Refine
Has Fulltext
- yes (643)
Year of publication
- 2016 (643) (remove)
Document Type
- Journal article (547)
- Doctoral Thesis (86)
- Book article / Book chapter (3)
- Preprint (3)
- Review (2)
- Master Thesis (1)
- Working Paper (1)
Language
- English (643) (remove)
Keywords
- Drosophila (7)
- Drosophila melanogaster (7)
- inflammation (7)
- vision (7)
- Fabry disease (6)
- breast cancer (6)
- phosphorylation (6)
- Boron (5)
- Taufliege (5)
- Trypanosoma brucei (5)
- genetics (5)
- mice (5)
- DNA (4)
- DNA damage (4)
- DNA methylation (4)
- EEG (4)
- MRSA (4)
- Pain (4)
- Staphylococcus aureus (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)
- Cancer genetics (3)
- Diborane (3)
- Enzyme replacement therapy (3)
- LHC (3)
- MRI (3)
- Multiple bonds (3)
- Myelin oligodendrocyte glycoprotein antibodies (MOG-IgG) (3)
- NLO Computations (3)
- Neuromyelitis optica spectrum disorders (NMOSD) (3)
- Optic neuritis (3)
- Transcriptome (3)
- Treatment (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)
- monocytes (3)
- multiple sclerosis (3)
- ovarian cancer (3)
- platelets (3)
- polymers (3)
- prostate cancer (3)
- sRNA (3)
- simulation (3)
- AAA (2)
- ADHD (2)
- Adult (2)
- Aminosäuren (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)
- Biradicals (2)
- Bone-marrow-transplantation (2)
- Bor (2)
- CMV (2)
- Campylobacter jejuni (2)
- Candida albicans (2)
- Carcinogenicity (2)
- Cell therapy (2)
- Cells (2)
- Central nervous system (2)
- Cerebrospinal fluid (2)
- Chemotherapy (2)
- China (2)
- Cycloaddition (2)
- Cytoskeleton (2)
- DNS (2)
- Diagnosis (2)
- Dionaea muscipula (2)
- Diseases (2)
- Down syndrome (2)
- Dyes (2)
- Electroencephalographie (2)
- Electrophysiology (2)
- Elektronenspin (2)
- Enzyme induction (2)
- Expression (2)
- Fluorescence (2)
- Galerkin-Methode (2)
- Gefühl (2)
- Gene (2)
- Genetics research (2)
- Genome (2)
- Genregulation (2)
- Germany (2)
- Graphen (2)
- Guidelines (2)
- HIV (2)
- HKT transporter (2)
- Humans (2)
- IAPS (2)
- In-vitro (2)
- Infections (2)
- Inflammation (2)
- Inhibitor (2)
- Kutikula (2)
- Leistungsbewertung (2)
- Longitudinally extensive transverse myelitis (LETM) (2)
- MDD (2)
- MEG (2)
- MODIS (2)
- MS (2)
- MYC (2)
- Mechanisms (2)
- Merkel cell carcinoma (2)
- Metabolism (2)
- Mice (2)
- Model (2)
- Molekularbiologie (2)
- Molekularstrahlepitaxie (2)
- Motivation (2)
- Multiple sclerosis (2)
- Nanodraht (2)
- Neisseria meningitidis (2)
- Neurofilament (2)
- Neurotrophic factors (2)
- Optimale Kontrolle (2)
- Outcome survey (2)
- Oxidative stress (2)
- P300 (2)
- PET (2)
- PRRT (2)
- Parkinson's disease (2)
- Parkinson’s disease (2)
- Phase-II (2)
- Posttranskriptionelle Regulation (2)
- Psychologie (2)
- Quantenpunkt (2)
- RHEED (2)
- RNA interference (2)
- Radio astronomy (2)
- Radioastronomie (2)
- Randomized controlled-trial (2)
- Rehabilitation (2)
- Relapse (2)
- Reproductive toxicity (2)
- Rezension (2)
- Silicones (2)
- Spermatogenesis (2)
- Spin (2)
- Stress (2)
- Systems (2)
- Tagesrhythmus (2)
- Therapy (2)
- Thyroid cancer (2)
- Tissue Engineering (2)
- Topologischer Isolator (2)
- Transcription (2)
- Validation (2)
- Venusfliegenfalle (2)
- absorption spectra (2)
- activation (2)
- adaption (2)
- adenosine (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)
- 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)
- imaging (2)
- in vitro (2)
- in-vivo (2)
- inflammatory bowel disease (2)
- innate immune system (2)
- insect brain (2)
- insulin (2)
- interaction (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)
- miRNS (2)
- microbiota (2)
- mouse (2)
- mouse models (2)
- movement disorders (2)
- multiple myeloma (2)
- mushroom body (2)
- mutation (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 cells (2)
- surfactants (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)
- AC Stark effect (1)
- ADHS (1)
- AFM (1)
- AIDS (1)
- AIRWAYS ICPs (1)
- ANTARES telescope (1)
- AP-1 (1)
- ARIA (1)
- AT/RT (1)
- Abschirmung (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)
- Addison's disease (1)
- Adhesion-GPCR (1)
- Adipokine (1)
- Adjuvans (1)
- Adjuvant (1)
- Adolescence (1)
- Adolescents (1)
- Adrenocortial carcinomas (1)
- Adult patients (1)
- Adultschlupfes (1)
- Affective processing (1)
- Affekt (1)
- Ag-DNA (1)
- Agalsidase beta (1)
- Aggregat <Chemie> (1)
- Aggression (1)
- Aggressive behaviour (1)
- Aging (1)
- Agoraphobia (1)
- Agricultural intensification (1)
- Aktive Galaxie (1)
- Aktiver galaktischer Kern (1)
- Akute myeloische Leukämie (1)
- Alpha therapy (1)
- Alpha-Aktivität (1)
- Alpha-Galactosidase (1)
- Alpha-synuclein oligomers (1)
- Alternative test methods (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)
- Angiopoietin-2 (1)
- Angiopoietin-like 4 (1)
- Angst (1)
- Angsterkrankungen (1)
- Animal models (1)
- Annapurna Conservation Area (1)
- Annotation (1)
- Anorexia nervosa (1)
- Anpassung (1)
- Antibody index (1)
- Antimikrobielle Peptide (1)
- Antisocial behavior (1)
- Anxiety (1)
- Anxiety sensitivity (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)
- Arabidopsis-thaliana (1)
- Arbitrary Lagrangian-Eulerian (1)
- Archaea (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)
- Assay (1)
- Association (1)
- Astrophysical Jet (1)
- Ataxia (1)
- Atomic force microscopy (1)
- Atrial natriuretic peptide (1)
- Attention Deficit Hyperactivity Disorder (ADHD) (1)
- Aufmerksamkeit (1)
- Aufmerksamkeitsdefizit-Syndrom (1)
- Autism (1)
- Autoimmune diseases (1)
- Autoimmunity (1)
- Autoinflammation (1)
- Aversive events (1)
- Aversive tension (1)
- Avoidance behavior (1)
- Axon degeneration (1)
- Axon growth (1)
- Axon guidance (1)
- Axonal transport (1)
- Axonschaden (1)
- Azathioprine (1)
- B cell (1)
- B-B bond (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)
- Bacteria (1)
- Bacterial community analysis (1)
- Bacterial meningitis (1)
- Bacterial symbionts (1)
- Barkhof criteria (1)
- Barratt Impulsiveness Scale (1)
- Bauchspeicheldrüsenkrebs (1)
- Bee abundance (1)
- Behavior (1)
- Behavioral neuroscience (1)
- Behçet’s disease (1)
- Berry phase (1)
- Beta-catenin (1)
- Bibel. Judit, 10-13 (1)
- Bierhefe (1)
- Big picture (1)
- Bildrekonstruktion (1)
- Biocompatibility (1)
- Biodegradable polymer scaffolds (1)
- Biodiversity assessment (1)
- Biodiversität (1)
- Biogenic (1)
- Bioinformatik (1)
- Bismutverbindungen (1)
- Blazar (1)
- Blazars (1)
- Blickbewegung (1)
- Blochmannia floridanus (1)
- Blood pressure (1)
- Bone disease (1)
- Bone marrow transplantantation (1)
- Bone morphogenetic protein-2 (1)
- Bone tissue engineering (1)
- Boron Chemistry (1)
- Borverbindungen (1)
- Bose gas (1)
- Bose-Fermi (1)
- Botulinustoxin (1)
- Bound-states (1)
- Bradyrhizobium (1)
- Bragg-reflection waveguide (1)
- Brain (1)
- Brain Computer Interface (1)
- Brainstem encephalitis (1)
- Breaking (1)
- Breast cancer (1)
- Breath tests (1)
- Broca (1)
- Butyrylcholinesterase (1)
- B‐cell lymphoma (1)
- C2-toxin (1)
- CA19-9 (1)
- CD11b+ myeloid cells (1)
- CD39 (1)
- CD73 (1)
- CD8 (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)
- Cadherin (CDH13) (1)
- Cadmiumtellurid (1)
- Calcineurin-NFATsignaling (1)
- Calculus of variations (1)
- Camponotus floridanus (1)
- Canada (1)
- Cancer (1)
- Carbamate (1)
- Carbon (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)
- Ceramide (1)
- Cerebellitis (1)
- Cerebral-ischemia (1)
- Cervical cancer (1)
- ChIP-sequencing (1)
- Charcot-Marie-Tooth (1)
- Chemerin (1)
- Chemerin processing (1)
- Chemicals (1)
- Chemistry (1)
- Childhood (1)
- Childhood medulloblastoma (1)
- Childrens-cancer (1)
- Chlorophyll fluorescence (1)
- Cholinesterase (1)
- Chordontonal organ (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)
- Chronobiologie (1)
- Cimex lectularius (1)
- Circadian clock (1)
- Clinical Genetics (1)
- Clinical practice guidelines (1)
- Clinical remission (1)
- Clinical trial (1)
- Cloud Computing (1)
- Cloud Gaming (1)
- Cloud computing (1)
- Cocalodinae (1)
- Cognitive Distortions (1)
- Cognitive Therapy (1)
- Coherent two-dimensional Spectroscopy (1)
- Cohort study (1)
- Coleoptera: Chrysomelidae (1)
- Collaboration (1)
- Colony growth (1)
- Combinatorial Background (1)
- Compressed Sensing (1)
- Computersimulation (1)
- Conditioning evidence (1)
- Conduct disorder (1)
- Conjugate arc therapy (1)
- Conjugated polymers (1)
- Context (1)
- Contextual fear (1)
- Contrast-enhanced CT (1)
- Control centrality (1)
- Copaxone® (1)
- Corona charged aerosol detector (1)
- Coronary artery disease (1)
- Cortical plasticity (1)
- Cost-benefit analysis (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)
- Cystic-fibriosis (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-Reparatur (1)
- DNS-Schädigung (1)
- DNS-Sequenz (1)
- DOTATOC (1)
- DPF3a (1)
- DYT1 (1)
- Danio-rerio (1)
- Dark Matter (1)
- Darmflora (1)
- Darmwandnervensystem (1)
- Deficit/hyperactivity disorder (1)
- Delphi Study (1)
- Dendritic cells (1)
- Densities (1)
- Dentate granule cells (1)
- Design (1)
- Devic syndrome (1)
- Devic’s syndrome (1)
- Diabetes mellitus (1)
- Diagnostic approach (1)
- Dictyostelium discoideum (1)
- Differential RNA-sequencing (1)
- Differentialgleichungssystem (1)
- Diisononyl phthalate (1)
- Dimer-Konfiguration (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)
- Doppelaufgabe (1)
- Dorsolateral prefrontal cortex (1)
- Dose reduction (1)
- Double-blind (1)
- Draize eye test (1)
- Drosha (1)
- Drosophilia (1)
- Drug development (1)
- Drug metabolism (1)
- Drug-free remission (1)
- Dual task (1)
- Duchenne muscular dystrophy (1)
- Dystonia (1)
- Dünndarm (1)
- E3 ligase (1)
- EANM (1)
- EBV (1)
- EDS (1)
- EIP on AHA (1)
- ELISPOT (1)
- ESTARFM (1)
- EU‐RHAB Registry (1)
- Early posterior negativity (1)
- Eating disorder (1)
- Echtzeitsystem (1)
- Ecological momentary assessment (1)
- Ecologically important traits (1)
- Edema (1)
- Effectors in plant pathology (1)
- Ehlers-Danlos syndrome (1)
- Eindringerkennung (1)
- Elective cesarean-section (1)
- Electroencephalography (1)
- Electron Spin Resonance (1)
- Elektronenspinresonanz (1)
- Elektronisches Bauelement (1)
- Elektrophysiologie (1)
- Elliptic equations (1)
- Embodiment (1)
- Embryonic stem cell (1)
- Emission (1)
- Emotion (1)
- Emotion regulation (1)
- Emotional expression (1)
- Emotionsregulation (1)
- Emotionsverarbeitung (1)
- Empathie (1)
- Enantiomere (1)
- Endosymbiosen (1)
- Endothelial growth-factor (1)
- Endothelium (1)
- Energy depletion (1)
- Energy transfer (1)
- Entanglement (1)
- Enteric nervous system (1)
- Enteric neuropathies (1)
- Enterische Glia (1)
- Enterovirus (1)
- Entwicklungsländer (1)
- Environment (1)
- Environmental enrichment (1)
- Enzym (1)
- Enzyme inhibitor (1)
- Epidemiological study (1)
- Epidemiology (1)
- Epidermal growth-factor (1)
- Epidermis (1)
- Epigenesis (1)
- Epigenetics (1)
- Epigenetik (1)
- Epigenetische Mechanismen (1)
- Episkin (1)
- Epitaxy (1)
- Epitope (1)
- Erlernte Hilflosigkeit (1)
- Erwachsener (1)
- Erweiterte Realität <Informatik> (1)
- Escherichia coli K1 (1)
- Ethanol (1)
- European Innovation Partnership on Active and Healthy Ageing (1)
- European Organization for Nuclear Research. ATLAS Collaboration (1)
- Evaluation (1)
- Event (1)
- Event-related potential (1)
- Evoked potentials (1)
- Evolutionspsychologie (1)
- Exciton-polariton condensate (1)
- Excitons (1)
- Exercise (1)
- Existenz schwacher Lösungen (1)
- Exosome (1)
- Extracorporeal Membrane Oxygenation (1)
- Extremwertstatistik (1)
- Exziton (1)
- Exzitonen (1)
- Eye gaze (1)
- F-18-FDG PET/CT (1)
- FANCM (1)
- FE (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)
- Fabry cardiomyopathy (1)
- Fabry nephropathy (1)
- Fabry-associated pain (1)
- Faces and scenes (1)
- Facial nerve palsy (1)
- Factor receptor (1)
- Familial Alzheimers-disease (1)
- Farbgebung (1)
- Farbstoff (1)
- FeS proteins (1)
- Federal Reserve (1)
- Fehlertoleranz (1)
- Female (1)
- Femtosekundenspektroskopie (1)
- Fermentation (1)
- Fermi liquid (1)
- Ferrite (1)
- Fertilität (1)
- Festkörperphysik (1)
- Fetal brain development (1)
- Fibroblasts (1)
- Fiels-effect transistors (1)
- Finanzkrise (1)
- Fischer 344 rats (1)
- Fish Sex determination (1)
- Flabarin (1)
- Flash relaxation kinetics (1)
- Flow cytometry (1)
- Fluorescein angiography (1)
- Fluorouracil (1)
- Foragers (1)
- Fotokatalyse (1)
- Fourier-transform spectroscopy (1)
- FoxQ2 (1)
- Framework <Informatik> (1)
- Frequency-response areas (1)
- Fresh Freeze Plasma (1)
- Frontal asymmetry (1)
- Frontal cortex (1)
- Functional hydrophilic polymers (1)
- Functionalization (1)
- Fungal (1)
- Fungal host response (1)
- Funktionelle Kernspintomografie (1)
- Funktionentheorie (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)
- GaAsSb (1)
- Galactic Ridge (1)
- Galactosidase-A gene (1)
- Gambler's Fallacy (1)
- Gamma (1)
- Gasionisationsdetektor (1)
- Gaze perception (1)
- Gehirn-Computer-Schnittstelle (1)
- Geißel <Biologie> (1)
- Geldpolitik (1)
- Gelernte Hilflosigkeit (1)
- Gene expression profiling (1)
- Gene expression regulation (1)
- Gene-expression (1)
- Genetic (1)
- Genetic regulatory networks (1)
- Genitoanal region (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)
- Gerichtete Erstarrung (1)
- Geschlechtsdifferenzierung (1)
- Gifsy-1 (1)
- Gimbaled tracking (1)
- Glasur (1)
- Glatiramer acetate (1)
- Glia (1)
- Globale Optimierung (1)
- Glucose metabolism (1)
- Glucose uptake (1)
- Glucosyltransferase (1)
- Glutamatergic synapses (1)
- Glutathione (1)
- GlyR receptors (1)
- Glycaemic control (1)
- Glücksspiel (1)
- Golgi (1)
- Gott (1)
- Governance (1)
- Graft versus Tumor (1)
- Graft-versus-leukemia (1)
- Graphene (1)
- Graphene nanoribbons (1)
- Graphenzeichnen (1)
- Group B Streptococcus (1)
- Growth; BMP-2 (1)
- Guanylyl cyclase-A (1)
- Guideline (1)
- Guillain-Barré-Syndrom (1)
- Guinea pig model (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)
- HKT1 (1)
- HMBPP (1)
- HPLC (1)
- HPV (1)
- HRXRD (1)
- Habitats (1)
- Halbleiter (1)
- Halbleiter-Supraleiter-Kontakt (1)
- Haloferax volcanii (1)
- Hamburg (1)
- Hamilton-Jacobi-Differentialgleichung (1)
- Head-injury (1)
- Hearing loss (1)
- Hearing-loss (1)
- Heart (1)
- Heart Period (1)
- Helicobacter pylori (1)
- Hemodynamic depression (1)
- Hemoglobin A1C (1)
- Hennighausen (1)
- Hepatitis B virus (1)
- Hepatitis C (1)
- Herpes simplex encephalitis (1)
- Herpes simplex virus (1)
- Heterocycles (1)
- Heterocyclische Verbindungen (1)
- Heterostruktur (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)
- Hippocampus (1)
- Hirschsprung disease (1)
- Hirschsprung disease liability (1)
- Histologic grade (1)
- Hoechst 33342 (1)
- Homeostatic plasticity (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)
- Hydrogen-peroxide (1)
- Hydroxymethyluracil (1)
- Hymenoptera (1)
- Hypertonic saline 7.5-percent (1)
- Hypertrophic cardiomyopathy (1)
- Hypertrophic pyloric-stenosis (1)
- IBA-1 (1)
- IGRT (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)
- IVIg (1)
- Identification (1)
- IgE (1)
- IgE sensitazion (1)
- Illumina Human Exome Bead Chip (1)
- Image interpretation (1)
- Imatinib (1)
- Immune tolerance (1)
- Immungene (1)
- Immunmodulation (1)
- Immunocompromised patient (1)
- Immunotherapy (1)
- Immunsuppression (1)
- Immuntherapie (1)
- Impurity Profiling (1)
- In vitro (1)
- In vitro skin irritation testing (1)
- In-vivo (1)
- InSAR (1)
- Incomplete contracts (1)
- Indian muntjac (1)
- Inferior Vena Cava (1)
- Inferior colliculus (1)
- Infinite Optimierung (1)
- Infliximab (1)
- Influenzae type B (1)
- Information (1)
- Information Integration Theory (1)
- Informationsverarbeitung (1)
- Inhibitory glycine receptor (1)
- Inner hair cell (1)
- Insect hosts (1)
- Insects (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)
- Interband cascade lasers (1)
- Interferon beta (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)
- Intestinal pseudoobstruction (1)
- Intracellular domain (1)
- Intracellular virulence (1)
- Intractable nausea and vomiting (1)
- Intravascular coagulation (1)
- Invasion (1)
- Invasive Aspergillosis (1)
- Invasive fungal-infections (1)
- Iran (1)
- Islamic glazes (1)
- Islamische Kunst (1)
- Islamische Staaten (1)
- IsrK (1)
- JR11 (1)
- Jak kinases (1)
- Janus kinase (1)
- Jasmonate perception (1)
- Jasmonic acid (1)
- Joint ownership (1)
- Josephson effect (1)
- Josephson-Kontakt (1)
- Joubert syndrome (1)
- Judgment (1)
- Judith und Holofernes (1)
- Jurkat T cells (1)
- Jurkat cells (1)
- K2–K model (1)
- KAT/HAT (1)
- Kapitalbewegung (1)
- Katalyse (1)
- Kenyon cells (1)
- Keramik (1)
- Kern-Schale-Struktur (1)
- Kernhülle (1)
- Kernproteine (1)
- Ketoacyl-ACP-Synthase <beta-> (1)
- Ketoacyl-ACP-synthase (1)
- Kidney function (1)
- Kleinsatellit (1)
- Klimawandel (1)
- Klimaänderung (1)
- Knochen (1)
- Knorpel (1)
- Knowledge Representation Layer (1)
- Kognition (1)
- Kohlberg (1)
- Komprimierte Abtastung (1)
- Konjugate (1)
- Konsumentenpsychologie (1)
- Kontinuitätsgleichung (1)
- Kosten-Nutzen-Analyse (1)
- Krankheit (1)
- Kreuzung (1)
- Kristallstruktur (1)
- Kutikularwachs (1)
- L. reuteri (1)
- LASP1 (1)
- LED (1)
- LIN-5 (1)
- LINC complex (1)
- LITAF (1)
- LOFAR (1)
- LPS (1)
- Lachsartige <Familie> (1)
- Lacking neurofilaments (1)
- Lactated ringers solution (1)
- Lag time (1)
- Landsat (1)
- Large T antigen (1)
- Large multicenter ADHD (1)
- Latin America (1)
- Leaderless transcript (1)
- Learned Helplessness (1)
- Lectins (1)
- Leistungsmotivation (1)
- Lepidoptera (1)
- Lernerfolg (1)
- Letter of Aristeas (1)
- Light Supersymmetric Particle (1)
- Light-emitting diodes (1)
- Lipid (1)
- Lipid metabolism (1)
- Liposomal amphotericin-B (1)
- Liquid-crystalline (1)
- Liver cirrhosis (1)
- Localized states (1)
- Locomotor activity (1)
- Locus (1)
- Long-range order (1)
- Longitudinally extensive transverse myelitis (1)
- Low-dose acyclovir (1)
- LpxC inhibitors (1)
- Lungenentzündung (1)
- Luxembourg (1)
- Lynx lynx (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)
- MMQ cells (1)
- MOG-IgG (1)
- MPACT (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)
- Magnetoelastizität (1)
- Major abdominal surgery (1)
- Makrozyklus (1)
- Male breast cancer (1)
- Male intromittent organ (1)
- Malignant melanoma (1)
- Management (1)
- Mandibular condyle (1)
- Mandibular continuity defects (1)
- Manifestation (1)
- Manual responses (1)
- Marcus inverted region (1)
- Marrow stromal cells (1)
- Mass (1)
- Mast cells (1)
- Mathematical modeling (1)
- Mathematische Modellierung (1)
- Matrix (1)
- Maus (1)
- McDonald criteria (1)
- Mechanorezeptor (1)
- Mechanosensation (1)
- Medical image reconstruction (1)
- Medical overuse (1)
- Medical students (1)
- Medicalization (1)
- Medien (1)
- Medienpsychologie (1)
- Medulloblastoma (1)
- Mehrfachtätigkeit (1)
- Meiosis (1)
- Melanom (1)
- Melanoma B16 (1)
- Melanoma Maintenance (1)
- Mellitus (1)
- Meningococcal serogroup C (1)
- Meningococci (1)
- Mensch (1)
- Mesenchymal stem cells (1)
- Mesenchymal stem/stromal cells (1)
- Mesenchymal transition (1)
- Mesocestoides corti (1)
- Messenger RNA (1)
- Meta-barcoding (1)
- Metagenom (1)
- Metallocene (1)
- Metallocenes (1)
- Methicillin resistant Staphylococcus aureus (1)
- Methodological quality (1)
- Methotrexate (1)
- Methylation (1)
- Methylierung (1)
- Methylome (1)
- MgAl LDH (1)
- Microcavity (1)
- Microenvironment (1)
- Microorganisms (1)
- Microtubules (1)
- Mid-infrared photoluminescence (1)
- Midline (1)
- Mikromagnetismus (1)
- Mindfulness (1)
- Miniaturisierung (1)
- Minimal supersymmetric model (1)
- Missense mutation (1)
- Mitomycin C (1)
- Mitsunobu (1)
- Modellierung (1)
- Modelling (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)
- Molekulargenetik (1)
- Molekülstruktur (1)
- Monoamine Oxidase/genetics (1)
- Monoklonaler Antikörper (1)
- Morbus Fabry (1)
- Mord (1)
- Mortality (1)
- Motoneuron (1)
- Motoneuron disease (1)
- Motoneuron diseases (1)
- Mouse model (1)
- Moving mesh method (1)
- Mt. Kinabalu (1)
- Mud (1)
- Multi-Stakeholder (1)
- Multibranched structures (1)
- Multicenter randomized-trial (1)
- Multiple drug resistance (1)
- Multiple myeloma (1)
- Multitasking (1)
- Mustang District (1)
- Mutations (1)
- Myc (1)
- Myelin oligodendrocyte glycoprotein (MOG) antibodies (1)
- Myelitis (1)
- Myeloma (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)
