Refine
Has Fulltext
- yes (862)
Is part of the Bibliography
- yes (862) (remove)
Year of publication
- 2016 (862) (remove)
Document Type
- Journal article (565)
- Doctoral Thesis (199)
- Complete part of issue (50)
- Book article / Book chapter (11)
- Review (9)
- Book (6)
- Preprint (6)
- Master Thesis (4)
- Jahresbericht (3)
- Working Paper (3)
Language
- English (642)
- German (216)
- Multiple languages (3)
- French (1)
Keywords
- University (47)
- Universität (47)
- Wuerzburg (47)
- Wurzburg (47)
- Würzburg (47)
- Drosophila (8)
- Rezension (8)
- Drosophila melanogaster (7)
- inflammation (7)
- vision (7)
- Fabry disease (6)
- Taufliege (6)
- Tissue Engineering (6)
- breast cancer (6)
- phosphorylation (6)
- Bor (5)
- Boron (5)
- Trypanosoma brucei (5)
- genetics (5)
- mice (5)
- DNA (4)
- DNA damage (4)
- DNA methylation (4)
- Diborane (4)
- EEG (4)
- MRSA (4)
- Pain (4)
- Quantenpunkt (4)
- Staphylococcus aureus (4)
- Topologischer Isolator (4)
- chronic kidney disease (4)
- deep brain stimulation (4)
- event-related potentials (4)
- gene expression (4)
- heterochromatin (4)
- immunofluorescence (4)
- lymphocytes (4)
- microRNA (4)
- oxidative stress (4)
- 5-Methylcytosine (3)
- Arabidopsis thaliana (3)
- Cancer genetics (3)
- Deutschland (3)
- Digital Humanities (3)
- Enzyme replacement therapy (3)
- Fußball (3)
- Gefühl (3)
- HIV (3)
- Inhibitor (3)
- Jahresbericht (3)
- LHC (3)
- MRI (3)
- Multiple bonds (3)
- Myelin oligodendrocyte glycoprotein antibodies (MOG-IgG) (3)
- NLO Computations (3)
- Neisseria meningitidis (3)
- Neuromyelitis optica spectrum disorders (NMOSD) (3)
- Optic neuritis (3)
- Stammzelltransplantation (3)
- Transcriptome (3)
- Treatment (3)
- Universität Würzburg (3)
- annual report (3)
- attention (3)
- biodiversity (3)
- biomarker (3)
- c-Fos (3)
- case report (3)
- circadian rhythms (3)
- collagens (3)
- colorectal cancer (3)
- cytokines (3)
- dopamine (3)
- electronic properties and materials (3)
- flow cytometry (3)
- humans (3)
- hyperexpression techniques (3)
- ischemic stroke (3)
- metabolism (3)
- miRNS (3)
- monocytes (3)
- multiple sclerosis (3)
- ovarian cancer (3)
- platelets (3)
- polymers (3)
- prostate cancer (3)
- sRNA (3)
- simulation (3)
- AAA (2)
- ADHD (2)
- ADHS (2)
- Abscisinsäure (2)
- Adult (2)
- Aggregat <Chemie> (2)
- Aminosäuren (2)
- Anionentranslokator (2)
- Antisense RNA (2)
- Anura (2)
- Apoptosis (2)
- Aristeas-Brief (2)
- Aromaticity (2)
- Aspergillus fumigatus (2)
- Autism spectrum disorders (2)
- Autoantibodies (2)
- B cells (2)
- BDNF (2)
- Bayern (2)
- Bildrekonstruktion (2)
- Bioinformatik (2)
- Biradicals (2)
- Bone-marrow-transplantation (2)
- CMV (2)
- Campylobacter jejuni (2)
- Candida albicans (2)
- Carbamate (2)
- Carcinogenicity (2)
- Cell therapy (2)
- Cells (2)
- Central nervous system (2)
- Ceramide (2)
- Cerebrospinal fluid (2)
- Chemotherapy (2)
- China (2)
- Compressed Sensing (2)
- Computer Center University of Wuerzburg (2)
- Cycloaddition (2)
- Cytoskeleton (2)
- DNS (2)
- DNS-Sequenz (2)
- Diabetes mellitus (2)
- Diagnosis (2)
- Digitalisierung (2)
- Dionaea muscipula (2)
- Diseases (2)
- Down syndrome (2)
- Dyes (2)
- Einzelphotonenemission (2)
- Electroencephalographie (2)
- Electrophysiology (2)
- Elektronenspin (2)
- Enzyme induction (2)
- Epigenetik (2)
- Expression (2)
- Fluorescence (2)
- Galerkin-Methode (2)
- Gene (2)
- Genetics research (2)
- Genome (2)
- Genregulation (2)
- Germany (2)
- Geschlechterforschung (2)
- Graphen (2)
- Guidelines (2)
- HKT transporter (2)
- Herzinsuffizienz (2)
- Heterocyclische Verbindungen (2)
- Heterostruktur (2)
- Hitzeschock-Proteine (2)
- Humans (2)
- IAPS (2)
- In vitro (2)
- In-vitro (2)
- Infections (2)
- Inflammation (2)
- Jugend (2)
- Kognition (2)
- Komprimierte Abtastung (2)
- Koordinationslehre (2)
- Kutikula (2)
- Leistungsbewertung (2)
- Lernen (2)
- Lewis-Addukt (2)
- Literaturwissenschaft (2)
- Longitudinally extensive transverse myelitis (LETM) (2)
- MDD (2)
- MEG (2)
- MODIS (2)
- MS (2)
- MYC (2)
- Maus (2)
- Mechanisms (2)
- Merkel cell carcinoma (2)
- Metabolism (2)
- Metakognition (2)
- Mice (2)
- Model (2)
- Molekularbiologie (2)
- Molekularstrahlepitaxie (2)
- Motivation (2)
- Motoneuron (2)
- Multiple sclerosis (2)
- Mädchen (2)
- Mädchenfußball (2)
- Nanodraht (2)
- Neurofilament (2)
- Neurotrophic factors (2)
- Online-Handel (2)
- Optimale Kontrolle (2)
- Optimierung (2)
- Optischer Resonator (2)
- Organische Synthese (2)
- Osteoarthritis (2)
- Outcome survey (2)
- Oxidative stress (2)
- Oxylipine (2)
- P300 (2)
- PET (2)
- PRRT (2)
- Parkinson's disease (2)
- Parkinson’s disease (2)
- Phase-II (2)
- Physikalische Eigenschaft (2)
- Pleistocene (2)
- Posttranskriptionelle Regulation (2)
- Protein (2)
- Psychologie (2)
- Quantendynamik (2)
- RHEED (2)
- RNA interference (2)
- Radio astronomy (2)
- Radioastronomie (2)
- Randomized controlled-trial (2)
- Rastertunnelmikroskopie (2)
- Rehabilitation (2)
- Relapse (2)
- Reproductive toxicity (2)
- Romanistik (2)
- Schlaganfall (2)
- Schmerzforschung (2)
- Schulbuch (2)
- Siliciumkomplexe (2)
- Silicones (2)
- Silylen (2)
- Sol-Gel-Verfahren (2)
- Spermatogenesis (2)
- Spin (2)
- Sprachentwicklung (2)
- Stammzellen (2)
- Stress (2)
- Systems (2)
- Säugling (2)
- TEVC (2)
- Tagesrhythmus (2)
- Text Encoding Initiative (2)
- Textanalyse (2)
- Therapy (2)
- Thyroid cancer (2)
- Transcription (2)
- Validation (2)
- Venusfliegenfalle (2)
- Virtual Reality (2)
- Virtuelle Realität (2)
- absorption spectra (2)
- activation (2)
- adaption (2)
- adenosine (2)
- adipose tissue (2)
- adulthood (2)
- adversity (2)
- animal behavior (2)
- animal model (2)
- antagonist (2)
- apoptosis (2)
- arabidopsis thaliana (2)
- auditory (2)
- bacteria (2)
- behavioral conditioning (2)
- bevacizumab (2)
- biological locomotion (2)
- biology (2)
- biomarkers (2)
- boron (2)
- c-Myc (2)
- cancer treatment (2)
- cardiac hypertrophy (2)
- cardiomyopathy (2)
- change detection (2)
- chemotherapy (2)
- children (2)
- circadian clock (2)
- condensed matter physics (2)
- conspicuous consumption (2)
- crystal structure (2)
- cytotoxicity (2)
- database (2)
- detoxification (2)
- diborenes (2)
- diffusion (2)
- discussion report (2)
- disease (2)
- electroencephalography (2)
- environmental exposure (2)
- enzyme replacement therapy (2)
- epithelial cells (2)
- evaluation (2)
- excited states (2)
- exercise (2)
- extracellular matrix (2)
- eye movements (2)
- fMRI (2)
- fear (2)
- fear conditioning (2)
- fluorescence (2)
- fluorescence microscopy (2)
- gastric cancer (2)
- gene-expression (2)
- genome (2)
- genotype (2)
- heat stress (2)
- honey bees (2)
- host-pathogen interactions (2)
- hydrolysis (2)
- hyperekplexia (2)
- imaging (2)
- in vitro (2)
- in-vivo (2)
- inflammatory bowel disease (2)
- innate immune system (2)
- insect brain (2)
- insulin (2)
- interaction (2)
- intracellular domain (2)
- learning (2)
- leukemia (2)
- lipidomics (2)
- lung cancer (2)
- lyso-Gb3 (2)
- macrophage (2)
- macrophages (2)
- magnetic resonance imaging (2)
- mammalian genomics (2)
- maternal exposure (2)
- memory (2)
- men who have sex with men (2)
- metallic trace elements (2)
- microbiota (2)
- molecular dynamics (2)
- mouse (2)
- mouse models (2)
- movement disorders (2)
- multiple myeloma (2)
- mushroom body (2)
- mutation (2)
- natural language processing (2)
- neuroinflammation (2)
- neuromelanin (2)
- neuronal plasticity (2)
- neurons (2)
- neutrino astronomy (2)
- next generation sequencing (2)
- nonsmooth optimization (2)
- obesity (2)
- optimal control (2)
- pain (2)
- pancreatic cancer (2)
- panic disorder (2)
- parietal hypoactivation (2)
- perception (2)
- photoperiodism (2)
- phylogenetic trees (2)
- plants (2)
- platelet activation (2)
- platelet aggregation (2)
- potassium (2)
- prenatal exposure (2)
- protein expression (2)
- protein-protein interaction (2)
- quantum dots (2)
- quantum mechanics (2)
- quantum physics (2)
- receptor tyrosine kinases (2)
- rehabilitation (2)
- repositories (2)
- retinoblastoma protein (2)
- risk factors (2)
- salinity stress (2)
- schizophrenia (2)
- semiconductors (2)
- sequestration (2)
- serotonin (2)
- serotonin transporter (2)
- sexual selection (2)
- signaling (2)
- sodium (2)
- solar cells (2)
- spintronics (2)
- stem cell transplantation (2)
- stem cells (2)
- surfactants (2)
- sustained fear (2)
- synapses (2)
- temperature (2)
- temporoparietal junction (2)
- tissue engineering (2)
- tool (2)
- topological insulators (2)
- transcription factors (2)
- virtual reality (2)
- virtuelle Realität (2)
- visualization (2)
- walking (2)
- xylem loading (2)
- 12-oxo-phytodienoic acid (1)
- 177Lu (1)
- 18F-FDG PET/CT (1)
- 1H-Magnetic resonance spectroscopy (1H-MRS) (1)
- 1st-line treatment (1)
- 2-Generation reproduction (1)
- 2-loop level (1)
- 2-photon absorption (1)
- 2-step IMRT (1)
- 2015 (1)
- 3D fluoroscopy (1)
- 3D mapping (1)
- 3D object recognition (1)
- 5-Fluorouracil (1)
- 5-HTT knockout mice (1)
- 5-HTTLPR (1)
- 6-percent hydroxyethyl starch (1)
- ABA (1)
- AC Stark effect (1)
- ADR-Richtlinie (1)
- AFM (1)
- AIDS (1)
- AIRWAYS ICPs (1)
- ANTARES telescope (1)
- AP-1 (1)
- ARDS (1)
- ARIA (1)
- ARPES (1)
- AT/RT (1)
- Abschirmung (1)
- Abuse (1)
- Access Structure (1)
- Acetylcholinesterase (1)
- Ackerschmalwand (1)
- Action potentials (1)
- Activation (1)
- Active Galaxies (1)
- Active galactic nucleus (1)
- Acute lymphocytic leukaemia (1)
- Acyrthosiphon pisum (1)
- Ad Philocratem (1)
- Adamantiades-Behçet disease (1)
- Adaptive Governance (1)
- Addendum (1)
- Addison's disease (1)
- Addukt (1)
- Adenoviren (1)
- Adhesion-GPCR (1)
- Adipokine (1)
- Adjuvans (1)
- Adjuvant (1)
- Adolescence (1)
- Adolescents (1)
- Adrenocortial carcinomas (1)
- Adsorptionsisotherme (1)
- Adult patients (1)
- Adultschlupfes (1)
- Affective processing (1)
- Affekt (1)
- Ag-DNA (1)
- Agalsidase beta (1)
- Aggression (1)
- Aggressive behaviour (1)
- Aging (1)
- Agoraphobia (1)
- Agricultural intensification (1)
- Aktive Galaxie (1)
- Aktiver galaktischer Kern (1)
- Akute lymphatische Leukämie (1)
- Akute myeloische Leukämie (1)
- Akzeptanz (1)
- Albrecht von Johansdorf (1)
- Alkyltrialkoxysilan (1)
- Alpha therapy (1)
- Alpha-Aktivität (1)
- Alpha-Galactosidase (1)
- Alpha-synuclein oligomers (1)
- Altern (1)
- Alternative Streitbeilegung (1)
- Alternative test methods (1)
- Altersversorgung (1)
- Altervorsorge (1)
- Alvis (1)
- Alzheimer (1)
- Alzheimer disease (1)
- Alzheimer's disease (1)
- Alzheimerkrankheit (1)
- Alzheimers disease (1)
- Alzheimers-disease (1)
- Alzheimer’s disease (1)
- Ameisenoogenese (1)
- Amino acids (1)
- Aminosäure (1)
- Amphibians (1)
- Amplification (1)
- Amygdala (1)
- Amyloid-beta oligomers; (1)
- Amyotrophic-lateral-sclerosis (1)
- Anas crecca (1)
- Anderson-Fabry Disease (1)
- Andreas Gryphius: "Ermordete Majestät. Oder Carolus Stuardus" (1)
- Angiopoietin-2 (1)
- Angiopoietin-like 4 (1)
- Angst (1)
- Angsterkrankungen (1)
- Animal models (1)
- Anionenkanal (1)
- Annapurna Conservation Area (1)
- Annotation (1)
- Anorexia nervosa (1)
- Anpassung (1)
- Antibody index (1)
- Antimikrobielle Peptide (1)
- Antisocial behavior (1)
- Antralfollikel (1)
- Anxiety (1)
- Anxiety sensitivity (1)
- Aorta (1)
- Aphthae (1)
- Aquaporin-4 antibodies (AQP4-Ig, NMO-IgG)G (1)
- Aquaporin-4 antibodies (AQP4-IgG) (1)
- Aquaporin-4 antibodies (AQP4-IgG, NMO-IgG) (1)
- Arabidopsis (1)
- Arabidopsis-thaliana (1)
- Arbitrary Lagrangian-Eulerian (1)
- Archaea (1)
- Archaeology (1)
- Archäobotanik (1)
- Archäologie (1)
- Archäometrie (1)
- Aristeas (1)
- Aristeas 〈Epistolographus, ca. v3. Jh.〉 (1)
- Aristeas, Epistolographus : Ad Philocratem (1)
- Aromaten (1)
- Aromatic Systems (1)
- Aromatic-hydrocarbon (1)
- Arthropods (1)
- Arzneimitteldesign (1)
- Arzneimittelforschung (1)
- Assay (1)
- Association (1)
- Astrophysical Jet (1)
- Ataxia (1)
- Atomic force microscopy (1)
- Atrial natriuretic peptide (1)
- Attention Deficit Hyperactivity Disorder (ADHD) (1)
- Auditorischer Kortex (1)
- Aufmerksamkeit (1)
- Aufmerksamkeitsdefizit-Syndrom (1)
- Augmented Reality (1)
- Auktion (1)
- Auskunftsdienst (1)
- Autism (1)
- Autoimmune diseases (1)
- Autoimmunity (1)
- Autoimmunität (1)
- Autoinflammation (1)
- Autonomie (1)
- Autophagie (1)
- Aversive events (1)
- Aversive tension (1)
- Avoidance behavior (1)
- Axon degeneration (1)
- Axon growth (1)
- Axon guidance (1)
- Axonal transport (1)
- Axonschaden (1)
- Azaborinine (1)
- Azathioprine (1)
- B cell (1)
- B-B bond (1)
- B-Lymphozyt (1)
- B-Zellen (1)
- B-cells (1)
- BCL6 (1)
- BDNF Val66Met (1)
- BMP-2 (1)
- BMP-2 delivery (1)
- BRAF (1)
- BRCA1 (1)
- BRCA1/2 (1)
- BRCA2 (1)
- BRENDA (1)
- BSTA (1)
- Babylotse-Plus (1)
- Bacteria (1)
- Bacterial community analysis (1)
- Bacterial meningitis (1)
- Bacterial symbionts (1)
- Bank (1)
- Bankenaufsicht (1)
- Bankenregulierung (1)
- Barkhof criteria (1)
- Barratt Impulsiveness Scale (1)
- Basel III (1)
- Bauchspeicheldrüsenkrebs (1)
- Bavaria (1)
- Bayerische Julius-Maximilians-Universität (Würzburg). Lehrstuhl für Vor- und Frühgeschichtliche Archäologie (1)
- Bee abundance (1)
- Behavior (1)
- Behavioral neuroscience (1)
- Behçet’s disease (1)
- Bericht (1)
- Berry phase (1)
- Beschichtung (1)
- Beschleunigungsgrundsatz (1)
- Beta-Rezeptor (1)
- Beta-catenin (1)
- Betriebliche Altersversorgung (1)
- Beugesehnennaht (1)
- Bewegungsstörung (1)
- Bibel <Esra> (1)
- Bibel <Nehemia> (1)
- Bibel. Exodus (1)
- Bibel. Exodus, 13,17-14,31 (1)
- Bibel. Judit (1)
- Bibel. Judit, 10-13 (1)
- Bibel. Lukasevangelium, 2,25-32 (1)
- Bierhefe (1)
- Big picture (1)
- Biocompatibility (1)
- Biodegradable polymer scaffolds (1)
- Biodiversity assessment (1)
- Biodiversität (1)
- Biogenic (1)
- Biographieforschung (1)
- Biographisches Interview (1)
- Bioinformatic (1)
- Biologischer Abbau (1)
- Biomarker (1)
- Biomaterial (1)
- Bioreaktorplattform (1)
- Bis(amidinato)silylen (1)
- Bis(guanidinato)silylen (1)
- Bis(triethoxysilyl)ethan (1)
- Bis-Tacrine (1)
- Bismutverbindungen (1)
- Blazar (1)
- Blazars (1)
- Blickbewegung (1)
- Blochmannia floridanus (1)
- Blood pressure (1)
- Blut-Hirn-Schranke (1)
- Blutgerinnungsfaktor XII (1)
- Bone disease (1)
- Bone marrow transplantantation (1)
- Bone morphogenetic protein-2 (1)
- Bone tissue engineering (1)
- Borirane (1)
- Boron Chemistry (1)
- Borverbindungen (1)
- Borylenkomplexe (1)
- Borylgruppe (1)
- Borylkomplexe (1)
- Bose gas (1)
- Bose-Fermi (1)
- Bosut-Kultur (1)
- Botulinustoxin (1)
- Bound-states (1)
- Bradyrhizobium (1)
- Bragg-reflection waveguide (1)
- Brain (1)
- Brain Computer Interface (1)
- Brainstem encephalitis (1)
- Brandes, Mark A., 1929-2011 (1)
- Breaking (1)
- Breast cancer (1)
- Breath tests (1)
- Broca (1)
- Bronzezeit (1)
- Brustkrebs (1)
- Burkholderia (1)
- Burkholderia pseudomallei (1)
- Butyrylcholinesterase (1)
- Bürgerliche Gesellschaft (1)
- B‐cell lymphoma (1)
- C2-toxin (1)
- C4bp (1)
- CA19-9 (1)
- CD11b+ myeloid cells (1)
- CD39 (1)
- CD73 (1)
- CD8 (1)
- CDH (1)
- CDH13 Expression (1)
- CDH13 mRNA (1)
- CHIP (1)
- CKD (1)
- CML (1)
- COD movements (1)
- COPD (1)
- CO\(_{2}\) exposure (1)
- CO\(_{2}\) signaling (1)
- CRISPR Cas9 (1)
- CRISPR Cas9 system (1)
- CSF (1)
- CSI (1)
- CSR (1)
- Cadherin (CDH13) (1)
- Cadmiumtellurid (1)
- Calcineurin-NFATsignaling (1)
- Calculus of variations (1)
- Camponotus floridanus (1)
- Canada (1)
- Cancer (1)
- Cancer biology (1)
- Canonical babbling (1)
- Carben (1)
- Carbenoid (1)
- Carbenoide (1)
- Carbon (1)
- Carbonyladdukte der Gruppe 8 (1)
- Carcinoma cells (1)
- Cardiology (1)
- Cardiovascular disease (1)
- Cardiovascular magnetic-resonance (1)
- Case Study Action Research (1)
- Case-Control Studies (1)
- CdTe (1)
- Cell lung canger (1)
- Cell replacement therapy (1)
- Cell reprogramming (1)
- Cell signalling (1)
- Cell-based assays (1)
- Cellular prion protein (1)
- Central hyperactivity (1)
- Central nervous system infection (1)
- Central spin (1)
- Central venous-pressure (1)
- Ceramid-reiche Membrandomänen (1)
- Ceramide-enriched membrane domains (1)
- Cerebellitis (1)
- Cerebral-ischemia (1)
- Cervical cancer (1)
- ChIP-sequencing (1)
- Charcot-Marie-Tooth (1)
- Chelat-Liganden (1)
- Chelatbildner (1)
- Chemerin (1)
- Chemerin processing (1)
- Chemicals (1)
- Chemische Synthese (1)
- Chemistry (1)
- Child Maltreatment (1)
- Child welfare (1)
- Childhood (1)
- Childhood medulloblastoma (1)
- Childrens-cancer (1)
- Chimerism (1)
- Chimärismus (1)
- Chinazoline (1)
- Chinazoliniumverbindungen (1)
- Chinazolinone (1)
- Chlorophyll fluorescence (1)
- Cholinesterase (1)
- Cholinesteraseinhibitor (1)
- Chondrozyten (1)
- Chondrozytentransplantation (1)
- Chordontonal organ (1)
- Christenverfolgung (1)
- Chromatographie (1)
- Chromone (1)
- Chromophor (1)
- Chromophores (1)
- Chromosomes (1)
- Chronic kidney disease (1)
- Chronic neuropathic pain (1)
- Chronic respiratory diseases (1)
- Chronic stress (1)
- Chronischer Schmerz (1)
- Chronistisches Geschichtswerk (1)
- Chronobiologie (1)
- Cimex lectularius (1)
- Circadian clock (1)
- Clinical Genetics (1)
- Clinical practice guidelines (1)
- Clinical remission (1)
- Clinical trial (1)
- Cloud computing (1)
- Cocalodinae (1)
- Cochlear-Implantat (1)
- Codex (1)
- Codierung (1)
- Cognitive Distortions (1)
- Cognitive Therapy (1)
- Coherent two-dimensional Spectroscopy (1)
- Cohort study (1)
- Coleoptera: Chrysomelidae (1)
- Collaboration (1)
- Colony growth (1)
- Color measurement (1)
- Combinatorial Background (1)
- Computer Games (1)
- Computersimulation (1)
- Computerspiel (1)
- Computertomografie (1)
- Conditioning evidence (1)
- Conduct disorder (1)
- Cone Beam CT (1)
- Conference (1)
- Conjugate arc therapy (1)
- Conjugated polymers (1)
- Connectivity (1)
- Construction-Integration-Model (1)
- Context (1)
- Contextual fear (1)
- Contrast-enhanced CT (1)
- Control centrality (1)
- Cooperation (1)
- Copaxone® (1)
- Corona charged aerosol detector (1)
- Coronary artery disease (1)
- Corrigenda (1)
- Cortical plasticity (1)
- Cotransporter 2 inhibition (1)
- Couch tracking (1)
- Coulomb-blockade (1)
- Critically-ill patients (1)
- Crowd sourcing (1)
- Crowdsourcing (1)
- Cruzi (1)
- CsrA (1)
- Cvi-0 (1)
- Cyclic GMP (1)
- Cyclic electron transport (1)
- Cyclo-AMP (1)
- Cyclo-GMP (1)
- Cystic-fibriosis (1)
- Cytokine (1)
- Cytokine GM-CSF (1)
- Cytokine receptors (1)
- Cytokines (1)
- Cytotoxic (1)
- Cytotoxic T lymphocytes (1)
- D313Y genotype (1)
- DAMGO (1)
- DARPA (1)
- DNA Methylation (1)
- DNA binding (1)
- DNA metabolism (1)
- DNA methylation dynamics (1)
- DNA sequencing (1)
- DNA-Methylierung (1)
- DNA-based species delimitation (1)
- DNA-encapsulated silver nanoclusters (1)
- DNS-Bindung (1)
- DNS-Methyltransferase (1)
- DNS-Reparatur (1)
- DNS-Schädigung (1)
- DOTATOC (1)
- DPF3a (1)
- DW-MRI (1)
- DYT1 (1)
- Danio-rerio (1)
- Dark Matter (1)
- Darmflora (1)
- Darmmotilitätsstörung (1)
- Darmwandnervensystem (1)
- Deficit/hyperactivity disorder (1)
- Defäkographie (1)
- Delphi Study (1)
- Dendritic cells (1)
- Densities (1)
- Dentate granule cells (1)
- Design (1)
- Deutschunterricht (1)
- Devic syndrome (1)
- Devic’s syndrome (1)
- Diagnostic accuracy (1)
- Diagnostic approach (1)
- Diagnostische Genauigkeit (1)
- Diboran(4) (1)
- Diboren (1)
- Diborene (1)
- Dichtegewichtung (1)
- Dictyostelium discoideum (1)
- Differential RNA-sequencing (1)
- Differentialgleichungssystem (1)
- Diffusions-MRT (1)
- Diffusionsgewichtete Magnetresonanztomographie (1)
- Digitale Textanalyse (1)
- Digitization (1)
- Diisononyl phthalate (1)
- Dimension 2 (1)
- Dimer-Konfiguration (1)
- Dimere (1)
- Dimere Tacrinverbindungen (1)
- Dimers (1)
- Dionaea-muscipula ellis (1)
- Diplopia Internuclear ophthalmoplegia (INO) (1)
- Discontinuous Galerkin method (1)
- Disease gene prioritization (1)
- Disease genetics (1)
- Disease prevalence (1)
- Distress (1)
- Diversity (1)
- Docking <Chemie> (1)
- Donor-stabilisiertes Silylen (1)
- Doppelaufgabe (1)
- Dorsolateral prefrontal cortex (1)
- Dose reduction (1)
- Double-blind (1)
- Draize eye test (1)
- Drei-Fünf-Halbleiter (1)
- Dried Blood Spots (1)
- Drosha (1)
- Drosophilia (1)
- Drug development (1)
- Drug metabolism (1)
- Drug-free remission (1)
- Dual task (1)
- Dublin-III-Abkommen (1)
- Duchenne muscular dystrophy (1)
- Durchstrahlungselektronenmikroskopie (1)
- Dynamic MR imaging (1)
- Dynamische MR-Bildgebung (1)
- Dystonia (1)
- Dünndarm (1)
- Dünndarmmotilität (1)
- Dünndarmperistaltik (1)
- E3 ligase (1)
- EANM (1)
- EBV (1)
- ECB (1)
- ECD-Spektroskopie (1)
- EDS (1)
- EIP on AHA (1)
- ELISPOT (1)
- ELSP (1)
- ERK (1)
- ESTARFM (1)
- EU‐RHAB Registry (1)
- EZB (1)
- Early posterior negativity (1)
- Early prevention (1)
- Early prevention program (1)
- Eating disorder (1)
- Echtzeitsystem (1)
- Ecological momentary assessment (1)
- Ecologically important traits (1)
- Economic Lot Scheduling Problem (1)
- Edema (1)
- Effectors in plant pathology (1)
- Effektivität (1)
- Ehlers-Danlos syndrome (1)
- Eindringerkennung (1)
- Einkommensteuer (1)
- Einstifttechnik (1)
- Einzelhandelsentwicklung (1)
- Einzelphotonenquelle (1)
- Elective cesarean-section (1)
- Electroencephalography (1)
- Electron Spin Resonance (1)
- Electronic commerce (1)
- Elektroencephalogramm (1)
- Elektrofahrzeug (1)
- Elektronenspinresonanz (1)
- Elektronenstruktur (1)
- Elektronisches Bauelement (1)
- Elektrophysiologie (1)
- Elektrospinning (1)
- Elliptic equations (1)
- Embeddedness (1)
- Embodiment (1)
- Embryonic stem cell (1)
- Emgering Markets (1)
- Emission (1)
- Emissionszertifikate (1)
- Emotion (1)
- Emotion regulation (1)
- Emotional expression (1)
- Emotionen (1)
- Emotionsregulation (1)
- Emotionsverarbeitung (1)
- Empathie (1)
- Enantiomere (1)
- Endorphin (1)
- Endosymbiosen (1)
- Endothelial growth-factor (1)
- Endothelium (1)
- Endothelzelle (1)
- Endothelzellen (1)
- Energieeinsparung (1)
- Energy depletion (1)
- Energy transfer (1)
- Entanglement (1)
- Entente Cordiale (1)
- Enteric nervous system (1)
- Enteric neuropathies (1)
- Enterische Glia (1)
- Enterovirus (1)
- Entscheidungsneutralität (1)
- Entwicklung (1)
- Entwicklungsländer (1)
- Entwicklungspsychologie (1)
- Environment (1)
- Environmental enrichment (1)
- Enzym (1)
- Enzyme inhibitor (1)
- Enzyminhibitor (1)
- Epidemiological study (1)
- Epidemiology (1)
- Epidermal growth-factor (1)
- Epidermis (1)
- Epigenesis (1)
- Epigenetics (1)
- Epigenetische Mechanismen (1)
- Episkin (1)
- Epitaxy (1)
- Epitope (1)
- Ereigniskorreliertes Potential (1)
- Erleben (1)
- Erlernte Hilflosigkeit (1)
- Ernährungstherapie (1)
- Erwachsener (1)
- Erweiterte Realität <Informatik> (1)
- Escherichia coli K1 (1)
- Ethanol (1)
- Europa (1)
- Europarecht (1)
- Europas Scheitern (1)
- European Central Bank (1)
- European Innovation Partnership on Active and Healthy Ageing (1)
- European Organization for Nuclear Research. ATLAS Collaboration (1)
- Europe’s failure (1)
- Europäische Zentralbank (1)
- Evaluation (1)
- Event (1)
- Event-related potential (1)
- Evoked potentials (1)
- Evolution (1)
- Evolutionspsychologie (1)
- Exciton-polariton condensate (1)
- Excitons (1)
- Exercise (1)
- Existenz schwacher Lösungen (1)
- Exosome (1)
- Experiencing (1)
- Experiment (1)
- Expositionstherapie (1)
- Extracorporeal Membrane Oxygenation (1)
- Extrembedingungen (1)
- Extremwertstatistik (1)
- Exziton (1)
- Exzitonen (1)
- Eye gaze (1)
- F-18-FDG PET/CT (1)
- FANCM (1)
- FE (1)
- FGF19 (1)
- FISH-CLEM (1)
- FOLFIRI (1)
- FOLFOX (1)
- FOSL1 (1)
- FP-CIT SPECT (1)
- FRET (1)
- FRET sensors (1)
- FT-IR spectroscopy (1)
- FWGE (1)
- FXIIa inhibitor rHA-Infestin (1)
- FXR (1)
- Fabry cardiomyopathy (1)
- Fabry nephropathy (1)
- Fabry-associated pain (1)
- Faces and scenes (1)
- Facial nerve palsy (1)
- Factor receptor (1)
- Fahrsimulator (1)
- Faktor H (1)
- Familial Alzheimers-disease (1)
- Families (1)
- Farbgebung (1)
- Farbmessung (1)
- Farbstoff (1)
- FeS proteins (1)
- Federal Reserve (1)
- Fehlertoleranz (1)
- Female (1)
- Femtosekundenspektroskopie (1)
- Fermentation (1)
- Fermi liquid (1)
- Ferrite (1)
- Ferrocenophane (1)
- Fertilität (1)
- Festkörperphysik (1)
- Fetal brain development (1)
- Fettgewebe (1)
- Feudvar (1)
- Fibroblastenwachstumsfaktor (1)
- Fibroblasts (1)
- Ficaria calthifolia (1)
- Ficaria verna (1)
- Fiels-effect transistors (1)
- Figurenkonstellation (1)
- Figurennetzwerke (1)
- Finanz- und Wirtschaftskrise (1)
- Finanzkrise (1)
- Fischer 344 rats (1)
- Fish Sex determination (1)
- Flabarin (1)
- Flachfaltbarkeit (1)
- Flash relaxation kinetics (1)
- Flat-foldability (1)
- Flow cytometry (1)
- Fluorescein angiography (1)
- Fluorouracil (1)
- Flächenbedarf (1)
- Flüchtlingskrise (1)
- Focusing (1)
- Foragers (1)
- Forschungsinfrastruktur (1)
- Forschungsparadigma (1)
- Fotokatalyse (1)
- Fourier-transform spectroscopy (1)
- FoxQ2 (1)
- Framework <Informatik> (1)
- Frequency-response areas (1)
- Fresh Freeze Plasma (1)
- Friedrich von Hausen (1)
- Frontal asymmetry (1)
- Frontal cortex (1)
- Fränkischens Schichtstufenland (1)
- Frühe Hilfen (1)
- Functional hydrophilic polymers (1)
- Functionalization (1)
- Fungal (1)
- Fungal host response (1)
- Funktion (1)
- Funktionelle Kernspintomografie (1)
- Funktionentheorie (1)
- Fußballverein (1)
- Förster resonance energy transfer (1)
- G Protein (1)
- G protein coupled receptors (1)
- G-protein coupled receptors (1)
- GABP (1)
- GLA mutation (1)
- GPCR (1)
- GWAS (1)
- GaAs/Luft-Braggspiegel (1)
- GaAsSb (1)
- Galactic Ridge (1)
- Galactosidase-A gene (1)
- Galliumarsenidlaser (1)
- Gambler's Fallacy (1)
- Gamma (1)
- Gasionisationsdetektor (1)
- Gaze perception (1)
- Gedenkschrift (1)
- Gehirn-Computer-Schnittstelle (1)
- Gehirnendothelzellen (1)
- Geistigbehindertenpädagogik (1)
- Geißel <Biologie> (1)
- Gelatine (1)
- Geldmarkt (1)
- Geldpolitik (1)
- Gelernte Hilflosigkeit (1)
- Gen Transfer (1)
- Gene expression profiling (1)
- Gene expression regulation (1)
- Gene-expression (1)
- Genetic (1)
- Genetic regulatory networks (1)
- Genexpression (1)
- Genitoanal region (1)
- Genmutation (1)
- Genom (1)
- Genome assembly (1)
- Genome comparison (1)
- Genome re-annotation (1)
- Genome-wide association studies (1)
- Genomics data sets (1)
- Genotype–phenotype correlations (1)
- Gentechnologie (1)
- Geografikum (1)
- Gerichtete Erstarrung (1)
- Gerichtsstandsvereinbarungen (1)
- German crusade poetry (1)
- Geschlechtsdifferenzierung (1)
- Gesundheitspersonal (1)
- Geteilte Intentionalität (1)
- Gewebekultur (1)
- Gifsy-1 (1)
- Gimbaled tracking (1)
- Glas (1)
- Glasur (1)
- Glatiramer acetate (1)
- Glia (1)
- Glioblastom (1)
- Global Governance (1)
- Globale Optimierung (1)
- Globalisierung (1)
- Glucose metabolism (1)
- Glucose uptake (1)
- Glucosyltransferase (1)
- Glutamatergic synapses (1)
- Glutathione (1)
- GlyR receptors (1)
- Glycaemic control (1)
- Glycinrezeptor (1)
- Glücksspiel (1)
- Golgi (1)
- Gore-Tex (1)
- Gott (1)
- Gott <Motiv> (1)
- Governance (1)
- Graft versus Tumor (1)
