Filtern
Volltext vorhanden
- ja (113)
Gehört zur Bibliographie
- ja (113) (entfernen)
Erscheinungsjahr
- 2024 (113) (entfernen)
Dokumenttyp
Sprache
- Englisch (113) (entfernen)
Schlagworte
- Tissue Engineering (6)
- Maschinelles Lernen (4)
- Entzündung (3)
- Induzierte pluripotente Stammzelle (3)
- Nanopartikel (3)
- Simulation (3)
- Thrombozyt (3)
- 3D-Druck (2)
- Bildgebendes Verfahren (2)
- Bioverfügbarkeit (2)
- Cancer (2)
- Immuntherapie (2)
- Kernspintomografie (2)
- Klimaänderung (2)
- Leistungsbewertung (2)
- Lithium-Ionen-Akkumulator (2)
- LoRaWAN (2)
- Machine Learning (2)
- Metaanalyse (2)
- Platelets (2)
- Quality of Experience (2)
- ROS (2)
- Streaming <Kommunikationstechnik> (2)
- Supramolekulare Chemie (2)
- Topologie (2)
- Topology (2)
- Transplantat-Wirt-Reaktion (2)
- Trust (2)
- Trypanosoma brucei (2)
- Vertrauen (2)
- Video Streaming (2)
- cell biology (2)
- mental health (2)
- translation (2)
- 19F-NMR (1)
- 3D muscle (1)
- 3D printing (1)
- 3D tumour model (1)
- 7 T (1)
- ALS (1)
- ATF4 (1)
- Academic Professionalisation (1)
- Accounts (1)
- Adaptorproteine (1)
- Adhesive Hydrogels (1)
- Adult Education (1)
- Akupunktur (1)
- Albendazol (1)
- Algorithmik (1)
- Algorithmische Geometrie (1)
- Algorithmus (1)
- Alpha (1)
- Alpha power (1)
- Alternative polyadenylation (1)
- Altersunterschied (1)
- Alzheimerkrankheit (1)
- Amyotrophic lateral sclerosis (1)
- Anorganische Polymere (1)
- Antibody (1)
- Approved immunomodulators (1)
- Arabidopsis thaliana (1)
- Arene-Fluoroarene (1)
- Arteriosklerose (1)
- Artery Models (1)
- Arthrose (1)
- Artificial Base Pair (1)
- Arzneimittelüberwachung (1)
- Aspergillus fumigatus (1)
- Atherosclerosis (1)
- AuNPs (1)
- Audiologie (1)
- Autodetachment (1)
- Automation (1)
- Automobilindustrie (1)
- Automorphismengruppe (1)
- Außenhandel (1)
- Avionik (1)
- B0 (1)
- BCA (1)
- Bacteria (1)
- Bakterielle Hirnhautentzündung (1)
- Band Structure (1)
- Bandstruktur (1)
- Barth Syndrome (1)
- Baumphysiologie (1)
- Bayerische Alpen <Motiv> (1)
- Begrenzte Staatlichkeit (1)
- Bericht (1)
- Bias (1)
- Bile (1)
- Bioaccessibility (1)
- Bioavailability (1)
- Biodistribution (1)
- Biofabrication (1)
- Biogenese (1)
- Bioinks (1)
- Biomechanics (1)
- Biopsychosocial (1)
- Biotransformation (1)
- Blut-Liquor-Schranke (1)
- Bodengeografie (1)
- Body movement (1)
- Bone marrow transplantation (1)
- Bor-Stickstoff Bindung (1)
- Brain endothelial cells (1)
- C-type natriuretic peptide (1)
- C.376A>G (p.S126G) (1)
- CAR T cell (1)
- CAR-T cell (1)
- CAR-T-Zell-Therapie (1)
- CD4+ T cell activation (1)
- COVID-19 (1)
- CRISPR/Cas-Methode (1)
- CRISPR/Cas9 (1)
- Cancer Metabolism (1)
- Cardiac MRI (1)
- Cartiage Integration (1)
- Cartilage defect (1)
- Cell culture (1)
- Cell migration (1)
- Chemie (1)
- Chemometric (1)
- China (1)
- Climate change (1)
- Co-culture (1)
- Cognition (1)
- Cognitive Load (1)
- Cognitive processing (1)
- Coherent Multidimensional Spectroscopy (1)
- Coherent Two-dimensional Nanoscopy (1)
- Collaborative Research Center (1)
- Colloidal stability (1)
- Computational Chemistry (1)
- Convolutional Neural Network (1)
- Corti-Organ (1)
- Covid-19 (1)
- Crosslinking (1)
- DCM genetic background (1)
- DExD/H box protein (1)
- DNA (1)
- DNA double-strand breaks (1)
- DNA-Methylation (1)
- DNA-encoded library synthesis (1)
- DNA-tagged amines (1)
- DNS (1)
- DYT-TOR1A (1)
- Darm (1)
- Darmepithel (1)
- Deep learning (1)
- Degradation (1)
- Demotic (1)
- Density Functional Theory (1)
- Depression (1)
- Deubiquitination (1)
- Dichtefunktionalformalismus (1)
- Differential Shannon Entropy (1)
- Dilation (1)
- Diskriminationslernen (1)
- Diskriminationstraining (1)
- Domain Knowledge (1)
- Drama (1)
- Drosophila (1)
- Drug delivery system (DDS) (1)
- Drug form selection (1)
- Dystonie (1)
- Dürrestress (1)
- East Africa (1)
- Ecological Momentary Assessments (1)
- Electrochemical Impedance Spectroscopy (1)
- Electrochemical and Mechanical Interplay (1)
- Electrode (1)
- Elektrochemie (1)
- Elektromobilität (1)
- Elektrophysiologie (1)
- Emotional Affect (1)
- Endobrachyösophagus (1)
- Energiehyperfläche (1)
- Energy Efficiency (1)
- Entropie (1)
- Entzündungsreaktion (1)
- Epidemiologie (1)
- Epigenetik (1)
- Epithelial lineage (1)
- Erwachsenenbildung (1)
- Esophageal adenocarcinoma (1)
- Esophageal disease (1)
- Evolutionspsychologie (1)
- Excipient selection (1)
- Expansion Microscopy (1)
- Experimental Biomedicine (1)
- Explainable AI (1)
- Explainable Artificial Intelligence (1)
- Fabry disease (1)
- Femtosecond Pulse Shaping (1)
- Festelektrolyt (1)
- Festkörperakkumulator (1)
- Festkörperbatterie (1)
- Festkörperelektrolyt (1)
- Fluid-Struktur-Wechselwirkung (1)
- Fluid-structure interaction (1)
- Fluorescence (1)
- Fluoreszenz (1)
- Fluoreszenzmikroskopie (1)
- Flux (1)
- Formulation (1)
- Formulierung (1)
- Fourier-transform spectral interferometry (1)
- FoxO3 (1)
- Fragile Staaten (1)
- Fragility (1)