- 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)
- Nanda-Hamner (1)
- Nanoparticles (1)
- Nanoröhre (1)
- Nanotubular coatings (1)
- Nanotubuläre Beschichtungen (1)
- Nanowire (1)
- Nasonia courtship (1)
- Natalizumab (1)
- Natural-history data (1)
- Naturtourismus (1)
- Natürliche Killerzelle (1)
- Near Miss (1)
- Neisseria gonorrhoeae (1)
- Nepal (1)
- Nesting resources (1)
- Netrin (1)
- Network (1)
- Neural crest cells (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)
- Neutrino Telescope (1)
- Neutrophil (1)
- Neutrophil granulocytes interaction (1)
- Neutrophiler Granulozyt (1)
- New Small Wheel (1)
- Nichtlineare Differentialgleichung (1)
- Nitric-oxide (1)
- Nodule (1)
- Non-coding RNAs (1)
- Non-ribosomal peptide synthetase (1)
- Normal breast (1)
- Nova (1)
- Nrf2 (1)
- NuMA (1)
- Numerische Strömungssimulation (1)
- Nurses (1)
- Nutzerstudie (1)
- OCB (1)
- OCSVM (1)
- OCT angiography (1)
- OECD guideline (1)
- OPS201 (1)
- Obesity (1)
- Oesling (1)
- Ofatumumab (1)
- Oilseed rape (1)
- Olfr1393 (1)
- Oligoclonal bands (1)
- OmoMYC (1)
- Oncology (1)
- Oncolytic action (1)
- One-photon (1)
- Ontologie <Wissensverarbeitung> (1)
- Oogenese (1)
- Oogenesis (1)
- Open Innovation (1)
- Open source reconstructed epidermis (1)
- Openfield test (1)
- Opsins (1)
- Optical properties (1)
- Optimal Control (1)
- Optimiertung (1)
- Optimierung (1)
- Optimization (1)
- Oral antidiabetic drugs (1)
- Oral squamous cell carcinoma (1)
- Organ motion (1)
- Organic Semiconductors (1)
- Organischer Halbleiter (1)
- Osteoarthritis (1)
- Osteoarthrosis (1)
- Osteogenic precursor cells (1)
- Outcome (1)
- Overdiagnosis (1)
- Oxidativer Stress (1)
- Oxide synthase gene (1)
- Oxygen (1)
- Oxygen diffusion hardening (1)
- P300 speller (1)
- P75 Neurotrophin receptor (1)
- PARROT (1)
- PBI cyclophane (1)
- PDE (1)
- PDEs (1)
- PDGF (1)
- PET/CT (1)
- PI3K isoforms (1)
- PI3K/Akt/mTOR (1)
- PICD (1)
- PKB/Akt phosphorylation (1)
- PSMA (1)
- PUMP (1)
- PVD Beschichtung (1)
- PVD coatings (1)
- PVD-Verfahren (1)
- Paediatric (1)
- Palladium-catalyzed silaboration (1)
- Panic Disorder/genetics (1)
- Panic Disorder/therapy (1)
- Panikstörung (1)
- Parabolic equations (1)
- Parametric down-conversion (1)
- Parasite (1)
- Parkinson disease (1)
- Partielle Differentialgleichung (1)
- Partielle Differentialgleichungen (1)
- Pathogenicity (1)
- Pathogens (1)
- Pathology (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)
- Perovskite (1)
- Personality (1)
- Perspektivenübernahme (1)
- Perylen-Farbstoffe (1)
- Perylene bisimide (1)
- Perylentetracarbonsäurederivate (1)
- Pflanzenschutzmittel (1)
- Phosphorylation (1)
- Photochemistry (1)
- Photosensibilisator (1)
- Photosystem I (1)
- Physics and instrumentation (1)
- Picosatellite (1)
- Pinus sylvestris L. (1)
- Pitrakinra (1)
- Placebo (1)
- Placebo-controlled trial (1)
- Plant Protection (1)
- Plant utricularia-gibba (1)
- Plants (1)
- Plasma extravasation (1)
- Plasma-membrane (1)
- Pleistocene (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)
- Polymer-peptide-conjugate (1)
- Polymerase chain raction (1)
- Polymerhalbleiter (1)
- Polyoxazoline (1)
- Polyphasic fluorescence rise (1)
- Polyphenols (1)
- Pontrjagin-Maximumprinzip (1)
- Pontryagins's maximum principle (1)
- Poor-prognosis (1)
- Porphyrin arrays (1)
- Positron-emission-tomography (1)
- Post-transcriptional regulation (1)
- Potential-energy curves (1)
- Pou2af1 (1)
- Preclinical evaluation (1)
- Predict fluid responsiveness (1)
- Pregnancy (1)
- Primary cell lines (1)
- Primary endosymbiont (1)
- Primitive neuroectodermal (1)
- Problem Gambling (1)
- Processing fluency (1)
- Programmed cell-death (1)
- Progressive motor neuronopathy (1)
- Progressive multifocal leukoencephalopathy (1)
- Progressive supranuclear palsy (1)
- Prolactin (1)
- Promoter (1)
- Promoter prediction (1)
- Property rights approach (1)
- Prostate-cancer (1)
- Protease inhibition (1)
- Protected areas (1)
- Protein (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)
- Pulmonary Embolism (1)
- Pulmonary hypertension (1)
- Puls-pressure variation (1)
- Purification (1)
- Pyrimidinone (1)
- QM/MM (1)
- QTL analysis (1)
- Quadruplex-DNS (1)
- Qualitative representation and reasoning (1)
- Quality of Experience (1)
- Quantenchromodynamik (1)
- Quantum dot (1)
- Quantum wells (1)
- Quecksilbertellurid (1)
- Queueing theory (1)
- RARRES2 (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)
- ROS (1)
- RU(CO)(3)CL(GLYCINATE) (1)
- RU-(II) complexes (1)
- RYGB (1)
- Racial differences (1)
- Radarsat-2 (1)
- Radio Interferometry (1)
- Radioindikator (1)
- Radionuclide Therapy (1)
- Radionuclide therapy (1)
- Radiopharmacy (1)
- Radiopharmaka (1)
- Radioteleskop (1)
- Radiotherapy (1)
- Rapid evolution (1)
- Rat (1)
- Rat mynteric plexus (1)
- Rating scale (1)
- Rats (1)
- RbdB (1)
- Reaction kinetics and dynamics (1)
- Reaktionsmechanismus (1)
- Reaktionspfadsuche (1)
- Reaktionszeit (1)
- Real-time PCR (1)
- Recurrent medulloblastoma (1)
- Redox environment (1)
- Regenerative medicine (1)
- Regionalentwicklung (1)
- Regulatory T cells (1)
- Regulatory T-cells (1)
- Regulatory-cells (1)
- Reinheitsanalytik (1)
- Reirradiation (1)
- Rekord (1)
- RelA (1)
- Relapsing-remitting MS (1)
- Relaxation Dynamics (1)
- Remotely Operate Vehicle (1)
- Reproduction (1)
- Respiratory insufficiency (1)
- Respiratory syncytial virus (1)
- Responses (1)
- Restaurierung (1)
- Restoration material (1)
- Retinal arterial macroaneurysms (1)
- Reveals (1)
- Rhabdoid 2007 (1)
- Rheumatoid arthritis (1)
- Rhodopsins (1)
- Rhombencephalitis (1)
- Ribosom (1)
- Ribosome profiling (1)
- Richness (1)
- Rictor-mTOR complex (1)
- Rituximab (1)
- Robertsonian translocation chromosomes (1)
- Robotic tracking (1)
- Ru(II)–Fe(II)–Ru(II) complex (1)
- Ruthenium (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)
- 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)
- Salmonella Typhimurium (1)
- Salmonella enterica (1)
- Salmonella-enteritidis (1)
- Sap47 (1)
- Sarah (1)
- Satellit (1)
- Sauerstoffdiffusionshärtung (1)
- Scaling up (1)
- Schizophrenia (1)
- Schlichte Funktion (1)
- Schmerzforschung (1)
- Schnitzler syndrome (1)
- Schwann cell dedifferentiation (1)
- Schwellenländer (1)
- Screening questionnaire (1)
- SdY (1)
- SdsR (1)
- Secondary tumours (1)
- Seeds (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)
- Sequence Analysis (1)
- Sequence identity (1)
- Si-rhodamine (1)
- Signal transduction (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)
- 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)
- Solid state physics (1)
- Sound detection threshold (1)
- South Africa (1)
- Soziale Phobie (1)
- Sparsity (1)
- Spectrum (1)
- Speedcourt (1)
- Spermatogenese (1)
- Spermienbildung (1)
- Spermiogenese (1)
- Spheno (1)
- Spielsucht (1)
- Spin echo (1)
- Spin-eins-System (1)
- Spinal Muscular-arthropy (1)
- Spinal muscular Atrophy (1)
- Spinale Muskelatrophie (1)
- Spontaneous facial EMG (1)
- Sputter deposition (1)
- Squamous-cell carcinoma (1)
- Squaraine (1)
- Sracking (1)
- Stage distribution (1)
- Stat3 (1)
- State (1)
- Stathmin (1)
- Stem cells (1)
- Stem cells plasticity (1)
- Sternentwicklung (1)
- Steuerhinterziehung (1)
- Steuern (1)
- Steueroase (1)
- Stochastischer Prozess (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)
- Studie (1)
- Sturge-Weber syndrom (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)
- Synaptic plasticity (1)
- Synaptische Transmission (1)
- Synovitis (1)
- Synthese (1)
- Synthesis (1)
- Synthetic Aperture Radar (SAR) (1)
- System involvement (1)
- T cell activation (1)
- T cell differentiation (1)
- T cells (1)
- T lymphocytes (1)
- T-Lymphozyt (1)
- T-cells (1)
- TBI (1)
- TCR diversity (1)
- TGF-β1 (1)
- TIG2 (1)
- TLR2 (1)
- TLR4 (1)
- TLR9 (1)
- TNF (1)
- TNFR2 (1)
- TNM staging (1)
- TRECs (1)
- TSPO (1)
- T\(_H\)17 cells (1)
- Tamm plasmons (1)
- Tantal (1)
- Tanzania (1)
- Targeted therapy (1)
- Task force (1)
- Task interference (1)
- Technology Acceptance (1)
- Teilchendetektor (1)
- Telekommunikationsnetz (1)
- Tellur (1)
- Tellurium (1)
- Temperaturabhängigkeit (1)
- Temperature rhythms (1)
- Temporal-lobe epilepsy (1)
- Temporomandibular disorders (1)
- Temporomandibular joint disc (1)
- Term follow-up (1)
- Terminology (1)
- TerraSAR-X (1)
- Test accuracy (1)
- Teststand (1)
- Tetrahydrochinazoline (1)
- Th17 (1)
- Theory of Mind (1)
- Thigmotaxis (1)
- Thin film growth (1)
- Thioredoxin (1)
- Thrombus formation (1)
- Ti(Ag) Beschichtungen (1)
- Ti(Ag) coatings (1)
- TiO\(_2\) (1)
- Time Calibration (1)
- Time-course (1)
- Tissue (1)
- Tissue engineering (1)
- Toll-like receptors (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)
- Transposon (1)
- Transposon insertion sequencing (1)
- Transverse Myelitis (1)
- Transverse myelitis (1)
- Tregs (1)
- Trennung (1)
- Trial (1)
- Trinidadian guppy (1)
- Trypanosoma-brucei (1)
- Trypanosomes (1)
- Tuberculosis (1)
- Tuberkelbakterium (1)
- Tuberkulose (1)
- Tumor-necrosis-factor (1)
- Tumorigenicity (1)
- Tumors (1)
- Type II quantum wells (1)
- Type-II quantum well (1)
- Typhimurium (1)
- Tyrosine phosphorylation (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)
- 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)
- Value ranges (1)
- Variants (1)
- Varicella-Zoster-Virus (1)
- Varicella-zoster-virus (1)
- Vascular plasticity (1)
- Venous Thrombosis (1)
- Ventricular-arrhythmias (1)
- Verbindungen (1)
- Verbraucher (1)
- Verhalten (1)
- Vertical integration (1)
- Verunreinigung (1)
- Very long baseline interferometry (1)
- Vgamma9Vdelta2 T cells (1)
- Viability (1)
- Vibronic contributions (1)
- Video Game QoS (1)
- Videospiel (1)
- Vigilance (1)
- Viral (1)
- Virotherapy (1)
- Virtual Reality (1)
- Virtual-reality (1)
- Virtuelle Realität (1)
- Virtuelles Netz (1)
- Virulenz (1)
- Virulenzfaktor (1)
- Visueller Reiz (1)
- Vivo (1)
- Vocal responses (1)
- Vortices (1)
- W-boson (1)
- WDR5 (1)
- WIMP (1)
- Wahrscheinlichkeitsrechnung (1)
- Wallemia ichthyophaga (1)
- Wasseroxidationsreaktion (1)
- Wasserspaltung (1)
- Weight (1)
- Wein (1)
- Weißer Zwerg (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)
- Wissensrepräsentation (1)
- Wnt signalling (1)
- Wonderful plants (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)
- Yersinia (1)
- Yield (1)
- Zebrafish (1)
- Zellskelett (1)
- Zellwand (1)
- Zenith Angle (1)
- Zinkselenid (1)
- \(^{68}\)Ga-Pentixafor (1)
- accumulation (1)
- acetyltransferases (1)
- achaete-scute homolog 1 (1)
- achievement motivation (1)
- acquired thermotolerance (1)
- acquisition (1)
- action potential (1)
- active transport (1)
- active zone (1)
- acute Graft versus Host Disease (1)
- acute lymphocytic leukaemia (1)
- adaptation models (1)
- adaptive immune system (1)
- adenocarcinoma of the ampulla of Vater (1)
- adenocarcinoma of the lung (1)
- adenomas (1)
- adenoviruses (1)
- adhesion (1)
- adipose (1)
- adipose tissue (1)
- adipose tissue dysfunction (1)
- adipose-derived stem cells (1)
- adjuvant (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)
- albumin excretion rate (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)
- 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)
- 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)
- 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)
- axonal damage (1)
- azidothymidine (1)
- azobenzenes (1)
- bacterial genetics (1)
- bacterial infection (1)
- bed bug (1)
- bee community (1)
- bees (1)
- behavior (1)
- benzoquinone (1)
- beta oscillations (1)
- beta-D-glucan (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)
- biodiversity assessment (1)
- bioenergetics (1)
- biofuels (1)
- biogenic volatile organic compounds (1)
- bioinformatics (1)
- bioinspired materials (1)
- biolog (1)
- biological mechanism (1)
- bioluminescence (1)
- bioluminescence imaging (1)
- biomarkers Myelomas (1)
- biomechanical test (1)
- biophotonic imaging (1)
- biopsy (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)
- boron (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)
- 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)
- 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)
- 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)
- 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)
- depreissia decipiens (1)
- depression (1)
- dermal melanocytosis (1)
- desert (1)
- desert plant (1)
- design (1)
- detrusor muscle (1)
- deuterostomes (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)
- dyspnea (1)
- early diagnosis (1)
- early literacy (1)
- early secretory pathway (1)
- echocardiography (1)
- economic growth (1)
- ecosystem services (1)
- ectotherms (1)
- edema (1)
- educación en medios (1)
- educational tool (1)
- effectiveness (1)
- electric field distribution (1)
- electrocardiography (1)
- electronic and spintronic devices (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)
- 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)
- 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)
- fabry disease (1)
- factor XII (1)
- familial amyloidotic polyneuropathy (1)
- fatal cardiovascular disease (1)
- fatigue (1)
- fatty liver (1)
- fear generalization (1)
- fear response (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)
- 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)
- gels (1)
- gemcitabine (1)
- gender (1)
- gene expression data (1)
- gene regulation in immune cells (1)
- genes (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)
- german multicenter (1)
- germinal center (1)
- germline (1)
- giant intracranial aneurysm (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-factor-receptor (1)
- guality-of-life (1)
- guidelines (1)
- gut microbiota (1)
- gynecologic surgical procedures/methods (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)
- 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)
- 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 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)
- hydrolysis (1)
- hydrophilic polymers (1)
- hyperekplexia (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)
- 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 (1)
- independent crossing (1)
- indirect detection (1)
- induce cyclooxygenase-2 expression (1)
- induced superconductivity (1)
- infant faces (1)
- infection control (1)
- infections (1)
- infinite dimensional optimization (1)
- inflammatory diseases (1)
- influenza A virus (1)
- influenza virus (1)
- informality (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)
- 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 domain (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)
- 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)
- ketogenic dients (1)
- kidney (1)
- kidney disease (1)
- kinematics (1)
- kinetics (1)
- knee rotator cuff (1)
- knees (1)
- knowledge-based systems (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)
- laparoscopy/methods (1)
- large-scale assessment (1)
- larval drosophila (1)
- lasers (1)
- late gadolinium enhancement (1)
- late-onset (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)
- lipid desaturation (1)
- liquid-metal-jet anode X-ray source (1)
- lithium (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)
- 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)
- 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 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)
- 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)
- 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)
- 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 dynamics (1)
- molecular mechanics (1)
- molecular neuroscience (1)
- molecular response in cml (1)
- molecular-structure (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)
- 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)
- music background (1)
- musical training (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 language processing (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)
- 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)
- organische Halbleiter (1)
- organoid culture (1)
- orthotopic xenograft (1)
- osteoporosis (1)
- otitis media (1)
- outer membrane protein (1)
- outer retinal tubulation (1)
- output elasticities (1)
- over-the-counter drugs (1)
- overload (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)
- pelvic organ prolapse/surgery (1)
- perforator (1)
- performance (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)
- 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)
- 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)
- 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 sclerosing cholangitis (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)
- pulmonary aspergillosis (1)
- pulmonary disease (1)
- pulmonary imaging (1)
- pulmonary toxicity (1)
- punishment (1)
- pustular exanthema (1)
- pyramidal neurons (1)
- quadcopter (1)
- quality-control (1)
- quantitative assessments (1)
- quantum billiard (1)
- quantum chemical analysis (1)
- quantum dot laser (1)
- quantum transport (1)
- queens (1)
- quinine (1)
- quorum sensing (QS) (1)
- radar (1)
- radial Loewner equation (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)
- 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)
- 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)
- robustness (1)
- root growth (1)
- rostral-migratory-stream (1)
- rotator cuff (1)
- rotavirus (1)
- rotors (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)
- 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)
- simultaneous embedding (1)
- single crystalline (1)
- single-molecule biophysics (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)
- social experience (1)
- sodium channel (1)
- sodium uptake (1)
- software (1)
- solubility (1)
- soluble guanylate cyclase (1)
- solvents (1)
- somatostatin receptor (1)
- sorafenib (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)
- statistical data (1)
- stellar evolution (1)
- stem cell transplantation (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)
- structured illumination microscopy (1)
- student simulation (1)
- subcutaneous adipose-tissue (1)
- subgingival (1)
- substantia nigra (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)
- sustained fear (1)
- swim test (1)
- swimming (1)
- synaptic connections (1)
- synaptic inhibition (1)
- synaptic plasticity (1)
- synaptic vesicles (1)
- synapticplasticity (1)
- syndrome (1)
- synthesis process (1)
- systemic immunosuppression (1)
- systemic inflammatory response syndrome (1)
- systemic sclerosis (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)
- 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)
- 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)
- triceps brachii (1)
- triglycerides (1)
- trimetallaborides (1)
- trisomy 21 (1)
- triterpenoids (1)
- tropical ecology (1)
- troponin T (1)
- trypanosoma brucei gambiense (1)
- tryptophan (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)
- upper body (1)
- upramolecular polymerization process (1)
- upstream regulator (1)
- urban growth modelling (1)
- urbanization (1)
- urinary incontinence/surgery (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)
- virtualized environments (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)
- 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)
- 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)
- Übergangsmetall (1)
- Übergewicht (1)
- π–π Stacking (1)
Institute
- Theodor-Boveri-Institut für Biowissenschaften (100)
- Medizinische Klinik und Poliklinik II (37)
- Physikalisches Institut (34)
- Institut für Psychologie (33)
- Neurologische Klinik und Poliklinik (32)
- Graduate School of Life Sciences (29)
- Medizinische Klinik und Poliklinik I (25)
- Julius-von-Sachs-Institut für Biowissenschaften (23)
- Rudolf-Virchow-Zentrum (23)
- Institut für Theoretische Physik und Astrophysik (21)
Schriftenreihe
Sonstige beteiligte Institutionen
- Bavarian Center for Applied Energy Research e.V. (ZAE Bayern) (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)
- Fachbereich Physik, Universität Konstanz, D-78464 Konstanz, Germany (1)
- Fraunhofer ISC (1)
- Fraunhofer Institute Interfacial Engineering and Biotechnology (IGB) (1)
- Klinik für Psychiatrie und Psychotherapie, Universität Würzburg (1)
- Lehrstuhl für Bioinformatik (1)
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.