- Graft-versus-leukemia (1)
- Graphene (1)
- Graphene nanoribbons (1)
- Graphenzeichnen (1)
- Grenzfläche (1)
- Grenzflächeneigenschaften (1)
- Group B Streptococcus (1)
- Growth; BMP-2 (1)
- Großbank (1)
- Grundschule (1)
- Guanylatcyclase (1)
- Guanylyl cyclase-A (1)
- Guanylyl-Cyclase (1)
- Guideline (1)
- Guillain-Barré-Syndrom (1)
- Guinea pig model (1)
- Gutmotility (1)
- Gα\(_{i1}\), Gα\(_{i2}\) and Gα\(_{i3}\) activation (1)
- H-1-NMR spectroscopy (1)
- HEY repressors (1)
- HFpEF (1)
- HFrEF (1)
- HIV infection (1)
- HIV infections (1)
- HIV neurocognitive impairment (1)
- HIV-1 subtype AG (1)
- HIV-Infektion (1)
- HKT1 (1)
- HMBPP (1)
- HPLC (1)
- HPLC-ECD-Kopplung (1)
- HPLC-ECD-coupling (1)
- HPV (1)
- HRXRD (1)
- Haager Konferenz für Internationales Privatrecht (1)
- Habitats (1)
- Halbleiter (1)
- Halbleiter-Supraleiter-Kontakt (1)
- Haloferax volcanii (1)
- Hamburg (1)
- Hamilton-Jacobi-Differentialgleichung (1)
- Hangstabilität (1)
- Hartmann von Aue (1)
- Hauptgruppen-Chemie (1)
- Head-injury (1)
- Health-care (1)
- Hearing loss (1)
- Hearing-loss (1)
- Heart (1)
- Heart Period (1)
- Helicobacter pylori (1)
- Hellenistisch-jüdische Literatur (1)
- Hemodynamic depression (1)
- Hemoglobin A1C (1)
- Hennighausen (1)
- Hepatitis B (1)
- Hepatitis B virus (1)
- Hepatitis C (1)
- Hermopolis (1)
- Herpes simplex encephalitis (1)
- Herpes simplex virus (1)
- Herz-Lungen-Maschine (1)
- Herzfrequenzvariabilität (1)
- Herzmuskel (1)
- Herzoperation (1)
- Heterocycles (1)
- Heterocyclische Carbene <-N> (1)
- HgTe (1)
- Higgs Boson (1)
- Higgs Mass (1)
- Higgs-boson (1)
- High efficiency (1)
- High performance (1)
- High-dose chemotherapy (1)
- High-energy emission (1)
- High-spontaneous rate (1)
- Highlights Lecture (1)
- Hilfesystem (1)
- Hippocampus (1)
- Hirschsprung disease (1)
- Hirschsprung disease liability (1)
- Histologic grade (1)
- Hochfrequenz-Oszillations-Ventilation (1)
- Hochrisikokarzinom der Prostata (1)
- Hochschuldidaktik (1)
- Hoechst 33342 (1)
- Hoffnungsträger (1)
- Holstein <Rind> (1)
- Homeostatic plasticity (1)
- Homoaromatisches System (1)
- Horizontal transfer (1)
- Hormesis (1)
- Hospitalization (1)
- Host adaptation (1)
- Hot Hand Fallacy (1)
- Hsp90 (1)
- Hueter interval (1)
- Human CDH13 (1)
- Human Physiome (1)
- Human Resource Management (1)
- Human and murine cancer cells (1)
- Human immunodefiency virus (1)
- Human prefrontal cortex (1)
- Hyaliner Gelenkknorpel (1)
- Hybridpolymer (1)
- Hybridpolymere (1)
- Hydrogel (1)
- Hydrogen-peroxide (1)
- Hydrolyse (1)
- Hydroxymethyluracil (1)
- Hymenoptera (1)
- Hyperekplexie (1)
- Hypertext (1)
- Hypertonic saline 7.5-percent (1)
- Hypertrophic cardiomyopathy (1)
- Hypertrophic pyloric-stenosis (1)
- Hypervalentes Molekül (1)
- Hyponatriämie (1)
- Hörrinde (1)
- IBA-1 (1)
- IGRT (1)
- III-V semiconductor quantum dot (1)
- IL-1 beta (1)
- IL-1 blockade (1)
- IL-10 (1)
- IL-12 family (1)
- IMAT (1)
- IMRT (1)
- IPND criteria (1)
- IPP (1)
- ITD (1)
- IVIg (1)
- Identification (1)
- Identifizierungspipeline (1)
- IgE (1)
- IgE sensitazion (1)
- IgG4 (1)
- Illumina Human Exome Bead Chip (1)
- Image interpretation (1)
- Imatinib (1)
- Iminoborane (1)
- Immune tolerance (1)
- Immungene (1)
- Immunmodulation (1)
- Immunocompromised patient (1)
- Immunotherapy (1)
- Immunsuppression (1)
- Immuntherapie (1)
- Imperial Rome (1)
- Impfstoff (1)
- Implantate (1)
- Impurity Profiling (1)
- In Vitro Kontrakturtest (1)
- In vitro skin irritation testing (1)
- In-vivo (1)
- InSAR (1)
- Incomplete contracts (1)
- Incunabula (1)
- Indian muntjac (1)
- Inferior Vena Cava (1)
- Inferior colliculus (1)
- Infinite Optimierung (1)
- Infliximab (1)
- Influenzae type B (1)
- Infomappe (1)
- Information (1)
- Information Integration Theory (1)
- Informationsverarbeitung (1)
- Inhibition (1)
- Inhibitory glycine receptor (1)
- Inkunabel (1)
- Inner hair cell (1)
- Insect hosts (1)
- Insects (1)
- Insolvenz (1)
- Insulating thin films (1)
- Insulator surfaces (1)
- Insulin therapy (1)
- Integrative Institutional Adaptation Assessment Framework (1)
- Intelligent Realtime Interactive System (1)
- Intelligent Virtual Environment (1)
- Intelligent mobile system (1)
- Intensity (1)
- Interactive Tree Of Life (iTOL) (1)
- Interaktive Echtzeitsysteme (1)
- Interaurale Zeitdifferenz (1)
- Interband cascade lasers (1)
- Interbankenmarkt (1)
- Interconnectedness (1)
- Interferon (1)
- Interferon beta (1)
- Interferonsignal (1)
- Interglacial (1)
- Interglazial (1)
- Interleukin IL-6 (1)
- Intermediate filaments (1)
- Internal transcription start site (1)
- International consensus diagnostic criteria for neuromyelitis optica spectrum disorders (1)
- Internationale Kapitalbewegung (1)
- Internet (1)
- Internet der Dinge (1)
- Internet of Things (1)
- Intervention (1)
- Interview (1)
- Intestinal pseudoobstruction (1)
- Intracellular domain (1)
- Intracellular virulence (1)
- Intractable nausea and vomiting (1)
- Intravascular coagulation (1)
- Intrinsische Gerinnungskaskade (1)
- Invasion (1)
- Invasive Aspergillosis (1)
- Invasive Mykosen bei immunsupprimierten Patienten (1)
- Invasive fungal-infections (1)
- Investitionsentscheidung (1)
- Investitionsverhalten (1)
- Ionenkanal (1)
- Iran (1)
- Islamic glazes (1)
- Islamische Kunst (1)
- Islamische Staaten (1)
- IsrK (1)
- JR11 (1)
- Jak kinases (1)
- Janus kinase (1)
- Jasmonate (1)
- Jasmonate perception (1)
- Jasmonic acid (1)
- Jean Monnet (1)
- Joint ownership (1)
- Josephson effect (1)
- Josephson-Kontakt (1)
- Joubert syndrome (1)
- Judgment (1)
- Judgments of Learning (1)
- Judith und Holofernes (1)
- Julius-Maximilians-Universität Würzburg (1)
- Julius-Maximilians-Universität Würzburg. Rechenzentrum (1)
- Jurkat T cells (1)
- Jurkat cells (1)
- Justizgewährleistungsanspruch (1)
- K2–K model (1)
- KAT/HAT (1)
- KLT (1)
- KT-1000 (1)
- Kallikrein-Kinin-System (1)
- Kanonisches Babbeln (1)
- Kapitalbewegung (1)
- Karyotyp (1)
- Katalyse (1)
- Kennlinie (1)
- Kenyon cells (1)
- Keramik (1)
- Kern-Schale-Struktur (1)
- Kernhülle (1)
- Kernproteine (1)
- Kernspintomografie (1)
- Ketoacyl-ACP-Synthase <beta-> (1)
- Ketoacyl-ACP-synthase (1)
- Kidney function (1)
- Kiesler, Reinhard (1)
- Kinase signaling (1)
- Kinderschlaf (1)
- Kinderschutz (1)
- Kindheit (1)
- Kleinkind (1)
- Kleinsatellit (1)
- Kleinwuchs (1)
- Klimawandel (1)
- Klimaänderung (1)
- Kniegelenk (1)
- Knielaxizität (1)
- Kniestabilitätsmessung (1)
- Knochen (1)
- Knochenheilung (1)
- Knock-Out <Molekulargenetik> (1)
- Knockdown (1)
- Knorpel (1)
- Knorpelrekonstruktion (1)
- Knorpelzelle (1)
- Knowledge Representation Layer (1)
- Kognitive Belastung (1)
- Kognitiver Prozess (1)
- Kohlberg (1)
- Kokultur (1)
- Kommunikation (1)
- Kommunikationsverhalten (1)
- Komplement <Immunologie> (1)
- Komplex-Chemie (1)
- Komplexe (1)
- Kompositschicht (1)
- Konjugate (1)
- Konsumentenpsychologie (1)
- Kontinuitätsgleichung (1)
- Kooperation (1)
- Koordinationsverbindung (1)
- Koronarchirurgie (1)
- Korrelation (1)
- Kortikobasales Syndrom (1)
- Kostengünstigkeit (1)
- Krankheit (1)
- Kreuzband (1)
- Kreuzbandriss (1)
- Kreuzung (1)
- Kriegspolitik (1)
- Kriegsvorbereitung (1)
- Kristallstruktur (1)
- Kritische Lebensereignisse (1)
- Kurzzeitphysik (1)
- Kutikularwachs (1)
- Körperselbstgefühl (1)
- Körperwahrnehmung (1)
- Künstliche Samenalterung (1)
- L. reuteri (1)
- LASP1 (1)
- LASP1 (LIM and SH3 Protein 1) (1)
- LASP1 (LIM und SH3 Protein 1) (1)
- LED (1)
- LIN-5 (1)
- LINC complex (1)
- LITAF (1)
- LOFAR (1)
- LPS (1)
- Lachsartige <Familie> (1)
- Lacking neurofilaments (1)
- Lactatdehydrogenase (1)
- Lactated ringers solution (1)
- Ladungstransfer (1)
- Lag time (1)
- Landau-Niveau (1)
- Landsat (1)
- Landschaftsentwicklung (1)
- Large T antigen (1)
- Large multicenter ADHD (1)
- Laserablation (1)
- Latin America (1)
- Law on Dispute Resolution for Consumers (VSBG) (1)
- Leaderless transcript (1)
- Leadership (1)
- Learned Helplessness (1)
- Lebensereignisforschung (1)
- Lebenslauf (1)
- Lebensqualität (1)
- Lectins (1)
- Legionella pneumophila (1)
- Legitimitätsdefizit (1)
- Lehrerhandreichung (1)
- Leistungsdiagnostik (1)
- Leistungsmessung (1)
- Leistungsmotivation (1)
- Leistungsvorhersage (1)
- Lepidoptera (1)
- Lernerfolg (1)
- Letter of Aristeas (1)
- Lexikographie (1)
- Licht-Materie-Wechselwirkung (1)
- Life-event-Forschung (1)
- Light Supersymmetric Particle (1)
- Light-emitting diodes (1)
- Lipid (1)
- Lipid metabolism (1)
- Liposomal amphotericin-B (1)
- Lipoxygenase (1)
- Lipoxygenase 6 (1)
- Liquid-crystalline (1)
- Liver cirrhosis (1)
- Lizenzvergabe (1)
- Localized states (1)
- Locomotor activity (1)
- Locus (1)
- Long-range order (1)
- Longitudinally extensive transverse myelitis (1)
- Losgröße (1)
- Lossequenzenplanung (1)
- Lossequenzproblem (1)
- Low-dose acyclovir (1)
- LpxC inhibitors (1)
- Lungenentzündung (1)
- Luxembourg (1)
- Luzindol Ileus (1)
- Lynx lynx (1)
- Lyoplant (1)
- Längsschnittuntersuchung (1)
- Löss (1)
- MACC1 (1)
- MACVIA (1)
- MAG3 (1)
- MAPK pathway (1)
- MBE (1)
- MDSC (1)
- MDSCs (1)
- MHC class I chain-related protein (1)
- MITE (1)
- MIZ1 (1)
- MLC tracking (1)
- MMP (Matrix-Metalloproteasen) (1)
- MMP (Matrix-Metalloproteases) (1)
- MMQ cells (1)
- MOG-IgG (1)
- MPACT (1)
- MPH (1)
- MPK12 (1)
- MR (1)
- MRI criteria (1)
- MSSM (1)
- MU-M (1)
- MYCN (1)
- Macrophage (1)
- Magnetic Resonance Imaging (1)
- Magnetic resonance imaging (1)
- Magnetische Wechselwirkung (1)
- Magnetoelastizität (1)
- Magnetpartikelbildgebung (1)
- Major abdominal surgery (1)
- Makropropositionen (1)
- Makrostruktur (1)
- Makrozyklus (1)
- Male breast cancer (1)
- Male intromittent organ (1)
- Malignant melanoma (1)
- Maligne Hyperthermie (1)
- Management (1)
- Mandibular condyle (1)
- Mandibular continuity defects (1)
- Manifestation (1)
- Manual responses (1)
- Marcophage-infectivity-potentiator-Protein (1)
- Marcus inverted region (1)
- Marginal zone lymphomas (1)
- Marginalien (1)
- Marginalzonen-Lymphome (1)
- Marine Le Pen (1)
- Mark A. Brandes (1)
- Marrow stromal cells (1)
- Mass (1)
- Massenbewegungen (1)
- Mast cells (1)
- Mathematical modeling (1)
- Mathematics Achievement (1)
- Mathematikbücher (1)
- Mathematikleistung (1)
- Mathematikunterricht (1)
- Mathematische Modellierung (1)
- Matrix (1)
- Matrix-Metalloproteasen (1)
- McDonald criteria (1)
- Mechanochemie (1)
- Mechanorezeptor (1)
- Mechanosensation (1)
- Mediation (1)
- Medical image reconstruction (1)
- Medical overuse (1)
- Medical students (1)
- Medicalization (1)
- Medien (1)
- Medienpsychologie (1)
- Medulloblastoma (1)
- Meerschweinchen (1)
- Mehrfachbindung (1)
- Mehrfachtätigkeit (1)
- Mehrschichtsystem (1)
- Meiosis (1)
- Melanom (1)
- Melanoma B16 (1)
- Melanoma Maintenance (1)
- Melatonin (1)
- Mellitus (1)
- Meningococcal serogroup C (1)
- Meningococci (1)
- Meningoencephalitis (1)
- Mensch (1)
- Menschen (1)
- Mesenchymal stem cells (1)
- Mesenchymal stem/stromal cells (1)
- Mesenchymal transition (1)
- Mesenchymale Stammzelle (1)
- Mesocestoides corti (1)
- Messenger RNA (1)
- Meta-barcoding (1)
- Metacognitive Knowledge (1)
- Metagenom (1)
- Metakognitives Wissen (1)
- Metallcarbonyle (1)
- Metallische Oberflächen (1)
- Metalloberfläche (1)
- Metallocene (1)
- Metallocenes (1)
- Metalloproteasen (1)
- Metallorganische Polymere (1)
- Methicillin resistant Staphylococcus aureus (1)
- Methodological quality (1)
- Methotrexate (1)
- Methylation (1)
- Methylierung (1)
- Methylome (1)
- Methylphenidat (1)
- MgAl LDH (1)
- Microcavity (1)
- Microenvironment (1)
- Microorganisms (1)
- Microtubules (1)
- Mid-infrared photoluminescence (1)
- Midline (1)
- Migros Sanal Market (1)
- Mikrokavität (1)
- Mikromagnetismus (1)
- Mikromorphologie (1)
- Mikrooptik (1)
- Mikropartikel (1)
- Mikrosäulenresonator (1)
- Mindfulness (1)
- Miniaturisierung (1)
- Minimal supersymmetric model (1)
- Mip-Inhibitor (1)
- Missense mutation (1)
- Mitomycin C (1)
- Mitsunobu (1)
- Mittelohrplastik (1)
- Model Checking (1)
- Modellierung (1)
- Modelling (1)
- Moden (1)
- Modul <Software> (1)
- Modularität (1)
- Moelucar beam epitaxy (1)
- Molecular Imaging (1)
- Molecular Structure (1)
- Molecular beam epitaxy (1)
- Molecular-dynamics (1)
- Molecular-weight heparin (1)
- Molecules (1)
- Molekularbewegung (1)
- Molekulardesign (1)
- Molekulargenetik (1)
- Molekülstruktur (1)
- Mongolische Rennmaus (1)
- Monoamine Oxidase/genetics (1)
- Monoklonaler Antikörper (1)
- Monozyt (1)
- Morbus Fabry (1)
- Mord (1)
- Morphotype (1)
- Mortality (1)
- Motilitydysfunction (1)
- Motoneuron disease (1)
- Motoneuron diseases (1)
- Motorisches Gleichgewicht (1)
- Mouse model (1)
- Moving mesh method (1)
- Mt. Kinabalu (1)
- Mud (1)
- Muli-Channel (1)
- Multi-Channel-Einzelhandel (1)
- Multi-Stakeholder (1)
- Multibranched structures (1)
- Multicenter randomized-trial (1)
- Multiple Sklerose (1)
- Multiple drug resistance (1)
- Multiple myeloma (1)
- Multiples Myelom (1)
- Multitasking (1)
- Museum (1)
- Museumspädagogik (1)
- Mustang District (1)
- Mutations (1)
- MyD88 (1)
- Myc (1)
- Myelin oligodendrocyte glycoprotein (MOG) antibodies (1)
- Myelitis (1)
- Myeloma (1)
- Mykosen (1)
- Myocardial fibrosis (1)
- Myocardial perfusion (1)
- Müller cells (1)
- N-Myc (1)
- N-heterocyclic carbenes (1)
- N-oleoyl serinol (1)
- N100 (1)
- N170 (1)
- NDI-H (1)
- NEUROWIND (1)
- NFkB-relatedgenes (1)
- NGS (1)
- NHC (1)
- NHCs (1)
- NIRS (1)
- NK (1)
- NK cells (1)
- NLO computations (1)
- NMD (1)
- NMO-IgG (1)
- NMOSD (1)
- NMR (1)
- NMR-spectroscopy (1)
- NO (1)
- NPU (1)
- NSCLC (1)
- NSG mice (1)
- Nachhaltigkeit (1)
- Nachruf (1)
- Nachwuchsarbeit (1)
- Nahinfrarotspektroskopie (1)
- Nahtmaterial mit Widerhaken (1)
- Namenkunde (1)
- Nanda-Hamner (1)
- Nanoparticles (1)
- Nanoröhre (1)
- Nanotubular coatings (1)
- Nanotubuläre Beschichtungen (1)
- Nanowire (1)
- Narkosezwischenfall (1)
- Nasonia courtship (1)
- Natalizumab (1)
- Natriumoxamat (1)
- Natural Language Processing (1)
- Natural-history data (1)
- Naturtourismus (1)
- Natürliche Killerzelle (1)
- Near Miss (1)
- Nebenläufigkeit (1)
- Nebenniere (1)
- Nebennierenerkrankung (1)
- Nebenniereninsuffizienz (1)
- Nebennierenkrise (1)
- Nebennierenrinde (1)
- Neisseria gonorrhoeae (1)
- Neolithic (1)
- Neolithikum (1)
- Nepal (1)
- Nesting resources (1)
- Netrin (1)
- Network (1)
- Networking (1)
- Netzwerkanalyse <Soziologie> (1)
- Neural crest cells (1)
- Neurale Stammzellen (1)
- Neuralgie (1)
- Neuroinfectiology (1)
- Neuromyelitis optica (NMO) (1)
- Neuromyelitis optica antibodies (NMO-IgG) (1)
- Neuropathic pain (1)
- Neuropathischer Schmerz (1)
- Neurosciences (1)
- Neurotropathic Factor (1)
- Neurovaskuläre Einheit (1)
- Neutrino Telescope (1)
- Neutrophil (1)
- Neutrophil granulocytes interaction (1)
- Neutrophiler Granulozyt (1)
- New Small Wheel (1)
- Next Generation Sequencing (1)
- Nichtlineare Differentialgleichung (1)
- Nichtstaatliche Organisation (1)
- Nichtunterscheidbarkeit (1)
- Nils Mohl (1)
- Nitric-oxide (1)
- Nodule (1)
- Non-coding RNAs (1)
- Non-ribosomal peptide synthetase (1)
- Nord-Süd-Gefälle (1)
- Norm (1)
- Normal breast (1)
- Nova (1)
- Nrf2 (1)
- NuMA (1)
- Numerische Strömungssimulation (1)
- Nurses (1)
- Nutzerstudie (1)
- OCB (1)
- OCR (1)
- OCSVM (1)
- OCT angiography (1)
- OECD guideline (1)
- OHADA (1)
- OMT (1)
- OPS201 (1)
- OST1 (1)
- Obesity (1)
- Ode an die Freude (1)
- Oesling (1)
- Ofatumumab (1)
- Oilseed rape (1)
- Olfr1393 (1)
- Oligoclonal bands (1)
- OmoMYC (1)
- Oncology (1)
- Oncolytic action (1)
- One-photon (1)
- Onkologie (1)
- Ontologie <Wissensverarbeitung> (1)
- Oogenese (1)
- Oogenesis (1)
- Oozyte (1)
- Opc (1)
- Open Innovation (1)
- Open source reconstructed epidermis (1)
- Openfield test (1)
- Opioide (1)
- Opportunistische Infektion (1)
- Opsins (1)
- Optical properties (1)
- Optimal Control (1)
- Optimiertung (1)
- Optimization (1)
- Optische Spektroskopie (1)
- Optische Zeichenerkennung (1)
- Oral antidiabetic drugs (1)
- Oral squamous cell carcinoma (1)
- Organ motion (1)
- Organic Semiconductors (1)
- Organisch-anorganischer Hybridwerkstoff (1)
- Organischer Halbleiter (1)
- Origami (1)
- Ormocer (1)
- Osteoarthrosis (1)
- Osteogenese (1)
- Osteogenic precursor cells (1)
- Outcome (1)
- Outright Monetary Transactions (1)
- Ovarielle Alterung (1)
- Overdiagnosis (1)
- Oxidativer Stress (1)
- Oxide synthase gene (1)
- Oxygen (1)
- Oxygen diffusion hardening (1)
- Oxyrhynchos (1)
- P300 speller (1)
- P75 Neurotrophin receptor (1)
- PARROT (1)
- PBI cyclophane (1)
- PDE (1)
- PDEs (1)
- PDGF (1)
- PEGIDA (1)
- PET/CT (1)
- PFE (1)
- PI3K isoforms (1)
- PI3K/Akt/mTOR (1)
- PICCS (1)
- PICD (1)
- PKB/Akt phosphorylation (1)
- PLGA (1)
- PPIase-Aktivität (1)
- PSMA (1)
- PUMP (1)
- PVD Beschichtung (1)
- PVD coatings (1)
- PVD-Verfahren (1)
- Paediatric (1)
- Paleoenvironment (1)
- Palladium-catalyzed silaboration (1)
- Palliativmedizin (1)
- Paläoklima (1)
- Paläopedologie (1)
- Paläoumwelt (1)
- Panic Disorder/genetics (1)
- Panic Disorder/therapy (1)
- Panikstörung (1)
- Paper-folding (1)
- Papierfalten (1)
- Parabolic equations (1)
- Parallelisierung (1)
- Parametric down-conversion (1)
- Parasite (1)
- Parkinson disease (1)
- Partielle Differentialgleichung (1)
- Partielle Differentialgleichungen (1)
- Partikel (1)
- Pathogenicity (1)
- Pathogens (1)
- Pathology (1)
- Pathophysiologie (1)
- Pathway (1)
- Patient-centered care (1)
- Patterns (1)
- Peptidase inhibitor 16 (PI16) (1)
- Peptidoglycan recognition (1)
- Performance Evaluation (1)
- Peripheral nervous system (1)
- Permeabilität (1)
- Permittivität (1)
- Perovskite (1)
- Perowskit (1)
- Perserzeit (1)
- Personality (1)
- Personenname (1)
- Perspektive (1)
- Perspektivenübernahme (1)
- Perylen-Farbstoffe (1)
- Perylene bisimide (1)
- Perylentetracarbonsäurederivate (1)
- Pflanzenschutzmittel (1)
- Pharmakodynamik (1)
- Philosophie (1)
- Philosophie der Emotionen (1)
- Phobie (1)
- Phosphane (1)
- Phosphodiesterase 3 (1)
- Phosphorylation (1)
- Photochemistry (1)
- Photolumineszenzspektroskopie (1)
- Photosensibilisator (1)
- Photosystem I (1)
- Physics and instrumentation (1)
- Physikalische Chemie (1)
- Picosatellite (1)
- Pinus sylvestris L. (1)
- Pipeline-Rechner (1)
- Pitrakinra (1)
- Placebo (1)
- Placebo-controlled trial (1)
- Plant Protection (1)
- Plant utricularia-gibba (1)
- Plants (1)
- Plasma extravasation (1)
- Plasma-membrane (1)
- Plasmakallikrein (1)
- Plasmakallikrein ischämischer Schlaganfall (1)
- Plasmazellinie (1)
- Plasmozytom (1)
- Plastizität (1)
- Pleistozän (1)
- Pluripotency (1)
- Pmn mutant mouse (1)
- Pneumococci (1)
- Pneumocystis-carinii-pneumonia (1)
- Podocarpus National Park (1)
- Poecilia reticulata (1)
- Polarimetric Synthetic Aperture Radar (PolSAR) (1)
- Polistine wasps (1)
- Polychromophores System (1)
- Polycistronic mRNA (1)
- Polylactid-co-Glycolid (1)
- Polymer-peptide-conjugate (1)
- Polymerase chain raction (1)
- Polymerase-Kettenreaktion (1)
- Polymerhalbleiter (1)
- Polymorphismus (1)
- Polyoxazoline (1)
- Polyphasic fluorescence rise (1)
- Polyphenols (1)
- Pontrjagin-Maximumprinzip (1)
- Pontryagins's maximum principle (1)
- Poor-prognosis (1)
- Porphyrin (1)
- Porphyrin arrays (1)
- Porphyrine (1)
- Poröse Medien (1)
- Poröser Stoff (1)
- Positron-emission-tomography (1)
- Post-transcriptional regulation (1)
- Postmoderne (1)
- Postovulatorische Alterung (1)
- Potential-energy curves (1)
- Pou2af1 (1)
- Preclinical evaluation (1)
- Predict fluid responsiveness (1)
- Pregnancy (1)
- Prehistory (1)
- Primary cell lines (1)
- Primary endosymbiont (1)
- Primary failure of eruption (1)
- Primitive neuroectodermal (1)
- Primär kutane Marginalzonen-Lymphome (1)
- Primäre Zahndurchbruchstörung (1)
- Prior Knowledge (1)
- Problem Gambling (1)
- Processing fluency (1)
- Prof. Dr. Paul Pauli (1)
- Profiling (1)
- Programmed cell-death (1)
- Progressive motor neuronopathy (1)
- Progressive multifocal leukoencephalopathy (1)
- Progressive supranuclear palsy (1)
- Prokura (1)
- Prolactin (1)
- Promoter (1)
- Promoter prediction (1)
- Property rights approach (1)
- Prostatakrebs (1)
- Prostate-cancer (1)
- Protease inhibition (1)
- Protected areas (1)
- Protection (1)
- Protein function prediction (1)
- Protein kinase B (1)
- Protein transduction (1)
- Proteogenomics (1)
- Proximal Method (1)
- Proximal-Punkt-Verfahren (1)
- Psychische Störung (1)
- Psychobiologie (1)
- Psychotherapie (1)
- Pulmonary Embolism (1)
- Pulmonary hypertension (1)
- Puls-pressure variation (1)
- Pulswellengeschwindigkeit (1)
- Puppenhandillusion (1)
- Purchasing (1)
- Purification (1)
- Pycnogenol (1)
- Pyrimidinone (1)
- Pädagogik (1)
- Pädiatrie (1)
- QM/MM (1)
- QTL analysis (1)
- QUAC1 (1)
- Quadruplex-DNS (1)
- Qualitative representation and reasoning (1)
- Quality of Experience (1)
- Quantenchromodynamik (1)
- Quantenkommunikation (1)
- Quantenmechanik (1)
- Quantitative Easing (1)
- Quantum dot (1)
- Quantum wells (1)
- Quartär (1)
- Quecksilbertellurid (1)
- Queueing theory (1)
- R-Typ (1)
- RAR (1)
- RARRES2 (1)
- RES-Oxylipine (1)
- RHE (1)
- RNA (1)
- RNA binding proteins (1)
- RNA isolation (1)
- RNA polymerase (1)
- RNA sequencing (RNA-Seq) (1)
- RNA-SEQ data (1)
- RNA-binding proteins (1)
- RNA-seq (1)
- RNAseq (1)
- RNS-Bindungsproteine (1)
- RNS-Interferenz (1)
- ROS (1)
- RSK (1)
- RU(CO)(3)CL(GLYCINATE) (1)
- RU-(II) complexes (1)
- RXR (1)
- RYGB (1)
- RZUW (1)
- Racial differences (1)
- Radarsat-2 (1)
- Radiale MR-Bildgebung (1)
- Radio Interferometry (1)
- Radioindikator (1)
- Radionuclide Therapy (1)
- Radionuclide therapy (1)
- Radiopharmacy (1)
- Radiopharmaka (1)
- Radioteleskop (1)
- Radiotherapy (1)
- Raf kinase inhibitor protein (1)
- Raf-Kinasen (1)
- Randbemerkung (1)
- Rapid evolution (1)
- Rastertunnelspektoskopie (1)
- Rat (1)
- Rat mynteric plexus (1)
- Rating scale (1)
- Rats (1)
- Raumklima (1)
- Raumwahrnehmung (1)
- RbdB (1)
- Reaction kinetics and dynamics (1)
- Reaktionskinetik (1)
- Reaktionsmechanismus (1)
- Reaktionspfadsuche (1)
- Reaktionszeit (1)
- Real time quantitative PCR (1)
- Real-time PCR (1)
- Rebreathing (1)
- Rechenzentrum Universität Würzburg (1)
- Recurrent medulloblastoma (1)
- Redox environment (1)
- Reduktion <Chemie> (1)
- Regenerative medicine (1)
- Regionalentwicklung (1)
- Regulatory T cells (1)
- Regulatory T-cells (1)
- Regulatory-cells (1)
- Reihenfolgeplanung (1)
- Reinheitsanalytik (1)
- Reirradiation (1)
- Rekord (1)
- RelA (1)
- Relapsing-remitting MS (1)
- Relaxation Dynamics (1)
- Remotely Operate Vehicle (1)
- Reproduction (1)
- Research Infrastructure (1)
- Respiratory insufficiency (1)
- Respiratory syncytial virus (1)
- Responses (1)
- Ressourcenallokation (1)
- Restaurierung (1)
- Restoration material (1)
- Retinal arterial macroaneurysms (1)
- Retrodigitalisierung (1)
- Rettung aus dem Schilfmeer (1)
- Reveals (1)
- Rezeption (1)
- Rhabdoid 2007 (1)
- Rheumatoid arthritis (1)
- Rhodopsins (1)
- Rhombencephalitis (1)
- Ribosom (1)
- Ribosome profiling (1)
- Richness (1)
- Richtlinie über alternative Streitbeilegung in Verbraucherangelegenheiten (1)
- Rictor-mTOR complex (1)
- Risiko (1)
- Risikobereitschaft (1)
- Risk (1)
- Rituximab (1)
- Robertsonian translocation chromosomes (1)
- Robotic tracking (1)
- Rolimeter (1)
- Romansitik (1)
- Ru(II)–Fe(II)–Ru(II) complex (1)
- Ruthenium (1)
- Römisches Reich (1)
- Röntgen-Photoelektronenspektroskopie (1)
- Röntgenstreuung (1)
- Rückatmungsmethode (1)
- S-HT (1)
- SABR (1)
- SAP47 gene (1)
- SAR (1)
- SBRT (1)
- SCD (1)
- SCORE (1)
- SEM (1)
- SERT (1)
- SFRP (1)
- SGLT2 inhibitor (1)
- SLAC1 (1)
- SNARE proteins (1)
- SNPs (1)
- SPECT (1)
- SSRI (1)
- SSTR (1)
- STAT3 activation (1)
- SUMO2 (1)
- SUN domain proteins (1)
- SVM (1)
- Saccades (1)
- Saccharomyces cerevisiae (1)
- Sagittalnahtsynostose (1)
- Salmonella Typhimurium (1)
- Salmonella enterica (1)
- Salmonella-enteritidis (1)
- Samen (1)
- Sap47 (1)
- Sarah (1)
- Satellit (1)
- Sauerstoffdiffusionshärtung (1)
- Sauerstofffehlstellen (1)
- Sauerstoffkonzentration (1)
- Saure Sphingomyelinase (1)
- Sb2Te3 (1)
- Scaffoldmaterialien (1)
- Scaling up (1)
- Schizophrenia (1)
- Schlafstörung (1)
- Schlaganfallprophylaxe (1)
- Schlichte Funktion (1)
- Schlichtung (1)
- Schließzelle (1)
- Schmalwand <Arabidopsis> (1)
- Schmerz (1)
- Schmerzmodulation (1)
- Schmerzreiz (1)
- Schnelle MR-Bildgebung (1)
- Schnitzler syndrome (1)
- Schulbucharbeit (1)
- Schulbuchzulassung (1)
- Schwangerschaft (1)
- Schwann cell dedifferentiation (1)
- Schwellenländer (1)
- Schädel-Hirn-Trauma (1)
- Screening (1)
- Screening questionnaire (1)
- SdY (1)
- SdsR (1)
- Secondary tumours (1)
- Seeds (1)
- Sekretion (1)
- Sekundarstufe (1)
- Selbstverwirklichung (1)
- Selective attention (1)
- Selektive Wahrnehmung (1)
- Selen (1)
- Selenium (1)
- Semantic Entity Model (1)
- Semiconductor (1)
- Semismooth Newton Method (1)
- Senescence (1)
- Sensors (1)
- Sentinel-1 (1)
- Sepsis (1)
- Septal bulge (1)
- Septuaginta (1)
- Sequence Analysis (1)
- Sequence identity (1)
- Sequenzierung (1)
- Serbien (1)
- Serubbabel (1)
- Si-rhodamine (1)
- Siedlungsarchäologie (1)
- Signal transduction (1)
- Signaltransduktion (1)
- Silanderivate (1)
- Silandiylverbindungen (1)
- Silicium(II) (1)
- Silicium(IV) (1)
- Siliciumverbindungen (1)
- Silylene (1)
- Simulation (1)
- Simulations (1)
- Single nucleotide change (1)
- Sinorhizobium fredii (1)
- Sinus floor augmentation (1)
- Six3/6 Wnt (1)
- Skin (1)
- Skin cancer screening (1)
- Sleep in children (1)
- Slow-transit constipation (1)
- Small fiber dysfunction (1)
- Smartphone (1)
- Smartphones (1)
- SnRK1 (1)
- Social Resilience (1)
- Social anxiety (1)
- Social entrainment (1)
- Social support (1)
- Social work (1)
- Software Engineering (1)
- Softwarewiederverwendung (1)
- Sol-Gel-Prozess (1)
- Solid state physics (1)
- Somatische Mutation (1)
- Sonderpädagogik (1)
- Sound detection threshold (1)
- South Africa (1)
- Soziale Bewegung (1)
- Soziale Phobie (1)
- Soziale Stabilität (1)
- Sozialphilosophie (1)
- Spaltöffnung (1)
- Sparsity (1)
- Spectrum (1)
- Speedcourt (1)
- Spektroskopie (1)
- Spermatogenese (1)
- Spermienbildung (1)
- Spermiogenese (1)
- Spheno (1)
- Sphingomyelinphosphodiesterase (1)
- Sphäroid (1)
- Spielfähigkeit (1)
- Spielsucht (1)
- Spin echo (1)
- Spin-eins-System (1)
- Spin-polarisierte Rastertunnelmikroskopie (1)
- Spinal Muscular-arthropy (1)
- Spinal muscular Atrophy (1)
- Spinale Muskelatrophie (1)
- Spinell (1)
- Spontaneous facial EMG (1)
- Spracherwerb (1)
- Sprachwissenschaft (1)
- Sputter deposition (1)
- Squamous-cell carcinoma (1)
- Squaraine (1)
- Sracking (1)
- Staatsanleihe (1)
- Stabilisierung (1)
- Stack-of-Stars Sequenz (1)
- Stack-of-Stars sequence (1)
- Stadtrandritter (1)
- Stage distribution (1)
- Stammzelle (1)
- Standard (1)
- Startle (1)
- Stat3 (1)
- State (1)
- Stathmin (1)
- Stationärer Handel (1)
- Stem cells (1)
- Stem cells plasticity (1)
- Sterbebegleitung (1)
- Stereochemie (1)
- Stereotype (1)
