Learning for Deep Reinforcement Learning in Inventory Management", proposes a method using Deep Reinforcement Learning (DRL) with synthetic and real data through transfer learning. This approach trains a generative model to learn demand distributions, generates synthetic data, and fine-tunes a DRL agent on a smaller real dataset. This method outperforms traditional approaches in controlled and practical settings, though further research is needed to generalize these findings.
Herstellung und Qualitätskontrolle einer vaskularisierten Trägerstruktur zur Blasenrekonstruktion
(2024)
Die regenerative Medizin gewinnt heutzutage immer mehr an Bedeutung. Der klinische Ersatz der Harnblase nach Tumoren oder bei Fehlbildungen stellt bis heute einen komplexen Eingriff mit zahlreichen Langzeitkomplikationen dar. Trotz etlicher Behandlungsmöglichkeiten können die aktuellen therapeutischen Maßnahmen nicht als langfristige Heilung angesehen werden. Meine Arbeit ist Teil einer präklinischen Großtierstudie zur Entwicklung eines neuartigen Blasenersatzes auf der Basis eines vaskularisierten Tissue-Engineering-Konstruktes. Mit der Herstellung eines vaskularisierten Augmentats (UroVaSc) wird ein Arzneimittel für neuartige Therapien (ATMP) für die Anwendung am Menschen entwickelt.
Unter Zuhilfenahme fortschrittlicher Verfahren aus dem Bereich des Tissue Engineerings wird ein Gewebe hergestellt, welches im Empfänger die beiden kritischen Punkte der Vernarbung und insbesondere bei jungen Empfängern die Problematik eines nicht mitwachsenden Gewebes reduzieren oder verhindern soll. Als Ausgangsmaterialien dienen ein Abschnitt porcinen Jejunums und eine porcine Hautbiopsie. In der klinischen Anwendung wird die Hautbiopsie dem Empfänger des Augmentats entnommen. Aus den beiden Ausgangsmaterialien werden als Zwischenprodukte dezellularisiertes Jejunum (BioVaSc) und aus der Hautbiopsie eine primäre, mikrovaskuläre Endothelzellkultur (mvEC) hergestellt. Die mvEC besiedeln die Gefäße der Trägerstruktur BioVaSc in einem Bioreaktorsystem und führen zum vaskularisierten Endprodukt, der UroVaSc.
Ziel der vorliegenden Arbeit war die Entwicklung eines dreidimensionalen, vaskularisierten Blasenaugmentats. Im Verlauf dieser Arbeit waren die Methoden der Isolation und Kultivierung der Zellen, die Rebesiedlung und Kultur des autologen Augmentats, als auch die Qualitätskontrolle unter den Richtlinien der Guten Herstellungspraxis zu etablieren.
Für die Isolierung der mvEC wurde ein Protokoll erarbeitet, mit dem sich die Zellen, trotz intraindividueller Unterschiede der Spendertiere, in ausreichender Zellzahl und Reinheit darstellen ließen. Des Weiteren wurde die endotheliale Rebesiedlung der Trägerstruktur erfolgreich durchgeführt und dies mit Hilfe zellbiologischer und immunhistologischer Methoden belegt. In der Risikobeurteilung des Herstellungsprozesses wurde die Überwachung des Inkubators als wichtigen Schritt zur Erhöhung der Produktqualität identifiziert, der in weiterführenden Arbeiten adressiert werden sollte. Auf Grundlage meiner Forschungsergebnisse und weiterer Forschungsarbeiten erfolgt derzeit die funktionale Testung des Endproduktes im Großtierversuch.
Mit der erfolgreichen Herstellung eines vaskularisierten Blasenaugmentats wird betroffenen Patienten eine neuartige Therapieoption eröffnet, welche die Aussicht auf eine Heilung schwerer Erkrankungen an der Blase ermöglicht.
Maladaptive avoidance behaviors can contribute to the maintenance of fear, anxiety, and anxiety disorders. It has been proposed that, throughout anxiety disorder progression, extensively repeated avoidance may become a habit (i.e., habitual avoidance) instead of being controlled by internal threat-related goals (i.e., goal-directed avoidance). However, the process of the acquisition of habitual avoidance in anxiety disorders is not yet well understood. Accordingly, the current thesis aimed to investigate experimentally whether trait anxiety and anxiety disorders are associated with an increased shift from goal-directed to habitual avoidance.
The aim of Study 1 was to develop an experimental operationalization of maladaptive habitual avoidance. To this end, we adapted a commonly used action control task, the outcome devaluation paradigm. In this task, habitual avoidance was operationalized as persistent responses after extensive training to avoid an unpleasant stimulus when the aversive outcome was devalued, i.e., when individuals knew the aversive outcome could not occur anymore. We included indicators for costly and low-cost habitual avoidance, whereby habitual avoidance was associated with a monetary cost, while low-cost habitual avoidance was not associated with monetary costs. In Experiment 1 of Study 1, a pronounced costly and non-costly outcome devaluation effect was observed. However, this result may have partly resulted from trial-and-error learning or a better-safe-than-sorry strategy since not instructions about the stimulus-response-outcome contingencies after the outcome devaluation procedure had been provided to the participants. In Experiment 2 of Study 1, instructions on these stimulus-response-outcome contingencies were included to prevent the potential confounders. As a result, we observed no indicators for costly habitual avoidance, but evidence for low-cost habitual avoidance, potentially because competing goal-directed responses could easily be implemented and inhibited costly habitual avoidance tendencies.
In Study 2, the strength of habitual avoidance acquisition was compared between participants with and without anxiety disorders, using the experimental task of Experiment 1 in Study 1. The results indicated that costly and low-cost habitual avoidance was not more pronounced in participants with anxiety disorders than in the healthy control group. However, in an exploratory subgroup comparison, panic disorder predicted more substantial habitual avoidance acquisition than social anxiety disorder.
In Study 3, we investigated whether trait anxiety as a risk factor for anxiety disorders is associated with a specific increased shift from goal-directed to habitual avoidance and approach. The task from the Experiment 1 of Study 1 was adapted to include parallel versions for operationalizing habitual avoidance and habitual approach responses. Using a within-subjects design, the individuals – pre-screened for high and low trait anxiety – took part in the approach and the avoidance outcome devaluation task version. The results suggested stronger non-costly habitual responses in more highly trait-anxious individuals independent of the task version, and suggested a tendency towards an impact of trait anxiety on costly habitual approach rather than on costly habitual avoidance.
In summary, individuals with high trait anxiety or anxiety disorders did not develop habitual avoidance more readily than individuals with low trait anxiety or without anxiety disorders. Therefore, this thesis does not support the assumption that an increased tendency to acquire habitual avoidance contributes to persistent maladaptive avoidance in anxiety disorders. The thesis also contributes to the discourse on the validity of outcome devaluation studies in general by highlighting the impact of task features, such as the instructions after the outcome devaluation procedure or the task difficulty in the test phase, on the experimental results. Such validity issues may partly explain the heterogeneity of findings in research with the outcome devaluation paradigm. We suggest ways towards more valid operationalizations of habitual avoidance in future studies.
The Western Honeybee (Apis mellifera) is among the most versatile species in the world. Its adaptability is rooted in thousands of the differently specialized individuals acting jointly together. Thus, bees that are able to handle a certain task or condition well can back up other individuals less capable to do so on the colony level. Vice versa, the latter individuals might perform better in other situations. This evolutionary recipe for success ensures the survival of colonies despite challenging habitat conditions. In this context, the ectoparasitic mite Varroa destructor reflects the most pronounced biotic challenge to honeybees worldwide. Without proper treatment, infested colonies rapidly dwindle and ultimately die. Nevertheless, resistance behaviours against this parasite have evolved in some populations through natural selection, enabling colonies to survive untreated. In this, different behaviours appear to be adapted to the respective habitat conditions and may complement each other. Yet, the why and how of this behavioural response to the mite remains largely unknown. My thesis focuses on the biological background of Varroa-resistance traits in honeybees and presents important findings for the comprehension of this complex host-parasite interaction. Based on this, I draw implications for both, applied bee breeding and scientific investigations in the field of Varroa-resistance. Specifically, I focus on two traits commonly found in resistant and, to a lower degree, also mite-susceptible colonies: decreased mite reproduction and the uncapping and subsequent recapping of sealed brood cells. Examining failures in the reproductive success of mites as a primary mechanism of Varroa-resistance, I was able to link them to specific bee behaviours and external factors. Since mite reproduction and the brood rearing of bees are inevitably connected, I first investigated the effects of brood interruption on the reproductive success of mites. Brood interruption decreased the reproductive success of mites both immediately and in the long term. By examining the causes of reproductive failure, I could show that this was mainly due to an increased share of infertile mites. Furthermore, I proved that interruption in brood rearing significantly increased the expression of recapping behaviour. These findings consequently showed a dynamic modulation of mite reproduction and recapping, as well as a direct effect of brood interruption on both traits. To further elucidate the plasticity in the expression of both traits, I studied mite reproduction, recapping behaviour and infestation levels over the course of three years. The resulting extensive dataset unveiled a significant seasonal variation in mite reproduction and recapping. In addition, I show that recapping decreases the reproductive success of mites by increasing delayed developing female offspring and cells lacking male offspring. By establishing a novel picture-based brood investigation method, I could furthermore show that both the removal of brood cells and recapping activity specifically target brood ages in which mite offspring would be expected. Recapping, however, did not cause infertility of mites. Considering the findings of my first study, this points towards complementary mechanisms.
This underlines the importance of increased recapping behaviour and decreased mite reproduction as resistance traits, while at the same time emphasising the challenges of reliable data acquisition. To pave the way for a practical application of these findings in breeding, we then investigated the heritability (i.e., the share of genotypic variation on the observed phenotypic variation) of the accounted traits. By elaborating comparable test protocols and compiling data from over 4,000 colonies, we could, for the first time, demonstrate that recapping of infested cells and decreased reproductive success of mites are heritable (and thus selectable) traits in managed honeybee populations.
My thesis proves the importance of recapping and decreased mite reproduction as resistance traits and therefore valuable goals for breeding efforts. In this regard, I shed light on the underlying mechanisms of both traits, and present clear evidence for their interaction and heritability.
1,1,2-trifluoroethene (HFO-1123) is intended for use as a refrigerant. Inhalation studies on HFO-1123 in rats suggested a low potential for toxicity, with no-observed-adverse-effect levels greater then 20,000 ppm. However, single inhalation exposure of Goettingen Minipigs and New Zealand White Rabbits resulted in mortality. It was assumed that conjugation of HFO-1123 with glutathione, via glutathione S-transferase, gives rise to S-(1,1,2-trifluoroethyl)-L-glutathione (1123-GSH), which is then transformed to the corresponding cysteine S-conjugate (S-(1,1,2-trifluoroethyl)-L-cysteine, 1123-CYS). Subsequent beta-lyase mediated cleavage of 1123-CYS may result in monofluoroacetic acid, a potent inhibitor of aconitase. Species-differences in 1123-GSH formation and 1123-CYS cleavage to MFA may explain species-differences in HFO-1123 toxicity.
This study was designed to test the hypothesis, that GSH-dependent biotransformation and subsequent beta-lyase mediated formation of monofluoroacetic acid, a potent inhibitor of aconitase in the citric acid cycle, may play a key role in HFO-1123 toxicity and to evaluate if species-differences in the extent of MFA formation may account for the species-differences in HFO-1123 toxicity. The overall objective was to determine species-differences in HFO-1123 biotransformation in susceptible vs. less susceptible species and humans as a basis for human risk assessment.
To this end, in vitro biotransformation of HFO-1123 and 1123-CYS was investigated in renal and hepatic subcellular fractions of mice, rats, humans, Goettingen Minipigs and NZW Rabbits. Furthermore, cytotoxicity and metabolism of 1123-CYS was assessed in cultured renal epithelial cells. Enzyme kinetic parameters for beta-lyase mediated cleavage of 1123-CYS in renal and hepatic cytosolic fractions were determined, and 19F-NMR was used to identify fluorine containing metabolites arising from 1123-CYS cleavage. Quantification of 1123-GSH formation in hepatic S9 fractions after incubation with HFO-1123 was performed by LC-MS/MS and hepatic metabolism of HFO-1123 was monitored by 19F-NMR.
Rates of 1123-GSH formation were increased in rat, mouse and NZW Rabbit compared to human and Goettingen hepatic S9, indicating increased GSH dependent biotransformation in rats, mouse and NZW Rabbits. NZW Rabbit hepatic S9 exhibited increased 1123-GSH formation in the presence compared to the absence of acivicin, a specific gamma-GT inhibitor. This indicates increased gamma-GT mediated cleavage of 1123-GSH in NZW Rabbit hepatic S9 compared to the other species. 19F-NMR confirmed formation of 1123-GSH as the main metabolite of GSH mediated biotransformation of HFO-1123 in hepatic S9 fractions next to F-. Increased F- formation was detected in NZW Rabbit and Goettingen Minipig hepatic S9 in the presence of an NADPH regenerating system, indicating a higher rate of CYP-450 mediated metabolism in these species. Based on these findings, it is possible that CYP-450 mediated metabolism may contribute to HFO-1123 toxicity.
In contrast to the increased formation of 1123-GSH in rat, mouse and NZW Rabbit hepatic S9 (compared to human and Goettingen Minipig), enzyme kinetic studies revealed a significantly higher beta-lyase activity towards 1123-CYS in renal cytosol of Goettingen Minipigs compared to cytosol from rats, mice, humans and NZW Rabbits. However, beta-lyase cleavage in renal NZW Rabbit cytosol was slightly increased compared to rat, mouse and human renal cytosols. 19F-NMR analysis confirmed increased time-dependent formation of MFA in renal Goettingen Minipig cytosol and NZW Rabbit (compared to human and rat cytosolic fractions). Three structurally not defined MFA-derivatives were detected exclusively in NZW Rabbit and Goettingen Minipig cytosols. Also, porcine kidney cells were more sensitive to cytotoxicity of 1123-CYS compared to rat and human kidney cells.
Overall, increased beta-lyase mediate cleavage of 1123-CYS to MFA in Goettingen Minipig and NZW Rabbit kidney (compared to human and rat) may support the hypothesis that enzymatic cleavage by beta-lyases may account for the species-differences in HFO-1123 toxicity. However, the extent of GST mediated biotransformation in the liver as the initial step in HFO-1123 metabolism does not fully agree with this hypothesis, since 1123-GSH formation occurs at higher rates in rat, mouse and NZW Rabbit S9 as compared to the Goettingen Minipig.
Based on the inconsistencies between the extent of GST and beta-lyase mediated biotransformation of HFO-1123 obtained by this study, a decisive statement about an increased biotransformation of HFO-1123 in susceptible species with a direct linkage to the species-specific toxicity cannot be drawn. Resulting from this, a clear and reliable conclusion regarding the risk for human health originating from HFO-1123 cannot be made. However, considering the death of Goettingen Minipigs and NZW Rabbits after inhalation exposure of HFO-1123 at concentrations great than 500 ppm and greater than 1250 ppm, respectively, this indicates a health concern for humans under peak exposure conditions. For a successful registration of HFO-1123 and its use as a refrigerant, further in vitro and in vivo investigations addressing uncertainties in the species-specific toxicity of HFO-1123 are urgently needed.
In this study, we developed an innovative nanoparticle formulation to facilitate the delivery of antitumor antibodies to tumor sites. The study commenced with the utilization of 13 bispecific antibody fusion proteins, which targeted the Fn14 receptor, thereby validating the pivotal role of crosslinking in Fn14 receptor activation. Subsequently, gold nanoparticles were activated using COOH-PEG-SH in combination with EDC/NHS, and subsequently conjugated with two Fn14-targeting antibodies, PDL192 and 5B6. Following this, a pH-sensitive shell was generated on the outer layer of the antibody-coupled gold nanoparticles through the application of chemically modified polylysine. The resultant complexes, termed MPL-antibody-AuNP, demonstrated a release profile reminiscent of the tumor microenvironment (TME). Notably, these complexes released antibody-AuNPs only in slightly acidic conditions while remaining intact in neutral or basic environments. Functionality analysis further affirmed the pH-sensitive property of MPL-antibody-AuNPs, demonstrating that the antibodies only initiated potent Fn14 activation in slightly acidic environments. This formulation holds potential for applicability to antibodies or ligands targeting the 80 TNFRSF family, given that gold nanoparticles successfully served as platforms for antibody crosslinking, thereby transforming these antibodies into potent agonists. Moreover, the TME disintegration profile of MPL mitigates the potential cytotoxic effects of antibodies, thereby circumventing associated adverse side effects. This study not only showcases the potential of nanoparticle formulations in targeted therapy, but also provides a solid foundation for further investigations on their clinical application in the context of targeting category II TNFRSF receptors with antibodies or ligands.
Innerhalb der Juvenilen Idiopathischen Arthritis (JIA) bilden Patienten mit Antinukleären Antikörpern (ANA) Subgruppen-übergreifend eine klinisch homogene Erkrankungsgruppe. Ob diesen klinischen Gemeinsamkeiten jedoch auch eine einheitliche Pathogenese zugrunde liegt, ist bisher unbekannt. Sogenannte periphere T-Helferzellen (TPH) spielen im Kontext zahlreicher Autoimmunerkrankungen eine entscheidende Rolle bei der Aktivierung autoreaktiver B-Zellen. Ziel dieser Arbeit war daher die phänotypische und funktionelle Analyse von PD-1hiCXCR5-CD4+ TPH-Zellen, sowie deren Verteilung in der Synovialflüssigkeit von Patienten unterschiedlicher Subgruppen der JIA.
Hierzu wurden Phänotyp und Zytokinprofil von PD-1hiCD4+ T-Zellen durchflusszytometrisch analysiert. Der funktionelle Einfluss von PD-1hiCD4+ T-Zellen auf die B-Zell-Differenzierung wurde mittels in vitro Kokulturen FACS-sortierter TPH-Zellen der Synovialflüssigkeit untersucht.
IL-21- und IL-17-produzierende T-Gedächtniszellen der Synovialflüssigkeit zeigten eine negative Korrelation zueinander. Die IL-21-Produktion ging besonders von PD-1hiCXCR5-HLA-DR+CD4+ T-Zellen aus, welche besonders in den Gelenken ANA-positiver JIA-Patienten akkumulierten. Diese Population zeigte phänotypische Ähnlichkeit mit TPH-Zellen und leistete in vitro effiziente B-Zell-Hilfe zu Plasmazelldifferenzierung und Immunglobulinsekretion, induzierte jedoch zudem einen CD21lo/-CD11c+T-bet+ Phänotyp in B-Zellen. Passend hierzu bestand auch ex vivo eine signifikante Korrelation zwischen TPH und CD21lo/-CD11c+T-bet+ doppelt-negativen B-Zellen (BDN).
Es konnte also die Expansion einer spezifischen T-Zellpopulation mit phänotypischen und funktionellen Charakteristika von TPH-Zellen beobachtet und deren funktioneller Zusammenhang mit CD21lo/-CD11c+T-bet+ BDN in der Synovialflüssigkeit von JIA-Patienten aufgezeigt werden. Dies könnte die Autoimmunantwort auf ubiquitäre Autoantigene innerhalb betroffener Gelenke ANA-positiver JIA-Patienten widerspiegeln.
The Macroeconomic Dimensions of Credit: A Comprehensive Analysis of Finance, Inequality and Growth
(2024)
Schumpeter's monetary growth theory is particularly influential for the modern understanding of the macroeconomic role of banks and credit. Based on this theory, this dissertation examines the macroeconomic role of the financial system, especially credit, in (1) generating economic growth, (2) directing economic resources and (3) distributing wealth.
Chapter 3 first shows empirically that 1) there is a positive correlation between the growth of credit and economic growth, even for developed countries, 2) no empirical correlation between household saving and economic growth can be established, and 3) there are both positive, negative and insignificant effects of credit on economic growth at country-specific level. Thus, there is broad empirical support for Schumpeter's monetary hypotheses.
A particularly interesting application of Schumpeter's growth theory can be seen in China. The results of the empirical study suggest that there is generally a positive correlation between credit and economic growth in China, that is, however, not linear in terms of regions, time and size of the financial system. Furthermore, the results in Chapter 4 suggest that credit-financed industrial policy in China may have contributed to more investment and GDP growth, although there are non-linearities between individual industries and types of companies.
Finally, Chapter 5 raises the question of the role of the financial system in the distribution of wealth. While credit to households and companies, together with indicators of working and saving behavior and the age structure of the population, are the most important determinants of wealth inequality, there are also various non-linearities in the relationship between credit and wealth inequality, including in relation to the level of development of financial systems and home ownership ratios.
Humans actively interact with the world through a wide range of body movements. To understand human cognition in its natural state, we need to incorporate ecologically relevant body movement into our account. One fundamental body movement during daily life is natural walking. Despite its ubiquity, the impact of natural walking on brain activity and cognition has remained a realm underexplored.
In electrophysiology, previous studies have shown a robust reduction of ongoing alpha power in the parieto-occipital cortex during body movements. However, what causes the reduction of ongoing alpha, namely whether this is due to body movement or prevalent sensory input changes, was unknown. To clarify this, study 1 was performed to test if the alpha reduction is dependent on visual input. I compared the resting state alpha power during natural walking and standing, in both light and darkness. The results showed that natural walking led to decreased alpha activity over the occipital cortex compared to standing, regardless of the lighting condition. This suggests that the movement-induced modulation of occipital alpha activity is not driven by visual input changes during walking. I argue that the observed alpha power reduction reflects a change in the state of the subject based on disinhibition induced by walking. Accordingly, natural walking might enhance visual processing and other cognitive processes that involve occipital cortical activity.
I first tested this hypothesis in vision. Study 2 was performed to examine the possible effects of natural walking across visual processing stages by assessing various neural markers during different movement states. The findings revealed an amplified early visual response, while a later visual response remain unaffected. A follow-up study 3 replicated the walking-induced enhancement of the early visual evoked potential and showed that the enhancement was dependent on specific stimulus-related parameters (eccentricity, laterality, distractor presence). Importantly, the results provided evidence that the enhanced early visual responses are indeed linked to the modulation of ongoing occipital alpha power. Walking also modulated the stimulus-induced alpha power. Specifically, it showed that when the target appeared in the fovea area without a distractor, walking exhibited a significantly reduced modulation of alpha power, and showed the largest difference to standing condition. This effect of eccentricity indicates that during later visual processing stages, the visual input in the fovea area is less processed than in peripheral areas while walking.
The two visual studies showed that walking leads to an enhancement in temporally early visual processes which can be predicted by the walking-induced change in ongoing alpha oscillation likely marking disinhibition. However, while walking affects neural markers of early sensory processes, it does not necessarily lead to a change in the behavioural outcome of a sensory task. The two visual studies suggested that the behavioural outcome seems to be mainly based on later processing stages.
To test the effects of walking outside the visual domain, I turned to audition in study 4. I investigated the influence of walking in a particular path vs. simply stepping on auditory processing. Specifically, the study tested whether enhanced processing due to natural walking can be found in primary auditory brain activity and whether the processing preferences are dependent on the walking path. In addition, I tested whether the changed spatial processing that was reported in previous visual studies can be seen in the auditory domain. The results showed enhanced sensory processing due to walking in the auditory domain, which was again linked to the modulation of occipital alpha oscillation. The auditory processing was further dependent on the walking path. Additionally, enhanced peripheral sensory processing, as found in vision, was also present in audition.
The findings outside vision supported the idea of natural walking affecting cognition in a rather general way. Therefore in my study 5, I examined the effect of natural walking on higher cognitive processing, namely divergent thinking, and its correlation with the modulation of ongoing alpha oscillation. I analyzed alpha oscillations and behavioural performance during restricted and unrestricted movement conditions while subjects completed a Guilford's alternate uses test. The results showed that natural walking, as well as missing body restriction, reduces the occipital alpha ongoing power independent of the task phase which goes along with higher test scores. The occipital alpha power reduction can therefore be an indicator of a changed state that allows improved higher cognitive processes.
In summary, the research presented in this thesis highlights that natural walking can change different processes in the visual and auditory domain as well as higher cognitive processes. The effect can be attributed to the movement of natural walking itself rather than to changes in sensory input during walking. The results further indicate that the walking-induced modulation of ongoing occipital alpha oscillations drives the cognitive effects. We therefore suggest that walking changes the inhibitory state which can influence awareness and attention. Such a mechanism could facilitate an adaptive enhancement in cognitive processes and thereby optimize movement-related behaviour such as navigation.
Cancer is one of the leading causes of death worldwide. Toxic contaminants in human food or medicinal products, such as substances like pyrrolizidine alkaloids (PAs), have been thought to contribute to cancer incidence. PAs are found in many plant species as secondary metabolites, and they may affect humans through contaminated food sources, herbal medicines, and dietary supplements. Hundreds of compounds belonging to PAs have been identified, differing in their chemical structures, either in their necine base moiety or esterification at their necic acid moiety. PAs undergo hepatic metabolism, and after this process, they can induce hepatotoxicity, genotoxicity, and carcinogenicity. However, the mechanism of inducing genotoxicity and carcinogenicity is still unclear and warrants further investigation.
Therefore, the present study aims to investigate the mechanism of genotoxicity induced by selected PAs with different chemical structures in in vitro systems. Primarily, human hepatoma HepG2 cells were utilized, and in co-culture, metabolically active HepG2 cells were combined with non-metabolically active human cervical HeLa H2B-GFP cells.
First, the genotoxicity of the PAs europine, lycopsamine, retrorsine, riddelliine, seneciphylline, echimidine, and lasiocarpine was investigated in the cytokinesis-block micronucleus (CBMN) assay. All seven selected PAs caused the formation of micronuclei in a dose-dependent manner, with the maximal increase of micronucleus formation ranging from 1.64 to 2.0 fold. The lowest concentrations at which significant induction of micronuclei was found were 3.2 µM for lasiocarpine and riddelliine, 32 µM for retrorsine and echimidine, and 100 µM for seneciphylline, europine, and lycopsamine. These results confirmed previously published potency rankings in the micronucleus assay.
The same PAs, with the exception of seneciphylline, were also investigated in a crosslink-modified comet assay, and reduced tail formation after hydrogen peroxide treatment was found in all diester-type PAs. Meanwhile, an equimolar concentration of the monoesters europine and lycopsamine did not significantly reduce DNA migration. Thus, the crosslinking activity was related to the ester type.
Next, the role of metabolic enzymes and membrane transporters in PA-induced genotoxicity was assessed. Ketoconazole (CYP 450-3A4 inhibitor) prevented lasiocarpine-induced micronucleus formation completely, while furafylline (CYP 450-1A2 inhibitor) reduced lasiocarpine-induced micronucleus formation, but did not abolish it completely. This implies that the CYP 450 enzymes play an important role in PA-induced genotoxicity.
Carboxylesterase 2 enzyme (CES 2) is commonly known to be involved in the detoxification of xenobiotics. Loperamide (CES 2 inhibitor) yielded an increased formation of lasiocarpine-induced micronuclei, revealing a possible role of CES-mediated detoxification in the genotoxicity of lasiocarpine. Also, intracellular glutathione (GSH) plays an important role in the detoxification of xenobiotics or toxins in the cells. Cells which had been pretreated with L-buthionine sulfoximine (BSO) to reduce GSH content were significantly more sensitive for the induction of micronucleus formation by lasiocarpine revealing the importance of GSH in PA-induced genotoxicity.
Quinidine (Q) and nelfinavir (NFR) are OCT1 and OATP1B1 influx transporter inhibitors, respectively, which reduced micronucleus induction by lasiocarpine (only quinidine significantly), but not completely, pointing to a relevance of OCT1 for PA uptake in HepG2 cells. Verapamil (V) and benzbromarone (Bz) are MDR1 and MRP2 efflux transporter inhibitors, respectively, and they caused a slightly increased micronucleus induction by lasiocarpine (significant only for benzbromarone) thus, revealing the role of efflux transporters in PA-induced genotoxicity.
The mechanistic approach to PA-induced genotoxicity was further studied based on oxidative stress via the formation of reactive oxygen species (ROS) in HepG2 cells. Overproduction of ROS can cross-link cellular macromolecules such as DNA, leading to genomic damage. An equimolar concentration of 10 µM of lasiocarpine (open-diester PA), riddelliine (cyclic-diester PA), and europine (monoester) significantly induced ROS production, with the highest ROS generation observed after lasiocarpine treatment, followed by riddelliine and then europine. No significant increase in ROS production was found with lycopsamine (10 µM; monoester PA), even at a higher concentration (320 µM). The generation of ROS by these PAs was further analyzed for confirmation by using 5 mM of the thiol radical scavenger antioxidant N-acetyl cysteine (NAC) combined with lasiocarpine, riddelliine, or europine. This analysis yielded a significant decrease in ROS after combining NAC with lasiocarpine, riddelliine, and europine. In addition, lasiocarpine, riddelliine, and europine induced a loss of mitochondrial membrane potential, pointing to mitochondria as the source of ROS generation.
In vivo, hepatic sinusoidal epithelial cells (HSECs) are known to be damaged first by PAs after hepatic metabolization, but HSECs themselves do not express the required metabolic enzymes for activation of PAs. To mimic this situation, HepG2 cells were used to metabolically activate PA in a co-culture with HeLa H2B-GFP cells as non-metabolically active neighbours. Due to the green fluorescent GFP label the HeLa cells could be identified easily based in the co-culture. The PAs europine, riddelliine and lasiocarpine induced micronucleus formation in HepG2 cells, and in HeLa H2B-GFP cells co-cultured with HepG2 cells, but not in HeLa H2B-GFP cells cultured alone. Metabolic inhibition of CYP 450 enzymes with ketoconazole abrogated micronucleus formation induced by the same PAs tested in the co-culture. The efflux transporter inhibitors verapamil and benzbromarone reduced the micronucleus formation in the co-culture. Furthermore, mitotic disturbances as an additional genotoxic mechanism of action were observed in HepG2 cells and in HeLa H2B-GFP cells co-cultured with HepG2 cells, but not in HeLa H2B-GFP cells cultured alone. Overall, we were able to show that PAs were activated by HepG2 cells and the metabolites induced genomic damage in co-cultured non-metabolically active green HeLa cells.
Finally, in HepG2 cells as well as the co-culture, combinations of PAs lasiocarpine and riddelliine favoured an additive effect rather than synergism. Thus, this study therefore provides support that the assumption of dose-addition can be applied in the characterization of the genotoxicity risk of PAs present in a mixture.
Diese retrospektive, naturalistische Studie beschäftigte sich mit dem Therapeutischen Drug Monitoring von Kindern und Jugendlichen unter Psychopharmakotherapie mit Escitalopram und Mirtazapin. Die Datenauswertung erfolgte anhand von klinischen Routinedaten aus dem TDM-Service des Speziallabors für TDM des Zentrums für psychische Gesundheit des Universitätsklinikums Würzburg. In der Studie wurden die Zusammenhänge zwischen Dosis, Serumkonzentration und positiver bzw. negativer klinischer Effekte, auch im Hinblick auf mögliche Einflussfaktoren wie Geschlecht, Alter, BMI-Status, Komedikation und Raucherstatus, untersucht. Ein weiteres Ziel der Arbeit war, Hinweise für die Definition eines altersspezifischen therapeutischen Referenzbereiches (Diagnoseübergreifend und Depressions-spezifisch) für Kinder und Jugendliche beider Medikamente zu gewinnen. Hierfür wurden für Escitalopram 41 Patienten im Alter zwischen elf und 18 Jahren und für Mirtazapin 23 Patienten im Alter von sechs bis 18 Jahren eingeschlossen und Daten zur Demographie, Serumkonzentrationsbestimmungen im Steady State, Schwere der Erkrankung (CGI-S), Therapieeffektivität (CGI-I) und Nebenwirkungen (UKU-Skala) ausgewertet.
Escitalopram: Die mittlere Tagesdosis betrug 14,8 mg, wobei die Serumkonzentrationen mit einer mittleren Konzentration von 32,2 ng/ml (SD= 26,6 ng/ml) zwischen sechs und 109 ng/ml schwankten. Bei 63,4 % der Patienten lag die ermittelte Serumkonzentration in dem für Erwachsene definierten therapeutischen Referenzbereich (15-80 ng/ml). Zwischen der Tagesdosis und der Serumkonzentration ergab sich eine auf dem 1 %-Niveau signifikante positive lineare Beziehung (rs= 0,46; p= 0,003). 65,9 % der Patienten respondierten seit Behandlungsbeginn. Zwischen der Serumkonzentration und dem therapeutischen Effekt (rs= 0,193; p= 0,282) und zwischen der Serumkonzentration und den Nebenwirkungen (r= 0,127; p= 0,467) konnte jeweils kein signifikanter Zusammenhang gefunden werden. Die Nebenwirkungsrate lag bei 25,7 %, wobei am häufigsten Spannung und innere Unruhe dokumentiert wurde. Mit der Idee, die Definition für den vorläufigen therapeutischen Referenzbereich sowohl der Konsensus-Leitlinie der AGNP (Hiemke et al., 2018) als auch von Hiemke (2019) zu berücksichtigen, wird als vorläufiger therapeutischer Referenzbereich für Escitalopram für Kinder und Jugendliche mit Depression eine untere Grenze zwischen 10 ng/ml bis 15 ng/ml und eine obere Grenze von 50 ng/ml vorgeschlagen. Dieser Bereich liegt niedriger als der für erwachsene Patienten definierte Bereich für Escitalopram von 15 bis 80 ng/ml.