- Fragilität (1)
- Funktechnik (1)
- Furcht (1)
- GPVI (1)
- Galle <Sekret> (1)
- Gasaustausch (1)
- Gastroesophageal reflux (1)
- Gelenkknorpel (1)
- Generalisierung (1)
- Genexpression (1)
- Geoarchäologie (1)
- Germany (1)
- Geschlecht (1)
- Gesichtsschmerz (1)
- Gewebemodell (1)
- Gold Nanoparticles (1)
- Gold- und Silbernanopartikel (1)
- Graft versus Host disease (1)
- Graft-versus-host disease (1)
- Graphen (1)
- Graphenzeichnen (1)
- HDAC (1)
- HFO-1123 (1)
- Haemophilus influenzae (1)
- Hebamme (1)
- Hematopoietic cell transplantation (1)
- Hemodynamics (1)
- Hemofiltration (1)
- Hereditary spastic paraplegia (1)
- Hereditäre spastsiche Paraplegie (1)
- Herzinfarkt (1)
- Herzmuskelkrankheit (1)
- Heuschrecken (1)
- Hirnendothelzellen (1)
- Histon-Deacetylase (1)
- Hochschule (1)
- Host-Guest Chemistry (1)
- Host-pathogen interaction (1)
- Human-Computer-Interaction (1)
- Hyaliner Knorpel (1)
- Hyrogels (1)
- Hämodynamik (1)
- Hôtel-Dieu de Paris (1)
- IENFD (1)
- ISS <Raumfahrt> (1)
- Idiopathische pulmonale Fibrose (1)
- Immune cells (1)
- Immunmodulation (1)
- In vitro model (1)
- In-Orbit demonstration (1)
- In-vitro-Kultur (1)
- Index (1)
- Indikator (1)
- Induced pluripotent stem cells (1)
- Infektion (1)
- Infektionsmodell (1)
- Infektionsprozess (1)
- Inflamamtion (1)
- Inflammation (1)
- Institutionenökonomie (1)
- Insulinsekretion (1)
- Integrated Defensive States (1)
- Intestinal metaplasia (1)
- Intra-Spacecraft Communication (1)
- Inversion Symmetry Breaking (1)
- Ischemic stroke (1)
- Jasmonate info (1)
- Jugend (1)
- Kaliumkanal (1)
- Katalyse (1)
- Klassische Konditionierung (1)
- Klimawandel (1)
- Kniegelenkarthrose (1)
- Knorpel (1)
- Kognition (1)
- Kognitive Verhaltenstherapie (1)
- Kommunikationstraining (1)
- Konfokale Mikroskopie (1)
- Konjugierte Polymere (1)
- Kraftfahrzeugindustrie (1)
- Krebs <Medizin> (1)
- Kutikula (1)
- Kutikularwachs (1)
- LC-MS/MS (1)
- Langerhans cells (1)
- Lasertherapie (1)
- Learning Settings (1)
- Lebenslauf (1)
- Lehrstoff (1)
- Leptomeningeal cells (1)
- Leptomeningealzellen (1)
- Lists (1)
- Lithium-Ion Battery (1)
- Lithium-Ionen Batterie (1)
- Localization (1)
- Lumineszenz (1)
- Lung squamous cancer cells (1)
- Lungenkrebs (1)
- MND (1)
- MRI (1)
- Magnetoelasticity (1)
- Magnetoelastizität (1)
- Magnetohydrodynamics (1)
- Magnetohydrodynamik (1)
- Measurement (1)
- Mebendazol (1)
- Media Equation (1)
- Media Research (1)
- Medinet Habu (1)
- Medizinprodukt (1)
- Melanom (1)
- Melt Electrowriting (1)
- Melt electrowriting (1)
- Mensch-Maschine-Kommunikation (1)
- Mercapturic acid pathway (1)
- Mercury telluride (1)
- Merocyanine (1)
- Messung (1)
- Metabolismus (1)
- Metakognition (1)
- Methylierung (1)
- Mevalonate Pathway (1)
- Microscopy (1)
- Mikroben (1)
- Mikrobiom <Genetik> (1)
- Mikroklima (1)
- Mikromorphologie (1)
- Mikroorganismus (1)
- Mikropartikel (1)
- Mikroskopie (1)
- Mikrotubuli (1)
- Mikrotubulus (1)
- Minimizing movements (1)
- Mitochondrium (1)
- Mobie EEG (1)
- Mobile Crowdsensing (1)
- Mobile Health (1)
- Model-Agnostic (1)
- Molekül (1)
- Monitoring (1)
- Motoneuron (1)
- Motoneuron-Krankheit (1)
- Motor neuron disease (1)
- Motorische Endplatte (1)
- Mucus (1)
- Myatrophische Lateralsklerose (1)
- Myc (1)
- N6-methyladenosine (m6A) (1)
- NMJ (neuromuscular junction) (1)
- NMR spectroscopy (1)
- NMR-Spektroskopie (1)
- NONO (1)
- NRF2 (1)
- Nachtschattengewächse (1)
- Nahrung (1)
- Nanoparticles (1)
- Natriuretisches Hormon (1)
- Natural walking (1)
- Natürliche Killerzelle (1)
- Navier-Stokes equations (1)
- Navier-Stokes-Gleichung (1)
- Neisseria meningitidis (1)
- Nervendegeneration (1)
- Neue Institutionenökonomik (1)
- Neue Medien (1)
- Neurodegenerative Erkrankung (1)
- Neuromuskuläre Endplatte (1)
- Neuronales Netz (1)
- Neutrophiler Granulozyt (1)
- Nonadiabatic Dynamics (1)
- OXPHOS (1)
- Oberfläche (1)
- Oncoprotein (1)
- Onkoprotein (1)
- Organ of Corti (1)
- Organoid (1)
- Ostraca (1)
- Oxidativer Stress (1)
- Oxytosis (1)
- PLEKHG5 (1)
- PROTACs (1)
- Paläopedologie (1)
- Parameter Quality Oil (1)
- Parkinson-Erkrankung (1)
- Parkinson-Krankheit (1)
- Parkinson’s Disease (1)
- Patch-Clamp-Methode (1)
- Paternal age effect (1)
- Perfusion Bioreactor (1)
- Perianova, Irina (1)
- Periaqueductal gray (1)
- Permeabilität (1)
- Personalisierung (1)
- Personality (1)
- Personalization (1)
- Persönlichkeit (1)
- Peyer's patch (1)
- Pflanzenhydraulik (1)
- Pflanzenökologie (1)
- Pharmacokinetic (1)
- Pharmazeutischer Hilfsstoff (1)
- Phase separation (1)
- Phosphoresence (1)
- Photoemissionselektronenmikroskopie (1)
- Photoswitch (1)
- Plant Biology (1)
- Plant Ecology (1)
- Plant hydraulic (1)
- Platelet-Membranglykoprotein p62 (1)
- Polyadenylierung (1)
- Polyarylenvinylene (1)
- Polygonzüge (1)
- Polyiminoboranes (1)
- Poorly water-soluble drug (1)
- Pornografie (1)
- Posttranslationale Änderung (1)
- Praziquantel (1)
- Primärprevention (1)