In vertebrates, one of the first recognizable sex differences in embryos is the onset of meiosis, known to be regulated by retinoic acid (RA) in mammals. We investigated in medaka a possible meiotic function of RA during the embryonic sex determination (SD) period and in mature gonads. We found RA mediated transcriptional activation in germ cells of both sexes much earlier than the SD stage, however, no such activity during the critical stages of SD. In adults, expression of the RA metabolizing enzymes indicates sexually dimorphic RA levels. In testis, RA acts directly in Sertoli, Leydig and pre-meiotic germ cells. In ovaries, RA transcriptional activity is highest in meiotic oocytes. Our results show that RA plays an important role in meiosis induction and gametogenesis in adult medaka but contrary to common expectations, not for initiating the first meiosis in female germ cells at the SD stage.
The main objectives of the KM3NeT Collaboration are (i) the discovery and subsequent observation of high-energy neutrino sources in the Universe and (ii) the determination of the mass hierarchy of neutrinos. These objectives are strongly motivated by two recent important discoveries, namely: (1) the high-energy astrophysical neutrino signal reported by IceCube and (2) the sizable contribution of electron neutrinos to the third neutrino mass eigenstate as reported by Daya Bay, Reno and others. To meet these objectives, the KM3NeT Collaboration plans to build a new Research Infrastructure consisting of a network of deep-sea neutrino telescopes in the Mediterranean Sea. A phased and distributed implementation is pursued which maximises the access to regional funds, the availability of human resources and the synergistic opportunities for the Earth and sea sciences community. Three suitable deep-sea sites are selected, namely off-shore Toulon (France), Capo Passero (Sicily, Italy) and Pylos (Peloponnese, Greece). The infrastructure will consist of three so-called building blocks. A building block comprises 115 strings, each string comprises 18 optical modules and each optical module comprises 31 photo-multiplier tubes. Each building block thus constitutes a three-dimensional array of photo sensors that can be used to detect the Cherenkov light produced by relativistic particles emerging from neutrino interactions. Two building blocks will be sparsely configured to fully explore the IceCube signal with similar instrumented volume, different methodology, improved resolution and
A highly significant excess of high-energy astrophysical neutrinos has been reported by the IceCube Collaboration. Some features of the energy and declination distributions of IceCube events hint at a North/South asymmetry of the neutrino flux. This could be due to the presence of the bulk of our Galaxy in the Southern hemisphere. The ANTARES neutrino telescope, located in the Mediterranean Sea, has been taking data since 2007. It offers the best sensitivity to muon neutrinos produced by galactic cosmic ray interactions in this region of the sky. In this letter a search for an extended neutrino flux from the Galactic Ridge region is presented. Different models of neutrino production by cosmic ray propagation are tested. No excess of events is observed and upper limits for different neutrino flux spectral indices Γ are set. For Γ=2.4 the 90% confidence level flux upper limit at 100 TeV for one neutrino flavour corresponds to Φ\(^{1f}_{0}\) (100 TeV) = 2.0 · 10\(^{−17}\) GeV\(^{−1}\) cm\(^{−2}\)s\(^{−1}\)sr\(^{−1}\). Under this assumption, at most two events of the IceCube cosmic candidates can originate from the Galactic Ridge. A simple power-law extrapolation of the Fermi-LAT flux to account for IceCube High Energy Starting Events is excluded at 90% confidence level.
A search for Secluded Dark Matter annihilation in the Sun using 2007-2012 data of the ANTARES neutrino telescope is presented. Three different cases are considered: a) detection of dimuons that result from the decay of the mediator, or neutrino detection from: b) mediator that decays into a dimuon and, in turn, into neutrinos, and c) mediator that decays directly into neutrinos. As no significant excess over background is observed, constraints are derived on the dark matter mass and the lifetime of the mediator.
A search for muon neutrinos originating from dark matter annihilations in the Sun is performed using the data recorded by the ANTARES neutrino telescope from 2007 to 2012. In order to obtain the best possible sensitivities to dark matter signals, an optimisation of the event selection criteria is performed taking into account the background of atmospheric muons, atmospheric neutrinos and the energy spectra of the expected neutrino signals. No significant excess over the background is observed and 90% C.L. upper limits on the neutrino flux, the spin-dependent and spin-independent WIMP-nucleon cross-sections are derived for WIMP masses ranging from 50 GeV to 5 TeV for the annihilation channels WIMP + WIMP→ b\(\overline{b}\), W\(^{+}\)W\(^{−}\) and τ\(^{+}\)τ\(^{−}\).
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.
An innovative framework has been developed for teamwork of two quadcopter formations, each having its specified formation geometry, assigned task, and matching control scheme. Position control for quadcopters in one of the formations has been implemented through a Linear Quadratic Regulator Proportional Integral (LQR PI) control scheme based on explicit model following scheme. Quadcopters in the other formation are controlled through LQR PI servomechanism control scheme. These two control schemes are compared in terms of their performance and control effort. Both formations are commanded by respective ground stations through virtual leaders. Quadcopters in formations are able to track desired trajectories as well as hovering at desired points for selected time duration. In case of communication loss between ground station and any of the quadcopters, the neighboring quadcopter provides the command data, received from the ground station, to the affected unit. Proposed control schemes have been validated through extensive simulations using MATLAB®/Simulink® that provided favorable results.
A centralized heterogeneous formation flight position control scheme has been formulated using an explicit model following design, based on a Linear Quadratic Regulator Proportional Integral (LQR PI) controller. The leader quadcopter is a stable reference model with desired dynamics whose output is perfectly tracked by the two wingmen quadcopters. The leader itself is controlled through the pole placement control method with desired stability characteristics, while the two followers are controlled through a robust and adaptive LQR PI control method. Selected 3-D formation geometry and static stability are maintained under a number of possible perturbations. With this control scheme, formation geometry may also be switched to any arbitrary shape during flight, provided a suitable collision avoidance mechanism is incorporated. In case of communication loss between the leader and any of the followers, the other follower provides the data, received from the leader, to the affected follower. The stability of the closed-loop system has been analyzed using singular values. The proposed approach for the tightly coupled formation flight of mini unmanned aerial vehicles has been validated with the help of extensive simulations using MATLAB/Simulink, which provided promising results.
The minimal clinically important difference (MCID) defines to what extent change on a health status instrument is clinically relevant, which aids scientists and physicians in measuring therapy effects. This is the first study that aimed to establish the MCID of the Clinical chronic obstructive pulmonary disease (COPD) Questionnaire (CCQ), the COPD Assessment Test (CAT) and the St George’s Respiratory Questionnaire (SGRQ) in the same pulmonary rehabilitation population using multiple approaches. In total, 451 COPD patients participated in a 3-week Pulmonary Rehabilitation (PR) programme (58 years, 65% male, 43 pack-years, GOLD stage II/III/IV 50/39/11%). Techniques used to assess the MCID were anchor-based approaches, including patient-referencing, criterion-referencing and questionnaire-referencing, and the distribution-based methods standard error of measurement (SEM), 1.96SEM and half standard deviation (0.5s.d.). Patient- and criterion-referencing led to MCID estimates of 0.56 and 0.62 (CCQ); 3.12 and 2.96 (CAT); and 8.40 and 9.28 (SGRQ). Questionnaire-referencing suggested MCID ranges of 0.28–0.61 (CCQ), 1.46–3.08 (CAT) and 6.86–9.47 (SGRQ). The SEM, 1.96SEM and 0.5s.d. were 0.29, 0.56 and 0.46 (CCQ); 3.28, 6.43 and 2.80 (CAT); 5.20, 10.19 and 6.06 (SGRQ). Pooled estimates were 0.52 (CCQ), 3.29 (CAT) and 7.91 (SGRQ) for improvement. MCID estimates differed depending on the method used. Pooled estimates suggest clinically relevant improvements needing to exceed 0.40 on the CCQ, 3.00 on the CAT and 7.00 on the SGRQ for moderate to very severe COPD patients. The MCIDs of the CAT and SGRQ in the literature might be too low, leading to overestimation of treatment effects for patients with COPD.
Background: There is much evidence that T cells are strongly involved in the pathogenesis of localized and systemic forms of scleroderma (SSc). A dysbalance between FoxP3+ regulatory CD4+ T cells (Tregs) and inflammatory T-helper (Th) 17 cells has been suggested. Methods: The study aimed (1) to investigate the phenotypical and functional characteristics of Th17 and Tregs in SSc patients depending on disease manifestation (limited vs. diffuse cutaneous SSc, dcSSc) and activity, and (2) the transcriptional level and methylation status of Th17- and Treg-specific transcription factors. Results: There was a concurrent accumulation of circulating peripheral IL-17-producing CCR6+ Th cells and FoxP3+ Tregs in patients with dcSSc. At the transcriptional level, Th17- and Treg-associated transcription factors were elevated in SSc. A strong association with high circulating Th17 and Tregs was seen with early, active, and severe disease presentation. However, a diminished suppressive function on autologous lymphocytes was found in SSc-derived Tregs. Significant relative hypermethylation was seen at the gene level for RORC1 and RORC2 in SSc, particularly in patients with high inflammatory activity. Conclusions: Besides the high transcriptional activity of T cells, attributed to Treg or Th17 phenotype, in active SSc disease, Tregs may be insufficient to produce high amounts of IL-10 or to control proliferative activity of effector T cells in SSc. Our results suggest a high plasticity of Tregs strongly associated with the Th17 phenotype. Future directions may focus on enhancing Treg functions and stabilization of the Treg phenotype.
Background
Optical coherence tomography angiography is a novel imaging technique that allows dyeless in vivo visualization of the retinal and choroidal vasculature. The purpose of this study was to describe optical coherence tomography (OCT) angiography findings in patients with retinal arterial macroaneurysms (RAMs).
Methods
Three eyes of three patients with RAMs were retrospectively included. Fundus photography, OCT, fluorescein angiography (FA), and OCT angiography were performed. The entire imaging data was analyzed in detail.
Results
OCT angiography could detect the RAMs noninvasively without dye injection. By simultaneously observing the OCT scans, it was possible to determine the depth of the RAMs in the retina, to detect the exact localization in relation to the main vessel, and to determine the level of blood flow in the RAMs.
Conclusions
OCT angiography can clearly visualize RAMs without use of a dye. It also allows layer-specific observation of blood flow in each layer of the RAM. OCT angiography provides additional dynamic information on RAMs, which is not obtained with FA and facilitates a better understanding of its morphology and activity. This information in combination with ICG and fluorescein angiography can help to optimize direct laser treatment.
NFATc1 supports imiquimod-induced skin inflammation by suppressing IL-10 synthesis in B cells
(2016)
Epicutaneous application of Aldara cream containing the TLR7 agonist imiquimod (IMQ) to mice induces skin inflammation that exhibits many aspects of psoriasis, an inflammatory human skin disease. Here we show that mice depleted of B cells or bearing interleukin (IL)-10-deficient B cells show a fulminant inflammation upon IMQ exposure, whereas ablation of NFATc1 in B cells results in a suppression of Aldara-induced inflammation. In vitro, IMQ induces the proliferation and IL-10 expression by B cells that is blocked by BCR signals inducing NFATc1. By binding to HDAC1, a transcriptional repressor, and to an intronic site of the Il10 gene, NFATc1 suppresses IL-10 expression that dampens the production of tumour necrosis factor-α and IL-17 by T cells. These data indicate a close link between NFATc1 and IL-10 expression in B cells and suggest NFATc1 and, in particular, its inducible short isoform, NFATc1/αA, as a potential target to treat human psoriasis.
We report a giant thermal shift of 2.1 MHz/K related to the excited-state zero-field splitting in the silicon vacancy centers in 4H silicon carbide. It is obtained from the indirect observation of the optically detected magnetic resonance in the excited state using the ground state as an ancilla. Alternatively, relative variations of the zero-field splitting for small temperature differences can be detected without application of radiofrequency fields, by simply monitoring the photoluminescence intensity in the vicinity of the level anticrossing. This effect results in an all-optical thermometry technique with temperature sensitivity of 100 mK/Hz\(^{1/2}\) for a detection volume of approximately 10\(^{−6}\) mm\(^3\). In contrast, the zero-field splitting in the ground state does not reveal detectable temperature shift. Using these properties, an integrated magnetic field and temperature sensor can be implemented on the same center.
RNA sequencing (RNA-seq) has become a powerful tool to understand molecular mechanisms and/or developmental programs. It provides a fast, reliable and cost-effective method to access sets of expressed elements in a qualitative and quantitative manner. Especially for non-model organisms and in absence of a reference genome, RNA-seq data is used to reconstruct and quantify transcriptomes at the same time. Even SNPs, InDels, and alternative splicing events are predicted directly from the data without having a reference genome at hand. A key challenge, especially for non-computational personnal, is the management of the resulting datasets, consisting of different data types and formats. Here, we present TBro, a flexible de novo transcriptome browser, tackling this challenge. TBro aggregates sequences, their annotation, expression levels as well as differential testing results. It provides an easy-to-use interface to mine the aggregated data and generate publication-ready visualizations. Additionally, it supports users with an intuitive cart system, that helps collecting and analysing biological meaningful sets of transcripts. TBro’s modular architecture allows easy extension of its functionalities in the future. Especially, the integration of new data types such as proteomic quantifications or array-based gene expression data is straightforward. Thus, TBro is a fully featured yet flexible transcriptome browser that supports approaching complex biological questions and enhances collaboration of numerous researchers.
The bis(N-heterocyclic carbene)(diphenylacetylene)palladium complex Pd(ITMe)\(_2\)(PhCCPh)] (ITMe=1,3,4,5-tetramethylimidazol-2-ylidene) acts as a highly active pre-catalyst in the diboration and silaboration of azobenzenes to synthesize a series of novel functionalized hydrazines. The reactions proceed using commercially available diboranes and silaboranes under mild reaction conditions.
A painful event establishes two opponent memories: cues that are associated with pain onset are remembered negatively, whereas cues that coincide with the relief at pain offset acquire positive valence. Such punishment-versus relief-memories are conserved across species, including humans, and the balance between them is critical for adaptive behaviour with respect to pain and trauma. In the fruit fly, Drosophila melanogaster as a study case, we found that both punishment-and relief-memories display natural variation across wild-derived inbred strains, but they do not covary, suggesting a considerable level of dissociation in their genetic effectors. This provokes the question whether there may be heritable inter-individual differences in the balance between these opponent memories in man, with potential psycho-clinical implications.
Lamivudine (3TC), a drug used in the treatment of HIV infection, needs to cross the plasma membrane to exert its therapeutic action. Human Organic cation transporter 1 (hOCT1), encoded by the SLC22A1 gene, is the transporter responsible for its uptake into target cells. As SLC22A1 is a highly polymorphic gene, the aim of this study was to determine how SNPs in the OCT1-encoding gene affected 3TC internalization and its interaction with other co-administered drugs. HEK293 cells stably transfected with either the wild type form or the polymorphic variants of hOCT1 were used to perform kinetic and drug-drug interaction studies. Protein co-immunoprecipitation was used to assess the impact of selected polymorphic cysteines on the oligomerization of the transporter. Results showed that 3TC transport efficiency was reduced in all polymorphic variants tested (R61C, C88R, S189L, M420del, and G465R). This was not caused by lack of oligomerization in case of variants located at the transporter extracellular loop (R61C and C88R). Drug-drug interaction measurements showed that co-administered drugs [abacavir (ABC), zidovudine (AZT), emtricitabine (FTC), tenofovir diproxil fumarate (TDF), efavirenz (EFV) and raltegravir (RAL)], differently inhibited 3TC uptake depending upon the polymorphic variant analyzed. These data highlight the need for accurate analysis of drug transporter polymorphic variants of clinical relevance, because polymorphisms can impact on substrate (3TC) translocation but even more importantly they can differentially affect drug-drug interactions at the transporter level.