Mirtazapin: Die mittlere Tagesdosis betrug 28,6 mg, wobei die Serumkonzentrationen mit einer mittleren Konzentration von 40,8 ng/ml (SD= 28,1 ng/ml) zwischen 13 und 130 ng/ml schwankten. Für 52,2 % der Patienten lag die Serumkonzentration in dem für Erwachsene definierten therapeutischen Referenzbereich (30-80 ng/ml). Zwischen der Tagesdosis und der Serumkonzentration ergab sich eine auf dem 1 %-Niveau signifikante positive Korrelation (rs= 0,655; p= 0,001). Hinsichtlich des Therapieeffektes respondierten 52,2 % der Patienten seit Behandlungsbeginn. Zwischen der Serumkonzentration und dem therapeutischen Effekt ergab sich ein auf dem 5 %-Niveau signifikanter positiver Zusammenhang (rs= 0,534; p= 0,015). Zwischen der Serumkonzentration und den Nebenwirkungen konnte kein signifikanter Zusammenhang gefunden werden (r= 0,240; p= 0,282). Die Nebenwirkungsrate lag bei 30,4 %, wobei Schläfrigkeit und Sedierung am häufigsten berichtet wurden. Als vorläufiger therapeutischer Referenzbereich für Mirtazapin für Kinder und Jugendliche mit Depression wird eine untere Grenze zwischen 15 ng/ml bis 20 ng/ml und eine obere Grenze von 50 ng/ml vorgeschlagen. Dieser Bereich liegt niedriger als der für erwachsene Patienten definierte Bereich für Mirtazapin von 30 bis 80 ng/ml.
Die Limitationen der vorliegenden naturalistischen Studie beachtend, sollten die Ergebnisse mit Vorsicht interpretiert und anhand einer größeren Stichprobe unter kontrollierteren Bedingungen überprüft werden.
Electrochemical impedance spectroscopy (EIS) is a valuable technique analyzing electrochemical behavior of biological systems such as electrical characterization of cells and biomolecules, drug screening, and biomaterials in biomedical field. In EIS, an alternating current (AC) power signal is applied to the biological system, and the impedance of the system is measured over a range of frequencies.
In vitro culture models of endothelial or epithelial barrier tissue can be achieved by culturing barrier tissue on scaffolds made with synthetic or biological materials that provide separate compartments (apical and basal sides), allowing for further studies on drug transport. EIS is a great candidate for non-invasive and real-time monitoring of the electrical properties that correlate with barrier integrity during the tissue modeling. Although commercially available transendothelial/transepithelial electrical resistance (TEER) measurement devices are widely used, their use is particularly common in static transwell culture. EIS is considered more suitable than TEER measurement devices in bioreactor cultures that involve dynamic fluid flow to obtain accurate and reliable measurements. Furthermore, while TEER measurement devices can only assess resistance at a single frequency, EIS measurements can capture both resistance and capacitance properties of cells, providing additional information about the cellular barrier's characteristics across various frequencies. Incorporating EIS into a bioreactor system requires the careful optimization of electrode integration within the bioreactor setup and measurement parameters to ensure accurate EIS measurements. Since bioreactors vary in size and design depending on the purpose of the study, most studies have reported using an electrode system specifically designed for a particular bioreactor. The aim of this work was to produce multi-applicable electrodes and established methods for automated non-invasive and real-time monitoring using the EIS technique in bioreactor cultures. Key to the electrode material, titanium nitride (TiN) coating was fabricated on different substrates (materials and shape) using physical vapor deposition (PVD) and housed in a polydimethylsiloxane (PDMS) structure to allow the electrodes to function as independent units. Various electrode designs were evaluated for double-layer capacitance and morphology using EIS and scanning electron microscopy (SEM), respectively. The TiN-coated tube electrode was identified as the optimal choice. Furthermore, EIS measurements were performed to examine the impact of influential parameters related to culture conditions on the TiN-coated electrode system. In order to demonstrate the versatility of the electrodes, these electrodes were then integrated into in different types of perfusion bioreactors for monitoring barrier cells. Blood-brain barrier (BBB) cells were cultured in the newly developed dynamic flow bioreactor, while human umblical vascular endothelial cells (HUVECs) and Caco-2 cells were cultured in the miniature hollow fiber bioreactor (HFBR). As a result, the TiN-coated tube electrode system enabled investigation of BBB barrier integrity in long-term bioreactor culture. While EIS measurement could not detect HUVECs electrical properties in miniature HFBR culture, there was the possibility of measuring the barrier integrity of Caco-2 cells, indicating potential usefulness for evaluating their barrier function. Following the bioreactor cultures, the application of the TiN-coated tube electrode was expanded to hemofiltration, based on the hypothesis that the EIS system may be used to monitor clotting or clogging phenomena in hemofiltration. The findings suggest that the EIS monitoring system can track changes in ion concentration of blood before and after hemofiltration in real-time, which may serve as an indicator of clogging of filter membranes. Overall, our research demonstrates the potential of TiN-coated tube electrodes for sensitive and versatile non-invasive monitoring in bioreactor cultures and medical devices.
Barth Syndrome (BTHS) is an inherited X-chromosomal linked disorder, characterized by early development of cardiomyopathy, immune system defects, skeletal muscle myopathy and growth retardation. The disease displays a wide variety of symptoms including heart failure, exercise intolerance and fatigue due to the muscle weakness. The cause of the disease are mutations in the gene encoding for the mitochondrial transacylase Tafazzin (TAZ), which is important for remodeling of the phospholipid cardiolipin (CL). All mutations result in a pronounced decrease of the functional enzyme leading to an increase of monolysocardiolipin (MLCL), the precursor of mature CL, and a decrease in mature CL itself. CL is a hallmark phospholipid of mitochondrial membranes, highly enriched in the inner mitochondrial membrane (IMM). It is not only important for the formation of the cristae structures, but also for the function of different protein complexes associated with the mitochondrial membrane. Reduced levels of mature CL cause remodeling of the respiratory chain supercomplexes, impaired respiration, defects in the Krebs cycle and a loss of mitochondrial calcium uniporter (MCU) protein. The defective Ca2+ handling causes impaired redox homeostasis and energy metabolism resulting in cellular arrhythmias and defective electrical conduction. In an uncompensated situation, blunting mitochondrial Ca2+ uptake provokes increased mitochondrial emission of H2O2 during workload transitions, related to oxidation of NADPH, which is required to regenerate anti-oxidative enzymes. However, in the hearts and cardiac myocytes of mice with a global knock-down of the Taz gene (Taz-KD), no increase in mitochondrial ROS was observed, suggesting that other metabolic pathways may have compensated for reduced Krebs cycle activation.
The healthy heart produces most of its energy by consuming fatty acids. In this study, the fatty acid uptake into mitochondria and their further degradation was investigated, which showed a switch of the metabolism in general in the Taz-KD mouse model. In vivo studies revealed an increase of glucose uptake into the heart and decreased fatty acid uptake and oxidation. Disturbed energy conversion resulted in activation of retrograde signaling pathways, implicating overall changes in the cell metabolism. Upregulated integrated stress response (ISR) was confirmed by increased levels of the downstream target, i.e., the activating transcription factor 4 (ATF4). A Tafazzin knockout mouse embryonal fibroblast cell model (TazKO) was used to inhibit the ISR using siRNA transfection or pharmaceutical inhibition. This verified the central role of
II
the ISR in regulating the metabolism in BTHS. Moreover, an increased metabolic flux into glutathione biosynthesis was observed, which supports redox homeostasis. In vivo PET-CT scans depicted elevated activity of the xCT system in the BTHS mouse heart, which transports essential amino acids for the biosynthesis of glutathione precursors. Furthermore, the stress induced signaling pathway also affected the glutamate metabolism, which fuels into the Krebs cycle via -ketoglutarate and therefore supports energy converting pathways. In summary, this thesis provides novel insights into the energy metabolism and redox homeostasis in Barth syndrome cardiomyopathy and its regulation by the integrated stress response, which plays a central role in the metabolic alterations. The aim of the thesis was to improve the understanding of these metabolic changes and to identify novel targets, which can provide new possibilities for therapeutic intervention in Barth syndrome.
In dieser Arbeit wurde durch das immunhistochemische Anfärben von nodalen (Natriumkanäle, NF), paranodalen (Caspr, NF) und internodalen (MBP) Proteinen der in Fingerhautbiopsien vorhanden Nervenfasern untersucht, ob eine Veränderung der typischen Verteilungsmuster dieser Proteine, eine demyelinisierende Polyneuropathie anzeigen kann. Dazu wurden am Universitätsklinikum Würzburg prospektiv 93 Polyneuropathie-Patienten und 25 Kontrollpersonen rekrutiert. Bei allen Patienten wurden Hautstanzbiospien am Zeigefinger durchgeführt. Bei 35 Patienten mit schweren oder unklaren Verläufen, wurden konsiliarisch Nervus suralis Biopsien durchgeführt. Aus einem Abschnitt von 27 dieser Biopsien, konnten im Rahmen dieser Arbeit Zupfnervenpräparate angefertigt und analog zu den Hautbiopsien ausgewertet werden. Aus der Routinediagnostik der Klinik flossen weiterhin die Ergebnisse der elektrophysiologischen Routinediagnostik und der Histologiebefund der Nervus suralis Biopsien in die Auswertung ein.
Zusammenfassend kamen veränderte Natriumkanalbanden in Fingerhautbiopsien signifikant häufiger bei Patienten mit elektrophysiologisch als demyelinisierend befundeten Polyneuropathien, als bei Patienten mit elektrophysiologisch als axonal befundeten Polyneuropathien vor. Vielfach fanden sich veränderte Natriumkanalbanden inmitten para- und internodal unauffälliger Schnürringe und umgekehrt. Diese Beobachtung stützt die bereits in Vorarbeiten vorgeschlagene und in der aktuellen Leitlinie zur Diagnostik für Polyneuropathien aufgegriffene Entität der Paranodopathien (Uncini, Susuki, & Yuki, 2013). Möglich wäre, dass eine veränderte Verteilung der Natriumkanäle die schnelle Leitfähigkeit beeinträchtigen und somit trotz intakter Bemarkung, elektrophysiologisch das Bild einer demyelinisierenden Neuropathie vermittelt. Ein direkter Zusammenhang zwischen dem Auftreten von doppelten und verlängerten Natriumkanalbanden und einzelnen Messwerten (z.B. Amplituden und Latenzzeiten) fand sich nicht. Auch in den Zupfnervenpräparaten der Nervus suralis Biopsien, konnten o.g. Verteilungsmuster untersucht werden. Deren Vorkommen zeigte sich als unabhängig vom elektrophysiologischen und histologischen Befund, von der Ätiologie der PNP und von den gefundenen Veränderungen in den Hautbiopsien des betreffenden Patienten.
Es zeigte sich, dass die unmittelbare postoperative gesundheitsbezogene Lebensqualität erwartungsgemäß deutlich eingeschränkt, jedoch nach circa sechs Monaten wieder auf dem Ausgangsniveau der präoperativen Ebene angekommen war. Sowohl die Symptomskalen als auch die Funktionsskalen zeigten statistisch signifikante Unterschiede der erhobenen Werte bezüglich des Vergleichs der präoperativen zu den postoperativen Daten, dasselbe ließ sich über die Werte im Rahmen der Verlaufskontrolle nach circa sechs Monaten erheben. Eine kurzfristige Einbuße der Lebensqualität durch einen stationären Krankenhausaufenthalt sowie einer operativen Versorgung erscheint logisch. Für die zukünftige Entscheidung vor allem auch für Personen, welche aufgrund einer benignen Leberraumforderung eine operative Versorgung erhalten sollen, ist zu sagen, dass die globale gesundheitsbezogene Lebensqualität postoperativ nach circa sechs Monaten gleich bzw. etwas gebessert ausfiel und somit eine Rechtfertigung der operativen Versorgung auch bei benignen Erkrankungen darstellen kann.
Ein wesentlicher Aspekt der Arbeit ist, dass gezeigt werden konnte, dass auch bei komplexen Lebereingriffen eine schnelle Rekonvaleszenz - mindestens auf das Niveau vor dem Eingriff - innerhalb der ersten sechs Monate zu erwarten ist. Die systematische Erfassung der Lebensqualität hilft die postoperativen Einschränkungen und die Rekonvaleszenz zu normieren.
Graphs provide a key means to model relationships between entities.
They consist of vertices representing the entities,
and edges representing relationships between pairs of entities.
To make people conceive the structure of a graph,
it is almost inevitable to visualize the graph.
We call such a visualization a graph drawing.
Moreover, we have a straight-line graph drawing
if each vertex is represented as a point
(or a small geometric object, e.g., a rectangle)
and each edge is represented as a line segment between its two vertices.
A polyline is a very simple straight-line graph drawing,
where the vertices form a sequence according to which the vertices are connected by edges.
An example of a polyline in practice is a GPS trajectory.
The underlying road network, in turn, can be modeled as a graph.
This book addresses problems that arise
when working with straight-line graph drawings and polylines.
In particular, we study algorithms
for recognizing certain graphs representable with line segments,
for generating straight-line graph drawings,
and for abstracting polylines.
In the first part, we first examine,
how and in which time we can decide
whether a given graph is a stick graph,
that is, whether its vertices can be represented as
vertical and horizontal line segments on a diagonal line,
which intersect if and only if there is an edge between them.
We then consider the visual complexity of graphs.
Specifically, we investigate, for certain classes of graphs,
how many line segments are necessary for any straight-line graph drawing,
and whether three (or more) different slopes of the line segments
are sufficient to draw all edges.
Last, we study the question,
how to assign (ordered) colors to the vertices of a graph
with both directed and undirected edges
such that no neighboring vertices get the same color
and colors are ascending along directed edges.
Here, the special property of the considered graph is
that the vertices can be represented as intervals
that overlap if and only if there is an edge between them.
The latter problem is motivated by an application
in automated drawing of cable plans with vertical and horizontal line segments,
which we cover in the second part.
We describe an algorithm that
gets the abstract description of a cable plan as input,
and generates a drawing that takes into account
the special properties of these cable plans,
like plugs and groups of wires.
We then experimentally evaluate the quality of the resulting drawings.
In the third part, we study the problem of abstracting (or simplifying)
a single polyline and a bundle of polylines.
In this problem, the objective is to remove as many vertices as possible from the given polyline(s)
while keeping each resulting polyline sufficiently similar to its original course
(according to a given similarity measure).
Anxiety patients overgeneralize fear, also because of an inability to perceptually discriminate threat and safety signals. Therefore, some studies have developed discrimination training that successfully reduced the occurrence of fear generalization. The present work is the first to take a treatment-like approach by using discrimination training after generalization has occurred. Therefore, two studies were conducted with healthy participants using the same fear conditioning and generalization paradigm, with two faces as conditioned stimuli (CSs), and four facial morphs between CSs as generalization stimuli (GSs). Only one face (CS+) was followed by a loud scream (unconditioned stimulus, US). In Study 1, participants underwent either fear-relevant (discriminating faces) or fear-irrelevant discrimination training (discriminating width of lines) or a non-discriminative control training between the two generalization tests, each with or without feedback (n = 20 each). Generalization of US expectancy was reduced more effectively by fear-relevant compared to fear-irrelevant discrimination training. However, neither discrimination training was more effective than non-discriminative control training. Moreover, feedback reduced generalization of US expectancy only in discrimination training. Study 2 was designed to replicate the effects of the discrimination-training conditions in a large sample (N = 244) and examine their benefits in individuals at risk for anxiety disorders. Again, feedback reduced fear generalization particularly well for US expectancy. Fear relevance was not confirmed to be particularly fear-reducing in healthy participants, but may enhance training effects in individuals at risk of anxiety disorder. In summary, this work provides evidence that existing fear generalization can be reduced by discrimination training, likely involving several (higher-level) processes besides perceptual discrimination (e.g., motivational mechanisms in feedback conditions). Its use may be promising as part of individualized therapy for patients with difficulty discriminating similar stimuli.
Sepsis ist ein häufiges und akut lebensbedrohliches Syndrom, das eine Organfunktionsstörung in Folge einer dysregulierten Immunantwort auf eine Infektion beschreibt. Eine frühzeitige Diagnosestellung und Therapieeinleitung sind von zentraler Bedeutung für das Überleben der Patient:innen. In einer Pilotstudie konnte unsere Forschungsgruppe mittels Durchflusszytometrie eine ausgeprägte Hyporeaktivität der Thrombozyten bei Sepsis nachweisen, die einen potenziell neuen Biomarker zur Sepsis-Früherkennung darstellt. Zur Evaluation des Ausmaßes und Entstehungszeitpunktes der detektierten Thrombozytenfunktionsstörung wurden im Rahmen der vorliegenden Arbeit zusätzlich zu Patient:innen mit Sepsis (SOFA-Score ≥ 2; n=13) auch hospitalisierte Patient:innen mit einer Infektion ohne Sepsis (SOFA-Score < 2; n=12) rekrutiert. Beide Kohorten wurden zu zwei Zeitpunkten (t1: <24h; t2: Tag 5-7) im Krankheitsverlauf mittels Durchflusszytometrie und PFA-200 untersucht und mit einer gesunden Kontrollgruppe (n=28) verglichen.
Phänotypische Auffälligkeiten der Thrombozyten bei Sepsis umfassten: (i) eine veränderte Expression verschiedener Untereinheiten des GPIb-IX-V-Rezeptorkomplexes, die auf ein verstärktes Rezeptor-Shedding hindeutet; (ii) ein ausgeprägtes Mepacrin-Beladungsdefizit, das auf eine zunehmend reduzierte Anzahl von δ-Granula entlang des Infektion-Sepsis Kontinuums hinweist; (iii) eine Reduktion endständig gebundener Sialinsäure im Sinne einer verstärkten Desialylierung. Die funktionelle Analyse der Thrombozyten bei Sepsis ergab bei durchflusszytometrischer Messung der Integrin αIIbβ3-Aktivierung (PAC-1-Bindung) eine ausgeprägte generalisierte Hyporeaktivität gegenüber multiplen Agonisten, die abgeschwächt bereits bei Infektion nachweisbar war und gemäß ROC-Analysen gut zwischen Infektion und Sepsis diskriminierte (AUC >0.80 für alle Agonisten). Im Gegensatz dazu zeigten Thrombozyten bei Sepsis und Analyse mittels PFA-200 unter Einfluss physiologischer Scherkräfte eine normale bis gar beschleunigte Aggregation.
Die Reaktivitätsmessung von Thrombozyten mittels Durchflusszytometrie stellt weiterhin einen vielversprechenden Biomarker für die Sepsis-Früherkennung dar. Für weitere Schlussfolgerungen ist jedoch eine größere Kohorte erforderlich. In nachfolgenden Untersuchungen sollten zudem mechanistische Ursachen der beschriebenen phänotypischen und funktionellen Auffälligkeiten von Thrombozyten bei Infektion und Sepsis z.B. mittels Koinkubationsexperimenten untersucht werden.
Die Jahresabschlussprüfung verfolgt das Ziel, die Verlässlichkeit der Rechnungslegung zu bestätigen. Folglich kann sie einen wesentlichen Beitrag zu einem hohen Informationsniveau an den Märkten leisten. Angesichts dieser großen ökonomischen Bedeutung unternimmt der deutsche Gesetzgeber zahlreiche Anstrengungen, um eine hohe Prüfungsqualität sicherzustellen.
Die Sichtung der Wirtschaftsprüferordnung zeigt hierbei, dass regulatorische Maßnahmen ergriffen werden, die am Kern der Jahresabschlussprüfung ansetzen, nämlich an den Berufsangehörigen selbst. So wurde der Zugang zum Berufsstand der vereidigten Buchprüfer mehrmals geschlossen und wiedereröffnet. Des Weiteren sind markante Anpassungen des Niveaus des Wirtschaftsprüfungsexamens im Zeitablauf zu erkennen. Bei der Jahresabschlussprüfung der Unternehmen von öffentlichem Interesse sind außerdem besondere Berufspflichten zu erfüllen. Zum einen ist diesen schweren Eingriffen in die Freiheit der Berufswahl und der Berufsausübung gemein, dass sie allesamt die Qualifikation des Abschlussprüfers adressieren. Zum anderen werden die entsprechenden Gesetzesänderungen mehrheitlich mit einer Stärkung der Prüfungsqualität begründet.
Fraglich ist, inwiefern jene Facetten der Prüferqualifikation tatsächlich einen Einfluss auf die Prüfungsqualität ausüben. Aufgrund mangelnder Evidenz ergibt sich die Notwendigkeit, eine empirische Studie am deutschen Prüfermarkt durchzuführen und somit den Beginn zur Schließung der identifizierten Forschungslücke zu setzen.
Das Ziel der vorliegenden Dissertation besteht folglich darin, den Zusammenhang zwischen der Prüferqualifikation und der Prüfungsqualität mittels Regressionsanalysen zu untersuchen. Dazu wurde ein einzigartiger Datensatz zu deutschen privaten prüfungspflichtigen Kapitalgesellschaften mit unkonsolidierten Finanz- und Prüferinformationen im Zeitraum 2006-2018 mit insgesamt 217.585 grundlegenden Beobachtungen erhoben, bereinigt und aufbereitet. Da die Prüfungsqualität nicht direkt beobachtbar ist, wird zwischen wahrgenommener Prüfungsqualität und tatsächlicher Prüfungsqualität unterschieden. Im Rahmen dieser Dissertation wird die wahrgenommene Prüfungsqualität über Fremdkapitalkosten und die tatsächliche Prüfungsqualität über absolute diskretionäre Periodenabgrenzungen approximiert.
Die Ergebnisse der Hauptregressionen zeigen überwiegend, dass kein Zusammenhang zwischen den Maßgrößen der Prüferqualifikation und der wahrgenommenen und tatsächlichen Prüfungsqualität besteht. Die Zusatz- und Sensitivitätsanalysen unterstützen diesen Befund. So können mit Blick auf die Berufszugangsregelungen keine Qualitätsunterschiede zwischen den Berufsständen der Wirtschaftsprüfer und der vereidigten Buchprüfer nachgewiesen werden. Auch innerhalb des Berufstandes der Wirtschaftsprüfer ergeben sich keine Hinweise auf ein Qualitätsgefälle zwischen den Prüfergruppen, die unterschiedliche Examensanforderungen durchlebt haben. Hinsichtlich der Berufsausübungsregelungen ist zu beobachten, dass die zusätzlichen Anforderungen an die Jahresabschlussprüfung der Unternehmen von öffentlichem Interesse nicht mit einer anderen Prüfungsqualität bei privaten Unternehmen verbunden sind. Die beschriebenen regulatorischen Schritte des Gesetzgebers im Bereich der Prüferqualifikation erscheinen somit im Lichte einer verbesserten Prüfungsqualität nicht zwingend gerechtfertigt.
Das regulatorische Gerüst-Protein LASP1, welches aus der Krebsforschung bekannt ist, wurde 2012 in humanen Makrophagen, den Protagonisten der Atherosklerose nachgewiesen. LASP1 ist durch seine Lokalisation an dynamischen Aktinskelettkonstruktionen (vgl. Invadopodien, Podosomen), nachweislich an Zellmigration, Proliferation und Invasionsfähigkeit bestimmter Tumorzellen beteiligt. Aufgrund einer großen Schnittmenge der Entstehungsmechanismen und zugrundeliegenden Signalwegen von Krebserkrankungen und Atherosklerose wurde LASP1 im Zusammenhang der Atherosklerose untersucht. In einem 16 Wochen Hochfettdiätversuch zeigten LASP1.Ldlr-/--Mäuse mehr atherosklerotische Läsionen in der Gesamtaorta als Ldlr-/--Tiere, was eine athero-protektive Rolle von LASP1 nahelegt. Passend hierzu führte Stimulation mit oxLDL in Makrophagen zu einer Hochregulation von LASP1. Zusätzlich internalisierten LASP1-/--Makrophagen signifikant mehr oxLDL im Vergleich zu LASP1-exprimierenden Zellen. Analog zu den Daten aus der Krebsforschung konnte eine reduzierte endotheliale Adhäsion sowie chemotaktische Migration von Ldlr.LASP1-/--Monozyten im Vergleich zu Ldlr-/-- Monozyten festgestellt werden. Dies ließe isoliert betrachtet eine pro-atherogene Rolle von LASP1 vermuten. Ein Nachweis von LASP1 im Zellkern von BMDMs konnte, zusätzlich zum fehlenden Shuttelproteinpartner ZO-2, nicht erbracht werden. Die Interaktion von LASP1 mit Transkriptionsfaktoren scheint daher unwahrscheinlich. Kongruent mit diesen Ergebnissen zeigte sich keine Veränderung der Transkription, der Proteinexpression sowie Sekretion von TNF! und ADAM17 durch den LASP1-KO. Insgesamt kommt LASP1 eine zweifellos komplexe Rolle in der Atherogenese zu. Die Ergebnisse der HFD-Versuche legen nahe, dass die primär anti-atherosklerotischen Einflüsse von LASP1 in vivo gegenüber den eher pro-atherosklerotischen Effekten des Proteins in vitro überwiegen.
Trust carries the capacity to shift the focus from risks to opportunities of a situation. Scientific studies from the field of trust research point out that besides situation-specific factors (i.e., stimuli of the environment), cross-situationally stable interindividual differences (i.e., personality) are involved in the emergence of trust. Stable interindividual differences are particularly influential to the subjective experience of situational conditions when crucial information is incomplete. The online shopping environment classifies as a prime example of markets with asymmetric information. Research has examined online consumer trust in the light of signaling theory to understand the effects of trust-enhancing signals. Previous research largely neglects interindividual differences in the perception, processing and reaction to these signals. Against this background, this scientific work has two primary objectives: the investigation of (1) interindividual differences in the evaluation of trust-enhancing signals and (2) a personality-based personalization of trust-enhancing signals in its effect on cognition and behavior. For this purpose, an interactive online shop setup was created, which served as realistic environmental framework. First, the results show a trust-enhancing effect of both objective and subjective personalization, with a superiority of subjective over objective personalization. Second, results suggest a particular susceptibility of the beliefs component of trust. Third, the results suggest that personalization exerts a specifically strong effect in what is, by definition, the particularly uncertain environment of credence goods. Fourth, results indicate that while the trust-enhancing effects of personalization operate (largely) independently of personality, the effect of personality on trust seems to depend on the condition of signal presentation. Taken together, the present work makes a contribution to understanding the effect of personality-adapted signaling environments on the emergence of trust and decision making in the specific context of B2C e-commerce.
Hintergrund: Depressionen zählen zu den häufigsten psychischen Erkrankungen. Depressive Symptome umfassen beeinträchtigte kognitive Funktionen, vegetative Beschwerden und ein verändertes emotionales Erleben. Die defizitäre Wahrnehmung interner körperlicher Signale wird sowohl mit der Pathogenese der Depression als auch mit Angststörungen in Verbindung gebracht. Interozeptive Genauigkeit (IAc) beschreibt dabei die Fähigkeit, körperliche Empfindungen wie den eigenen Herzschlag akkurat wahrzunehmen und wird mit einer Herzwahrnehmungsaufgabe erfasst. In bildgebenden Verfahren wie der funktionellen Magnetresonanztomografie (fMRT) war eine niedrigere IAc mit einer verringerten Inselaktivität assoziiert. Während der Ruhezustandsmessung des Gehirns (resting-state fMRT) kann in Abwesenheit einer Aufgabe die intrinsische Aktivität des Gehirns gemessen werden. Dies ermöglicht die Identifizierung von kortikalen Netzwerken. Depressive Patienten weisen eine veränderte funktionelle Konnektivität innerhalb und zwischen einzelnen Netzwerken wie dem Salience Network (SN), welchem die Insel zugerechnet wird, und dem Default Mode Network (DMN) auf. Bisherige Studien, in denen überwiegend jüngere depressive Patienten untersucht wurden, kamen jedoch hinsichtlich der IAc und den kortikalen Netzwerken zu inkonsistenten Ergebnissen. Insbesondere ist unklar, inwieweit sich die IAc nach einem Therapieansprechen verändert, von der Herzratenvariabilität (HRV) moduliert wird und welche Auswirkungen dies auf die funktionelle Konnektivität kortikaler Netzwerke hat.
Ziele: Eine veränderte IAc und HRV wie auch funktionelle Konnektivitätsunterschiede im DMN und SN könnten Biomarker der Depression darstellen. Im Rahmen einer Längsschnittuntersuchung wurde getestet, ob ältere depressive Patienten über eine verringerte IAc, eine geringere HRV und über eine veränderte funktionelle Konnektivität im SN sowie DMN verfügen. Darüber hinaus sollte erforscht werden, in welchem Ausmaß sich Patienten, die auf die Behandlung ansprachen (Responder), von sogenannten Non-Respondern in Bezug auf die IAc, die HRV, das SN und das DMN unterschieden.
Methoden: In Studie 1 (Baseline) wurden 30 größtenteils medizierte, schwer depressive Patienten (> 50 Jahre) und 30 gesunde Kontrollprobanden untersucht. Die IAc wurde in einer Herzwahrnehmungsaufgabe ermittelt und die HRV bestimmt. Zusätzlich wurde eine resting-state fMRT durchgeführt. Eine funktionelle Konnektivitätsanalyse für Saatregionen im SN und DMN wurde mit einem saatbasierten Ansatz (seed-to-voxel) durchgeführt. Für eine Subgruppenanalyse wurde die Patientengruppe in ängstlich-depressive und nicht-ängstlich depressive Patienten unterteilt.
In Studie 2 (sechs Monate Follow-up) wurde die Studienkohorte nochmals untersucht. Es nahmen 21 Personen der Patientengruppe und 28 Probanden der Kontrollgruppe teil. Wiederum wurden die IAc und die HRV bestimmt. Außerdem fand eine resting-state fMRT-Messung statt. Die Patientengruppe wurde unterteilt in depressive Responder und Non-Responder.
Ergebnisse: In Studie 1 zeigten depressive Patienten eine funktionelle Hypokonnektivität zwischen einzelnen Saatregionen der Insel (SN) und Teilen des superioren frontalen Gyrus, des supplementärmotorischen Cortex, des lateralen okzipitalen Cortex sowie des Okzipitalpols. Zudem wiesen depressive Patienten zwischen der Saatregion im anterioren Teil des DMN und der Insel sowie dem Operculum eine erhöhte funktionelle Konnektivität auf. Die Gruppen unterschieden sich nicht in der IAc und der HRV. Ängstlich-depressive Patienten zeigten eine höhere funktionelle Konnektivität innerhalb der Insel als nicht-ängstlich depressive Patienten, jedoch zeigten sich keine Unterschiede in der IAc und der HRV.
In Studie 2 wiesen depressive Non-Responder im Vergleich zu Respondern eine Hyperkonnektivität zwischen dem posterioren DMN und dem Frontalpol sowie zwischen dem posterioren DMN und temporalen Arealen im SN auf. Keine funktionellen Konnektivitätsunterschiede zeigten sich für die Saatregionen im SN. Depressive Responder, Non-Responder und die Kontrollprobanden unterschieden sich in ihrer IAc und HRV nicht.
Schlussfolgerungen: Die Ergebnisse der Studien unterstreichen, dass bei depressiven Patienten, Respondern und Non-Respondern Unterschiede in der intrinsischen Gehirnaktivität funktioneller Netzwerke bestehen, jedoch nicht in der akkuraten Wahrnehmung des eigenen Herzschlages und der HRV. Therapeutische Interventionen, die auf eine Verbesserung der IAc abzielen, könnten insbesondere für Non-Responder dennoch eine zusätzliche Behandlungsmöglichkeit darstellen. Für eine personalisierte Medizin könnte die weitere Erforschung von kortikalen Netzwerken einen wesentlichen Beitrag leisten, um ein individuelles Therapieansprechen zu prädizieren.
The goal of this thesis is to study the topological and algebraic properties of the quasiconformal automorphism groups of simply and multiply connected domains in the complex plain, in which the quasiconformal automorphism groups are endowed with the supremum metric on the underlying domain. More precisely, questions concerning central topological properties such as (local) compactness, (path)-connectedness and separability and their dependence on the boundary of the corresponding domains are studied, as well as completeness with respect to the supremum metric. Moreover, special subsets of the quasiconformal automorphism group of the unit disk are investigated, and concrete quasiconformal automorphisms are constructed. Finally, a possible application of quasiconformal unit disk automorphisms to symmetric cryptography is presented, in which a quasiconformal cryptosystem is defined and studied.
Idiopathic Pulmonary Fibrosis (IPF) is a progressive parenchymal lung disease with limited therapeutic treatments. Pathologically altered lung fibroblasts, called myofibroblasts, exhibit increased proliferation, migration, and collagen production, and drive IPF development and progression. Fibrogenic factors such as Platelet derived growth factor-BB (PDGF-BB) contribute to these pathological alterations. Endogenous counter-regulating factors are barely known. Published studies have described a protective role of exogenously administered C-type Natriuretic Peptide (CNP) in pathological tissue remodeling, for example in heart and liver fibrosis. CNP and its cyclic GMP producing guanylyl cyclase B (GC-B) receptor are expressed in the lungs, but it is unknown whether CNP can attenuate lung fibrosis by this pathway. To address this question, we performed studies in primary cultured lung fibroblasts.