- Professionalisierung (1)
- Protein corona (1)
- Psychische Belastung (1)
- Psychische Gesundheit (1)
- Psychological factors (1)
- Psychotherapie (1)
- Quantitative 1H NMR (1)
- Quantum Chemistry (1)
- Quantum Plasmonics (1)
- Quantum Spin Hall (1)
- Quantum dynamics (1)
- Quasiconformal automorphism (1)
- Quasikonforme Abbildung (1)
- Quecksilbertellurid (1)
- RBM20 mutations (1)
- RNA virus (1)
- RNS-Viren (1)
- ROR2 (1)
- Rac1 (1)
- Ratte (1)
- Raumfahrttechnik (1)
- Reaction Mechanism (1)
- Real-Space Obstruction (1)
- Red Fruit Oil (1)
- Relaxation (1)
- Resilienz (1)
- Retinoesäure (1)
- Retinoic acid (1)
- Rheologie (1)
- Ribosome (1)
- Ribosome biogenesis (1)
- Risikoanalyse (1)
- Rothe method (1)
- SOD1 (1)
- SV/TPC1 (1)
- Salmonella typhimurium (1)
- Scherverhalten (1)
- Schlaganfall (1)
- Schleim (1)
- Self-Assembly (1)
- Sex/Gender (1)
- Shear stress indicator (1)
- Shimming (1)
- Silicon-Boron Exchange (1)
- Silizium-Bor Austausch (1)
- Sinneszelle (1)
- Small intestine (1)
- Solanaceae (1)
- Solanum species (1)
- Solubilisation (1)
- Sonderforschungsbereich Transregio 240 (1)
- Spaltöffnung (1)
- Spermium (1)
- Spin-Bahn-Wechselwirkung (1)
- Spin-Orbit Coupling (1)
- Staat (1)
- Stammzellen (1)
- Staphylococcus aureus (1)
- Stat3 (1)
- State (1)
- Stoffwechsel (1)
- Stomaschluss (1)
- Strategisches Management (1)
- Strecken (1)
- Stress (1)
- Stressbewältigung (1)
- Stressreaktion (1)
- Stroma (1)
- Structured Illumination Microscopy (1)
- Störungstheorie (1)
- Supersaturation (1)
- Supramolecular Interaction (1)
- Supraparticle (1)
- Surface (1)
- Symmetrie (1)
- T-Lymphozyt (1)
- T-cell (1)
- THz (1)
- TMD (1)
- TNBC (1)
- TNF (1)
- Targeted therapies (1)
- Tax Receipts (1)
- Telomer <Molekulargenetik> (1)
- Theoretical Chemistry (1)
- Theoretische Chemie (1)
- Thioether-Poly(glycidol)-Beschichtung (1)
- Thrombo-inflammation (1)
- Training von Patienten und Angehörigen (1)
- Transfer (1)
- Transgener Organismus (1)
- Transkriptionsfaktor (1)
- Transpiration <Pflanzen> (1)
- Trauma (1)
- Tree physiology (1)
- Trifluoroethene (1)
- Trockenstress (1)
- Trust Measurement (1)
- Tumor models (1)
- Tumormikroumgebung (1)
- U1 snRNA (1)
- Ubiquitin (1)
- Ugi-azide reaction (1)
- Ultrahigh field (1)
- Ultraweitband (1)
- Umweltpolitik (1)
- Uniform topology (1)
- VSG (1)
- Valscularization (1)
- Variant Surface Glycoprotein (1)
- Vascular system (1)
- Vertisol (1)
- Vicia faba (1)
- Virtual Human (1)
- Virtual Reality (1)
- Virtuelle Realität (1)
- Voice Assistants (1)
- Walking (1)
- West Africa (1)
- Wireless Network (1)
- Wirt-Erreger Interaktion (1)
- Wurmmittel (1)
- XNA (1)
- YTH reader proteins (1)
- Zeitdiskrete Approximation (1)
- Zelle (1)
- Zellkultur (1)
- Zellmigration (1)
- Zentralnervensystem (1)
- Zersetzungsprozess (1)
- aberrant transcripts (1)
- absorption (1)
- adaptivity (1)
- adjustment (1)
- adolescents (1)
- adult development (1)
- agar (1)
- albumin (1)
- algorithms (1)
- all solid-state battery (1)
- alternative intronic polyadenylation (1)
- alveolar gas exchange (1)
- alveolarer Gasaustausch (1)
- atomic mutagenesis (1)
- autoantibody (aAb) (1)
- automotive industry (1)
- belief bias (1)
- biotic interactions (1)
- boron-nitrogen bond (1)
- brain tumor (1)
- bush ecotone (1)
- cancer therapy (1)
- cardiac imaging (1)
- catalysis (1)
- cell therapy (1)
- chemistry (1)
- childbirth (1)
- chronic constriction nerve injury (1)
- chronic pain (1)
- classical conditioning (1)
- clay (1)
- clinical neurology (1)
- clinical phenotype (1)
- cognitive-behavioral therapy (1)
- communication training (1)
- complex regional pain syndrome (1)
- complexity (1)
- conditional Knockout (1)
- contractility (1)
- convolutional neural network (1)
- coupled electron-nuclear motion (1)
- crystallization (1)
- cuticular transpiration barrier (1)
- cuticular waxes (1)
- cyclophane (1)
- data-driven in silico modeling (1)
- datengesteuerte in silico Modellierung (1)
- dead organic material (1)
- decoherence (1)
- decomposition (1)
- deep brain stimulation (1)
- demethylase enzymes FTO and ALKBH5 (1)
- depression (1)
- depressiveness (1)
- dermal B cells (1)
- developmental biology (1)
- diabetes (1)
- differential diagnosis (1)
- dilated cardiomyopathy with ataxia (1)
- dilated cardiomyopathy with ataxia (DCMA) (1)
- discrimination training (1)
- disease model (1)
- dopamine (1)
- drug delivery (1)
- drug formulation (1)
- early cosmology (1)
- early-onset isolated dystonia (1)
- electric mobility (1)
- electrochemistry (1)
- electrophoresis (1)
- elevational gradients (1)
- emissions leakage (1)
- emotional dysregulation (1)
- enantioselectivity (1)
- entropy (1)
- environmental policy (1)
- epidemiology (1)
- etiology (1)
- extraoral intervention (1)
- fear generalization (1)
- fibromyalgia syndrome (1)
- frameshifting (1)
- fruit cuticle (1)
- g-factor (1)
- gene-environmental interaction (1)
- general medicine (1)
- generalized anxiety disorder (1)