Among the numerous routes organic chemists have developed to synthesize benzene derivatives and heteroaro- matic compounds, transition-metal-catalyzed cycloaddition reactions are the most elegant. In contrast, cycloaddition reactions of heavier alkene and alkyne analogues, though limited in scope, proceed uncatalyzed. In this work we present the first spontaneous cycloaddition reactions of lighter alkene and alkyne analogues. Selective addition of unactivated alkynes to boron–boron multiple bonds under ambient con- ditions yielded diborocarbon equivalents of simple aromatic hydrocarbons, including the first neutral 6p-aromatic dibora- benzene compound, a 2 p-aromatic triplet biradical 1,3-dibor- ete, and a phosphine-stabilized 2 p-homoaromatic 1,3-dihydro- 1,3-diborete. DFT calculations suggest that all three com- pounds are aromatic and show frontier molecular orbitals matching those of the related aromatic hydrocarbons, C6H6 and C4H42+, and homoaromatic C4H5+.
Among the numerous routes organic chemists have developed to synthesize benzene derivatives and heteroaro- matic compounds, transition-metal-catalyzed cycloaddition reactions are the most elegant. In contrast, cycloaddition reactions of heavier alkene and alkyne analogues, though limited in scope, proceed uncatalyzed. In this work we present the first spontaneous cycloaddition reactions of lighter alkene and alkyne analogues. Selective addition of unactivated alkynes to boron–boron multiple bonds under ambient con- ditions yielded diborocarbon equivalents of simple aromatic hydrocarbons, including the first neutral 6 π-aromatic dibora- benzene compound, a 2 π-aromatic triplet biradical 1,3-dibor- ete, and a phosphine-stabilized 2 π-homoaromatic 1,3-dihydro- 1,3-diborete. DFT calculations suggest that all three com- pounds are aromatic and show frontier molecular orbitals matching those of the related aromatic hydrocarbons, C\(_6\)H\(_6\) and C\(_4\)H\(_4\)\(^{2+}\), and homoaromatic C\(_4\)H\(_5\)\(^+\).
Room temperature hydrogenation of an SIDep-stabilized diboryne (SIDep = 1,3-bis(diethylphenyl)-4,5-dihydroimidazol-2-ylidene) and a CAAC-supported diboracumulene (CAAC = 1-(2,6- diisopropylphenyl)-3,3,5,5-tetramethylpyrrolidin-2-ylidene) provided the first selective route to the corresponding 1,2-dihydrodiborenes. DFT calculations showed an overall exothermic (ΔG = 19.4 kcal mol\(^{-1}\) two-step asynchronous H\(_2\) addition mechanism proceeding via a bridging hydride.
Adjuvants are compounds added to an agrochemical spray formulation to improve or modify the action of an active ingredient (AI) or the physico-chemical characteristics of the spray liquid. Adjuvants can have more than only one distinct mode of action (MoA) during the foliar spray application process and they are generally known to be the best tools to improve agrochemical formulations. The main objective for this work was to elucidate the basic MoA of adjuvants by uncoupling different aspects of the spray application. Laboratory experiments, beginning from retention and spreading characteristics, followed by humectant effects concerning the spray deposit on the leaf surface and ultimately the cuticular penetration of an AI, were figured out to evaluate overall in vivo effects of adjuvants which were also obtained in a greenhouse spray test. For this comprehensive study, the surfactant classes of non-ionic sorbitan esters (Span), polysorbates (Tween) and oleyl alcohol polyglycol ether (Genapol O) were generally considered because of their common promoting potential in agrochemical formulations and their structural diversity.
The reduction of interfacial tension is one of the most crucial physico-chemical properties of surfactants. The dynamic surface tension (DST) was monitored to characterise the surface tension lowering behaviour which is known to influence the droplet formation and retention characteristics. The DST is a function of time and the critical time frame of droplet impact might be at about 100 ms. None of the selected surfactants were found to lower the surface tension sufficiently during this short timeframe (chapter I). At ca. 100 ms, Tween 20 resulted in the lowest DST value. When surfactant monomers are fully saturated at the droplet-air-interface, an equilibrium surface tension (STeq) value can be determined which may be used to predict spreading or run-off effects. The majority of selected surfactants resulted in a narrow distribution of STeq values, ranging between 30 and 45 mN m- 1. Nevertheless, all surfactants were able to decrease the surface tension considerably compared to pure water (72 mN m- 1). The influence of different surfactants on the wetting process was evaluated by studying time-dependent static contact angles on different surfaces and the droplet spread area on Triticum aestivum leaves after water evaporation. The spreading potential was observed to be better for Spans than for Tweens. Especially Span 20 showed maximum spreading results. To transfer laboratory findings to spray application, related to field conditions, retention and leaf coverage was measured quantitatively on wheat leaves by using a variable track sprayer. Since the retention process involves short time dynamics, it is well-known that the spray retention on a plant surface is not correlated to STeq but to DST values. The relationship between DST at ca. 100 ms and results from the track sprayer showed increasing retention results with decreasing DST, whereas at DST values below ca. 60 mN m- 1 no further retention improvement could be observed.
Under field conditions, water evaporates from the droplet within a few seconds to minutes after droplet deposition on the leaf surface. Since precipitation of the AI must essentially being avoided by holding the AI in solution, so-called humectants are used as tank-mix adjuvants. The ability of pure surfactants to absorb water from the surrounding atmosphere was investigated comprehensively by analysing water sorption isotherms (chapter II). These isotherms showed an exponential shape with a steep water sorption increase starting at 60% to 70% RH. Water sorption was low for Spans and much more distinct for the polyethoxylated surfactants (Tweens and Genapol O series). The relationship between the water sorption behaviour and the molecular structure of surfactants was considered as the so-called humectant activity. With an increasing ethylene oxide (EO) content, the humectant activity increased concerning the particular class of Genapol O. However, it could be shown that the moisture absorption across all classes of selected surfactants correlates rather better with their hydrophilic-lipophilic balance values with the EO content.
All aboveground organs of plants are covered by the cuticular membrane which is therefore the first rate limiting barrier for AI uptake. In vitro penetration experiments through an astomatous model cuticle were performed to study the effects of adjuvants on the penetration of the lipophilic herbicide Pinoxaden (PXD) (chapter III). In order to understand the influence of different adjuvant MoA like humectancy, experiments were performed under three different humidity levels. No explicit relationship could be found between humidity levels and the PXD penetration which might be explained by the fact that humidity effects would rather affect hydrophilic AIs than lipophilic ones. Especially for Tween 20, it became obvious that a complex balance between multiple MoA like spreading, humectancy and plasticising effects have to be considered.
Greenhouse trials, focussing the adjuvant impact on in vivo action of PXD, were evaluated on five different grass-weed species (chapter III). Since agrochemical spray application and its following action on living plants also includes translocation processes in planta and species dependent physiological effects, this investigation may help to simulate the situation on the field. Even though the absolute weed damage was different, depending both on plant species and also on PXD rates, adjuvant effects in greenhouse experiments displayed the same ranking as in cuticular penetration studies: Tween 20 > Tween 80 > Span 20 ≥ Span 80.
Thus, the present work shows for the first time that findings obtained in laboratory experiments can be successfully transferred to spray application studies on living plants concerning adjuvant MoA. A comparative analysis, using radar charts, could demonstrate systematic derivations from structural similarities of adjuvants to their MoA (summarising discussion and outlook). Exemplarily, Tween 20 and Tween 80 cover a wide range of selected variables by having no outstanding MoA improving one distinct process during foliar application, compared to non-ethoxylated Span 20 and Span 80 which primarily revealed a surface active action. Most adjuvants used in this study represent polydisperse mixtures bearing a complex distribution of EO and aliphatic chains. From this study it seems alike that adjuvants having a wide EO distribution offer broader potential than adjuvants with a small EO distribution. It might be a speculation that due to this broad distribution of single molecules, all bearing their individual specific physico-chemical nature, a wide range of properties concerning their MoA is covered.
Background:
Memory reconsolidation is the direct effect of memory reactivation followed by stabilization of newly synthesized proteins. It has been well proven that neural encoding of both newly and reactivated memories requires synaptic plasticity. Brain derived neurotrophic factor (BDNF) has been extensively investigated regarding its role in the formation of synaptic plasticity and in the alteration of fear memories. However, its role in fear reconsolidation is still unclear; hence, the current study has been designed to investigate the role of the BDNF val66met polymorphism (rs6265) in fear memory reconsolidation in humans.
Methods:
An auditory fear-conditioning paradigm was conducted, which comprised of three stages (acquisition, reactivation, and spontaneous recovery). One day after fear acquisition, the experimental group underwent reactivation of fear memory followed by the extinction training (reminder group), whereas the control group (non-reminder group) underwent only extinction training. On day 3, both groups were subjected to spontaneous recovery of earlier learned fearful memories. The treat-elicited defensive response due to conditioned threat was measured by assessing the skin conductance response to the conditioned stimulus. All participants were genotyped for rs6265.
Results:
The results indicate a diminishing effect of reminder on the persistence of fear memory only in the Met-allele carriers, suggesting a moderating effect of the BDNF polymorphism in fear memory reconsolidation.
Conclusions:
Our findings suggest a new role for BDNF gene variation in fear memory reconsolidation in humans.
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.
Background
Differential RNA-Seq (dRNA-Seq) is a recently developed method of performing primary transcriptome analyses that allows for the genome-wide mapping of transcriptional start sites (TSSs) and the identification of novel transcripts. Although the transcriptomes of diverse bacterial species have been characterized by dRNA-Seq, the transcriptome analysis of archaeal species is still rather limited. Therefore, we used dRNA-Seq to characterize the primary transcriptome of the model archaeon Haloferax volcanii.
Results
Three independent cultures of Hfx. volcanii grown under optimal conditions to the mid-exponential growth phase were used to determine the primary transcriptome and map the 5′-ends of the transcripts. In total, 4749 potential TSSs were detected. A position weight matrix (PWM) was derived for the promoter predictions, and the results showed that 64 % of the TSSs were preceded by stringent or relaxed basal promoters. Of the identified TSSs, 1851 belonged to protein-coding genes. Thus, fewer than half (46 %) of the 4040 protein-coding genes were expressed under optimal growth conditions. Seventy-two percent of all protein-coding transcripts were leaderless, which emphasized that this pathway is the major pathway for translation initiation in haloarchaea. A total of 2898 of the TSSs belonged to potential non-coding RNAs, which accounted for an unexpectedly high fraction (61 %) of all transcripts. Most of the non-coding TSSs had not been previously described (2792) and represented novel sequences (59 % of all TSSs). A large fraction of the potential novel non-coding transcripts were cis-antisense RNAs (1244 aTSSs). A strong negative correlation between the levels of antisense transcripts and cognate sense mRNAs was found, which suggested that the negative regulation of gene expression via antisense RNAs may play an important role in haloarchaea. The other types of novel non-coding transcripts corresponded to internal transcripts overlapping with mRNAs (1153 iTSSs) and intergenic small RNA (sRNA) candidates (395 TSSs).
Conclusion
This study provides a comprehensive map of the primary transcriptome of Hfx. volcanii grown under optimal conditions. Fewer than half of all protein-coding genes have been transcribed under these conditions. Unexpectedly, more than half of the detected TSSs belonged to several classes of non-coding RNAs. Thus, RNA-based regulation appears to play a more important role in haloarchaea than previously anticipated.
Clostridial neurotoxins (botulinum toxins and tetanus toxin) disrupt neurotransmitter release by cleaving neuronal SNARE proteins. We generated transgenic flies allowing for conditional expression of different botulinum toxins and evaluated their potential as tools for the analysis of synaptic and neuronal network function in Drosophila melanogaster by applying biochemical assays and behavioral analysis. On the biochemical level, cleavage assays in cultured Drosophila S2 cells were performed and the cleavage efficiency was assessed via western blot analysis. We found that each botulinum toxin cleaves its Drosophila SNARE substrate but with variable efficiency. To investigate the cleavage efficiency in vivo, we examined lethality, larval peristaltic movements and vision dependent motion behavior of adult Drosophila after tissue-specific conditional botulinum toxin expression. Our results show that botulinum toxin type B and botulinum toxin type C represent effective alternatives to established transgenic effectors, i.e. tetanus toxin, interfering with neuronal and non-neuronal cell function in Drosophila and constitute valuable tools for the analysis of synaptic and network function.
To simplify a judgment, people often base it on easily accessible information. One cue that is usually readily available is processing fluency – a metacognitive feeling of ease of cognitive processing. Consequently, processing fluency is used as a cue for many different types of judgment, such as judgment of truth, confidence, and novelty. The present work describes results of three studies investigating various aspects of processing fluency effects on judgment.
Processing fluency has been sometimes equated with speed of a cognitive process. Therefore, response times have been used for evaluation of processing fluency. However, response times in experimental tasks often do not encompass only the time needed for a given process, but also the time needed for a decision based on the resulting information. The study described in Chapter II uses a novel experimental method that enables separation of reading and decision times. The results show that people make a decision about liking of pseudowords faster when the pseudowords are hard-to-pronounce (i.e., disfluent) than when they are moderate in pronounceability. This suggests that response times cannot be used as a proxy for processing fluency when they include the time needed to make a decision.
One of the studies of judgmental effects of processing fluency showed that food additives with easier pronounceable names are judged to be less harmful than those with hard-to-pronounce names. While people encounter food additives that are safe more often, this environmental association may be in the opposite direction for some categories of objects. For example, people are more likely to see names of especially dangerous criminals in the news. Chapter III describes a study which initially tested whether the fluency-safety association may be in the opposite direction for some categories of objects as a consequence of this selective exposure to especially dangerous exemplars. The results did not show support for this hypothesis. Furthermore, subsequent studies suggest that the previously found association between fluency and safety is replicable with the original stimuli used in the previous research, but not with newly constructed stimuli.
Chapter IV describes a study which applied a finding from the processing fluency literature to a positive psychology exercise in order to increase its effectiveness. Namely, the experiment manipulated the number of good things that participants listed daily for two weeks as part of the exercise. While listing more things was considered harder, the number of things listed each day had no effect on effectiveness of the exercise.
According to the Selective Accessibility Model of anchoring, the comparison question in the standard anchoring paradigm activates information that is congruent with an anchor. As a consequence, this information will be more likely to become the basis for the absolute judgment which will therefore be assimilated toward the anchor. However, if the activated information overlaps with information that is elicited by the absolute judgment itself, the preceding comparative judgment should not exert an incremental effect and should fail to result in an anchoring effect. The present studies find this result when the comparative judgment refers to a general category and the absolute judgment refers to a subset of the general category that was activated by the anchor value. For example, participants comparing the average annual temperature in New York City to a high 102 °F judged the average winter, but not summer temperature to be higher than participants making no comparison. On the other hand, participants comparing the annual temperature to a low –4 °F judged the average summer, but not winter temperature to be lower than control participants. This pattern of results was shown also in another content domain. It is consistent with the Selective Accessibility Model but difficult to reconcile with other main explanations of the anchoring effect.
In the present work, a simulation system is proposed that can be used as an educational tool by physicians in training basic skills of minimally invasive vascular interventions. In order to accomplish this objective, initially the physical model of the wire proposed by Konings has been improved. As a result, a simpler and more stable method was obtained to calculate the equilibrium configuration of the wire. In addition, a geometrical method is developed to perform relaxations. It is particularly useful when the wire is hindered in the physical method because of the boundary conditions. Then a recipe is given to merge the physical and the geometrical methods, resulting in efficient relaxations. Moreover, tests have shown that the shape of the virtual wire agrees with the experiment. The proposed algorithm allows real-time executions, and furthermore, the hardware to assemble the simulator has a low cost.
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.
Role of PTEN in Oxidative Stress and DNA Damage in the Liver of Whole-Body Pten Haplodeficient Mice
(2016)
Type 2 diabetes (T2DM) and obesity are frequently associated with non-alcoholic fatty liver disease (NAFLD) and with an elevated cancer incidence. The molecular mechanisms of carcinogenesis in this context are only partially understood. High blood insulin levels are typical in early T2DM and excessive insulin can cause elevated reactive oxygen species (ROS) production and genomic instability. ROS are important for various cellular functions in signaling and host defense. However, elevated ROS formation is thought to be involved in cancer induction. In the molecular events from insulin receptor binding to genomic damage, some signaling steps have been identified, pointing at the PI3K/AKT pathway. For further elucidation Phosphatase and Tensin homolog (Pten), a tumour suppressor phosphatase that plays a role in insulin signaling by negative regulation of PI3K/AKT and its downstream targets, was investigated here. Dihydroethidium (DHE) staining was used to detect ROS formation in immortalized human hepatocytes. Comet assay and micronucleus test were performed to investigate genomic damage in vitro. In liver samples, DHE staining and western blot detection of HSP70 and HO-1 were performed to evaluate oxidative stress response. DNA double strand breaks (DSBs) were detected by immunohistostaining. Inhibition of PTEN with the pharmacologic inhibitor VO-OHpic resulted in increased ROS production and genomic damage in a liver cell line. Knockdown of Pten in a mouse model yielded increased oxidative stress levels, detected by ROS levels and expression of the two stress-proteins HSP70 and HO-1 and elevated genomic damage in the liver, which was significant in mice fed with a high fat diet. We conclude that PTEN is involved in oxidative stress and genomic damage induction in vitro and that this may also explain the in vivo observations. This further supports the hypothesis that the PI3K/AKT pathway is responsible for damaging effects of high levels of insulin.
Several cohort studies showed that obesity increases the risk of chronic disease such as T2DM, hypertension and non-alcoholic fatty liver disease and various types of cancer. Different factors were described that might be involving in these diseases in obesity. Some of these suggested factors were chronic infection, elevated free fatty acids, increased ROS formation, mitochondrial dysfunction and raised NAPDH oxidase activity. Obesity is a multifactorial disease and it is very hard to distinguish between all of these factors. In this study, we wanted to focus on the association between obesity, oxidative stress and genomic damage in kidney, liver and colon, which are the most relevant organs for cancer risk according to the cohort studies. Our findings indicated elevated oxidative stress in kidney, liver and colon together with elevated lipid, RNA and DNA oxidation in the whole body. Additionally, we were able to show increased DNA damage in kidney, liver and colon.
Since obesity has become an epidemic all over the world, possible therapeutic applications such as life style changes (diet and sport), pharmacological supplements and various type of surgeries are increasing. As a second question, we focused on the effect of weight loss, which is supplied either by Roux-en-Y gastric bypass surgery or by caloric restriction designed in a way to provide the same extent of weight loss, on oxidative stress and genomic damage. Our results indicated that weight loss either by gastric bypass surgery or by caloric restriction led to reduced oxidative stress and genomic damage in kidney, liver and colon. We could not find any difference between the weight loss methods, except the DNA oxidation and repair marker urinary 8-oxodG, which was still elevated after RYGB, but not after caloric restriction.
It is known that hyperinsulinemia and in the long term T2DM are among the biggest concerns in obese individuals. Since we know the mutagenic potential of elevated insulin levels from previous data in our working group, the correlation between the highly mutagenic DNA DBSs marker, γ-H2AX and the plasma insulin level was tested and the findings indicated a positive correlation. In order to demonstrate the association between insulin-related oxidative stress and genomic damage, we used in vitro and in vivo models with Pten deficiency. In this part of study, the work was focused on liver.
Pten is a known negative regulator of the PI3K/Akt pathway, which is responsible for the elevated NADPH oxidase activity and mitochondrial dysfunction through elevated insulin levels. Pten inhibition or deficiency were used to sensitize the system to insulin. Non-transformed immortalized human hepatocytes were used to show the mutagenic potential of elevated insulin and these in vitro data revealed once more the link between insulin signaling, elevated oxidative stress and genomic damage. Since the metabolic function of the liver is not only due to the extent of the hepatic insulin response but is also affected by systemic interactions, a whole-body Pten haplodeficient mouse model with an additional Pten+/-/Akt2-/- group was utilized for in vivo investigation of insulin-mediated toxicity. Our findings in this model suggested that Pten deficiency alone can cause an increase in oxidative stress. HFD alone was sufficient to increase the expression of HO-1 and genomic damage significantly. Moreover, the combination (whole-body Pten haplodeficient mice fed with HFD) showed significantly elevated oxidative stress and genomic damage in mouse liver. However, Akt2 knockout could only reduce the oxidative stress and DNA damage in high fat diet fed mice significantly.