To examine the effects of the CNP/GC-B pathway on PDGF-BB-induced collagen
production, proliferation, and migration in vitro, lung fibroblasts were cultured from wildtype control and GC-B knockout mice. Human lung fibroblasts from patients with IPF and healthy controls were obtained from the UGMLC Biobank. In RIA experiments, CNP, at 10nM and 100nM, markedly and similarly increased cGMP levels in both the murine and human lung fibroblasts, demonstrating GC-B/cGMP signaling. CNP reduced PDGF-BB induced proliferation and migration of lung fibroblasts in BrdU incorporation and gap closure assays, respectively. CNP strongly decreased PDGF-BB-induced collagen 1/3 expression as measured by immunocytochemistry and immunoblotting. Importantly, the protective actions of CNP were preserved in IPF fibroblasts. It is known that the profibrotic actions of PDGF-BB are partly mediated by phosphorylation and nuclear export of Forkhead Box O3 (FoxO3), a transcription factor downregulated in IPF. CNP prevented PDGF-BB elicited FoxO3 phosphorylation and nuclear exclusion in both murine and human control and IPF fibroblasts. CNP signaling and functions were abolished in GC-B-deficient lung fibroblasts.
Taken together, the results show that CNP moderates the PDGF-BB-induced activation and differentiation of human and murine lung fibroblasts to myofibroblasts. This effect is mediated CNP-dependent by GC-B/cGMP signaling and FoxO3 regulation. To follow up the patho-physiological relevance of these results, we are generating mice with fibroblast-restricted GC-B deletion for studies in the model of bleomycin-induced pulmonary fibrosis.
Die Bauchlagerung von intubierten ARDS-Patient/innen mit einer schlechten Oxygenierung wird laut Leitlinie seit mehreren Jahren als supportive Therapiemaßnahme empfohlen. Im Rahmen der COVID-19 Pandemie wurde nun erstmalig die Bauchlagerung auch bei hypoxämischen, nicht-intubierten Patient/innen untersucht. Diese Fragestellung wurde in der vorliegenden Arbeit mittels einer systematischen Übersichtsarbeit betrachtet. Aufgrund der aktuellen Pandemiesituation wurden neben ARDS-Patient/innen im Allgemeinen insbesondere COVID-19 Patient/innen mit einem akuten Lungenversagen als Subgruppe untersucht.
Am 21.11.2020 wurde eine systematische Suche nach Studien in den Datenbanken MEDLINE, Cochrane COVID-19 Study Register und Living Overview of the Evidence platform durchgeführt. Die Ergebnisse wurden, wo möglich, in Form einer Meta-Analyse zusammengefasst, in Tabellen darstellt oder deskriptiv beschrieben. Das Risiko für Bias wurde jeweils für die eingeschlossenen kontrollierten Studien mittels ROBINS-I beurteilt. Die Vertrauenswürdigkeit der Evidenz der gesamten Arbeit wurde mit Hilfe des GRADE-Ansatzes untersucht.
Insgesamt wurden 30 Studien eingeschlossen, davon 4 kontrollierte Studien, keine RCTs. In 3 der kontrollierten Studien wurde die Bauchlagerung bei COVID-19 Patient/innen untersucht, in einer bei Patient/innen mit einem anderweitig verursachten ARDS. Es ist unklar, ob die Bauchlagerung die Intubationsrate (RR = 0,92; 95% KI: 0,59 - 1,44; I² = 65%; sehr niedrige Vertrauenswürdigkeit der Evidenz), die Mortalität (RR = 0,55; 95% KI: 0,23 - 1,30; I² = 60%; sehr niedrige Vertrauenswürdigkeit der Evidenz) und die Wahrscheinlichkeit für eine Aufnahme auf die Intensivstation (RR = 0,94; 95% KI: 0,54 - 1,63; I2 = 71%; sehr niedrige Vertrauenswürdigkeit der Evidenz) verringern kann. Auch für die anderen betrachteten Endpunkte konnte kein signifikanter Effekt der Bauchlagerung nachgewiesen werden Im Vergleich der Subgruppen „Nicht-COVID-19“ (8 Studien) und „COVID-19“ (22 Studien) konnten in Bezug auf alle betrachteten Endpunkte keine relevanten Unterschiede festgestellt werden.
Insgesamt ist die Evidenz nicht ausreichend, um Vor- und Nachteile der Bauchlagerung für nicht-intubierte ARDS Patient/innen gegenüber der üblichen Rückenlagerung aufzuzeigen und diese für die Praxis zu empfehlen.
Für den Funktionserhalt nach einer Fragilitätsfraktur ist eine stabile Osteosynthese, welche eine frühfunktionelle Nachbehandlung zur Vermeidung längerer Immobilität erlaubt, mit suffizienter Reposition essenziell. Die stabile Osteosynthese kann in osteoporotischem Knochen jedoch durch dessen schwache biomechanische Eigenschaften limitiert sein. Indem die in-situ-Implantataugmentation mit Knochenzement die Belastbarkeit des Knochens in Implantatnähe verbessert, kann auch in osteoporotischem Knochen eine stabile Osteosynthese erreicht werden.
Ziel dieser Studie war es, eine vielversprechende Formulierung eines Magnesiumphosphatzementes so weiterzuentwickeln, dass deren Anwendung bei der in-situ-Implantataugmentation möglich wurde. In einem zweiten Schritt sollte die Formulierung gegenüber kommerziell erhältlichen Knochenzementen durch die Materialprüfung im Druckversuch und mithilfe eines biomechanischen Testmodells evaluiert werden.
Die Vorversuche offenbarten die Nachteile der konventionellen, wasserbasierten Magnesiumphosphatzementformulierung bei der in-situ-Implantataugmentation: „Filter Pressing“ und eine unpassende Viskosität limitierten die Anwendung. Erst die Formulierung als vorgemischte Magnesiumphosphat-Paste mit Propan-1,2,3,-triol als Bindemittel verbesserte die Injizierbarkeit und ermöglichte eine verlässliche in-situ- Implantataugmentation.
Bei der Zementevaluation zeigte Traumacem™ V+ als PMMA-Zement die höchste Kompressionsfestigkeit im Druckversuch, die höchste Rotationsstabilität in der Torsionsprüfung und eine sehr gute Injizierbarkeit. Paste-CPC und MgPO-Paste zeigten sich in Druckversuch und Torsionsprüfung untereinander vergleichbar, wobei die MgPO-Paste tendenziell eine initial höhere Stabilität aufweist. Für den Parameter Normalisiertes Drehmoment zeigten alle Zementgruppen einen statistisch signifikanten Unterschied zur Kontrollgruppe, was den stabilitätssteigernden Effekt aller verwendeten Knochenzemente demonstriert. Es konnte kein Effekt der in-situ-Implantataugmentation auf Phimax, also auf den, bis zum maximalen Drehmoment gefahrenen Winkel, gefunden werden. Die Korrelation zwischen Drehmoment und Knochendichte zeigte den Zusammenhang zwischen Rotationsstabilität und Knochendichte für die Kontrollgruppe, welcher jedoch bei Zementaugmentation mit Traumacem™ V+ und MgPO-Paste verschwand.
Zusammengefasst wurde in dieser Studie erstmals eine biologisch vorteilhafte MgPO- Paste für den Einsatz bei der in-situ-Implantataugmentation entwickelt und verwendet. Weiter konnte der stabilitätssteigernde Effekt der Zementaugmentation mit dieser MgPO-Paste, sowie mit den Knochenzementen Traumacem™ V+ und Paste-CPC, für TFNA-Schenkelhalsklingen im isolierten Femurkopf-Modell gezeigt werden. Der Einsatz der MgPO-Paste bei der in-situ-Implantataugmentation bedarf bis zur eventuellen Marktreife einer Verbesserung der Injizierbarkeit sowie der Evaluation in klinischen Studien.
Darf es etwas mehr sein? Neuroenhancement im Studium – eine Befragung an Würzburger Hochschulen
(2024)
Neuroenhancement (NE) bezeichnet die Einnahme psychotroper Substanzen mit dem Ziel der geistigen Leistungssteigerung oder Beruhigung. NE wird durch gesunde Perso- nen genutzt. Es besteht somit keine Indikation zur Einnahme psychotroper Wirkstoffe. Zum NE genutzte Substanzen sind z.B. Koffeintabletten, verschreibungspflichtige Medi- kamente oder illegale Substanzen. Die bisherige Forschung findet Hinweise auf einen Zusammenhang zwischen NE und ADHS-Symptomen, einigen Aspekten psychischer Gesundheit, sowie Substanzkonsum. Bisher gibt es keine Forschung zu NE am Hoch- schulstandort Würzburg.
Es wurde eine anonyme online Querschnittsbefragung im ersten Quartal 2021 durchge- führt. Eingeladen waren 5600 Studierende der Julius-Maximilians-Universität Würzburg und der Hochschule für angewandte Wissenschaften Würzburg Schweinfurt. Der Frage- bogen bestand aus 53 Items und enthielt u. a. die folgenden validierten Messinstrumente: ASRS, PSS-10, PHQ-4 und AUDIT-C.
Die Response Rate lag bei 18% (n = 1011). Das Wissen über NE war weit unter den Stu- dierenden verbreitet. Die Prävalenz für Neuroenhancement im Studium lag bei 12.7%. Die drei meistgenannten Substanzen waren Koffeintabletten (6.6%), Cannabis (4.5%) und Methylphenidat (4.3%). Häufigster Anlass für NE war die Prüfungsvorbereitung. Es zeigten sich deutliche Unterschiede zwischen den Fachbereichen, u.a. hinsichtlich der Prävalenz von NE. ADHS-Symptomen, Stress, Ängstlichkeit, und Depressivität waren positiv mit NE assoziiert. Ein stärkerer Effekt ergab sich für den Zusammenhang zwi- schen NE und riskanten Alkoholkonsum bzw. Tabakkonsum. Diese Ergebnisse wurden durch eine binomial logistische Regression bestätigt.
Die konsumierten Substanzen, das Wissen über NE, die Prävalenz von NE und die Gründe für dessen Nutzung fügen sich nahtlos in die bisherige Forschung ein. Auch die Assoziation zwischen ADHS-Symptomen, Stress, Ängstlichkeit, Depressivität, riskan- tem Alkoholkonsum und Tabakkonsum bestätigt bisherige Forschungsergebnisse.
Es konnte gezeigt werden, dass rund ein Zehntel der Studierenden NE bereits genutzt haben. In Anbetracht der gesundheitlichen Gefahren, die mit NE einhergehen ist die Etab- lierung bzw. der Ausbau von Aufklärung-, Beratungs- und Hilfsangeboten für Studie- rende anzustreben sowie weitere Forschung zum Thema indiziert.
Die molekularen Parameter PSMA-TV und TL-PSMA im 68Ga-PSMA PET/CT leiten sich ab von MTV und TLG im FDG PET/CT. Mit der vorliegenden Arbeit wurden die Grenzen neuer Autosegmentierungsprogramme durch eine maximale Belastung mit großen Tumorvolumina von Patienten unter taxanbasierter Chemotherapie ausgelotet. Die Programme Syngo.via und FIJI kamen zu vergleichbaren Ergebnissen. Patienten mit einem Gleason Score von 8-10 zeigten unter Therapie eine signifikante Zunahme des PSMA-TV und TL-PSMA im Gegensatz zu Patienten mit Gleason Score 6-7b. Ein hoher PSA-Wert korrelierte zu allen Zeitpunkten signifikant mit einem hohen PSMA-TV und TL-PSMA, ebenso korrelierte ein steigender PSA-Wert signifikant mit steigenden Werten in PSMA-TV und TL-PSMA. Patienten mit einem biochemischen Progress und einem Progress nach modifiziertem PERCIST zeigten vor Therapie ein signifikant höheres PSMA-TV und TL-PSMA als Patienten ohne Progress und unter Therapie eine signifikante Zunahme des PSMA-TV und TL-PSMA im Vergleich zu Patienten ohne Progress. Eine Einteilung des Therapieansprechens aller Patienten in CR, PR, SD und PD nach PSMA-TV, TL-PSMA, PSA-Wert und modifiziertem PERCIST stimmte nicht in allen Patienten überein. Ein signifikant kürzeres Gesamtüberleben zeigten lediglich Patienten mit einem nach dem PSA-Wert definiertem Progress. Im praktischen Vergleich der beiden Programme benötigte Syngo.via für eine komplette Segmentierung signifikant mehr Zeit als FIJI, vor allem da der Wechsel von VOI zu VOI signifikant länger dauerte. Unabhängig vom Autosegmentierungsprogramm dauerte eine komplette Segmentierung länger, je größer das PSMA-TV und das TL-PSMA war, je mehr VOIs das Programm automatisch setzte und je mehr VOIs manuell gelöscht und neu gesetzt wurden. In der Gesamtschau bieten PSMA-TV und TL-PSMA in Kombination mit den sich schnell weiterentwickelnden Autosegmentierungs-Programmen die Möglichkeit, auch sehr hohe Tumorlasten des PCas objektiv und vergleichbar zu beschreiben.
Diese retrospektive Studie an der Universitätsklinik Würzburg diente der Beurteilung der longitudinalen Funktion in Bezug auf die Gesamtmortalität bei Patienten mit HFmrEF und HFrEF. Die Gruppierung erfolgte anhand der jeweiligen Baseline LVEF. Eine weitere Unterteilung erfolgte in eine ischämische oder nicht-ischämische Genese der HF. Die Subgruppen wurden anhand der Baseline klinischen Charakteristika sowie der echokardiographischen Parameter verglichen. Hier ließ sich ein relativ ähnliches Patientenklientel mit vergleichbarem Alter, Geschlecht, BMI sowie kardialen Risikofaktoren zeigen. Signifikante Unterschiede ergab der Vergleich des NYHA-Stadiums, der Nierenfunktion sowie des Auftretens von Myokardinfarkten.
Die Veränderung der LVEF über die Zeit hat einen zentralen Stellenwert zur Evaluation des Outcomes von Patienten mit HFmrEF und HFrEF. Eine Verbesserung der LVEF fand sich signifikant häufiger bei HFrEF Patienten als bei HFmrEF Patienten, welche über die Zeit signifikant häufiger eine stabile LVEF aufwiesen.
Außerdem war nach Auswertung der Überlebenskurven nach Kaplan-Meier in HFmrEF Patienten eine verbesserte oder unveränderte LVEF über die Zeit mit einem besseren Überleben verbunden, vor allem bei Patienten mit ischämischer Ätiologie. In der HFrEF Gruppe konnte gezeigt werden, dass sowohl Patienten mit ischämischer als auch mit nicht-ischämischer Ätiologie bei Vorliegen einer verbesserten oder unveränderten LVEF über die Zeit ein besseres Outcome aufwiesen.
Eine erniedrigte MAPSE bedeutete vor allem bei HFmrEF Patienten mit nicht-ischämischer Ätiologie ein schlechteres Outcome.
Die Ergebnisse dienten unter anderem der weiteren Charakterisierung der HFmrEF und HFrEF Gruppe sowie der Identifikation von Faktoren zur Beurteilung der Veränderung der LVEF über die Zeit und der Prognose des Langzeitüberlebens beider Gruppen. Ziel für die Zukunft sollte sein, auch für HFmrEF Patienten evidenzbasierte Herzinsuffizienz Therapien zu etablieren.
Die von Friedhelm Brusniak und Ulrich Konrad betreute und angenommene Dissertation nimmt den Briefwechsel zwischen August Heinrich Hoffmann von Fallersleben und dem jüngeren Augsburger Kapellmeister und Komponisten Hans Michael Schletterer in den Jahren 1862 bis 1873 in den Blick und dokumentiert dabei Hoffmanns Einfluss auf den Entstehungsprozess der Vertonungen seiner Lieder, besonders seiner Kinderlieder. Die Arbeit beleuchtet zudem den Erfahrungsschatz, den sich der ‚Dichter-Sänger‘ Hoffmann von Fallersleben auch durch die Zusammenarbeit mit anderen Musikern seiner Zeit, vorrangig Ludwig Christian Erk (1807–1883) und Ernst Heinrich Leopold Richter (1805–1876), erworben hatte. Darüber hinaus werden in der Korrespondenz Themen des gesellschaftlichen und politischen Lebens, der privaten und beruflichen Situation beider wie auch Hoffmanns Rolle als väterlicher Berater Schletterers berührt. Die Arbeit darf als neuer substantieller Beitrag der Hoffmann-Forschung und der interdisziplinären Liedforschung angesehen werden, der insbesondere der Kinderliedforschung neue Impulse verleiht.
Helically Twisted Graphene Nanoribbons: Bottom-up Stereospecific Synthesis and Characterization
(2024)
Over the past decade, substantial progress has been made in synthesizing atomically precise carbon nanostructures, with a focus on graphene nanoribbons (NRs) through advanced synthetic techniques. Despite these advancements, precise control over the stereochemistry of twisted NRs remains challenging. This thesis introduces a strategic approach to achieve absolute control over the single-handed helical conformation in a cove-edged NR, utilizing enantiopure [n]helicenes as a molecular wrench to intricately dictate the overall conformation of the NR.
Enantiopure [7]helicenes were stitched to the terminal K-regions of a conjugated pyrene NR using a stereospecific and site-selective palladium(II)-catalyzed annulative π-extension (APEX) reaction, resulting in a helically twisted NR with an end-to-end twist of 171°, the second-largest twist reported so far in the literature for twistacenes. The helical end-to-end twist increases with each addition of benzene ring to the central acene core, suggesting that the extra strain induced by the terminal [7]helicenes maintains such a high level of twist.
The quantum chemical calculations were conducted to investigate the impact of twisting on the conformational population. At room temperature, the central backbone of the nanoribbon adopts the twisted helicity opposite to that of the attached [7]helicene, constituting around 99% of the molecular population. For instance, (P)-[7]helicenes produce a left-handed helical nanoribbon, while (M)-[7]helicenes produce a right-handed helical nanoribbon. In the presence of helicenes of opposite chirality, the nanoribbon adopts a waggling conformation. The helically twisted nanoribbons are conformationally robust, as variable temperature chiroptical measurements showed no change in CD and CPL spectra. The proposed strategy, involving the late-stage addition of [n]helicene units through the APEX reaction, appears promising for streamlining the synthesis of diverse cove edge NR variants with desired conformations.
In addition to single-handed helically twisted nanoribbons, the symmetry-based functional properties of C2 and C1 symmetric pyrene-fused single and double [n]helicene compounds were studied. Owing to its higher structural rigidity, the C1 symmetric heptagonal ring-containing molecules exhibited exceptional configurational stability along with remarkable chiroptical properties compared to their C2 symmetric as well as pristine helicene congeners.
The WHO-designated neglected-disease pathogen Chlamydia trachomatis (CT) is a gram-negative bacterium responsible for the most frequently diagnosed sexually transmitted infection worldwide. CT infections can lead to infertility, blindness and reactive arthritis, among others. CT acts as an infectious agent by its ability to evade the immune response of its host, which includes the impairment of the NF-κB mediated inflammatory response and the Mcl1 pro-apoptotic pathway through its deubiquitylating, deneddylating and transacetylating enzyme ChlaDUB1 (Cdu1). Expression of Cdu1 is also connected to host cell Golgi apparatus fragmentation, a key process in CT infections.
Cdu1 may this be an attractive drug target for the treatment of CT infections. However, a lead molecule for the development of novel potent inhibitors has been unknown so far. Sequence alignments and phylogenetic searches allocate Cdu1 in the CE clan of cysteine proteases. The adenovirus protease (adenain) also belongs to this clan and shares a high degree of structural similarity with Cdu1. Taking advantage of topological similarities between the active sites of Cdu1 and adenain, a target-hopping approach on a focused set of adenain inhibitors, developed at Novartis, has been pursued. The thereby identified cyano-pyrimidines represent the first active-site directed covalent reversible inhibitors for Cdu1. High-resolution crystal structures of Cdu1 in complex with the covalently bound cyano-pyrimidines as well as with its substrate ubiquitin have been elucidated. The structural data of this thesis, combined with enzymatic assays and covalent docking studies, provide valuable insights into Cdu1s activity, substrate recognition, active site pocket flexibility and potential hotspots for ligand interaction. Structure-informed drug design permitted the optimization of this cyano-pyrimidine based scaffold towards HJR108, the first molecule of its kind specifically designed to disrupt the function of Cdu1. The structures of potentially more potent and selective Cdu1 inhibitors are herein proposed.
This thesis provides important insights towards our understanding of the structural basis of ubiquitin recognition by Cdu1, and the basis to design highly specific Cdu1 covalent inhibitors.
Interactions between host and pathogen determine the development, progression and outcomes
of disease. Medicine benefits from better descriptions of these interactions through increased
precision of prevention, diagnosis and treatment of diseases. Single-cell genomics is a
disruptive technology revolutionizing science by increasing the resolution with which we study
diseases. Cell type specific changes in abundance or gene expression are now routinely investigated
in diseases. Meanwhile, detecting cellular phenotypes across diseases can connect
scientific fields and fuel discovery. Insights acquired through systematic analysis of high resolution
data will soon be translated into clinical practice and improve decision making. Therefore,
the continued use of single-cell technologies and their application towards clinical samples will
improve molecular interpretation, patient stratification, and the prediction of outcomes.
In the past years, I was fortunate to participate in interdisciplinary research groups bridging
biology, clinical research and data science. I was able to contribute to diverse projects through
computational analysis and biological interpretation of sequencing data. Together, we were
able to discover cellular phenotypes that influence disease progression and outcomes as well
as the response to treatment. Here, I will present four studies that I have conducted in my PhD.
First, we performed a case study of relapse from cell-based immunotherapy in Multiple Myeloma.
We identified genomic deletion of the epitope as mechanism of immune escape and implicate
heterozygosity or monosomy of the genomic locus at baseline as a potential risk factor. Second,
we investigated the pathomechanisms of severe COVID-19 at the earliest stage of the COVID-
19 pandemic in Germany in March 2020. We discovered that profibrotic macrophages and
lung fibrosis can be caused by SARS-CoV-2 infection. Third, we used a mouse model of chronic
infection with Staphylococcus aureus that causes Osteomyelitis similar to the human disease.
We were able to identify dysregulated immunometabolism associated with the generation of
myeloid-derived suppressor cells (MDSC). Fourth, we investigated Salmonella infection of the
human small intestine in an in vitro model and describe features of pathogen invasion and host
response.
Overall, I have been able to successfully employ single-cell sequencing to discover important
aspects of diseases ranging from development to treatment and outcome. I analyzed samples
from the clinics, human donors, mouse models and organoid models to investigate different
aspects of diseases and managed to integrate data across sample types, technologies and
diseases. Based on successful studies, we increased our efforts to combine data from multiple
sources to build comprehensive references for the integration of large collections of clinical
samples. Our findings exemplify how single-cell sequencing can improve clinical research and
highlights the potential of mechanistic discoveries to drive precision medicine.
This thesis investigates the charged moments and the symmetry-resolved
entanglement entropy in the context of the AdS3/CFT2 duality. In the
first part, I focus on the holographic U(1) Chern-Simons-Einstein gravity,
a toy model of AdS3/CFT2 with U(1) Kac-Moody symmetry. I
start with the vacuum background with a single entangling interval. I
show that, apart from a partition function in the grand canonical ensemble,
the charged moments can also be interpreted as the two-point
function of vertex operators on the replica surface. For the holographic
description, I propose a duality between the bulk U(1) Wilson line and
the boundary vertex operators. I verify this duality by deriving the
effective action for the Chern-Simons fields and comparing the result
with the vertex correlator. In the twist field approach, I show that the
charged moments are given by the correlation function of the charged
twist operators and the additional background operators. To solve the
correlation functions involved, I prove the factorization of the U(1) extended
conformal block into a U(1) block and a Virasoro block. The
general expression for the U(1) block is derived by directly summing
over the current descendant states, and the result shows that it takes
an identical form as the vertex correlators. This leads to the conclusion
that the disjoint Wilson lines compute the neutral U(1) block. The final
result for the symmetry-resolved entanglement entropy shows that
it is always charge-independent in this model. In the second part, I
study charged moments in higher spin holography, where the boundary
theory is a CFT with W3 symmetry. I define the notion of the
higher spin charged moments by introducing a spin-3 modular charge
operator. Restricting to the vacuum background with a single entangling
interval, I employ the grand canonical ensemble interpretation
and calculate the charged moments via the known higher spin black
hole solution. On the CFT side, I perform a perturbative expansion for
the higher spin charged moments in terms of the connected correlation
functions of the spin-3 modular charge operators. Using the recursion
relation for the correlation functions of the W3 currents, I evaluate the
charged moments up to the quartic order of the chemical potential. The
final expression matches with the holographic result. My results both
for U(1) Chern-Simons Einstein gravity and W3 higher spin gravity
constitute novel checks of the AdS3/CFT2 correspondence.
Colorectal cancer (CRC) is the second most common tumour disease in Germany, with the sequential accumulation of certain mutations playing a decisive role in the transition from adenoma to carcinoma. In particular, deregulation of the Wnt signalling pathway and the associated deregulated expression of the MYC oncoprotein play a crucial role. Targeting MYC thus represents an important therapeutic approach in the treatment of tumours. Since direct inhibition of MYC is challenging, various approaches have been pursued to date to target MYC indirectly. The MYC 5' UTR contains an internal ribosomal entry site (IRES), which has a particular role in the initiation of MYC translation, especially in multiple myeloma. As basis for this work, it was hypothesised on the basis of previous data that translation of MYC potentially occurs via its IRES in CRC as well. Based on this, two IRES inhibitors were tested for their potential to regulate MYC expression in CRC cells. In addition, alternative, 5’ UTR-dependent translation of MYC and interacting factors were investigated. EIF3D was identified as a MYC 5' UTR binding protein which has the potential to regulate MYC expression in CRC. The results of this work suggest that there is a link between eIF3D and MYC expression/translation, rendering eIF3D a potential therapeutic target for MYC-driven CRCs.
Defensive behaviors in response to threats are key factors in maintaining mental and physical health, but their phenomenology remains poorly understood. Prior work reported an inhibition of oculomotor activity in response to avoidable threat in humans that reminded of freezing behaviors in rodents. This notion of a homology between defensive responding in rodents and humans was seconded by concomitant heart rate decrease and skin conductance increase. However, several aspects of this presumed defense state remained ambiguous. For example, it was unclear whether the observed oculomotor inhibition would 1) robustly occur during preparation for threat-avoidance irrespective of task demands, 2) reflect a threat-specific defensive state, 3) be related to an inhibition of somatomotor activity as both motion metrics have been discussed as indicators for freezing behaviors in humans, and 4) manifest in unconstrained settings.
We thus embarked on a series of experiments to unravel the robustness, threat-specificity, and validity of previously observed (oculo)motor and autonomic dynamics upon avoidable threat in humans. We provided robust evidence for reduced gaze dispersion, significantly predicting the speed of subsequent motor reactions across a wide range of stimulus contexts. Along this gaze pattern, we found reductions in body movement and showed that the temporal profiles between gaze and body activity were positively related within individuals, suggesting that both metrics reflect the same construct. A simultaneous activation of the parasympathetic (i.e., heart rate deceleration) and sympathetic (i.e., increased skin conductance and pupil dilation) nervous system was present in both defensive and appetitive contexts, suggesting that these autonomic dynamics are not only sensitive to threat but reflecting a more general action-preparatory mechanism. We further gathered evidence for two previously proposed defensive states involving a decrease of (oculo)motor activity in a naturalistic, unconstrained virtual reality environment. Specifically, we observed a state consisting of a cessation of ongoing behaviors and orienting upon relatively distal, ambiguous threat (Attentive Immobility) while an entire immobilization and presumed allocation of attention to the threat stimulus became apparent upon approaching potential threat (Immobility under Attack).
Taken together, we provided evidence for specific oculomotor and autonomic dynamics upon increasing levels of threat that may inspire future translational work in rodents and humans on shared mechanisms of threat processing, ultimately supporting the development of novel therapeutic approaches.
Among the defense strategies developed in microbes over millions of years, the innate adaptive CRISPR-Cas immune systems have spread across most of bacteria and archaea. The flexibility, simplicity, and specificity of CRISPR-Cas systems have laid the foundation for CRISPR-based genetic tools. Yet, the efficient administration of CRISPR-based tools demands rational designs to maximize the on-target efficiency and off-target specificity. Specifically, the selection of guide RNAs (gRNAs), which play a crucial role in the target recognition of CRISPR-Cas systems, is non-trivial. Despite the fact that the emerging machine learning techniques provide a solution to aid in gRNA design with prediction algorithms, design rules for many CRISPR-Cas systems are ill-defined, hindering their broader applications.
CRISPR interference (CRISPRi), an alternative gene silencing technique using a catalytically dead Cas protein to interfere with transcription, is a leading technique in bacteria for functional interrogation, pathway manipulation, and genome-wide screens. Although the application is promising, it also is hindered by under-investigated design rules. Therefore, in this work, I develop a state-of-art predictive machine learning model for guide silencing efficiency in bacteria leveraging the advantages of feature engineering, data integration, interpretable AI, and automated machine learning. I first systematically investigate the influential factors that attribute to the extent of depletion in multiple CRISPRi genome-wide essentiality screens in Escherichia coli and demonstrate the surprising dominant contribution of gene-specific effects, such as gene expression level. These observations allowed me to segregate the confounding gene-specific effects using a mixed-effect random forest (MERF) model to provide a better estimate of guide efficiency, together with the improvement led by integrating multiple screens. The MERF model outperformed existing tools in an independent high-throughput saturating screen. I next interpret the predictive model to extract the design rules for robust gene silencing, such as the preference for cytosine and disfavoring for guanine and thymine within and around the protospacer adjacent motif (PAM) sequence. I further incorporated the MERF model in a web-based tool that is freely accessible at www.ciao.helmholtz-hiri.de.
When comparing the MERF model with existing tools, the performance of the alternative gRNA design tool optimized for CRISPRi in eukaryotes when applied to bacteria was far from satisfying, questioning the robustness of prediction algorithms across organisms. In addition, the CRISPR-Cas systems exhibit diverse mechanisms albeit with some similarities. The captured predictive patterns from one dataset thereby are at risk of poor generalization when applied across organisms and CRISPR-Cas techniques. To fill the gap, the machine learning approach I present here for CRISPRi could serve as a blueprint for the effective development of prediction algorithms for specific organisms or CRISPR-Cas systems of interest. The explicit workflow includes three principle steps: 1) accommodating the feature set for the CRISPR-Cas system or technique; 2) optimizing a machine learning model using automated machine learning; 3) explaining the model using interpretable AI. To illustrate the applicability of the workflow and diversity of results when applied across different bacteria and CRISPR-Cas systems, I have applied this workflow to analyze three distinct CRISPR-Cas genome-wide screens. From the CRISPR base editor essentiality screen in E. coli, I have determined the PAM preference and sequence context in the editing window for efficient editing, such as A at the 2nd position of PAM, A/TT/TG downstream of PAM, and TC at the 4th to 5th position of gRNAs. From the CRISPR-Cas13a screen in E. coli, in addition to the strong correlation with the guide depletion, the target expression level is the strongest predictor in the model, supporting it as a main determinant of the activation of Cas13-induced immunity and better characterizing the CRISPR-Cas13 system. From the CRISPR-Cas12a screen in Klebsiella pneumoniae, I have extracted the design rules for robust antimicrobial activity across K. pneumoniae strains and provided a predictive algorithm for gRNA design, facilitating CRISPR-Cas12a as an alternative technique to tackle antibiotic resistance.
Overall, this thesis presents an accurate prediction algorithm for CRISPRi guide efficiency in bacteria, providing insights into the determinants of efficient silencing and guide designs. The systematic exploration has led to a robust machine learning approach for effective model development in other bacteria and CRISPR-Cas systems. Applying the approach in the analysis of independent CRISPR-Cas screens not only sheds light on the design rules but also the mechanisms of the CRISPR-Cas systems. Together, I demonstrate that applied machine learning paves the way to a deeper understanding and a broader application of CRISPR-Cas systems.