- genetics (1)
- genome integrity (1)
- geoarcheology (1)
- globotriaosylceramide (1)
- glycine receptor (GlyR) (1)
- graph drawing (1)
- graphs (1)
- haemophilus influenzae (1)
- haemostasis (1)
- hearing (1)
- hedge index (1)
- hedgerow (1)
- hereditary spastic paraplegia (1)
- heterogeneous firms (1)
- history of midwifery (1)
- host-guest (1)
- human intestinal epithelium (1)
- iPSC (1)
- iPSC-derived CMs (iPSC-CMs) (1)
- immunology (1)
- immunotherapy (1)
- in vitro Testmodell (1)
- in vitro model system of inherited cardiomyopathies (1)
- inclusion (1)
- income inequality (1)
- individual characteristics (1)
- induced pluripotent stem cells (1)
- induced pluripotent stem cells (iPSCs) (1)
- infection (1)
- infectionmodel (1)
- infectionprocess (1)
- inflammation (1)
- information-theoretical (1)
- insulin (1)
- interactive simulation (1)
- interaktive Simulation (1)
- intestinal mucus (1)
- intestinal permeability (1)
- isocyanide multicomponent reactions (1)
- lactams (1)
- leaf cuticle (1)
- lithium-ion battery (1)
- local point-spread function (1)
- luminal Ca2+ sensing sites (1)
- luminale Ca2+-Sensorstellen (1)
- luminescence (1)
- lung cancer (1)
- machine learning (1)
- magnetic resonance imaging (1)
- mast cells (1)
- mechanism (1)
- medical students (1)
- megakaryocytes (1)
- melanoma (1)
- menschliches Darmepithel (1)
- metabolism (1)
- metacognition (1)
- metacognitive activation (1)
- miRNS (1)
- microRNA (1)
- microRNA biogenesis (1)
- microbes (1)
- microbiology (1)
- micromorphology (1)
- microphysiologic 3D tumour model (1)
- midwife (1)
- midwifery (1)
- midwifery education (1)
- midwifery training (1)
- minimum leaf conductance (1)
- mitochondria (1)
- modified inflation (1)
- modified nucleosides (1)
- molecular biology (1)
- molecular biopharmaceutics (1)
- monogenetic cardiomyopathies (1)
- motivated beliefs (1)
- movement disorders (1)
- mucin (1)
- myocardial infarction (1)
- neutrophils (1)
- new institutional economics (1)
- nociceptive Schwann cells (1)
- nonsuicidal self-injury (NSSI) (1)
- nuclear magnetic resonance spectroscopy (1)
- obstetrics (1)
- oculomotor control (1)
- offshoring (1)
- older adults (1)
- pain pattern (1)
- paleopedology (1)
- pancreas (1)
- patient and caregiver education (1)
- perception and action (1)
- peripheral nerve trauma (1)
- permeability (1)
- permeance (1)
- pig (1)
- piperacillin (1)
- piperacillin/tazobactam (1)
- plant-herbivore-interactions (1)
- platelet (1)
- platelets (1)
- polylines (1)
- poor water-soluble drugs (1)
- practice testing (1)
- preschool (1)
- programmed ribosomal frameshifting (1)
- progressive encephalitis with rigidity and myoclonus (PERM) (1)
- prosocial (1)
- prosocial behavior (1)
- prosociality (1)
- protein binding (1)
- protein folding (1)
- psychological interventions (1)
- psychotherapy (1)
- qubit (1)
- qubit interaction (1)
- rRNA processing (1)
- repair and replication (1)
- resolution (1)
- retrieval practice (1)
- ribosome profiling (1)
- saccades (1)
- schistosmiasis (1)
- school (1)
- sedimentology (1)
- semi-natural habitat (1)
- sense of agency (1)
- sensory neurons (1)
- sex differences (1)
- simulation (1)
- skin punch biopsy (1)
- small fiber neuropathy (1)
- social interaction (1)
- soil (1)
- soil-transmitted helminthiases (1)
- solid tumour (1)
- solid-state electrolyte (1)
- stiff-person syndrome (SPS) (1)
- straight-line segments (1)
- strategic management (1)
- stress management (1)
- stress response (1)
- striatum (1)
- stroke (1)
- succession (1)
- suicidality (1)
- systematic review (1)
- tazobactam (1)
- telomere-associated protein (1)
- temporal binding (1)
- testing effect (1)
- theoretical chemistry (1)
- thiol starvation (1)
- thrombo-inflammation (1)
- tissue model (1)
- tissue resident T cells (1)
- transcription factor SPT5 (1)
- transfer (1)
- transition (1)
- transitional shrubland (1)
- true bug (1)
- tumor growth (1)
- tumour microenvironment (1)
- tumour stroma (1)
- ultrafiltration (1)
- vacuole (1)
- variants of unknown significance (1)
- variational network (1)
- water loss (1)
- Ätiologie (1)
- α-Galactosidase A (1)
- β cell (1)
Institut
- Graduate School of Life Sciences (45)
- Theodor-Boveri-Institut für Biowissenschaften (11)
- Institut für Psychologie (8)
- Neurologische Klinik und Poliklinik (8)
- Institut für Pharmazie und Lebensmittelchemie (6)
- Institut für Informatik (5)
- Rudolf-Virchow-Zentrum (5)
- Deutsches Zentrum für Herzinsuffizienz (DZHI) (4)
- Institut für Funktionsmaterialien und Biofabrikation (4)
- Institut für Organische Chemie (4)
Schriftenreihe
Sonstige beteiligte Institutionen
- Department of Mathematical Analysis, Faculty of Mathematics and Physics, Charles University in Prague (1)
- Department of Molecular Biology, University Medical Centre Göttingen, Göttingen 37073, Germany (1)
- Deutsches Krebsforschungszentrum Heidelberg (1)
- Deutsches Zentrum für Luft- und Raumfahrt e.V. (1)