All these findings demonstrated that obesity can induce oxidative stress and genomic damage. Elevated insulin levels are associated with obesity-mediated oxidative stress and genomic damage. However, the underlying mechanisms are surely multifaceted and complicated. For example, Pten as oncogene might also induce other mechanisms besides the elevation of the PI3K/Akt pathway activity.
In conclusion, it is clear that oxidative stress and DNA damage are linked to obesity and that weight loss can reduce these two factors. Since DNA-damage is associated with an elevated cancer risk, it might be logical to use an antioxidant therapy in obese individuals to reduce the side effects and oxidative stress dependent mutagenicity and cancer risk in these individuals. However, much more research will be needed to support this idea experimentally.
Wiskott–Aldrich syndrome (WAS) is caused by loss-of-function mutations in theWASp gene.
Decreased cellular responses in WASp-deficient cells have been interpreted to mean that
WASp directly regulates these responses in WASp-sufficient cells. Here, we identify an
exception to this concept and show that WASp-deficient dendritic cells have increased
activation of Rac2 that support cross-presentation to CD8þ T cells. Using two different skin
pathology models, WASp-deficient mice show an accumulation of dendritic cells in the skin
and increased expansion of IFNg-producing CD8þ T cells in the draining lymph node and
spleen. Specific deletion of WASp in dendritic cells leads to marked expansion of CD8þ
T cells at the expense of CD4þ T cells. WASp-deficient dendritic cells induce increased
cross-presentation to CD8þ T cells by activating Rac2 that maintains a near neutral pH of
phagosomes. Our data reveals an intricate balance between activation of WASp and Rac2
signalling pathways in dendritic cells.
Toxic trace elements in maternal and cord blood and social determinants in a Bolivian mining city
(2016)
This study assessed lead, arsenic, and antimony in maternal and cord blood, and associations between maternal concentrations and social determinants in the Bolivian mining city of Oruro using the baseline assessment of the ToxBol/Mine-Niño birth cohort. We recruited 467 pregnant women, collecting venous blood and sociodemographic information as well as placental cord blood at birth. Metallic/semimetallic trace elements were measured using inductively coupled plasma mass spectrometry. Lead medians in maternal and cord blood were significantly correlated (Spearman coefficient = 0.59; p < 0.001; 19.35 and 13.50 μg/L, respectively). Arsenic concentrations were above detection limit (3.30 μg/L) in 17.9 % of maternal and 34.6 % of cord blood samples. They were not associated (Fischer’s p = 0.72). Antimony medians in maternal and cord blood were weakly correlated (Spearman coefficient = 0.15; p < 0.03; 9.00 and 8.62 μg/L, respectively). Higher concentrations of toxic elements in maternal blood were associated with maternal smoking, low educational level, and partner involved in mining.
Toxic trace elements in maternal and cord blood and social determinants in a Bolivian mining city
(2016)
This study assessed lead, arsenic, and antimony in maternal and cord blood, and associations between maternal concentrations and social determinants in the Bolivian mining city of Oruro using the baseline assessment of the ToxBol/Mine-Nino birth cohort. We recruited 467 pregnant women, collecting venous blood and sociodemographic information as well as placental cord blood at birth. Metallic/semimetallic trace elements were measured using inductively coupled plasma mass spectrometry. Lead medians in maternal and cord blood were significantly correlated (Spearman coefficient=0.59; p<0.001; 19.35 and 13.50 μg/L, respectively). Arsenic concentrations were above detection limit (3.30 μg/L) in 17.9% of maternal and 34.6% of cord blood samples. They were not associated (Fischer's p=0.72). Antimony medians in maternal and cord blood were weakly correlated (Spearman coefficient=0.15; p<0.03; 9.00 and 8.62 μg/L, respectively). Higher concentrations of toxic elements in maternal blood were associated with maternal smoking, low educational level, and partner involved in mining.
African trypanosomes thrive in the bloodstream and tissue spaces of a wide range of mammalian hosts. Infections of cattle cause an enormous socio-economic burden in sub-Saharan Africa. A hallmark of the trypanosome lifestyle is the flagellate’s incessant motion. This work details the cell motility behavior of the four livestock-parasites Trypanosoma vivax, T. brucei, T. evansi and T. congolense. The trypanosomes feature distinct swimming patterns, speeds and flagellar wave frequencies, although the basic mechanism of flagellar propulsion is conserved, as is shown by extended single flagellar beat analyses. Three-dimensional analyses of the trypanosomes expose a high degree of dynamic pleomorphism, typified by the ‘cellular waveform’. This is a product of the flagellar oscillation, the chirality of the flagellum attachment and the stiffness of the trypanosome cell body. The waveforms are characteristic for each trypanosome species and are influenced by changes of the microenvironment, such as differences in viscosity and the presence of confining obstacles. The distinct cellular waveforms may be reflective of the actual anatomical niches the parasites populate within their mammalian host. T. vivax displays waveforms optimally aligned to the topology of the bloodstream, while the two subspecies T. brucei and T. evansi feature distinct cellular waveforms, both additionally adapted to motion in more confined environments such as tissue spaces. T. congolense reveals a small and stiff waveform, which makes these parasites weak swimmers and destined for cell adherence in low flow areas of the circulation. Thus, our experiments show that the differential dissemination and annidation of trypanosomes in their mammalian hosts may depend on the distinct swimming capabilities of the parasites.
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.
Atypical teratoid rhabdoid tumors (AT/RT) are characterized by mutations and subsequent inactivation of SMARCB1 (INI1, hSNF5), a predilection for very young children and an unfavorable outcome. The European Registry for rhabdoid tumors (EU‐RHAB) was established to generate a common European database and to establish a standardized treatment regimen as the basis for phase I/II trials. Thus, genetic analyses, neuropathologic and radiologic diagnoses, and a consensus treatment regimen were prospectively evaluated. From 2005 to 2009, 31 patients with AT/RT from four countries were recruited into the registry study Rhabdoid 2007 and treated with systemic and intraventricular chemotherapy. Eight patients received high‐dose chemotherapy, 23 radiotherapy, and 17 maintenance therapy. Reference evaluations were performed in 64% (genetic analyses, FISH, MLPA, sequencing) up to 97% (neuropathology, INI1 stain). Germ‐line mutations (GLM) were detected in 6/21 patients. Prolonged overall survival was associated with age above 3 years, radiotherapy and achievement of a complete remission. 6‐year overall and event‐free survival rates were 46% (±0.10) and 45% (±0.09), respectively. Serious adverse events and one treatment‐related death due to insufficiency of a ventriculo peritoneal shunt (VP‐shunt) and consecutive herniation were noted. Acquisition of standardized data including reference diagnosis and a standard treatment schedule improved data quality along with a survival benefit. Treatment was feasible with significant but manageable toxicity. Although our analysis is biased due to heterogeneous adherence to therapy, EU‐RHAB provides the best available basis for phase I/II clinical trials.
Advances in stem cell research have allowed the development of 3-dimensional (3D) primary cell cultures termed organoid cultures, as they closely mimic the in vivo organization of different cell lineages. Bridging the gap between 2-dimensional (2D) monotypic cancer cell lines and whole organisms, organoids are now widely applied to model development and disease. Organoids hold immense promise for addressing novel questions in host-microbe interactions, infectious diseases and the resulting inflammatory conditions. Researchers have started to use organoids for modeling infection with pathogens, such as Helicobacter pylori or Salmonella enteritica, gut- microbiota interactions and inflammatory bowel disease. Future studies will broaden the spectrum of microbes used and continue to establish organoids as a standard model for human host-microbial interactions. Moreover, they will increasingly exploit the unique advantages of organoids, for example to address patient-specific responses to microbes.
In order to select the appropriate behavior, it is important to choose the right behavior at the right time out of many options. It still remains unclear nowadays how exactly this is managed. To address this question, I expose flies (Drosophila melanogaster) to uncontrollable stress to study their behavior under restrictive circumstances by using the so-called shock box. Exposing animals to uncontrollable stress may have an impact on subsequent behavior and can last for some time. The animal learns that whatever it does, it cannot change the situation and therefore can develop something called learned helplessness. The term was first conceptualized by two American psychologists Maier and Seligman (1967), who discovered this phenomenon while doing experiments with dogs. They found out that dogs which are exposed to inescapable stress, later fail in a learning task (‘shuttle box’).
In this work the walking patterns of three different types of experimental flies, walking in a small dark chamber, were evaluated. Using the triadic design (Seligman and Maier, 1967), flies were either exposed to electric shock randomly (yoked), could turn it off by being active (master) or did not receive punishment at all (control). Master flies were shocked whenever they sat for more than 0.9 seconds. At the same time yoked flies received a shock as well independent of what they were doing, to ensure the same amount of shocks received and to create random punishment pattern for the yoked group. With this so-called no-idleness paradigm flies were conditioned either 10 minutes, which resulted in a short (3 minutes) after-effect, or 20 minutes that turned out to be more stable (10 minutes).
In a second part, the behavior during the 20 minute conditioning and a 10 minutes post-test was described in detail. Female flies of the yoked group developed lower activity levels, longer pauses and walked more slowly than master and control flies during conditioning. In the time after the shocks while still in the box, the yoked flies also reduced the frequency and duration of walking bouts as well as their walking speed. Additionally, they took more time to resume walking after the onset of an electric shock than master flies (escape latency) and turned out to make less pauses lasting between 1-1.5 seconds which supports the finding concerning the escape latency.
Male flies, tested under the same conditions, showed a slightly weaker after-effect regarding the difference between master and yoked during conditioning and post-test when compared to female flies.
When comparing the 20 minutes conditioning with subsequent 10 minutes test in the heat and the shock box in parallel, one finds the same effect: Flies which do not have control over the shocks, lower their activity, make less but longer pauses and walk more slowly than their respective master flies. Despite the similar effect of heat and shock on the flies, some differences between the devices occurred, which can partly be explained by different humidity conditions as well as by different surfaces within the chambers.
When the control over the shocks is given back to the yoked flies, it takes them about seven minutes to realize it. One could also show that dopamine levels in the brain were reduced in comparison to flies which did not receive shocks. Yoked flies also were impaired in a place learning task (place learning) and their reaction to light (exit from the box towards the light) directly after conditioning.
After characterizing the walking behavior in the chambers, the study deals with the question whether the effects observed in the chambers transfer to different environments.
In free walk they only differed from flies which did not receive electric shocks and no effect of uncontrollability was transferred to courtship behavior. Handling as the cause could be excluded. Since handling could be exclude to be the cause of losing the effect, I assumed that the behavior shown in the boxes are context depend.
Not only were the after-effects of inescapable shock subject of the current research also the impact of the rearing situation on the response to electric shock was investigated in the present study. Flies which grew up in a single-reared situation turned out to be less affected by inescapable stress in both sexes.
In the next part, the first steps to unravel the neuronal underpinning were taken. A mutant – fumin – which is defective in the dopamine re-uptake transporter showed less reaction to inescapable foot shocks, while a mutant for the gene which encodes an adenylate cyclase (rutabaga2080) resulted in a good score during conditioning, but showed no stable after-effect. Downregulating the expression of the adenylate cyclase gene (rutabaga) in different parts of the mushroom bodies showed, that rutabaga is necessary in the α’β’-lobes for expressing the differences between master and yoked flies in the no-idleness paradigm. The study further confirmed previous findings, that rutabaga is needed in operant but not in classical conditioning.
As a result, the study could show that not the stimulus itself causes the state of uncontrollability but the fact that the fly learned that it was not in control of the stimulus. This state turned out to be context and time dependent.
Like other animals flies develop a state of learned helplessness in response to unescapable aversive events. To show this, two flies, one 'master', one 'yoked', are each confined to a dark, small chamber and exposed to the same sequence of mild electric shocks. Both receive these shocks when the master fly stops walking for more than a second. Behavior in the two animals is differently affected by the shocks. Yoked flies are transiently impaired in place learning and take longer than master flies to exit from the chamber towards light. After the treatment they walk more slowly and take fewer and shorter walking bouts. The low activity is attributed to the fly's experience that its escape response, an innate behavior to terminate the electric shocks, does not help anymore. Earlier studies using heat pulses instead of electric shocks had shown similar effects. This parallel supports the interpretation that it is the uncontrollability that induces the state.
To protect the health of human and environment, the European Union implemented the REACH regulation for chemical substances. REACH is an acronym for Registration, Evaluation, Authorization, and Restriction of Chemicals. Under REACH, the authorities have the task of assessing chemical substances, especially those that might pose a risk to human health or environment. The work under REACH is scientifically, technically and procedurally a complex and knowledge-intensive task that is jointly performed by the European Chemicals Agency and member state authorities in Europe. The assessment of substances under REACH conducted in the German Environment Agency is supported by the knowledge-based system KnowSEC, which is used for the screening, documentation, and decision support when working on chemical substances. The software KnowSEC integrates advanced semantic technologies and strong problem solving methods. It allows for the collaborative work on substances in the context of the European REACH regulation. We discuss the applied methods and process models and we report on experiences with the implementation and use of the system.
Purpose: In hepatocellular carcinoma patients with large or multinodal tumors, where curative treatment options are not feasible, transarterial therapies play a major role. Transarterial chemoembolization (TACE) with drug-eluting beads (DEB-TACE) is a promising new approach due to higher intratumoral and lower systemic concentration of the chemotherapeutic agent compared to conventional TACE (cTACE).
Patients and methods: In a retrospective analysis, 32 patients with hepatocellular carcinoma who received either DEB or a cTACE were compared regarding survival time, disease recurrence, and side effects such as pain and fever.
Results: No significant differences could be detected between the cTACE and DEB-TACE groups with regard to mean hospital stay, appearance of postinterventional fever, or 30-day mortality. However, the application of intravenous analgesics as postinterventional pain medication was needed more often in patients treated with DEB-TACE (57.1% vs 12.5%, P=0.0281). The overall median survival after the initial procedure was 10.8 months in the cTACE group and 9.2 months in the DEB-TACE group, showing no significant difference.
Conclusion: No survival benefit for patients treated with either DEB-TACE or cTACE was observed. Surprisingly, a higher rate of postinterventional pain could be detected after DEB-TACE.
Attention-Deficit/Hyperactivity Disorder (ADHD) is characterized by symptoms of inattentiveness and hyperactivity/impulsivity. Besides, increasing evidence points to ADHD patients showing emotional dysfunctions and concomitant problems in social life. However, systematic research on emotional dysfunctions in ADHD is still rare, and to date most studies lack conceptual differentiation between emotion processing and emotion regulation. The aim of this thesis was to systematically investigate emotion processing and emotion regulation in adult ADHD in a virtual reality paradigm implementing social interaction. Emotional reactions were assessed on experiential, physiological, and behavioral levels.
Experiment 1 was conducted to develop a virtual penalty kicking paradigm implying social feedback and to test it in a healthy sample. This paradigm should then be applied in ADHD patients later on. Pleasant and unpleasant trials in this paradigm consisted of hits respectively misses and subsequent feedback from a virtual coach. In neutral trials, participants were teleported to different spots of the virtual stadium. Results indicated increased positive affectivity (higher valence and arousal ratings, higher zygomaticus activations, and higher expression rates of positive emotional behavior) in response to pleasant compared to neutral trials. Reactions to unpleasant trials were contradictory, indicating increased levels of both positive and negative affectivity, compared to neutral trials. Unpleasant vs. neutral trials revealed lower valence ratings, higher arousal ratings, higher zygomaticus activations, slightly lower corrugator activations, and higher expression rates of both positive and negative emotional behavior. The intensity of emotional reactions correlated with experienced presence in the virtual reality.
To better understand the impact of hits or misses per se vs. hits or misses with coach feedback healthy participants’ emotional reactions, only 50% of all shots were followed by coach feedback in experiment 2. Neutral trials consisted of shots over the free soccer field which were followed by coach feedback in 50 % of all trials. Shots and feedback evoked more extreme valence and arousal ratings, higher zygomaticus activations, lower corrugator activations, and higher skin conductance responses than shots alone across emotional conditions. Again, results speak for the induction of positive emotions in pleasant trials whereas the induction of negative emotions in unpleasant trials seems ambiguous. Technical improvements of the virtual reality were reflected in higher presence ratings than in experiment 1.
Experiment 3 investigated emotional reactions of adult ADHD patients and healthy controls after emotion processing and response-focused emotion regulation. Participants successively
went through an ostensible online ball-tossing game (cyber ball) inducing negative emotions, and an adapted version of the virtual penalty kicking game. Throughout cyber ball, participants were included or ostracized by two other players in different experimental blocks. Participants were instructed to explicitly show, not regulate, or hide their emotions in different experimental blocks. Results provided some evidence for deficient processing of positive emotions in ADHD. Patients reported slightly lower positive affect than controls during cyber ball, gave lower valence ratings than controls in response to pleasant penalty kicking trials, and showed lower zygomaticus activations than controls especially during penalty kicking. Patients in comparison with controls showed slightly increased processing of unpleasant events during cyber ball (higher ratings of negative affect, especially in response to ostracism), but not during penalty kicking. Patients showed lower baseline skin conductance levels than controls, and impaired skin conductance modulations. Compared to controls, patients showed slight over-expression of positive as well as negative emotional behavior. Emotion regulation analyses revealed no major difficulties of ADHD vs. controls in altering their emotional reactions through deliberate response modulation. Moreover, patients reported to habitually apply adaptive emotion regulation strategies even more frequently than controls. The analyses of genetic high-risk vs. low-risk groups for ADHD across the whole sample revealed similar results as analyses for patients vs. controls for zygomaticus modulations during emotion processing, and for modulations of emotional reactions due to emotion regulation.
To sum up, the virtual penalty kicking paradigm proved to be successful for the induction of positive, but not negative emotions. The importance of presence in virtual reality for the intensity of induced emotions could be replicated. ADHD patients showed impaired processing of primarily positive emotions. Aberrations in negative emotional responding were less clear and need further investigation. Results point to adult ADHD in comparison to healthy controls suffering from baseline deficits in autonomic arousal and deficits in arousal modulation. Deficits of ADHD in the deliberate application of response-focused emotion regulation could not be found.
Killing the cMSSM softly
(2016)
We investigate the constrained Minimal Supersymmetric Standard Model (cMSSM) in the light of constraining experimental and observational data from precision measurements, astrophysics, direct supersymmetry searches at the LHC and measurements of the properties of the Higgs boson, by means of a global fit using the program Fittino. As in previous studies, we find rather poor agreement of the best fit point with the global data. We also investigate the stability of the electro-weak vacuum in the preferred region of parameter space around the best fit point. We find that the vacuum is metastable, with a lifetime significantly longer than the age of the Universe. For the first time in a global fit of supersymmetry, we employ a consistent methodology to evaluate the goodness-of-fit of the cMSSM in a frequentist approach by deriving p values from large sets of toy experiments. We analyse analytically and quantitatively the impact of the choice of the observable set on the p value, and in particular its dilution when confronting the model with a large number of barely constraining measurements. Finally, for the preferred sets of observables, we obtain p values for the cMSSM below 10 %, i.e. we exclude the cMSSM as a model at the 90 % confidence level.
Age‐dependent transcriptional and epigenomic responses to light exposure in the honey bee brain
(2016)
Light is a powerful environmental stimulus of special importance in social honey bees that undergo a behavioral transition from in-hive to outdoor foraging duties. Our previous work has shown that light exposure induces structural neuronal plasticity in the mushroom bodies (MBs), a brain center implicated in processing inputs from sensory modalities. Here, we extended these analyses to the molecular level to unravel light-induced transcriptomic and epigenomic changes in the honey bee brain. We have compared gene expression in brain compartments of 1- and 7-day-old light-exposed honey bees with age-matched dark-kept individuals. We have found a number of differentially expressed genes (DEGs), both novel and conserved, including several genes with reported roles in neuronal plasticity. Most of the DEGs show age-related changes in the amplitude of light-induced expression and are likely to be both developmentally and environmentally regulated. Some of the DEGs are either known to be methylated or are implicated in epigenetic processes suggesting that responses to light exposure are at least partly regulated at the epigenome level. Consistent with this idea light alters the DNA methylation pattern of bgm, one of the DEGs affected by light exposure, and the expression of microRNA miR-932. This confirms the usefulness of our approach to identify candidate genes for neuronal plasticity and provides evidence for the role of epigenetic processes in driving the molecular responses to visual stimulation.
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.
Background
Ovarian cancer is mostly associated with pathologically regulated permeability of peritoneal vessels, leading to ascites. Here, we investigated the molecular regulation of endothelial permeability by the vascular endothelial growth factor (VEGF) and both tight and adherens junction proteins (VE-cadherin and claudin 5) with regards to the tumor biology of different ovarian cancer types.