In 2020, cancer was the leading cause of death worldwide, accounting for nearly 10 million deaths. Lung cancer was the most common cancer, with 2.21 million cases per year in both sexes. This non-homogeneous disease is further subdivided into small cell lung cancer (SCLC, 15%) and non-small cell lung cancer (NSCLC, 85%). By 2023, the American Cancer Society estimates that NSCLC will account for 13% of all new cancer cases and 21% of all estimated cancer deaths. In recent years, the treatment of patients with NSCLC has improved with the development of new therapeutic interventions and the advent of targeted and personalised therapies. However, these advances have only marginally improved the five-year survival rate, which remains alarmingly low for patients with NSCLC. This observation highlights the importance of having more appropriate experimental and preclinical models to recapitulate, identify and test novel susceptibilities in NSCLC. In recent years, the Trp53fl/fl KRaslsl-G12D/wt mouse model developed by Tuveson, Jacks and Berns has been the main in vivo model used to study NSCLC. This model mimics ADC and SCC to a certain extent. However, it is limited in its ability to reflect the genetic complexity of NSCLC. In this work, we use CRISPR/Cas9 genome editing with targeted mutagenesis and gene deletions to recapitulate the conditional model. By comparing the Trp53fl/fl KRaslsl- G12D/wt with the CRISPR-mediated Trp53mut KRasG12D, we demonstrated that both showed no differences in histopathological features, morphology, and marker expression. Furthermore, next-generation sequencing revealed a very high similarity in their transcriptional profile. Adeno-associated virus-mediated tumour induction and the modular design of the viral vector allow us to introduce additional mutations in a timely manner. CRISPR-mediated mutation of commonly mutated tumour suppressors in NSCLC reliably recapitulated the phenotypes described in patients in the animal model. Lastly, the dual viral approach could induce the formation of lung tumours not only in constitutive Cas9 expressing animals, but also in wildtype animals. Thus, the implementation of CRISPR genome editing can rapidly advance the repertoire of in vivo models for NSCLC research. Furthermore, it can reduce the necessity of extensive breeding.
Physical regimes characterized by low Mach numbers and steep stratifications pose severe challenges to standard finite volume methods. We present three new methods specifically designed to navigate these challenges by being both low Mach compliant and well-balanced. These properties are crucial for numerical methods to efficiently and accurately compute solutions in the regimes considered.
First, we concentrate on the construction of an approximate Riemann solver within Godunov-type finite volume methods. A new relaxation system gives rise to a two-speed relaxation solver for the Euler equations with gravity. Derived from fundamental mathematical principles, this solver reduces the artificial dissipation in the subsonic regime and preserves hydrostatic equilibria. The solver is particularly stable as it satisfies a discrete entropy inequality, preserves positivity of density and internal energy, and suppresses checkerboard modes.
The second scheme is designed to solve the equations of ideal MHD and combines different approaches. In order to deal with low Mach numbers, it makes use of a low-dissipation version of the HLLD solver and a partially implicit time discretization to relax the CFL time step constraint. A Deviation Well-Balancing method is employed to preserve a priori known magnetohydrostatic equilibria and thereby reduces the magnitude of spatial discretization errors in strongly stratified setups.
The third scheme relies on an IMEX approach based on a splitting of the MHD equations. The slow scale part of the system is discretized by a time-explicit Godunov-type method, whereas the fast scale part is discretized implicitly by central finite differences. Numerical dissipation terms and CFL time step restriction of the method depend solely on the slow waves of the explicit part, making the method particularly suited for subsonic regimes. Deviation Well-Balancing ensures the preservation of a priori known magnetohydrostatic equilibria.
The three schemes are applied to various numerical experiments for the compressible Euler and ideal MHD equations, demonstrating their ability to accurately simulate flows in regimes with low Mach numbers and strong stratification even on coarse grids.
Two-dimensional lattices are in the focus of research in modern solid state physics due to their novel and exotic electronic properties with tremendous potential for seminal future applications. Of particular interest within this research field are quantum spin Hall insulators which are characterized by an insulating bulk with symmetry-protected metallic edge states. For electrons within these one-dimensional conducting channels, spin-momentum locking enables dissipationless transport - a property which promises nothing short of a revolution for electronic devices. So far, however, quantum spin Hall materials require enormous efforts to be realized such as cryogenic temperatures or ultra-high vacuum. A potential candidate to overcome these shortcomings are two-dimensional lattices of the topological semi-metal antimony due to their potential to host the quantum spin Hall effect while offering improved resilience against oxidation.
In this work, two-dimensional lattices of antimony on different substrates, namely Ag(111), InSb(111) and SiC(0001), are investigated regarding their atomic structure and electronic properties with complimentary surface sensitive techniques. In addition, a systematic oxidation study compares the stability of Sb-SiC(0001) with that of the two-dimensional topological insulators bismuthene-SiC(0001) and indenene-SiC(0001).
A comprehensive experimental analysis of the \((\sqrt{3}\times\sqrt{3})R30^\circ\) Sb-Ag(111) surface, including X-ray standing wave measurements, disproves the proclaimed formation of a buckled antimonene lattice in literature. The surface lattice can instead be identified as a metallic Ag\(_2\)Sb surface alloy.
Antimony on InSb(111) shows an unstrained Volmer-Weber island growth due to its large lattice mismatch to the substrate. The concomitant moir\'{e} situation at the interface imprints mainly in a periodic height corrugation of the antimony islands which as observed with scanning tunneling microscopy. On islands with various thicknesses, quasiparticle interference patterns allow to trace the topological surface state of antimony down to the few-layer limit.
On SiC(0001), two different two-dimensional antimony surface reconstructions are identified. Firstly, a metallic triangular $1\times1$ lattice which constitutes the antimony analogue to the topological insulator indenene. Secondly, an insulating asymmetric kagome lattice which represents the very first realized atomic surface kagome lattice.
A comparative, systematic oxidation study of elemental (sub-)monolayer materials on SiC(0001) reveals a high sensitivity of indenene and bismuthene to small dosages of oxygen. An improved resilience is found for Sb-SiC(0001) which, however, oxidizes nevertheless if exposed to oxygen. These surface lattices are therefore not suitable for future applications without additional protective measures.
Vorliegende Untersuchung am Universitätsklinikum Würzburg sowie die Befragung von Anästhesisten/Anästhesistinnen im Raum der 3 DACH-Länder zeigen, dass bildgebende Verfahren bei Säuglingen mit einer niedrigen Rate an Komplikationen, zumeist in medikamentöser Sedierung mit Propofol, durchgeführt werden. Wie international üblich ist im Säuglingsalter die Magnetresonanztomographie das bildgebende Verfahren der Wahl und wird, mit überzeugender Häufigkeit, erfolgreich durchgeführt.
Die Untersuchung am Universitätsklinikum Würzburg legt nahe, dass männliche Säuglinge häufiger eine Bildgebung benötigen und häufiger höheren ASA-Kategorie zugeschrieben werden. Dabei scheinen sie auch häufiger Komplikationen zu erleben und bedürfen daher besonderer Aufmerksamkeit. Eine eventuelle Alternative zur Sedierung kann dabei die „feed-and-sleep“ Methode darstellen. In unserer Umfrage konnten wir erheben, dass diese Methode bisher wenig verbreitet ist, obwohl in diesem Zusammenhang eventuell Abläufe und Prozesszeiten strukturiert und optimiert werden können, da beispielsweise die Nachüberwachung entfällt. Vorstellbar wäre beispielsweise, mehrere Säuglinge zum gleichen Zeitpunkt ins MRT zu bestellen, um gegebenenfalls den am frühesten eingeschlafenen Säugling vorzuziehen. Diese Methode sollte zukünftig Einzug in die wissenschaftliche Untersuchung von bildgebenden Verfahren bei Säuglingen finden.
Die Umfrage im deutschsprachigen Raum zeigt eine Leitlinien-gerechte Betreuung von Säuglingen für bildgebende Verfahren, die mit einer hohen Qualität, und zumeist erfolgreich von erfahrenen Anästhesisten/Anästhesistinnen durchgeführt wird. Eventuelle Verbesserungen können im Bereich der Ausbildung nachfolgender Ärztinnen/Ärzte und in der häufigeren Verwendung der „feed-and-sleep“ Methode liegen, die vielen Kollegen/Kolleginnen bekannt ist, aber nur selten durchgeführt wird.
Ziel ist eine qualitativ hochwertige, schnellstmöglich durchgeführte Bildgebung, die ohne oder mit der niedrigst möglichen Dosierung eines sedierenden Medikamentes zu erreichen ist.
Evaluierung prognostischer und prädiktiver Biomarker beim neoadjuvant vorbehandelten Rektumkarzinom
(2024)
Fragestellung. Osteopontin (OPN) kann im Blut nachgewiesen werden und wird bei vielen Tumorentitäten exprimiert, wie auch der Tyrosinkinaserezeptor c-Met und sein Ligand, das Zytokin Hepatocyte Growth Factor (HGF). In der vorliegenden Arbeit untersuchten wir die prognostische und prädiktive Wertigkeit der Plasmakonzentrationen von OPN, c-Met und HGF bei Patienten mit lokal fortgeschrittenem Rektumkarzinom (LARC).
Methodik. Das Plasma von 63 Patienten mit LARC wurde untersucht. Die Blutentnahmen (EDTA-Plasma) erfolgten vor Therapiebeginn sowie im Verlauf. Die Plasmaspiegel von OPN, c-Met und HGF wurden mittels Enzyme-Linked Immunosorbent Assay analysiert. Die Konzentrationen wurden auf eine Korrelation mit den klinischen Parametern untersucht.
Ergebnisse. 68 Patienten wurden neoadjuvant mit einer Radiochemotherapie behandelt, 63 Blutproben wurden untersucht. Initial befanden sich nach UICC 14 Patienten in Stadium II, 47 in Stadium III und 7 in Stadium IV. Das mediane Follow-Up betrug 29,87 Monate. 20 der 68 Patienten (29,4 %) verstarben, 19 entwickelten Fernmetastasen. OPN korrelierte signifikant mit dem Überleben (p=0,001). OPN-Werte korrelierten mit dem pT-Stadium (R:0,445 p=0,018) und dem pUICC-Stadium (R:0,412 p=0,018), sowie mit dem Auftreten von Fernmetastasen (R:0,271 p=0,031). Eine Korrelation zwischen OPN und dem Therapieansprechen konnte gezeigt werden: pathologisch komplette Remission (pCR) (R:0,379 p=0,001), NAR-Score (R:0,373 p=0,015), TRG (R:0,380 p=0,020). Die logistische Regressionsanalyse ergab eine Prädiktivität OPNs für pCR (OR:0,990 p=0,009), NAR-Score (OR:1,008 p=0,007), TRG (OR:0,459 p=0,008). C-Met und HGF korrelierten nicht mit dem Überleben. Für c-Met und HGF ergab sich keine Korrelation zu initialen klinischen Daten und Therapieansprechen. Die logistische Regression ergab keinen prädiktiven Wert.
Schlussfolgerung. Die Plasmakonzentration von OPN besitzt prognostische und prädiktive Wertigkeit beim LARC. Die Konzentrationen von c-Met und HGF sind nicht prognostisch für das Überleben oder prädiktiv für das Therapieansprechen.
Die 2009 erstmals entdeckte Spezies C. auris erlangte binnen kürzester Zeit zunehmend weltweite Aufmerksamkeit. Vor allem die Tendenz der Multiresistenzentwicklung und das rasche Auslösen von nosokomialen Infektionen erschweren den Umgang und die Therapie von C. auris Infektionen im Vergleich zu anderen Candida Spezien. Diese Dissertationsarbeit umfasst eine systematische Resistenzanalyse der im NRZMyk vorhandenen Stammsammlung aus C. auris und C. parapsilosis Isolaten, um Aufschluss über den Wirkmechanismus von Amphotericin B in Hefepilzen zu erlangen. Anhand der zunächst durchgeführten Amphotericin B-Resistenztestungen kristallisierten sich CAU37 und CAU43 mit MHK-Werten bis zu 12 µg/ml als stark Amphotericin B-resistente Isolate heraus. Die Analyse der Sequenzierungsergebnisse zeigte bei beiden Stämmen eine Mutation im ERG4 Gen an Position 576, welche nicht eindeutig als alleinige Ursache für die verminderte Amphotericin B-Empfindlichkeit festgelegt werden konnte. Dennoch wurde im Rahmen eines Survival Assays bei beiden Amphotericin B-resistenten Isolaten anfänglich eine konzentrationsabhängige Aktivität gegenüber Amphotericin B festgestellt, bevor ein Nachwachsen der Kulturen beobachtet wurde. Somit wurde die Vermutung aufgestellt, dass lediglich ein Teil der aufgebrachten Candida-Zellen abgetötet wird und dies in einer Vermehrung der überlebenden Zellen resultiert. Des Weiteren konnte im Rahmen von Resistenztestungen mit dem Sphingolipidinhibitor Myriocin nachgewiesen werden, dass vor allem in Amphotericin B-resistenten Isolaten eine deutliche Wirkungsverstärkung des Polyens hervorgerufen wird. Diese Sensitivitätssteigerung ist allgemein bei allen C. auris Isolaten zu beobachten, fällt bei resistenten Stämmen jedoch deutlich stärker aus. Hierdurch kam die Annahme auf, dass Amphotericin B-Resistenzen auch in möglichen Veränderungen des Sphingolipid-Haushaltes begründet sein könnten. Darüber hinaus scheint Myriocin keinen Einfluss auf Fluconazol-resistente oder FKS-mutierte Echinocandin-resistente C. auris Stämme zu haben. Das ebenfalls untersuchte und von Myriocin abgeleitete Medikament Fingolimod hatte jedoch ebenfalls keinen wirkungsverstärkenden Effekt. Allerdings reagierte ein Großteil der C. auris Isolate (57,6 %) sensitiv gegenüber dem neusten medizinisch bekannten Triazol Isavuconazol und es konnte erstmalig ein ECV-Wert von 0,03125 µg/ml festgelegt werden. Ein valider Vergleich von C. auris zu C. parapsilosis war aufgrund der mangelnden Anzahl an C. parapsilosis Isolaten jedoch nicht möglich
Trotz zahlreicher medizinischer Fortschritte sind Krebserkrankungen weiterhin eine der häufigsten Todesursachen weltweit (Bhupender S. Chhikara und Keykavous Parang 2023). Dabei ist das Multiple Myelom (MM) die zweithäufigste Krebserkrankung des blutbildenden Systems und für ca. 20% aller Todesfälle durch hämatologische Erkrankungen verantwortlich (Derlin und Bannas 2014). Die Krankheit gilt als schwer heilbar, die Patienten leiden unter schwerwiegenden Symptomen und die aktuelle Standardtherapie mittels hochdosierter Chemotherapeutika geht mit starken Nebenwirkungen einher (Cowan et al. 2022). Insofern besteht ein großes Interesse daran, neue und ergänzende Behandlungsmethoden zu finden. In der Forschung etablierte und bereits mit vielversprechenden Ergebnissen an Menschen mit anderen Krebserkrankungen getestete Verfahren sind die Methionin- (MetR) (Kaiser 2020) bzw. Cysteinrestriktion (CysR) (Garcia-Bermudez et al. 2020). Deshalb wurde in der vorliegenden Arbeit in vitro überprüft, ob diese Methoden grundsätzlich einen möglichen Ansatz für die Therapie des MM darstellen. Untersucht wurden die murine MPC11- sowie die humanen L363- und KMS12-BM-Zelllinien des MM. Dabei konnte die antiproliferative Wirkung der Restriktionen bestätigt werden. Darüber hinaus wurde nachgewiesen, dass der Mangel der Aminosäuren nicht über endogene Stoffwechselwege kompensiert werden kann, die Zellen also von der exogenen Zufuhr abhängig sind. Des Weiteren wurde das Metabolom der MPC11-Zellen unter MetR massenspektrometrisch analysiert und ein charakteristischer „metaboler Fingerabdruck“ erstellt. Die Proliferationshemmung ohne Rückgang der Zellzahlen unter den Anfangswert zusammen mit den die gesunde Morphologie der Zellen dokumentierenden EVOS Bildern belegt das Vorliegen eines Low-Energy-Metabolismus (LEM) ohne Absterben der Zellen (Schmitz et al. 2021a). Als geeignete Marker (charakteristischer „metabolen Fingerabdruck“) für einen MetR induzierten LEM eignen sich das bereits in L929-Zellen herauskristallisierte Absinken des Kreatins, der Aminosäuren und Purine bzw. Pyrimidine sowie der Anstieg des Acetoacetats. In den MPC11-Zellen kommen zusätzlich eine Zunahme der Folsäure und eine Abnahme des SAM, SAH und MTA aus dem Methionin- bzw. MTA-Zyklus, des Pentose-5-Phosphats aus dem Pentose-Phosphat-Weg und des Hexose- und Glyceralphosphats sowie des Pyruvats und des Laktats aus der Glykolyse hinzu. Kein klassischer Marker für einen LEM, aber aufgrund des signifikanten Anstiegs dennoch als auffällige Abweichung unter MetR zusätzlich erwähnenswert, ist der deutliche Anstieg des Cystins.
In dieser Arbeit wurde der Impfstatus der Würzburger Medizinstudierenden von 2004-2020 entsprechend der jeweils im sechsten Semester geltenden STIKO Empfehlungen ausgewertet (im folgenden Impfquote genannt) und mit den Ergebnissen von Studien an Universitäten in Frankfurt, Bochum und Dresden, sowie der Allgemeinbevölkerung und dem medizinischen Personal in Deutschland verglichen. Außerdem wurde ausgewertet, inwiefern das Angebot der Nachimpfungen im Impfkurs angenommen wurde und mögliche Zusammenhänge mit aufgedeckten Impflücken wurden diskutiert.
Bei manchen impfpräventablen Infektionskrankheiten (IPIE) wie Pertussis war von 2004-2020 ein deutlicher Anstieg der Impfquote (von <2% auf knapp 90%) zu beobachten, bei anderen, wie Tetanus war bereits seit 2004 eine Impfquote von etwa 75-90% zu sehen, der über die gesamte Beobachtungszeit auf etwa 85-90% anstieg.
Im Vergleich zu anderen Studien mit Medizinstudierenden anderer Universitäten in Deutschland schnitten die Würzburger Medizinstudierenden in Bezug auf Masern, Mumps, Röteln und Varizellen mit Impfquoten um die 80-90% oder höher im Vergleich zu 73-86% in den anderen Städten durchweg besser ab. Bei Hepatitis B war anfangs eine vergleichbare (65-90%), später eine höhere Impfquote (um die 80%) als in den Vergleichsstudien (um die 40%) zu beobachten. In Bezug auf Tetanus (Impfquote im Schnitt 85,2%), Diphtherie (Impfquote im Schnitt 82,9%), Pertussis (Impfquote im Schnitt 49,3%) und Influenza (Impfung in Vorsaison im Schnitt bei 29,3%) waren die Daten aus Würzburg gut mit den Daten aus Vorstudien in ähnlichen Zeiträumen vergleichbar.
Im Vergleich zu Daten zur Impfquote bei Meningokokken und HPV aus der Allgemeinbevölkerung lagen die Würzburger Medizinstudierenden von 2017-2020 über den dort verzeichneten Werten (48% zu 29% bzw. 63% zu 53). Im Vergleich zu Daten der Impfsurveillance des RKI aus 2020 zeigte sich der Effekt der Impfempfehlung bei Kindern (Meningokokken: 90% der 4-7 Jährigen, HPV: 63,3% der 14 Jährigen). Bei der Pneumokokken Impfung gaben – obwohl die STIKO Empfehlung nicht auf medizinisches Personal zutrifft – 10,8% der Studierenden an, mindestens einmal geimpft zu sein. Dies könnte ein erhöhtes Gesundheitsbewusstsein der Medizinstudierenden widerspiegeln.
Zusammenfassend kann gesagt werden, dass der Anteil der Würzburger Medizinstudierenden, deren Impfstatus für die einzelnen IPIE den STIKO Empfehlungen für medizinisches Personal entsprach, über die Jahre 2004 bis 2020 angestiegen ist. Zum Großteil lag der Anteil der Studierenden mit Impfstatus entsprechend den STIKO Empfehlungen über dem aus den Studien der anderen Universitäten.
Trotzdem blieben noch deutliche Lücken im Impfstatus, bspw. bei Pertussis oder Masern, und Wissen der Würzburger Medizinstudierenden bestehen. Diese Lücken werden sich auf Dauer in die Ärzteschaft und schließlich auch in die Empfehlungen durch das ärztliche Personal fortsetzen. Deshalb sollte ein besonderer Fokus auf die Verbesserung des Impfstatus Medizinstudierender gelegt werden, beispielsweise durch regelmäßige verpflichtende Kontrollen durch Betriebärzt*in, intensivierte Lehre sowie bessere Aufklärung bereits zu Beginn des Studiums.
Das Format des Impfkurses, wie er in Würzburg durchgeführt wird, scheint ein gut gewähltes Format, um den Studierenden die Möglichkeit zu geben, ihren eigenen Impfstatus zu überprüfen und diesen weiter zu verbessern. Die Impfquote der Studierenden lag in den Jahren 2014 bis 2020 – den Jahren, in denen die Nachimpfungen im Kurs erfasst wurden – im Schnitt nach dem Kurs bei fast allen IPIE über 90%. Nur bei Pertussis lag die Impfquote nach dem Kurs bei 83,4% (vgl. vor dem Kurs 68,4%). Durch nationale Vereinheitlichung der Lehre im NKLM zum Thema Impfen, frühe Auseinandersetzung mit dem Thema und regelmäßige Überprüfung des eigenen Impfstatus sowie niederschwellige Impfangebote im Medizinstudium, kann einerseits eine Verbesserung des Impfstatus von Medizinstudierenden erreicht werden. Andererseits können so auch insgesamt bessere Impfquoten in der Bevölkerung durch die verbesserte Ausbildung von Ärztinnen bereits im Medizinstudium erzielt werden.
In this thesis, a model of the dynamics during the landing phase of an interplanetary lander mission is developed in a 3 DOF approach with the focus lying on landing by propulsive means. Based on this model, a MATLAB simulation was developed with the goal of enabling an estimation of the performance and especially the required fuel amount of a propulsive landing system on Venus. This landing system is modeled to be able to control its descent using thrusters and to perform a stable landing at a specified target location. Using this simulation, the planetary environments of Mars and Venus can be simulated and the impact of wind, atmospheric density and gravity as well as of using different thrusters on the fuel consumption and landing abilities of the simulated landing system can be investigated. The comparability of these results with the behavior of real landing systems is validated in this thesis by simulating the Powered Descent Phase of the Mars 2020 mission and comparing the results to the data the Mars 2020 descent stage has collected during this phase of its landing. Further, based on the simulation, the minimal necessary fuel amount for a successful landing on Venus has been determined for different scenarios. The simulation along with these results are a contribution to the research of this thesis’s supervisor Clemens Riegler, M.Sc., who will use them for a comparison of different types of landing systems in the context of his doctoral thesis.
Mit dem Projekt SEED werden E-Portfolios für die Lehre an der Julius-Maximilians-Universität Würzburg erschlossen. E-Portfolios ermöglichen es, Lehren und Lernen kompetenzorientiert weiterzuentwickeln und den individuellen Reflexionsanteil eines wissenschaftlichen Studiums im Sinne der Ausbildung professioneller Handlungsfähigkeit zu stärken. Insgesamt wurden sieben Nutzungsszenarien herausgearbeitet. Sie zeigen exemplarisch, auf welche Weise E-Portfolios in der Hochschullehre eingesetzt werden können. Vier Prüfungsvarianten helfen, beim Prüfen mittels E-Portfolios sowohl fachliche als auch reflexive Anteile abzubilden.
The SEED project is developing ePortfolios for teaching at the Julius-Maximilians-Universität Würzburg. ePortfolios make it possible to further develop teaching and learning in a competence-oriented manner and to strengthen the individual reflection aspect of academic studies to support training professional skills. A total of seven use cases were developed. They provide examples of how ePortfolios can be used in university teaching. Four exam variants help to illustrate both subject-specific and reflective components when examining using ePortfolios.
Human prosociality, encompassing generosity, cooperation, and volunteering, holds a vital role in our daily lives. Over the last decades, the question of whether prosociality undergoes changes over the adult lifespan has gained increased research attention. Earlier studies suggested increased prosociality in older compared to younger individuals. However, recent meta-analyses revealed that this age effect might be heterogeneous and modest. Moreover, the contributing factors and mechanisms behind these age-related variations remain to be identified. To unravel age-related differences in prosociality, the first study of this dissertation employed a meta-analytical approach to summarize existing findings and provide insight into their heterogeneity by exploring linear and quadratic age effects on self-reported and behavioral prosociality. Additionally, two empirical research studies investigated whether these age-related differences in prosociality were observed in real life, assessed through ecological momentary assessment (Study 2), and in a controlled laboratory setting by applying a modified dictator game (Study 3). Throughout these three studies, potential underlying behavioral and computational mechanisms were explored. The outcome of the meta-analysis (Study 1) revealed small linear age effects on prosociality and significant age group differences between younger and older adults, with higher levels of prosociality in older adults. Explorative evidence emerged in favor of a quadratic age effect on behavioral prosociality, indicating the highest levels in midlife. Additionally, heightened prosocial behavior among middle-aged adults was observed compared to younger adults, whereas no significant differences in prosocial behavior were noted between middle-aged and older adults. Situational and contextual features, such as the setting of the study and specific paradigm characteristics, moderated the age-prosociality relationship, highlighting the importance of the (social) context when studying prosociality. For Study 2, no significant age effect on real-life prosocial behavior was observed. However, evidence for a significant linear and quadratic age effect on experiencing empathy in real life emerged, indicating a midlife peak. Additionally, across all age groups, the link between an opportunity to empathize and age significantly predicted real-life prosocial behavior. This effect, indicating higher levels of prosocial behavior when there was a situation possibly evoking empathy, was most pronounced in midlife. Study 3 presented age differences in how older and younger adults integrate values related to monetary gains for self and others to make a potential prosocial decision. Younger individuals effectively combined both values in a multiplicative fashion, enhancing decision-making efficiency. Older adults showed an additive effect of values for self and other and displayed increased decision-making efficiency when considering the values separately. However, among older adults, individuals with better inhibitory control were better able to integrate information about both values in their decisions. Taken together, the findings of this dissertation offer new insights into the multi-faceted nature of prosociality across adulthood and the mechanisms that help explain these age-related disparities. While this dissertation observed increasing prosociality across the adult lifespan, it also questions the assumption that older adults are inherently more prosocial. The studies highlight midlife as a potential peak period in social development but also emphasize the importance of the (social) context and that different operationalizations might capture distinct facets of prosociality. This underpins the need for a comprehensive framework to understand age effects of prosociality better and guide potential interventions.
The pancreas is the key organ for the maintenance of euglycemia. This is regulated in particular by α-cell-derived glucagon and β-cell-derived insulin, which are released in response to nutrient deficiency and elevated glucose levels, respectively. Although glucose is the main regulator of insulin secretion, it is significantly enhanced by various potentiators.
Platelets are anucleate cell fragments in the bloodstream that are essential for hemostasis to prevent and stop bleeding events. Besides their classical role, platelets were implemented to be crucial for other physiological and pathophysiological processes, such as cancer progression, immune defense, and angiogenesis. Platelets from diabetic patients often present increased reactivity and basal activation. Interestingly, platelets store and release several substances that have been reported to potentiate insulin secretion by β-cells. For these reasons, the impact of platelets on β-cell functioning was investigated in this thesis.
Here it was shown that both glucose and a β-cell-derived substance/s promote platelet activation and binding to collagen. Additionally, platelet adhesion specifically to the microvasculature of pancreatic islets was revealed, supporting the hypothesis of their influence on glucose homeostasis. Genetic or pharmacological ablation of platelet functioning and platelet depletion consistently resulted in reduced insulin secretion and associated glucose intolerance. Further, the platelet-derived lipid fraction was found to enhance glucose-stimulated insulin secretion, with 20-hydroxyeicosatetraenoic acid (20-HETE) and possibly also lyso-precursor of platelet-activating factor (lysoPAF) being identified as crucial factors. However, the acute platelet-stimulated insulin secretion was found to decline with age, as did the levels of platelet-derived 20-HETE. In addition to their direct stimulatory effect on insulin secretion, specific defects in platelet activation have also been shown to affect glucose homeostasis by potentially influencing islet vascular development. Taking together, the results of this thesis suggest a direct and indirect mechanism of platelets in the regulation of insulin secretion that ensures glucose homeostasis, especially in young individuals.
Die alveoläre Echinokokkose (AE), die durch den Fuchsbandwurm Echinococcus multilocularis verursacht wird, ist eine seltene jedoch schwere und oft tödlich verlaufende Erkrankung. Aufgrund der späten Diagnosestellung sind kurative Behandlungsmethoden häufig nicht durchführbar und als einzige Behandlungsmöglichkeit bleibt eine lebenslange und nebenwirkungsreiche Therapie mit Benzimidazolen. Verbesserte Therapieoptionen durch die Entwicklung neuer Medikamente sind dringend notwendig. Hierfür kann es hilfreich sein die Biologie des Fuchsbandwurmes und die Kommunikationswege zwischen Parasit und Wirt zu verstehen. Bereits in vorherigen Arbeiten als auch in dieser Arbeit erwiesen sich evolutionsgeschichtlich konservierte Signalwege als Kommunikationsweg zwischen dem Fuchsbandwurm und seinem Wirt von zentraler Rolle.
Die Entschlüsselung des Echinococcus-Genoms gab Hinweise darauf, dass ein Mitglied der Tumornekrosefaktor-Rezeptor-Superfamilie, jedoch kein endogener TNF α ähnlicher Ligand im Genom kodiert wird. Ein Mitglied der TNFR-Superfamilie des Fuchsbandwurmes (EmTNFR) wurde in dieser Arbeit als membranständiger Rezeptor mit einer intrazellulären Todesdomäne (DD) und hoher Ähnlichkeit zum humanen Typ 16 der TNF-Rezeptor-Superfamilie, auch 〖p75〗^NTR genannt, charakterisiert. Sowohl in bioinformatischen als auch in Sequenzanalysen wurden drei alternative Splicing-Formen von emtnfr (emtnfr, emtnfr-v2 und emtnfr-v3) nachgewiesen. emtnfr-v2 entsteht durch Alternatives Splicing und kodiert ein Protein, das keine intrazelluläre Todesdomäne besitzt. emtnfr-v3 verwendet einen alternativen Transkriptionstart und wird von den letzten 3 Exons von emtnfr kodiert. emtnfr-v3, kodiert ein Protein ohne extrazelluläre Region, aber mit intrazellulärer Todesdomäne. Ein löslicher TNF-Rezeptor konnte auf Proteinebene nicht nachgewiesen werden. Aufgrund von phylogenetischen Analysen und der Rezeptor-Struktur ist zu vermuten, dass EmTNFR ein p75NTR Homolog ist und damit der ursprünglichen Form der TNF-Rezeptoren entspricht. Mitglieder eines intrazellulären TNF-Signalweges wurden in bioinformatischen Analysen beim Fuchsbandwurm E. multilocularis identifiziert.
Expressionsuntersuchungen zeigten sowohl in Trankriptomdaten als auch auf Proteinebene eine starke Expression von EmTNFR in Primärzellen und im Metazestoden (MZ), dem pathogenen Stadium für den Zwischenwirt. Echinococcus-Stammzellkulturen zeigten nach RNA-Interferenz-basiertem Knockdown des EmTNFR-kodierenden Gens deutliche Entwicklungsdefekte. Des Weiteren zeigten Echinococcus-Stammzellkulturen nach einer Behandlung mit TNF-α, einem potentiellen Liganden des TNF-Rezeptors und einem zentralen Zytokin in der Immunabwehr des Zwischenwirtes, Entwicklungsfortschritte, wie eine verbesserte Bildung von MZ aus Stammzellen. Zusätzlich wurde in whole-mount in situ Hybridisierungs-Versuchen eine ubiquitäre Expression von emtnfr in der Germinalschicht des MZ sowie eine Spezifität von emtnfr für den MZ, welcher ursächlich für die AE ist, nachgewiesen. Somit scheinen sowohl EmTNFR als auch TNF-α eine wichtige Funktion bei der Entwicklung und Etablierung des Fuchsbandwurmes während der frühen Phase der Infektion des Zwischenwirtes zu haben. TNF-α könnte ein weiterer Faktor für den ausgeprägten Organtropismus des Parasiten zur Leber sein, denn dort bestehen durch Kupfferzellen produzierte hohe lokale Konzentration von TNF-α.
Zusammenfassend deuten die hier erarbeiteten Daten darauf hin, dass EmTNFR über die Bindung von Wirts-TNF-α bei der frühen Entwicklung des Echincoccus-Metazestoden eine Rolle spielt.
The aim of the present work was to improve drug monitoring in patients with various diseases in the context of precision medicine. This was pursued through the development and validation of mass spectrometric methods for determining the drug concentrations of kinase inhibitors and their clinical application. Besides conventional approaches to determine plasma level concentrations, the focus was also on alternative sampling techniques using volumetric absorptive microsampling (VAMS).
A conventional LC-MS/MS method was developed for the determination of cabozantinib in human EDTA plasma and validated according to the guidelines of the European and United States drug authorities (EMA, FDA). The method met the required criteria for linearity, accuracy and precision, selectivity, sensitivity, and stability of the analyte. Validation was also performed for dilution integrity, matrix effect, recovery, and carry-over, with results also in accordance with the requirements. The importance of monitoring the exposure of cabozantinib was demonstrated by a clinical case report of a 34-year-old female patient with advanced adrenocortical carcinoma who also required hemodialysis due to chronic kidney failure. Expected cabozantinib plasma concentrations were simulated for this off-label use based on a population pharmacokinetic model. It was shown that the steady state trough levels were much lower than expected but could not be explained by hemodialysis. Considering the critical condition and potential drug-drug interaction with metyrapone, a substance the patient had taken among several others during the observation period, individual pharmacokinetics could consequently not be estimated without drug monitoring.