- Eberhard Karls Universität Tübingen (1)
- European Space Agency (1)
- Experimental Physics V, University of Wuerzburg (1)
- Fraunhofer Insitut für Silicatforschung ISC (1)
- Fraunhofer-Institute for Silicate Research ISC (1)
- Göttingen Center for Molecular Biosciences, Georg- August University Göttingen, Göttingen 37077, Germany (1)
EU-Projektnummer / Contract (GA) number
- 759139 (2)
Background
Complex regional pain syndrome (CRPS) develops after injury and is characterized by disproportionate pain, oedema, and functional loss. CRPS has clinical signs of neuropathy as well as neurogenic inflammation. Here, we asked whether skin biopsies could be used to differentiate the contribution of these two systems to ultimately guide therapy. To this end, the cutaneous sensory system including nerve fibres and the recently described nociceptive Schwann cells as well as the cutaneous immune system were analysed.
Methods
We systematically deep-phenotyped CRPS patients and immunolabelled glabrous skin biopsies from the affected ipsilateral and non-affected contralateral finger of 19 acute (< 12 months) and 6 chronic (> 12 months after trauma) CRPS patients as well as 25 sex- and age-matched healthy controls (HC). Murine foot pads harvested one week after sham or chronic constriction injury were immunolabelled to assess intraepidermal Schwann cells.
Results
Intraepidermal Schwann cells were detected in human skin of the finger—but their density was much lower compared to mice. Acute and chronic CRPS patients suffered from moderate to severe CRPS symptoms and corresponding pain. Most patients had CRPS type I in the warm category. Their cutaneous neuroglial complex was completely unaffected despite sensory plus signs, e.g. allodynia and hyperalgesia. Cutaneous innate sentinel immune cells, e.g. mast cells and Langerhans cells, infiltrated or proliferated ipsilaterally independently of each other—but only in acute CRPS. No additional adaptive immune cells, e.g. T cells and plasma cells, infiltrated the skin.
Conclusions
Diagnostic skin punch biopsies could be used to diagnose individual pathophysiology in a very heterogenous disease like acute CRPS to guide tailored treatment in the future. Since numbers of inflammatory cells and pain did not necessarily correlate, more in-depth analysis of individual patients is necessary.
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.
The cystine/glutamate antiporter xCT is an important source of cysteine for cancer cells. Once taken up, cystine is reduced to cysteine and serves as a building block for the synthesis of glutathione, which efficiently protects cells from oxidative damage and prevents ferroptosis. As melanomas are particularly exposed to several sources of oxidative stress, we investigated the biological role of cysteine and glutathione supply by xCT in melanoma. xCT activity was abolished by genetic depletion in the Tyr::CreER; Braf\(^{CA}\); Pten\(^{lox/+}\) melanoma model and by acute cystine withdrawal in melanoma cell lines. Both interventions profoundly impacted melanoma glutathione levels, but they were surprisingly well tolerated by murine melanomas in vivo and by most human melanoma cell lines in vitro. RNA sequencing of human melanoma cells revealed a strong adaptive upregulation of NRF2 and ATF4 pathways, which orchestrated the compensatory upregulation of genes involved in antioxidant defence and de novo cysteine biosynthesis. In addition, the joint activation of ATF4 and NRF2 triggered a phenotypic switch characterized by a reduction of differentiation genes and induction of pro-invasive features, which was also observed after erastin treatment or the inhibition of glutathione synthesis. NRF2 alone was capable of inducing the phenotypic switch in a transient manner. Together, our data show that cystine or glutathione levels regulate the phenotypic plasticity of melanoma cells by elevating ATF4 and NRF2.
Deep Learning (DL) models are trained on a downstream task by feeding (potentially preprocessed) input data through a trainable Neural Network (NN) and updating its parameters to minimize the loss function between the predicted and the desired output. While this general framework has mainly remained unchanged over the years, the architectures of the trainable models have greatly evolved. Even though it is undoubtedly important to choose the right architecture, we argue that it is also beneficial to develop methods that address other components of the training process. We hypothesize that utilizing domain knowledge can be helpful to improve DL models in terms of performance and/or efficiency. Such model-agnostic methods can be applied to any existing or future architecture. Furthermore, the black box nature of DL models motivates the development of techniques to understand their inner workings. Considering the rapid advancement of DL architectures, it is again crucial to develop model-agnostic methods.