- Sternentwicklung (1)
- Steuerhinterziehung (1)
- Steuern (1)
- Steueroase (1)
- Steuerrecht (1)
- Stickstoffmonoxid (1)
- Stochastischer Prozess (1)
- Stoffwechsel (1)
- Stoffwechselinhibitoren (1)
- Strafrecht (1)
- Strafvollzug (1)
- Strahlentherapie (1)
- Strains (1)
- Stratified scree (1)
- Streptococcus suis (1)
- Stress prevention (1)
- Stress responses (1)
- Stringent response (1)
- Stringente Antwort (1)
- Stringente Kontrolle (1)
- Stroke (1)
- Struktur (1)
- Struktur-Eigenschafts-Beziehung (1)
- Strukturbasiertes Wirkstoffdesign (1)
- Strukturreform (1)
- Studie (1)
- Sturge-Weber syndrom (1)
- Succinylcholin (1)
- Succinylcholine (1)
- Supersymmetry Breaking (1)
- Supply Chain (1)
- Suppression (1)
- Surface states (1)
- Survival (1)
- Survival analysis (1)
- Susceptibility loci (1)
- Sustainable HRM (1)
- Sustainable Nature Based Tourism Development Institutions (1)
- Sustained attention (1)
- Syap1 localization (1)
- Symbiose (1)
- Synapse (1)
- Synaptic plasticity (1)
- Synaptische Transmission (1)
- Synovitis (1)
- Synthese (1)
- Synthesis (1)
- Synthetic Aperture Radar (SAR) (1)
- System involvement (1)
- Systemisches Risiko (1)
- Südafrika (1)
- Südkorea (1)
- Südosteuropa (1)
- T cell activation (1)
- T cell differentiation (1)
- T cells (1)
- T lymphocytes (1)
- T-Lymphozyt (1)
- T-Zellen (1)
- T-cells (1)
- TASK (1)
- TBI (1)
- TCR diversity (1)
- TDM (1)
- TEI (Text Encoding Initiative) (1)
- TEI-Kodierung (1)
- TGF-β1 (1)
- TIG2 (1)
- TLR2 (1)
- TLR4 (1)
- TLR9 (1)
- TNF (1)
- TNFR2 (1)
- TNM staging (1)
- TRECs (1)
- TRESK (1)
- TSPO (1)
- T\(_H\)17 cells (1)
- Tacrin (1)
- Tagung (1)
- Talentförderung (1)
- Tamm plasmons (1)
- Tamm-Plasmonen (1)
- Tansania (1)
- Tantal (1)
- Tanzania (1)
- Targeted therapy (1)
- Task force (1)
- Task interference (1)
- Technology Acceptance (1)
- Teilchendetektor (1)
- Teillose (1)
- Telekommunikationsnetz (1)
- Tellur (1)
- Tellurium (1)
- Temperaturabhängigkeit (1)
- Temperature rhythms (1)
- Temporal-lobe epilepsy (1)
- Temporomandibular disorders (1)
- Temporomandibular joint disc (1)
- Tenorrhaphy (1)
- Tensile strength (1)
- Term follow-up (1)
- Terminology (1)
- TerraSAR-X (1)
- Tesseract (1)
- Test accuracy (1)
- Teststand (1)
- Tetrahydrochinazoline (1)
- Text analysis (1)
- Textedition (1)
- Textverstehen (1)
- Th17 (1)
- The New Empire (1)
- Theory of Mind (1)
- Therapeutisches Drug Monitoring (1)
- Thermische Konversion (1)
- Thigmotaxis (1)
- Thin film growth (1)
- Thioredoxin (1)
- Thrombus formation (1)
- Thymus (1)
- Ti(Ag) Beschichtungen (1)
- Ti(Ag) coatings (1)
- TiO\(_2\) (1)
- Tiermodell (1)
- Time Calibration (1)
- Time-course (1)
- Tissue (1)
- Tissue engineering (1)
- Toll like receptors (1)
- Toll-like Rezeptoren (1)
- Toll-like receptors (1)
- Tomografie (1)
- Topic Modeling (1)
- Total Variation (1)
- Tourette syndrome (1)
- Tourismus (1)
- TraDIS (1)
- Trans-reservatrol (1)
- Transaction costs (1)
- Transcription initiation (1)
- Transcription start site (1)
- Transferases (1)
- Transgenic mice (1)
- Transient-Absorption Sectroscopy (1)
- Transition Metals (1)
- Transkription <Genetik> (1)
- Transkriptionsfaktor (1)
- Transkriptom (1)
- Transovarial transmission (1)
- Transpiration <Pflanzen> (1)
- Transport (1)
- Transportbarriere (1)
- Transporteigenschaft (1)
- Transportlosgröße (1)
- Transposon (1)
- Transposon insertion sequencing (1)
- Transverse Myelitis (1)
- Transverse myelitis (1)
- Traveling Wave Magnetic Particle Imaging (1)
- Tregs (1)
- Trennung (1)
- Trial (1)
- Trinidadian guppy (1)
- Tropenkrankheit (1)
- Trost (1)
- Trypanosoma-brucei (1)
- Trypanosomes (1)
- Tuberculosis (1)
- Tuberkelbakterium (1)
- Tuberkulose (1)
- Tumor-necrosis-factor (1)
- Tumorhypoxie (1)
- Tumorigenicity (1)
- Tumors (1)
- Tumorzelle (1)
- Tympanoplastik Typ 3 (1)
- Typ-1-Diabetes (1)
- Type II quantum wells (1)
- Type-II quantum well (1)
- Typhimurium (1)
- Tyrosine phosphorylation (1)
- Türkei (1)
- UMTS-Auktion (1)
- USA (1)
- USA300 (1)
- USP9X (1)
- UV/Vis spectroscopy (1)
- Ube2S (1)
- Ubiquitin-conjugating (E2) enzymes (1)
- Ulcerative colitis (1)
- Ultrafast Spectroscopy (1)
- Ultrakurzzeitspektroskopie (1)
- Unionsbürgerschaft (1)
- Universitätsbibliothek Würzburg (1)
- Unternehmensgröße (1)
- Urteilen (1)
- Uterine tumors (1)
- Uveitis (1)
- VACV (1)
- VBM (1)
- VE-cadherin (1)
- VEGF (1)
- VMAT (1)
- Vaccination (1)
- Vaccine (1)
- Vaccinia virus (1)
- Vacuum chambers (1)
- Vagus (1)
- Value ranges (1)
- Variantcalling (1)
- Variants (1)
- Varicella-Zoster-Virus (1)
- Varicella-zoster-virus (1)
- Variety (1)
- Varietät (1)
- Vascular plasticity (1)
- Vatin-Kultur (1)
- Venous Thrombosis (1)
- Ventricular-arrhythmias (1)
- Verbindungen (1)
- Verbraucher (1)
- Verbraucherschutz (1)
- Verbraucherstreitbeilegungsgesetz (VSBG) (1)
- Verdeutschingswörterbuch (1)
- Vereinte Nationen (1)
- Verhalten (1)
- Verlustausgleich (1)
- Verteilte Bragg-Reflexion (1)
- Verteilungsverfahren (1)
- Vertical integration (1)
- Verunreinigung (1)
- Very long baseline interferometry (1)
- Vgamma9Vdelta2 T cells (1)
- Viability (1)
- Vibronic contributions (1)
- Vigilance (1)
- Viral (1)
- Virotherapy (1)
- Virtual-reality (1)
- Virtuelles Netz (1)
- Virulenz (1)
- Virulenzfaktor (1)
- Visueller Reiz (1)
- Vitamin A (1)
- Vivo (1)
- Vocal responses (1)
- Vojvodina (1)
- Volatile Anästhetika (1)
- Vor- und Frühgeschichte (1)
- Vorabentscheidungsverfahren (1)
- Vortices (1)
- Vorwissen (1)
- Vulgata (1)
- W-boson (1)
- WDR5 (1)
- WIMP (1)
- Wachstumsfaktoren (1)
- Wahrnehmung (1)
- Wahrscheinlichkeitsrechnung (1)
- Wallemia ichthyophaga (1)
- Warburg, Otto (1)
- Warburg-Effekt (1)
- Wasseroxidationsreaktion (1)
- Wasserspaltung (1)
- Weight (1)
- Wein (1)
- Weißer Zwerg (1)
- Wellenpaket (1)
- Werkstoff (1)
- West Africa (1)
- Williamsia sp. ARP1 (1)
- Wilms tumor (1)
- Wilms tumor protein 1 (1)
- Wingerchuk criteria 2006 and 2015 (1)
- Winkel (1)
- Wirt (1)
- Wirtschaftsrecht (1)
- Wirtschaftsverwaltungsrecht (1)
- Wissensrepräsentation (1)
- Wnt signalling (1)
- Wonderful plants (1)
- World War I (1)
- Wurzelfüllung (1)
- Wurzelkanalbehandlung (1)
- Wüstenpflanze (1)
- X-ray analysis (1)
- X-ray microscopy (1)
- X. couchianus (1)
- X. hellerii (1)
- XIAP (1)
- XPS (1)
- Xiphophorus (1)
- Xiphophorus fish (1)
- YB-1 (1)
- Yersinia (1)
- Yield (1)
- Zahndurchbruch (1)
- Zebrafish (1)
- Zeitschrift (1)
- Zelldifferenzierung (1)
- Zellskelett (1)
- Zellwand (1)
- Zenith Angle (1)
- Zentrale Toleranz (1)
- Zeolith (1)
- Zinkselenid (1)
- Zirkulardichroismus (1)
- Zufriedenheit (1)
- Zuhören (1)
- Zuwanderung (1)
- Zuwendung (1)
- Zweidimensionale elektronische Spektroskopie (1)
- Zytokin (1)
- Zytokingenpolymorphismus (1)
- \(^{68}\)Ga-Pentixafor (1)
- acceptance (1)
- accumulation (1)
- acetyltransferases (1)
- achaete-scute homolog 1 (1)
- achievement motivation (1)
- acid sphingomyelinase (1)
- acquired thermotolerance (1)
- acquisition (1)
- action potential (1)
- active accelerator pedal (1)
- active transport (1)
- active zone (1)
- acute Graft versus Host Disease (1)
- acute lymphoblastic leukaemia (1)
- acute lymphocytic leukaemia (1)
- adaptation models (1)
- adaptive immune system (1)
- adduct (1)
- adenocarcinoma of the ampulla of Vater (1)
- adenocarcinoma of the lung (1)
- adenomas (1)
- adenovirale Transduktion (1)
- adenoviruses (1)
- adhesion (1)
- adipose (1)
- adipose tissue dysfunction (1)
- adipose-derived stem cells (1)
- adjuvant (1)
- administration (1)
- adolescence (1)
- adult ADHD (1)
- adult attention deficit/hyperactivity disorder (1)
- adults (1)
- aerodynamics (1)
- age factors (1)
- age-related macular degeneration (1)
- aged (1)
- aged 80 and over (1)
- aggregation (1)
- aggressiveness (1)
- agri-environment schemes (1)
- agriculture (1)
- aktuelle Situation (1)
- akute lymphatische Leukämie bei Kindern (1)
- albumin excretion rate (1)
- alfa-cyano-4-hydroxycinnamat (1)
- alfabetización mediática (1)
- algorithm (1)
- aliphatic compounds (1)
- alkenes (1)
- allergy (1)
- allogeneic hematopoietic stem cell transplantation (1)
- allogeneic stem cell transplantation (1)
- allostatic load (1)
- alpha-galactosidase A (1)
- alternative to animal testing (1)
- alternatives (1)
- amber codon suppression (1)
- amino acid (1)
- amino-acids (1)
- aminoquinolinium salts (1)
- amphotericin B (1)
- amplicon sequencing (1)
- analgesia (1)
- analysis of variance (1)
- anaplastic medulloblastoma (1)
- anastomotic leakage (1)
- anatomical landmark (1)
- anchoring (1)
- anemia (1)
- aneurysm surgery (1)
- angiogenesis (1)
- angiogenic cytokines (1)
- angiography (1)
- angular schematization (1)
- animal models (1)
- animal movement (1)
- animals (1)
- anionic dimetalloborylene complexes (1)
- anisotropy energy (1)
- annotation (1)
- anorganisch-organische Hybridpolymere (1)
- ant oogenesis (1)
- ant-mimicking spiders (1)
- antennas (1)
- anterior optic tubercle (1)
- antero-posterior axis (1)
- anthropogenic activities (1)
- anti-hDEC205-WT1 antibody fusion protein (1)
- anti-tumor effects (1)
- antibacterial activity (1)
- anticipation (1)
- anticipatory planning (1)
- anticoagulants (1)
- antidepressants (1)
- antidiabetic agents (1)
- antiferromagnet (1)
- antileukemia vaccine (1)
- antimicrobial peptides (1)
- antimicrobial resistance (1)
- antimycotics (1)
- antioxidants (1)
- antiretroviral therapy (1)
- antitumor immune response (1)
- antiviral immunity (1)
- antiviral treatment (1)
- ants (1)
- anxiety disorders (1)
- anxiety-like behavior (1)
- análisis transnacional (1)
- aphasia (1)
- applied physics (1)
- approach (1)
- appropriate costs (1)
- aquaporin 4 (1)
- aquaporin-4 antibodies (AQP4-IgG) (1)
- aqueous-solution (1)
- arabidopsis (1)
- arabidopsis-thaliana (1)
- archaeometry (1)
- arctic (1)
- army ants (1)
- arousal (1)
- artificial diet (1)
- ascites (1)
- aspergillus fumigatus (1)
- assembly (1)
- assembly chaperone (1)
- assistive technology (1)
- association (1)
- associative memory (1)
- asthma (1)
- astrocytes (1)
- atmospheric chemistry (1)
- atopic-dermatitis (1)
- atrial fibrillation (1)
- attentional bias (1)
- attraction (1)
- audio stimulus (1)
- auditorisch (1)
- auditory stimulation (1)
- autism (1)
- autism spectrum disorder (1)
- autoantibody (1)
- autoimmunity (1)
- autophagy (1)
- autoradiography (1)
- av-ECLA (1)
- axonal damage (1)
- axonaler Transport (1)
- azidothymidine (1)
- azobenzenes (1)
- bAV (1)
- bacterial genetics (1)
- bacterial infection (1)
- barbed suture (1)
- batch shipments (1)
- bed bug (1)
- bee community (1)
- bees (1)
- behavior (1)
- benzoquinone (1)
- beta oscillations (1)
- beta-D-glucan (1)
- beta-adrenerge Signalwege (1)
- beta-blockers (1)
- beta2-adrenoceptor knockout (1)
- beta3 CL 316,243 (1)
- bilateral BAS model (1)
- biliary-tract cancer (1)
- binding components (1)
- bio-orthogonal chemistry (1)
- biochemistry (1)
- biocompatibility (1)
- biocompatible patch (1)
- biodegradierbar (1)
- biodiversity assessment (1)
- bioenergetics (1)
- biofuels (1)
- biogenic volatile organic compounds (1)
- bioinformatics (1)
- bioinspired materials (1)
- biokompatibler Patch (1)
- biolog (1)
- biological mechanism (1)
- bioluminescence (1)
- bioluminescence imaging (1)
- biomarkers Myelomas (1)
- biomechanical test (1)
- biophotonic imaging (1)
- biopsy (1)
- bioreactor plattform (1)
- biosensors (1)
- birth cohort (1)
- bis-terpyridyl ligands (1)
- bismuth (1)
- black lipid bilayer (1)
- blastemal (1)
- blood (1)
- blood coagulation (1)
- blood flow (1)
- blood plasma (1)
- blood pressure (1)
- blood pressure monitoring (1)
- body mass index (1)
- body weight (1)
- body weight regulation (1)
- bone (1)
- bone imaging (1)
- bone metastases (1)
- bone morphogenic protein 2 (1)
- boron-nitride (1)
- botulinum toxin (1)
- boundary labeling (1)
- brain computer interface (1)
- brain derived neurotrophic factor (1)
- brain response (1)
- brain swelling (1)
- brain tumor (1)
- brain-computer interface (1)
- brain-computer interface (BCI) (1)
- brain-injury (1)
- break-in parties (1)
- breast cancer subtypes (1)
- breast-cancer (1)
- brefeldin-a (1)
- broodtranslocation (1)
- bug riptortus-pedestris (1)
- bull’s eye plot (1)
- butyrophilin 3A (1)
- cAMP (1)
- caenorhabditis elegans (1)
- cag pathogenicity island (1)
- calcification (1)
- calcineurin signaling cascade (1)
- calcitonin gene-related peptide (1)
- calcium sensitivity (1)
- calcium signaling (1)
- calorie content (1)
- calyx (1)
- camelina-sativa (1)
- camponotus ants (1)
- campylobacter jejuni infection (1)
- campylobacter-jejuni (1)
- cancer biology (1)
- cancer cells (1)
- cancer chemotherapy (1)
- cancer detection and diagnosis (1)
- cancer risk (1)
- cancer stem cells (1)
- canopy spiders (1)
- capacitance (1)
- capital flows (1)
- carbenes (1)
- cardiac (1)
- cardiac arrest documentation (1)
- cardiac pacing (1)
- cardiac tissue engineering (1)
- cardiopulmonary resuscitation (1)
- cardiorespiratory disease (1)
- cardiovascular (1)
- cardiovascular disease (1)
- cardiovascular outcomes (1)
- care (1)
- carotid arteries (1)
- cartilage (1)
- cascade reactions (1)
- cell biology (1)
- cell compartmentation (1)
- cell cycle and cell division (1)
- cell cycle arrest (1)
- cell death (1)
- cell differentiation (1)
- cell labeling (1)
- cell membranes (1)
- cell motility (1)
- cell proliferation (1)
- cell signalling (1)
- cell staining (1)
- cell vaccines (1)
- cellular imaging (1)
- central complex (1)
- central lung (1)
- central nervous system (1)
- cephalosporin-resistant gram-negative bacteria (1)
- cerebral blood flow (1)
- cervical dystonia (1)
- cesioflammea (1)
- cestodes (1)
- chalcogenide (1)
- chemokine receptor-4 (1)
- chemoselective (1)
- chemosensitivity (1)
- chemotaxis (1)
- child development (1)
- child memory (1)
- childhood asthma (1)
- childhood maltreatment (1)
- chip analyses (1)
- chiral separation (1)
- chirale Trennung (1)
- chloroquine (1)
- chordal Loewner equation (1)
- chorioretinal lesions (1)
- chromatin (1)
- chromism (1)
- chronic myelogenous leukemia (1)
- chronic myeloid leukemia (1)
- chronic obstructive (1)
- chronic pain (1)
- chronic periodontitis (1)
- chronic respiratory-diseases (1)
- chronische Hyponatriämie (1)
- chronobiology (1)
- circularly-polarized light (1)
- classical novae (1)
- classification (1)
- classification and labeling (1)
- claudin 5 (1)
- climate factors (1)
- climate impact (1)
- clinical (1)
- clinical trial (1)
- clinical-practice (1)
- clip control (1)
- cloning (1)
- closed-loop (1)
- cloud gap filling (1)
- cluster-RCT (1)
- cnl-Meningokokken (1)
- co-adaptive (1)
- coagulation factor XIIa (1)
- coatings (1)
- cochlear nucleus neurons (1)
- coconut cocos-nucifera (1)
- coexistence (1)
- cognition (1)
- cognition development (1)
- cognitive functions (1)
- coherence (1)
- coherence analysis (1)
- coherent light (1)
- collagen (1)
- colony survival (1)
- color vision (1)
- colouring agents (1)
- common factors (1)
- common teal (1)
- community ecology (1)
- community-dwelling (1)
- comparative HRM (1)
- competency based teaching (1)
- complexes (1)
- complication (1)
- composites (1)
- compounds (1)
- computed tomography (1)
- computed tomography (CT) (1)
- computer-assisted (1)
- conditioned response (1)
- conductance (1)
- conductive hearing loss (1)
- cone beam CT (1)
- cones (1)
- confocal laser microscopy (1)
- congenital ocular motor apraxia (1)
- conservation law (1)
- consistent partial least squares (1)
- consumer psychology (1)
- contact activation system (1)
- contact representation (1)
- contrast (1)
- convection (1)
- conversion (1)
- converting enzyme-inhibition (1)
- coping with challenge (1)
- copper (1)
- corneal equivalent (1)
- corporate restructuring (1)
- correlation function (1)
- correlation properties (1)
- correlative light and electron microscopy (1)
- corticobasal syndrome (1)
- corticosteroids and cyclophosphamide (1)
- costly (1)
- costly signaling (1)
- couplers (1)
- critical limits (1)
- crop pollination (1)
- cropland vegetation phenology (1)
- cross-modal action (1)
- cross-species comparison (1)
- crossnational analysis (1)
- cryptogenic stroke (1)
- crystal-structure (1)
- curricula (1)
- currículo de la educación en medios (1)
- currículum (1)
- cuticular leaf wax (1)
- cuticular transpiration (1)
- cuticular water permeability (1)
- cuticular wax (1)
- cutin (1)
- cyclic perylene bisimide (1)
- cyclic test (1)
- cycloid psychoses (1)
- cytokinins (1)
- cytoplasm (1)
- cytoplasmic staining (1)
- cytoskeleton dynamics (1)
- cytosol (1)
- cytostatic (1)
- dRNA-Seq (1)
- damped-oscillator-model of photoperiodic clock (1)
- daratumumab monotherapy (1)
- dark matter (1)
- dark matter detectors (1)
- dark matter experiments (1)
- data mining/methods (1)
- decision making (1)
- decision support (1)
- deep sea neutrino telescope (1)
- deficient mutant (1)
- dehydration (1)
- delineation (1)
- democracy (1)
- dendric cells (1)
- dendritic cell-targeting (1)
- density functional calculations (1)
- density weighting (1)
- depreissia decipiens (1)
- depression (1)
- dermal melanocytosis (1)
- desert (1)
- desert plant (1)
- design (1)
- detrusor muscle (1)
- deuterostomes (1)
- deutsche Kreuzzugslyrik (1)
- development (1)
- developmental biology (1)
- developmental delay (1)
- developmental disorders (1)
- devices for energy harvesting (1)
- diabetes (1)
- diabolical points (1)
- diagnosis (1)
- diapause (1)
- diarrhea (1)
- dichroism (1)
- dichthadiigynes (1)
- dicyclohexyl phthalate (1)
- dietary sodium restriction (1)
- diffuse (1)
- dilaboration (1)
- dimer (1)
- dimerization (1)
- direct anterior approach (1)
- direct stochasticoptical reconstruction microscopy (1)
- directional solidification (1)
- discordance (1)
- disease risk-factors (1)
- disease-activity score (1)
- distance running (1)
- distributed control (1)
- disulfide bonds (1)
- dogs (1)
- dopamine transporters (1)
- dopaminergics (1)
- dorsolateral prefrontal cortex (1)
- dosimetry (1)
- dot probe (1)
- draft genome (1)
- dressed states (1)
- drug (1)
- drug adherence (1)
- drug treatment (1)
- drug-eluting beads (1)
- drug-minded protein (1)
- dsRNA binding protein (1)
- dual function (1)
- dual polarimetry (1)
- dunce (1)
- dyes/pigments (1)
- dynamic testing (1)
- dyspnea (1)
- e-impact (1)
- early diagnosis (1)
- early literacy (1)
- early secretory pathway (1)
- echocardiography (1)
- eco mode (1)
- eco-driving (1)
- economic growth (1)
- ecosystem services (1)
- ectotherms (1)
- edema (1)
- educación en medios (1)
- educational tool (1)
- effectiveness (1)
- efficiency (1)
- elderly (1)
- electric field distribution (1)
- electric vehicle (1)
- electrocardiography (1)
- electronic and spintronic devices (1)
- electrospinning (1)
- ellipsoid (1)
- elliptic PDE (1)
- embryonic stem cells (1)
- emerging markets (1)
- emissions (1)
- emotion (1)
- emotion processing (1)
- emotion regulation (1)
- emotional design (1)
- emotional regulation (1)
- emotions (1)
- empagliflozin (1)
- end-state comfort effect (1)
- endemism (1)
- endocrine therapy (1)
- endogenous opioids (1)
- endoplasmic-reticulum (1)
- endosomes (1)
- endosponge (1)
- endosymbiosis (1)
- endothelial cells (1)
- endovascular treatment (1)
- endurance (1)
- energy density (1)
- energy deprivation (1)
- enhanced green fluorescent protein (1)
- enoyl-ACP reductase inhibitors (1)
- enseñanzapor por competencias (1)
- enteric pathogens (1)
- entropy production (1)
- enzyme (1)
- enzyme purification (1)
- enzyme regulation (1)
- enzyme structure (1)
- enzymes (1)
- epidermis (1)
- epigenetic silencing (1)
- epigenetics (1)
- epilepsy (1)
- epithelial-mesenchymal transition (1)
- erythrocytes (1)
- essential tremor (1)
- ethanol (1)
- euchromatin (1)
- european leukemia net (1)
- eutrino physics (1)
- evolutionary consumer psychology (1)
- evolutionary fixation (1)
- evolutionary psychology (1)
- ex vivo (1)
- exciton coupling (1)
- exciton transfer (1)
- exciton-polariton (1)
- exciton-polariton condensates (1)
- excitons (1)
- excretory-secretory (1)
- executive function training (1)
- exocrine glands (1)
- expectation (1)
- experience (1)
- experimental cerebral malaria (1)
- experimental design (1)
- expert systems (1)
- export (1)
- eye irritation testing (1)
- eyes (1)
- fHbp (1)
- fabry disease (1)
- factor XII (1)
- familial amyloidotic polyneuropathy (1)
- fast MR imaging (1)
- fatal cardiovascular disease (1)
- fatigue (1)
- fatty liver (1)
- fear generalization (1)
- fear response (1)
- feeling of bodily self (1)
- female (1)
- female choice (1)
- females (1)
- fentanyl (1)
- ferromagnet (1)
- ferromagnetism (1)
- fertility (1)
- fetal brain development (1)
- fetal testis (1)
- fibroblast (1)
- fibromyalgia syndrome (1)
- field (1)
- field boundaries (1)
- field free point (FFP) (1)
- financial crises (1)
- fine-needle-aspiration (1)
- fine-scale mapping (1)
- finger protein 11 (1)
- fingers (1)
- fish (1)
- fish model (1)
- flagella (1)
- flagellum (1)
- flavonoid (1)
- fluorescence recovery after photobleaching (1)
- fluorescence spectra (1)
- fluorescent dyes (1)
- fluorescent-probes (1)
- fluorophore (1)
- fluorophores (1)
- focal (1)
- follicular T helper cells (1)
- food consumption (1)
- food-cues (1)
- foraging (1)
- force relationship (1)
- forest edges (1)
- forest fragmentation (1)
- forest hedges (1)
- forest specialists (1)
- formación de profesorado (1)
- formation flight (1)
- frontal cortex (1)
- fruit-flies (1)
- fully automatic (1)
- function identification (1)
- functional magnetic resonance imaging (1)
- fungal disease (1)
- fungal host response (1)
- fungal infection (1)
- fungicide (1)
- gait analysis (1)
- galactomannan (1)
- gamma delta T cells (1)
- gamma radiation (1)
- gap junction (1)
- gastrointestinal disease (1)
- gastrointestinal dysfunction (1)
- gastrointestinal tract (1)
- gaze independence (1)
- gefitinib (1)
- geistige Behinderung (1)
- gels (1)
- gemcitabine (1)
- gender (1)
- gene expression data (1)
- gene regulation in immune cells (1)
- gene transfer (1)
- genes (1)
- genetic cytokine polymorphism (1)
- genetic dissection (1)
- genetic polymorphisms (1)
- genetics memory (1)
- genome assembly (1)
- genome integrity (1)
- genome sequencing (1)
- genome stability (1)
- genome-wide association study (1)
- geographic biases (1)
- geographical variation (1)
- geomorphology (1)
- gepaarte Vagusnerv-Stimulation (1)
- german multicenter (1)
- germinal center (1)
- germline (1)
- giant intracranial aneurysm (1)
- girls (1)
- girls' football (1)
- glands (1)
- glioblastoma (1)
- global dataset (1)
- global reporting initiative (1)
- glucocorticoid receptor (1)
- glucocorticoid replacement therapy (1)
- glucose handling (1)
- glucose lowering agent (1)
- glucose metabolism (1)
- glutamate (1)
- glycation end products (1)
- glycemic control (1)
- glycine (1)
- gonad development (1)
- goutallier (1)
- granules (1)
- graph drawing (1)
- ground states (1)
- group 3 (1)
- group refractive index (1)
- growth factors (1)
- growth-factor-receptor (1)
- guality-of-life (1)
- guidelines (1)
- gut microbiota (1)
- gynecologic surgical procedures/methods (1)
- göttliches Handeln (1)
- hOCT1 (1)
- habitat use (1)
- hadronic colliders (1)
- halophilic fungus (1)
- hands (1)
- happiness (1)
- hazard perception (1)
- health monitoring (1)
- health risk assessment (1)
- health status (1)
- health status instruments (1)
- health-assessment questionnaire (1)
- heart (1)
- heart disease (1)
- heart failure (1)
- hebräisch (1)
- helicobacter (1)
- hematological disorders (1)
- hematopoietic SCT (1)
- hematopoietic stem cells (1)
- hemoglobin (1)
- hepatic stellate cells (1)
- hepatocellular carcinoma (1)
- heteromorphic sex chromosomes (1)
- heterozygosity (1)
- heuristics and biases (1)
- high resolution visualisation (1)
- high-altitude training (1)
- high-intensity interval training (1)
- high-intensity training (1)
- high-osmolarity glycerol (HOG) (1)
- high-risk hematology (1)
- high-risk prostate cancer (1)
- high-throughput (1)
- high-throughput screening (1)
- highly-active antiretroviral therapy (1)
- hip (1)
- hip replacement (1)
- hippocampal neurogenesis (1)
- hippocampus (1)
- histologic diversity (1)
- histology (1)
- histone H3 (1)
- histone acetylation (1)
- histone γH2AX (1)
- histopathology (1)
- historische Situation (1)
- homeostasisIon channels (1)
- homochirality (1)
- honeybee (1)
- hormona therapy (1)
- hormones (1)
- host cells (1)
- hour-glass (1)
- hourglass clock (1)
- human (1)
- human biomarker (1)
- human brain microvascular endothelial cells (1)
- human cell nucleus (1)
- human cholangiocellular carcinoma (1)
- human chromosome 6 (1)
- human ectoparasite (1)
- human hematopoiesis (1)
- human intrahepatic cholangiocarcinoma (1)
- human retinal pigment epithelium (1)
- humoral immunity (1)
- hybrid state (1)
- hydnocarpin (1)
- hydrogen bonding (1)
- hydrogenation (1)
- hydrophilic polymers (1)
- hypermethylated DNA (1)
- hypermethylation (1)
- hypersensitivity (1)
- hyperspectral autofluorescence imaging (1)
- hypertension (1)
- hyperthermia (1)
- hypertonic solution (1)
- hypertrophic cardiomyopathy (1)
- hyponatremia (1)
- hypothalamus (1)
- hypoxia-inducible factor 3A (1)
- höherkoordiniertes Silicium (1)
- iNOS (1)
- iberis amara extract (1)
- image data (1)
- image processing (1)
- image quality (1)
- immersion (1)
- immersive classroom (1)
- immersive classroom management (1)
- immune activation (1)
- immune cell recruitment (1)
- immune cells (1)
- immune escape (1)
- immune genes (1)
- immune response (1)
- immune-responses (1)
- immunoglobulin-e (1)
- immunohistochemistry (1)
- immunological reactivity (1)
- immunoreactive neurons (1)
- impulsivity (1)
- impurity profiling (1)
- in vitro Modell (1)
- in vitro contracture test (1)
- in-vitro (1)
- independent crossing (1)
- indian hedgehoc (1)
- indirect detection (1)
- induce cyclooxygenase-2 expression (1)
- induced superconductivity (1)
- induziert pluripotente Stammzelle (1)
- infant faces (1)
- infection control (1)
- infections (1)
- infinite dimensional optimization (1)
- inflammatory diseases (1)
- inflammatory pain (1)
- influenza A virus (1)
- influenza virus (1)
- informality (1)
- inhaltliche Richtigkeit (1)
- inherited metabolic disorders (1)
- innexins (1)
- insect flight (1)
- insects (1)
- insertable cardiac monitor (1)
- instructional support (1)
- insulin resistance (1)
- insulin signaling (1)
- insulin tolerance test (1)
- integraed care (1)
- integrins (1)
- intelligent vehicles (1)
- intensification (1)
- intensive glucose control (1)
- interaction partners (1)
- interband cascade laser (1)
- interface properties (1)
- interferon alpha (IFNα) (1)
- interferon alpha signalling (1)
- interferon signaling (1)
- interferon-alpha (1)
- interleukin-1β (1)
- interleukins (1)
- internalization (1)
- interstitial duplications (1)
- intestinal in vitro model (1)
- intestinal-type adenocarcinoma (1)
- intestine (1)