In addition, a VAMS method for simultaneous determination of ten kinase inhibitors from capillary blood was developed. This microsampling technique was mainly characterized by the collection of a defined volume of blood, which could be dried and subsequently analyzed. The guidelines for bioanalytical method validation of the EMA and FDA were also used for this evaluation. As the nature of dried blood samples differs from liquid matrices, further parameters were investigated. These include the investigation of the hematocrit effect, process efficiency, and various stability conditions, for example at increased storage temperatures. The validation showed that the developed method is suitable to analyze dried matrix samples accurate, precise, and selective for all analytes. Apart from the stability tests, all acceptance criteria were met. The decreased stability of two analytes was probably due to the reproducible but reduced recovery. In vitro studies provided results on the VAMS-to-plasma correlation to predict the analyte distribution between both matrices, at least in an exploratory manner. It revealed a heterogeneous picture of analytes with different VAMS-to-plasma distributions. Furthermore, the analysis of 24 patient samples indicated the applicability of at-home VAMS. Both should be confirmed later as part of the clinical validation.
The clinical investigation of the VAMS method pursued two objectives. On the one hand, the simultaneous collection of VAMS and serum samples should enable a conversion of the determined concentrations and, on the other hand, the feasibility of autonomous microsampling at home should be examined more closely. For the former, it could be shown that different conversion methods are suitable for converting VAMS concentrations into serum levels. The type of conversion was secondary for the prediction. However, the previously defined criteria could not be fulfilled for all five kinase inhibitors investigated. The framework conditions of the study led to increased variability, especially for analytes with short half-life. A low and varying hematocrit, caused by the underlying disease, also made prediction difficult for a specific patient collective. For the second objective, investigating the feasibility of VAMS, different aspects were considered. It could be shown that the majority of patients support home-based microsampling. The acceptance is likely to increase even further when microsampling is no longer part of a non-interventional study, but participation is accompanied by targeted monitoring and subsequent adjustment of the therapy. The fact that additional training increases understanding of the correct sampling procedure is also a source of confidence. Demonstrated stability during storage under real-life conditions underlines the practicality of this sampling technique.
Taken together, mass spectrometric methods for both plasma and VAMS could be developed and validated, and their clinical application could be successfully demonstrated. The availability of simple bioanalytical methods to determine kinase inhibitor exposure could improve access to prospective studies and thus facilitate the implementation of routine therapeutic drug monitoring.
Sprech- und Stimmstörungen sind häufige Symptome der Idiopathischen Parkinson Erkrankung (IPS), wobei bis zu 89% der Patienten im Verlauf der Krankheit unter einer Dysarthrie leiden. Die Tiefenhirnstimulation des Nucleus subthalamicus (STN-DBS) ist eine etablierte Behandlung für die motorischen Symptome des IPS (Allert et al., 2004). Während STN-DBS positive Effekte auf einige Teilfunktionsbereiche der Dysarthrie zu haben scheint, berichten die meisten Studien entweder über keine Verbesserung oder eine Verschlechterung der Sprech- und Stimmfunktionen nach Implantation der STN-DBS (Tsuboi et al., 2015; Wang et al., 2003; Wertheimer et al., 2014). Klinische Erfahrungswerte sowie Fallberichte und Studien lassen vermuten, dass diese sprachtherapeutisch relevanten Nebenwirkungen unabhängig von der therapeutischen Wirksamkeit der STN-DBS sind und daher als unerwünschte, aber nicht therapieimmanente Interferenzfaktoren anzusehen sind (Bouthour et al., 2018), die es genauer zu untersuchen gilt, da die Lebensqualität von IPS-Erkrankten als stark einschränkend wahrgenommen wird (Hariz et al., 2010). Eine aufwendige und methodisch fundierte Klassifizierung wurde von Tsuboi und Kollegen vorgenommen, die im Zusammenhang mit STN-DBS fünf Cluster von Sprech- und Stimmstörungen identifizierten (Tanaka et al., 2020; Tsuboi et al., 2015, 2017). Dazu zählten die Phänotypen „spastische Dysarthrie“, „Stottern“, „rigid-hypokinetischer Typ“, „behauchte Stimme“ und „gepresste Stimme“.
Erste Hinweise lassen darauf schließen, dass die Nebenwirkungen von STN-DBS auf die Stimulation spezifischer Gehirnkreise zurückzuführen sein könnte (Fox et al., 2014). In dieser Arbeit wird eine retrospektive Studie mit STN-DBS stimulierten IPS Erkrankten vorgestellt, die sprachtherapeutisch relevante Sprech- und Stimmstörungen unter zwei Bedingungen bewertet (ein- und ausgeschaltete Stimulation) sowie eine prospektive Studie mit den beiden gleichen Bedingungen. Beide Studien haben das Ziel einer Replizierbarkeit der Ergebnisse von Tsuboi et al. (2015, 2017). Die zweite prospektive Studie bezieht außerdem konnektombasierte Daten ein.
Die Ergebnisse beider Studien lassen quantitativ keine Signifikanzen hinsichtlich der o.g. dysarthrischen Phänotypen zu, quantitativ lassen sich jedoch deutliche Tendenzen ähnlich der Ausgangsstudie erkennen. Zudem wurden das Cluster „Stottern“ in der retrospektiven Studie als weiteres möglicherweise STN-DBS immantentes Cluster identifiziert. In der prospektiven Studie wurde ein Cluster hinzugefügt, da in den Beurteilungen zusätzlich die Symptomatik „hasty speech“ oder auch „hastiges Sprechen“ beobachtet wurde.
African trypanosomes are unicellular parasites that cause nagana and sleeping sickness in livestock and man, respectively. The major pathogens for the animal disease include Trypanosoma vivax, T. congolense, and T. brucei brucei, whereas T. b. gambiense and T. b. rhodesiense are responsible for human infections. Given that the bloodstream form (BSF) of African trypanosomes is exclusively extracellular, its cell surface forms a critical boundary with the host environment. The cell surface of the BSF African trypanosomes is covered by a dense coat of immunogenic variant surface glycoproteins (VSGs). This surface protein acts as an impenetrable shield that protects the cells from host immune factors and is also involved in antibody clearance and antigenic variation, which collectively ensure that the parasite stays ahead of the host immune system. Gene expression in T. brucei is markedly different from other eukaryotes: most genes are transcribed as long polycistronic units, processed by trans-splicing a 39-nucleotide mini exon at the 5′ and polyadenylation at the 3′ ends of individual genes to generate the mature mRNA.
Therefore, gene expression in T. brucei is regulated post-transcriptionally, mainly by the action of RNA binding proteins (RBPs) and conserved elements in the 3′ untranslated regions (UTR) of transcripts. The expression of VSGs is highly regulated, and only a single VSG gene is expressed at a time from one of the ~15 subtelomeric domains termed bloodstream expression sites (BES). When cells are engineered to simultaneously express two VSGs, the total VSG mRNA do not exceed the wild type amounts. This suggests that a robust VSG mRNA balancing mechanism exists in T. brucei. The present study uses inducible and constitutive expression of ectopic VSG genes to show that the endogenous VSG mRNA is regulated only if the second VSG is properly targeted to the ER. Additionally, the endogenous VSG mRNA response is triggered when high amounts of the GFP reporter with a VSG 3′UTR is targeted to the ER. Further evidence that non-VSG ER import signals can efficiently target VSGs to the ER is presented. This study suggests that a robust trans-regulation of the VSG mRNA is elicited at the ER through a feedback loop to keep the VSG transcripts in check and avoid overshooting the secretory pathway capacity.
Further, it was shown that induction of expression of the T. vivax VSG ILDat1.2 in T. brucei causes a dual cell cycle arrest, with concomitant upregulation of the protein associated with differentiation (PAD1) expression. It could be shown that T. vivax VSG ILDat1.2 can only be sufficiently expressed in T. brucei after replacing its native GPI signal peptide with that of a T. brucei VSG. Taken together, these data indicate that inefficient VSG GPI anchoring and expression of low levels of the VSG protein can trigger differentiation from slender BSF to stumpy forms. However, a second T. vivax VSG, ILDat2.1, is not expressed in T. brucei even after similar modifications to its GPI signals. An X-ray crystallography approach was utilized to solve the N-terminal domain (NTD) structure of VSG ILDat1.2. This is first structure of a non-T. brucei VSG, and the first of a surface protein of T. vivax to be solved. VSG ILDat1.2 NTD maintains the three-helical bundle scaffold conserved in T. brucei surface proteins. However, it is likely that there are variations in the architecture of the membrane proximal region of the ILDat1.2 NTD and its CTD from T. brucei VSGs. The tractable T. brucei system is presented as a model that can be used to study surface proteins of related trypanosome species, thus creating avenues for further characterization of trypanosome surface coats.
Colorectal Cancer (CRC) is the third most common cancer in the US. The majority of CRC cases are due to deregulated WNT-signalling pathway. These alterations are mainly caused by mutations in the tumour suppressor gene APC or in CTNNB1, encoding the key effector protein of this pathway, β-Catenin. In canonical WNT-signalling, β-Catenin activates the transcription of several target genes, encoding for proteins involved in proliferation, such as MYC, JUN and NOTCH. Being such a critical regulator of these proto-oncogenes, the stability of β-Catenin is tightly regulated by the Ubiquitin-Proteasome System. Several E3 ligases that ubiquitylate and degrade β-Catenin have been described in the past, but the antagonists, the deubiquitylases, are still unknown. By performing an unbiased siRNA screen, the deubiquitylase USP10 was identified as a de novo positive regulator of β-Catenin stability in CRC derived cells. USP10 has previously been shown in the literature to regulate both mutant and wild type TP53 stability, to deubiquitylate NOTCH1 in endothelial cells and to be involved in the regulation of AMPKα signalling. Overall, however, its role in colorectal tumorigenesis remains controversial. By analysing publicly available protein and gene expression data from colorectal cancer patients, we have shown that USP10 is strongly upregulated or amplified upon transformation and that its expression correlates positively with CTNNB1 expression. In contrast, basal USP10 levels were found in non-transformed tissues, but surprisingly USP10 is upregulated in intestinal stem cells. Endogenous interaction studies in CRC-derived cell lines, with different extend of APCtruncation, revealed an APC-dependent mode of action for both proteins. Furthermore, by utilising CRISPR/Cas9, shRNA-mediated knock-down and overexpression of USP10, we could demonstrate a regulation of β-Catenin stability by USP10 in CRC cell lines. It is widely excepted that 2D cell culture systems do not reflect complexity, architecture and heterogeneity and are therefore not suitable to answer complex biological questions. To overcome this, we established the isolation, cultivation and genetically modification of murine intestinal organoids and utilised this system to study Usp10s role ex vivo. By performing RNA sequencing, dependent on different Usp10 levels, we were able to recapitulate the previous findings and demonstrated Usp10 as important regulator of β-dependent regulation of stem cell homeostasis. Since genetic depletion of USP10 resulted in down-regulation of β-Catenin-dependent transcription, therapeutic intervention of USP10 in colorectal cancer was also investigated. Commercial and newly developed inhibitors were tested for their efficacy against USP10, but failed to significantly inhibit USP10 activity in colorectal cancer cells. To validate the findings from this work also in vivo, development of a novel mouse model for colorectal cancer has begun. By combining CRISPR/Cas9 and classical genetic engineering with viral injection strategies, WT and genetically modified mice could be transformed and, at least in some animals, intestinal lesions were detectable at the microscopic level. The inhibition of USP10, which we could describe as a de novo tumour-specific regulator of β-Catenin, could become a new therapeutic strategy for colorectal cancer patients.
This dissertation explores the development and assessment of inhibitory control – a crucial component of executive functions – in young children. Inhibitory control, defined as the ability to suppress inappropriate responses (Verbruggen & Logan, 2008), is essential for adaptable and goal-oriented behavior. The rapid and non-linear development of this cognitive function in early childhood presents unique challenges for accurate assessment. As children age, they often exhibit a ceiling effect in terms of response accuracy (Petersen et al., 2016), underscoring the need to consider response latency as well. Ideally, combining response latency with accuracy could yield a more precise measure of inhibitory control (e.g., Magnus et al., 2019), facilitating a detailed tracking of developmental changes in inhibitory control across a wider age spectrum. The three studies of this dissertation collectively aim to clarify the relationship between response accuracy, response latency, and inhibitory control across different stages of child development. Each study utilizes a computerized Pointing Stroop Task (Berger et al., 2000) to measure inhibitory control, examining the task's validity and the integration of dual metrics for a more comprehensive evaluation.
The first study focuses on establishing the validity of using both response accuracy and latency as indicators of inhibitory control. Utilizing the framework of explanatory item-response modeling (De Boeck & Wilson, 2004), the study revealed how the task characteristics congruency and item position influence both the difficulty level and timing aspects in young children’s responses in the computerized Pointing Stroop task. Further, this study found that integrating response accuracy with latency, even in a basic manner, provides additional insights. Building upon these findings, the second study investigates the nuances of integrating response accuracy and latency, examining whether this approach can account for age-related differences in inhibitory control. It also explores whether response latencies may contain different information depending on the age and proficiency of the children. The study leverages novel and established methodological perspectives to integrate response accuracy and latency into a single metric, showing the potential applicability of different approaches for assessing inhibitory control development. The third study extends the investigation to a longitudinal perspective, exploring the dynamic relationship between response accuracy, latency, and inhibitory control over time. It assesses whether children who achieve high accuracy at an earlier age show faster improvement in response latency, suggesting a non-linear maturation pathway of inhibitory control. The study also examines if the predictive value of early response latency for later fluid intelligence is dependent on the response accuracy level.
Together, these empirical studies contribute to a more robust understanding of the complex interaction between inhibitory control, response accuracy, and response latency, facilitating valid evaluations of cognitive capabilities in children. Moreover, the findings may have practical implications for designing educational strategies and clinical interventions that address the developmental trajectory of inhibitory control. The nuanced approach advocated in this dissertation suggests prioritizing accuracy in assessment and interventions during the early stages of children's cognitive development, gradually shifting the focus to response latency as children mature and secure their inhibitory control abilities.
Colon carcinomas (CRC) are statistically among the most fatal cancer types and hence one of the top reasons for premature mortality in the developed world. CRC cells are characterized by high proliferation rates caused by deregulation of gene transcription of proto-oncogenes and general chromosomal instability. On macroscopic level, CRC cells show a strongly altered nutrient and energy metabolism.
This work presents research to understand general links between the metabolism and transcription alteration. Mainly focussing on glutamine dependency, shown in colon carcinoma cells and expression pathways of the pro-proliferation protein c-MYC.
Previous studies showed that a depletion of glutamine in the cultivation medium of colon carcinoma cell lines caused a proliferation arrest and a strong decrease of overall c-MYC levels. Re-addition of glutamine quickly replenished c-MYC levels through an unknown mechanism. Several proteins altering this regulation mechanism were identified and proposed as possible starting point for further in detail studies to unveil the precise biochemical pathway controlling c-MYC translation repression and reactivation in a rapid manner.
On a transcriptional level the formation of RNA:DNA hybrids, so called R-loops, was observed under glutamine depleted conditions. The introduction and overexpression of RNaseH1, a R-loop degrading enzyme, in combination with an ectopically expressed c-MYC variant, independent of cellular regulation mechanisms by deleting the regulatory 3’-UTR of the c-MYC gene, lead to a high rate of apoptotic cells in culture. Expression of a functionally inactive variant of RNaseH1 abolished this effect. This indicates a regulatory function of R-loops formed during glutamine starvation in the presence of c-MYC protein in a cell. Degradation of R-loops and high c-MYC levels in this stress condition had no imminent effect on the cell cycle progression is CRC cells but disturbed the nucleotide metabolism. Nucleotide triphosphates were strongly reduced in comparison to starving cells without R-loop degradation and proliferating cells.
This study proposes a model of a terminal cycle of transcription termination, unregulated initiation and elongation of transcription leading to a depletion of energy resources of cells. This could finally lead to high apoptosis of the cells. Sequencing experiments to determine a coinciding of termination sites and R-loop formation sides failed so far but show a starting point for further studies in this essential survival mechanism involving R-loop formation and c-MYC downregulation.
Die vorliegende Studie untersuchte den Effekt von Levosimendan auf die mitochondriale Funktionen im Herzmuskel, insbesondere im Zusammenhang mit dem Ischämie/Reperfusions-Schaden. Methoden: In der Studie wurde ein retrogrades Langendorff-Modell verwendet, um die Auswirkungen von Levosimendan, dem Ischämie/Reperfusions-Schaden sowie deren Kombination auf die mitochondrialen Funktionen im Herzmuskel zu untersuchen. Dazu wurden vier verschiedene Gruppen von Rattenherzen entsprechend den experimentellen Bedingungen perfundiert, und ihre Funktionen wurden analysiert. Ergebnisse: Der Ischämie/Reperfusions-Schaden beeinträchtigte die myokardiale Ventrikelfunktion. Zusätzlich wurde eine Hypopolarisation des mithochondrialen Membranpotentials in den mit Levosimendan oder Ischämie behandelten Gruppen festgestellt. Die ATP-Synthese in den Gruppen mit Levosimendan und Ischämie war reduziert. Schlussfolgerung: Levosimendan zeigt signifikante Einflüsse auf die Atmungsfunktion der mitochondrialen Komplexe IV und V sowie auf das Membranpotential. Diese Phänomene könnten einem mito-K+ ATP-abhängigen Mechanismus zugrunde liegen. Obwohl Levosimendan während des Ischämie/Reperfusionsschadens eine protektive Wirkung hinsichtlich einer Ca2+- Überlastung aufweist, bleibt der kumulative Einfluss der beeinträchtigten ATP-Generierung auf die gesamte Myokardfunktion zu klären.
Der MPFL-Ersatz ist ein gängiges Therapieverfahren zur Behandlung einer patellofemoralen Instabilität. Die Operationstechniken unterscheiden sich zumeist an der patellaren Fixationsmethode und der Auswahl der Transplantate. Biomechanische Studien, welche sich mit den Eigenschaften implantatfreier ossärer Fixationsmethoden beim MPFL-Ersatz unter Verwendung künstlicher Transplantate beschäftigen gibt es nach aktueller Recherche nicht. Ziel dieser Arbeit war es, die biomechanischen Eigenschaften zweier patellarer Bohrkanalfixationstechniken beim MPFL-Ersatz mit unterschiedlichem künstlichen Bandersatzmaterial zu ermitteln. Die Hypothese war, dass die biomechanischen Eigenschaften in Elongation, Steifigkeit, Primärstabilität und maximaler Ausreißkraft mit denen der bereits etablierten Verfahren und dem nativen MPFL vergleichbar sind. Hierzu wurden 80 porcine Kniescheiben randomisiert in 8 Gruppen aufgeteilt und getestet. In den Gruppen 1-4 wurden parallele, transpatellare Bohrkanäle mit Tapes der Breiten 2 mm, 3 mm, 4 mm und 5 mm getestet. In den Gruppen 5-8 wurden V-Kanal-Fixationsmethoden mit Bändern der Breite von 2 mm, 3 mm, 4 mm und 5 mm untersucht. Zusätzlich wurden die biomechanischen Grundeigenschaften der nativen Tapes ermittelt. Alle Tests durchliefen jeweils drei Messabschnitte. Hierbei fand zunächst eine Präkonditionierung mit 10 Zyklen zwischen 5 N und 20 N statt. Daraufhin folgte eine zyklische Belastung mit 1000 Zyklen zwischen 5 N und 50 N. Am Ende wurde eine maximale Kraftapplikation bis zum Versagen der Fixationskomplexe durchgeführt. Im Rahmen der Messungen wurden Elongation, Steifigkeit, Yield Load und Maximum Load bestimmt. Es konnten Unterschiede zwischen den beiden Fixationsmethoden und den verwendeten Tapes festgestellt werden. Alle acht Gruppen zeigten eine höhere Primärstabilität als das humane MPFL. Bezogen auf die biomechanischen Eigenschaften und den Versagensmechanismus konnte in dieser Studie ein Vorteil der parallelen transpatellaren Bohrkanäle gegenüber den V- Kanaltechniken festgestellt werden. Die Werte mit der höchsten maximalen Ausreißkraft wurden in Gruppe 3 (631,6 ± 83,1 N) und Gruppe 1 (592,9 ± 170,1 N) gemessen. Diese zeigten eine höhere Primärstabilität mit geringerer Elongation und Steifigkeit im Vergleich zu den in der aktuellen Literatur beschriebenen biomechanischen Studien, welche sich mit unterschiedlichen und teilweise bereits etablierten MPFL-Ersatzverfahren beschäftigten. Eine implantatfreie MPFL-Rekonstruktion mit transpatellaren parallelen Bohrkanälen unter Verwendung eines 2 mm Fiber Tapes (Fa. Arthrex) oder eines 4 mm Tapes (Fa. Topester) könnten dementsprechend eine gute Alternative zur operativen Therapie einer patellofemoralen Instabilität sein.
Structure and dynamics of the plasma membrane: a single-molecule study in \(Trypanosoma\) \(brucei\)
(2024)
The unicellular, flagellated parasite Trypanosoma brucei is the causative agent of human African sleeping sickness and nagana in livestock. In the last decades, it has become an established eukaryotic model organism in the field of biology, as well as in the interdisciplinary field of biophysics. For instance, the dense variant surface glycoprotein (VSG) coat offers the possibility to study the dynamics of GPI-anchored proteins in the plasma membrane of living cells. The fluidity of the VSG coat is not only an interesting object of study for its own sake, but is critically important for the survival of the parasite in the mammalian host. In order to maintain the integrity of the coat, the entire VSG coat is recycled within a few minutes. This is surprisingly fast for a purely diffusive process with the flagellar pocket (FP) as the sole site for endo- and exocytosis. Previous studies characterising VSG dynamics using FRAP reported diffusion coefficients that were not sufficient to to enable fast turnover based on passive VSG randomisation on the trypanosome surface.
In this thesis, live-cell single-molecule fluorescence microscopy (SMFM) was employed to elucidate whether VSG diffusion coefficients were priorly underestimated or whether directed forces could be involved to bias VSGs towards the entrance of the FP. Embedding the highly motile trypanosomes in thermo-stable hydrogels facilitated the investigation of VSG dynamics on living trypanosomes at the mammalian host's temperature of 37°C. To allow for a spatial correlation of the VSG dynamics to the FP entrance, a cell line was employed harbouring a fluorescently labelled structure as a reference. Sequential two-colour SMFM was then established to allow for recording and registration of the dynamic and static single-molecule information.
In order to characterise VSG dynamics, an algorithm to obtain reliable information from short trajectories was adapted (shortTrAn). It allowed for the quantification of the local dynamics in two distinct scenarios: diffusion and directed motion. The adaptation of the algorithm to the VSG data sets required the introduction of an additional projection filter. The algorithm was further extended to take into account the localisation errors inherent to single-particle tracking. The results of the quantification of diffusion and directed motion were presented in maps of the trypanosome surface, including an outline generated from a super-resolved static structure as a reference. Information on diffusion was displayed in one map, an ellipse plot. The colour code represented the local diffusion coefficient, while the shape of the ellipses provided an indication of the diffusion behaviour (aniso- or isotropic diffusion). The eccentricity of the ellipses was used to quantify deviations from isotropic diffusion. Information on directed motion was shown in three maps: A velocity map, representing the amplitude of the local velocities in a colour code. A quiver plot, illustrating the orientation of directed motion, and a third map which indicated the relative standard error of the local velocities colour-coded. Finally, a guideline based on random walk simulations was used to identify which of the two motion scenarios dominated locally. Application of the guideline to the VSG dynamics analysed by shortTrAn yielded supermaps that showed the locally dominant motion mode colour-coded.
I found that VSG dynamics are dominated by diffusion, but several times faster than previously determined. The diffusion behaviour was additionally characterised by spatial heterogeneity. Moreover, isolated regions exhibiting the characteristics of round and elongated traps were observed on the cell surface. Additionally, VSG dynamics were studied with respect to the entrance of the FP. VSG dynamics in this region displayed similar characteristics compared to the remainder of the cell surface and forces biasing VSGs into the FP were not found.
Furthermore, I investigated a potential interference of the attachment of the cytoskeleton to the plasma membrane with the dynamics of VSGs which are anchored to the outer leaflet of the membrane. Preliminary experiments were conducted on osmotically swollen trypanosomes and trypanosomes depleted for a microtubule-associated protein anchoring the subpellicular microtubule cytoskeleton to the plasma membrane. The measurements revealed a trend that detachment of the cytoskeleton could be associated with a reduction in the VSG diffusion coefficient and a loss of elongated traps. The latter could be an indication that these isolated regions were caused by underlying structures associated with the cytoskeleton.
The measurements on cells with an intact cytoskeleton were complemented by random walk simulations of VSG dynamics with the newly determined diffusion coefficient on long time scales not accessible in experiments. Simulations showed that passive VSG randomisation is fast enough to allow for a turnover of the full VSG coat within a few minutes. According to an estimate based on the known rate of endocytosis and the newly determined VSG diffusion coefficient, the majority of exocytosed VSGs could escape from the FP to the cell surface without being immediately re-endocytosed.
Plants are able to sense mechanical forces in order to defend themselves against predators,
for instance by synthesizing repellent compounds. Very few plants evolved extremely sensitive
tactile abilities that allow them to perceive, interpret and respond by rapid movement in the
milliseconds range. One such rarity is the charismatic Venus flytrap (Dionaea muscipula) - a
carnivorous plant which relies on its spectacular active trapping strategy to catch its prey. The
snapping traps are equipped with touch-specialised trigger hairs, that upon bending elicit an
action potential (AP). This electrical signal originates within the trigger hairs’ mechanosensory
cells and further propagates throughout the whole trap, alerting the plant of potential prey.
Two APs triggered within thirty seconds will set off the trap and more than five APs will
initiate the green stomach formation for prey decomposition and nutrient uptake. Neither
the molecular components of the plant’s AP nor the Venus flytrap’s fast closure mechanism
have been fully elucidated yet. Therefore, the general objective of this study is to expound
on the molecular basis of touch perception: from AP initiation to trap closure and finally to
stomach formation.
The typical electrical signal in plants lasts for minutes and its shape is determined by the
intensity of the mechanical force applied. In contrast, the Venus flytrap’s one-second AP is of
all-or-nothing type, similar in shape to the animal AP. In order to gain more insight into the
molecular components that give rise to the Venus flytrap’s emblematic AP, the transcriptomic
landscape of its unique mechanotransducer - the trigger hair – was compared to the rest
of the non-specialised tissues and organs. Additionally, the transcriptome of the electrically
excitable fully-developed adult trap was compared to non-excitable juvenile traps that are
unable to produce sharp APs. Together, the two strategies helped with the identification of
electrogenic channels and pumps for each step of the AP as follows: (1) the most specific to
the trigger hair was the mechanosensitive channel DmMSL10, making up the best candidate for
the initial AP depolarization phase, (2) the K+ outward rectifier DmSKOR could be responsible
for repolarisation, (3) further, the proton pump DmAHA4, might kick in during repolarisation
and go on with hyperpolarisation and (4) the hyperpolarization- and acid-activated K+ inward
rectifier KDM1 might contribute to the re-establishment of electrochemical gradient and
the resting potential. Responsible for the AP-associated Ca2+ wave and electrical signal
propagation, the glutamate-like receptor DmGLR3.6 was also enriched in the trigger hairs.
Together, these findings suggest that the reuse of genes involved in electrical signalling in
ordinary plants can give rise to the Venus flytrap’s trademark AP.
The Venus flytrap has been cultivated ever since its discovery, generating more than one
hundred cultivars over the years. Among them, indistinguishable from a normal Venus flytrap
at first sight, the ’ERROR’ cultivar exhibits a peculiar behaviour: it is unable to snap its traps
upon two APs. Nevertheless, it is still able to elicit normal APs. To get a better understanding
of the key molecular mechanisms and pathways that are essential for a successful trap closure,
the ’ERROR’ mutant was compared to the functional wild type.
Timelapse photography led to the observation that the ’ERROR’ mutants were able to leisurely
half close their traps when repeated mechanostimulation was applied (10 minutes after 20
APs, 0.03 Hz). As a result of touch or wounding in non-carnivorous plants, jasmonic acid
(JA) is synthesized, alerting the plants of potential predators. Curiously, the JA levels were reduced upon mechanostimulation and completely impaired upon wounding in the ’ERROR’
mutant. In search of genes accountable for the ’ERROR’ mutant’s defects, the transcriptomes
of the two phenotypes were compared before and after mechanostimulation (1h after 10
APs, 0.01 Hz). The overall dampened response of the mutant compared to the wild type,
was reflected at transcriptomic level as well. Only about 50% of wild type’s upregulated
genes after touch stimulation were differentially expressed in ’ERROR’ and they manifested
only half of the wild type’s expression amplitude. Among unresponsive functional categories
of genes in ’ERROR’ phenotype, there were: cell wall integrity surveilling system, auxin
biosynthesis and stress-related transcription factors from the ethylene-responsive AP2/ERF and
C2H2-ZF families. Deregulated Ca2+-decoding as well as redox-related elements together with
JA-pathway components might also contribute to the malfunctioning of the ’ERROR’ mutant. As
the mutant does not undergo full stomach formation after mechanical treatment, these missing
processes represent key milestones that might mediate growth-defence trade-offs under JA
signalling. This confirms the idea that carnivory has evolved by recycling the already available
molecular machineries of the ubiquitous plant immune system.
To better understand the mutant’s defect in the trap snapping mechanism, the ground states
(unstimulated traps) of the two phenotypes were compared. In this case, many cell wall-related
genes (e.g. expansins) were downregulated in the ’ERROR’ mutant. For the first time, these
data point to the importance of a special cell wall architecture of the trap, that might confer
the mechanical properties needed for a functional buckling system - which amplifies the speed
of the trap closure.
This study provides candidate channels for each of the AP phases that give rise to and shape
the sharp Venus flytrap-specific AP. It further underlines the possible contribution of the cell
wall architecture to the metastable ready-to-snap configuration of the trap before stimulation
- which might be crucial for the buckling-dependent snapping. And finally, it highlights
molecular milestones linked to defence responses that ensure trap morphing into a green
stomach after mechanostimulation. Altogether, these processes prove to be interdependent
and essential for a successful carnivorous lifestyle.
The immune system is responsible for the preservation of homeostasis whenever a given organism is exposed to distinct kinds of perturbations. Given the complexity of certain organisms like mammals, and the diverse types of challenges that they encounter (e.g. infection or disease), the immune system evolved to harbor a great variety of distinct immune cell populations with specialized functions. For instance, the family of T cells is sub-divided into conventional (Tconv) and unconventional T cells (UTCs). Tconv form part of the adaptive arm of the immune system and are comprised of αβ CD4+ or CD8+ cells that differentiate from naïve to effector and memory populations upon activation and are essential during infection and cancer. Furthermore, UTCs, which include γδ T cells, NKT and MAIT, are involved in innate and adaptive immune responses, due to their dual mode of activation, through cytokines (innate-like) or TCR (adaptive), and function. Despite our understanding of the basic functions of T cells in several contexts, a great number of open questions related to their basic biology remain. For instance, the mechanism behind the differentiation of naïve CD4+ and CD8+ T cells into effector and memory populations is not fully understood. Moreover, the exact function and relevance of distinct UTC subpopulations in a physiological context have not been fully clarified. Here, we investigated the factors mediating naïve CD8+ T cell differentiation into effector and memory cells. By using flow cytometry, mass spectrometry, enzymatic assays, and transgenic mouse models, we found that the membrane bound enzyme sphingomyelin-phosphodiesterase acid-like 3b (Smpdl3b) is crucial for the maintenance of memory CD8+ T cells. Our data show that the absence of Smpdl3b leads to diminished CD8+ T cell memory, and a loss of stem-like memory populations due to an aggravated contraction. Our scRNA-seq data suggest that Smpdl3b could be involved in clathrinmediated endocytosis through modulation of Huntingtin interacting protein 1 (Hip1) levels, likely regulating TCR-independent signaling events. Furthermore, in this study we explored the role of UTCs in lymph node-specific immune responses. By using transgenic mouse models for photolabeling, lymph node transplantation models, infection models and flow cytometry, we demonstrate that S1P regulates the migration of tissue-derived UTC from tissues to draining lymph nodes, resulting in heterogeneous immune responses mounted by lymph nodes draining different tissues. Moreover, our unbiased scRNAseq and single lineage-deficient mouse models analysis revealed that all UTC lineages (γδ T cells, NKT and MAIT) are organized in functional units, based on transcriptional homogeneity, shared microanatomical location and migratory behavior, and numerical and functional redundancy. Taken together, our studies describe additional cell intrinsic (Smpdl3b) and extrinsic (S1Pmediated migration) functions of sphingolipid metabolism modulating T cell biology. We propose the S1P/S1PR1/5 signaling axis as the potential survival pathway for Smpdl3b+ memory CD8+ T cells and UTCs, mainly in lymph nodes. Possibly, Smpdl3b regulates S1P/S1PR signaling by balancing ligandreceptor endocytosis, while UTCs migrate to lymph nodes during homeostasis to be exposed to specific levels of S1P that assure their maintenance. Our results are clinically relevant, since several drugs modulating the S1P/S1PR signaling axis or the levels of Smpdl3b are currently used to treat human diseases, such as multiple sclerosis and B cell-mediated diseases. We hope that our discoveries will inspire future studies focusing on sphingolipid metabolism in immune cell biology.
