Refine
Year of publication
- 2019 (627) (remove)
Document Type
- Journal article (418)
- Doctoral Thesis (163)
- Book article / Book chapter (23)
- Preprint (19)
- Conference Proceeding (1)
- Other (1)
- Report (1)
- Working Paper (1)
Language
- English (627) (remove)
Keywords
- Animal Studies (24)
- Cultural Animal Studies (24)
- Cultural Studies (24)
- Ecocriticism (24)
- Environmental Humanities (24)
- Human-Animal Studies (24)
- Literary Studies (24)
- boron (11)
- apoptosis (8)
- Tissue Engineering (6)
- inflammation (6)
- ischemic stroke (6)
- measles virus (5)
- DNA methylation (4)
- Drosophila melanogaster (4)
- Hydrogel (4)
- Maschinelles Lernen (4)
- Neisseria meningitidis (4)
- Spektroskopie (4)
- Taufliege (4)
- children (4)
- deep brain stimulation (4)
- infection (4)
- multiple myeloma (4)
- sphingolipids (4)
- tissue engineering (4)
- virtual reality (4)
- Übergangsmetalloxide (4)
- 3D tissue model (3)
- 3D-Druck (3)
- Ancistrocladaceae (3)
- Candida albicans (3)
- Chronobiologie (3)
- Elektrophysiologie (3)
- Exziton (3)
- Fluoreszenzmikroskopie (3)
- GABA (3)
- Genexpression (3)
- Leistungsbewertung (3)
- Maus (3)
- Megakaryozyt (3)
- Meningitis (3)
- Monte-Carlo (3)
- Physics (3)
- Raman-Spektroskopie (3)
- Schlaganfall (3)
- Serotonin (3)
- Soziale Wahrnehmung (3)
- Staphylococcus aureus (3)
- Survival (3)
- Ureaplasma parvum (3)
- Ureaplasma urealyticum (3)
- aging (3)
- blood–brain barrier (3)
- boranes (3)
- cancer (3)
- cancer therapy (3)
- climate change (3)
- colorectal cancer (3)
- cytokines (3)
- cytotoxicity (3)
- death receptors (3)
- epigenetics (3)
- gephyrin (3)
- in vitro (3)
- length of stenosis (3)
- leukemic cells (3)
- lysosome (3)
- machine learning (3)
- metagenomics (3)
- microbiome (3)
- p53 (3)
- presence (3)
- remote sensing (3)
- stem cells (3)
- ubiquitin (3)
- 2Dimensionale Spektroskopie (2)
- 3D (2)
- 3D printing (2)
- AdS/CFT (2)
- Aggregation (2)
- Angst (2)
- Annotation (2)
- Anxiety (2)
- Aufmerksamkeit (2)
- B-MYB (2)
- Bees (2)
- Bilanzpolitik (2)
- Bildverarbeitung (2)
- Bioinformatik (2)
- Biomaterial (2)
- Biomedical engineering (2)
- Blutgerinnung (2)
- C-reactive protein (2)
- CXCR4 (2)
- Cancer (2)
- Channelrhodopsin (2)
- Chlamydia trachomatis (2)
- Colonization (2)
- Constraints (2)
- Cross-Section (2)
- Cryo-EM (2)
- DNA damage (2)
- Decay (2)
- Deutschland (2)
- Drosophila (2)
- EEA (2)
- Ecology (2)
- Exercise capacity (2)
- Expression (2)
- FKBP5 (2)
- GABAA receptors (2)
- Gedächtnis (2)
- HBMEC (2)
- HBV (2)
- HIV (2)
- Hadron colliders (2)
- Halbleiter (2)
- HeLa cells (2)
- Imaging techniques (2)
- Impact (2)
- Implantat (2)
- In vitro (2)
- Inhibitor (2)
- KDELR2 (2)
- Kernspintomografie (2)
- Knochenzement (2)
- Kognition (2)
- Lungenkrebs (2)
- MSC (2)
- Machine Learning (2)
- Melanoma (2)
- Merocyanine (2)
- Metabolomics (2)
- Metadynamics (2)
- Methylation (2)
- Mitose (2)
- Molekulargenetik (2)
- Muscarinrezeptor (2)
- NHC (2)
- Naphthylisochinolinalkaloide (2)
- Neurons (2)
- Optimierung (2)
- Optogenetik (2)
- PIP2 (2)
- Pair Production (2)
- Parton Distributions (2)
- Parton distributions (2)
- Perylenderivate (2)