- intracellular hydrogen-peroxide (1)
- intracellular membranes (1)
- intracellular receptors (1)
- intracellular transport (1)
- intrachromosomal telomeric sequences (1)
- intraoperative (1)
- intraoperative radiotherapy (1)
- intraosseous (1)
- intrasexual competition (1)
- intrathecal application (1)
- intrazelluläre Domäne (1)
- intrusion detection (1)
- invasive aspergillosis (1)
- invasive fungal infections (1)
- invasive meningococcal disease (1)
- invasive vascular interventions (1)
- investigación (1)
- investigación de currículo universitario (1)
- inflammatory response (1)
- iota-toxin (1)
- iron (1)
- irrigated cropland extent (1)
- jasmonates (1)
- jasmonic acid biosynthesis (1)
- judgment (1)
- jump-diffusion processes (1)
- jumping spiders (1)
- junction proteins (1)
- kardiales Gewebe (1)
- kardiales Tissue Engineering (1)
- karyotypes (1)
- ketogenic dients (1)
- kidney (1)
- kidney disease (1)
- kinematics (1)
- kinetic study (1)
- kinetics (1)
- kinetische Untersuchung (1)
- knee rotator cuff (1)
- knees (1)
- knotenlose Sehnennaht (1)
- knowledge-based systems (1)
- kolorektale Karzinomzelllinien (1)
- kongenitale Zwerchfellhernie (1)
- kutikuläre Wasserpermeabilität (1)
- kutikuläres Blattwachs (1)
- lamivudine (1)
- land and water management (1)
- land-cover change (1)
- land-use change (1)
- landsat central asia (1)
- landscape compositionv (1)
- landscape development (1)
- language acquisition (1)
- laparoscopy/methods (1)
- large-scale assessment (1)
- larval drosophila (1)
- lasers (1)
- late gadolinium enhancement (1)
- late-onset (1)
- laterale Verdichtung (1)
- leaf beetle (1)
- learning outcomes (1)
- left ventricular hypertrophy (1)
- leg cramps (1)
- legionary ants (1)
- leukemia inhibitory factor (1)
- life history (1)
- light pulses (1)
- light sources (1)
- light-induced gene expression (1)
- light-matter coupling (1)
- light-trapping (1)
- light–matter interaction (1)
- linkage (1)
- linkes Vorhofohr (1)
- lipid desaturation (1)
- liquid-metal-jet anode X-ray source (1)
- lithium (1)
- liturgy (1)
- liver metastasis (1)
- lncRNAs (1)
- localization micoscopy (1)
- locked-in syndrome (1)
- locomotion (1)
- locomotor activity (1)
- long ncRNA (1)
- long-term survivors (1)
- lot streaming (1)
- low Mach number flows (1)
- low-threshold fibers (1)
- lower body (1)
- luciferase (1)
- lung and intrathoracic tumors (1)
- lungfish (1)
- lutetium-177 (1)
- lux (1)
- luxury brands (1)
- lymph node dissection (1)
- lymph nodes (1)
- lymphocyte differentiation (1)
- lymphoma (1)
- lysosomal storage disease (1)
- mRNA (1)
- machine leaning (1)
- macrocycle (1)
- macroecology (1)
- macrophage infectivity potentiator (1)
- magnetic dopants (1)
- magnetic fields (1)
- magnetic properties and materials (1)
- magnetic resonance spectroscopy (1)
- magnetic susceptibility (1)
- magnetism (1)
- magnetized sphere/cylinder (1)
- main-group chemistry (1)
- male rats (1)
- mammography (1)
- managing big data (1)
- mandible (1)
- marrow stromal cells (1)
- mass index (1)
- maternal behavior (1)
- mathematical model (1)
- mathematical modeling (1)
- matrix element effects (1)
- matrix metalloproteinases (1)
- maturation (1)
- max-linear model (1)
- max-stable process (1)
- mechanical energy (1)
- mechanical thrombectomy (1)
- mechanism (1)
- mechanisms (1)
- media education (1)
- media literacy (1)
- media psychology (1)
- medical collateral ligament (1)
- medical rehabilitation (1)
- meiotic ‘superring’ (1)
- melanoma (1)
- melanoma therapy (1)
- meliponines (1)
- membrane biophysics (1)
- membrane proteins (1)
- memory formation (1)
- men (1)
- meningococcal disease (1)
- merocyanines (1)
- mesenchymal stem cells (1)
- mesenchymal stem-cells (1)
- mesenchymale Stammzellen (1)
- messenger RNA (1)
- metabolic risk (1)
- metabolic syndrome (1)
- metacognitive prompting (1)
- metagenomics (1)
- metal borylene complexes (1)
- metal caponyls (1)
- metal cluster (1)
- metal-cluster hybrid systems (1)
- metal-to-ligand charge transfer (MLCT) (1)
- metallaboranes (1)
- metamorphosis (1)
- methylation (1)
- methylphenidate (1)
- miRNA (1)
- miRNA expression (1)
- miRNAs (1)
- micro-level analysis (1)
- microRNA-221 (1)
- microRNAs (1)
- microbiology (1)
- microcavity exciton polaritons (1)
- microcrystalline zinc hydroxyapatiteimpact (1)
- microglomeruli (1)
- microlaser (1)
- micronuclei (1)
- microprocessor (1)
- microscopy (1)
- microvascular endothelial cells (1)
- microwave radiation (1)
- middle Aged (1)
- middle ear (1)
- middle ear implant (1)
- migration (1)
- minimally conscious state (1)
- minimally important difference (1)
- minimally-invasive (1)
- minimum (1)
- mismatch (1)
- mitogen activated protein kinase (MAPK) (1)
- mitosis (1)
- mixed hearing loss (1)
- mobile devices (1)
- mobiler Auskunftsdienst (1)
- model (1)
- model following (1)
- modeling (1)
- modis (1)
- modulated arc therapy (1)
- modulation spectroscopy (1)
- molar tooth sign (1)
- molecular beam epitaxy (1)
- molecular biology (1)
- molecular biology of cytokines (1)
- molecular imaging (1)
- molecular mechanics (1)
- molecular neuroscience (1)
- molecular response in cml (1)
- molecular-structure (1)
- molekulardynamische Simulationen (1)
- monetary policy (1)
- monoclonal antibody 103.2 (1)
- monoclonal antibody 20.1 (1)
- monoclonial gammopathy (1)
- monocyte subset (1)
- monotone drawing (1)
- moral judgment (1)
- morphotypes (1)
- moths (1)
- motion (1)
- motor axonal neuropathy (1)
- motor control (1)
- motor development (1)
- mouse model (1)
- mouse models DNA damage (1)
- mouse-brain (1)
- mucosa (1)
- mucosal inflammation (1)
- multi-drug resistance (1)
- multifaceted approaches (1)
- multifocal choroiditis (1)
- multihit targeting (1)
- multimetallic complexes (1)
- multimodal (1)
- multimorbidity (1)
- multiple myeloma Lesions (1)
- multiple sequence alignments (1)
- multiple sklerosis (1)
- multipotente Stammzelle (1)
- music background (1)
- musical training (1)
- muskuloskelettalen Bildgebung (1)
- mutation detection (1)
- myeloma cells (1)
- myocardial infarction (1)
- myocardial lipid content (1)
- myocardial fibrosis (1)
- myocarditis (1)
- myocardium (1)
- myocyte (1)
- n-hexyl phthalate (1)
- nab-paclitaxel (1)
- naive T cells (1)
- nano LDH (1)
- nanoagent (1)
- nanographene (1)
- nanoparticle albumin-bound paclitaxel (1)
- nanophysics (1)
- nanotube (1)
- native chemical ligation (1)
- natural genetic variation (1)
- natural products (1)
- neck circumference (1)
- needle surface waxes (1)
- neoadjuvant (1)
- neovascularization, physiologic (1)
- nerve fibers (1)
- nerve ultrasonography (1)
- nervous-system (1)
- nervous-sytem (1)
- neural circuits (1)
- neural stem-cells (1)
- neuroendocrine tumor (1)
- neuroendocrine tumor (NET) (1)
- neurogenic locus notch homolog (1)
- neuroimaging (1)
- neuroimmunology (1)
- neuromyelitis optica (1)
- neuromyelitis optica spectrum disorders (NMOSD) (1)
- neuronal tracing (1)
- neuropathy (1)
- neuropeptides (1)
- neuroplasticity (1)
- neurotoxins (1)
- neurotransmission (1)
- neutralino (1)
- neutralizing antibody (1)
- neutrino detectors (1)
- neutrino emission (1)
- neutrino mass hierarchy (1)
- neutrino telescope (1)
- neutrophil (1)
- neutrophils (1)
- nhba (1)
- niche dynamics (1)
- nicht-visuell (1)
- nicotinic acetylcholine receptors (1)
- nitric oxide (1)
- nitrites (1)
- no-flow fraction (1)
- nocebo hyperalgesia (1)
- nodes of Ranvier (1)
- noise and multimode dynamics (1)
- non-crop habitats (1)
- non-destructive testing (1)
- non-invasive biomarkers (1)
- non-motor features (1)
- non-visual (1)
- nonadiabatic dynamics (1)
- nonlinear dynamics (1)
- norovirus (1)
- nuclear power (1)
- nuclear reactions (1)
- nuclear staining (1)
- nucleation elongation (1)
- nucleation-elongation model (1)
- nucleoside transporter (1)
- numerical hydrodynamics (1)
- numerische Hydrodynamik (1)
- nurses (1)
- obsessive-compulsive disorder (1)
- octopamine (1)
- off-targets (1)
- offshore (1)
- oil storage (1)
- older people (1)
- olfaction (1)
- olfactory receptor (1)
- oncology (1)
- oncolytic virus therapy (1)
- one-electron oxidation (1)
- online adaption (1)
- online monitoring system (1)
- online tool (1)
- onset craniopharyngioma (1)
- ontologies (1)
- open surgical repair (1)
- opponent processes (1)
- optic neuritis (1)
- optical coherence tomography (1)
- optical response (1)
- optics and photonics (1)
- optimal control theory (1)
- optoelectronics (1)
- ordinal categorical indicators (1)
- organic (1)
- organic synthesis (1)
- organische Halbleiter (1)
- organofunctionalized alkoxysilanes (1)
- organofunktionelle Alkoxysilane (1)
- organoid culture (1)
- orthotopic xenograft (1)
- osteogenes Potential (1)
- osteogenic potential (1)
- osteoporosis (1)
- otitis media (1)
- outer membrane protein (1)
- outer retinal tubulation (1)
- output elasticities (1)
- over-the-counter drugs (1)
- overload (1)
- oxide heterostructures (1)
- oxygen vacancies (1)
- oxygen-metabolism (1)
- oxytocin (1)
- p27(KIP1) (1)
- pCa (1)
- pICln (1)
- pacbio correction (1)
- palladium (1)
- pancreatobiliary type (1)
- panobinostat (1)
- parainfluenza virus (1)
- parasite biology (1)
- parasitic cell cycles (1)
- parasitic diseases (1)
- parasitic life cycles (1)
- parasitology (1)
- parental origin (1)
- partial integro-differential Fokker-Planck Equation (1)
- particle physics (1)
- pathogens (1)
- pathway analysis (1)
- patient education (1)
- pedagogy (1)
- pedagogía (1)
- pediatric brain tumor (1)
- pediatric hematology oncology (1)
- peer-to-peer Auskunftsdienst (1)
- pelvic organ prolapse/surgery (1)
- perforator (1)
- performance (1)
- performance diagnostics (1)
- performance monitoring (1)
- performance parameters (1)
- periodontal health (1)
- peripheral artery occlusive disease (1)
- peripheral injury (1)
- peripheral nerve (1)
- peripheral neuropathy (1)
- peripheral vision (1)
- peripheral-blood (1)
- perylene bisimide hydrogels (1)
- perylene dyes (1)
- phage display (1)
- phakomatosis pigmentovascularis (1)
- pharmacogenetics (1)
- phase transitions and critical phenomena (1)
- phasematching (1)
- phenology (1)
- phenomenology (1)
- phenotype (1)
- phenotypic microarray (1)
- phobische Stimuli (1)
- phonological awareness (1)
- phonological training (1)
- phosphoantigen (1)
- phosphocholine (1)
- phosphoproteomics (1)
- photoactivation (1)
- photoinduced electron transfer (1)
- photon bunching (1)
- photon lasing (1)
- photon statistics (1)
- photonics (1)
- photoperiodic time mesurement (1)
- photoreceptors (1)
- phototransduction (1)
- phyllosphere (1)
- phylotypic (1)
- physical therapy modalities (1)
- physicians (1)
- physiological traits (1)
- phytoprostanes (1)
- piRNA (1)
- pig model (1)
- pigment (1)
- pinned orbital moments (1)
- pitcher-plant mosquito (1)
- pituitary adenomas (1)
- pituitary gland (1)
- placebo hypoalgesia (1)
- planarian (1)
- planning variability (1)
- plans (1)
- plant cuticle (1)
- plant symbioses (1)
- plaque (1)
- plaque formation (1)
- plasma extravasation (1)
- plasmid copy number (1)
- plasminogen (1)
- plasticity (1)
- platelet dysfunction (1)
- platyhelminthes (1)
- polarimetric decomposition (1)
- polarition condensate (1)
- polariton laser (1)
- polarity effects (1)
- polarization vision (1)
- pollen analysis (1)
- pollution functions (1)
- polychoric correlation (1)
- polycyclic aromatic hydrocarbons (1)
- polymer characterization (1)
- polymer synthesis (1)
- polyomavirus (1)
- polypyridyl complexes (1)
- polysensitization (1)
- popliteal aneurysm (1)
- porphyrin chemistry (1)
- portable XRF (1)
- positive and negative affect (1)
- positive lymph node (1)
- positron emission tomography/computed tomography (1)
- post-processing (1)
- post-traumatic stress disorder (1)
- postoperative complications/epidemiology (1)
- postpartum (1)
- posttranslational modifications (1)
- pre-speech development (1)
- precedes multiple-myeloma (1)
- pregnancy (1)
- pregnancy gingivitis (1)
- preprocessing (1)
- preschool children (1)
- presence (1)
- preservice teacher education (1)
- prevention (1)
- prey selection (1)
- primary cutaneous marginal zone lymphomas (1)
- primary sclerosing cholangitis (1)
- principle of acceleration (1)
- probiotic lozenges (1)
- process mining (1)
- progenitors (1)
- prognosis (1)
- proliferating cell nuclear antigen (PCNA) (1)
- promoter affinity (1)
- promoter invasion (1)
- propensity score matching (1)
- prophage (1)
- prospective study (1)
- prostate-cancer (1)
- protein engineering (1)
- protein nebulization (1)
- protein phosphorylation (1)
- protein synthesis (1)
- protein translocation (1)
- protein ubiquitination (1)
- proteomes (1)
- proteomic analysis (1)
- proteomics (1)
- protocadherin gamma cluster (1)
- protophormia terraenovae (1)
- proximal method (1)
- proximal methods (1)
- pseudocarcinomatous hyperplasia (1)
- psoriasis (1)
- psychological placebo intervention (1)
- psychotherapeutic intervention (1)
- psychotherapeutische Intervention (1)
- pulmonary aspergillosis (1)
- pulmonary disease (1)
- pulmonary imaging (1)
- pulmonary toxicity (1)
- punishment (1)
- pustular exanthema (1)
- pyramidal neurons (1)
- pädiatrischen Tumoren (1)
- qRT-PCR (1)
- quadcopter (1)
- quality-control (1)
- quantitative assessments (1)
- quantum billiard (1)
- quantum chemical analysis (1)
- quantum dot laser (1)
- quantum dynamics (1)
- quantum transport (1)
- queens (1)
- quinine (1)
- quorum sensing (QS) (1)
- radar (1)
- radial Loewner equation (1)
- radial MR imaging (1)
- radiation sensitivity (1)
- radiation-therapy (1)
- radioactive waste (1)
- radiotherapy (1)
- rainforest (1)
- random forest models (1)
- randomized controlled clinical trial (1)
- randomized trial (1)
- ranscription factors (1)
- rare SNP (1)
- rare diseases (1)
- rats (1)
- reaction mechanism (1)
- reaction mechanisms (1)
- reaction-diffusion (1)
- reactive electrophilic species (1)
- reactive oxygen species (1)
- reaktive elektrophile Spezies (1)
- real-time PCR (1)
- receptor (1)
- receptor tyrosine kinase (1)
- recombinant proteins (1)
- recombinat-human-erythropoietin (1)
- reconsolidation (1)
- reconstruction (1)
- reconstructive surgical procedures/methods (1)
- recurrence (1)
- reflection (1)
- refugee crises (1)
- regenerative braking (1)
- regressive (1)
- regulatory T cells (1)
- reinforcement sensitivity theory (1)
- relapsed (1)
- relapsed and refractory (1)
- relaxation (1)
- relief (1)
- renal scintigraphy (1)
- renal system (1)
- renoprotection (1)
- repair and replication (1)
- repeated shuttle sprints (1)
- repeats (1)
- replication (1)
- reported outcomes (1)
- reporter genes (1)
- reproducible science (1)
- reproductive and developmental toxicity (1)
- reproductive character displacement (1)
- reproductive diapause (1)
- research (1)
- resolution limit (1)
- resource availability (1)
- respiratory syncytial virus (1)
- response inhibition (1)
- retinal dystrophies (1)
- retinal neuro-axonal damage (1)
- retro-cue (1)
- retrospective Studies (1)
- return to work (1)
- reverse transcriptase (1)
- reward (1)
- rheumatology (1)
- rhinitis (1)
- rhythmic components (1)
- ribavirin serum levels (1)
- ribonuclease H (1)
- ribosome (1)
- rice (1)
- right angle crossing (1)
- right inferior frontalgyrus (1)
- risk factor (1)
- risk-assesment (1)
- roaming reference (1)
- robustness (1)
- root growth (1)
- rostral-migratory-stream (1)
- rotator cuff (1)
- rotavirus (1)
- rotors (1)
- roving reference (1)
- rubber hand illusion (1)
- safety (1)
- salmonella (1)
- salmonids (1)
- salvage radiotherapy (1)
- sampling bias (1)
- sampling method (1)
- sarcoidosis (1)
- sarcopenia (1)
- sarcopterygian fish (1)
- scaffold (1)
- scalable quadcopter (1)
- sclerostin (1)
- second hit (1)
- secondary CNV (1)
- secondary lung tumors (1)
- seedlings (1)
- seeds (1)
- segmentation (1)
- selective accessibility (1)
- self-assembly (1)
- self-management (1)
- self-regulated learning (1)
- self-renewal (1)
- semantic technologies (1)
- semi-natural habitats (1)
- semismooth Newton method (1)
- sensory cues (1)
- sensory perception (1)
- sequencing protocol (1)
- serial RNA interactome capture (1)
- service infrastructure (1)
- settlement expansion (1)
- setup verification (1)
- sex pheromone (1)
- sexual development (1)
- shRNA (1)
- shock response (1)
- short Synacthen test (1)
- short-term memory (1)
- short-term methylphenidate brain (1)
- shoulder surgery (1)
- sialic acids (1)
- side effects (1)
- side-peak emission (1)
- signal peptides (1)
- signal transduction (1)
- signaling pathway (1)
- signalling pathways (1)
- silaboration (1)
- silybin (1)
- simulation system (1)
- simultane Losgrößen- und Reihenfolgeplanung (1)
- simultaneous embedding (1)
- single crystalline (1)
- single-molecule biophysics (1)
- site-controlled quantum dot (1)
- skeleton (1)
- skin anatomy (1)
- skin blood flow (1)
- skin cancer (1)
- skin conductance (1)
- skin diseases (1)
- skin equivalents (1)
- skin physiology (1)
- skinned fibers (1)
- sky-compass orientation (1)
- sleep (1)
- slope deposits (1)
- small RNA-sequencing (1)
- small cell lung cancer (1)
- small interfering RNAs (1)
- smooth orthogonal drawing (1)
- snRNPs (1)
- soccer (1)
- social experience (1)
- sodium channel (1)
- sodium uptake (1)
- software (1)
- solubility (1)
- soluble guanylate cyclase (1)
- solvents (1)
- somatic mutations (1)
- somatische Mutationen (1)
- somatostatin receptor (1)
- sorafenib (1)
- sp2-sp3 (1)
- spatial attention (1)
- speciation (1)
- species distribution model (1)
- species diversification (1)
- specific phobia (1)
- speckle tracking imaging (1)
- spectral characterization (1)
- spectral karyotyping (1)
- spectral-domain optical coherence tomography (1)
- spectroscopy (1)
- speed (1)
- sperm head formation (1)
- spermiogenesis (1)
- spillover (1)
- spin distribution (1)
- spin response (1)
- spine radiosurgery (1)
- spiroborates (1)
- sports technology (1)
- stage renal-disease (1)
- stage specific regulation (1)
- stalking predators (1)
- standard semiconductor laser (1)
- standards (1)
- static mixer (1)
- static test (1)
- stationärer Handel (1)
- statistical data (1)
- stellar evolution (1)
- stent implantation (1)
- sterol pathway (1)
- strained molecules (1)
- stress markers (1)
- stress signaling cascade (1)
- stressful life events (1)
- stroke (1)
- stroke prevention (1)
- stroke rehabilitation (1)
- structural equation models (1)
- structure (1)
- structure-based drug design (1)
- structured illumination microscopy (1)
- student simulation (1)
- sub-batches (1)
- subcutaneous adipose-tissue (1)
- subgingival (1)
- substantia nigra (1)
- substantive correctness (1)
- subthalamic nucleus (1)
- sun (1)
- super-resolution imaging (1)
- super-resolution microscopy (1)
- superconductors (1)
- supercurrent (1)
- superficial peroneal nerve (1)
- superradiant pulse emission (1)
- supersymmetry (1)
- support vector machines (1)
- suppression (1)
- supramolecular polymerization (1)
- sural nerve (1)
- surgery (1)
- surgical Mesh (1)
- surgical aneurysm treatment (1)
- survival (1)
- susceptibility (1)
- sustainability reporting (1)
- swim test (1)
- swimming (1)
- synaptic connections (1)
- synaptic inhibition (1)
- synaptic plasticity (1)
- synaptic vesicles (1)
- synapticplasticity (1)
- synaptische Funktion (1)
- syndrome (1)
- synthesis process (1)
- systemic immunosuppression (1)
- systemic inflammatory response syndrome (1)
- systemic sclerosis (1)
- tDCS (1)
- tactil (1)
- tactile (1)
- targeted re-sequencing (1)
- targets (1)
- tax arbitrage (1)
- tax haven (1)
- tax havens (1)
- taxonomic biases (1)
- taxonomy (1)
- team sport (1)
- technische Qualität (1)
- teeth (1)
- telomere length (1)
- telomeres (1)
- terminal alkynes (1)
- test facility (1)
- testosterone (1)
- testosterone production (1)
- tetrametallaborides (1)
- tetraorganoborate salt (1)
- therapy (1)
- thermal adaptation (1)
- thermonukelare Reaktionen (1)
- thermoregulation (1)
- thermotolerance (1)
- think-aloud data (1)
- thrombopoiesis (1)
- thrombus formation (1)
- thymectomy (1)
- tibial fracture fixation (1)
- tibial head fracture (1)
- time resolved spectroscopy (1)
- time series (1)
- time series analysis (1)
- time-resolved photoelectron spectroscopy (1)
- to-height ratio (1)
- tolerability (1)
- tomographic imaging method (1)
- tooth eruption (1)
- topological insulator (1)
- torque (1)
- total electric field (1)
- trachea (1)
- tracking (1)
- traffic (1)
- trafficking (1)
- training (1)
- training adaptation (1)
- training load (1)
- trans-splicing (1)
- transarterial chemoembolization (1)
- transcranial direct current stimulation (1)
- transcriptional profiling (1)
- transcriptome (1)
- transcriptome analysis (1)
- transfection (1)
- transferability (1)
- transient absorption (1)
- transition charge (1)
- transition density (1)
- transition dipole moment (1)
- transition temperature (1)
- translation (1)
- translational panic model (1)
- transperineal ultrasound (1)
- transpiration barrier (1)
- transporter protein associated with antigen processing-1 (TAP1) (1)
- transporters (1)
- transposable elements (1)
- treatment (1)
- treatment guidelines (1)
- tremor (1)
- tribes (1)
- triceps brachii (1)
- triglycerides (1)
- trimetallaborides (1)
- trisomy 21 (1)
- triterpenoids (1)
- tropical ecology (1)
- tropische Infektionskrankheiten (1)
- troponin T (1)
- trypanosoma brucei gambiense (1)
- tryptophan (1)
- trägerbasiertes Obturationssystem (1)
- tumor associated macrophages (1)
- tumor cell (1)
- tumor growth (1)
- tumor size (1)
- tundra (1)
- twin suppression (1)
- two-dimensional materials (1)
- two-dimensional nanostructures (1)
- tympanic membrane (1)
- type 2 diabetes (1)
- types of government (1)
- typically real functions (1)
- tyrosine kinase inhibitors (1)
- ubiquitin (1)
- ultimatum game (1)
- ultrasound (1)
- ultrastructure (1)
- ultraviolet light (1)
- undetermined significance (1)
- unfolded protein response (1)
- univalent functions (1)
- unmanned aerial vehicle (1)
- unnatural amino acid (1)
- unresponsive wakefulness syndrome (1)
- unstructured data (1)
- unstrukturierte Daten (1)
- upper body (1)
- upramolecular polymerization process (1)
- upstream regulator (1)
- urban growth modelling (1)
- urbanization (1)
- urinary incontinence/surgery (1)
- usability (1)
- user-centered design (1)
- uterine prolapse/surgery (1)
- uveal melanoma (1)
- v (1)
- vagina/surgery (1)
- valence (1)
- validation (1)
- vapor-liquid-solid (1)
- variant of unknown significance (1)
- vascular permeability (1)
- vascular type (1)
- vascularization (1)
- vasculitis (1)
- vasoconstriction (1)
- vegetation dynamics (1)
- vegetative state (1)
- vehicle dynamics (1)
- velocity (1)
- vertebral metastases (1)
- vertebrates (1)
- vesicles (1)
- vessel patency (1)
- vibration (1)
- vibroplasty (1)
- viral carcinogenesis (1)
- viral load (1)
- viral replication (1)
- viral shedding (1)
- virtual agent interaction (1)
- virtual reality T-maze (1)
- virtual reality training (1)
- virtual screening (1)
- virtualized environments (1)
- virtuelles Screening (1)
- visceral adiposity (1)
- viscosity (1)
- visual acuity (1)
- visual evoked potentials (1)
- visual orientation (1)
- visual working memory (1)
- visuell (1)
- vitamin D (1)
- volatile (1)
- volatile anesthetics (1)
- vorsprachliche Entwicklung (1)
- warranty of justice (1)
- wasp-mimicking (1)
- water (1)
- water oxidation reation (1)
- wave functions (1)
- wearable technologies (1)
- weight drop (1)
- weight gain (1)
- weight of evidence (1)
- whole genome duplications (1)
- whole genome sequencing (1)
- whole-body electromyostimulation (1)
- whole-genome shotgun sequencing (1)
- wild plant pollination (1)
- wine fermentation (1)
- wissenschaftlicher Nachwuchs (1)
- withdrawal (1)
- word clouds (1)
- words (1)
- work ability (1)
- work-related medical rehabilitation (1)
- working memory (1)
- wyeomyia smithii (1)
- xenopus oocytes (1)
- µ-Opioid receptor (1)
- Ältere (1)
- Ökonomischer Gewinn (1)
- Übergangsmetall (1)
- Übergangsmetallchloride (1)
- Übergangsmetallkomplexe (1)
- Übergangsmetalloxide (1)
- Übergewicht (1)
- Übertragung (1)
- überlappende Fertigung (1)
- π–π Stacking (1)
Institute
- Theodor-Boveri-Institut für Biowissenschaften (107)
- Universität - Fakultätsübergreifend (49)
- Medizinische Klinik und Poliklinik II (42)
- Physikalisches Institut (41)
- Graduate School of Life Sciences (40)
- Institut für Psychologie (37)
- Neurologische Klinik und Poliklinik (35)
- Medizinische Klinik und Poliklinik I (29)
- Julius-von-Sachs-Institut für Biowissenschaften (26)
- Rudolf-Virchow-Zentrum (23)
Schriftenreihe
Sonstige beteiligte Institutionen
- Alte Geschichte (1)
- Bavarian Center for Applied Energy Research e.V. (ZAE Bayern) (1)
- Bayerisches Geoinstitut, Universität Bayreuth (1)
- Beuth Hochschule für Technik Berlin (1)
- CUHAS Catholic University of Health and Allied Sciences Mwanza (1)
- Center for Nanosystems Chemistry (1)
- Department of Chemistry, Sungkyunkwan University, 440-746 Suwon, Republic of Korea (1)
- EMBL Mouse Biology Unit, Monterotondo, Italien (1)
- ESPCI Paris (1)
- Experimental Radiation Oncology, Department of Radiation Oncology, University Medical Center Mannheim (1)
Agricultural intensification often leads to fragmentation of natural habitats, such as forests, and thereby negatively affects forest specialist species. However, human introduced habitats, such as hedges, may counteract negative effects of forest fragmentation and increase dispersal, particularly of forest specialists. We studied effects of habitat type (forest edge versus hedge) and hedge isolation from forests (connected versus isolated hedge) in agricultural landscapes on abundance, species richness and community composition of mice, voles and shrews in forest edges and hedges. Simultaneously to these effects of forest edge/hedge type we analysed impacts of habitat structure, namely percentage of bare ground and forest edge/hedge width, on abundance, species richness and community composition of small mammals. Total abundance and forest specialist abundance (both driven by the most abundant species Myodes glareolus, bank vole) were higher in forest edges than in hedges, while hedge isolation had no effect. In contrast, abundance of habitat generalists was higher in isolated compared to connected hedges, with no effect of habitat type (forest edge versus hedge). Species richness as well as abundance of the most abundant habitat generalist Sorex araneus (common shrew), were not affected by habitat type or hedge isolation. Decreasing percentage of bare ground and increasing forest edge/hedge width was associated with increased abundance of forest specialists, while habitat structure was unrelated to species richness or abundance of any other group. Community composition was driven by forest specialists, which exceeded habitat generalist abundance in forest edges and connected hedges, while abundances were similar to each other in isolated hedges. Our results show that small mammal forest specialists prefer forest edges as habitats over hedges, while habitat generalists are able to use unoccupied ecological niches in isolated hedges. Consequently even isolated hedges can be marginal habitats for forest specialists and habitat generalists and thereby may increase regional farmland biodiversity.