To grow larger, insects must shed their old rigid exoskeleton and replace it with a new one. This process is called molting and the motor behavior that sheds the old cuticle is called ecdysis. Holometabolic insects have pupal stages in between their larval and adult forms, during which they perform metamorphosis. The pupal stage ends with eclosion, i.e., the emergence of the adult from the pupal shell. Insects typically eclose at a specific time during the day, likely when abiotic conditions are at their optimum. A newly eclosed insect is fragile and needs time to harden its exoskeleton. Hence, eclosion is regulated by sophisticated developmental and circadian timing mechanisms.
In Drosophila melanogaster, eclosion is limited to a daily time window in the morning, regarded as the “eclosion gate”. In a population of laboratory flies entrained by light/dark cycles, most of the flies eclose around lights on. This rhythmic eclosion pattern is controlled by the circadian clock and persists even under constant conditions.
Developmental timing is under the control of complex hormonal signaling, including the steroid ecdysone, insulin-like peptides, and prothoracicotropic hormone (PTTH). The interactions of the central circadian clock in the brain and a peripheral clock in the prothoracic gland (PG) that produces ecdysone are important for the circadian timing of eclosion. These two clocks are connected by a bilateral pair of peptidergic PTTH neurons (PTTHn) that project to the PG. Before each molt, the ecdysone level rises and then falls shortly before ecdysis. The falling ecdysone level must fall below a certain threshold value for the eclosion gate to open. The activity of PTTHn is inhibited by short neuropeptide F (sNPF) from the small ventrolateral neurons (sLNvs) and inhibition is thought to lead to a decrease in ecdysone production.
The general aim of this thesis is to further the understanding of how the circadian clock and neuroendocrinal pathways are coordinated to drive eclosion rhythmicity and to identify when these endocrinal signaling pathways are active. In Chapter I, a series of conditional PTTHn silencing-based behavioral assays, combined with neuronal activity imaging techniques such as non-invasive ARG-Luc show that PTTH signaling is active and required shortly before eclosion and may serve to phase-adjust the activity of the PG at the end of pupal development. Trans-synaptic anatomical stainings identified the sLNvs, dorsal neurons 1 (DN1), dorsal neurons 2 (DN2), and lateral posterior neurons (LPNs) clock neurons as directly upstream of the PTTHn.
Eclosion motor behavior is initiated by Ecdysis triggering hormone (ETH) which activates a pair of ventromedial (Vm) neurons to release eclosion hormone (EH) which positively feeds back to the source of ETH, the endocrine Inka cells. In Chapter II trans-synaptic tracing showed that most clock neurons provide input to the Vm and non-canonical EH neurons. Hence, clock can potentially influence the ETH/EH feedback loop. The activity profile of the Inka cells and Vm neurons before eclosion is described. Vm and Inka cells are active around seven hours before eclosion. Interestingly, all EH neurons appear to be exclusively peptidergic.
In Chapter III, using chemoconnectomics, PTTHns were found to express receptors for sNPF, allatostatin A (AstA), allatostatin C (AstC), and myosuppressin (Ms), while EH neurons expressed only Ms and AstA receptors. Eclosion assays of flies with impaired AstA, AstC, or Ms signaling do not show arrhythmicity under constant conditions. However, optogenetic activation of the AstA neurons strongly suppresses eclosion.
Chapter IV focuses on peripheral ventral’ Tracheal dendrite (v’Td) and class IV dendritic arborization (C4da) neurons. The C4da neurons mediate larval light avoidance through endocrine PTTH signaling. The v’Td neurons mainly receive O2/CO2 input from the trachea and are upstream of Vm neurons but are not required for eclosion rhythmicity. Conditional ablation of the C4da neurons or torso (receptor of PTTH) knock-out in the C4da neurons impaired eclosion rhythmicity. Six to seven hours before eclosion, PTTHn, C4da, and Vm neurons are active based on ARG-Luc imaging. Thus, C4da neurons may indirectly connect the PTTHn to the Vm neurons.
In summary, this thesis advances our knowledge of the temporal activity and role of PTTH signaling during pupal development and rhythmic eclosion. It further provides a comprehensive characterization of the synaptic and peptidergic inputs from clock neurons to PTTHn and EH neurons. AstA, AstC, and Ms are identified as potential modulators of eclosion circuits and suggest an indirect effect of PTTH signaling on EH signaling via the peripheral sensory C4da neurons.
A novel USP11-TCEAL1-mediated mechanism protects transcriptional elongation by RNA Polymerase II
(2024)
Deregulated expression of MYC oncoproteins is a driving event in many human cancers. Therefore, understanding and targeting MYC protein-driven mechanisms in tumor biology remain a major challenge.
Oncogenic transcription in MYCN-amplified neuroblastoma leads to the formation of the MYCN-BRCA1-USP11 complex that terminates transcription by evicting stalling RNAPII from chromatin. This reduces cellular stress and allows reinitiation of new rounds of transcription. Basically, tumors with amplified MYC genes have a high demand on well orchestration of transcriptional processes-dependent and independent from MYC proteins functions in gene regulation. To date, the cooperation between promoter-proximal termination and transcriptional elongation in cancer cells remains still incomplete in its understanding.
In this study the putative role of the dubiquitinase Ubiquitin Specific Protease 11 (USP11) in transcription regulation was further investigated. First, several USP11 interaction partners involved in transcriptional regulation in neuroblastoma cancer cells were identified. In particular, the transcription elongation factor A like 1 (TCEAL1) protein, which assists USP11 to engage protein-protein interactions in a MYCN-dependent manner, was characterized. The data clearly show that TCEAL1 acts as a pro-transcriptional factor for RNA polymerase II (RNAPII)-medi- ated transcription. In detail, TCEAL1 controls the transcription factor S-II (TFIIS), a factor that assists RNAPII to escape from paused sites. The findings claim that TCEAL1 outcompetes the transcription elongation factor TFIIS in a non-catalytic manner on chromatin of highly expressed genes. This is reasoned by the need regulating TFIIS function in transcription. TCEAL1 equili- brates excessive backtracking and premature termination of transcription caused by TFIIS.
Collectively, the work shed light on the stoichiometric control of TFIIS demand in transcriptional regulation via the USP11-TCEAL1-USP7 complex. This complex protects RNAPII from TFIIS-mediated termination helping to regulate productive transcription of highly active genes in neuroblastoma.
Das maligne Melanom, eine der seltensten, aber gleichzeitig auch die tödlichste dermatologische Malignität, gekennzeichnet durch die Neigung zu einer frühen Metastasierung sowie die rasche Entwicklung von Therapieresistenzen, zählt zu den Tumorentitäten mit dem höchsten Anstieg der Inzidenz weltweit. Mausmodelle werden häufig verwendet, um die Melanomagenese zu erforschen und neue effektive therapeutische Strategien zu entwickeln, spiegeln die menschliche Physiologie allerdings nur unzureichend wider. In zweidimensionalen (2D) Zellkulturen mangelt es dagegen an wichtigen Komponenten der Mikroumgebung des Tumors und dem dreidimensionalen Gewebekontext. Um dieses Manko zu beheben und die Entwicklung von auf den Menschen übertragbaren Tumormodellen in der onkologischen Forschung voranzutreiben, wurde als Alternative zu Zellkulturen und Tierversuchen humane organotypische dreidimensionale (3D) Melanom-Modelle als in vitro Testsystem für die Bewertung der Wirksamkeit von anti-Tumor Therapeutika entwickelt.
Im Zuge dieser Arbeit konnte das in vitro Melanom-Modell entscheidend weiterentwickelt werden. So konnten Modelle unterschiedlichster Komplexität etabliert werden, wobei abhängig von der Fragestellung einfachere epidermale bis hin zu unterschiedlich komplexen Vollhautmodellen Anwendung finden. Durch Simulation der Tumor-Mikroumgebung eignen sich diese zur präklinischen Validierung neuer Tumor-Therapeutika, sowie der Erforschung pathologischer Vorgänge, von der Tumor-Formierung bis zur Metastasierung. Zudem konnten erfolgreich unterschiedlichste humane Melanomzelllinien ins Modell integriert werden; dadurch, dass sich diese durch ihre Treibermutationen, die zur Krankheitsentstehung beitragen, unterscheiden, stellen sie unterschiedliche Ansprüche an potentielle therapeutische Angriffspunkte und ermöglichen das Widerspiegeln vieler Melanom-Subtypen im Modell. Ferner ist es möglich, verschiedene Stadien der Tumor-Entwicklung über die Zugabe von Melanomzellen in Einzelsuspension bzw. von Melanom-Sphäroiden widerzuspiegeln. Es konnte für bestimmte Therapie-Ansätze, wie zielgerichtete Therapien, z.B. die Gabe von sich in der Klinik im Einsatz befindlicher BRAF-/MEK-Inhibitoren, gezeigt werden, dass sich die etablierten Modelle hervorragend als präklinische Testsysteme zur Wirksamkeitsbewertung eignen. Zudem bieten sich einzigartige Möglichkeiten, um die Interaktion humaner Tumorzellen und gesunder Zellen in einem Gewebeverband zu untersuchen. Ferner konnten drei neue technische Analyse-Verfahren zur nicht-invasiven Detektion der Tumor- Pro- und Regression, Beurteilung der Wirksamkeit von potenziellen Anti-Tumor-Therapien sowie der Evaluierung des Tumor-Metabolismusses implementiert werden. Perspektivisch ermöglichen immun-kompetente Melanom-Modelle die Austestung neuer Immun- und Zelltherapien in einem voll humanen System; gleichzeitig leisten die etablierten Modelle einen signifikanten Beitrag zur Reduktion von Tierexperimenten.
The hallmark oncoprotein Myc is a major driver of tumorigenesis in various human cancer entities. However, Myc’s structural features make it challenging to develop small molecules against it. A promising strategy to indirectly inhibit the function of Myc is by targeting its interactors. Many Myc-interacting proteins have reported scaffolding functions which are difficult to target using conventional occupancy- driven inhibitors. Thus, in this thesis, the proteolysis targeting chimera (PROTAC) approach was used to target two oncoproteins interacting with Myc which promote the oncogenicity of Myc, Aurora-A and WDR5. PROTACs are bifunctional small molecules that bind to the target protein with one ligand and recruit a cellular E3- ligase with the other ligand to induce target degradation via the ubiquitin- proteasome system. So far, the most widely used E3-ligases for PROTAC development are Cereblon (CRBN) and von Hippel–Lindau tumor suppressor (VHL). Furthermore, there are cases of incompatibility between some E3-ligases and proteins to bring about degradation. Hence there is a need to explore new E3- ligases and a demand for a tool to predict degradative E3-ligases for the target protein in the PROTAC field.
In the first part, a highly specific mitotic kinase Aurora-A degrader, JB170, was developed. This compound utilized Aurora-A inhibitor alisertib as the target ligand and thalidomide as the E3-ligase CRBN harness. The specificity of JB170 and the ternary complex formation was supported by the interactions between Aurora-A and CRBN. The PROTAC-mediated degradation of Aurora-A induced a distinct S- phase defect rather than mitotic arrest, shown by its catalytic inhibition. The finding demonstrates that Aurora-A has a non-catalytic role in the S-phase. Furthermore, the degradation of Aurora-A led to apoptosis in various cancer cell lines.
In the second part, two different series of WDR5 PROTACs based on two protein- protein inhibitors of WDR5 were evaluated. The most efficient degraders from both series recruited VHL as a E3-ligase and showed partial degradation of WDR5. In addition, the degradation efficiency of the PROTACs was significantly affected by the linker nature and length, highlighting the importance of linker length and composition in PROTAC design. The degraders showed modest proliferation defects at best in cancer cell lines. However, overexpression of VHL increased the degradation efficiency and the antiproliferative effect of the PROTACs.
In the last part, a rapamycin-based assay was developed to predict the degradative E3-ligase for a target. The assay was validated using the WDR5/VHL and Aurora- A/CRBN pairs. The result that WDR5 is degraded by VHL but not CRBN and Aurora-A is degraded by CRBN, matches observations made with PROTACs. This technique will be used in the future to find effective tissue-specific and essential E3-ligases for targeted degradation of oncoproteins using PROTACs.
Collectively, the work presented here provides a strategy to improve PROTAC development and a starting point for developing Aurora-A and WDR5 PROTACs for cancer therapy.
In vitro models mimic the tissue-specific anatomy and play essential roles in personalized medicine and disease treatments. As a sophisticated manufacturing technology, 3D printing overcomes the limitations of traditional technologies and provides an excellent potential for developing in vitro models to mimic native tissue. This thesis aims to investigate the potential of a high-resolution 3D printing technology, melt electrowriting (MEW), for fabricating in vitro models. MEW has a distinct capacity for depositing micron size fibers with a defined design. In this thesis, three approaches were used, including 1) extending the MEW polymer library for different biomedical applications, 2) developing in vitro models for evaluation of cell growth and migration toward the different matrices, and 3) studying the effect of scaffold designs and biochemical cues of microenvironments on cells.
First, we introduce the MEW processability of (AB)n and (ABAC)n segmented copolymers, which have thermally reversible network formulation based on physical crosslinks. Bisurea segments are combined with hydrophobic poly(dimethylsiloxane) (PDMS) or hydrophilic poly(propylene oxide)-poly(ethylene oxide)-poly(propylene oxide) (PPO-PEG-PPO) segments to form the (AB)n segmented copolymers. (ABAC)n segmented copolymers contain all three segments: in addition to bisurea, both hydrophobic and hydrophilic segments are available in the same polymer chain, resulting in tunable mechanical and biological behaviors. MEW copolymers either support cells attachment or dissolve without cytotoxic side effects when in contact with the polymers at lower concentrations, indicating that this copolymer class has potential in biological applications. The unique biological and surface properties, transparency, adjustable hydrophilicity of these copolymers could be beneficial in several in vitro models.
The second manuscript addresses the design and development of a melt electrowritten competitive 3D radial migration device. The approach differs from most of the previous literature, as MEW is not used here to produce cell invasive scaffolds but to fabricate an in vitro device. The device is utilized to systematically determine the matrix which promotes cell migration and growth of glioblastoma cells. The glioblastoma cell migration is tested on four different Matrigel concentrations using a melt electrowritten radial device. The glioblastoma U87 cell growth and migration increase at Matrigel concentrations 6 and 8 mg mL-1 In the development of this radial device, the accuracy, and precision of melt electrowritten circular shapes were investigated. The results show that the printing speed and design diameter are essential parameters for the accuracy of printed constructs. It is the first instance where MEW is used for the production of in vitro devices.
The influence of biochemical cues and scaffold designs on astrocytes and glioblastoma is investigated in the last manuscript. A fiber comprising the box and triangle-shaped pores within MEW scaffolds are modified with biochemical cues, including RGD and IKVAV peptides using a reactive NCO-sP(EO-stat-PO) macromer. The results show that astrocytes and glioblastoma cells exhibit different phenotypes on scaffold designs and peptide-coated scaffolds.
Dieser Kurzbericht beleuchtet die Einsatzmöglichkeiten von Kleinsatelliten in der extraterrestrischen Forschung und zeigt auf welche technologischen Herausforderungen sich bei ihrem Einsatz ergeben. Die präsentierten Ergebnisse sind Teil der SATEX Untersuchung (FKZ 50OO2222). In diesem Dokument werden zunächst die allgemeinen Einsatzmöglichkeiten von Kleinsatelliten in der Extraterrestrik anhand ausgewählter Beispielmissionen beleuchtet. Daraufhin erfolgt die Erörterung spezifischer technischer Herausforderungen und Umweltbedingungen bei cislunaren und interplanetaren Kleinsatellitenmissionen, gefolgt von einer kurzen Präsentation von Nutzerwünsche aus Deutschland für Missionen zur Erforschung des Weltraums. Zum Abschluss werden zehn konkrete, im Rahmen der Untersuchung ermittelte, Missionsideen vorgestellt und bewertet. Schließlich erfolgt die Zusammenfassung der wichtigsten Erkenntnisse und Empfehlungen.
Dieser Kurzbericht beleuchtet die Einsatzmöglichkeiten von Kleinsatelliten in der extraterrestrischen Forschung und zeigt auf welche technologischen Herausforderungen sich bei ihrem Einsatz ergeben. Die präsentierten Ergebnisse sind Teil der SATEX Untersuchung (FKZ 50OO2222). In diesem Dokument werden zunächst die allgemeinen Einsatzmöglichkeiten von Kleinsatelliten in der Extraterrestrik anhand ausgewählter Beispielmissionen beleuchtet. Daraufhin erfolgt die Erörterung spezifischer technischer Herausforderungen und Umweltbedingungen bei cislunaren und interplanetaren Kleinsatellitenmissionen, gefolgt von einer kurzen Präsentation von Nutzerwünsche aus Deutschland für Missionen zur Erforschung des Weltraums. Zum Abschluss werden zehn konkrete, im Rahmen der Untersuchung ermittelte, Missionsideen vorgestellt und bewertet. Schließlich erfolgt die Zusammenfassung der wichtigsten Erkenntnisse und Empfehlungen.
Im Zeitalter der sozialen Medien ist es für viele Eltern zur Gewohnheit geworden, nicht nur sich selbst, sondern auch das eigene Kind der Internetgemeinschaft zu präsentieren. Diese Praxis wird als "Sharenting" ("to share" + "parenting“) bezeichnet. So kommt es, dass mittlerweile ein Großteil der Kinder bereits in sehr jungen Jahren einen - unfreiwilligen - digitalen Fußabdruck hinterlässt. Der freizügige Umgang mit den Daten des Kindes bringt zahlreiche rechtliche Probleme mit sich, welche an den Schnittstellen des Rechts zum Schutz der Persönlichkeit, des Datenschutzrechts und des Familienrechts zu verorten sind. Am Beispiel der Plattformen Facebook, Instagram und WhatsApp lotet Katharina Theresa Starz die Grenzen des rechtlich Zulässigen aus und zeigt auf, welche Konsequenzen sich ergeben können, wenn ebendiese Grenzen von den Eltern überschritten werden.
Forests are essential sources of tangible and intangible benefits, but global climate change associated with recurrent extreme drought episodes severely affects forest productivity due to extensive tree die-back. On that, it appeals to an urgency for large-scale reforestation efforts to mitigate the impact of climate change worldwide; however, there is a lack of understanding of drought-effect on sapling growth and survival mechanisms. It is also challenging to anticipate how long trees can survive and when they succumb to drought. Hence, to ensure success of reforestation programs and sustainable forest productivity, it is essential to identify drought-resistant saplings. For that, profound knowledge of hydraulic characteristics is needed. To achieve this, the study was split into two phases which seek to address (1) how the hydraulic and anatomical traits influence the sapling’s growth rate under drought stress. (2) how plant water potential regulation and physiological traits are linked to species’ water use strategies and their drought tolerance.
The dissertation is assembled of two study campaigns carried out on saplings at the Chair of Botany II, University of Würzburg, Germany. The first study involved three ecologically important temperate broadleaved tree species — saplings of 18-month (Acer pseudoplatanus, Betula pendula, and Sorbus aucuparia) — grown from seeds in contrasting conditions (inside a greenhouse and outside), with the latter being subjected to severe natural heat waves. In the second study, two additional temperate species (Fagus sylvatica and Tilia cordata) were added. The drying-out event was conducted using a randomised blocked design by monitoring plant water status in a climate-controlled chamber and a greenhouse.
In campaign I, I present the result based on analysed data of 82 plants of temperate deciduous species and address the juvenile growth rate trade-off with xylem safety-efficiency. Our results indicate biomass production varies considerably due to the contrasted growing environment. High hydraulic efficiency is necessary for increased biomass production, while safety-efficiency traits are decoupled and species-specific. Furthermore, productivity was linked considerably to xylem safety without revealing a well-defined pattern among species. Moreover, plasticity in traits differed between stressed and non-stressed plants. For example, safety-related characteristics were more static than efficiency-related traits, which had higher intra-specific variation. Moreover, we recorded anatomical and leaf traits adjustments in response to a stress condition, but consistency among species is lacking.
In campaign II, I combined different ways to estimate the degree of isohydry based on water potential regulation and connected the iso-anisohydric spectrum (i.e., hydroscape area, HSA) to hydraulic traits to elucidate actual plant performance during drought. We analysed plant water potential regulation (Ψpd and Ψmd) and stomatal conductance of 28-29 month saplings of five species. I used a linear mixed modelling approach that allowed to control individual variations to describe the water potential regulation and tested different conceptual definitions of isohydricity. The combined methods allowed us to estimate species' relative degree of isohydry. Further, we examined the traits coordination, including hydraulic safety margin, HSM; embolism resistance, P88; turgor loss, Ψtlp; stomata closure, Ps90; capacitance, C; cuticular conductance, gmin, to determine time to hydraulic failure (Thf). Thf is the cumulative effect of time to stomata closure (Tsc) and time after stomatal closure to catastrophic hydraulic failure (Tcrit).
Our results show the species' HSA matches their stomatal stringency, which confirms the relationship between stomatal response and leaf water potential decline. Species that close stomata at lower water potential notably had a larger HSA. Isohydric behaviour was mostly associated with leaf hydraulic traits and poorly to xylem safety traits. Species' degree of isohydry was also unrelated to the species' time to death during drying-out experiments. This supports the notion that isohydry behaviours are linked to water use rather than drought survival strategies. Further, consistent with our assumptions, more isohydric species had larger internal water storage and lost their leaf turgor at less negative water potentials. Counter to our expectations, neither embolism resistance nor the associated hydraulic safety margins were related to metrics of isohydry. Instead, our results indicate traits associated with plant drought response to cluster along two largely independent axes of variation (i.e., stomatal stringency and xylem safety). Furthermore, on the temporal progression of plant drought responses, stomatal closure is critical in coordinating various traits to determine species' hydraulic strategies. Desiccation avoidance strategy was linked to Tsc and coordinated traits response of Ps90, Ψtlp, and HSA, whereas desiccation tolerance was related to Tcrit and traits such as lower P88 value, high HSM, and lower gmin. Notably, the shoot capacitance (C) is crucial in Thf and exhibits dichotomous behaviour linked to both Tsc and Tcrit.
In conclusion, knowledge of growth rate trade-offs with xylem safety-efficiency combined with traits linked to species’ hydraulic strategies along the isohydry could substantially enhance our ability to identify drought-resistant saplings to ensure the success of reforestation programs and predicting sensitivity to drought for achieving sustainable forest ecosystems.
Allogeneic hematopoietic cell transplantation (Allo-HCT) is the main and only treatment for many malignant and non-malignant haematological disorders. Even though the treatment has improved through the years and patient life expectancy has increased, graft versus host disease (GvHD) is still considered the main obstacle and one of the main reasons for increased mortality. Furthermore, improved patient’s survival and life expectancy brought into question the late post-HCT complications. The leading cause of late death after allo-HCT is the relapse of primary disease as well as chronic GvHD (cGvHD). However, a clear relationship was also described with pulmonary complications, endocrine dysfunction and infertility, and cataracts in post-HCT patients. In the last years big concern regarding a cumulative cardiovascular incidence in long-term survivors has been raised. Severe cardiovascular disease (CVD) is caused by atherosclerosis which is considered a chronic inflammatory disease of blood vessels. As such, it takes a long time from endothelial damage, as the onset event, and followed plaque formation to a manifestation of severe consequences, such as stroke, coronary heart disease, or peripheral arterial disease. Endothelial damage is well documented in patients post-HCT. In the context of allo-HCT, the endothelial damage is induced by the conditioning regimen with or without total body irradiation (TBI). Furthermore, endothelial cells (ECs) have been documented as a target of GvHD and increased concentration of circulating endothelial cells (CEC) coinciding with an increase in the number of circulating alloreactive T cells. According to 2021 ESC Guidelines on CVD prevention, the main atherosclerotic CVD (ASCVD) risk factors are blood apolipoprotein B (ApoB)-containing lipoproteins (of which low-density lipoprotein (LDL) is the most abundant), high blood pressure, cigarette smoking and diabetes mellitus (DM). GvHD is considered a high-risk factor for the onset of dyslipidaemia, hypertension, and DM. Overall, the risk of premature cardiovascular death is 2.7 fold increased in comparison to the general population, while the cumulative incidence of cardiovascular complications was shown to be up to 47% at ten years after reduced intensity conditioning (RIC), post-HCT. However, up to date, there are no available studies elucidating the interconnection between GvHD and atherosclerosis. The goal of this study was, therefore, to investigate the involvement of GvHD in the progression of atherosclerosis as well as to elucidate whether cytotoxic, CD8+ T cells that were shown to play a significant role in endothelial damage during the course of skin GvHD on one hand, and inducers of formation of unstable plaque on the other, are involved in this interconnection. For that purpose we established a novel minor histocompatibility anti gens (miHAg) allo-HCT Western diet (WD)-induced atherosclerosis mouse model. We were able to show that GvHD has a significant impact on atherosclerosis development in B6.Ldlr−/− recipient mice even in the absence of overt clinical disease activity. It seems that the impact is at least partly induced by CD8+ T cells, that showed significantly increased infiltration of aortic lesions in mice facing subclinical GvHD. As studies have shown in regular atherosclerotic mouse models as well as in humans, these CD8+ T cells exhibited not only increased expression of genes involved in activation, survival and differentiation to cytotoxic phenotype, but also some genes pointing out their exhaustion, that were absent in CD4+ T cell cluster. When anti-CD8β antibody was applied once per week along with WD feeding for eight weeks, the plaque formation was significantly reduced in aorta and aortic root pointing out the importance of these cells in an alloreactivity induced lesion formation. Furthermore, anti-CD8β treatment led to significantly decreased necrotic core formation followed by overall increase in plaque stability. Strikingly, bone marrow plus T cells (BMT) recipients fed WD showed significantly increased serum cholesterol levels in comparison to bone marrow (BM) (a group lacking alloreactive T cells that induce GvHD). This effect was reversed when anti-CD8β treatment was applied, suggesting, at least partly, an impact of alloreactive CD8+ T cells on cholesterol levels. Expression of genes responsible for lipid metabolism pointed out the tendency of the liver to regulate the increased cholesterol levels, however, the mechanism behind this phenotype still remains to be revealed. On the other hand, the impact of obesity, induced by chronic high-fat diet (HFD) feeding, has been shown to be an independent risk factor for gastrointestinal GvHD. Similarly, in major histocompatibility complex (MHC) disparate allo-HCT mouse model, we have noticed that even short-term WD intake leads to a significant decrease in survival of mice post-HCT. When the concentration of transplanted alloreactive T cells was reduced, the survival was improved, pointing out the involvement of these cells in the pathogenesis. Additionally, bioluminescence imaging (BLI) during initiation and effector phase of acute GvHD (aGvHD) revealed increased infiltration of alloreactive T cells in mice fed WD. Studies in an obesity model, we could confirm the involvement of specifically CD4+ T cells in WD induced impact, as the relative number of these cells was significantly increased in small intestine on day six post-HCT in mice fed WD. This increased intestinal infiltration was preceded by increase in the number of alloreactive T cells expressing intestine homing receptor (α4β7 integrin) in peripheral lymph nodes (LNs). Even though the number of T cells was not changed in the spleen of WD fed mice, the subset of CD4+ and CD8+ T cells that were highly secreting TNFα was increased as well as the expression of genes regulating pro-inflammatory cytokines such as IL-6 and interferon (IFN)γ pointing out significant WD-induced inflammation. Moreover, slight tendency towards increased intestinal permeability and load of translocated luminal bacteria, that we observed, could induce severe endotoxemia and dysregulated systemic immune response that could lead to detrimental induction of cell death. Justifying our speculations, we noted increased levels of transaminases and an increase in lactate dehydrogenase (LDH) levels (pointing out significant tissue damages). However, the exact mechanism behind this detrimental WD impact still remains to be elucidated.
Binge Eating Disorder (BED) is a common, early-onset mental health condition characterised by uncontrollable episodes of overeating followed by negative emotions such as guilt and shame. An improved understanding of the neurocognitive mechanisms underlying BED is central to the development of more targeted and effective treatments. This thesis comprises a systematic review and three empirical studies contributing to this endeavour.
BED can be thought of as a disorder of cognitive-behavioural control. Indeed, self-report evidence points towards enhanced impulsivity and compulsivity in BED. However, retrospective self-reports do not capture the mechanisms underlying impulsive and compulsive lapses of control in the moment. The systematic review therefore focussed on the experimental literature on impulsivity and compulsivity in BED. The evidence was very mixed, although there was some indication of altered goal-directed control and behavioural flexibility in BED. We highlight poor reliability of experimental paradigms and the failure to properly account for weight status as potential reasons for inconsistencies between studies. Moreover, we propose that impulsivity and/or compulsivity may be selectively enhanced in negative mood states in BED and may therefore not be consistently detected in lab-based studies.
In the empirical studies, we explored the role of behavioural flexibility in BED using experimental and neuroimaging methods in concert with computational modelling. In the first empirical study, we assessed the reliability of a common measure of behavioural flexibility, the Probabilistic Reversal Learning Task (PRLT). We demonstrate that the behavioural and computational metrics of the PRLT have sufficient reliability to justify past and future applications if calculated using hierarchical modelling. This substantially improves reliability by reducing error variance. The results support the use of the PRLT in the second and third empirical studies on development and BED.
Because a majority of patients develop BED as adolescents or young adults, we speculated that it may emerge as a consequence of disrupted or deficient
maturation of behavioural flexibility. Little is known about typical development in this domain. We therefore investigated normative development of reversal learning from adolescence to adulthood in the second empirical study. Typically- developing adolescents exhibited less adaptive and more erratic and explorative behaviour than adults. This behaviour was accounted for by reduced sensitivity to positive feedback in a reinforcement learning model, and partially mediated by reduced activation reflecting uncertainty in the medial prefrontal cortex, a region known to mature substantially during adolescence.
In the third empirical study, we investigated reversal learning in BED, paying special attention to potential biases associated with learning from wins vs learning from losses. We speculated that negative urgency could make it more difficult for BED patients to learn and make decisions under pressure to avoid losses. To dissociate between effects of excess weight and BED, we collected data from obese individuals with and without BED as well as normal-weight controls. As hypothesised, there were subtle neurocognitive differences between obese participants with and without BED with regard to learning to obtain rewards and to avoid losses. Obese individuals showed relatively impaired learning to obtain rewards, while BED patients showed relatively impaired learning to avoid losses. This was reflected in differential learning signals in the brain and associated with BED symptom severity.
In sum, this thesis shows that the evidence on impulsivity and compulsivity in BED is inconsistent and offers potential explanations for this inconsistency. It highlights the need for reliability in interindividual difference research and indicates ways to improve it. Further, it charts the typical development of reversal learning from adolescence to adulthood and underscores the relevance of exploration in the context of learning and decision-making in adolescence. Finally, it demonstrates qualitative differences between BED and obesity, hinting at a pivotal role of aversive states in loss of control in BED.
The field of photopharmacology has attracted considerable attention due to applying the spatial and temporal precision of light to pharmacological systems. Photoswitchable biologically active compounds have proven useful in the field of G protein-coupled receptors (GPCRs), which are of tremendous therapeutic relevance. Generally, the pharmacology of GPCRs is complex, perhaps even more complex than originally thought. Suitable tools are required to dissect the different signalling pathways and mechanisms and to unravel how they are connected in a holistic image. This is reflected in the enormous scientific interest in CB2R, as the neuroprotective and immunomodulatory effects attributed to CB2R agonists have not yet translated into effective therapeutics. This work focused on the development of a novel photoswitchable scaffold based on the privileged structure of benzimidazole and its application in photoswitchable CB2R ligands as photopharmacological tools for studying the CB2R.
The visible-light photoswitchable ligand 10d enables the investigation of CB2R activation with regard to βarr2 bias, exhibiting a unique pharmacological profile as a “cis-on” affinity switch at receptor level and as a “trans-on” efficacy-switch in βarr2-mediated receptor internalization. The novel photoswitchable scaffold developed in this work further serves as a guide for the development of novel photoswitchable GPCR ligands based on the privileged structure of benzimidazole. To obtain a different tool compound for studying CB2R activation and signalling mechanisms, a previously reported putatively dualsteric CB2R ligand was rendered photoswitchable, by linking the orthosteric agonist to a CB2R-selective PAM via photoswitchable azobenzene. Compound 27-para exhibits a desirable “cis-on” behaviour across all investigated assays with >10-fold higher potency compared to its trans-isomer and can be used as an efficacy-switch employing specific concentrations.
The evolutionary success of higher plants is largely attributed to their tremendous developmental
plasticity, which allows them to cope with adverse conditions. However, because these adaptations
require investments of resources, they must be tightly regulated to avoid unfavourable trade-offs.