Methods
Serum and ascites samples before and after surgery, as well as peritoneal biopsies of 68 ovarian cancer patients and 20 healthy controls were collected. In serum and ascites VEGF protein was measured by ELISA. In peritoneal biopsies co-localization of VE-cadherin and claudin 5 was investigated using immunohistochemical dual staining. In addition, the gene expression of VE-cadherin and claudin 5 was quantified by Real-time PCR. Differences in VEGF levels, VE-cadherin and claudin 5 gene expression were analyzed in relation to various tumor characteristics (tumor stage, grading, histological subtypes, resection status after surgery) and then compared to controls. Furthermore, human primary ovarian cancer cells were co-cultured with human umbilical vein endothelial cells (HUVEC) and changes in VE-cadherin and claudin 5 were investigated after VEGF inhibition.
Results
VEGF was significantly increased in tumor patients in comparison to controls and accumulates in ascites. The highest VEGF levels were found in patients diagnosed with advanced tumor stages, with tumors of poor differentiation, or in the group of solid / cystic-solid tumors. Patients with residual tumor after operation showed significantly higher levels of VEGF both before and after surgery as compared to tumor-free resected patients. Results of an immunohistochemical double-staining experiment indicated co-localization of VE-cadherin and claudin 5 in the peritoneal vasculature. Compared to controls, expression of VE-cadherin and claudin 5 was significantly suppressed in peritoneal vessels of tumor patients, but there were no significant differences regarding VE-cadherin and claudin 5 expression in relation to different tumor characteristics. A significant positive correlation was found between VE-cadherin and claudin 5 expression. VEGF inhibition in vitro was associated with significant increase in VE-cadherin and claudin 5.
Conclusions
Our results indicate that increased peritoneal permeability in ovarian cancer is due to down-regulation of adhesion proteins via tumor derived VEGF. Advanced ovarian cancer with aggressive tumor biology may be associated with early dysregulation of vascular permeability leading to ascites. These patients may benefit from therapeutic VEGF inhibition.
Two thematic complexes were addressed within this work. One part is related to improvements and new implementations into the CAST program package. Thereby the main focus laid on the delivery of a tool which can be used to characterize complex reactions and their mechanisms. But also within the new force field (FF) method (SAPT-FF) within the CAST program, several improvements were made. The second topic is related to the description of dye molecules and their spectral properties. The main focus within these studies was set on the influence of the environment on these properties. In the first topic improvements of the local acting NEB (nudged elastic band) methods were included and the number of available methods was extended. The initial pathway generation was improved by implementing the IDPP (image dependent pair potential) method and a new method was implemented for describing temperature dependent pathways. Additionally, improvements have been made to the optimization routines (global NEB). As a second part the Pathopt (PO) method was considerably improved. In the beginning of the work the original PO idea was used. In this approach one starts with a global optimization on one n-1 dimensional hyperplane which divides the reaction into two sub-areas for obtaining guesses of TSs (transition states). These found TS guesses were used to optimize to the ”true” TS. Starting from the optimized ones a relaxation to the next connected minima is done. This idea has been automatically implemented and extended to several number of hyperplanes. In this manner a group of pathsegments is obtained which needs to be connected, but within this work it was realized that such a procedure might be not very efficient. Therefore, a new strategy was implemented which is founded on the same constrained global optimization scheme (MCM) for which the user defines the number of hyperplanes generated. The number of such generated hyperplanes should be large enough
134
to describe the space between the concerning reactants in a sufficient way. The found minima are directly used to built up the reaction pathway. For this purpose a RMSD (root mean square deviation) criterion is used to walk along ways of minimal change from one to another hyperplane. To prove the implementations various test calculations were carried out and extensions included to prove the capabilities of the new strategy. Related to these tests a new strategy for applying the move steps in MCM (Monte Carlo with minimization) was realized which is also related to the question of the coordinates representation. We were able to show that the hopping steps in MCM can be improved by applying Cartesian steps in combination of random dihedral moves with respect to the constraint. In this way it was possible to show that a large variety of systems can be treated. An additional chapter shows the improvements of the SAPT-FF implementation and related test cases. It was possible to treat benzene dimer and cluster systems of different sizes consistently also in accordance with high level ab initio based approaches. Furthermore, we showed that the SAPT-FF with the right parameters outperforms the standard AMOEBA implementation which is the basis of the SAPT-FF implementation. In the last three chapters deal with the description of perlyene-based dyes. In the first smaller chapter ground state chemistry description of macro cycles of PBI (perylene bisimide) derivatives were investigated. Therefore, AFM (atomic force microscopy) based pictures were explained within our study. The methods to explain aggregation behavior in dependency of the ring size were MD simulations and configuration studies. The last two chapters deal with opto-electronic or photo-physical properties of PBI and PTCDA (perylene-3,4,9,10-tetracarboxylic dianhydride). In detail, we investigated the role of the environment and the aggregate or crystal surrounding by applying different models. In that way implicit and explicit solvation models, the size of aggregates and vibration motions were used. In the case of PBI the recent work is found on preliminary studies related to my bachelor thesis and extends it. It was shown that the direct influence of a polarizable surrounding, as well as explicit inclusion of solvent molecules on the overall description of the excitations and nature of the excited states is weaker as one might expect. However the inclusion of intra-molecular degrees of freedom showed a stronger influence on the state characteristics and can induce a change of the order of states within the dimer picture. For the PTCDA molecule the main focus was set on the description of the absorption spectrum of crystalline thin films. Related to this older works exist which already gave a description and assignment of the absorption band, but are based on different approaches compared to the one used in this work. We used the supermolecule ansatz, whereas the environment and different aggregate sizes were investigated. Within the dimer based approach we were able to show that using continuum solvation (IEFPCM/COSMO) based description for the environment the relative order of states remains unchanged. Similar to the PBI calculations the influence of the vibrational motions /distortions is larger. The simulation of the crystal environment by using QM/MM (quantum mechanics/molecular mechanics) approaches delivered that an asymmetric charge distribution might induce a localization of the excitation and a stronger mixing of states. For obtaining further insights we go beyond the dimer picture and aggregates of different sizes were used, whereas the simulations up to the octadecamer mono- and even dual-layer stack were carried out. Within these calculations it was shown that the H-coupling is dominating over a weaker J-coupling between different stacks. Additionally the calculations based on DFT (density functional theory) and semi-empirics showed that the lowest state in terms of energy are mostly of Frenkel type, whereas the higher lying states are CT ones which mix with embedded Frenkel type states. The first band of the absorption spectrum was explained by inclusion of vibrational motions within the stacks which induce an intensity gain of the first excited state. This intensity was not explainable by using the undistorted stacks. Also relaxations at the crystal surface might play a role, but are experimentally not explainable.
Although the concept of botanical carnivory has been known since Darwin's time, the molecular mechanisms that allow animal feeding remain unknown, primarily due to a complete lack of genomic information. Here, we show that the transcriptomic landscape of the Dionaea trap is dramatically shifted toward signal transduction and nutrient transport upon insect feeding, with touch hormone signaling and protein secretion prevailing. At the same time, a massive induction of general defense responses is accompanied by the repression of cell death-related genes/processes. We hypothesize that the carnivory syndrome of Dionaea evolved by exaptation of ancient defense pathways, replacing cell death with nutrient acquisition.
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.
Background
The impact of sex on cardiac morphology and function in chronic volume overload has been described in detail. However, the relation between sex and contractile properties at the actin-myosin level has not been well defined. Therefore, we evaluated the influence of sex on the contractile capacities of patients with chronic volume overload.
Methods
In 36 patients (18 males, 65 ± 9 years; 18 females, 65 ± 13 years) scheduled for elective mitral valve surgery due to severe mitral regurgitation (MR) with preserved left ventricular function, right auricle samples were obtained prior to extracorporal circulation. The fibers were prepared and skinned and exposed to a gradual increase in the calcium concentration (from pCa of 6.5–4.0) for calcium-induced force-developing measurements. Calcium sensitivity was also measured and recorded.
Results
The pCa-force relationship of the fibers obtained from males and females was significantly different, with the force values of the female fibers greater than those of male fibers at maximum calcium concentrations (pCa of 4.0: 3.6 ± 0.3 mN versus 3.2 ± 0.4 mN, p 0.02) and pCa of 4.5 2.6 ± 0.6 versus 2.0 ± 0.5, p 0.002). In contrast, the force values of female fibers were lower at mean calcium concentrations compared to those of male fibers (at 5.5 and pCa of 6.0: 1.0 ± 0.3 mN versus 1.2 ± 0.5 mN, p 0.04; 0.61 ± 0.05 versus 0.88 ± 0.09, p 0.04).
Calcium sensitivity was observed at pCa of 5.0 in females and pCa of 4.5 in males.
Conclusion
This study demonstrated that female fibers from patients exposed to chronic volume overload developed higher force values at a given calcium concentration compared to fibers from male patients. We assume that female patients might tap the full force potential, which is required when exposed to the highest calcium concentrations in our experimental cycle. The calcium sensitivity among genders was significantly different, with the results suggesting that males have higher calcium sensitivity and might compensate for lower force values at maximal calcium concentrations by a higher affinity for calcium. Hence, female patients with MR seem to work more “energy efficient”.
Unique features of a global human ectoparasite identified through sequencing of the bed bug genome
(2016)
The bed bug, Cimex lectularius, has re-established itself as a ubiquitous human ectoparasite throughout much of the world during the past two decades. This global resurgence is likely linked to increased international travel and commerce in addition to widespread insecticide resistance. Analyses of the C. lectularius sequenced genome (650 Mb) and 14,220 predicted protein-coding genes provide a comprehensive representation of genes that are linked to traumatic insemination, a reduced chemosensory repertoire of genes related to obligate hematophagy, host–symbiont interactions, and several mechanisms of insecticide resistance. In addition, we document the presence of multiple putative lateral gene transfer events. Genome sequencing and annotation establish a solid foundation for future research on mechanisms of insecticide resistance, human–bed bug and symbiont–bed bug associations, and unique features of bed bug biology that contribute to the unprecedented success of C. lectularius as a human ectoparasite.
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 objective of this study was to identify unknown modulators of Calcineurin (Cn)-NFAT signaling. Measurement of NFAT reporter driven luciferase activity was therefore utilized to screen a human cardiac cDNA-library (~10\(^{7}\) primary clones) in C2C12 cells through serial dilutions until single clones could be identified. This extensive screening strategy culminated in the identification of SUMO2 as a most efficient Cn-NFAT activator. SUMO2-mediated activation of Cn-NFAT signaling in cardiomyocytes translated into a hypertrophic phenotype. Prohypertrophic effects were also observed in mice expressing SUMO2 in the heart using AAV9 (Adeno-associated virus), complementing the in vitro findings. In addition, increased SUMO2-mediated sumoylation in human cardiomyopathy patients and in mouse models of cardiomyopathy were observed. To decipher the underlying mechanism, we generated a sumoylation-deficient SUMO2 mutant (ΔGG). Surprisingly, ΔGG replicated Cn-NFAT-activation and the prohypertrophic effects of native SUMO2, both in vitro and in vivo, suggesting a sumoylation-independent mechanism. Finally, we discerned a direct interaction between SUMO2 and CnA, which promotes CnA nuclear localization. In conclusion, we identified SUMO2 as a novel activator of Cn-NFAT signaling in cardiomyocytes. In broader terms, these findings reveal an unexpected role for SUMO2 in cardiac hypertrophy and cardiomyopathy, which may open the possibility for therapeutic manipulation of this pathway.
Biochemical and molecular characterization of an original master sex determining gene in Salmonids
(2016)
Sexual development is a fundamental and versatile process that shapes animal morphology, physiology and behavior. The underlying developmental process is composed of the sex determination and the sex differentiation. Sex determination mechanisms are extremely labile among taxa. The initial triggers of the sex determination process are often genetics called sex determining genes. These genes are expressed in the bipotential gonad and tilt the balance to a developmental program allowing the differentiation of either a testis or an ovary. Fish represent a large and fascinating vertebrate group to study both sex determination and sex differentiation mechanisms. To date, among the known sex determining genes, three gene families namely sox, dmrt and TGF-β factors govern this developmental program. As exception to this rule, sdY “sexually dimorphic on the Y” does not belong to one of these families as it comes from the duplication / evolution of an ancestor gene related to immunity, i.e., the interferon related factor 9, irf9. sdY is the master sex determining gene in salmonids, a group of fishes that include species such as rainbow trout and Atlantic salmon. The present study was aimed to firstly characterize the features of SdY protein. Results indicate that SdY is predominantly localized in the cytoplasm tested in various fish and mammalian cell lines and confirmed by different methods. Predictive in silico analysis revealed that SdY is composed of a β-sandwich core surrounded by three α-helices as well specific characteristics conferring a putative protein-protein interaction site. Secondly, the study was aimed to understand how SdY could trigger testicular differentiation. SdY is a truncated divergent version of Irf9 that has a conserved protein-protein domain but lost the DNA interaction domain of its ancestor gene. It was then hypothesized that SdY could initiate testicular differentiation by protein-protein interactions. To evaluate this we first conducted a yeast-two-hybrid screen that revealed a high proportion of transcription factors including fox proteins. Using various biochemical and cellular methods we confirm an interaction between SdY and Foxl2, a major transcription factor involved in ovarian differentiation and identity maintenance. Interestingly, the interaction of SdY with Foxl2 leads to nuclear translocation of SdY from the cytoplasm. Furthermore, this SdY translocation mechanism was found to be specific to fish Foxl2 and to a lesser extend Foxl3 and not other Fox proteins or mammalian FoxL2. In addition, we found that this interaction allows the stabilization of SdY and prevents its degradation. Finally, to better decipher SdY action we used as a model a mutated version of SdY that was identified in XY females of Chinook salmon natural population. Results show that this mutation induces a local conformation defect obviously leading to a misfolded protein and a quick degradation. Moreover, the mutated version compromised the interaction with Foxl2 defining a minimal threshold to induce testicular differentiation. Altogether results from my thesis propose that SdY would trigger testicular differentiation in salmonids by preventing Foxl2 to promote ovarian differentiation. Further research should be now carried out on how this interaction of SdY and Foxl2 acts in-vivo.
Background
\(^{177}\)Lu is used in peptide receptor radionuclide therapies for the treatment of neuroendocrine tumors. Based on the recent literature, SST2 antagonists are superior to agonists in tumor uptake. The compound OPS201 is the novel somatostatin antagonist showing the highest SST2 affinity. The aim of this study was to measure the in vivo biodistribution and dosimetry of \(^{177}\)Lu-OPS201 in five anesthetized Danish Landrace pigs as an appropriate substitute for humans to quantitatively assess the absorbed doses for future clinical applications.
Results
\(^{177}\)Lu-OPS201 was obtained with a specific activity ranging from 10 to 17 MBq/μg. Prior to administration, the radiochemical purity was measured as s > 99.7 % in all cases. After injection, fast clearance of the compound from the blood stream was observed. Less than 5 % of the injected activity was presented in blood 10 min after injection. A series of SPECT/CT and whole-body scans conducted until 10 days after intravenous injection showed uptake mostly in the liver, spine, and kidneys. There was no visible uptake in the spleen. Blood samples were taken to determine the time-activity curve in the blood. Time-activity curves and time-integrated activity coefficients were calculated for the organs showing visible uptake. Based on these data, the absorbed organ dose coefficients for a 70-kg patient were calculated with OLINDA/EXM. For humans after an injection of 5 GBq \(^{177}\)Lu-OPS201, the highest predicted absorbed doses are obtained for the kidneys (13.7 Gy), the osteogenic cells (3.9 Gy), the urinary bladder wall (1.8 Gy), and the liver (1.0 Gy). No metabolites of 177Lu-OPS201 were found by radio HPLC analysis. None of the absorbed doses calculated will exceed organ toxicity levels.
Conclusions
The \(^{177}\)Lu-OPS201 was well tolerated and caused no abnormal physiological or behavioral signs. In vivo distributions and absorbed doses of pigs are comparable to those observed in other publications. According to the biodistribution data in pigs, presented in this work, the expected radiation exposure in humans will be within the acceptable range.
Background:
Similar to tumor cells, activated T-lymphocytes generate ATP mainly by glycolytic degradation of glucose. Lymphocyte glucose uptake involves non-concentrative glucose carriers of the GLUT family. In contrast to GLUT isoforms, Na+-coupled glucose-carrier SGLT1 accumulates glucose against glucose gradients and is effective at low extracellular glucose concentrations. The present study explored expression and regulation of SGLT1 in activated murine splenic cytotoxic T cells (CTLs) and human Jurkat T cells.
Methods:
FACS analysis, immunofluorescence, confocal microscopy, chemiluminescence and Western blotting were employed to estimate SGLT1 expression, function and regulation in lymphocytes, as well as dual electrode voltage clamp in SGLT1 ± JAK3 expressing Xenopus oocytes to quantify the effect of janus kinase3 (JAK3) on SGLT1 function.
Results:
SGLT1 is expressed in murine CTLs and also in human Jurkat T cells. 2-(N-(7-nitrobenz-2-oxa-1,3-diazol-4-yl)amino)-2-deoxyglucose uptake was significantly decreased by SGLT1-blocker phloridzin (0.2 mM) and by pharmacological inhibition of JAK3 with WHI-P131 (156 µM), WHI-P154 (11.2 µM) and JAK3 inhibitor VI (0.5 µM). Electrogenic glucose transport (Iglucose) in Xenopus oocytes expressing human SGLT1 was increased by additional expression of human wild type JAK3, active A568VJAK3 but not inactive K851AJAK3. Coexpression of JAK3 enhanced the maximal transport rate without significantly modifying affinity of the carrier. Iglucose in SGLT1+JAK3 expressing oocytes was significantly decreased by WHI-P154 (11.2 µM). JAK3 increased the SGLT1 protein abundance in the cell membrane. Inhibition of carrier insertion by brefeldin A (5 µM) in SGLT1+JAK3 expressing oocytes resulted in a decline of Iglucose, which was similar in presence and absence of JAK3.
Conclusions:
SGLT1 is expressed in murine cytotoxic T cells and human Jurkat T cells and significantly contributes to glucose uptake in those cells post activation. JAK3 up-regulates SGLT1 activity by increasing the carrier protein abundance in the cell membrane, an effect enforcing cellular glucose uptake into activated lymphocytes and thus contributing to the immune response.
Exciton coupling is of fundamental importance and determines functional properties of organic dyes in (opto-)electronic and photovoltaic devices. Here we show that strong exciton coupling is not limited to the situation of equal chromophores as often assumed. Quadruple dye stacks were obtained from two bis(merocyanine) dyes with same or different chromophores, respectively, which dimerize in less-polar solvents resulting in the respective homo- and heteroaggregates. The structures of the quadruple dye stacks were assigned by NMR techniques and unambiguously confirmed by single-crystal X-ray analysis. The heteroaggregate stack formed from the bis(merocyanine) bearing two different chromophores exhibits remarkably different ultraviolet/vis absorption bands compared with those of the homoaggregate of the bis(merocyanine) comprising two identical chromophores. Quantum chemical analysis based on an extension of Kasha’s exciton theory appropriately describes the absorption properties of both types of stacks revealing strong exciton coupling also between different chromophores within the heteroaggregate.
Next-to-leading-order electroweak corrections to pp -> W\(^{+}\)W\(^{-}\) -> 4 leptons at the LHC
(2016)
We present results of the first calculation of next-to-leading-order electroweak corrections to W-boson pair production at the LHC that fully takes into account leptonic W-boson decays and off-shell effects. Employing realistic event selections, we discuss the corrections in situations that are typical for the study of W-boson pairs as a signal process or of Higgs-boson decays H → WW∗, to which W-boson pair production represents an irreducible background. In particular, we compare the full off-shell results, obtained treating the W-boson resonances in the complex-mass scheme, to previous results in the so-called double-pole approximation, which is based on an expansion of the loop amplitudes about the W resonance poles. At small and intermediate scales, i.e. in particular in angular and rapidity distributions, the two approaches show the expected agreement at the level of fractions of a percent, but larger differences appear in the TeV range. For transverse-momentum distributions, the differences can even exceed the 10% level in the TeV range where “background diagrams” with one instead of two resonant W bosons gain in importance because of recoil effects.
Background:
Attention deficit/hyperactivity disorder has been shown to affect working memory, and fMRI studies in children and adolescents with attention deficit/hyperactivity disorder report hypoactivation in task-related attentional networks. However, studies with adult attention deficit/hyperactivity disorder patients addressing this issue as well as the effects of clinically valid methylphenidate treatment are scarce. This study contributes to closing this gap.
Methods:
Thirty-five adult patients were randomized to 6 weeks of double-blind placebo or methylphenidate treatment. Patients completed an fMRI n-back working memory task both before and after the assigned treatment, and matched healthy controls were tested and compared to the untreated patients.