Optical properties of AlSb/InAs/GaInSb/InAs/AlSb quantum wells (QWs) grown on an InAs substrate were investigated from the point of view of room temperature emission in the mid- and long-wavelength infrared ranges. By means of two independent techniques of optical spectroscopy, photoreflectance and temperature-dependent photoluminescence, it was proven that the main process limiting the performance of such InAs substrate-based type II structures is related to the escape of carriers from the hole ground state of the QW. Two nonradiative recombination channels were identified. The main process was attributed to holes tunneling to the valence band of the GaAsSb spacing layer and the second one with trapping of holes by native defects located in the same layer.
Aim
This 12-week prospective, randomized, double-blind, two-center trial evaluated the impact of a microcrystalline zinc hydroxyapatite (mHA) dentifrice on plaque formation rate (PFR) in chronic periodontitis patients. We hypothesized that mHA precipitates cause delayed plaque development when compared to a fluoridated control (AmF/SnF\(_{2}\)), and therefore would improve periodontal health.
Material & Methods
At baseline and after 4 and 12 weeks, PFR and other clinical and microbiological parameters were recorded. Seventy periodontitis patients received a mHA or AmF/SnF\(_{2}\) dentifrice as daily oral care without hygiene instructions. Four weeks after baseline, participants received full mouth debridement and continued using the dentifrices for another 8 weeks.
Results
Primary outcome PFR did not change statistically significantly from baseline to weeks 4 and 12, neither in mHA (n = 33; 51.7±17.2% vs. 48.5±16.65% vs. 48.4±19.9%) nor in AmF/SnF2-group (n = 34; 52.3±17.5% vs. 52.5±21.3% vs. 46.1±21.8%). Secondary clinical parameters such as plaque control record, gingival index, bleeding on probing, and pocket probing depth improved, but between-group differences were not statistically significant. Microbiological analyses showed similar slight decreases in colony-forming units in both groups.
Conclusion
In patients with mild-to-moderate periodontitis, periodontal therapy and use of a mHA-or AmF/SnF\(_{2}\) dentifrice without instructions induced comparable improvements in periodontal health but did not significantly reduce the PFR.
Gaze-independent brain-computer interfaces (BCIs) are a possible communication channel for persons with paralysis. We investigated if it is possible to use auditory stimuli to create a BCI for the Japanese Hiragana syllabary, which has 46 Hiragana characters. Additionally, we investigated if training has an effect on accuracy despite the high amount of different stimuli involved. Able-bodied participants (N = 6) were asked to select 25 syllables (out of fifty possible choices) using a two step procedure: First the consonant (ten choices) and then the vowel (five choices). This was repeated on 3 separate days. Additionally, a person with spinal cord injury (SCI) participated in the experiment. Four out of six healthy participants reached Hiragana syllable accuracies above 70% and the information transfer rate increased from 1.7 bits/min in the first session to 3.2 bits/min in the third session. The accuracy of the participant with SCI increased from 12% (0.2 bits/min) to 56% (2 bits/min) in session three. Reliable selections from a 10 × 5 matrix using auditory stimuli were possible and performance is increased by training. We were able to show that auditory P300 BCIs can be used for communication with up to fifty symbols. This enables the use of the technology of auditory P300 BCIs with a variety of applications.
Comparison of nonculture blood-based tests for diagnosing invasive aspergillosis in an animal model
(2016)
The European Aspergillus PCR Initiative (EAPCRI) has provided recommendations for the PCR testing of whole blood (WB) and serum/plasma. It is important to test these recommended protocols on nonsimulated "in vivo" specimens before full clinical evaluation. The testing of an animal model of invasive aspergillosis (IA) overcomes the low incidence of disease and provides experimental design and control that is not possible in the clinical setting. Inadequate performance of the recommended protocols at this stage would require reassessment of methods before clinical trials are performed and utility assessed. The manuscript describes the performance of EAPCRI protocols in an animal model of invasive aspergillosis. Blood samples taken from a guinea pig model of IA were used for WB and serum PCR. Galactomannan and beta-D-glucan detection were evaluated, with particular focus on the timing of positivity and on the interpretation of combination testing. The overall sensitivities for WB PCR, serum PCR, galactomannan, and beta-D-glucan were 73%, 65%, 68%, and 46%, respectively. The corresponding specificities were 92%, 79%, 80%, and 100%, respectively. PCR provided the earliest indicator of IA, and increasing galactomannan and beta-D-glucan values were indicators of disease progression. The combination of WB PCR with galactomannan and beta-D-glucan proved optimal (area under the curve AUC], 0.95), and IA was confidently diagnosed or excluded. The EAPRCI-recommended PCR protocols provide performance comparable to commercial antigen tests, and clinical trials are warranted. By combining multiple tests, IA can be excluded or confirmed, highlighting the need for a combined diagnostic strategy. However, this approach must be balanced against the practicality and cost of using multiple tests.
Transposon insertion sequencing is a high-throughput technique for assaying large libraries of otherwise isogenic transposon mutants providing insight into gene essentiality, gene function and genetic interactions. We previously developed the Transposon Directed Insertion Sequencing (TraDIS) protocol for this purpose, which utilizes shearing of genomic DNA followed by specific PCR amplification of transposon-containing fragments and Illumina sequencing. Here we describe an optimized high-yield library preparation and sequencing protocol for TraDIS experiments and a novel software pipeline for analysis of the resulting data. The Bio-Tradis analysis pipeline is implemented as an extensible Perl library which can either be used as is, or as a basis for the development of more advanced analysis tools. This article can serve as a general reference for the application of the TraDIS methodology.
Most research on human fear conditioning and its generalization has focused on adults whereas only little is known about these processes in children. Direct comparisons between child and adult populations are needed to determine developmental risk markers of fear and anxiety. We compared 267 children and 285 adults in a differential fear conditioning paradigm and generalization test. Skin conductance responses (SCR) and ratings of valence and arousal were obtained to indicate fear learning. Both groups displayed robust and similar differential conditioning on subjective and physiological levels. However, children showed heightened fear generalization compared to adults as indexed by higher arousal ratings and SCR to the generalization stimuli. Results indicate overgeneralization of conditioned fear as a developmental correlate of fear learning. The developmental change from a shallow to a steeper generalization gradient is likely related to the maturation of brain structures that modulate efficient discrimination between danger and (ambiguous) safety cues.
Maintenance of hematopoietic stem cells and their potential to give rise to progenitors of differentiated lymphoid and myeloid cells are accomplished by a network of regulatory processes. As a part of this network, the heteromeric transcription factor GA-binding protein (GABP) plays a crucial role in self-renewal of murine hematopoietic and leukemic stem cells. Here, we report the consequences of functional impairment of GABP in human hematopoietic and in leukemic stem/progenitor cells. Ectopic overexpression of a dominant-negative acting GABP mutant led to impaired myeloid differentiation of CD34\(^{+}\) hematopoietic stem/progenitor cells obtained from healthy donors. Moreover, drastically reduced clonogenic capacity of leukemic stem/progenitor cells isolated from bone marrow aspirates of chronic myeloid leukemia (CML) patients underlines the importance of GABP on stem/progenitor cell maintenance and confirms the relevance of GABP for human myelopoiesis in healthy and diseased states.
Background
Direct interaction between Red blood cells (RBCs) and platelets is known for a long time. The bleeding time is prolonged in anemic patients independent of their platelet count and could be corrected by transfusion of RBCs, which indicates that RBCs play an important role in hemostasis and platelet activation. However, in the last few years, opposing mechanisms of platelet inhibition by RBCs derived nitric oxide (NO) were proposed. The aim of our study was to identify whether RBCs could produce NO and activate soluble guanylate cyclase (sGC) in platelets.
Methods
To test whether RBCs could activate sGC under different conditions (whole blood, under hypoxia, or even loaded with NO), we used our well-established and highly sensitive models of NO-dependent sGC activation in platelets and activation of purified sGC. The activation of sGC was monitored by detecting the phosphorylation of Vasodilator Stimulated Phosphoprotein (VASPS239) by flow cytometry and Western blot. ANOVA followed by Bonferroni’s test and Student’s t-test were used as appropriate.
Results
We show that in the whole blood, RBCs prevent NO-mediated inhibition of ADP and TRAP6-induced platelet activation. Likewise, coincubation of RBCs with platelets results in strong inhibition of NO-induced sGC activation. Under hypoxic conditions, incubation of RBCs with NO donor leads to Hb-NO formation which inhibits sGC activation in platelets. Similarly, RBCs inhibit activation of purified sGC, even under conditions optimal for RBC-mediated generation of NO from nitrite.
Conclusions
All our experiments demonstrate that RBCs act as strong NO scavengers and prevent NO-mediated inhibition of activated platelets. In all tested conditions, RBCs were not able to activate platelet or purified sGC.
In computer-supported learning environments, the deployment of self-regulatory skills represents an essential prerequisite for successful learning. Metacognitive prompts are a promising type of instructional support to activate students’ strategic learning activities. However, despite positive effects in previous studies, there are still a large number of students who do not benefit from provided support. Therefore, it may be necessary to consider explicitly the conditions under which a prompt is beneficial for a student, i.e., so-called adaptive scaffolding. The current study aims to (i) classify the effectiveness of prompts on regulatory behavior, (ii) investigate the correspondence of the classification with learning outcome, and (iii) discover the conditions under which prompts induce regulatory activities (i.e., the proper temporal positioning of prompts). The think-aloud data of an experiment in which metacognitive prompts supported the experimental group (n = 35) was used to distinguish between effective and non-effective prompts. Students’ activities preceding the prompt presentation were analyzed using data mining and process mining techniques. The results indicate that approximately half of the presented prompts induced metacognitive learning activities as expected. Moreover, the number of induced monitoring activities correlates positively with transfer performance. Finally, the occurrence of orientation and monitoring activities, which are not well-embedded in the course of learning, increases the effectiveness of a presented prompt. In general, our findings demonstrate the benefits of investigating metacognitive support using process data, which can provide implications for the design of effective instructional support.
Frank-Rutger Hausmann war Professor für Romanische Philologie (Schwerpunkt französische und italienische Literatur) in Freiburg, Aachen und wiederum Freiburg. Hausmann hat sich zudem intensiv mit der Fachgeschichte der deutschen Romanistik und der Geisteswissenschaften allgemein beschäftigt. Für die zweite Ausgabe der promptus-Interviewreihe durften wir ihn nach seiner Perspektive auf die historische und aktuelle Situation der Romanistik befragen. Er arbeitet momentan u.a. an einem Romanistenlexikon, das online veröffentlicht wird, und hat das Romanistenarchiv in Augsburg gegründet.
Die Zeitschrift promptus – Würzburger Beiträge zur Romanistik richtet sich an alle NachwuchswissenschaftlerInnen im Bereich der romanistischen Sprach- und Literaturwissenschaft sowie der Fachdidaktik. Das Ziel der Zeitschrift ist die Förderung der romanistischen Forschung im Allgemeinen und des wissenschaftlichen Nachwuchses der Romanistik im Besonderen. Sie versteht sich damit als Impulsgeber für junge romanistische Forschung, ohne sich dabei thematisch zu beschränken.
Genetic Dissection of Aversive Associative Olfactory Learning and Memory in Drosophila Larvae
(2016)
Memory formation is a highly complex and dynamic process. It consists of different phases, which depend on various neuronal and molecular mechanisms. In adult Drosophila it was shown that memory formation after aversive Pavlovian conditioning includes—besides other forms—a labile short-term component that consolidates within hours to a longer-lasting memory. Accordingly, memory formation requires the timely controlled action of different neuronal circuits, neurotransmitters, neuromodulators and molecules that were initially identified by classical forward genetic approaches. Compared to adult Drosophila, memory formation was only sporadically analyzed at its larval stage. Here we deconstruct the larval mnemonic organization after aversive olfactory conditioning. We show that after odor-high salt conditioning larvae form two parallel memory phases; a short lasting component that depends on cyclic adenosine 3’5’-monophosphate (cAMP) signaling and synapsin gene function. In addition, we show for the first time for Drosophila larvae an anesthesia resistant component, which relies on radish and bruchpilot gene function, protein kinase C activity, requires presynaptic output of mushroom body Kenyon cells and dopamine function. Given the numerical simplicity of the larval nervous system this work offers a unique prospect for studying memory formation of defined specifications, at full-brain scope with single-cell, and single-synapse resolution.
The transcriptional coactivator Bob1 promotes the development of follicular T helper cells via Bcl6
(2016)
Follicular T helper (Tfh) cells are key regulators of the germinal center reaction and long-term humoral immunity. Tfh cell differentiation requires the sustained expression of the transcriptional repressor Bcl6; however, its regulation in CD4\(^+\) T cells is incompletely understood. Here, we report that the transcriptional coactivator Bob1, encoded by the Pou2af1 gene, promotes Bcl6 expression and Tfh cell development. We found that Bob1 together with the octamer transcription factors Oct1/Oct2 can directly bind to and transactivate the Bcl6 and Btla promoters. Mixed bone marrow chimeras revealed that Bob1 is required for the expression of normal levels of Bcl6 and BTLA, thereby controlling the pool size and composition of the Tfh compartment in a T cell-intrinsic manner. Our data indicate that T cell-expressed Bob1 is directly involved in Tfh cell differentiation and required for mounting normal T cell-dependent B-cell responses.
This paper provides an overview of current progress in the technological advances and the use of deep brain stimulation (DBS) to treat neurological and neuropsychiatric disorders, as presented by participants of the Fourth Annual DBS Think Tank, which was convened in March 2016 in conjunction with the Center for Movement Disorders and Neurorestoration at the University of Florida, Gainesveille FL, USA. The Think Tank discussions first focused on policy and advocacy in DBS research and clinical practice, formation of registries, and issues involving the use of DBS in the treatment of Tourette Syndrome. Next, advances in the use of neuroimaging and electrochemical markers to enhance DBS specificity were addressed. Updates on ongoing use and developments of DBS for the treatment of Parkinson's disease, essential tremor, Alzheimer's disease, depression, post-traumatic stress disorder, obesity, addiction were presented, and progress toward innovation(s) in closed-loop applications were discussed. Each section of these proceedings provides updates and highlights of new information as presented at this year's international Think Tank, with a view toward current and near future advancement of the field.
Aims: We set out to investigate the antibacterial activity of a new Mn-based photoactivated carbon monoxide-releasing molecule (PhotoCORM, [Mn(CO)\(_3\)(tpa-kappa\(^3\)N)]\(^+\)) against an antibiotic-resistant uropathogenic strain (EC958) of Escherichia coli. Results: Activated PhotoCORM inhibits growth and decreases viability of E. coli EC958, but non-illuminated carbon monoxide-releasing molecule (CORM) is without effect. NADH-supported respiration rates are significantly decreased by activated PhotoCORM, mimicking the effect of dissolved CO gas. CO from the PhotoCORM binds to intracellular targets, namely respiratory oxidases in strain EC958 and a bacterial globin heterologously expressed in strain K-12. However, unlike previously characterized CORMs, the PhotoCORM is not significantly accumulated in cells, as deduced from the cellular manganese content. Activated PhotoCORM reacts avidly with hydrogen peroxide producing hydroxyl radicals; the observed peroxide-enhanced toxicity of the PhotoCORM is ameliorated by thiourea. The PhotoCORM also potentiates the effect of the antibiotic, doxycycline. Innovation: The present work investigates for the first time the antimicrobial activity of a light-activated PhotoCORM against an antibiotic-resistant pathogen. A comprehensive study of the effects of the PhotoCORM and its derivative molecules upon illumination is performed and mechanisms of toxicity of the activated PhotoCORM are investigated. Conclusion: The PhotoCORM allows a site-specific and time-controlled release of CO in bacterial cultures and has the potential to provide much needed information on the generality of CORM activities in biology. Understanding the mechanism(s) of activated PhotoCORM toxicity will be key in exploring the potential of this and similar compounds as antimicrobial agents, perhaps in combinatorial therapies with other agents.
Endogenous Testosterone and Exogenous Oxytocin Modulate Attentional Processing of Infant Faces
(2016)
Evidence indicates that hormones modulate the intensity of maternal care. Oxytocin is known for its positive influence on maternal behavior and its important role for childbirth. In contrast, testosterone promotes egocentric choices and reduces empathy. Further, testosterone decreases during parenthood which could be an adaptation to increased parental investment. The present study investigated the interaction between testosterone and oxytocin in attentional control and their influence on attention to baby schema in women. Higher endogenous testosterone was expected to decrease selective attention to child portraits in a face-in-the-crowd-paradigm, while oxytocin was expected to counteract this effect. As predicted, women with higher salivary testosterone were slower in orienting attention to infant targets in the context of adult distractors. Interestingly, reaction times to infant and adult stimuli decreased after oxytocin administration, but only in women with high endogenous testosterone. These results suggest that oxytocin may counteract the adverse effects of testosterone on a central aspect of social behavior and maternal caretaking.
G-protein coupled receptors (GPCRs) can activate a heterotrimeric G-protein complex with subsecond kinetics. Genetically encoded biosensors based on Förster resonance energy transfer (FRET) are ideally suited for the study of such fast signaling events in single living cells. Here we report on the construction and characterization of three FRET biosensors for the measurement of Gα\(_{i1}\), Gα\(_{i2}\) and Gα\(_{i3}\) activation. To enable quantitative long-term imaging of FRET biosensors with high dynamic range, fluorescent proteins with enhanced photophysical properties are required. Therefore, we use the currently brightest and most photostable CFP variant, mTurquoise2, as donor fused to Gα\(_{i}\) subunit, and cp173Venus fused to the Gγ\(_{2}\) subunit as acceptor. The Gα\(_{i}\) FRET biosensors constructs are expressed together with Gβ\(_{1}\) from a single plasmid, providing preferred relative expression levels with reduced variation in mammalian cells. The Gα\(_{i}\) FRET sensors showed a robust response to activation of endogenous or over-expressed alpha-2A-adrenergic receptors, which was inhibited by pertussis toxin. Moreover, we observed activation of the Gα\(_{i}\) FRET sensor in single cells upon stimulation of several GPCRs, including the LPA\(_{2}\), M\(_{3}\) and BK\(_{2}\) receptor. Furthermore, we show that the sensors are well suited to extract kinetic parameters from fast measurements in the millisecond time range. This new generation of FRET biosensors for Gα\(_{i1}\), Gα\(_{i2}\) and Gα\(_{i3}\) activation will be valuable for live-cell measurements that probe Gα\(_{i}\) activation.
Background and Purpose
Ischemic stroke provokes severe brain damage and remains a predominant disease in industrialized countries. The coagulation factor XII (FXII)-driven contact activation system plays a central, but not yet fully defined pathogenic role in stroke development. Here, we investigated the efficacy of the FXIIa inhibitor rHA-Infestin-4 in a rat model of ischemic stroke using both a prophylactic and a therapeutic approach.
Methods
For prophylactic treatment, animals were treated intravenously with 100 mg/kg rHA-Infestin-4 or an equal volume of saline 15 min prior to transient middle cerebral artery occlusion (tMCAO) of 90 min. For therapeutic treatment, 100 mg/kg rHA-Infestin-4, or an equal volume of saline, was administered directly after the start of reperfusion. At 24 h after tMCAO, rats were tested for neurological deficits and blood was drawn for coagulation assays. Finally, brains were removed and analyzed for infarct area and edema formation.
Results
Within prophylactic rHA-Infestin-4 treatment, infarct areas and brain edema formation were reduced accompanied by better neurological scores and survival compared to controls. Following therapeutic treatment, neurological outcome and survival were still improved although overall effects were less pronounced compared to prophylaxis.
Conclusions
With regard to the central role of the FXII-driven contact activation system in ischemic stroke, inhibition of FXIIa may represent a new and promising treatment approach to prevent cerebral ischemia/reperfusion injury.
Traditionally, adversity was defined as the accumulation of environmental events (allostatic load). Recently however, a mismatch between the early and the later (adult) environment (mismatch) has been hypothesized to be critical for disease development, a hypothesis that has not yet been tested explicitly in humans. We explored the impact of timing of life adversity (childhood and past year) on anxiety and depression levels (N = 833) and brain morphology (N = 129). Both remote (childhood) and proximal (recent) adversities were differentially mirrored in morphometric changes in areas critically involved in emotional processing (i.e. amygdala/hippocampus, dorsal anterior cingulate cortex, respectively). The effect of adversity on affect acted in an additive way with no evidence for interactions (mismatch). Structural equation modeling demonstrated a direct effect of adversity on morphometric estimates and anxiety/depression without evidence of brain morphology functioning as a mediator. Our results highlight that adversity manifests as pronounced changes in brain morphometric and affective temperament even though these seem to represent distinct mechanistic pathways. A major goal of future studies should be to define critical time periods for the impact of adversity and strategies for intervening to prevent or reverse the effects of adverse childhood life experiences.
Invasive aspergillosis (IA) is a devastating opportunistic infection and its treatment constitutes a considerable burden for the health care system. Immunocompromised patients are at an increased risk for IA, which is mainly caused by the species Aspergillus fumigatus. An early and reliable diagnosis is required to initiate the appropriate antifungal therapy. However, diagnostic sensitivity and accuracy still needs to be improved, which can be achieved at least partly by the definition of new biomarkers. Besides the direct detection of the pathogen by the current diagnostic methods, the analysis of the host response is a promising strategy toward this aim. Following this approach, we sought to identify new biomarkers for IA. For this purpose, we analyzed gene expression profiles of hematological patients and compared profiles of patients suffering from IA with non-IA patients. Based on microarray data, we applied a comprehensive feature selection using a random forest classifier. We identified the transcript coding for the S100 calcium-binding protein B (S100B) as a potential new biomarker for the diagnosis of IA. Considering the expression of this gene, we were able to classify samples from patients with IA with 82.3% sensitivity and 74.6% specificity. Moreover, we validated the expression of S100B in a real-time reverse transcription polymerase chain reaction (RT-PCR) assay and we also found a down-regulation of S100B in A. fumigatus stimulated DCs. An influence on the IL1B and CXCL1 downstream levels was demonstrated by this S100B knockdown. In conclusion, this study covers an effective feature selection revealing a key regulator of the human immune response during IA. S100B may represent an additional diagnostic marker that in combination with the established techniques may improve the accuracy of IA diagnosis.