Most of the resources required are macronutrients based on carbon and nitrogen. Limitations in the
availability of these nutrients have major effects on gene expression, metabolism, and overall plant
morphology. These changes are largely mediated by the highly conserved master kinase SNF1-RELATED
PROTEIN KINASE1 (SnRK1), which represses growth and induces catabolic processes. Downstream of
SnRK1, a hub of heterodimerising group C and S1 BASIC LEUCINE ZIPPER (bZIP) transcription factors has
been identified. These bZIPs act as regulators of nutrient homeostasis and are highly expressed in
strong sink tissues, such as flowers or the meristems that initiate lateral growth of both shoots and
roots. However, their potential involvement in controlling developmental responses through their
impact on resource allocation and usage has been largely neglected so far. Therefore, the objective of
this work was to elucidate the impact of particularly S1 bZIPs on gene expression, metabolism, and
plant development.
Due to the high homology and suspected partial redundancy of S1 bZIPs, higher order loss-of-function
mutants were generated using CRISPR-Cas9. The triple mutant bzip2/11/44 showed a variety of robust
morphological changes but maintained an overall growth comparable to wildtype plants. In detail
however, seedlings exhibited a strong reduction in primary root length. In addition, floral transition
was delayed, and siliques and seeds were smaller, indicating a reduced supply of resources to the shoot
and root apices. However, lateral root density and axillary shoot branching were increased, suggesting
an increased ratio of lateral to apical growth in the mutant. The full group S1 knockout
bzip1/2/11/44/53 showed similar phenotypes, albeit far more pronounced and accompanied by
growth retardation. Metabolomic approaches revealed that these architectural changes were
accompanied by reduced sugar levels in distal sink tissues such as flowers and roots. Sugar levels were
also diminished in leaf apoplasts, indicating that long distance transport of sugars by apoplastic phloem
loading was impaired in the mutants. In contrast, an increased sugar supply to the proximal axillary
buds and elevated starch levels in the leaves were measured. In addition, free amino acid levels were
increased in bzip2/11/44 and bzip1/2/11/44/53, especially for the important transport forms
asparagine and glutamine. The increased C and N availability in the proximal tissues could be the cause
of the increased axillary branching in the mutants.
To identify bZIP target genes that might cause the observed shifts in metabolic status, RNAseq
experiments were performed. Strikingly, clade III SUGARS WILL EVENTUALLY BE EXPORTED (SWEET)
8
genes were abundant among the differentially expressed genes. As SWEETs are crucial for sugar export
to the apoplast and long-distance transport through the phloem, their reduced expression is likely to
be the cause of the observed changes in sugar allocation. Similarly, the reduced expression of
GLUTAMINE AMIDOTRANSFERASE 1_2.1 (GAT1_2.1), which exhibits glutaminase activity, could be an
explanation for the abundance of glutamine in the mutants. Additional experiments (ATAC-seq, DAPseq, PTA, q-RT-PCR) supported the direct induction of SWEETs and GAT1_2.1 by S1 bZIPs. To confirm
the involvement of these target genes in the observed S1 bZIP mutant phenotypes, loss-of-function
mutants were obtained, which showed moderately increased axillary branching. At the same time, the
induced overexpression of bZIP11 in axillary meristems had the opposite effect.
Collectively, a model is proposed for the function of S1 bZIPs in regulating sink tissue development. For
efficient long-distance sugar transport, bZIPs may be required to induce the expression of clade III
SWEETs. Thus, reduced SWEET expression in the S1 bZIP mutants would lead to a decrease in apoplastic
sugar loading and a reduced supply to distal sinks such as shoot or root apices. The reduction in longdistance transport could lead to sugar accumulation in the leaves, which would then increasingly be
transported via symplastic routes towards proximal sinks such as axillary branches and lateral roots or
sequestered as starch. The reduced GAT1_2.1 levels lead to an abundance of glutamine, a major
nitrogen transport form. The combined effect on C and N allocation results in increased nutrient
availability in proximal tissues, promoting the formation of lateral plant organs. Alongside emerging
evidence highlighting the power of bZIPs to steer nutrient allocation in other species, a novel but
evolutionary conserved role for S1 bZIPs as regulators of developmental plasticity is proposed, while
the generation of valuable data sets and novel genetic resources will help to gain a deeper
understanding of the molecular mechanisms involved
Die distale Radiusfraktur gehört zu den häufigsten Frakturen in Deutschland mit einem Inzidenzanstieg im Alter unter Betonung des weiblichen Geschlechts. Dabei zeigt sich ein zunehmender Trend in Richtung operative Versorgung, allen voran die Versorgung mittels winkelstabiler Plattensysteme. Instabile, distale Radiusfrakturen werden dabei vor geplanter operativer Versorgung im Rahmen der Initialbehandlung üblicherweise geschlossen reponiert und im Gipsverband retiniert. Ziel der vorliegenden monozentrischen, prospektiv randomisierten Studie mit zwei Studiengruppen war es herauszufinden, ob sich das Unterlassen der Reposition vor geplanter Operation nachteilig auf das Schmerzniveau in der präoperativen Phase auswirkt und ob sich durch die Dislokation Nachteile in Bezug auf den Nervus medianus im Sinne eines Traktionsschadens sowie bezüglich des klinisch-radiologischen Ausheilungsergebnisses zeigen.
Die Studie zeigte, dass das Schmerzempfinden während der präoperativen Gipsbehandlung unabhängig von einer vorherigen Reposition war. Für den primären Endpunkt an Tag 1 nach der Akutbehandlung konnte statistisch signifikante Nichtunterlegenheit der Gruppe ohne Reposition gegenüber der Gruppe mit Reposition nachgewiesen werden. Gleiches galt für Tag 2, sowohl für die absoluten Schmerzniveaus als auch für die Schmerzlinderung.
Das Unterlassen der Reposition hatte zudem keine nachteiligen Effekte auf den Nervus medianus.
Gleiches zeigte sich für das klinische und radiologische Ausheilungsergebnis. Für die funktionellen DASH- und Krimmer-Scores konnte ein Jahr postoperativ ebenfalls statistisch signifikante Nichtunterlegenheit der Gruppe ohne Reposition nachgewiesen werden.
Diese Erkenntnisse bestätigen die in der Literatur vorhandenen Ergebnisse verschiedener Studien dahingehend, dass das Unterlassen der Reposition keine nachteiligen Effekte auf das postoperative Outcome hat. Einige Studien verdeutlichen zudem, dass es nach Reposition, insbesondere bei Vorliegen gewisser Risiko- und Instabilitätsfaktoren, ohnehin zur sekundären Dislokation kommt, sodass die generelle Notwendigkeit der Reposition vor Gipsanlage sowohl vor einer operativen als auch vor einer konservativen Weiterbehandlung angezweifelt werden
muss.
Ziel der vorliegenden Studie war es zu untersuchen, ob anhand geometrischer Merkmale der HWK im Kindesalter eine sichere individuelle Vorhersage der Morphologie der HWK zum Ende der Entwicklung möglich ist. Hierdurch könnte eine Individualisierung der CVM-Methode und somit eine Einschätzung des bereits verstrichenen Wachstums erfolgen.
Zu diesem Zweck wurden insgesamt 1377 FRS-Aufnahmen von 267 Patienten – 110 weibliche und 157 männliche – aus dem Archiv der Poliklinik für Kieferorthopädie des Universitätsklinikums Würzburg digitalisiert und untersucht. Die HWK wurden im Programm OnyxCeph (Herst.: Image Instruments GmbH) quantifiziert und die berechneten Werte mit der Software SPSS statistisch ausgewertet. Mittels linearer Regressionen wurde versucht, anhand der Morphologie der Wirbelkörper vor dem puberalen Wachstumsschub auf die Geometrie der HWK im Erwachsenenalter zu schließen. Zur Illustrierung wurden Streudiagramm und die dazugehörigen Abfolgen von Röntgenbildern dargestellt.
Eine Schätzung der Geometrie der HWK im Erwachsenenalter würde bei den separat betrachteten Parametern und bei einer gemeinsamen Betrachtung der Parameter kaum zu korrekten Einschätzungen führen.
Die Streudiagramme mit den Bilderabfolgen stützen diese These ebenfalls und illustrieren die mögliche Fehleinschätzung der Geometrie.
Die Ergebnisse der Studie zeigen erneut, dass die Geometrie der HWK im Erwachsenenalter sehr variabel ist, wie komplex die Entwicklung der HWK ist und dass anhand ihrer Geometrie im Kindesalter keine sichere Einschätzung der skelettalen Reife möglich ist.
Eine Individualisierung der CVM-Methode ist anhand der in dieser Studie untersuchten Parameter nicht möglich. Somit lässt sich schlussfolgern, dass die CVM-Methode nicht als alleinige Methode zur präzisen skelettalen Alterseinschätzung verlässlich genutzt werden kann, sondern für eine sichere Beurteilung weitere Reifeindikatoren hinzugezogen werden sollten. Allerdings sollten hierzu zusätzliche radiologische Untersuchungen, wie beispielsweise die Handröntgenaufnahme, nur dann durchgeführt werden, wenn diese dem ALARA-Prinzip entsprechen.
The goal of this thesis was to investigate the influence of rotational restriction between individual parts and of the varying electron density in the bridging unit of D B A systems on the exchange interaction 2J, and thus the electronic coupling between a donor state and an acceptor state. A better understanding of how to influence the underlaying spin dynamics in such donor acceptor systems can open up the door to new technologies, such as modern molecular electronics or optoelectronic devices.
Therefore, three series of molecules consisting of a TAA electron donor, a TTC or ATC bridging unit and a PDI electron acceptor were studied. To investigate the influence of rotational restriction on 2J and the electronic coupling, a series of four rotationally hindered triads (chapter 6) was synthesised. The dihedral angle between the TAA and the TTC as well as between the TTC and the PDI was restricted by ortho methyl groups at the phenylene linkers of the connecting ends to the TTC bridge, producing a twist around the linking single bond which minimises the π overlap. The triads exhibit varying numbers of ortho methyl groups and therefore different degrees of rotational restriction. In order to shine light on the influence of varying electron density on 2J and the electronic coupling, a series of four substituted triptycene triads (chapter 7) was synthesised. The electron density in the TTC bridging unit was varied by electron donating and electron withdrawing groups in 12,13 position of the TTC bridging unit and thus varying its HOMO/LUMO energy. The last series of two anthracene bridge triads (chapter 8) connected both approaches by restricting the rotation with ortho methyl groups and simultaneously by varying the bridge energies.
In order to obtain the electronic properties, steady state absorption and emission spectra of all triads were investigated (chapter 4). Here, all triads show spectral features associated with the separate absorption bands of TAA and the PDI moiety. The reduced QYs, compared to the unsubstituted PDI acceptor, indicate a non radiative quenching mechanism in all triads. The CV data (chapter 5) were used to calculate the energies of possible CSSs and those results were used to assign the CR dynamics into the different Marcus regions. fs TA measurements reveal that all triads form a CSS upon excitation of the PDI moiety. The lifetimes of the involved states and the rate constants were determined by global exponential fits and global target analysis. The CR dynamics upon depopulation of the CSSs were investigated using external magnetic field dependent ns TA spectroscopy. The ns TA maps show that all triads recombine via CRT pathway populating the local 3PDI state in toluene and provided the respective lifetimes. The approximate QYs of triplet formation were determined using actinometry. The magnetic field dependent ns TA data reveal the exchange interaction 2J between singlet and triplet CSS for each triad. Those magnetic field dependent ns TA data in toluene were furthermore treated using a quantum mechanical simulation (done by U.E. Steiner) to extract the rate constants kT and kS for CRT and CRS, respectively. However, the error margins of kS were rather wide. Finally, the electronic couplings between the donor and the acceptor states were obtained by combining the aforementioned experimental results of the rate constants and applying the Bixon Jortner theoretical description of diabatic ET and Andersons perturbative theory of the exchange coupling. Therefore, the experimentally determined values of 2J and the calculated values of kCS and kT were used. The rate constant kS was calculated based on the electronic coupling V1CSS 1S0.
The rotationally hindered triads (chapter 6) show a strong influence of the degree of rotational restriction on the lifetimes and rate constants of the CS processes. The rate constants of CS are increasing with increasing rotational freedom. The magnetic field dependent decay data show that the exchange interactions increase with increasing rotational freedom. Based on the CR dynamics, the calculated electronic couplings of the ET processes reflect the same trend along the series. Here, only singlet couplings turned out to be strongly influenced while the triplet couplings are not. Therefore, this series shows that the ET dynamics of donor acceptor systems can strongly be influenced by restricting the rotational freedom.
In the substituted triptycene triads (chapter 7), decreasing electron density in the bridging unit causes a decrease of the CS rate constants. The magnetic field dependent decay data show that with decreasing electron density in the bridge the exchange interaction decreases. The CR dynamics-based rate constants and the electronic couplings follow the same trend as the exchange interaction. This series shows that varying the HOMO/LUMO levels of the connecting bridge between donor and acceptor strongly influences the ET processes.
In the anthracene bridge triads (chapter 8), the CS process is slow in both triads. The CR was fast in the anthracene triad and is slowed down in the methoxy substituted anthracene bridge triad. The increase of the exchange interaction with increasing electron density in the bridge was more pronounced than in the substituted triptycene triads. Thus, the variation of electron density in the bridge strongly influences the ET processes even though the rotation is restricted.
In this thesis, it was shown that the influence of the rotational hindrance as well as the electron density in a connecting bridge have strong influence on all ET processes and the electronic coupling in donor acceptor systems. These approaches can therefore be used to modify magnetic properties of new materials.
Ende des 19. Jahrhunderts standen sich in Deutschland zwei verschiedene Arten psychiatrischer Institutionen gegenüber, die Anstaltspsychiatrien auf der einen, die universitären psychiatrischen Kliniken auf der anderen Seite. Die psychiatriehistorische Forschung widmete sich überwiegend psychiatrischen Anstalten während Kliniken hier unterrepräsentiert sind. Die vorliegende Arbeit möchte zur historischen Kenntnis universitärer psychiatrischer Einrichtungen beitragen. Hierzu werden die Charakteristika einer psychiatrischen Klinik um 1900 anhand des Beispiels der psychiatrischen Klinik der Universität Würzburg betrachtet. Der Fokus liegt hierbei neben Lage und Aufbau der Klinik sowie deren Personal auf den drei Bereichen Patient*innen, Forschung und Lehre.
This work presents the first ILT observations of high redshift blazars and their study in terms of jet evolution, morphology, and interaction with the surrounding medium. Each of these represents a highly topical area of astronomywith a large number of open questions. To better understand Active Galactic Nuclei (AGN) and their fundamental inner workings, new techniques are needed to exploit the full potential of the next generation of radio interferometers. Some of these tools are presented here and applied to one of the latest generation of software radio telescopes. A major focus of the studies presented is on the unification model, where the observed blazars are discussed for their properties to be rotated counterparts of Fanaroff-Riley Class II (FR-II) radio galaxies, when classified as Flat Spectrum Radio Quasars (FSRQs). In addition, multiwavelength information has been included in the analysis. Both studies are feasibility studies that will serve as a basis for future similar studies. The characteristics discussed and their interpretation do not allow conclusions to be drawn for their respective populations. However, by applying them to a larger number of targets, population studies will be possible. The first chapters introduce the necessary topics, AGN, principles of radio observations and ILT, in the necessary depth to provide the reader with a solid knowledge base. They are particularly important for understanding the current limits and influences of uncertainties in the observation, calibration and imaging process. But they also shed light on realistic future improvements. A particular focus is on the development and evolution of the LOw-Frequency ARray (LOFAR)-Very Long Baseline Interferometry (VLBI) pipeline. With the tools at hand, the first study addresses the high redshift blazar S5 0836+710 $(z=2.218)$, which has been observed at various wavelengths and resolutions. It has a disrupted one-sided jet with an associated extended region further out. Despite the excellent wavelength coverage, only the additional ILT observations provided a complete picture of the source. With the data, the extended region could be classified as a hotspot moving at slightly relativistic speeds.. With the ILT data it was also possible to extract the flux of the core region of the AGN, and in projection to reveal the mixed counter-hotspot behind it. This also allowed constraints on jet parameters and environmental properties to be modelled, which were previously inconclusive. Technically, this study shows that the ILT can be used as an effective VLBI array for compact sources with small angular scales. However, the detection of faint components beyond redshifts of $z=2$ may require the capabilities of the Square Kilometre Array (SKA) to provide a significant number of detections to enable statistical conclusions. The second study uses a much improved calibration pipeline to analyse the high redshift blazar GB1508+5714 $(z=4.30)$. The ILT data revealed a previously unseen component in the eastern direction. A spectral index map was generated from the Karl G. Jansky Very Large Array (VLA) data, showing spectral index values of $-1.2_{-0.2}^{+0.4}$ for the western component, steeper than $-1.1$ for the eastern region, and $0.023 \pm 0.007$ for the core. Using the information provided by the ILT observation, as well as multi-wavelength information from other observations ranging from the long radio wavelengths to the $\gamma$ regime, four models were developed to interpret the observed flux with different emission origins. This also allowed to test a proposed interaction channel of the electrons provided by the jet, to cool off via inverse compton scattering with the Cosmic Microwave Background (CMB) photons, rather than by the usual synchrotron emission. This is referred to as cmb quenching in the literature, which could be shown in the study, to be necessary in any case. Finally, one of the four models was considered in which the hotspots in the detected components are unresolved and mixed by the lobe emission, with the X-ray emission coming from the lobes and partially mixed by the bright core region. The results of this preferred model are consistent with hotspots in a state of equipartition and lobes almost so. The study shows that high redshift blazars can be studied with the ILT, and expanding the sample of high redshift blazars resolved at multiple frequencies will allow a statistical study of the population. Finally, this work successfully demonstrates the powerful capabilities of the ILT to address questions that were previously inaccessible. The current state of the LOFAR-VLBI pipeline, when properly executed, allows work on the most challenging objects and will only improve in the future. In particular, this gives a glimpse of the possibilities that SKA will bring to astronomy.
Die vorliegende Arbeit thematisiert die Aktivität des autonomen Nervensystems im Vergleich vor versus nach bariatrischer Operation bei ProbandInnen mit morbider Adipositas. Wir untersuchten, ob die Operation und der damit einhergehende Gewichtsverlust drei Monate nach dem bariatrischen Eingriff zu einer Veränderung der Aktivität des autonomen Nervensystems im thorakalen und im motorischen/peripheren Kompartiment führt. Als Parameter dienen für das thorakale Kompartiment die Herzfrequenzvariabilität und für das periphere/motorische Kompartiment vaskuläre (lnRHI und AI) und sudomotorische (Schweißvolumen, Antwortlatenz) Parameter.
Unsere Ergebnisse im thorakalen Kompartiment zeigen einen Anstieg der Herzfrequenzvariabilität 3 Monate nach bariatrischer Operation. Wir schließen uns daher der Hypothese an, die mit morbider Adipositas assoziierte Erhöhung der sympathischen Aktivität im thorakalen Kompartiment könne durch bariatrische Operationen reversibel sein. Im peripheren/motorischen Kompartiment können wir keine eindeutige Veränderung der Aktivität des autonomen Nervensystems vor versus nach bariatrischer Operation beobachten. Andere Studien konnten hierzu deutlichere Ergebnisse erheben, die ebenfalls eine erhöhte sympathische Aktivität im motorischen Kompartiment zeigten, welche nach bariatrischer Operation reversibel war.
Insgesamt können wir die These einer autonomen Imbalance bei Adipositas sowie einer Verringerung der sympathischen Aktivität im thorakalen Kompartiment nach bariatrischer Operation unterstützen. Die Veränderungen im autonomen Nervensystem leisten möglicherweise einen Beitrag zur Verbesserung der kardiovaskulären Gesundheit und der metabolischen Situation nach der bariatrischen Operation.
The expression of the MYC proto-oncogene is elevated in a large proportion of patients with pancreatic ductal adenocarcinoma (PDAC). Previous findings in PDAC have shown that this increased MYC expression mediates immune evasion and promotes S-phase progression. How these functions are mediated and whether a downstream factor of MYC mediates these functions has remained elusive. Recent studies identifying the MYC interactome revealed a complex network of interaction partners, highlighting the need to identify the oncogenic pathway of MYC in an unbiased manner.
In this work, we have shown that MYC ensures genomic stability during S-phase and prevents transcription-replication conflicts. Depletion of MYC and inhibition of ATR kinase showed a synergistic effect to induce DNA damage. A targeted siRNA screen targeting downstream factors of MYC revealed that PAF1c is required for DNA repair and S-phase progression. Recruitment of PAF1c to RNAPII was shown to be MYC dependent. PAF1c was shown to be largely dispensable for cell proliferation and regulation of MYC target genes.
Depletion of CTR9, a subunit of PAF1c, caused strong tumor regression in a pancreatic ductal adenocarcinoma model, with long-term survival in a subset of mice. This effect was not due to induction of DNA damage, but to restoration of tumor immune surveillance.
Depletion of PAF1c resulted in the release of RNAPII with transcription elongation factors, including SPT6, from the bodies of long genes, promoting full-length transcription of short genes. This resulted in the downregulation of long DNA repair genes and the concomitant upregulation of short genes, including MHC class I genes. These data demonstrate that a balance between long and short gene transcription is essential for tumor progression and that interference with PAF1c levels shifts this balance toward a tumor-suppressive transcriptional program. It also directly links MYC-mediated S-phase progression to immune evasion. Unlike MYC, PAF1c has a stable, known folded structure; therefore, the development of a small molecule targeting PAF1c may disrupt the immune evasive function of MYC while sparing its physiological functions in cellular growth.
Zahlreiche Studien zeigten, dass perioperatives Bridging der oralen Antikoagulation zu einem erhöhten Blutungsrisiko führt. Ursache hierfür könnte eine zu aggressive Herangehensweise bezüglich der Dosierung des Bridgings sein. Daher war das Ziel dieser Arbeit herauszufinden, ob ein Risiko-adjustiertes Bridging-Schema in der elektiven Allgemein- und Viszeralchirurgie zu einem geringeren Auftreten von postoperativen Blutungsereignissen führt und ob trotzdem ein adäquater Schutz vor thromboembolischen Ereignissen gegeben ist. Hierfür wurde retrospektiv und monozentrisch das Auftreten der genannten postoperativen Ereignisse in zwei Zeiträumen untersucht. Das erste Studienintervall erstreckte sich von Januar 2011 bis Dezember 2014 und spiegelt die Ereignisraten vor der internen Leitlinienänderung wider. Es wurden 263 Personen eingeschlossen. Das zweite Intervall begann im Januar 2017 und endete im Dezember 2019, in diesem wurden 271 Personen untersucht. Zwischen diesen beiden Zeiträumen wurde eine überarbeitete klinikinterne Bridging-Leitlinie etabliert, welche an das individuelle thromboembolische Risiko, Alter, Gewicht und die Nierenfunktion der Patientinnen und Patienten angepasst war. Postoperative Major- (8.4% vs. 4.1%, p=0.039) und Minor-Blutungen (13.7% vs. 6.3%, p=0.004) nahmen im zweiten Intervall signifikant ab, während das thromboembolische Risiko weiterhin niedrig blieb (0.8% vs. 1.1%, p=1). Außerdem zeigte sich, dass es zu keiner signifikanten Zunahme der Mortalität, der Reoperationen, der Länge des postoperativen stationären Aufenthalts oder der Erythrozytenkonzentrat-Transfusionen kam. Die Ergebnisse dieser Arbeit zeigen, dass die differenzierte Bridging-Leitlinie für die Allgemein- und Viszeralchirurgie mit einer signifikant erniedrigten Blutungsrate assoziiert ist und eine Anpassung des Bridgings an die patientenspezifischen Risikofaktoren wichtig ist.
Enterokokken gehören zu den bedeutendsten nosokomialen Keimen. Die Verbreitung von Multiresistenzen bei diesen Keimen stellt das deutsche Gesundheitssystem aufgrund von wenigen verbleibenden Therapieoptionen von Infektionen vor große Probleme. Die KRINKO des Robert-Koch-Instituts empfiehlt als mögliche Präventionsmaßnahme ein regelmäßiges Screening auf Enterokokken mit Vancomycin- bzw. Linezolid-Resistenzen. Ziel dieser Arbeit war es, ein kulturelles Screeningverfahren für Linezolid-resistente Enterokokken (LRE) zu entwickeln und dieses anschließend im Routinescreening des Universitätsklinikums Würzburg zu etablieren. Es wurde ein Verfahren entwickelt, welches sich aus einem Anreicherungsschritt mit 3 mg/l Linezolid versetzter selektiver Enterococcosel-Bouillon und einer anschließenden Subkultivierung auf Linezolid-Enterococcosel-Agar mit 4 mg/l Linezolid zusammensetzt. In einer Simulation von klinischen Bedingungen zeigte sich eine gute Sensitivität und Spezifität. Das entwickelte Screeningverfahren wurde mit einem geringen Sensitivitätsverlust und ohne zusätzliche Belastung für die Patienten in das bestehende Routinescreening für Vancomycin-resistente Enterokokken des Universitätsklinikums Würzburg eingegliedert. Die nachgewiesen LRE zeigten unterschiedliche Resistenzmechanismen, wobei bei dem Großteil der Isolate Resistenzgene nachgewiesen werden konnten. Des Weiteren zeigte sich ein breit gestreuter genetischer Hintergrund. Viele der Isolate gehörten genetischen Gruppen an, welche bisher kaum in hospitalisierten Patienten nachgewiesen wurden. Durch die labortechnische Weiterentwicklung von Screeningverfahren für LRE können diese möglicherweise bald routinemäßig in vielen Kliniken etabliert werden.
Die systolische Ejektionszeit (SET) und die prä-Ejektionszeit (pET) sind Zeitintervalle, die sich zuverlässig mittels transthorakaler Echokardiographie erheben lassen und wichtige Aspekte in der kardialen Leistungsdiagnostik abbilden. Gleichwohl gibt es bislang für diese systolischen Zeitintervalle keine Normwerte. Die vorliegende Arbeit analysierte echokardiographische Daten von 4965 ProbandInnen der STAAB-Studie, einer umfänglich phänotypisierten populationsbasierten Kohortenstudie mit dem Ziel der Erstellung von Normwerten für die systolischen Zeitintervalle sowie der Identifizierung und Quantifizierung ihrer Determinanten mittels multivariable Regressionsanalysen.
Aufgrund der starken Abhängigkeit der SET von der Herzfrequenz wurde die herzfrequenzkorrigierte SETc eingeführt, die in Anlehnung an die QTc-Zeit nach Fridericia berechnet wurde ("SET" /∛("RR-Intervall" )). Die Normwerte wurden anhand der gesunden Untergruppe (definiert durch Abwesenheit von kardiovaskulären Risikofaktoren oder Erkrankungen; N=966) aus STAAB generiert. Dem starken Einfluss von Geschlecht und Alter wurde dabei Rechnung getragen, indem für SET, SETc und pET alters- und geschlechtsspezifische Referenzwerte berechnet wurden. SETc war stark korreliert mit linksventrikulärer Ejektionsfraktion sowie enddiastolischem Volumen und Schlagvolumen. Zudem zeigte sich ein deutlicher Zusammenhang von SETc mit spezifischen Markern der Nachlast (Ea und Ees).
Aus der großen Liste der klinischen Marker, die in STAAB erhoben wurden, ergab sich eine größere Anzahl von Einflussfaktoren. Bedeutsame Determinanten der systolischen Zeitintervalle waren insbesondere das metabolische Syndrom (sowie dessen Komponenten), das Rauchverhalten und die Einnahme von β Blockern.
Die Ergebnisse zeigen, dass die systolischen Zeitintervalle, insbesondere SETc, reliable Informationen über das kardiale Kontraktionsverhalten liefern können. Derzeit werden neue Substanzklassen untersucht, die unter anderem über die Modifizierung von SET wirken sollen. Hier zu nennen sind insbesondere Myosin-Aktivatoren bei Herzinsuffizienz mit reduzierter Pumpfunktion wie zum Beispiel Omecamtiv Mecarbil oder Myosin-Inhibitoren bei Hypertropher Obstruktiver Kardiomyopathie. Die hierzu laufenden Studien betrachten auch die Effekte dieser Medikamente auf die systolischen Zeitintervalle als bedeutsame Surrogate der klinischen Effekte und letztlich der Prognose. Die nun vorliegenden Normwerte dieser Zeitintervalle erlauben es, die pathologisch veränderten Werte bei diesen spezifischen Krankheitsbildern und klinischen Studien besser einzuordnen und zu verstehen.
Trotz stetiger Weiterentwicklung und Verbesserungen in chirurgischen Anastomosetechniken treten postoperative Pankreasfisteln (POPF) in 20 - 25 % der Patienten und Patientinnen als Komplikation nach partieller Pankreatikoduodenektomie (PPD) auf. Kommt es zu einer kombinierten Leckage aus Gallen- und Pankreassekret, wurde in dieser Arbeit die Definition einer komplizierten POPF (CPPF) eingeführt, welche eine seltene, aber schwerwiegende und gefährliche postoperative Komplikation darstellt. Neben einer Relaparotomie kann eine Restpankreatektomie als ultima ratio zur Beherrschung dieser schweren Komplikation notwendig werden, welche mit einer Mortalität von 50 % verbunden ist. Die Internationale Studiengruppe der Pankreaschirurgie (ISGPS) entwickelte ein Klassifikationssystem für POPF, welches auf Abweichungen der üblichen postoperativen Behandlungsstrategie beruht. Jedoch wurden keine spezifischen Behandlungsalgorithmen bzw. Therapiekonzepte, insbesondere im Falle einer CPPF, vorgeschlagen.
In dieser Arbeit soll die therapeutische Effektivität einer perkutanen transhepatischen Cholangiodrainage (PTCD) bei Patienten und Patientinnen mit einer CPPF evaluiert werden. Dazu wurde eine retrospektive Analyse an Patienten und Patientinnen durchgeführt, welche eine CPPF nach PPD entwickelten. Die Patienten und Patientinnen wurden hinsichtlich der gewählten Behandlungsstrategie, des Outcomes, postoperativer Komplikationen nach Clavien-Dindo-Klassifikation, des CCI (Comprehensive Complication Index), der 30- und 90-Tage-Mortalität sowie Restpankreatektomie, postoperativer Arrosionsblutungen und der Hospitalisierungsdauer nach Behandlung einer CPPF analysiert.
Zwischen 2007 und 2018 entwickelten 56 (19,1 %) von insgesamt 293 Patienten und Patientinnen eine relevante POPF (ISGPS Grad B/C) nach einer Pankreaskopfresektion. Darunter wurden 17 Patienten und Patientinnen mit einer komplizierten POPF (CPPF) identifiziert. 11 Patienten und Patientinnen erhielten als Behandlung eine PTCD und sechs Patienten und Patientinnen erhielten eine chirurgisch eingebrachte transhepatische Cholangiodrainage (CTCD) im Rahmen eines Revisionseingriffes. Es wurde keine Restpankreatektomie oder Reoperation nach einer initialen PTCD Therapie notwendig. In 4 von 17 Fällen kam es zu postoperativen Blutungen nach Einbringen einer transhepatischen Cholangiodrainage, der mediane CCI lag bei 44 ± 17,3, die mediane Hospitalisierungsdauer betrug 36 ± 19,2 Tage, die 30-Tage-Mortalität war 0 % und die 90-Tage-Mortalität 17,7 %. Es wurde kein Sterbefall in Verbindung mit einer PTCD beobachtet.
Mit Hilfe dieser Studie kann gezeigt werden, dass eine PTCD eine praktikable, sichere und effektive Behandlungsoption für Patienten und Patientinnen mit einer CPPF bietet. Die Separierung von Galle und Pankreassaft stellt eine neuartige Behandlungsoption in ausgewählten Patienten und Patientinnen mit ausreichend drainierter CPPF nach PPD dar.
Fusobacterium nucleatum is an emerging cancer-associated bacterium belonging to the Fusobacteriota phylum, which is evolutionary distant from all model bacteria. Recent analysis generated global fusobacterial RNA maps, which enabled the discovery of 24 small noncoding RNAs (sRNAs) in F. nucleatum. Notably, the σE-dependent sRNA FoxI and FoxJ act as a posttranscriptional regulator of several cell envelope proteins. The σE-dependent sRNAs in Escherichia coli and Salmonella require the RNA chaperone Hfq for their functions. Intriguingly, F. nucleatum seems to have no homologs of the three common RNA-binding proteins (RBPs) CsrA, Hfq and ProQ. However, it remains unclear if other families of RBPs act in concert with FoxI, FoxJ and other fusobacterial sRNAs.
This work has successfully established a 14-mer capture tagged-sRNA affinity purification procedure initially using 6S RNA as a proof-of-concept. Applying this method to 19 different F. nucleatum sRNAs led to a comprehensive mapping of sRNA-binding proteins in this bacterium. This screen identified a total of 75 proteins significantly enriched across all sRNAs and prominent in ribosomal proteins, uncharacterized proteins and enzymes associated with metabolism. This work further focused on the homologs of two KH domain proteins KhpA and KhpB, which were recently recognized as global RBPs in various Gram-positive bacteria such as Streptococcus pneumoniae, Clostridioides difficile, and Enterococcus faecalis.