In this thesis, we explore six principles that incorporate domain knowledge to understand or improve models. They are applied either on the input or output side of the trainable model. Each principle is applied to at least two DL tasks, leading to task-specific implementations. To understand DL models, we propose to use Generated Input Data coming from a controllable generation process requiring knowledge about the data properties. This way, we can understand the model’s behavior by analyzing how it changes when one specific high-level input feature changes in the generated data. On the output side, Gradient-Based Attribution methods create a gradient at the end of the NN and then propagate it back to the input, indicating which low-level input features have a large influence on the model’s prediction. The resulting input features can be interpreted by humans using domain knowledge.
To improve the trainable model in terms of downstream performance, data and compute efficiency, or robustness to unwanted features, we explore principles that each address one of the training components besides the trainable model. Input Masking and Augmentation directly modifies the training input data, integrating knowledge about the data and its impact on the model’s output. We also explore the use of Feature Extraction using Pretrained Multimodal Models which can be seen as a beneficial preprocessing step to extract useful features. When no training data is available for the downstream task, using such features and domain knowledge expressed in other modalities can result in a Zero-Shot Learning (ZSL) setting, completely eliminating the trainable model. The Weak Label Generation principle produces new desired outputs using knowledge about the labels, giving either a good pretraining or even exclusive training dataset to solve the downstream task. Finally, improving and choosing the right Loss Function is another principle we explore in this thesis. Here, we enrich existing loss functions with knowledge about label interactions or utilize and combine multiple task-specific loss functions in a multitask setting.
We apply the principles to classification, regression, and representation tasks as well as to image and text modalities. We propose, apply, and evaluate existing and novel methods to understand and improve the model. Overall, this thesis introduces and evaluates methods that complement the development and choice of DL model architectures.
Dipolar merocyanines are very attractive supramolecular building blocks, as they combine interesting functional properties with strong, directional intermolecular interactions. The pyridine dioxocyano-pyridine (PYOP) chromophore (Chapter 2.2), used in this thesis, stands out because of its exceptionally high ground state dipole moment (g ~ 17 D), in combination with the option to retain good solubility also in unpolar solvents, by decoration with solubilizing groups.
The reliable binding motif of anti-parallel -stacking due to dipole-dipole interactions has allowed the design of molecular building blocks that form assemblies of predictable geometry. The intense unstructured charge transfer UV/Vis absorption band (eg ~ 10.7 D) is a result of the dominant contribution of the zwitterionic resonance structure which brings the PYOP chromophore just beyond the cyanine limit in solvents of low polarity (c2 = 0.60, 1,4 dioxane). The high sensitivity of the S0 – S1 UV/Vis absorption band to the environment manifests itself in a pronounced negative solvatochromism and strong H-type exciton coupling within -stacked PYOP assemblies. In accordance with the classical molecular exciton theory, an increasing hypsochromic shift of the dominant absorption band of these H aggregates can be observed as the stack size increases up to about six chromophores, where it levels out at about max ~ 440 nm (CHCl3). This allows a uniquely simple estimation of the number of interacting chromophores within the self-assembled structure from a single UV/Vis absorption spectrum of an aggregate.
The defined and well investigated PYOP dimer formation was employed in this thesis to probe the applicability and limitations of concentration-, temperature-, and solvent-dependent self-assembly studies (Chapter 3). Straightforward theoretical models to evaluate datasets of concentration-, temperature-, and solvent-dependent UV/Vis absorption by nonlinear regression analysis were derived for the case of dimer formation (Chapter 2.1). Although the dimer model is well known and widely applied in literature, this detailed derivation is helpful to understand assumptions and potential problems of the different approaches for the determination of thermodynamic parameters. This helps to decide on the most appropriate method to analyse a system of interest. In this regard it should be noted that covering a large portion of the self-assembly process with the experimental data is a prerequisite for the accuracy of the analysis. Additionally, many of the insights can also be transferred to other self-assembly systems like supramolecular polymerization or host-guest interactions.
The concentration-dependent analysis is the most straightforward method to investigate self-assembly equilibria. No additional assumptions, besides mass balance and mass action law, are required. Since it includes the least number of parameters (only K, if M/D are known), it is the most, or even only, reliable method, to elucidate the self-assembly mechanism of an unknown system by model comparison. To cover a large concentration range, however, the compound must be soluble enough and generally sample amounts at least in the low mg scale must be available.
The temperature-dependent analysis has the advantage that all thermodynamic parameters G0, H0 and S0 can be obtained from a single sample in one automated measurement. However, the accessible temperature-range is experimentally often quite limited and dependent on the solvent. For systems which do not show the transition from monomer to aggregate in a narrow temperature range, as given for, e.g., cooperative aggregation or processes with a high entropy contribution, often not the entire self-assembly process can be monitored. Furthermore, the assumptions of temperature-independent extinction coefficients of the individual species as well as temperature-independent H0 and S0 must be met. Monte Carlo simulations of data sets demonstrated that even minor changes in experimental data can significantly impact the optimized values for H0 and S0. This is due to the redundancy of these two parameters within the model framework and even small thermochromic effects can significantly influence the results. The G0 value, calculated from H0 and S0, is, however, still rather reliable.
Solvent-dependent studies can often cover the entire self-assembly process from monomeric (agg = 0) to the fully aggregated state (agg = 1). However, for dyes with strong solvatochromic effects, such as the dipolar merocyanines investigated in this thesis, the results are affected. Also, the assumption of a linear relation of the binding energy G0 and the fraction of denaturating solvent f, which is based on linear free energy relationships between G0 and the solvent polarity, can lead to errors. Especially when specific solvent effects are involved.
For the evaluation of experimental data by nonlinear regression, general data analysis software can be used, where user-defined fit models and known parameters can be implemented as desired. Alternatively, multiple specialized programs for analysing self-assembly data are available online. While the latter programs are usually more user-friendly, they have the disadvantage of being a “black box” where only pre-implemented models can be used without the option for the user to adapt models or parameters for a specific system.
In Chapter 3 comprehensive UV/Vis absorption datasets are presented for the dimerization of merocyanine derivative 1 in 1,4-dioxane, which allowed for the first time a direct comparison of the results derived from concentration-, temperature-, and solvent-dependent self-assembly studies.