Purpose
Wilms tumor (WT) is the most common pediatric renal tumor. Treatment planning under International Society of Paediatric Oncology (SIOP) protocols is based on staging and histologic assessment of response to preoperative chemotherapy. Despite high overall survival (OS), many relapses occur in patients without specific risk factors, and many successfully treated patients are exposed to treatments with significant risks of late effects. To investigate whether molecular biomarkers could improve risk stratification, we assessed 1q status and other potential copy number biomarkers in a large WT series.
Materials and Methods
WT nephrectomy samples from 586 SIOP WT 2001 patients were analyzed using a multiplex ligation-dependent probe amplification (MLPA) assay that measured the copy number of 1q and other regions of interest.
Results
One hundred sixty-seven (28%) of 586 WTs had 1q gain. Five-year event-free survival (EFS) was 75.0% in patients with 1q gain (95% CI, 68.5% to 82.0%) and 88.2% in patients without gain (95% CI, 85.0% to 91.4%). OS was 88.4% with gain (95% CI, 83.5% to 93.6%) and 94.4% without gain (95% CI, 92.1% to 96.7%). In univariable analysis, 1q gain was associated with poorer EFS (P<.001; hazard ratio, 2.33) and OS (P=.01; hazard ratio, 2.16). The association of 1q gain with poorer EFS retained significance in multivariable analysis adjusted for 1p and 16q loss, sex, stage, age, and histologic risk group. Gain of 1q remained associated with poorer EFS in tumor subsets limited to either intermediate-risk localized disease or nonanaplastic localized disease. Other notable aberrations associated with poorer EFS included MYCN gain and TP53 loss.
Conclusion
Gain of 1q is a potentially valuable prognostic biomarker in WT, in addition to histologic response to preoperative chemotherapy and tumor stage.
Enhanced expression of the MYC transcription factor is observed in the majority of tumors. Two seemingly conflicting models have been proposed for its function: one proposes that MYC enhances expression of all genes, while the other model suggests gene-specific regulation. Here, we have explored the hypothesis that specific gene expression profiles arise since promoters differ in affinity for MYC and high-affinity promoters are fully occupied by physiological levels of MYC. We determined cellular MYC levels and used RNA- and ChIP-sequencing to correlate promoter occupancy with gene expression at different concentrations of MYC. Mathematical modeling showed that binding affinities for interactions of MYC with DNA and with core promoter-bound factors, such as WDR5, are sufficient to explain promoter occupancies observed in vivo. Importantly, promoter affinity stratifies different biological processes that are regulated by MYC, explaining why tumor-specific MYC levels induce specific gene expression programs and alter defined biological properties of cells.
Hyponatremia (HN) is a common condition, with a large number of etiologies and a complicated treatment. Although chronic HN has been shown to be a predictor of poor outcome, sodium-increasing treatments in chronic stable and asymptomatic HN have not proven to increase life expectancy. For symptomatic HN, in contrast, the necessity for urgent treatment has broadly been accepted to avoid the development of fatal cerebral edema. On the other hand, a too rapid increase of serum sodium in chronic HN may result in cerebral damage due to osmotic demyelinisation. Recently, administration of hypertonic saline bolus has been recommended as first-line treatment in patients with moderate-to-severe symptomatic HN. This approach is easy to memorize and holds the potential to greatly facilitate the initial treatment of symptomatic HN. First-line treatment of chronic HN is fluid restriction and if ineffective treatment with tolvaptan or in some patients other agents should be considered. A number of recommendations and guidelines have been published on HN. In the present review, the management of patients with HN in relation to everyday clinical practice is summarized with focus on the acute management.
Background
Invasive fungal infections with Candida albicans (C. albicans) occur frequently in extremely low birthweight (ELBW) infants and are associated with poor outcome. Phagocytosis of C.albicans initializes apoptosis in monocytes (phagocytosis induced cell death, PICD). PICD is reduced in neonatal cord blood monocytes (CBMO).
Hypothesis
Phagocytosis of C. albicans causes PICD which differs between neonatal monocytes (CBMO) and adult peripheral blood monocytes (PBMO) due to lower stimulation of TLR-mediated immune responses.
Methods
The ability to phagocytose C. albicans, expression of TLRs, the induction of apoptosis (assessment of sub-G1 and nick-strand breaks) were analyzed by FACS. TLR signalling was induced by agonists such as lipopolysaccharide (LPS), Pam3Cys, FSL-1 and Zymosan and blocked (neutralizing TLR2 antibodies and MYD88 inhibitor).
Results
Phagocytic indices of PBMO and CBMO were similar. Following stimulation with agonists and C. albicans induced up-regulation of TLR2 and consecutive phosphorylation of MAP kinase P38 and expression of TNF-α, which were stronger on PBMO compared to CBMO (p < 0.005). Downstream, TLR2 signalling initiated caspase-3-dependent PICD which was found reduced in CBMO (p < 0.05 vs PBMO).
Conclusion
Our data suggest direct involvement of TLR2-signalling in C. albicans-induced PICD in monocytes and an alteration of this pathway in CBMO.
Base J, β-D-glucosyl-hydroxymethyluracil, is a chromatin modification of thymine in the nuclear DNA of flagellated protozoa of the order Kinetoplastida. In Trypanosoma brucei, J is enriched, along with histone H3 variant (H3.V), at sites involved in RNA Polymerase (RNAP) II termination and telomeric sites involved in regulating variant surface glycoprotein gene (VSG) transcription by RNAP I. Reduction of J in T. brucei indicated a role of J in the regulation of RNAP II termination, where the loss of J at specific sites within polycistronic gene clusters led to read-through transcription and increased expression of downstream genes. We now demonstrate that the loss of H3.V leads to similar defects in RNAP II termination within gene clusters and increased expression of downstream genes. Gene derepression is intensified upon the subsequent loss of J in the H3.V knockout. mRNA-seq indicates gene derepression includes VSG genes within the silent RNAP I transcribed telomeric gene clusters, suggesting an important role for H3.V in telomeric gene repression and antigenic variation. Furthermore, the loss of H3.V at regions of overlapping transcription at the end of convergent gene clusters leads to increased nascent RNA and siRNA production. Our results suggest base J and H3.V can act independently as well as synergistically to regulate transcription termination and expression of coding and non-coding RNAs in T. brucei, depending on chromatin context (and transcribing polymerase). As such these studies provide the first direct evidence for histone H3.V negatively influencing transcription elongation to promote termination.
We demonstrated previously that phosphocholine and phosphocholine-modified macromolecules efficiently inhibit ATP-dependent release of interleukin-1β from human and murine monocytes by a mechanism involving nicotinic acetylcholine receptors (nAChR). Interleukin-1β is a potent pro-inflammatory cytokine of innate immunity that plays pivotal roles in host defence. Control of interleukin-1β release is vital as excessively high systemic levels cause life threatening inflammatory diseases. In spite of its structural similarity to acetylcholine, there are no other reports on interactions of phosphocholine with nAChR. In this study, we demonstrate that phosphocholine inhibits ion-channel function of ATP receptor P2X7 in monocytic cells via nAChR containing α9 and α10 subunits. In stark contrast to choline, phosphocholine does not evoke ion current responses in Xenopus laevis oocytes, which heterologously express functional homomeric nAChR composed of α9 subunits or heteromeric receptors containing α9 and α10 subunits. Preincubation of these oocytes with phosphocholine, however, attenuated choline-induced ion current changes, suggesting that phosphocholine may act as a silent agonist. We conclude that phophocholine activates immuno-modulatory nAChR expressed by monocytes but does not stimulate canonical ionotropic receptor functions.
Attraction to ethanol is common in both flies and humans, but the neuromodulatory mechanisms underlying this innate attraction are not well understood. Here, we dissect the function of the key regulator of serotonin signaling—the serotonin transporter–in innate olfactory attraction to ethanol in Drosophila melanogaster. We generated a mutated version of the serotonin transporter that prolongs serotonin signaling in the synaptic cleft and is targeted via the Gal4 system to different sets of serotonergic neurons. We identified four serotonergic neurons that inhibit the olfactory attraction to ethanol and two additional neurons that counteract this inhibition by strengthening olfactory information. Our results reveal that compensation can occur on the circuit level and that serotonin has a bidirectional function in modulating the innate attraction to ethanol. Given the evolutionarily conserved nature of the serotonin transporter and serotonin, the bidirectional serotonergic mechanisms delineate a basic principle for how random behavior is switched into targeted approach behavior.
Background
A phase I/II study and subsequent phase III study (MPACT) reported significant correlations between CA19-9 decreases and prolonged overall survival (OS) with nab-paclitaxel plus gemcitabine (nab-P + Gem) treatment for metastatic pancreatic cancer (MPC). CA19-9 changes at week 8 and potential associations with efficacy were investigated as part of an exploratory analysis in the MPACT trial.
Patients and methods
Untreated patients with MPC (N = 861) received nab-P + Gem or Gem alone. CA19-9 was evaluated at baseline and every 8 weeks.
Results
Patients with baseline and week-8 CA19-9 measurements were analyzed (nab-P + Gem: 252; Gem: 202). In an analysis pooling the treatments, patients with any CA19-9 decline (80%) versus those without (20%) had improved OS (median 11.1 versus 8.0 months; P = 0.005). In the nab-P + Gem arm, patients with (n = 206) versus without (n = 46) any CA19-9 decrease at week 8 had a confirmed overall response rate (ORR) of 40% versus 13%, and a median OS of 13.2 versus 8.3 months (P = 0.001), respectively. In the Gem-alone arm, patients with (n = 159) versus without (n = 43) CA19-9 decrease at week 8 had a confirmed ORR of 15% versus 5%, and a median OS of 9.4 versus 7.1 months (P = 0.404), respectively. In the nab-P + Gem and Gem-alone arms, by week 8, 16% (40/252) and 6% (13/202) of patients, respectively, had an unconfirmed radiologic response (median OS 13.7 and 14.7 months, respectively), and 79% and 84% of patients, respectively, had stable disease (SD) (median OS 11.1 and 9 months, respectively). Patients with SD and any CA19-9 decrease (158/199 and 133/170) had a median OS of 13.2 and 9.4 months, respectively.
Conclusion
This analysis demonstrated that, in patients with MPC, any CA19-9 decrease at week 8 can be an early marker for chemotherapy efficacy, including in those patients with SD. CA19-9 decrease identified more patients with survival benefit than radiologic response by week 8.
Large-Scale Assessment of a Fully Automatic Co-Adaptive Motor Imagery-Based Brain Computer Interface
(2016)
In the last years Brain Computer Interface (BCI) technology has benefited from the development of sophisticated machine leaning methods that let the user operate the BCI after a few trials of calibration. One remarkable example is the recent development of co-adaptive techniques that proved to extend the use of BCIs also to people not able to achieve successful control with the standard BCI procedure. Especially for BCIs based on the modulation of the Sensorimotor Rhythm (SMR) these improvements are essential, since a not negligible percentage of users is unable to operate SMR-BCIs efficiently. In this study we evaluated for the first time a fully automatic co-adaptive BCI system on a large scale. A pool of 168 participants naive to BCIs operated the co-adaptive SMR-BCI in one single session. Different psychological interventions were performed prior the BCI session in order to investigate how motor coordination training and relaxation could influence BCI performance. A neurophysiological indicator based on the Power Spectral Density (PSD) was extracted by the recording of few minutes of resting state brain activity and tested as predictor of BCI performances. Results show that high accuracies in operating the BCI could be reached by the majority of the participants before the end of the session. BCI performances could be significantly predicted by the neurophysiological indicator, consolidating the validity of the model previously developed. Anyway, we still found about 22% of users with performance significantly lower than the threshold of efficient BCI control at the end of the session. Being the inter-subject variability still the major problem of BCI technology, we pointed out crucial issues for those who did not achieve sufficient control. Finally, we propose valid developments to move a step forward to the applicability of the promising co-adaptive methods.
While an increasing number of conserved small regulatory RNAs (sRNAs) are known to function in general bacterial physiology, the roles and modes of action of sRNAs from horizontally acquired genomic regions remain little understood. The IsrK sRNA of Gifsy-1 prophage of Salmonella belongs to the latter class. This regulatory RNA exists in two isoforms. The first forms, when a portion of transcripts originating from isrK promoter reads-through the IsrK transcription-terminator producing a translationally inactive mRNA target. Acting in trans, the second isoform, short IsrK RNA, binds the inactive transcript rendering it translationally active. By switching on translation of the first isoform, short IsrK indirectly activates the production of AntQ, an antiterminator protein located upstream of isrK. Expression of antQ globally interferes with transcription termination resulting in bacterial growth arrest and ultimately cell death. Escherichia coli and Salmonella cells expressing AntQ display condensed chromatin morphology and localization of UvrD to the nucleoid. The toxic phenotype of AntQ can be rescued by co-expression of the transcription termination factor, Rho, or RNase H, which protects genomic DNA from breaks by resolving R-loops. We propose that AntQ causes conflicts between transcription and replication machineries and thus promotes DNA damage. The isrK locus represents a unique example of an island-encoded sRNA that exerts a highly complex regulatory mechanism to tune the expression of a toxic protein.
Under adequate conditions, cavity polaritons form a macroscopic coherent quantum state, known as polariton condensate. Compared to Wannier-Mott excitons in inorganic semiconductors, the localized Frenkel excitons in organic emitter materials show weaker interaction with each other but stronger coupling to light, which recently enabled the first realization of a polariton condensate at room temperature. However, this required ultrafast optical pumping, which limits the applications of organic polariton condensates. We demonstrate room temperature polariton condensates of cavity polaritons in simple laminated microcavities filled with biologically produced enhanced green fluorescent protein (eGFP). The unique molecular structure of eGFP prevents exciton annihilation even at high excitation densities, thus facilitating polariton condensation under conventional nanosecond pumping. Condensation is clearly evidenced by a distinct threshold, an interaction-induced blueshift of the condensate, long-range coherence, and the presence of a second threshold at higher excitation density that is associated with the onset of photon lasing.
Course of disease in multifocal choroiditis lacking sufficient immunosuppression: a case report
(2016)
Background:
Multifocal choroiditis with panuveitis is a rare disease. The educational merit of this case presentation results from the good documentation and the impressive ocular fundus pictures.
Case presentation:
We illustrate the 3-year course of disease in a 22-year-old myopic white woman with multifocal choroiditis with panuveitis and secondary choroidal neovascularization. The activity of the disease was evaluated clinically by optical coherence tomography and fluorescein angiography. Choroidal neovascularization was treated by intravitreal bevacizumab (2.5 mg/0.1 ml). Our patient lacked systemic therapy for the first 11 months because of noncompliance.
Conclusions:
The case is remarkable as the delayed onset of peripheral lesions and the additional existence of high myopia made diagnosis difficult. In addition, it demonstrates that full outbreak of disease with multiple central and peripheral fundus lesions and secondary choroidal neovascularization can develop without systemic treatment.
Before the introduction of erythropoiesis-stimulating agents (ESAs) in 1989, repeated transfusions given to patients with end-stage renal disease caused iron overload, and the need for supplemental iron was rare. However, with the widespread introduction of ESAs, it was recognized that supplemental iron was necessary to optimize hemoglobin response and allow reduction of the ESA dose for economic reasons and recent concerns about ESA safety. Iron supplementation was also found to be more efficacious via intravenous compared to oral administration, and the use of intravenous iron has escalated in recent years. The safety of various iron compounds has been of theoretical concern due to their potential to induce iron overload, oxidative stress, hypersensitivity reactions, and a permissive environment for infectious processes. Therefore, an expert group was convened to assess the benefits and risks of parenteral iron, and to provide strategies for its optimal use while mitigating the risk for acute reactions and other adverse effects.
We present evidence for the existence of a hybrid state of Tamm plasmons and microcavity exciton polaritons in a II-VI material based microcavity sample covered with an Ag metal layer. The bare cavity mode shows a characteristic anticrossing with the Tamm-plasmon mode, when microreflectivity measurements are performed for different detunings between the Tamm plasmon and the cavity mode. When the Tamm-plasmon mode is in resonance with the cavity polariton four hybrid eigenstates are observed due to the coupling of the cavity-photon mode, the Tamm-plasmon mode, and the heavy- and light-hole excitons. If the bare Tamm-plasmon mode is tuned, these resonances will exhibit three anticrossings. Experimental results are in good agreement with calculations based on the transfer matrix method as well as on the coupled-oscillators model. The lowest hybrid eigenstate is observed to be red shifted by about 13 meV with respect to the lower cavity polariton state when the Tamm plasmon is resonantly coupled with the cavity polariton. This spectral shift which is caused by the metal layer can be used to create a trapping potential channel for the polaritons. Such channels can guide the polariton propagation similar to one-dimensional polariton wires.
Blood glucose control is the primary strategy to prevent complications in diabetes. At the onset of kidney disease, therapies that inhibit components of the renin angiotensin system (RAS) are also indicated, but these approaches are not wholly effective. Here, we show that once daily administration of the novel glucose lowering agent, empagliflozin, an SGLT2 inhibitor which targets the kidney to block glucose reabsorption, has the potential to improve kidney disease in type 2 diabetes. In male db/db mice, a 10-week treatment with empagliflozin attenuated the diabetes-induced upregulation of profibrotic gene markers, fibronectin and transforming-growth-factor-beta. Other molecular (collagen IV and connective tissue growth factor) and histological (tubulointerstitial total collagen and glomerular collagen IV accumulation) benefits were seen upon dual therapy with metformin. Albuminuria, urinary markers of tubule damage (kidney injury molecule-1, KIM-1 and neutrophil gelatinase-associated lipocalin, NGAL), kidney growth, and glomerulosclerosis, however, were not improved with empagliflozin or metformin, and plasma and intra-renal renin activity was enhanced with empagliflozin. In this model, blood glucose lowering with empagliflozin attenuated some molecular and histological markers of fibrosis but, as per treatment with metformin, did not provide complete renoprotection. Further research to refine the treatment regimen in type 2 diabetes and nephropathy is warranted.
Recently, a genome-wide analysis identified DNA methylation of the HIF3A (hypoxia-inducible factor 3A) as strongest correlate of BMI. Here we tested the hypothesis that HIF3A mRNA expression and CpG-sites methylation in adipose tissue (AT) and genetic variants in HIF3A are related to parameters of AT distribution and function. In paired samples of subcutaneous AT (SAT) and visceral AT (VAT) from 603 individuals, we measured HIF3A mRNA expression and analyzed its correlation with obesity and related traits. In subgroups of individuals, we investigated the effects on HIF3A genetic variants on its AT expression (N = 603) and methylation of CpG-sites (N = 87). HIF3A expression was significantly higher in SAT compared to VAT and correlated with obesity and parameters of AT dysfunction (including CRP and leucocytes count). HIF3A methylation at cg22891070 was significantly higher in VAT compared to SAT and correlated with BMI, abdominal SAT and VAT area. Rs8102595 showed a nominal significant association with AT HIF3A methylation levels as well as with obesity and fat distribution. HIF3A expression and methylation in AT are fat depot specific, related to obesity and AT dysfunction. Our data support the hypothesis that HIF pathways may play an important role in the development of AT dysfunction in obesity.
Gefitinib, an EGFR tyrosine kinase inhibitor, is used as FDA approved drug in breast cancer and non-small cell lung cancer treatment. However, this drug has certain side effects and complications for which the underlying molecular mechanisms are not well understood. By systems biology based in silico analysis, we identified off-targets of gefitinib that might explain side effects of this drugs. The crystal structure of EGFR-gefitinib complex was used for binding pocket similarity searches on a druggable proteome database (Sc-PDB) by using IsoMIF Finder. The top 128 hits of putative off-targets were validated by reverse docking approach. The results showed that identified off-targets have efficient binding with gefitinib. The identified human specific off-targets were confirmed and further analyzed for their links with biological process and clinical disease pathways using retrospective studies and literature mining, respectively. Noticeably, many of the identified off-targets in this study were reported in previous high-throughput screenings. Interestingly, the present study reveals that gefitinib may have positive effects in reducing brain and bone metastasis, and may be useful in defining novel gefitinib based treatment regime. We propose that a system wide approach could be useful during new drug development and to minimize side effect of the prospective drug.
Objective:
To assess the therapy-related risk of malignancies in mitoxantrone-treated patients with multiple sclerosis.
Methods:
This retrospective observational cohort study included all mitoxantrone-treated patients with multiple sclerosis seen at our department between 1994 and 2007. We collected follow-up information on medically confirmed malignancies, life status, and cause of death, as of 2010. Malignancy rates were compared to the German national cancer registry matched for sex, age, and year of occurrence.
Results:
Follow-up was completed in 676 of 677 identified patients. Median follow-up time was 8.7 years (interquartile range 6.8-11.2), corresponding to 6,220 person-years. Median cumulative mitoxantrone dose was 79.0 mg/m(2) (interquartile range 50.8-102.4). Thirty-seven patients (5.5%) were diagnosed with a malignancy after mitoxantrone initiation, revealing a standardized incidence ratio of 1.50 (95% confidence interval CI] 1.05-2.08). Entities included breast cancer (n = 9), colorectal cancer (n = 7), acute myeloid leukemia (n = 4, 0.6%), and others (each entity n = 1 or 2). The standardized incidence ratio of colorectal cancer was 2.98 (95% CI 1.20-6.14) and of acute myeloid leukemia 10.44 (95% CI 3.39-24.36). It was not increased for other entities including breast cancer. Multivariate Cox regression identified higher age at treatment initiation but neither cumulative mitoxantrone dose (>75 vs 75 mg/m(2)) nor treatment with other immunosuppressive drugs or sex as a risk factor. Fifty-five patients had died, among them 12 of a malignancy and 43 reportedly of other causes.
Conclusions:
While the overall incidence of malignancies was only mildly increased, the risk of leukemia and colorectal cancer was heightened. If confirmed, posttherapy colonoscopy could become advisable.
The unification of two major approaches to moral judgment is the purpose of the present approach. Kohlberg's well-known stage theory assumes a sequence of discrete stages that underlie all moral judgment. Stage theory recognizes the problem of integrating considerations but gives no way to solve such integration, even with information from any one stage. And, of course, the stage concept denies any significant integration from different stages. Thus, research on moral judgment needs to study the integration problem which can be tested within Anderson's theory of information integration. The main purpose of the present study was to extend this unificationist approach to the issue of sexual morality. A novel task presents information from two very different stages. The results showed that in contrast to discreteness the stage informers were positively correlated in punishment judgments of both genders about consensual sex of juveniles. Furthermore, the subjects integrated considerations from those very different stages also in contrast to the hypothesis that only a single stage was operative at any time.
Sequence Logos and its variants are the most commonly used method for visualization of multiple sequence alignments (MSAs) and sequence motifs. They provide consensus-based summaries of the sequences in the alignment. Consequently, individual sequences cannot be identified in the visualization and covariant sites are not easily discernible. We recently proposed Sequence Bundles, a motif visualization technique that maintains a one-to-one relationship between sequences and their graphical representation and visualizes covariant sites. We here present Alvis, an open-source platform for the joint explorative analysis of MSAs and phylogenetic trees, employing Sequence Bundles as its main visualization method. Alvis combines the power of the visualization method with an interactive toolkit allowing detection of covariant sites, annotation of trees with synapomorphies and homoplasies, and motif detection. It also offers numerical analysis functionality, such as dimension reduction and classification. Alvis is user-friendly, highly customizable and can export results in publication-quality figures. It is available as a full-featured standalone version (http://www.bitbucket.org/rfs/alvis) and its Sequence Bundles visualization module is further available as a web application (http://science-practice.com/projects/sequence-bundles).
Mutation Detection in Patients with Retinal Dystrophies Using Targeted Next Generation Sequencing
(2016)
Retinal dystrophies (RD) constitute a group of blinding diseases that are characterized by clinical variability and pronounced genetic heterogeneity. The different nonsyndromic and syndromic forms of RD can be attributed to mutations in more than 200 genes. Consequently, next generation sequencing (NGS) technologies are among the most promising approaches to identify mutations in RD. We screened a large cohort of patients comprising 89 independent cases and families with various subforms of RD applying different NGS platforms. While mutation screening in 50 cases was performed using a RD gene capture panel, 47 cases were analyzed using whole exome sequencing. One family was analyzed using whole genome sequencing. A detection rate of 61% was achieved including mutations in 34 known and two novel RD genes. A total of 69 distinct mutations were identified, including 39 novel mutations. Notably, genetic findings in several families were not consistent with the initial clinical diagnosis. Clinical reassessment resulted in refinement of the clinical diagnosis in some of these families and confirmed the broad clinical spectrum associated with mutations in RD genes.
Introduction
Interferon alpha (IFNα) is routinely used in the clinical practice for adjuvant systemic melanoma therapy. Understanding the molecular mechanism of IFNα effects and prediction of response in the IFNα therapy regime allows initiation and continuation of IFNα treatment for responder and exclusion of non-responder to avoid therapy inefficacy and side-effects. The transporter protein associated with antigen processing-1 (TAP1) is part of the MHC class I peptide-loading complex, and important for antigen presentation in tumor and antigen presenting cells. In the context of personalized medicine, we address this potential biomarker TAP1 as a target of IFNα signalling.
Results
We could show that IFNα upregulates TAP1 expression in peripheral blood mononuclear cells (PBMCs) of patients with malignant melanoma receiving adjuvant high-dose immunotherapy. IFNα also induced expression of TAP1 in mouse blood and tumor tissue and suppressed the formation of melanoma metastasis in an in vivo B16 tumor model. Besides its expression, TAP binding affinity and transport activity is induced by IFNα in human monocytic THP1 cells. Furthermore, our data revealed that IFNα clearly activates phosphorylation of STAT1 and STAT3 in THP1 and A375 melanoma cells. Inhibition of Janus kinases abrogates the IFNα-induced TAP1 expression. These results suggest that the JAK/STAT pathway is a crucial mediator for TAP1 expression elicited by IFNα treatment.
Conclusion
We suppose that silencing of TAP1 expression provides tumor cells with a mechanism to escape cytotoxic T-lymphocyte recognition. The observed benefit of IFNα treatment could be mediated by the shown dual effect of TAP1 upregulation in antigen presenting cells on the one hand, and of TAP1 upregulation in ‘silent’ metastatic melanoma cells on the other hand. In conclusion, this work contributes to a better understanding of the mode of action of IFNα which is essential to identify markers to predict, assess and monitor therapeutic response of IFNα treatment in the future.
Prey selection is a key factor shaping animal populations and evolutionary dynamics. An optimal forager should target prey that offers the highest benefits in terms of energy content at the lowest costs. Predators are therefore expected to select for prey of optimal size. Stalking predators do not pursue their prey long, which may lead to a more random choice of prey individuals. Due to difficulties in assessing the composition of available prey populations, data on prey selection of stalking carnivores are still scarce. We show how the stalking predator Eurasian lynx (Lynx lynx) selects prey individuals based on species identity, age, sex and individual behaviour. To address the difficulties in assessing prey population structure, we confirm inferred selection patterns by using two independent data sets: (1) data of 387 documented kills of radio-collared lynx were compared to the prey population structure retrieved from systematic camera trapping using Manly’s standardized selection ratio alpha and (2) data on 120 radio-collared roe deer were analysed using a Cox proportional hazards model. Among the larger red deer prey, lynx selected against adult males—the largest and potentially most dangerous prey individuals. In roe deer lynx preyed selectively on males and did not select for a specific age class. Activity during high risk periods reduced the risk of falling victim to a lynx attack. Our results suggest that the stalking predator lynx actively selects for size, while prey behaviour induces selection by encounter and stalking success rates.
Bioluminescent reporter genes, such as those from fireflies and bacteria, let researchers use light production as a non-invasive and non-destructive surrogate measure of microbial numbers in a wide variety of environments. As bioluminescence needs microbial metabolites, tagging microorganisms with luciferases means only live metabolically active cells are detected. Despite the wide use of bioluminescent reporter genes, very little is known about the impact of continuous (also called constitutive) light expression on tagged bacteria. We have previously made a bioluminescent strain of Citrobacter rodentium, a bacterium which infects laboratory mice in a similar way to how enteropathogenic Escherichia coli (EPEC) and enterohaemorrhagic E. coli (EHEC) infect humans. In this study, we compared the growth of the bioluminescent C. rodentium strain ICC180 with its non-bioluminescent parent (strain ICC169) in a wide variety of environments. To understand more about the metabolic burden of expressing light, we also compared the growth profiles of the two strains under approximately 2,000 different conditions. We found that constitutive light expression in ICC180 was near-neutral in almost every non-toxic environment tested. However, we also found that the non-bioluminescent parent strain has a competitive advantage over ICC180 during infection of adult mice, although this was not enough for ICC180 to be completely outcompeted. In conclusion, our data suggest that constitutive light expression is not metabolically costly to C. rodentium and supports the view that bioluminescent versions of microbes can be used as a substitute for their non-bioluminescent parents to study bacterial behaviour in a wide variety of environments.
In patients with low-risk breast cancer, intraoperative radiotherapy (IORT) during breast-conserving surgery is a novel and convenient treatment option for delivering a single high dose of irradiation directly to the tumour bed. However, edema and fibrosis can develop after surgery and radiotherapy, which can subsequently impair quality of life. TGF-β is a strong inducer of the extracellular matrix component hyaluronan (HA). TGF-β expression and HA metabolism can be modulated by irradiation experimentally, and are involved in edema and fibrosis. We therefore hypothesized that IORT may regulate these factors.Wound fluid (WF) draining from breast lumpectomy sites was collected and levels of TGF-β1 and HA were determined by ELISA. Proliferation and marker expression was analyzed in primary lymphatic endothelial cells (LECs) treated with recombinant TGF-β or WF. Our results show that IORT does not change TGF-β1 or HA levels in wound fluid draining from breast lumpectomy sites, and does not lead to accumulation of sHA oligosaccharides. Nevertheless, concentrations of TGF-β1 were high in WF from patients regardless of IORT, at concentrations well above those associated with fibrosis and the suppression of LEC identity. Consistently, we found that TGF-β in WF is active and inhibits LEC proliferation. Furthermore, all three TGF-β isoforms inhibited LEC proliferation and suppressed LEC marker expression at pathophysiologically relevant concentrations.
Given that TGF-β contributes to edema and plays a role in the regulation of LEC identity, we suggest that inhibition of TGF-β directly after surgery might prevent the development of side effects such as edema and fibrosis.
Previous research found that men conspicuously consume luxury products to attract a mate and to signal their mate value. However, these studies have yet neglected to investigate the function of male conspicuous consumption in same-sex competition. Given that intersexual selection and intrasexual selection are closely related processes, it stands to reason that a further function of male conspicuous consumption could be to impress and deter same-sex rivals. An 2 (intrasexual competition context vs. control) × 2 (conspicuous luxury vs. inconspicuous nonluxury) between-subjects experimental study conducted with an Amazon Mechanical Turk sample (N = 160) revealed that men reported both higher liking of and an intent to purchase a conspicuous luxury car compared to an inconspicuous nonluxury car due to increased feelings of social status. This effect was stronger in the intrasexual competition than in the control context. An additional perception study using a single-factor between-subjects design (conspicuous luxury vs. inconspicuous nonluxury car) among German men (N = 405) indicated that male participants rated a man who displayed a conspicuous luxury car more as a rival and mate poacher and less as a friend. They further perceived him to be superior on various mate value characteristics (i.e., attractiveness, intelligence, ambition, and status) and rated him as more oriented toward short-term mating. In sum, our findings add to previous research in the field of evolutionary consumer psychology by suggesting that male conspicuous consumption of luxuries may also serve a function in male–male competition.