Comparative analyses revealed conserved domain composition and gene synteny of KhpA and KhpB across F. nucleatum, S. pneumoniae, C. difficle and E. faecalis, indicating conserved roles of these proteins in bacteria. Further protein-protein interaction assays and global RNA targets profiling demonstrated that KhpA and KhpB form dimers and act together as broad RBPs, binding to sRNAs, mRNAs and tRNAs in F. nucleatum. Further functional characterizations unveiled that KhpA/B are required for the growth of F. nucleatum under nutrient limitation conditions and impact cell morphology. Additionally, the two RBPs also influence global gene expression in F. nucleatum affecting various bacterial physiological processes, including ethanolamine utilization.
In summary, this work established a sRNA-centric approach for screening sRNA-binding proteins in F. nucleatum. Further, the assay could be applied in other non-model organisms and is feasible to screen multiple sRNA baits in parallel for sRNA-interactors. By applying this procedure to nearly all known fusobacterial sRNAs, this work generated an extensive map of sRNA-interacting proteins in F. nucleatum. Molecular and genetic studies identified that KhpA/B act as major RBPs and gene regulators in F. nucleatum, representing important first steps in elucidating key players of post-transcriptional control at the root of the bacterial phylogenetic tree.
Die Arbeit befasst sich mit der Akademisierung und Professionalisierung der Zahnheilkunde, insbesondere der Zahnchirurgie, in Würzburg und Unterfranken im 19. Jahrhundert. Dies wurde insbesondere anhand des zahnchirurgischen Teils der Lehrchirurgischen Instrumentensammlung der Universität Würzburg bzw. des Juliusspitals erforscht. Der zahnchirurgische Teil der Instrumentensammlung war bisher noch nicht erforscht worden und besteht aktuell aus 34+1 Instrumenten, die für diese Arbeit komplett katalogisiert wurden. Für die Entwicklung der Instrumente im Verlauf des 19. Jahrhunderts wurde die Provenienz der Teilsammlung ergründet und diese in den Kontext der Akademisierungsbewegung des 19. Jahrhunderts eingeordnet.
Die Forschung wurde anhand der tatsächlich in der Praxis tätigen und nach und nach akademisch ausgebildeten Personen nachvollzogen. Hierzu wurden neben den Instrumenten als Quelle die Adressbücher der Stadt Würzburg und die Matrikel-, Personal- und Vorlesungsverzeichnisse der Universität Würzburg des gesamten 19. Jahrhunderts systematisch durchgearbeitet. Außerdem wurden Lehrbücher aus dem nichtakademischen zahnchirurigischen Bereich (Bader) mit denen aus dem sich beginnenden akademischen Bereich analysiert. Anhand dieser Forschungsarbeit konnte dargelegt werden, dass die Zahnchirurgie sich analog zur Chiurgie aus dem handwerklichen Bereich abgekoppelt und nach und nach auf verschiedenen Stufen akademisiert hat. Die Zahnchirurgie hat sich "von unten nach oben" durch das Bestreben nichtakademisch ausgebildeter Menschen akademisiert.
In der vorliegenden Dissertationsarbeit wurden Sphäroide aus mesenchymalen Stammzellen aus dem Fettgewebe oder dem Knochenmark mittels der Micromold-Methode hergestellt. Den Sphäroiden wurden entweder Calciumphosphat- oder Calcium-Magnesium-Phosphat-Partikel hinzugefügt. Zum einen sollte überprüft werden, ob die Zugabe von Partikeln die osteogene Differenzierung der Sphäroide fördert und somit zur weiteren Entwicklung von körpereigenem Knochenersatzmaterial in der regenerativen Medizin beiträgt. Zum anderen sollte festgestellt werden, ob eine der beiden Biokeramiken hinsichtlich der osteogenen Differenzierung überlegen ist.
The relation between LV function and cardiac MRI tissue characteristics in separate myocardial segments and their change over time has yet to be explored in myocarditis. Thus, our research aimed to investigate possible associations between global and regional myocardial T1 and T2 times and peak strain in patients with suspected myocarditis.
From 2012 to 2015, 129 patients with clinically suspected myocarditis of the prospective, observational MyoRacer-Trial underwent systematic biventricular EMB at baseline and cardiac MRI at baseline and after three months as a follow-up. We divided the LV myocardium into 17 segments and estimated the segmental myocardial strain using FT. We registered T1 and T2 maps to the cine sequences and transferred the segmentations used for FT to ensure conformity of the myocardial segments. Multi-level multivariable linear mixed effects regression was applied to investigate the relation of segmental myocardial strain to relaxation times and their respective change from baseline to follow-up.
We found a significant improvement in myocardial peak strain from baseline to follow-up (p < 0.001; all p-values given for likelihood ratio tests) and significant associations between higher T1 and T2 times and lower segmental myocardial peak strain (p ranging from < 0.001 to 0.049). E.g., regression coefficient (Reg. coef.) for segmental radial peak strain in short axis view (SRPS_SAX) and T1 time: -1.9, 95% CI (-2.6;-1.2) %/100 ms, p < 0.001. A decrease in T1 and T2 times from baseline to follow-up was also significantly related to a recovery of segmental peak strains (p ranging from < 0.001 to 0.050). E.g., Reg. coef. for SRPS_SAX per ΔT1: -1.8, 95% CI (-2.5;-1.0) %/100 ms, p < 0.001. Moreover, the higher the baseline T1 time, the more substantial the functional recovery from baseline to follow-up (p ranging from 0.004 to 0.042, e.g., for SRPS_SAX: Reg. coef. 1.3, 95% CI (0.4;2.1) %/100 ms, p 0.004). We did not find an effect modification by the presence of myocarditis in the EMB (p > 0.1).
Our cross-sectional and longitudinal analyses provide evidence of dose-dependent correlations between T1 and T2 relaxation times and myocardial peak strain in patients with clinical presentation of myocarditis, regardless of the EMB result. Thus, assessing strain values and mapping relaxation times helps estimate the functional prognosis in patients with clinically suspected myocarditis.
The focus of this thesis is on analysing a linear stochastic partial differential equation (SPDE) with a bounded domain. The first part of the thesis commences with an examination of a one-dimensional SPDE. In this context, we construct estimators for the parameters of a parabolic SPDE based on discrete observations of a solution in time and space on a bounded domain. We establish central limit theorems for a high-frequency asymptotic regime, showing substantially smaller asymptotic variances compared to existing estimation methods. Moreover, asymptotic confidence intervals are directly feasible. Our approach builds upon realized volatilities and their asymptotic illustration as the response of a log-linear model with a spatial explanatory variable. This yields efficient estimators based on realized volatilities with optimal rates of convergence and minimal variances. We demonstrate our results by Monte Carlo simulations.
Extending this framework, we analyse a second-order SPDE model in multiple space dimensions in the second part of this thesis and develop estimators for the parameters of this model based on discrete observations in time and space on a bounded domain. While parameter estimation for one and two spatial dimensions was established in recent literature, this is the first work that generalizes the theory to a general, multi-dimensional framework. Our methodology enables the construction of an oracle estimator for volatility within the underlying model. For proving central limit theorems, we use a high-frequency observation scheme. To showcase our results, we conduct a Monte Carlo simulation, highlighting the advantages of our novel approach in a multi-dimensional context.
Cognition refers to the ability to of animals to acquire, process, store and use vital information from the environment. Cognitive processes are necessary to predict the future and reduce the uncertainty of the ever-changing environment. Classically, research on animal cognition focuses on decisive cognitive tests to determine the capacity of a species by the testing the ability of a few individuals. This approach views variability between these tested key individuals as unwanted noise and is thus often neglected. However, inter-individual variability provides important insights to behavioral plasticity, cognitive specialization and brain modularity. Honey bees Apis mellifera are a robust and traditional model for the study of learning, memory and cognition due to their impressive capabilities and rich behavioral repertoire. In this thesis I have applied a novel view on the learning abilities of honey bees by looking explicitly at individual differences in a variety of learning tasks. Are some individual bees consistently smarter than some of her sisters? If so, will a smart individual always perform good independent of the time, the context and the cognitive requirements or do bees show distinct isolated ‘cognitive modules’?
My thesis presents the first comprehensive investigation of consistent individual differences in the cognitive abilities of honey bees. To speak of an individual as behaving consistently, a crucial step is to test the individual multiple times to examine the repeatability of a behavior. I show that free-flying bees remain consistent in a visual discrimination task for three consecutive days. Successively, I explored individual consistency in cognitive proficiency across tasks involving different sensory modalities, contexts and cognitive requirements. I found that free-flying bees show a cognitive specialization between visual and olfactory learning but remained consistent across a simple discrimination task and a complex concept learning task. I wished to further explore individual consistency with respect to tasks of different cognitive complexity, a question that has never been tackled before in an insect. I thus performed a series of four experiments using either visual or olfactory stimuli and a different training context (free-flying and restrained) and tested bees in a discrimination task, reversal learning and negative patterning. Intriguingly, across all these experiments I evidenced the same results: The bees’ performances were consistent across the discrimination task and reversal learning and negative patterning respectively. No association was evidenced between reversal learning and negative patterning. After establishing the existence of consistent individual differences in the cognitive proficiency of honey bees I wished to determine factors which could underlie these differences. Since genetic components are known to underlie inter-individual variability in learning abilities, I studied the effects of genetics on consistency in cognitive proficiency by contrasting bees originating from either from a hive with a single patriline (low genetic diversity) or with multiple patrilines (high genetic diversity). These two groups of bees showed differences in the patterns of individually correlated performances, indicating a genetic component accounts for consistent cognitive individuality. Another major factor underlying variability in learning performances is the individual responsiveness to sucrose solution and to visual stimuli, as evidenced by many studies on restrained bees showing a positive correlation between responsiveness to task relevant stimuli and learning performances. I thus tested whether these relationships between sucrose/visual responsiveness and learning performances are applicable for free-flying bees. Free-flying bees were again subjected to reversal learning and negative patterning and subsequently tested in the laboratory for their responsiveness to sucrose and to light. There was no evidence of a positive relationship between sucrose/visual responsiveness and neither performances of free-flying bees in an elemental discrimination, reversal learning and negative patterning. These findings indicate that relationships established between responsiveness to task relevant stimuli and learning proficiency established in the laboratory with restrained bees might not hold true for a completely different behavioral context i.e. for free-flying bees in their natural environment.
These results show that the honey bee is an excellent insect model to study consistency in cognitive proficiency and to identify the underlying factors. I mainly discuss the results with respect to the question of brain modularity in insects and the adaptive significance of individuality in cognitive abilities for honey bee colonies. I also provide a proposition of research questions which tie in this theme of consistent cognitive proficiency and could provide fruitful areas for future research.
Kovalente Inhibition stellt einen effektiven Weg dar, die Verweildauer des Liganden innerhalb einer Bindetasche zu erhöhen. In dieser Arbeit wurden theoretische Methoden angewendet, um die Reaktivität und den nichtkovalenten Zustand vor der Reaktion zu modellieren. Im Rahmen einer Fallstudie zu Cathepsin K wurden nichtkovalente Modelle von kovalenten Inhibitoren generiert. Für verschiedene Komplexe aus Cathepsin K und einem kovalent gebundenem Liganden wurde der Zustand vor der Reaktion modelliert und dessen Stabilität im Rahmen einer klassischen MD-Simulation überprüft. Die Stabilität des Warheads in der Bindetasche hing hauptsächlich vom gewählten Protonierungszustand der katalytischen Aminosäuren ab. Für eine Reihe von Inhibitoren der ChlaDUB1 wurde ein Protokoll aus quantenmechanischen Rechnungen genutzt, um die Reaktivität verschiedener Warheads abzuschätzen. Die erhaltenen Aktivierungsenergien korrelierten mit experimentell bestimmten Raten zur Inaktivierung des Enzyms. Im Rahmen eines Wirkstoffdesign-Projektes zur Deubiquitinase USP28 wurden von unpublizierten Kristallstrukturen ausgehend erste Docking-Experimente durchgeführt. Es konnte gezeigt werden, dass ein literaturbekannter Inhibitor von USP28 mit einem Warhead so modifiziert werden kann, dass die reaktive Einheit in direkter Nachbarschaft zu einem Cystein positioniert wird. Für diese Warheads wurden ebenfalls quantenmechanische Rechnungen zur Bestimmung der Aktivierungsenergie durchgeführt. Um besser nachvollziehen zu können, warum bei einem Photoswitch-Inhibitor der Butyrylcholin-Esterase der cis-Zustand des Moleküls besser inhibiert als der trans-Zustand, wurde eine Docking-Studie des Zustandes vor der Reaktion durchgeführt. Es konnte ein qualitatives Modell aufgestellt werden, das zeigt, dass der trans-Zustand aufgrund seiner längeren Form mit wichtigen Aminosäuren am Eingang der Bindungstasche kollidiert.
OSM, ein Vertreter der IL-6-Typ-Zytokine, ist nicht nur für entzündliche, sondern auch für metabolische Prozesse von Bedeutung. Vorarbeiten der Arbeitsgruppe GEIER/HERMANNS und Studien von KOMORI et al. legen protektive Eigenschaften des Zytokins nahe, da Mäuse, denen OSMR fehlte, Charakteristika des metabolischen Syndroms aufwiesen. Zur eingehenderen Untersuchung der von OSM vermittelten Wirkung auf den murinen Lipidstoffwechsel wurden zwei für die NAFLD und Atherosklerose anfällige Modelle herangezogen und jeweils in Gegenwart und Abwesenheit des Osmr studiert: Weibliche Apoe-/-(Osmr-/-) und Ldlr-/-(Osmr-/-) Mäuse wurden über einen Zeitraum von zwölf Wochen mit westlicher Diät gefüttert, wöchentlich gewogen, am Ende der Diät geopfert und geerntet. Wildtypische C57Bl/6-Mäuse erfuhren die gleiche Behandlung und dienten als Referenzgruppe. Im Rahmen des Promotionsprojektes wurden Leberfettgehalt, Serumlipidspiegel, Lipoproteinfraktionen und Stuhllipide von Apoe-deletierten Mäusen bestimmt und mit bereits vorhandenen Daten der Ldlr-/-(Osmr-/-) und wildtypischen Mäuse in Beziehung gesetzt. Expressionsanalysen von am Lipidstoffwechsel beteiligten Genen in Darm-, Leber- und Fettgewebe trugen dazu bei, OSM-abhängige Regulationen aufzudecken.
Ldlr-/- Tiere nahmen unter der Diät exzessiv zu, hatten hohe Serumspiegel an Leptin, Gluco-se und Lipiden, eine Lebersteatose und, begleitet von einer Induktion des Vldlr, erhöhte inflammatorische Marker im visceralen Fettgewebe. Der zusätzliche Knockout des Osmr ging mit einer geringeren Vldlr-Expression im Fettgewebe und einer hepatozytären Induktion von Cyp7a1 einher und resultierte in einem metabolisch günstigeren Phänotyp. Apoe-defiziente Tiere unterschieden sich hinsichtlich ihrer Gewichtszunahme nicht von Ldlr-/-Osmr-/- und C57Bl/6-Mäusen. Überraschenderweise zeigten sich im Serum von Apoe-/-Osmr-/- jedoch gegenüber Apoe-/- Mäusen erhöhte Konzentrationen des Gesamt- und VLDL-Cholesterins, der Triglyceride und freien Fettsäuren. Obwohl Lebern der Apoe-/-Osmr-/- Mäuse geringere Ldlr- und Lrp1-mRNA-Spiegel als die der Apoe-/- Mäuse aufwiesen, hatten sie einen höheren hepatischen Cholesteringehalt. Bei gesteigerter Cpt1a-Expression fiel der hepatische Tri-glyceridgehalt Apoe-deletierter Mäuse geringer aus als in Ldlr-/-(Osmr-/-) und wildtypischen Tieren. Unter Umgehung einer Fettgewebsentzündung präsentierten Apoe-defiziente Mäuse Hinweise einer inflammatorischen Leberschädigung, die pathogenetisch am ehesten mit einer gestörten Cholesterinhomöostase in Verbindung zu bringen war.
Abhängig vom genetischen Hintergrund des Mausmodells hatte OSM schützende oder schädliche Effekte auf den Lipidmetabolismus. Die Ergebnisse der vorliegenden Arbeit betonen die entscheidende Bedeutung entzündlicher, von OSM modulierter Prozesse für den Fettstoffwechsel in Leber- und Fettgewebe. Weiterführende Experimente sind nötig, um die den Beobachtungen zugrunde liegenden molekularen Mechanismen zu entschlüsseln.
FKBP5 stellt im Stresssystem der HPA-Achse ein zentrales Gen bei der Regulation der Sensitivität des Glukokortikoidrezeptors und somit der Reaktion auf Stress dar. Zur Adaptation an Umwelteinflüsse ist es selbst in ein komplexes System von Regulationsmechanismen eingebettet, die unter anderem epigenetische Modifikationen in Form von DNA-Methylierung umfassen. Bisherige Studien legen eine starke Assoziation von FKBP5 zu stressinduzierten psychischen Erkrankungen nahe und weisen auf eine Dysregulation der HPA-Achse als möglichen Pathomechanismus hin. Für die enge klinische Interaktion von Depression und Herzinsuffizienz sowie eine ebenfalls vermutete Rolle der HPA-Achse in der Pathogenese letzterer, könnte FKBP5 daher ein entscheidendes Bindeglied darstellen. Gleichzeitig bietet die Identifikation einer über FKBP5 ausgedrückten Dysregulation der HPA-Achse einen biologischen Befund, der als Marker für das Ansprechen einer antidepressiven Therapie herangezogen werden könnte. Ziel dieser Arbeit war daher die Untersuchung eines möglichen Einflusses regulatorischer Parameter von FKBP5 auf die Herzinsuffizienz sowie eine Prüfung dieser als mögliche Biomarker für einen Erfolg der antidepressiven Therapie.
Dazu wurden Blutproben von ProbandInnen der GEParD- bzw. DaCFail-Studie mit Depression, Herzinsuffizienz sowie gesunde Kontrollen untersucht. Durch Pyrosequenzierung bisulfitkonvertierter DNA erfolgte die Bestimmung der Methylierung regulatorischer CpGs. Die Messung der relativen mRNA-Expression erfolgte durch den Einsatz einer qPCR.
In der Auswertung fand sich keine differentielle mRNA-Expression oder Methylierung zwischen den vier Untersuchungsgruppen. Allerdings reagierten depressive PatientInnen verglichen mit der Kontrollgruppe mit einer geringeren Zunahme der mRNA-Expression als Reaktion auf den mDST. Das Therapieansprechen in der Depressionsgruppe wiederum war mit einer niedrigeren Methylierung auf CpG7 sowie einer höheren mRNA-Expression zu Therapiebeginn assoziiert. Im Behandlungsverlauf führte eine Abnahme der mRNA-Expression bei den Respondern zu einer Annäherung beider Gruppen.
Diese Arbeit konnte keine Hinweise für eine Rolle von FKBP5 in der Pathogenese der Herzinsuffizienz finden. Allerdings zeigten die Befunde zur Regulation des Gens bei Glukokortikoidstimulation eine hohe Konstanz zu vorherigen Ergebnissen. In diesen Kontext reihen sich auch die Ergebnisse für das Therapieansprechen ein, die aufgrund einer Herabregulation der HPA-Achse im Therapieverlauf die Idee einer ursächlichen HPA-Dysregulation in der Gruppe der Responder bekräftigen. Für sich allein genommen lassen sich mRNA-Expression und Methylierung aufgrund mangelnder Sensitivität und Spezifität nicht als Biomarker für das Therapieansprechen einsetzen. Die bisherigen Befunde bestärken aber eine mögliche Rolle in einer Batterie unterschiedlicher Biomarker auf verschiedenen Ebenen, wie Klinik, Psychometrie und Physiologie.
In der Pathogenese der Psoriasis spielen IL 17 und die Plastizität von Tregs zu Th17 Zellen mit Produktion proinflammatorischer Zytokine sowie die möglicherweise reduzierte suppressive Funktion von Tregs eine entscheidende Rolle. Wir versuchten daher in unserer Arbeit einen Überblick über die T Zellverteilung im peripherem Blut bei PSO und HC zu erhalten und die Reaktion der Zellen auf IL 17, anti IL 17 und Secukinumab sowie ein Th 17 induzierendes Milieu im Vergleich von PSO und HC zu evaluieren.
In der Analyse der PBMCs von PSO und HC konnten bei PSO tendenziell weniger inflammatorische Marker, wahrscheinlich aufgrund der niedrigen Krankheitsaktivität und der bereits eingeleiteten medikamentösen Therapie festgestellt werden.
Nach Isolierung der Tregs und Kultivierung konnten bei PSO im Vergleich zu HC erhöhte inflammatorische Marker nachgewiesen werden. Dies kann an der höheren Plastizität von Tregs bei PSO ex vivo ohne den Einfluss einer medikamentösen Therapie hin zu inflammatorischen Zellen.
In den Suppressionsversuchen zeigte sich sowohl bei PSO als auch bei HC unter Th17 Milieu eine verminderte Inhibition der PBMCs durch die autologen Tregs.
Ursächlich hierfür könnte eine Dysregulation der Tregs durch das Th17 Milieu oder eine Auswirkung des Th17-induzierenden Cocktails auf die PBMCs im Sinne einer Effektorresistenz gegenüber den Tregs sein.
Eine Veränderung der Suppression ergab sich für IL 17 oder anti IL 17 nicht. Unter der gleichzeitigen Kultivierung mit Secukinumab und einem Th17 induzierendem Cocktail konnte keine verbesserte Inhibition festgestellt werden.
Insgesamt bestätigt die Arbeit eine Instabilität der Tregs bei PSO mit der Möglichkeit der Plastizität zu Th17 Zellen unter proinflammatorischem Milieu, sowie einen Verlust der Suppressionsfähigkeit durch eine Treg Dysfunktion oder eine erhöhte Effektorresistenz. Für IL 17 oder die Blockade von IL 17 durch monoklonale Antikörper konnte in unserer Studie kein Einfluss festgestellt werden.
Die Blut-Hirn-Schranke (BHS) stellt eine selektiv durchlässige Barriere dar, die den Austausch von Stoffen zwischen Blut und ZNS kontrolliert und so neuroprotektiv wirkt. Sie verhindert allerdings nicht nur die Passage toxischer Metaboliten, sondern verwehrt auch vielen therapeutischen Wirkstoffen den Zugang zum Gehirn. Die Forschung an Methoden zum Erreichen höherer Arzneimittelkonzentrationen im Gehirn ist deshalb essenziell für die Behandlung zerebraler Erkrankungen wie dem zerebral metastasierten Mammakarzinom. Ziel dieser Arbeit war es deshalb, Wirkstoffe zu identifizieren, die die Permeabilität der BHS erhöhen.
Die Substanzdatenbank LO1208 von Sigma-Aldrich wurde im Rahmen eines HTS auf ihre permeabilitätsbeeinflussenden Eigenschaften untersucht. Hierbei konnten
31 Substanzen identifiziert werden, welche die Permeabilität von BLECs um mindestens 50 % erhöhen. Aus diesen wurden 4-Amino-1,8-naphthalimid (PARP-Inhibitor) und GW2974 (TKI) für eine genauere Analyse ausgewählt. Als dritter Wirkstoff wurde Ibuilast (Inhibitor der PDE4, des MIF sowie des Toll-like-Rezeptor-4) untersucht, wobei dieser keine signifikante Veränderung der Permeabilität bewirkt. Die Messung des TEERs und der Permeabilität für Fluorescein bestätigten die Ergebnisse aus dem HTS, welches demnach zukünftig für Permeabilitätstests eingesetzt werden kann. Die Zellviabilität wird durch 4 Amino-1,8-naphthalmid nicht beeinflusst. GW2974 und Ibudilast zeigen bei
500 µM einen toxischen Einfluss auf MCF-7-Zellen. BLECs werden durch 100 µM GW2974 gehemmt. Es konnte gezeigt werden, dass die erhöhte Permeabilität mit einer Veränderung der TJ-Proteinexpression einhergeht. 4-Amino-1,8-naphthalimid senkt die Expression von Occludin auf mRNA- und Proteinebene. GW2974 vermindert zusätzlich die Expression von VE-Cadherin, Claudin-5 und ZO-1. Darüber hinaus wurde die Wirkung auf Effluxpumpen untersucht. Die Ergebnisse der mRNA- und Protein-expression weichen voneinander ab, weshalb eine genauere Untersuchung der Translationsvorgänge sinnvoll erscheint. Glut-1 wird in GW2974 behandelten Zellen überexprimiert, was auf eine erhöhte Aktivität der BLECs hinweist.
GW2974 und 4-Amino-1,8-naphthalimid könnten durch ihre permeabilitätssteigernde Wirkung die Ansprechrate einer systemischen Behandlung von PatientInnen mit einem zerebral metastasierten Mammakarzinom erhöhen und somit ihre Prognose verbessern. Detaillierte Studien zu Kombinationstherapien, den notwendigen Wirkstoff-konzentrationen und eventuellen negativen neurologischen Wirkungen sollten erwogen werden.
Als Systemsprenger menschlicher Ordnungen und Wissenschaftstraditionen finden sich Flechten auf der ganzen Welt und bleiben doch oft unbemerkt. Das macht den Symbionten aus Pilz und Alge in urbanen, ländlichen und digitalen Räumen interessant für eine alltagswissenschaftliche Untersuchung.
Menschliche Geschichten über Flechten sind gefüllt mit Vermutungen, Hörensagen und Assoziationen. Denn augenscheinlich sind Flechten in Deutschland wieder auf dem Vormarsch, sitzen vermehrt in den geliebten Obstbäumen, erobern Denkmäler oder die heimischen Terrassen. Der Pilz im Symbionten wird als Gefahr für Leib und Leben erzählt, die pflanzliche Alge hingegen als Schmuck und natürliches Heilmittel. Ihre Auf- und Abwertung gibt viel über die Ordnungen des Anthropozäns preis.
Kommen die Flechten selbst zu Wort, verfliegen diese kurzweiligen Narrative. Unbemerkt schaffen sie es durch das Bewachsen und Einfärben von Oberflächen, dass Menschen Räume anders lesen. Flechten geben uns nicht nur ein Gefühl von Zeit, die schon vergangen ist, sondern formen redundante Wege von Wasser, Licht und Berührung nach. Anhand der Flechte als ästhetischer Erfahrung wird hier ihre enorme Wirkmacht auf menschliche Alltage herausgearbeitet.
Die Erleichterung von einem körperlichen Schmerzreiz besitzt appetitiven Charakter (Leknes et al., 2008; 2011; Seymour et al., 2005), aktiviert belohnungsassoziierte Hirnstrukturen (Leknes et al., 2011; Leknes & Brock, 2014; Leknes & Tracey, 2008; Navratilova & Porreca, 2014) und fördert durch ihre Konditionierbarkeit als Erleichterungslernen bezeichnete appetitive Lern- und Konditionierungsprozesse (Andreatta et al., 2010, 2012; 2013; 2017; Gerber et al., 2014; Tanimoto et al., 2004; Yarali et al., 2008).
Die vorliegende Arbeit bestätigt das angewandte Versuchsparadigma als valides Modell für Erleichterungslernen im Menschen und zeigt erstmals, dass der appetitive Charakter von Schmerzerleichterung auch in Jugendlichen konditionierbar ist. Erfolgreiches Erleichterungslernen zeigte sich dabei in der untersuchten Stichprobe lediglich auf impliziter, nicht aber auf expliziter, kognitiver Ebene. Dies stützt Thesen und vorherige Forschungsbefunde einer Dualität assoziativen Lernens in ein implizites Lernen, welches vornehmlich subkortikale Strukturen erfordert und ein explizites Lernen, das vorrangig kortikale Strukturen wie den präfrontalen Cortex involviert (Andreatta et al., 2010; Strack & Deutsch, 2004; Williams et al., 2001). Die Beobachtungen einer differenten Furcht- versus Erleichterungs-Extinktion bestärken die Thesen eines diversen neuronalen Hintergrunds dieser beiden Lernformen (Diegelmann et al., 2013; Gerber et al., 2014; Yarali et al., 2009; Yarali & Gerber, 2010). Gleichzeitig werfen die Studienergebnisse die Frage auf, ob und inwiefern im Erleichterungslernen von Jugendlichen Unterschiede zu jenem in Erwachsenen bestehen.
Die Hypothese einer verstärkten Akquisition von Erleichterungslernen bei Jugendlichen mit NSSV im Vergleich zu gesunden Jugendlichen ließ sich in der vorliegenden Studie nicht bestätigen. Somit liefern die Ergebnisse keinen direkten Hinweis darauf, dass ein verstärktes Lernen durch Schmerzerleichterung an der Ätiopathogenese von NSSV beteiligt sein könnte. Die vorliegende Arbeit zeigte vielmehr die Tendenz eines abgeschwächten impliziten Erleichterungslernens bei den Jugendlichen mit NSSV. Die tendenziellen Gruppenunterschiede ließen sich nicht hinreichend durch eine differente aktuelle Stimmungslage oder durch eine unterschiedlich starke Ausprägung aversiver emotionaler Anspannungen oder momentaner Angstaffekte erklären. Innerhalb der Gruppe Jugendlicher mit NSSV zeigte sich auch kein Hinweis darauf, dass der Erfolg von Erleichterungslernen vom Schweregrad des NSSV oder von der aktuellen Einnahme von Antidepressiva abhängig sein könnte. Explorative Analysen ergaben, dass Gruppeneffekte in der vorliegenden Studie womöglich aufgrund einer statistischen Unterschätzung, bedingt durch einen zu geringen Stichprobenumfang, nicht das Signifikanzniveau erreichten und dass Unterschiede im Erleichterungslernen von Jugendlichen mit und ohne NSSV tatsächlich sogar noch stärker ausgeprägt sein könnten. Somit sollte die vorliegende Arbeit als Pilotstudie für zukünftige größer angelegte Studien zu Erleichterungslernen bei NSSV betrachtet werden.
Zukünftige Studien erscheinen insbesondere sinnvoll mit Blick auf die hohe klinische sowie gesellschaftliche Relevanz von NSSV für welches, trotz der hohen Prävalenzen und des deutlich erhöhten Morbiditäts- und Mortalitätsrisikos, zum aktuellen Zeitpunkt noch keine hinreichenden Erklärungsmodelle bestehen. Die Studie bestätigte das Vorliegen eines erhöhten Grades aversiver emotionaler Anspannung in Jugendlichen mit NSSV, welcher zuvor nur an Erwachsenen mit einer BPD untersucht und festgestellt worden war (Niedtfeld et al., 2010; Stiglmayr et al., 2005). Die Abnahme negativer Affekte bei den Jugendlichen mit NSSV im Studienverlauf repliziert die Ergebnisse vorheriger Studien, in denen eine Reduktion selbst-berichteter negativer Affekte durch die Beendigung eines Schmerzreizes beobachtet wurde (Bresin et al., 2010; Bresin & Gordon, 2013). Damit bestärken die Studienergebnisse bestehende Erklärungsmodelle für NSSV, welche eine entscheidende Beteiligung der körperlichen Schmerzen und der Schmerzerleichterung bei der Selbstverletzung an der Affektregulation vermuten. Weiterhin wirft die vorliegende Arbeit die Frage auf, welche Rolle eine veränderte Wahrnehmung von Schmerz und Schmerzerleichterung in der Ätiopathogenese von NSSV einnimmt und wie diese sich auf Lernprozesse auswirkt.
Insgesamt erbrächten weitere Erkenntnisse über den potenziellen Zusammenhang von NSSV und abweichendem Erleichterungslernen ein besseres Verständnis für Mechanismen der Entstehung und Aufrechterhaltung von NSSV und böten zudem möglicherweise Ansätze für neue Therapiemöglichkeiten des Störungsbildes.
p97 uses the energy of ATP hydrolysis to unfold and thereby segregate proteins. It is involved in various cellular processes such as proteasomal degradation, DNA damage repair, autophagy, and endo-lysosomal trafficking. The specificity for these processes is controlled by more than 30 regulatory cofactors.
Interactions of p97 with cofactors and target proteins are known to be highly dynamic and transient. To identify new interaction partners and to uncover novel cellular functions of p97, the interactome of endogenous p97 was determined by using in cellulo crosslinking followed by immunoprecipitation and mass spectrometry. Myoferlin (MYOF) was identified as a novel interactor of p97 and the interaction was validated in reciprocal immunoprecipitation experiments for different cell lines.
The ferlin family member MYOF is a tail-anchored membrane protein containing multiple C2 domains. MYOF is involved in various membrane repair and trafficking processes such as the endocytic recycling of cell surface receptors. The MYOF interactome was determined by mass spectrometry. Among others, the p97 cofactor PLAA, CD71 and Rab14 were identified as common interactors of p97 and MYOF. Immunoprecipitation experiments with PLAA KO cells revealed that the interaction between MYOF and p97 depends on PLAA. Immunofluorescence microscopy showed a co-localization of MYOF with Rab14 and Rab11, which are both involved in endocytic recycling pathways. Furthermore, immunofluoroscence experiments revealed that MYOF and the p97 cofactor PLAA are localized to Rab14- and Rab5-positive endosomal compartments.
Using p97 inhibitors and p97 trapping mutants, the presence of p97 at MYOF-positive and Rab14-positive structures could be demonstrated. Consistent with this finding, the endocytic recycling of transferrin was delayed upon inhibition of p97. Taken together, this work identified MYOF as a novel interactor of p97 and suggests a role for p97 in the recycling of endocytic cargo.