The results for the binding constant K and corresponding G0 from the concentration- and temperature-dependent analysis were in very good agreement, also in comparison to the results from ITC. For the temperature-dependent analysis, though, multiple datasets of samples with different concentration had to be evaluated simultaneously to cover a meaningful part of the self-assembly process. Furthermore, a significant dependence of the optimized parameters H0 and S0 on the wavelength chosen for the analysis was observed. This can be rationalized by the small thermochromic shifts of both the monomer and the dimer UV/Vis absorption band. The results from the solvent-dependent evaluation showed the largest deviation, as expected for the highly solvatochromic merocyanine dye.
However, even here by evaluation at 491 and 549 nm the deviation for G0 was only 2.5 kJ mol1 (9%) with respect to the results from the concentration-dependent analysis (G0 = 29.1 kJ mol1). Thus, despite the strong solvatochromism of the dipolar chromophore, it can still be considered a reliable method for estimating the binding strength. Furthermore, multiple repetitions of the concentration-, temperature-, and solvent-dependent studies provided insight into the reproducibility of the results and possible sources of experimental errors. In all cases, the deviations of the results were small (G0 < 0.4 kJ mol1) and within the same range as the fit error from the nonlinear regression analysis.
The insights from these studies were an important basis for the in-depth investigation of a more complex supramolecular system in Chapter 4, as a single method is often not enough to capture the full picture of a more complicated self-assembly process. To elucidate the anti-cooperative self-assembly of the chiral merocyanine 2, a combination of multiple techniques had to be applied.
Solvent-dependent UV/Vis absorption studies in CH2Cl2/MCH mixtures showed the step-wise assembly of the merocyanine monomer (max(M) = 549 nm, CH2Cl2) to first a dimer (max(D) = 498 nm, CH2Cl2/MCH 15:85) by dipole-dipole interactions, and then a -stacked higher aggregate (max(H) = 477 nm, MCH), with pronounced H-type coupling.
The thermodynamic evaluation of this data, however, suffered from the severe solvatochromism, especially of the monomeric species (max(M, CH2Cl2) = 549 nm, max(M, MCH) = 596 nm). Therefore, concentration-dependent studies were performed at three different temperatures (298, 323, 353 K) to elucidate the self-assembly mechanism and determine reliable thermodynamic parameters. The studies at elevated temperatures were hereby necessary, to obtain experimental data over a larger agg--range. Due to the pronounced difference in the thermodynamic driving force for dimerization and higher aggregate formation (KD/K5 = 6500) a concentration range exists in MCH where almost exclusively the dimer species of 2 is present, before further self-assembly by dispersion interactions occurs. Therefore, the data could be evaluated independently for the two self-assembly steps. The self-assembly of dimers into the higher aggregate could not be described by the isodesmic model but was fitted satisfactorily to a pentamer model. This rather small size of about ten -stacked PYOP chromophores was, furthermore, consistently indicated by AFM, VPO and DOSY NMR measurements. Based on 1D and 2D NMR data as well as the strong bisignate CD signal of the higher aggregate in combination with TD-DFT calculations, a P-helical stack is proposed as its structure. The small size can be rationalized by the anti-cooperative self-assembly mechanism and the sterical demand of the solubilizing trialkoxyphenyl and the chiral tetralin substituents. Additionally, the aliphatic shell formed by the solubilizing chains around the polar chromophore stack, can account for the exceptionally high solubility of 2 in MCH (> 15 mg mL1). These combined studies of the self-assembly process enabled the identification of suitable conditions for the investigation of fluorescence properties of the individual aggregate species. Aggregation-induced emission enhancement was observed for the almost non-emissive monomer (Fl(M) = 0.23%), which can be rationalized by the increasing rigidification within the dimer (Fl(D) = 2.3%) and the higher aggregate (Fl(H) = 4.5%). The helical chirality of the PYOP decamer stack, furthermore, gave rise to a strong CPL signal with a large glum value of 0.011.
The important conclusion of this thesis is that the temperature- and solvent-dependent analyses are valid alternatives to the classical concentration-dependent analysis to determine thermodynamic parameters of self-assembly equilibria. Although, for a specific supramolecular system, one approach might be favourable over the others for a variety of reasons. The experimental limitations often demand a combination of techniques to fully elucidate a self-assembly process and to gain insights in the aggregate structure. The anti-cooperative merocyanine self-assembly, which was described here for the first time for the PYOP merocyanine 2, is no exception. Besides the interest in the merocyanine assemblies from a structural and functional point of view, the insights gained from the presented studies can also be transferred to other self-assembly systems and be a guide to find the most appropriate analysis technique.
Theory and simulation of ultrafast autodetachment dynamics and nonradiative relaxation in molecules
(2024)
In this thesis, theoretical approaches for the simulation of electron detachment processes in molecules following vibrational or electronic excitation are developed and applied. These approaches are based on the quantum-classical surface-hopping methodology, in which nuclear motion is treated classically as an ensemble of trajectories in the potential of quantum-mechanically described electronic degrees of freedom.
The slowly activating vacuolar SV/TPC1 channel is ubiquitously expressed in plants and provides a large cation conductance in the vacuolar membrane. Thereby, monovalent (K+, Na+) and in principle also divalent cations, such as Ca2+, can pass through the channel. The SV/TPC1 channel is activated upon membrane depolarization and cytosolic Ca2+ but inhibited by luminal calcium. With respect to the latter, two luminal Ca2+ binding sites (site 1 Asp240/Asp454/Glu528, site 2 Glu239/Asp240/Glu457) were identified to coordinate luminal Ca2+. In this work, the characteristics of the SV/TPC1 channels in terms of regulation and function were further elucidated, focusing on the TPC1s of Arabidopsis thaliana and Vicia faba. For electrophysiological analysis of the role of distinct pore residues for channel gating and luminal Ca2+ sensing, TPC1 channel variants were generated by site-directed mutagenesis and transiently expressed as eGFP/eYFP-fusion constructs in Arabidopsis thaliana mesophyll protoplasts of the TPC1 loss-of-function mutant attpc1-2.