Ex situ analyses on topological insulator films require protection against surface contamination during air exposure. This work reports on a technique that combines deposition of protective capping just after epitaxial growth and its mechanical removal inside ultra-high vacuum systems. This method was applied to Bi2Te3 films with thickness varying from 8 to 170 nm. Contrarily to other methods, this technique does not require any sputtering or thermal annealing setups installed inside the analyzing system and preserves both film thickness and surface characteristics. These results suggest that the technique presented here can be expanded to other topological insulator materials.
Dyspnea is common in many cardiorespiratory diseases. Already the anticipation of this aversive symptom elicits fear in many patients resulting in unfavorable health behaviors such as activity avoidance and sedentary lifestyle. This study investigated brain mechanisms underlying these anticipatory processes. We induced dyspnea using resistive-load breathing in healthy subjects during functional magnetic resonance imaging. Blocks of severe and mild dyspnea alternated, each preceded by anticipation periods. Severe dyspnea activated a network of sensorimotor, cerebellar, and limbic areas. The left insular, parietal opercular, and cerebellar cortices showed increased activation already during dyspnea anticipation. Left insular and parietal opercular cortex showed increased connectivity with right insular and anterior cingulate cortex when severe dyspnea was anticipated, while the cerebellum showed increased connectivity with the amygdala. Notably, insular activation during dyspnea perception was positively correlated with midbrain activation during anticipation. Moreover, anticipatory fear was positively correlated with anticipatory activation in right insular and anterior cingulate cortex. The results demonstrate that dyspnea anticipation activates brain areas involved in dyspnea perception. The involvement of emotion-related areas such as insula, anterior cingulate cortex, and amygdala during dyspnea anticipation most likely reflects anticipatory fear and might underlie the development of unfavorable health behaviors in patients suffering from dyspnea.
Tumor models based on cancer cell lines cultured two-dimensionally (2D) on plastic lack histological complexity and functionality compared to the native microenvironment. Xenogenic mouse tumor models display higher complexity but often do not predict human drug responses accurately due to species-specific differences. We present here a three-dimensional (3D) in vitro colon cancer model based on a biological scaffold derived from decellularized porcine jejunum (small intestine submucosa+mucosa, SISmuc). Two different cell lines were used in monoculture or in coculture with primary fibroblasts. After 14 days of culture, we demonstrated a close contact of human Caco2 colon cancer cells with the preserved basement membrane on an ultrastructural level as well as morphological characteristics of a well-differentiated epithelium. To generate a tissue-engineered tumor model, we chose human SW480 colon cancer cells, a reportedly malignant cell line. Malignant characteristics were confirmed in 2D cell culture: SW480 cells showed higher vimentin and lower E-cadherin expression than Caco2 cells. In contrast to Caco2, SW480 cells displayed cancerous characteristics such as delocalized E-cadherin and nuclear location of beta-catenin in a subset of cells. One central drawback of 2D cultures-especially in consideration of drug testing-is their artificially high proliferation. In our 3D tissue-engineered tumor model, both cell lines showed decreased numbers of proliferating cells, thus correlating more precisely with observations of primary colon cancer in all stages (UICC I-IV). Moreover, vimentin decreased in SW480 colon cancer cells, indicating a mesenchymal to epithelial transition process, attributed to metastasis formation. Only SW480 cells cocultured with fibroblasts induced the formation of tumor-like aggregates surrounded by fibroblasts, whereas in Caco2 cocultures, a separate Caco2 cell layer was formed separated from the fibroblast compartment beneath. To foster tissue generation, a bioreactor was constructed for dynamic culture approaches. This induced a close tissue-like association of cultured tumor cells with fibroblasts reflecting tumor biopsies. Therapy with 5-fluorouracil (5-FU) was effective only in 3D coculture. In conclusion, our 3D tumor model reflects human tissue-related tumor characteristics, including lower tumor cell proliferation. It is now available for drug testing in metastatic context-especially for substances targeting tumor-stroma interactions.
We present a consistent renormalization scheme for the CP-conserving Two-Higgs-Doublet Model based on (MS)over-bar renormalization of the mixing angles and the soft-Z 2-symmetry-breaking scale M sb in the Higgs sector. This scheme requires to treat tadpoles fully consistently in all steps of the calculation in order to provide gauge-independent S-matrix elements. We show how bare physical parameters have to be defined and verify the gauge independence of physical quantities by explicit calculations in a general R ξ -gauge. The procedure is straightforward and applicable to other models with extended Higgs sectors. In contrast to the proposed scheme, the (MS)over-bar renormalization of the mixing angles combined with popular on-shell renormalization schemes gives rise to gauge-dependent results already at the one-loop level. We present explicit results for electroweak NLO corrections to selected processes in the appropriately renormalized Two-Higgs-Doublet Model and in particular discuss their scale dependence.
Nosological delineation of congenital ocular motor apraxia type Cogan: an observational study
(2016)
Background
The nosological assignment of congenital ocular motor apraxia type Cogan (COMA) is still controversial. While regarded as a distinct entity by some authorities including the Online Mendelian Inheritance in Man catalog of genetic disorders, others consider COMA merely a clinical symptom.
Methods
We performed a retrospective multicenter data collection study with re-evaluation of clinical and neuroimaging data of 21 previously unreported patients (8 female, 13 male, ages ranging from 2 to 24 years) diagnosed as having COMA.
Results
Ocular motor apraxia (OMA) was recognized during the first year of life and confined to horizontal pursuit in all patients. OMA attenuated over the years in most cases, regressed completely in two siblings, and persisted unimproved in one individual. Accompanying clinical features included early onset ataxia in most patients and cognitive impairment with learning disability (n = 6) or intellectual disability (n = 4). Re-evaluation of MRI data sets revealed a hitherto unrecognized molar tooth sign diagnostic for Joubert syndrome in 11 patients, neuroimaging features of Poretti-Boltshauser syndrome in one case and cerebral malformation suspicious of a tubulinopathy in another subject. In the remainder, MRI showed vermian hypo-/dysplasia in 4 and no abnormalities in another 4 patients. There was a strong trend to more severe cognitive impairment in patients with Joubert syndrome compared to those with inconclusive MRI, but otherwise no significant difference in clinical phenotypes between these two groups.
Conclusions
Systematical renewed analysis of neuroimaging data resulted in a diagnostic reappraisal in the majority of patients with early-onset OMA in the cohort reported here. This finding poses a further challenge to the notion of COMA constituting a separate entity and underlines the need for an expert assessment of neuroimaging in children with COMA, especially if they show cognitive impairment.
The EANM 2015 Annual Congress, held from October 10th to 14th in Hamburg, Germany, was outstanding in many respects. With 5550 participants, this was by far the largest European congress concerning nuclear medicine. More than 1750 scientific presentations were submitted, with more than 250 abstracts from young scientists, indicating that the future success of our discipline is fuelled by a high number of young individuals becoming involved in a multitude of scientific activities. Significant improvements have been made in molecular imaging of cancer, particularly in prostate cancer. PSMA-directed PET/CT appears to become a new gold standard for staging and restaging purposes. Novel tumour specific compounds have shown their potential for target identification also in other solid neoplasms and further our understanding of tumour biology and heterogeneity. In addition, a variety of nuclear imaging techniques guiding surgical interventions have been introduced. A particular focus of the congress was put on targeted, radionuclide based therapies. Novel theranostic concepts addressing also tumour entities with high incidence rates such as prostate cancer, melanoma, and lymphoma, have shown effective anti-tumour activity. Strategies have been presented to improve further already established therapeutic regimens such as somatostatin receptor based radio receptor therapy for treating advanced neuroendocrine tumours. Significant contributions were presented also in the neurosciences track. An increasing number of target structures of high interest in neurology and psychiatry are now available for PET and SPECT imaging, facilitating specific imaging of different subtypes of dementia and movement disorders as well as neuroinflammation. Major contributions in the cardiovascular track focused on further optimization of cardiac perfusion imaging by reducing radiation exposure, reducing scanning time, and improving motion correction. Besides coronary artery disease, many contributions focused on cardiac inflammation, cardiac sarcoidosis, and specific imaging of large vessel vasculitis. The physics and instrumentation track included many highlights such as novel, high resolution scanners. The most noteworthy news and developments of this meeting were summarized in the highlights lecture. Only 55 scientific contributions were mentioned, and hence they represent only a brief summary, which is outlined in this article. For a more detailed view, all presentations can be accessed by the online version of the European Journal of Nuclear Medicine and Molecular Imaging (Volume 42, Supplement 1).
Patients with genetic cardiomyopathy that involves myocardial hypertrophy often develop clinically relevant arrhythmias that increase the risk of sudden death. Consequently, guidelines for medical device therapy were established for hypertrophic cardiomyopathy, but not for conditions with only anecdotal evidence of arrhythmias, like Fabry cardiomyopathy. Patients with Fabry cardiomyopathy progressively develop myocardial fibrosis, and sudden cardiac death occurs regularly. Because 24-hour Holier electrocardiograms (ECGs) might not detect clinically important arrhythmias, we tested an implanted loop recorder for continuous heart rhythm surveillance and determined its impact on therapy. This prospective study included 16 patients (12 men) with advanced Fabry cardiomyopathy, relevant hypertrophy, and replacement fibrosis in "loco typico." No patients previously exhibited clinically relevant arrhythmias on Holier ECGs. Patients received an implantable loop recorder and were prospectively followed with telemedicine for a median of 1.2 years (range 0.3 to 2.0 years). The primary end point was a clinically meaningful event, which required a therapy change, captured with the loop recorder. Patients submitted data regularly (14 +/- 11 times per month). During follow-up, 21 events were detected (including 4 asystole, i.e., ECG pauses >= 3 seconds) and 7 bradycardia events; 5 episodes of intermittent atrial fibrillation (>3 minutes) and 5 episodes of ventricular tachycardia (3 sustained and 2 nonsustained). Subsequently, as defined in the primary end point, 15 events leaded to a change of therapy. These patients required therapy with a pacemaker or cardioverter defibrillator implantation and/or anticoagulation therapy for atrial fibrillation. In conclusion, clinically relevant arrhythmias that require further device and/or medical therapy are often missed with Holier ECGs in patients with advanced stage Fabry cardiomyopathy, but they can be detected by telemonitoring with an implantable loop recorder.
Massively increasing global incidences of colorectal cancer require efficient treatment and prevention strategies. Here, we report unexpected anticancerogenic effects of hydroethanolic Iberis amara extract (IAE), which is known as a widely used phytomedical product for treating gastrointestinal complaints. IAE significantly inhibited the proliferation of HT-29 and T84 colon carcinoma cells with an inhibitory concentration (IC\(_{50}\)) of 6 and 9 μg/ml, respectively, and further generated inhibitory effects in PC-3 prostate and MCF7 breast cancer cells. Inhibition of proliferation in HT-29 cells was associated with a G2/M phase cell cycle arrest including reduced expression of various regulatory marker proteins. Notably, in HT-29 cells IAE further induced apoptosis by intracellular formation of reactive oxygen species (ROS). Consistent with predictions derived from our in vitro experiments, bidaily oral gavage of 50 mg/kg of IAE over 4 weeks resulted in significant inhibition of tumor growth in a mouse HT-29 tumor xenograft model. Taken together, Iberis amara extracts could become useful alternatives for preventing and treating the progression of colon cancer.
Insects inhabiting the temperate zones measure seasonal changes in day or night length to enter the overwintering diapause. Diapause induction occurs after the duration of the night exceeds a critical night length (CNL). Our understanding of the time measurement mechanisms is continuously evolving subsequent to Bünning’s proposal that circadian systems play the clock role in photoperiodic time measurement (Bünning, 1936). Initially, the photoperiodic clocks were considered to be either based on circadian oscillators or on simple hour-glasses, depending on ‘positive’ or ‘negative’ responses in Nanda–Hamner and Bünsow experiments (Nanda & Hammer, 1958; Bünsow, 1960).
However, there are also species whose responses can be regarded as neither ‘positive’, nor as ‘negative’, such as the Northern Drosophila species Drosophila ezoana, which is investigated in the present study. In addition, modelling efforts show that the ‘positive’ and ‘negative’ Nanda–Hamner responses can also be provoked by circadian oscillators that are damped to different degrees: animals with highly sustained circadian clocks will respond ‘positive’ and those with heavily damped circadian clocks will respond ‘negative’. In the present study, an experimental assay is proposed that characterizes the photoperiodic oscillators by determining the effects of non-24-h light/dark cycles (T-cycles) on critical night length. It is predicted that there is (i) a change in the critical night length as a function of T-cycle period in sustained-oscillator-based clocks and (ii) a fxed night-length measurement (i.e. no change in critical night length) in damped-oscillator-based clocks. Drosophila ezoana flies show a critical night length of approximately 7 h irrespective of T-cycle period, suggesting a damped-oscillator-based photoperiodic clock. The conclusion is strengthened by activity recordings revealing that the activity rhythm of D. ezoana flies also dampens in constant darkness.
Chronobiological studies of individual activity rhythms in social insects can be constrained by the artificial isolation of individuals from their social context. We present a new experimental set-up that simultaneously measures the temperature rhythm in a queen-less but brood raising mini colony and the walking activity rhythms of singly kept honey bees that have indirect social contact with it. Our approach enables monitoring of individual bees in the social context of a mini colony under controlled laboratory conditions. In a pilot experiment, we show that social contact with the mini colony improves the survival of monitored young individuals and affects locomotor activity patterns of young and old bees. When exposed to conflicting Zeitgebers consisting of a light-dark (LD) cycle that is phase-delayed with respect to the mini colony rhythm, rhythms of young and old bees are socially synchronized with the mini colony rhythm, whereas isolated bees synchronize to the LD cycle. We conclude that the social environment is a stronger Zeitgeber than the LD cycle and that our new experimental set-up is well suited for studying the mechanisms of social entrainment in honey bees.
Ampullary carcinoma is a rare tumor and evidence on the treatment of recurrent metastatic disease is scarce. We report the case of a 60-year-old patient with an R0-resected node-positive adenocarcinoma of the papilla of Vater of an initially diagnosed intestinal subtype who developed pulmonary metastases 2 months after adjuvant gemcitabine chemotherapy and, subsequently, liver metastases. Palliative combination chemotherapy with standard regimens for intestinal-type adenocarcinoma (FOLFOX and FOLFIRI) failed. However, subsequent combination chemotherapy with nanoparticle albumin-bound paclitaxel and gemcitabine, a regimen with proven efficacy in metastatic adenocarcinoma of the pancreas, resulted in a durable, very good partial remission. Treatment was manageable and well tolerated. Primary tumor and metastatic tissue were reassessed by immunohistochemistry and had to be reclassified to a mixed phenotype containing predominant elements of the pancreatobiliary subtype. Our case suggests that combination chemotherapy with nanoparticle albumin-bound paclitaxel and gemcitabine could represent a promising option for the treatment of this rare disease and warrants further investigation within controlled clinical trials. Moreover, thorough characterization of ampullary carcinomas by histomorphology and additional immunohistochemistry should become mandatory in order to start a chemotherapeutic regimen tailored for the definitive subtype.
Purpose:
Discovery of candidate spectra for abundant fluorophore families in human retinal pigment epithelium (RPE) by ex vivo hyperspectral imaging.
Methods:
Hyperspectral autofluorescence emission images were captured between 420 and 720 nm (10-nm intervals), at two excitation bands (436–460, 480–510 nm), from three locations (fovea, perifovea, near-periphery) in 20 normal RPE/Bruch's membrane (BrM) flatmounts. Mathematical factorization extracted a BrM spectrum (S0) and abundant lipofuscin/melanolipofuscin (LF/ML) spectra of RPE origin (S1, S2, S3) from each tissue.
Results:
Smooth spectra S1 to S3, with perinuclear localization consistent with LF/ML at all three retinal locations and both excitations in 14 eyes (84 datasets), were included in the analysis. The mean peak emissions of S0, S1, and S2 at λ\(_{ex}\) 436 nm were, respectively, 495 ± 14, 535 ± 17, and 576 ± 20 nm. S3 was generally trimodal, with peaks at either 580, 620, or 650 nm (peak mode, 650 nm). At λ\(_{ex}\) 480 nm, S0, S1, and S2 were red-shifted to 526 ± 9, 553 ± 10, and 588 ± 23 nm, and S3 was again trimodal (peak mode, 620 nm). S1 often split into two spectra, S1A and S1B. S3 strongly colocalized with melanin. There were no significant differences across age, sex, or retinal location.
Conclusions:
There appear to be at least three families of abundant RPE fluorophores that are ubiquitous across age, retinal location, and sex in this sample of healthy eyes. Further molecular characterization by imaging mass spectrometry and localization via super-resolution microscopy should elucidate normal and abnormal RPE physiology involving fluorophores.
Translational Relevance:
Our results help establish hyperspectral autofluorescence imaging of the human retinal pigment epithelium as a useful tool for investigating retinal health and disease.
Fluorescence enhancement of a high-mobility polymer semiconductor is achieved via energy transfer to a higher fluorescence quantum yield squaraine dye molecule on 50 ps timescales. In organic light-emitting diodes, an order of magnitude enhancement of the external quantum efficiency is observed without reduction in the charge-carrier mobility resulting in radiances of up to 5 W str\(^{-1}\) m\(^{-2}\) at 800 nm.
This study aimed to evaluate the tumorigenic potential of functionalising poly(LLA-co-CL) scaffolds. The copolymer scaffolds were functionalised with nanodiamonds (nDP) or with nDP and physisorbed BMP-2 (nDP-PHY) to enhance osteoinductivity. Culturing early neoplastic dysplastic keratinocytes (DOK\(^{Luc}\)) on nDP modified scaffolds reduced significantly their subsequent sphere formation ability and decreased significantly the cells' proliferation in the supra-basal layers of in vitro 3D oral neoplastic mucosa (3D-OT) when compared to DOK\(^{Luc}\) previously cultured on nDP-PHY scaffolds. Using an in vivo non-invasive environmentally-induced oral carcinogenesis model, nDP scaffolds were observed to reduce bioluminescence intensity of tumours formed by DOK\(^{Luc}\) + carcinoma associated fibroblasts (CAF). nDP modification was also found to promote differentiation of DOK\(^{Luc}\) both in vitro in 3D-OT and in vivo in xenografts formed by DOKLuc alone. The nDP-PHY scaffold had the highest number of invasive tumours formed by DOK\(^{Luc}\) + CAF outside the scaffold area compared to the nDP and control scaffolds. In conclusion, in vitro and in vivo results presented here demonstrate that nDP modified copolymer scaffolds are able to decrease the tumorigenic potential of DOK\(^{Luc}\), while confirming concerns for the therapeutic use of BMP-2 for reconstruction of bone defects in oral cancer patients due to its tumour promoting capabilities.
Herein, we report the one-pot synthesis of an electron-poor nanographene containing dicarboximide groups at the corners. We efficiently combined palladium-catalyzed Suzuki-Miyaura cross-coupling and dehydrohalogenation to synthesize an extended two-dimensional pi-scaffold of defined size in a single chemical operation starting from N-(2,6-diisopropylphenyl)-4,5-dibromo-1,8-naphthalimide and a tetrasubstituted pyrene boronic acid ester as readily accessible starting materials. The reaction of these precursors under the conditions commonly used for Suzuki-Miyaura cross-coupling afforded a C\(_{64}\) nanographene through the formation of ten C-C bonds in a one-pot process. Single-crystal X-ray analysis unequivocally confirmed the structure of this unique extended aromatic molecule with a planar geometry. The optical and electrochemical properties of this largest ever synthesized planar electron-poor nanographene skeleton were also analyzed.
Background
Tropical mountain forests are hotspots of biodiversity hosting a huge but little known diversity of insects that is endangered by habitat destruction and climate change. Therefore, rapid assessment approaches of insect diversity are urgently needed to complement slower traditional taxonomic approaches. We empirically compare different DNA-based species delimitation approaches for a rapid biodiversity assessment of hyperdiverse leaf beetle assemblages along an elevational gradient in southern Ecuador and explore their effect on species richness estimates.
Methodology/Principal Findings
Based on a COI barcode data set of 674 leaf beetle specimens (Coleoptera: Chrysomelidae) of 266 morphospecies from three sample sites in the Podocarpus National Park, we employed statistical parsimony analysis, distance-based clustering, GMYC- and PTP-modelling to delimit species-like units and compared them to morphology-based (parataxonomic) species identifications. The four different approaches for DNA-based species delimitation revealed highly similar numbers of molecular operational taxonomic units (MOTUs) (n = 284–289). Estimated total species richness was considerably higher than the sampled amount, 414 for morphospecies (Chao2) and 469–481 for the different MOTU types. Assemblages at different elevational levels (1000 vs. 2000 m) had similar species numbers but a very distinct species composition for all delimitation methods. Most species were found only at one elevation while this turnover pattern was even more pronounced for DNA-based delimitation.
Conclusions/Significance
Given the high congruence of DNA-based delimitation results, probably due to the sampling structure, our study suggests that when applied to species communities on a regionally limited level with high amount of rare species (i.e. ~50% singletons), the choice of species delimitation method can be of minor relevance for assessing species numbers and turnover in tropical insect communities. Therefore, DNA-based species delimitation is confirmed as a valuable tool for evaluating biodiversity of hyperdiverse insect communities, especially when exact taxonomic identifications are missing.
Objective
To analyse the role of multibiomarker disease activity (MBDA) score in predicting disease relapses in patients with rheumatoid arthritis (RA) in sustained remission who tapered disease modifying antirheumatic drug (DMARD) therapy in RETRO, a prospective randomised controlled trial.
Methods
MBDA scores (scale 1-100) were determined based on 12 inflammation markers in baseline serum samples from 94 patients of the RETRO study. MBDA scores were compared between patients relapsing or remaining in remission when tapering DMARDs. Demographic and disease-specific parameters were included in multivariate logistic regression analysis for defining predictors of relapse.
Results
Moderate-to-high MBDA scores were found in 33% of patients with RA overall. Twice as many patients who relapsed (58%) had moderate/high MBDA compared with patients who remained in remission (21%). Baseline MBDA scores were significantly higher in patients with RA who were relapsing than those remaining in stable remission (N=94; p=0.0001) and those tapering/stopping (N=59; p=0.0001). Multivariate regression analysis identified MBDA scores as independent predictor for relapses in addition to anticitrullinated protein antibody (ACPA) status. Relapse rates were low (13%) in patients who were MBDA-/ACPA-, moderate in patients who were MBDA+/ACPA- (33.3%) and MBDA-ACPA+ (31.8%) and high in patients who were MBDA+/ACPA+ (76.4%).
Conclusions
MBDA improved the prediction of relapses in patients with RA in stable remission undergoing DMARD tapering. If combined with ACPA testing, MBDA allowed prediction of relapse in more than 80% of the patients.
Trial registration number EudraCT
2009-015740-42.
Reduced dimensionality and symmetry breaking at interfaces lead to unusual local magnetic configurations, such as glassy behavior, frustration or increased anisotropy. The interface between a ferromagnet and an antiferromagnet is such an example for enhanced symmetry breaking. Here we present detailed X-ray magnetic circular dichroism and X-ray resonant magnetic reflectometry investigations on the spectroscopic nature of uncompensated pinned magnetic moments in the antiferromagnetic layer of a typical exchange bias system. Unexpectedly, the pinned moments exhibit nearly pure orbital moment character. This strong orbital pinning mechanism has not been observed so far and is not discussed in literature regarding any theory for local magnetocrystalline anisotropy energies in magnetic systems. To verify this new phenomenon we investigated the effect at different temperatures. We provide a simple model discussing the observed pure orbital moments, based on rotatable spin magnetic moments and pinned orbital moments on the same atom. This unexpected observation leads to a concept for a new type of anisotropy energy.
Out of the myriad of potential DNA binding sites of the glucocorticoid receptor (GR) found in the human genome, only a cell-type specific minority is actually bound, indicating that the presence of a recognition sequence alone is insufficient to specify where GR binds. Cooperative interactions with other transcription factors (TFs) are known to contribute to binding specificity. Here, we reasoned that sequence signals preventing GR recruitment to certain loci provide an alternative means to confer specificity. Motif analyses uncovered candidate Negative Regulatory Sequences (NRSs) that interfere with genomic GR binding. Subsequent functional analyses demonstrated that NRSs indeed prevent GR binding to nearby response elements. We show that NRS activity is conserved across species, found in most tissues and that they also interfere with the genomic binding of other TFs. Interestingly, the effects of NRSs appear not to be a simple consequence of changes in chromatin accessibility. Instead, we find that NRSs interact with proteins found at sub-nuclear structures called paraspeckles and that these proteins might mediate the repressive effects of NRSs. Together, our studies suggest that the joint influence of positive and negative sequence signals partition the genome into regions where GR can bind and those where it cannot.
Background
Fabry disease (FD) is an X-linked multisystemic disorder with a heterogeneous phenotype. Especially atypical or late-onset type 2 phenotypes present a therapeutical dilemma.
Methods
To determine the clinical impact of the alpha-Galactosidase A (GLA) p.A143T/ c.427G > A variation, we retrospectively analyzed 25 p.A143T patients in comparison to 58 FD patients with other missense mutations.
Results
p.A143T patients suffering from stroke/ transient ischemic attacks had slightly decreased residual GLA activities, and/or increased lyso-Gb3 levels, suspecting FD. However, most male p.A143T patients presented with significant residual GLA activity (~50 % of reference), which was associated with normal lyso-Gb3 levels. Additionally, p.A143T patients showed less severe FD-typical symptoms and absent FD-typical renal and cardiac involvement in comparison to FD patients with other missense mutations. Two tested female p.A143T patients with stroke/TIA did not show skewed X chromosome inactivation. No accumulation of neurologic events in family members of p.A143T patients with stroke/transient ischemic attacks was observed.
Conclusions
We conclude that GLA p.A143T seems to be most likely a neutral variant or a possible modifier instead of a disease-causing mutation. Therefore, we suggest that p.A143T patients with stroke/transient ischemic attacks of unknown etiology should be further evaluated, since the diagnosis of FD is not probable and subsequent ERT or chaperone treatment should not be an unreflected option.
Infections of the central nervous system (CNS) are infrequently diagnosed in immunocompetent patients, but they do occur in a significant proportion of patients with hematological disorders. In particular, patients undergoing allogeneic hematopoietic stem-cell transplantation carry a high risk for CNS infections of up to 15%. Fungi and Toxoplasma gondii are the predominant causative agents. The diagnosis of CNS infections is based on neuroimaging, cerebrospinal fluid examination and biopsy of suspicious lesions in selected patients. However, identification of CNS infections in immunocompromised patients could represent a major challenge since metabolic disturbances, side-effects of antineoplastic or immunosuppressive drugs and CNS involvement of the underlying hematological disorder may mimic symptoms of a CNS infection. The prognosis of CNS infections is generally poor in these patients, albeit the introduction of novel substances (e.g. voriconazole) has improved the outcome in distinct patient subgroups. This guideline has been developed by the Infectious Diseases Working Party (AGIHO) of the German Society of Hematology and Medical Oncology (DGHO) with the contribution of a panel of 14 experts certified in internal medicine, hematology/oncology, infectious diseases, intensive care, neurology and neuroradiology. Grades of recommendation and levels of evidence were categorized by using novel criteria, as recently published by the European Society of Clinical Microbiology and Infectious Diseases.
Aggressiveness is a behavioral trait that has the potential to be harmful to individuals and society. With an estimated heritability of about 40%, genetics is important in its development. We performed an exploratory genome-wide association (GWA) analysis of childhood aggressiveness in attention deficit hyperactivity disorder (ADHD) to gain insight into the underlying biological processes associated with this trait. Our primary sample consisted of 1,060 adult ADHD patients (aADHD). To further explore the genetic architecture of childhood aggressiveness, we performed enrichment analyses of suggestive genome-wide associations observed in aADHD among GWA signals of dimensions of oppositionality (defiant/vindictive and irritable dimensions) in childhood ADHD (cADHD). No single polymorphism reached genome-wide significance (P<5.00E-08). The strongest signal in aADHD was observed at rs10826548, within a long noncoding RNA gene (beta = -1.66, standard error (SE) = 0.34, P = 1.07E-06), closely followed by rs35974940 in the neurotrimin gene (beta = 3.23, SE = 0.67, P = 1.26E-06). The top GWA SNPs observed in aADHD showed significant enrichment of signals from both the defiant/vindictive dimension (Fisher's P-value = 2.28E-06) and the irritable dimension in cADHD (Fisher's P-value = 0.0061). In sum, our results identify a number of biologically interesting markers possibly underlying childhood aggressiveness and provide targets for further genetic exploration of aggressiveness across psychiatric disorders.
The current diagnostic criteria of the Diagnostic and Statistical Manual of Mental Disorders are being challenged by the heterogeneity and the symptom overlap of psychiatric disorders. Therefore, a framework toward a more etiology-based classification has been initiated by the US National Institute of Mental Health, the research domain criteria project. The basic neurobiology of human psychiatric disorders is often studied in rodent models. However, the differences in outcome measurements hamper the translation of knowledge. Here, we aimed to present a translational panic model by using the same stimulus and by quantitatively comparing the same outcome measurements in rodents, healthy human subjects and panic disorder patients within one large project. We measured the behavioral–emotional and bodily response to CO\(_{2}\) exposure in all three samples, allowing for a reliable cross-species comparison. We show that CO\(_{2}\) exposure causes a robust fear response in terms of behavior in mice and panic symptom ratings in healthy volunteers and panic disorder patients. To improve comparability, we next assessed the respiratory and cardiovascular response to CO\(_{2}\), demonstrating corresponding respiratory and cardiovascular effects across both species. This project bridges the gap between basic and human research to improve the translation of knowledge between these disciplines. This will allow significant progress in unraveling the etiological basis of panic disorder and will be highly beneficial for refining the diagnostic categories as well as treatment strategies.
Hsp90 inhibition ameliorates CD4\(^{+}\) T cell-mediated acute Graft versus Host disease in mice
(2016)
Introduction:
For many patients with leukemia only allogeneic bone marrow transplantion provides a chance of cure. Co‐transplanted mature donor T cells mediate the desired Graft versus Tumor (GvT) effect required to destroy residual leukemic cells. The donor T cells very often, however, also attack healthy tissue of the patient inducing acute Graft versus Host Disease (aGvHD)—a potentially life‐threatening complication.
Methods:
Therefore, we used the well established C57BL/6 into BALB/c mouse aGvHD model to evaluate whether pharmacological inhibition of heat shock protein 90 (Hsp90) would protect the mice from aGvHD.
Results:
Treatment of the BALB/c recipient mice from day 0 to +2 after allogeneic CD4\(^{+}\) T cell transplantation with the Hsp90 inhibitor 17‐(dimethylaminoethylamino)‐17‐demethoxygeldanamycin (DMAG) partially protected the mice from aGvHD. DMAG treatment was, however, insufficient to prolong overall survival of leukemia‐bearing mice after transplantation of allogeneic CD4\(^{+}\) and CD8\(^{+}\) T cells. Ex vivo analyses and in vitro experiments revealed that DMAG primarily inhibits conventional CD4\(^{+}\) T cells with a relative resistance of CD4\(^{+}\) regulatory and CD8\(^{+}\) T cells toward Hsp90 inhibition.
Conclusions:
Our data, thus, suggest that Hsp90 inhibition might constitute a novel approach to reduce aGvHD in patients without abrogating the desired GvT effect.