Results:
There were no whole-brain differences between any of the groups. However, when specified regions of interest were investigated, the patient group showed enhanced BOLD responses in dorsal and ventral areas before treatment. This increase was correlated with performance across all participants and with attention deficit/hyperactivity disorder symptoms in the patient group. Furthermore, we found an effect of treatment in the right superior frontal gyrus, with methylphenidate-treated patients exhibiting increased activation, which was absent in the placebo-treated patients.
Conclusions:
Our results indicate distinct activation differences between untreated adult attention deficit/hyperactivity disorder patients and matched healthy controls during a working memory task. These differences might reflect compensatory efforts by the patients, who are performing at the same level as the healthy controls. We furthermore found a positive effect of methylphenidate on the activation of a frontal region of interest. These observations contribute to a more thorough understanding of adult attention deficit/hyperactivity disorder and provide impulses for the evaluation of therapy-related changes.
Lungfish and coelacanths are the only living sarcopterygian fish. The phylogenetic relationship of lungfish to the last common ancestor of tetrapods and their close morphological similarity to their fossil ancestors make this species uniquely interesting. However their genome size, the largest among vertebrates, is hampering the generation of a whole genome sequence. To provide a partial solution to the problem, a high-coverage lungfish reference transcriptome was generated and assembled. The present findings indicate that lungfish, not coelacanths, are the closest relatives to land-adapted vertebrates. Whereas protein-coding genes evolve at a very slow rate, possibly reflecting a “living fossil” status, transposable elements appear to be active and show high diversity, suggesting a role for them in the remarkable expansion of the lungfish genome. Analyses of single genes and gene families documented changes connected to the water to land transition and demonstrated the value of the lungfish reference transcriptome for comparative studies of vertebrate evolution.
Background
Salvage radiotherapy (SRT) is clinically established in prostate cancer (PC) patients with PSA persistence or biochemical relapse (BCR) after prior radical surgery. PET/CT imaging prior to SRT may be performed to localize disease recurrence. The recently introduced \(^{68}\)Ga-PSMA outperforms other PET tracers for detection of recurrence and is therefore expected also to impact radiation planning.
Forty-five patients with PSA persistence (16 pts) or BCR (29 pts) after prior prostatectomy, scheduled to undergo SRT of the prostate bed, underwent \(^{68}\)Ga-PSMA PET/CT. The median PSA level was 0.67 ng/ml. The impact of \(^{68}\)Ga-PSMA PET/CT on the treatment decision was assessed. Patients with oligometastatic (≤5 lesions) PC underwent radiotherapy (RT), with the extent of the RT area and dose escalation being based on PET positivity.
Results
Suspicious lesions were detected in 24/45 (53.3 %) patients. In 62.5 % of patients, lesions were only detected by 68Ga-PSMA PET. Treatment was changed in 19/45 (42.2 %) patients, e.g., extending SRT to metastases (9/19), administering dose escalation in patients with morphological local recurrence (6/19), or replacing SRT by systemic therapy (2/19). 38/45 (84.4 %) followed the treatment recommendation, with data on clinical follow-up being available in 21 patients treated with SRT. All but one showed biochemical response (mean PSA decline 78 ± 19 %) within a mean follow-up of 8.12 ± 5.23 months.
Conclusions
\(^{68}\)Ga-PSMA PET/CT impacts treatment planning in more than 40 % of patients scheduled to undergo SRT. Future prospective studies are needed to confirm this significant therapeutic impact on patients prior to SRT.
Staphylococcus aureus is a prevalent commensal bacterium which represents one of the leading causes in health care-associated bacterial infections worldwide and can cause a variety of different diseases ranging from simple abscesses to severe and life threatening infections including pneumonia, osteomyelitis and sepsis.
In recent times multi-resistant strains have emerged, causing severe problems in nosocomial as well as community-acquired (CA) infection settings, especially in the United States (USA). Therefore S. aureus has been termed as a superbug by the WHO, underlining the severe health risk originating from it. Today, infections in the USA are dominated by S. aureus genotypes which are classified as USA300 and USA400, respectively. Strains of genotype USA300 are responsible for about 70% of the CA infections.
The molecular mechanisms which render S. aureus such an effective pathogen are still not understood in its entirety. For decades S. aureus was thought to be a strictly extracellular pathogen relying on pore-forming toxins like α-hemolysin to damage human cells and tissue. Only recently it has been shown that S. aureus can enter non-professional phagocytes, using adhesins like the fibronectin-binding proteins which mediate an endocytotic uptake into the host cells. The bacteria are consequently localized to endosomes, where the degradation of enclosed bacterial cells through phagosome maturation would eventually occur.
S. aureus can avoid degradation, and translocate to the cellular cytoplasm, where it can replicate. The ability to cause this so-called phagosomal escape has mainly been attributed to a family of amphiphilic peptides called phenol soluble modulins (PSMs), but as studies have shown, they are not sufficient.
In this work I used a transposon mutant library in combination with automated fluorescence microscopy to screen for genes involved in the phagosomal escape process and intracellular survival of S. aureus. I thereby identified a number of genes, including a non-ribosomal peptide synthetase (NRPS). The NRPS, encoded by the genes ausA and ausB, produces two types of small peptides, phevalin and tyrvalin. Mutations in the ausAB genes lead to a drastic decrease in phagosomal escape rates in epithelial cells, which were readily restored by genetic complementation in trans as well as by supplementation of synthetic phevalin. In leukocytes, phevalin interferes with calcium fluxes and activation of neutrophils and promotes cytotoxicity of intracellular bacteria in both, macrophages and neutrophils. Further ausAB is involved in survival and virulence of the bacterium during mouse lung pneumoniae.
The here presented data demonstrates the contribution of the bacterial cyclic dipeptide phevalin to S. aureus virulence and suggests, that phevalin directly acts on a host cell target to promote cytotoxicity of intracellular bacteria.
Community-acquired (CA) Staphylococcus aureus cause various diseases even in healthy individuals. Enhanced virulence of CA-strains is partly attributed to increased production of toxins such as phenol-soluble modulins (PSM). The pathogen is internalized efficiently by mammalian host cells and intracellular S. aureus has recently been shown to contribute to disease. Upon internalization, cytotoxic S. aureus strains can disrupt phagosomal membranes and kill host cells in a PSM-dependent manner. However, PSM are not sufficient for these processes. Here we screened for factors required for intracellular S. aureus virulence. We infected escape reporter host cells with strains from an established transposon mutant library and detected phagosomal escape rates using automated microscopy. We thereby, among other factors, identified a non-ribosomal peptide synthetase (NRPS) to be required for efficient phagosomal escape and intracellular survival of S. aureus as well as induction of host cell death. By genetic complementation as well as supplementation with the synthetic NRPS product, the cyclic dipeptide phevalin, wild-type phenotypes were restored. We further demonstrate that the NRPS is contributing to virulence in a mouse pneumonia model. Together, our data illustrate a hitherto unrecognized function of the S. aureus NRPS and its dipeptide product during S. aureus infection.
Classical novae are thermonuclear explosions occurring on the surface of white dwarfs.
When co-existing in a binary system with a main sequence or more evolved star, mass
accretion from the companion star to the white dwarf can take place if the companion
overflows its Roche lobe. The envelope of hydrogen-rich matter which builds on
top of the white dwarf eventually ignites under degenerate conditions, leading to
a thermonuclear runaway and an explosion in the order of 1046 erg, while leaving
the white dwarf intact. Spectral analyses from the debris indicate an abundance of
isotopes that are tracers of nuclear burning via the hot CNO cycle, which in turn
reveal some sort of mixing between the envelope and the white dwarf underneath.
The exact mechanism is still a matter of debate.
The convection and deflagration in novae develop in the low Mach number regime.
We used the Seven League Hydro code (SLH ), which employs numerical schemes
designed to correctly simulate low Mach number flows, to perform two and three-
dimensional simulations of classical novae. Based on a spherically-symmetric model
created with aid of a stellar evolution code, we developed our own nova model and
tested it on a variety of numerical grids and boundary conditions for validation. We
focused on the evolution of temperature, density and nuclear energy generation rate at
the layers between white dwarf and envelope, where most of the energy is generated,
to understand the structure of the transition region, and its effect on the nuclear
burning. We analyzed the resulting dredge-up efficiency stemming from the convective
motions in the envelope. Our models yield similar results to the literature, but seem
to depend very strongly on the numerical resolution. We followed the evolution of
the nuclear species involved in the CNO cycle and concluded that the thermonuclear
reactions primarily taking place are those of the cold and not the hot CNO cycle.
The reason behind this could be that under the conditions generally assumed for
multi-dimensional simulations, the envelope is in fact not degenerate. We performed
initial tests for 3D simulations and realized that alternative boundary conditions are
needed.
Previous studies of social phobia have reported an increased vigilance to social threat cues but also an avoidance of socially relevant stimuli such as eye gaze. The primary aim of this study was to examine attentional mechanisms relevant for perceiving social cues by means of abnormalities in scanning of facial features in patients with social phobia. In two novel experimental paradigms, patients with social phobia and healthy controls matched on age, gender and education were compared regarding their gazing behavior towards facial cues. The first experiment was an emotion classification paradigm which allowed for differentiating reflexive attentional shifts from sustained attention towards diagnostically relevant facial features. In the second experiment, attentional orienting by gaze direction was assessed in a gaze-cueing paradigm in which non-predictive gaze cues shifted attention towards or away from subsequently presented targets. We found that patients as compared to controls reflexively oriented their attention more frequently towards the eyes of emotional faces in the emotion classification paradigm. This initial hypervigilance for the eye region was observed at very early attentional stages when faces were presented for 150 ms, and persisted when facial stimuli were shown for 3 s. Moreover, a delayed attentional orienting into the direction of eye gaze was observed in individuals with social phobia suggesting a differential time course of eye gaze processing in patients and controls. Our findings suggest that basic mechanisms of early attentional exploration of social cues are biased in social phobia and might contribute to the development and maintenance of the disorder.
The aim of this study was to evaluate the effect of a repeated sprint training with multi-directional change-of-direction (COD) movements (RSmulti) compared to repeated shuttle sprints (RSS) on variables related to COD speed and reactive agility. Nineteen highly-trained male U15 soccer players were assigned into two groups performing either RSmulti or RSS. For both groups, each training session involved 20 repeated 15 s sprints interspersed with 30 s recovery. With RSmulti the COD movements were randomized and performed in response to a visual stimulus, while the RSS involved predefined 180° COD movements. Before and following the six training sessions, performance in the Illinois agility test (IAT), COD speed in response to a visual stimulus, 20 m linear sprint time and vertical jumping height were assessed. Both groups improved their performance in the IAT (p < 0.01, ES = 1.13; p = 0.01, ES = 0.55). The COD speed in response to a visual stimulus improved with the RSmulti (p < 0.01, ES = 1.03), but not the RSS (p = 0.46, ES = 0.28). No differences were found for 20 m sprint time (P=0.73, ES = 0.07; p = 0.14, ES = 0.28) or vertical jumping height (p = 0.46, ES = 0.11; p = 0.29, ES = 0.12) for the RSmulti and RSS, respectively. In conclusion, performance in the IAT improved with the RSmulti as well as RSS. With the RSmulti however, the COD movements are performed in response to a visual stimulus, which may result in specific adaptations that improve COD speed and reactive agility in young highly trained soccer players.
Objective: This clinical practice guideline addresses the diagnosis and treatment of primary adrenal insufficiency. Participants: The Task Force included a chair, selected by The Clinical Guidelines Subcommittee of the Endocrine Society, eight additional clinicians experienced with the disease, a methodologist, and a medical writer. The co-sponsoring associations (European Society of Endocrinology and the American Association for Clinical Chemistry) had participating members. The Task Force received no corporate funding or remuneration in connection with this review. Evidence: This evidence-based guideline was developed using the Grading of Recommendations, Assessment, Development, and Evaluation (GRADE) system to determine the strength of recommendations and the quality of evidence.
Consensus Process: The evidence used to formulate recommendations was derived from two commissioned systematic reviews as well as other published systematic reviews and studies identified by the Task Force. The guideline was reviewed and approved sequentially by the Endocrine Society's Clinical Guidelines Subcommittee and Clinical Affairs Core Committee, members responding to a web posting, and the Endocrine Society Council. At each stage, the Task Force incorporated changes in response to written comments.
Conclusions: We recommend diagnostic tests for the exclusion of primary adrenal insufficiency in all patients with indicative clinical symptoms or signs. In particular, we suggest a low diagnostic (and therapeutic) threshold in acutely ill patients, as well as in patients with predisposing factors. This is also recommended for pregnant women with unexplained persistent nausea, fatigue, and hypotension. We recommend a short corticotropin test (250 mu g) as the "gold standard" diagnostic tool to establish the diagnosis. If a short corticotropin test is not possible in the first instance, we recommend an initial screening procedure comprising the measurement of morning plasma ACTH and cortisol levels. Diagnosis of the underlying cause should include a validated assay of autoantibodies against 21-hydroxylase. In autoantibody-negative individuals, other causes should be sought. We recommend once-daily fludrocortisone (median, 0.1 mg) and hydrocortisone (15-25 mg/d) or cortisone acetate replacement (20-35 mg/d) applied in two to three daily doses in adults. In children, hydrocortisone (similar to 8 mg/m\(^2\)/d) is recommended. Patients should be educated about stress dosing and equipped with a steroid card and glucocorticoid preparation for parenteral emergency administration. Follow-up should aim at monitoring appropriate dosing of corticosteroids and associated autoimmune diseases, particularly autoimmune thyroid disease.
The glycoprotein sclerostin has been identified as a negative regulator of bone growth. It exerts its function by interacting with the Wnt co-receptor LRP5/6, blocks the binding of Wnt factors and thereby inhibits Wnt signalling. Neutralizing anti-sclerostin antibodies are able to restore Wnt activity and enhance bone growth thereby presenting a new osteoanabolic therapy approach for diseases such as osteoporosis. We have generated various Fab antibodies against human and murine sclerostin using a phage display set-up. Biochemical analyses have identified one Fab developed against murine sclerostin, AbD09097 that efficiently neutralizes sclerostin's Wnt inhibitory activity. In vitro interaction analysis using sclerostin variants revealed that this neutralizing Fab binds to sclerostin's flexible second loop, which has been shown to harbour the LRP5/6 binding motif. Affinity maturation was then applied to AbD09097, providing a set of improved neutralizing Fab antibodies which particularly bind human sclerostin with enhanced affinity. Determining the crystal structure of AbD09097 provides first insights into how this antibody might recognize and neutralize sclerostin. Together with the structure–function relationship derived from affinity maturation these new data will foster the rational design of new and highly efficient anti-sclerostin antibodies for the therapy of bone loss diseases such as osteoporosis.
DNA-stabilized silver clusters (Ag-DNA) show excellent promise as a multi-functional nanoagent for molecular investigations in living cells. The unique properties of these fluorescent nanomaterials allow for intracellular optical sensors with tunable cytotoxicity based on simple modifications of the DNA sequences. Three Ag-DNA nanoagent designs are investigated, exhibiting optical responses to the intracellular environments and sensing-capability of ions, functional inside living cells. Their sequence-dependent fluorescence responses inside living cells include (1) a strong splitting of the fluorescence peak for a DNA hairpin construct, (2) an excitation and emission shift of up to 120 nm for a single-stranded DNA construct, and (3) a sequence robust in fluorescence properties. Additionally, the cytotoxicity of these Ag-DNA constructs is tunable, ranging from highly cytotoxic to biocompatible Ag-DNA, independent of their optical sensing capability. Thus, Ag-DNA represents a versatile live-cell nanoagent addressable towards anti-cancer, patient-specific and anti-bacterial applications.
MeDALL (Mechanisms of the Development of ALLergy; EU FP7-CP-IP; Project No: 261357; 2010-2015) has proposed an innovative approach to develop early indicators for the prediction, diagnosis, prevention and targets for therapy. MeDALL has linked epidemiological, clinical and basic research using a stepwise, large-scale and integrative approach: MeDALL data of precisely phenotyped children followed in 14 birth cohorts spread across Europe were combined with systems biology (omics, IgE measurement using microarrays) and environmental data. Multimorbidity in the same child is more common than expected by chance alone, suggesting that these diseases share causal mechanisms irrespective of IgE sensitization. IgE sensitization should be considered differently in monosensitized and polysensitized individuals. Allergic multimorbidities and IgE polysensitization are often associated with the persistence or severity of allergic diseases. Environmental exposures are relevant for the development of allergy-related diseases. To complement the population-based studies in children, MeDALL included mechanistic experimental animal studies and in vitro studies in humans. The integration of multimorbidities and polysensitization has resulted in a new classification framework of allergic diseases that could help to improve the understanding of genetic and epigenetic mechanisms of allergy as well as to better manage allergic diseases. Ethics and gender were considered. MeDALL has deployed translational activities within the EU agenda.
Action Plan B3 of the European Innovation Partnership on Active and Healthy Ageing (EIP on AHA) focuses on the integrated care of chronic diseases. Area 5 (Care Pathways) was initiated using chronic respiratory diseases as a model. The chronic respiratory disease action plan includes (1) AIRWAYS integrated care pathways (ICPs), (2) the joint initiative between the Reference site MACVIA-LR (Contre les MAladies Chroniques pour un VIeillissement Actif) and ARIA (Allergic Rhinitis and its Impact on Asthma), (3) Commitments for Action to the European Innovation Partnership on Active and Healthy Ageing and the AIRWAYS ICPs network. It is deployed in collaboration with the World Health Organization Global Alliance against Chronic Respiratory Diseases (GARD). The European Innovation Partnership on Active and Healthy Ageing has proposed a 5-step framework for developing an individual scaling up strategy: (1) what to scale up: (1-a) databases of good practices, (1-b) assessment of viability of the scaling up of good practices, (1-c) classification of good practices for local replication and (2) how to scale up: (2-a) facilitating partnerships for scaling up, (2-b) implementation of key success factors and lessons learnt, including emerging technologies for individualised and predictive medicine. This strategy has already been applied to the chronic respiratory disease action plan of the European Innovation Partnership on Active and Healthy Ageing.
Anisotropy of dose contributions-an instrument to upgrade real time IMRT and VMAT adaptation?
(2016)
Purpose:
To suggest a definition of dose deposition anisotropy for the purpose of ad hoc adaptation of intensity modulated arc therapy (IMRT) and volumetric arc therapy (VMAT), particularly in the vicinity of important organs at risk (OAR), also for large deformations.
Methods:
Beam's-eye-view (BEV) based fluence warping is a standard adaptation method with disadvantages for strongly varying OAR shapes. 2-Step-adaptation overcomes these difficulties by a deeper analysis of the 3D properties of adaptation processes, but requires separate arcs for every OAR to spare, which makes it impractical for cases with multiple OARs. The authors aim to extend the 2-Step method to arbitrary intensity modulated plan by analyzing the anisotropy of dose contributions. Anisotropy was defined as a second term of Fourier transformation of gantry angle dependent dose contributions. For a cylindrical planning target volume (PTV) surrounding an OAR of varying diameter, the anisotropy and the dose-normalized anisotropy were analyzed for several scenarios of optimized fluence distributions. 2-Step adaptation to decreasing and increasing OAR diameter was performed, and compared to a usual fluence based adaptation method. For two clinical cases, prostate and neck, the VMAT was generated and the behavior of anisotropy was qualitatively explored for deformed organs at risk. #
Results:
Dose contribution anisotropy in the PTV peaks around nearby OARs. The thickness of the "anisotropy wall" around OAR increases for increasing OAR radius, as also does the width of 2-Step dose saturating fluence peak adjacent to the OAR K. Bratengeier et al., "A comparison between 2-Step IMRT and conventional IMRT planning," Radiother. Oncol. 84, 298-306 (2007)]. Different optimized beam fluence profiles resulted in comparable radial dependence of normalized anisotropy. As predicted, even for patient cases, anisotropy was inflated even more than increasing diameters of OAR.
Conclusions:
For cylindrically symmetric cases, the dose distribution anisotropy defined in the present work implicitly contains adaptation-relevant information about 3D relationships between PTV and OAR and degree of OAR sparing. For more complex realistic cases, it shows the predicted behavior qualitatively. The authors claim to have found a first component for advancing a 2-Step adaptation to a universal adaptation algorithm based on the BEV projection of the dose anisotropy. Further planning studies to explore the potential of anisotropy for adaptation algorithms using phantoms and clinical cases of differing complexity will follow.