1. As visualized by confocal fluorescence laser-scanning microscopy, all AtTPC1 (WT, E605A/Q, D606N, D607N, E605A/D606N, E605Q/D606N/D607N, E457N/E605A/D606N) and VfTPC1 channel variants (WT, N458E/A607E/ N608D) were correctly targeted to the vacuole membrane.
2. Patch-clamp studies revealed that removal of one of the negative charges at position Glu605 or Asp606 was already sufficient to promote voltage-dependent channel activation with higher voltage sensitivity. The combined neutralization of these residues (E605A/D606N), however, was required to additionally reduce the luminal Ca2+ sensitivity of the AtTPC1 channel, leading to hyperactive AtTPC1 channels. Thus, the residues Glu605/Asp606 are functionally coupled with the voltage sensor of AtTPC1 channel, thereby modulating channel gating, and form a novel luminal Ca2+ sensing site 3 in AtTPC1 at the luminal entrance of the ion transport pathway.
3. Interestingly, this novel luminal Ca2+ sensing site 3 (Glu605/Asp606) and Glu457 from the luminal Ca2+ sensing site 2 of the luminal Ca2+-sensitive AtTPC1 channel were neutralized by either asparagine or alanine in the TPC1 channel from Vicia faba and many other Fabaceae. Moreover, the VfTPC1 was validated to be a hyperactive TPC1 channel with higher tolerance to luminal Ca2+ loads which was in contrast to the AtTPC1 channel features. As a result, VfTPC1 but not AtTPC1 conferred the hyperexcitability of vacuoles. When AtTPC1 was mutated for the three VfTPC1-homologous polymorphic site residues, the AtTPC1 triple mutant (E457N/E605A/D606N) gained VfTPC1-like characteristics. However, when VfTPC1 was mutated for the three AtTPC1-homologous polymorphic site residues, the VfTPC1 triple mutant (N458E/A607E/N608D) still sustained VfTPC1-WT-like features. These findings indicate that the hyperactivity of VfTPC1 is achieved in part by the loss of negatively charged amino acids at positions that - as part of the luminal Ca2+ sensing sites 2 and 3 – are homologous to AtTPC1-Glu457/Glu605/Asp606 and are likely stabilized by other unknown residues or domains.
4.The luminal polymorphic pore residues (Glu605/Asp606 in AtTPC1) apparently do not contribute to the unitary conductance of TPC1. Under symmetrical K+ conditions, a single channel conductance of about 80 pS was determined for AtTPC1 wild type and the AtTPC1 double mutant E605A/D606A. This is in line with the three-fold higher unitary conductance of VfTPC1 (232 pS), which harbors neutral luminal pore residues at the homologous sites to AtTPC1.
In conclusion, by studying TPC1 channel from Arabidopsis thaliana and Vicia faba, the present thesis provides evidence that the natural TPC1 channel variants exhibit differences in voltage gating, luminal Ca2+ sensitivity and luminal Ca2+ binding sites.
Learning accompanies us throughout our lives, from early childhood education through
school, training and university to learning at work. However, much of what we learn is quickly
forgotten. The use of practice tests is a learning strategy that contributes to the acquisition of
sustainable knowledge, i.e. knowledge that is permanently available and can be retrieved when
it is needed. This dissertation first presents findings from previous research on testing in real
educational contexts and discusses theoretically why certain learner or situational
characteristics might influence the effectiveness of the testing effect. Furthermore, a cycle of
three experiments is presented, which were used to investigate whether the positive effect of
practice tests on retention (testing effect) depends on personal or situational characteristics and
also promotes the retention of lecture content that was not directly tested (transfer) in the context
of regular psychology lectures in teacher training courses. In an additional chapter, feedback
from students on the implementation of the study in the classroom context is examined in more
detail. Finally, the results of the three studies are discussed and placed in relation to the theories
presented. The central conclusion from the studies presented is that the testing effect appears to
be a very effective learning strategy that can be used effectively in university teaching and leads
to better learning outcomes regardless of learner characteristics. However, the practice tests
should cover the entire range of relevant content, as transfer effects to non-tested content are
not to be expected.
Exploring and explaining diversity and patterns of stateness is crucial for understanding causes of efficiency, duration, or the collapse of a state. The new Stateness Index (StIx) contributes to the conceptual and analytical debate on stateness and state fragility. StIx is a tool for measuring stateness and state quality since 1950 that includes country-ranking through aggregated and disaggregated data to advance performance comparison and policy analysis. This article first sums up the main theoretical aspects, followed by descriptive results.
Hereditary spastic paraplegias (HSPs) are genetically-determined, neurodegenerative disorders characterized by progressive weakness and spasticity of the lower limbs. Spastic paraplegia type 11 (SPG11) is a complicated form of HSP, which is caused by mutations in the SPG11 gene encoding spatacsin, a protein possibly involved in lysosomal reformation. Based on our previous studies demonstrating that secondary neuroinflammation can be a robust amplifier of various genetically-mediated diseases of both the central and peripheral nervous system, we here test the possibility that neuroinflammation may modify the disease outcome also in a mouse model for SPG11. Spg11-knockout (Spg11-/-) mice develop early walking pattern and behavioral abnormalities, at least partially reflecting motor, and behavioral changes typical for patients. Furthermore, we detected a progressive increase in axonal damage and axonal spheroid formation in the white and grey matter compartments of the central nervous system of Spg11-/- mice. This was accompanied by a concomitant substantial increase of secondary inflammation by cytotoxic CD8+ and CD4+ T-lymphocytes. We here provide evidence that disease-related changes can be ameliorated/delayed by the genetic deletion of the adaptive immune system. Accordingly, we provide evidence that repurposing clinically approved immunomodulators (fingolimod/FTY720 or teriflunomide), that are in use for treatment of multiple sclerosis (MS), also improve disease symptoms in mice, when administered in an early (before neural damage) or late (after/during neural damage) treatment regime.
This work provides strong evidence that immunomodulation can be a therapeutic option for the still untreatable SPG11, including its typical neuropsychological features. This poses the question if inflammation is not only a disease amplifier in SPG11 but can act as a unifying factor also for other genetically mediated disorders of the CNS. If true, this may pave the way to therapeutic options in a wide range of still untreatable, primarily genetic, neurological disorders by repurposing approved immunomodulators.