The genomes of kinetoplastids are organized into polycistronic gene clusters that are flanked by the modified DNA base J. Previous work has established a role of base J in promoting RNA polymerase II termination in Leishmania spp. where the loss of J leads to termination defects and transcription into adjacent gene clusters. It remains unclear whether these termination defects affect gene expression and whether read through transcription is detrimental to cell growth, thus explaining the essential nature of J. We now demonstrate that reduction of base J at specific sites within polycistronic gene clusters in L. major leads to read through transcription and increased expression of downstream genes in the cluster. Interestingly, subsequent transcription into the opposing polycistronic gene cluster does not lead to downregulation of sense mRNAs. These findings indicate a conserved role for J regulating transcription termination and expression of genes within polycistronic gene clusters in trypanosomatids. In contrast to the expectations often attributed to opposing transcription, the essential nature of J in Leishmania spp. is related to its role in gene repression rather than preventing transcriptional interference resulting from read through and dual strand transcription.
The second messenger cyclic AMP (cAMP) plays an important role in synaptic plasticity. Although there is evidence for local control of synaptic transmission and plasticity, it is less clear whether a similar spatial confinement of cAMP signaling exists. Here, we suggest a possible biophysical basis for the site-specific regulation of synaptic plasticity by cAMP, a highly diffusible small molecule that transforms the physiology of synapses in a local and specific manner. By exploiting the octopaminergic system of Drosophila, which mediates structural synaptic plasticity via a cAMP-dependent pathway, we demonstrate the existence of local cAMP signaling compartments of micrometer dimensions within single motor neurons. In addition, we provide evidence that heterogeneous octopamine receptor localization, coupled with local differences in phosphodiesterase activity, underlies the observed differences in cAMP signaling in the axon, cell body, and boutons.
Macrophages express TNFR1 as well as TNFR2 and are also major producers of tumor necrosis factor (TNF), especially upon contact with pathogen-associated molecular patterns. Consequently, TNF not only acts as a macrophage-derived effector molecule but also regulates the activity and viability of macrophages. Here, we investigated the individual contribution of TNFR1 and TNFR2 to TNF-induced cell death in macrophages. Exclusive stimulation of TNFR1 showed no cytotoxic effect whereas selective stimulation of TNFR2 displayed mild cytotoxicity. Intriguingly, the latter was strongly enhanced by the caspase inhibitor zVAD-fmk. The strong cytotoxic activity of TNFR2 in the presence of zVAD-fmk was reversed by necrostatin-1, indicating necroptotic cell death. TNFR1- and TNF-deficient macrophages turned out to be resistant against TNFR2-induced cell death. In addition, the cIAP-depleting SMAC mimetic BV6 also enforced TNF/TNFR1-mediated necroptotic cell death in the presence of zVAD-fmk. In sum, our data suggest a model in which TNFR2 sensitizes macrophages for endogenous TNF-induced TNFR1-mediated necroptosis by the known ability of TNFR2 to interfere with the survival activity of TRAF2-cIAP1/2 complexes.
In invertebrates, small interfering RNAs are at the vanguard of cell-autonomous antiviral immunity. In contrast, antiviral mechanisms initiated by interferon (IFN) signaling predominate in mammals. Whilst mammalian IFN-induced miRNA are known to inhibit specific viruses, it is not known whether host-directed microRNAs, downstream of IFN-signaling, have a role in mediating broad antiviral resistance. By performing an integrative, systematic, global analysis of RNA turnover utilizing 4-thiouridine labeling of newly transcribed RNA and pri/pre-miRNA in IFN-activated macrophages, we identify a new post-transcriptional viral defense mechanism mediated by miR-342-5p. On the basis of ChIP and site-directed promoter mutagenesis experiments, we find the synthesis of miR-342-5p is coupled to the antiviral IFN response via the IFN-induced transcription factor, IRF1. Strikingly, we find miR-342-5p targets mevalonate-sterol biosynthesis using a multihit mechanism suppressing the pathway at different functional levels: transcriptionally via SREBF2, post-transcriptionally via miR-33, and enzymatically via IDI1 and SC4MOL. Mass spectrometry-based lipidomics and enzymatic assays demonstrate the targeting mechanisms reduce intermediate sterol pathway metabolites and total cholesterol in macrophages. These results reveal a previously unrecognized mechanism by which IFN regulates the sterol pathway. The sterol pathway is known to be an integral part of the macrophage IFN antiviral response, and we show that miR-342-5p exerts broad antiviral effects against multiple, unrelated pathogenic viruses such Cytomegalovirus and Influenza A (H1N1). Metabolic rescue experiments confirm the specificity of these effects and demonstrate that unrelated viruses have differential mevalonate and sterol pathway requirements for their replication. This study, therefore, advances the general concept of broad antiviral defense through multihit targeting of a single host pathway.
Background
Currently ketogenic diets (KDs) are hyped as an anti-tumor intervention aimed at exploiting the metabolic abnormalities of cancer cells. However, while data in humans is sparse, translation of murine tumor models to the clinic is further hampered by small sample sizes, heterogeneous settings and mixed results concerning tumor growth retardation. The aim was therefore to synthesize the evidence for a growth inhibiting effect of KDs when used as a monotherapy in mice.
Methods
We conducted a Bayesian random effects meta-analysis on all studies assessing the survival (defined as the time to reach a pre-defined endpoint such as tumor volume) of mice on an unrestricted KD compared to a high carbohydrate standard diet (SD). For 12 studies meeting the inclusion criteria either a mean survival time ratio (MR) or hazard ratio (HR) between the KD and SD groups could be obtained. The posterior estimates for the MR and HR averaged over four priors on the between-study heterogeneity τ\(^{2}\) were MR = 0.85 (95% highest posterior density interval (HPDI) = [0.73, 0.97]) and HR = 0.55 (95% HPDI = [0.26, 0.87]), indicating a significant overall benefit of the KD in terms of prolonged mean survival times and reduced hazard rate. All studies that used a brain tumor model also chose a late starting point for the KD (at least one day after tumor initiation) which accounted for 26% of the heterogeneity. In this subgroup the KD was less effective (MR = 0.89, 95% HPDI = [0.76, 1.04]).
Conclusions
There was an overall tumor growth delaying effect of unrestricted KDs in mice. Future experiments should aim at differentiating the effects of KD timing versus tumor location, since external evidence is currently consistent with an influence of both of these factors.
Introduction
A novel neurostimulation system allows steering current in horizontal directions by combining segmented leads and multiple independent current control. The aim of this study was to evaluate directional DBS effects on parkinsonian motor features and adverse effects of subthalamic neurostimulation.
Methods
Seven PD patients implanted with the novel directional DBS system for bilateral subthalamic DBS underwent an extended monopolar review session during the first postoperative week, in which current thresholds were determined for rigidity control and stimulation-induced adverse effects using either directional or ring-mode settings.
Results
Effect or adverse effect thresholds were modified by directional settings for each of the 14 STN leads. Magnitude of change varied markedly between leads, as did orientation of optimal horizontal current steering.
Conclusion
Directional current steering through chronically implanted segmented electrodes is feasible, alters adverse effect and efficacy thresholds in a highly individual manner, and expands the therapeutic window in a monopolar review as compared to ring-mode DBS.
In a standard semiconductor laser, electrons and holes recombine via stimulated emission to emit coherent light, in a process that is far from thermal equilibrium. Exciton-polariton condensates–sharing the same basic device structure as a semiconductor laser, consisting of quantum wells coupled to a microcavity–have been investigated primarily at densities far below the Mott density for signatures of Bose-Einstein condensation. At high densities approaching the Mott density, exciton-polariton condensates are generally thought to revert to a standard semiconductor laser, with the loss of strong coupling. Here, we report the observation of a photoluminescence sideband at high densities that cannot be accounted for by conventional semiconductor lasing. This also differs from an upper-polariton peak by the observation of the excitation power dependence in the peak-energy separation. Our interpretation as a persistent coherent electron-hole-photon coupling captures several features of this sideband, although a complete understanding of the experimental data is lacking. A full understanding of the observations should lead to a development in non-equilibrium many-body physics.
Activation of the basal ganglia has been shown during the preparation and execution of movement. However, the functional interaction of cortical and subcortical brain areas during movement and the relative contribution of dopaminergic striatal innervation remains unclear. We recorded local field potential (LFP) activity from the subthalamic nucleus (STN) and high-density electroencephalography (EEG) signals in four patients with Parkinson’s disease (PD) off dopaminergic medication during a multi-joint motor task performed with their dominant and non-dominant hand. Recordings were performed by means of a fully-implantable deep brain stimulation (DBS) device at 4 months after surgery. Three patients also performed a single-photon computed tomography (SPECT) with [123I]N-ω-fluoropropyl-2β-carbomethoxy-3β-(4-iodophenyl)nortropane (FP-CIT) to assess striatal dopaminergic innervation. Unilateral movement execution led to event-related desynchronization (ERD) followed by a rebound after movement termination event-related synchronization (ERS) of oscillatory beta activity in the STN and primary sensorimotor cortex of both hemispheres. Dopamine deficiency directly influenced movement-related beta-modulation, with greater beta-suppression in the most dopamine-depleted hemisphere for both ipsi- and contralateral hand movements. Cortical-subcortical, but not interhemispheric subcortical coherencies were modulated by movement and influenced by striatal dopaminergic innervation, being stronger in the most dopamine-depleted hemisphere. The data are consistent with a role of dopamine in shielding subcortical structures from an excessive cortical entrapment and cross-hemispheric coupling, thus allowing fine-tuning of movement.
Cholangiocarcinoma (CCA) is a heterogeneous group of malignancies with features of biliary tract differentiation. CCA is the second most common primary liver tumour and the incidence is increasing worldwide. CCA has high mortality owing to its aggressiveness, late diagnosis and refractory nature. In May 2015, the "European Network for the Study of Cholangiocarcinoma" (ENS-CCA: www.enscca.org or www.cholangiocarcinoma.eu) was created to promote and boost international research collaboration on the study of CCA at basic, translational and clinical level. In this Consensus Statement, we aim to provide valuable information on classifications, pathological features, risk factors, cells of origin, genetic and epigenetic modifications and current therapies available for this cancer. Moreover, future directions on basic and clinical investigations and plans for the ENS-CCA are highlighted.
Background
The aim of the present study was to assess manifestations of and applied treatment concepts for females with Fabry disease (FD) according to the current European Fabry Guidelines.
Methods
Between 10/2008 and 12/2014, data from the most recent visit of 261 adult female FD patients from six German Fabry centers were retrospectively analyzed. Clinical presentation and laboratory data, including plasma lyso-Gb3 levels were assessed.
Results
Fifty-five percent of females were on enzyme replacement therapy (ERT), according to recent European FD guidelines. Thirty-three percent of females were untreated although criteria for ERT initiation were fulfilled. In general, the presence of left ventricular hypertrophy (LVH) seemed to impact more on ERT initiation than impaired renal function. In ERT-naïve females RAAS blockers were more often prescribed if LVH was present rather than albuminuria. Affected females with missense mutations showed a similar disease burden compared to females with nonsense mutations. Elevated plasma lyso-Gb3 levels in ERT-naïve females seem to be a marker of disease burden, since patients showed comparable incidences of organ manifestations even if they were ~8 years younger than females with normal lyso-Gb3 levels.
Conclusion
The treatment of the majority of females with FD in Germany is in line with the current European FD guidelines. However, a relevant number of females remain untreated despite organ involvement, necessitating a careful reevaluation of these females.
Patients with chronic kidney disease (CKD) exhibit an increased cancer risk compared to a healthy control population. To be able to estimate the cancer risk of the patients and to assess the impact of interventional therapies thereon, it is of particular interest to measure the patients’ burden of genomic damage. Chromosomal abnormalities, reduced DNA repair, and DNA lesions were found indeed in cells of patients with CKD. Biomarkers for DNA damage measurable in easily accessible cells like peripheral blood lymphocytes are chromosomal aberrations, structural DNA lesions, and oxidatively modified DNA bases. In this review the most common methods quantifying the three parameters mentioned above, the cytokinesis-block micronucleus assay, the comet assay, and the quantification of 8-oxo-7,8-dihydro-2′-deoxyguanosine, are evaluated concerning the feasibility of the analysis and regarding the marker’s potential to predict clinical outcomes.
Mining biomedical images towards valuable information retrieval in biomedical and life sciences
(2016)
Biomedical images are helpful sources for the scientists and practitioners in drawing significant hypotheses, exemplifying approaches and describing experimental results in published biomedical literature. In last decades, there has been an enormous increase in the amount of heterogeneous biomedical image production and publication, which results in a need for bioimaging platforms for feature extraction and analysis of text and content in biomedical images to take advantage in implementing effective information retrieval systems. In this review, we summarize technologies related to data mining of figures. We describe and compare the potential of different approaches in terms of their developmental aspects, used methodologies, produced results, achieved accuracies and limitations. Our comparative conclusions include current challenges for bioimaging software with selective image mining, embedded text extraction and processing of complex natural language queries.
The formation of macromolecular complexes within the crowded environment of cells often requires aid from assembly chaperones. PRMT5 and SMN complexes mediate this task for the assembly of the common core of pre-mRNA processing small nuclear ribonucleoprotein particles (snRNPs). Core formation is initiated by the PRMT5-complex subunit pICln, which pre-arranges the core proteins into spatial positions occupied in the assembled snRNP. The SMN complex then accepts these pICln-bound proteins and unites them with small nuclear RNA (snRNA). Here, we have analyzed how newly synthesized snRNP proteins are channeled into the assembly pathway to evade mis-assembly. We show that they initially remain bound to the ribosome near the polypeptide exit tunnel and dissociate upon association with pICln. Coincident with its release activity, pICln ensures the formation of cognate heterooligomers and their chaperoned guidance into the assembly pathway. Our study identifies the ribosomal quality control hub as a site where chaperone-mediated assembly of macromolecular complexes can be initiated.
Serotonergic modulation of 'waiting impulsivity' is mediated by the impulsivity phenotype in humans
(2016)
In rodents, the five-choice serial reaction time task (5-CSRTT) has been established as a reliable measure of waiting impulsivity being defined as the ability to regulate a response in anticipation of reinforcement. Key brain structures are the nucleus accumbens (NAcc) and prefrontal regions (for example, pre- and infralimbic cortex), which are, together with other transmitters, modulated by serotonin. In this functional magnetic resonance imaging study, we examined 103 healthy males while performing the 5-CSRTT measuring brain activation in humans by means of a paradigm that has been widely applied in rodents. Subjects were genotyped for the tryptophan hydroxylase-2 (TPH2; G-703T; rs4570625) variant, an enzyme specific for brain serotonin synthesis. We addressed neural activation patterns of waiting impulsivity and the interaction between the NAcc and the ventromedial prefrontal cortex (vmPFC) using dynamic causal modeling. Genetic influence was examined via interaction analyses between the TPH2 genotype (GG homozygotes vs T allele carriers) and the degree of impulsivity as measured by the 5-CSRTT. We found that the driving input of the vmPFC was reduced in highly impulsive T allele carriers (reflecting a reduced top-down control) in combination with an enhanced response in the NAcc after correct target processing (reflecting an augmented response to monetary reward). Taken together, we found a high overlap of our findings with reports from animal studies in regard to the underlying cognitive processes, the brain regions associated with waiting impulsivity and the neural interplay between the NAcc and vmPFC. Therefore, we conclude that the 5-CSRTT is a promising tool for translational studies.
Background
Genetic code expansion has developed into an elegant tool to incorporate unnatural amino acids (uAA) at predefined sites in the protein backbone in response to an amber codon. However, recombinant production and yield of uAA comprising proteins are challenged due to the additional translation machinery required for uAA incorporation.
Results
We developed a microtiter plate-based high-throughput monitoring system (HTMS) to study and optimize uAA integration in the model protein enhanced green fluorescence protein (eGFP). Two uAA, propargyl-L-lysine (Plk) and (S)-2-amino-6-((2-azidoethoxy) carbonylamino) hexanoic acid (Alk), were incorporated at the same site into eGFP co-expressing the native PylRS/tRNAPyl CUA pair originating from Methanosarcina barkeri in E. coli. The site-specific uAA functionalization was confirmed by LC-MS/MS analysis. uAA-eGFP production and biomass growth in parallelized E. coli cultivations was correlated to (i) uAA concentration and the (ii) time of uAA addition to the expression medium as well as to induction parameters including the (iii) time and (iv) amount of IPTG supplementation. The online measurements of the HTMS were consolidated by end point-detection using standard enzyme-linked immunosorbent procedures.
Conclusion
The developed HTMS is powerful tool for parallelized and rapid screening. In light of uAA integration, future applications may include parallelized screening of different PylRS/tRNAPyl CUA pairs as well as further optimization of culture conditions.
Maintaining the integrity of the cuticular transpiration barrier even at elevated temperatures is of vital importance especially for hot-desert plants. Currently, the temperature dependence of the leaf cuticular water permeability and its relationship with the chemistry of the cuticles are not known for a single desert plant. This study investigates whether (i) the cuticular permeability of a desert plant is lower than that of species from non-desert habitats, (ii) the temperature-dependent increase of permeability is less pronounced than in those species and (iii) whether the susceptibility of the cuticular permeability barrier to high temperatures is related to the amounts or properties of the cutin or the cuticular waxes. We test these questions with Rhazya stricta using the minimum leaf water vapour conductance (gmin) as a proxy for cuticular water permeability. gmin of R. stricta (5.41 × 10\(^{-5}\) m s\(^{-1}\) at 25 °C) is in the upper range of all existing data for woody species from various non-desert habitats. At the same time, in R. stricta, the effect of temperature (15-50 °C) on gmin (2.4-fold) is lower than in all other species (up to 12-fold). Rhazya stricta is also special since the temperature dependence of gmin does not become steeper above a certain transition temperature. For identifying the chemical and physical foundation of this phenomenon, the amounts and the compositions of cuticular waxes and cutin were determined. The leaf cuticular wax (251.4 μg cm\(^{-2}\)) is mainly composed of pentacyclic triterpenoids (85.2% of total wax) while long-chain aliphatics contribute only 3.4%. In comparison with many other species, the triterpenoid-to-cutin ratio of R. stricta (0.63) is high. We propose that the triterpenoids deposited within the cutin matrix restrict the thermal expansion of the polymer and, thus, prevent thermal damage to the highly ordered aliphatic wax barrier even at high temperatures.
In the current study, electroencephalography (EEG) was recorded simultaneously with facial electromyography (fEMG) to determine whether emotional faces and emotional scenes are processed differently at the neural level. In addition, it was investigated whether these differences can be observed at the behavioural level via spontaneous facial muscle activity. Emotional content of the stimuli did not affect early P1 activity. Emotional faces elicited enhanced amplitudes of the face-sensitive N170 component, while its counterpart, the scene-related N100, was not sensitive to emotional content of scenes. At 220-280 ms, the early posterior negativity (EPN) was enhanced only slightly for fearful as compared to neutral or happy faces. However, its amplitudes were significantly enhanced during processing of scenes with positive content, particularly over the right hemisphere. Scenes of positive content also elicited enhanced spontaneous zygomatic activity from 500-750 ms onwards, while happy faces elicited no such changes. Contrastingly, both fearful faces and negative scenes elicited enhanced spontaneous corrugator activity at 500-750 ms after stimulus onset. However, relative to baseline EMG changes occurred earlier for faces (250 ms) than for scenes (500 ms) whereas for scenes activity changes were more pronounced over the whole viewing period. Taking into account all effects, the data suggests that emotional facial expressions evoke faster attentional orienting, but weaker affective neural activity and emotional behavioural responses compared to emotional scenes.
Evaluation of clinical parameters influencing the development of bone metastasis in breast cancer
(2016)
Background
The development of metastases is a negative prognostic parameter for the clinical outcome of breast cancer. Bone constitutes the first site of distant metastases for many affected women. The purpose of this retrospective multicentre study was to evaluate if and how different variables such as primary tumour stage, biological and histological subtype, age at primary diagnosis, tumour size, the number of affected lymph nodes as well as grading influence the development of bone-only metastases.
Methods
This retrospective German multicentre study is based on the BRENDA collective and included 9625 patients with primary breast cancer recruited from 1992 to 2008. In this analysis, we investigated a subgroup of 226 patients with bone-only metastases. Association between bone-only relapse and clinico-pathological risk factors was assessed in multivariate models using the tree-building algorithms “exhausted CHAID (Chi-square Automatic Interaction Detectors)” and CART(Classification and Regression Tree), as well as radial basis function networks (RBF-net), feedforward multilayer perceptron networks (MLP) and logistic regression.
Results
Multivariate analysis demonstrated that breast cancer subtypes have the strongest influence on the development of bone-only metastases (χ2 = 28). 29.9 % of patients with luminal A or luminal B (ABC-patients) and 11.4 % with triple negative BC (TNBC) or HER2-overexpressing tumours had bone-only metastases (p < 0.001). Five different mathematical models confirmed this correlation. The second important risk factor is the age at primary diagnosis. Moreover, BC subcategories influence the overall survival from date of metastatic disease of patients with bone-only metastases. Patients with bone-only metastases and TNBC (p < 0.001; HR = 7.47 (95 % CI: 3.52–15.87) or HER2 overexpressing BC (p = 0.007; HR = 3.04 (95 % CI: 1.36–6.80) have the worst outcome compared to patients with luminal A or luminal B tumours and bone-only metastases.
Conclusion
The bottom line of different mathematical models is the prior importance of subcategories of breast cancer and the age at primary diagnosis for the appearance of osseous metastases. The primary tumour stage, histological subtype, tumour size, the number of affected lymph nodes, grading and NPI seem to have only a minor influence on the development of bone-only metastases.
Diabolical points (spectral degeneracies) can naturally occur in spectra of two-dimensional quantum systems and classical wave resonators due to simple symmetries. Geometric Berry phase is associated with these spectral degeneracies. Here, we demonstrate a diabolical point and the corresponding Berry phase in the spectrum of hybrid light-matter quasiparticles—exciton-polaritons in semiconductor microcavities. It is well known that sufficiently strong optical pumping can drive exciton-polaritons to quantum degeneracy, whereby they form a macroscopically populated quantum coherent state similar to a Bose-Einstein condensate. By pumping a microcavity with a spatially structured light beam, we create a two-dimensional quantum billiard for the exciton-polariton condensate and demonstrate a diabolical point in the spectrum of the billiard eigenstates. The fully reconfigurable geometry of the potential walls controlled by the optical pump enables a striking experimental visualization of the Berry phase associated with the diabolical point. The Berry phase is observed and measured by direct imaging of the macroscopic exciton-polariton probability densities.
Background
Epigenetic modifications may play a relevant role in the pathogenesis of human abdominal aortic aneurysm (AAA). The aim of the study was therefore to investigate histone acetylation and expression of corresponding lysine [K] histone acetyltransferases (KATs) in AAA.
Results
A comparative study of AAA tissue samples (n = 37, open surgical intervention) and healthy aortae (n = 12, trauma surgery) was performed using quantitative PCR, immunohistochemistry (IHC), and Western blot. Expression of the KAT families GNAT (KAT2A, KAT2B), p300/CBP (KAT3A, KAT3B), and MYST (KAT5, KAT6A, KAT6B, KAT7, KAT8) was significantly higher in AAA than in controls (P ≤ 0.019). Highest expression was observed for KAT2B, KAT3A, KAT3B, and KAT6B (P ≤ 0.007). Expression of KAT2B significantly correlated with KAT3A, KAT3B, and KAT6B (r = 0.705, 0.564, and 0.528, respectively, P < 0.001), and KAT6B with KAT3A, KAT3B, and KAT6A (r = 0.407, 0.500, and 0.531, respectively, P < 0.05). Localization of highly expressed KAT2B, KAT3B, and KAT6B was further characterized by immunostaining. Significant correlations were observed between KAT2B with endothelial cells (ECs) (r = 0.486, P < 0.01), KAT3B with T cells and macrophages, (r = 0.421 and r = 0.351, respectively, P < 0.05), KAT6A with intramural ECs (r = 0.541, P < 0.001) and with a contractile phenotype of smooth muscle cells (SMCs) (r = 0.425, P < 0.01), and KAT6B with T cells (r = 0.553, P < 0.001). Furthermore, KAT2B was associated with AAA diameter (r = 0.382, P < 0.05), and KAT3B, KAT6A, and KAT6B correlated negatively with blood urea nitrogen (r = −0.403, −0.408, −0.478, P < 0.05). In addtion, acetylation of the histone substrates H3K9, H3K18 and H3K14 was increased in AAA compared to control aortae.
Conclusions
Our results demonstrate that aberrant epigenetic modifications such as changes in the expression of KATs and acetylation of corresponding histones are present in AAA. These findings may provide new insight in the pathomechanism of AAA.
Background
Antimicrobial resistance has been declared by the World Health Organization as a threat to the public health. The aim of this study was to analyze antimicrobial resistance patterns of the common pathogens occurring at the Bugando Medical Centre (BMC), Mwanza, Tanzania to provide data for antimicrobial stewardship programmes.
Methods
A total of 3330 microbiological culture results scripts representing non-repetitive specimens reported between June 2013 and May 2015 were retrieved and analyzed for pathogens and their susceptibility patterns using STATA-11 software.
Results
Out of 3330 specimens, 439 (13.2%) had positive culture. Staphylococcus aureus (n = 100; 22.8%), Klebsiella pneumoniae (n = 65; 14.8%) and Escherichia coli (n = 41; 9.3%) were the most frequently isolated bacteria. Of 78 Staphylococcus aureus tested, 27 (34.6%) were found to be methicillin resistant Staphylococcus aureus (MRSA). Rates of resistance of Klebsiella pneumoniae and Escherichia coli isolates to third generation cephalosporins were 38.5% (25/65) and 29.3% (12/41) respectively. Staphylococcus aureus and Klesbiella pneumoniae were commonly isolated from bloodstream infections while Escherichia coli and Pseudomonas aeruginosa were the predominant isolates from urinary tract and wounds infections respectively. Of 23 Salmonella species isolated, 22 (95%) were recovered from the blood. Nine of the 23 Salmonella species isolates (39%) were found to be resistant to third generation cephalosporins. The resistance rate of gram-negative bacteria to third generation cephalosporins increased from 26.5% in 2014 to 57.9% in 2015 (p = 0.004) while the rate of MRSA decreased from 41.2% in 2013 to 9.5% in 2015 (p = 0.016). Multidrug-resistant gram-negative isolates were commonly isolated from Intensive Care Units and it was noted that, the majority of invasive infections were due to gram-negative bacteria.
Conclusion
There is an increase in proportion of gram-negative isolates resistant to third generation cephalosporins. The diversity of potential pathogens resistant to commonly prescribed antibiotics underscores the importance of sustained and standardized antimicrobial resistance surveillance and antibiotic stewardship programmes in developing countries.
Reconstructing and understanding the Human Physiome virtually is a complex mathematical problem, and a highly demanding computational challenge. Mathematical models spanning from the molecular level through to whole populations of individuals must be integrated, then personalized. This requires interoperability with multiple disparate and geographically separated data sources, and myriad computational software tools. Extracting and producing knowledge from such sources, even when the databases and software are readily available, is a challenging task. Despite the difficulties, researchers must frequently perform these tasks so that available knowledge can be continually integrated into the common framework required to realize the Human Physiome. Software and infrastructures that support the communities that generate these, together with their underlying standards to format, describe and interlink the corresponding data and computer models, are pivotal to the Human Physiome being realized. They provide the foundations for integrating, exchanging and re-using data and models efficiently, and correctly, while also supporting the dissemination of growing knowledge in these forms. In this paper, we explore the standards, software tooling, repositories and infrastructures that support this work, and detail what makes them vital to realizing the Human Physiome.
Entropy production in industrial economies involves heat currents, driven by gradients of temperature, and particle currents, driven by specific external forces and gradients of temperature and chemical potentials. Pollution functions are constructed for the associated emissions. They reduce the output elasticities of the production factors capital, labor, and energy in the growth equation of the capital-labor-energy-creativity model, when the emissions approach their critical limits. These are drawn by, e.g., health hazards or threats to ecological and climate stability. By definition, the limits oblige the economic actors to dedicate shares of the available production factors to emission mitigation, or to adjustments to the emission-induced changes in the biosphere. Since these shares are missing for the production of the quantity of goods and services that would be available to consumers and investors without emission mitigation, the “conventional” output of the economy shrinks. The resulting losses of conventional output are estimated for two classes of scenarios: (1) energy conservation; and (2) nuclear exit and subsidies to photovoltaics. The data of the scenarios refer to Germany in the 1980s and after 11 March 2011. For the energy-conservation scenarios, a method of computing the reduction of output elasticities by emission abatement is proposed.
Otitis media (OM) is a common pediatric disease for which systemic antibiotics are often prescribed. While local treatment would avoid the systemic treatment side-effects, the tympanic membrane (TM) represents an impenetrable barrier unless surgically breached. We hypothesized that the TM might harbor innate biological mechanisms that could mediate trans-TM transport. We used two M13-bacteriophage display biopanning strategies to search for mediators of trans-TM transport. First, aliquots of linear phage library displaying 10\(^{10th}\) 12mer peptides were applied on the TM of rats with active bacterial OM. The middle ear (ME) contents were then harvested, amplified and the preparation re-applied for additional rounds. Second, the same naïve library was sequentially screened for phage exhibiting TM binding, internalization and then transit. Results revealed a novel set of peptides that transit across the TM to the ME in a time and temperature dependent manner. The peptides with highest transport capacities shared sequence similarities. Historically, the TM was viewed as an impermeable barrier. However, our studies reveal that it is possible to translocate peptide-linked small particles across the TM. This is the first comprehensive biopanning for the isolation of TM transiting peptidic ligands. The identified mechanism offers a new drug delivery platform into the ME.
Background
Ribavirin blood levels vary considerably between patients with standard weight-based dosing. Their impact on sustained virological response (SVR) with pegylated interferon and ribavirin is controversial, but has mostly been studied before the IL28b gene polymorphism as a possible confounder was discovered.
Methods
The impact of serum ribavirin trough levels at week 4, at the end of treatment and of mean levels across the entire antiviral treatment with pegylated interferon and ribavirin on relapse, SVR rates and anemia was retrospectively studied by univariate and multivariable logistic regression analyses in 214 patients with HCV genotype 1–4 infection, including 88 patients with available IL28b genotyping.
Results
Mean ribavirin levels varied between 0.68–5.65 mg/l and significantly differed between patients with or without SVR. By multivariable regression including age, sex, HCV viral load, HCV genotype, liver fibrosis stage, prior treatments, immunosuppression and IL28b genotype, ribavirin levels consistently displayed significant influence on SVR and relapse without indication for a specific importance of higher concentrations early or late in the treatment course. Although hemoglobin decline was on average more pronounced in patients with higher ribavirin levels, hemoglobin remained relatively stable in a significant proportion of these, indicating that ribavirin levels alone are insufficient to predict anemia.
Conclusion
While data are scarce to draw conclusions applicable for modern DAA therapies, these results support ribavirin treatment based on serum levels instead of purely weight-based dosing in combination with pegylated interferon.
One of the most intricate issues of nuclear power is the long-term safety of repositories for radioactive waste. These repositories can have an impact on future generations for a period of time orders of magnitude longer than any known civilization. Several countries have considered copper as an outer corrosion barrier for canisters containing spent nuclear fuel. Among the many processes that must be considered in the safety assessments, radiation induced processes constitute a key-component. Here we show that copper metal immersed in water uptakes considerable amounts of hydrogen when exposed to γ-radiation. Additionally we show that the amount of hydrogen absorbed by copper depends on the total dose of radiation. At a dose of 69 kGy the uptake of hydrogen by metallic copper is 7 orders of magnitude higher than when the absorption is driven by H\(_{2}\)(g) at a pressure of 1 atm in a non-irradiated dry system. Moreover, irradiation of copper in water causes corrosion of the metal and the formation of a variety of surface cavities, nanoparticle deposits, and islands of needle-shaped crystals. Hence, radiation enhanced uptake of hydrogen by spent nuclear fuel encapsulating materials should be taken into account in the safety assessments of nuclear waste repositories.