Highly Strained Heterocycles Constructed from Boron–Boron Multiple Bonds and Heavy Chalcogens
(2016)
The reactions of a diborene with elemental selenium or tellurium are shown to afford a diboraselenirane or diboratellurirane, respectively. These reactions are reminiscent of the sequestration of subvalent oxygen and nitrogen in the formation of oxiranes and aziridines; however, such reactivity is not known between alkenes and the heavy chalcogens. Although carbon is too electronegative to affect the reduction of elements with lower relative electronegativity, the highly reducing nature of the B B double bond enables reactions with Se0 and Te0. The capacity of multiple bonds between boron atoms to donate electron density is highlighted in reactions where diborynes behave as nucleophiles, attacking one of the two Te atoms of diaryltellurides, forming salts consisting of diboratellurenium cations and aryltelluride anions.
Treatment of an anionic dimanganaborylene complex ([{Cp(CO)\(_2\)Mn}\(_2\)B]\(^-\)) with coinage metal cations stabilized by a very weakly coordinating Lewis base (SMe\(_2\)) led to the coordination of the incoming metal and subsequent displacement of dimethylsulfide in the formation of hexametalladiborides featuring planar four-membered M\(_2\)B\(_2\) cores (M = Cu, Au) comparable to transition metal clusters constructed around four-membered rings composed solely of coinage metals. The analogies between compounds consisting of B\(_2\)M\(_2\) units and M\(_4\) (M = Cu, Au) units speak to the often overlooked metalloid nature of boron. Treatment of one of these compounds (M = Cu) with a Lewis-basic metal fragment (Pt(PCy\(_3\))\(_2\)) led to the formation of a tetrametallaboride featuring two manganese, one copper and one platinum atom, all bound to boron in a geometry not yet seen for this kind of compound. Computational examination suggests that this geometry is the result of d\(^{10}\)-d\(^{10}\) dispersion interactions between the copper and platinum fragments.
Unsaturated bridges that link the two cyclopentadienyl ligands together in strained ansa metallocenes are rare and limited to carbon-carbon double bonds. The synthesis and isolation of a strained ferrocenophane containing an unsaturated two-boron bridge, isoelectronic with a C=C double bond, was achieved by reduction of a carbene-stabilized 1,1’-bis(dihaloboryl)ferrocene. A combination of spectroscopic and electrochemical measurements as well as density functional theory (DFT) calculations was used to assess the influence of the unprecedented strained cis configuration on the optical and electrochemical properties of the carbene-stabilized diborene unit. Initial reactivity studies show that the dibora[2]ferrocenophane is prone to boron-boron double bond cleavage reactions.
Herein, we describe the selective formation of a stable neutral spiroborate radical by one-electron oxidation of the corresponding tetraorganoborate salt Li[B(C\(_4\)Ph\(_4\))\(_2\)], formally containing a tetrahedral borate centre and a s-cis-butadiene radical cation as the spin-bearing site. Spectroscopic and computational methods have been used to determine the spin distribution and the chromism observed in the solid state.
Feasibility Study on a Microwave-Based Sensor for Measuring Hydration Level Using Human Skin Models
(2016)
Tissue dehydration results in three major types of exsiccosis—hyper-, hypo-, or isonatraemia. All three types entail alterations of salt concentrations leading to impaired biochemical processes, and can finally cause severe morbidity. The aim of our study was to demonstrate the feasibility of a microwave-based sensor technology for the non-invasive measurement of the hydration status. Electromagnetic waves at high frequencies interact with molecules, especially water. Hence, if a sample contains free water molecules, this can be detected in a reflected microwave signal. To develop the sensor system, human three-dimensional skin equivalents were instituted as a standardized test platform mimicking reproducible exsiccosis scenarios. Therefore, skin equivalents with a specific hydration and density of matrix components were generated and microwave measurements were performed. Hydration-specific spectra allowed deriving the hydration state of the skin models. A further advantage of the skin equivalents was the characterization of the impact of distinct skin components on the measured signals to investigate mechanisms of signal generation. The results demonstrate the feasibility of a non-invasive microwave-based hydration sensor technology. The sensor bears potential to be integrated in a wearable medical device for personal health monitoring.
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.
Whole Genome Duplications Shaped the Receptor Tyrosine Kinase Repertoire of Jawed Vertebrates
(2016)
The receptor tyrosine kinase (RTK) gene family, involved primarily in cell growth and differentiation, comprises proteins with a common enzymatic tyrosine kinase intracellular domain adjacent to a transmembrane region. The amino-terminal portion of RTKs is extracellular and made of different domains, the combination of which characterizes each of the 20 RTK subfamilies among mammals. We analyzed a total of 7,376 RTK sequences among 143 vertebrate species to provide here the first comprehensive census of the jawed vertebrate repertoire. We ascertained the 58 genes previously described in the human and mouse genomes and established their phylogenetic relationships. We also identified five additional RTKs amounting to a total of 63 genes in jawed vertebrates. We found that the vertebrate RTK gene family has been shaped by the two successive rounds of whole genome duplications (WGD) called 1R and 2R (1R/2R) that occurred at the base of the vertebrates. In addition, the Vegfr and Ephrin receptor subfamilies were expanded by single gene duplications. In teleost fish, 23 additional RTK genes have been retained after another expansion through the fish-specific third round (3R) of WGD. Several lineage-specific gene losses were observed. For instance, birds have lost three RTKs, and different genes are missing in several fish sublineages. The RTK gene family presents an unusual high gene retention rate from the vertebrate WGDs (58.75% after 1R/2R, 64.4% after 3R), resulting in an expansion that might be correlated with the evolution of complexity of vertebrate cellular communication and intracellular signaling.
A site specific perturbation of a photo-excited molecular aggregate can lead to a localization of excitonic energy. We investigate this localization dynamics for laser-prepared excited states. Changing the parameters of the electric field significantly influences the exciton localization which offers the possibility for a selective control of this process. This is demonstrated for aggregates possessing a single vibrational degree of freedom per monomer unit. It is shown that the effects identified for the molecular dimer can be generalized to larger aggregates with a high density of vibronic states.
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).
Over the last 20 years, there has been increasing focus on the development of novel stem cell based therapies for the treatment of disorders and diseases affecting the enteric nervous system (ENS) of the gastrointestinal tract (so-called enteric neuropathies). Here, the idea is that ENS progenitor/stem cells could be transplanted into the gut wall to replace the damaged or absent neurons and glia of the ENS. This White Paper sets out experts' views on the commonly used methods and approaches to identify, isolate, purify, expand and optimize ENS stem cells, transplant them into the bowel, and assess transplant success, including restoration of gut function. We also highlight obstacles that must be overcome in order to progress from successful preclinical studies in animal models to ENS stem cell therapies in the clinic.
Limited comprehension of aneurysm pathology has led to inconclusive results from clinical trials. miRNAs are key regulators of post-translational gene modification and are useful tools in elucidating key features of aneurysm pathogenesis in distinct entities of abdominal and popliteal aneurysms. Here, surgically harvested specimens from 19 abdominal aortic aneurysm (AAA) and 8 popliteal artery aneurysm (PAA) patients were analyzed for miRNA expression and histologically classified regarding extracellular matrix (ECM) remodeling and inflammation. DIANA-based computational target prediction and pathway enrichment analysis verified our results, as well as previous ones. miRNA-362, -19b-1, -194, -769, -21 and -550 were significantly down-regulated in AAA samples depending on degree of inflammation. Similar or inverse regulation was found for miR-769, 19b-1 and miR-550, -21, whereas miR-194 and -362 were unaltered in PAA. In situ hybridization verified higher expression of miR-550 and -21 in PAA compared to AAA and computational analysis for target genes and pathway enrichment affirmed signal transduction, cell-cell-interaction and cell degradation pathways, in line with previous results. Despite the vague role of miRNAs for potential diagnostic and treatment purposes, the number of candidates from tissue signature studies is increasing. Tissue morphology influences subsequent research, yet comparison of distinct entities of aneurysm disease can unravel core pathways.
Background
The vascular type represents a very rare, yet the clinically most fatal entity of Ehlers-Danlos syndrome (EDS). Patients are often admitted due to arterial bleedings and the friable tissue and the altered coagulation contribute to the challenge in treatment strategies. Until now there is little information about clotting characteristics that might influence hemostasis decisively and eventually worsen emergency situations.
Results
22 vascular type EDS patients were studied for hemoglobin, platelet volume and count, Quick and activated partial thromboplastin time, fibrinogen, factor XIII, von Willebrand disease, vitamin D and platelet aggregation by modern standard laboratory methods. Results show a high prevalence of over 50 % for platelet aggregation disorders in vascular type EDS patients, especially for collagen and epinephrine induced tests, whereas the plasmatic cascade did not show any alterations. Additionally, more than half of the tested subjects showed low vitamin D serum levels, which might additionally affect vascular wall integrity.
Conclusion
The presented data underline the importance of detailed laboratory screening methods in vascular type EDS patients in order to allow for targeted application of platelet-interacting substances that might be of decisive benefit in the emergency setting.
Background
Diabetes mellitus (DM) is the leading cause of end-stage renal disease. Little is known about practice patterns of anti-diabetic therapy in the presence of chronic kidney disease (CKD) and correlates with glycaemic control. We therefore aimed to analyze current antidiabetic treatment and correlates of metabolic control in a large contemporary prospective cohort of patients with diabetes and CKD.
Methods
The German Chronic Kidney Disease (GCKD) study enrolled 5217 patients aged 18–74 years with an estimated glomerular filtration rate (eGFR) between 30–60 mL/min/1.73 m2 or proteinuria >0.5 g/d. The use of diet prescription, oral anti-diabetic medication, and insulin was assessed at baseline. HbA1c, measured centrally, was the main outcome measure.
Results
At baseline, DM was present in 1842 patients (35 %) and the median HbA1C was 7.0 % (25th–75th percentile: 6.8–7.9 %), equalling 53 mmol/mol (51, 63); 24.2 % of patients received dietary treatment only, 25.5 % oral antidiabetic drugs but not insulin, 8.4 % oral antidiabetic drugs with insulin, and 41.8 % insulin alone. Metformin was used by 18.8 %. Factors associated with an HbA1C level >7.0 % (53 mmol/mol) were higher BMI (OR = 1.04 per increase of 1 kg/m2, 95 % CI 1.02–1.06), hemoglobin (OR = 1.11 per increase of 1 g/dL, 95 % CI 1.04–1.18), treatment with insulin alone (OR = 5.63, 95 % CI 4.26–7.45) or in combination with oral antidiabetic agents (OR = 4.23, 95 % CI 2.77–6.46) but not monotherapy with metformin, DPP-4 inhibitors, or glinides.
Conclusions
Within the GCKD cohort of patients with CKD stage 3 or overt proteinuria, antidiabetic treatment patterns were highly variable with a remarkably high proportion of more than 50 % receiving insulin-based therapies. Metabolic control was overall satisfactory, but insulin use was associated with higher HbA1C levels.
Small satellites contribute significantly in the rapidly evolving innovation in space engineering, in particular in distributed space systems for global Earth observation and communication services. Significant mass reduction by miniaturization, increased utilization of commercial high-tech components, and in particular standardization are the key drivers for modern miniature space technology.
This thesis addresses key fields in research and development on miniature satellite technology regarding efficiency, flexibility, and robustness. Here, these challenges are addressed by the University of Wuerzburg’s advanced pico-satellite bus, realizing a generic modular satellite architecture and standardized interfaces for all subsystems. The modular platform ensures reusability, scalability, and increased testability due to its flexible subsystem interface which allows efficient and compact integration of the entire satellite in a plug-and-play manner.
Beside systematic design for testability, a high degree of operational robustness is achieved by the consequent implementation of redundancy of crucial subsystems. This is combined with efficient fault detection, isolation and recovery mechanisms. Thus, the UWE-3 platform, and in particular the on-board data handling system and the electrical power system, offers one of the most efficient pico-satellite architectures launched in recent years and provides a solid basis for future extensions.
The in-orbit performance results of the pico-satellite UWE-3 are presented and summarize successful operations since its launch in 2013. Several software extensions and adaptations have been uploaded to UWE-3 increasing its capabilities. Thus, a very flexible platform for in-orbit software experiments and for evaluations of innovative concepts was provided and tested.
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 animal diet of the carnivorous Venus flytrap, Dionaea muscipula, contains a sodium load that enters the capture organ via an HKT1-type sodium channel, expressed in special epithelia cells on the inner trap lobe surface. DmHKT1 expression and sodium uptake activity is induced upon prey contact. Here, we analyzed the HKT1 properties required for prey sodium osmolyte management of carnivorous Dionaea. Analyses were based on homology modeling, generation of model-derived point mutants, and their functional testing in Xenopus oocytes. We showed that the wild-type HKT1 and its Na\(^+\)- and K\(^+\)-permeable mutants function as ion channels rather than K\(^+\) transporters driven by proton or sodium gradients. These structural and biophysical features of a high-capacity, Na\(^+\)-selective ion channel enable Dionaea glands to manage prey-derived sodium loads without confounding the action potential-based information management of the flytrap.
The Venus Flytrap Dionaea muscipula Counts Prey-Induced Action Potentials to Induce Sodium Uptake
(2016)
Carnivorous plants, such as the Venus flytrap (Dionaea muscipula), depend on an animal diet when grown in nutrient-poor soils. When an insect visits the trap and tilts the mechanosensors on the inner surface, action potentials (APs) are fired. After a moving object elicits two APs, the trap snaps shut, encaging the victim. Panicking preys repeatedly touch the trigger hairs over the subsequent hours, leading to a hermetically closed trap, which via the gland-based endocrine system is flooded by a prey-decomposing acidic enzyme cocktail. Here, we asked the question as to how many times trigger hairs have to be stimulated (e.g., now many APs are required) for the flytrap to recognize an encaged object as potential food, thus making it worthwhile activating the glands. By applying a series of trigger-hair stimulations, we found that the touch hormone jasmonic acid (JA) signaling pathway is activated after the second stimulus, while more than three APs are required to trigger an expression of genes encoding prey-degrading hydrolases, and that this expression is proportional to the number of mechanical stimulations. A decomposing animal contains a sodium load, and we have found that these sodium ions enter the capture organ via glands. We identified a flytrap sodium channel DmHKT1 as responsible for this sodium acquisition, with the number of transcripts expressed being dependent on the number of mechano-electric stimulations. Hence, the number of APs a victim triggers while trying to break out of the trap identifies the moving prey as a struggling Na+-rich animal and nutrition for the plant.
The Venus flytrap Dionaea muscipula counts prey-induced action potentials to induce sodium uptake
(2016)
Carnivorous plants, such as the Venus flytrap (Dionaea muscipula), depend on an animal diet when grown in nutrient-poor soils. When an insect visits the trap and tilts the mechanosensors on the inner surface, action potentials (APs) are fired. After a moving object elicits two APs, the trap snaps shut, encaging the victim. Panicking preys repeatedly touch the trigger hairs over the subsequent hours, leading to a hermetically closed trap, which via the gland-based endocrine system is flooded by a prey-decomposing acidic enzyme cocktail. Here, we asked the question as to how many times trigger hairs have to be stimulated (e.g., now many APs are required) for the flytrap to recognize an encaged object as potential food, thus making it worthwhile activating the glands. By applying a series of trigger-hair stimulations, we found that the touch hormone jasmonic acid (JA) signaling pathway is activated after the second stimulus, while more than three APs are required to trigger an expression of genes encoding prey-degrading hydrolases, and that this expression is proportional to the number of mechanical stimulations. A decomposing animal contains a sodium load, and we have found that these sodium ions enter the capture organ via glands. We identified a flytrap sodium channel DmHKT1 as responsible for this sodium acquisition, with the number of transcripts expressed being dependent on the number of mechano-electric stimulations. Hence, the number of APs a victim triggers while trying to break out of the trap identifies the moving prey as a struggling Na\(^+\)-rich animal and nutrition for the plant.
Enterovirus D68 (EV-D68) has been recognised as a worldwide emerging pathogen associated with severe respiratory symptoms since 2009. We here report EV-D68 detection in hospitalised patients with acute respiratory infection admitted to three tertiary hospitals in Germany between January 2013 and December 2014. From a total of 14,838 respiratory samples obtained during the study period, 246 (1.7%) tested enterovirus-positive and, among these, 39 (15.9%) were identified as EV-D68. Infection was observed in children and teenagers (0–19 years; n=31), the majority (n=22) being under five years-old, as well as in adults > 50 years of age (n=8). No significant difference in prevalence was observed between the 2013 and 2014 seasons. Phylogenetic analyses based on viral protein 1 (VP1) sequences showed co-circulation of different EV-D68 lineages in Germany. Sequence data encompassing the entire capsid region of the genome were analysed to gain information on amino acid changes possibly relevant for immunogenicity and revealed mutations in two recently described pleconaril binding sites.
This paper concerns the an intelligent mobile application for spatial design support and security domain. Mobility has two aspects in our research: The first one is the usage of mobile robots for 3D mapping of urban areas and for performing some specific tasks. The second mobility aspect is related with a novel Software as a Service system that allows access to robotic functionalities and data over the Ethernet, thus we demonstrate the use of the novel NVIDIA GRID technology allowing to virtualize the graphic processing unit. We introduce Complex Shape Histogram, a core component of our artificial intelligence engine, used for classifying 3D point clouds with a Support Vector Machine. We use Complex Shape Histograms also for loop closing detection in the simultaneous localization and mapping algorithm. Our intelligent mobile system is built on top of the Qualitative Spatio-Temporal Representation and Reasoning framework. This framework defines an ontology and a semantic model, which are used for building the intelligent mobile user interfaces. We show experiments demonstrating advantages of our approach. In addition, we test our prototypes in the field after the end-user case studies demonstrating a relevant contribution for future intelligent mobile systems that merge mobile robots with novel data centers.
Background: The trophic, anti-apoptotic and regenerative effects of bone marrow mesenchymal stromal cells (MSC) may reduce neuronal cell loss in neurodegenerative disorders.
Methods: We used MSC as a novel candidate therapeutic tool in a pilot phase-I study for patients affected by progressive supranuclear palsy (PSP), a rare, severe and no-option form of Parkinsonism. Five patients received the cells by infusion into the cerebral arteries. Effects were assessed using the best available motor function rating scales (UPDRS, Hoehn and Yahr, PSP rating scale), as well as neuropsychological assessments, gait analysis and brain imaging before and after cell administration.
Results: One year after cell infusion, all treated patients were alive, except one, who died 9 months after the infusion for reasons not related to cell administration or to disease progression (accidental fall). In all treated patients motor function rating scales remained stable for at least six-months during the one-year follow-up.
Conclusions: We have demonstrated for the first time that MSC administration is feasible in subjects with PSP. In these patients, in whom deterioration of motor function is invariably rapid, we recorded clinical stabilization for at least 6 months. These encouraging results pave the way to the next randomized, placebo-controlled phase-II study that will definitively provide information on the efficacy of this innovative approach.
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.
Mushroom body defect is required in parallel to Netrin for midline axon guidance in Drosophila
(2016)
The outgrowth of many neurons within the central nervous system is initially directed towards or away from the cells lying at the midline. Recent genetic evidence suggests that a simple model of differential sensitivity to the conserved Netrin attractants and Slit repellents is insufficient to explain the guidance of all axons at the midline. In the Drosophila embryonic ventral nerve cord, many axons still cross the midline in the absence of the Netrin genes (NetA and NetB) or their receptor frazzled. Here we show that mutation of mushroom body defect (mud) dramatically enhances the phenotype of Netrin or frazzled mutants, resulting in many more axons failing to cross the midline, although mutations in mud alone have little effect. This suggests that mud, which encodes a microtubule-binding coiled-coil protein homologous to NuMA and LIN-5, is an essential component of a Netrin-independent pathway that acts in parallel to promote midline crossing. We demonstrate that this novel role of Mud in axon guidance is independent of its previously described role in neural precursor development. These studies identify a parallel pathway controlling midline guidance in Drosophila and highlight a novel role for Mud potentially acting downstream of Frizzled to aid axon guidance.
The linear and nonlinear optical properties of a series of oligomeric squaraine dyes were investigated by one-photon absorption spectroscopy (1PA) and two-photon absorption (2PA) induced fluorescence spectroscopy. The superchromophores are based on two indolenine squaraine dyes with transoid (SQA) and cisoid configuration (SQB). Using these monomers, linear dimers and trimers as well as star-shaped trimers and hexamers with benzene or triphenylamine cores were synthesised and investigated. The red-shifted and intensified 1PA spectra of all superchromophores could well be explained by exciton coupling theory. In the linear chromophore arrangements we also found superradiance of fluorescence but not in the branched systems. Furthermore, the 2PA showed enhanced cross sections for the linear oligomers but only additivity for the branched systems. This emphasizes that the enhancement of the 2PA cross section in the linear arrangements is probably caused by orbital interactions of higher excited configurations.