- Pontryagin maximum principle (2)
- Positronen-Emissions-Tomografie (2)
- Quanten-Vielteilchensysteme (2)
- Quantum Information (2)
- Quantum many-body systems (2)
- RNA-seq (2)
- Radiative-corrections (2)
- Reduction (2)
- Regenerative Medizin (2)
- Röntgen-Photoelektronenspektroskopie (2)
- S-ADAPT (2)
- SQH method (2)
- Screening (2)
- Selbstorganisation (2)
- Sentinel-1 (2)
- Signaltransduktion (2)
- Simulation (2)
- Solution-state NMR (2)
- Stem cells (2)
- Supramolekulare Chemie (2)
- TNF receptor superfamily (2)
- TNF superfamily (2)
- TNFR1 (2)
- TRAIL (2)
- Tanzania (2)
- Telekommunikationsnetz (2)
- Thrombozyt (2)
- Top-Quark (2)
- VEGF (2)
- Vaskularisierung (2)
- Verhalten (2)
- Zellteilung (2)
- adolescents (2)
- allometric scaling (2)
- antibiotics (2)
- antibody (2)
- antibody fusion proteins (2)
- artemisinin (2)
- bacteria (2)
- biofabrication (2)
- blood-brain barrier (2)
- body composition (2)
- body size (2)
- bone (2)
- bone adhesive (2)
- cAArC (2)
- calcium phosphate cement (2)
- cardiomyopathy (2)
- carotid atherosclerosis (2)
- carotid stenosis (2)
- carotid ultrasound (2)
- caspase-8 (2)
- cell death (2)
- cell imaging (2)
- cell therapy (2)
- chemistry (2)
- complexes (2)
- copper (2)
- cystic fibrosis patients (2)
- dSTORM (2)
- degree of stenosis (2)
- dendritic cells (2)
- density functional calculations (2)
- depression (2)
- diazepam (2)
- dopamine (2)
- drug delivery (2)
- ecology (2)
- endothelium (2)
- evolution (2)
- exciton-exciton (2)
- fluorescence (2)
- genetics (2)
- genome annotation (2)
- genome assembly (2)
- geomorphology (2)
- glioblastoma multiforme (2)
- glucocorticoid receptor (2)
- healthy volunteers (2)
- hydroboration (2)
- hydrogel (2)
- immunotherapy (2)
- information extraction (2)
- inhibitory neurotransmission (2)
- interleukin-8 (2)
- irradiation (2)
- knockout (2)
- macrophages (2)
- magnetic resonance imaging (2)
- measurement (2)
- megakaryopoiesis (2)
- melt electrospinning writing (2)
- meningitis (2)
- mental health (2)
- mesencephalic locomotor region (2)
- metabolic adaptation (2)
- migration (2)
- mitochondria (2)
- mouse (2)
- multiple bonding (2)
- multiple sclerosis (2)
- natural language processing (2)
- neuroinflammation (2)
- neurology (2)
- neuroprotection (2)
- next generation sequencing (2)
- oncolytic virus (2)
- optimal drug combination (2)
- optogenetics (2)
- outcome (2)
- performance (2)
- photothrombotic stroke (2)
- platelets (2)
- polycyclic aromatic hydrocarbons (2)
- polymers (2)
- population pharmacokinetics (2)
- prostate cancer (2)
- radicals (2)
- reactive oxygen species (2)
- recurrence (2)
- relapse (2)
- rheumatoid arthritis (2)
- ring-expansion reaction (2)
- screening (2)
- secondary prevention (2)
- smartphone app (2)
- social attention (2)
- stroke (2)
- structure (2)
- subthalamic nucleus (2)
- surgery (2)
- survival (2)
- synthesis (2)
- targeted therapy (2)
- tight junction (2)
- trade-offs (2)
- two-photon excited fluorescence (2)
- wound healing (2)
- (classical and atypical) Werner syndrome (1)
- (hem)ITAM signaling (1)
- + (1)
- ++ (1)
- 1,2-additions (1)
- 18F-FDS (1)
- 2 Jets (1)
- 2-deoxy-2-18F-fluoro-D-sorbitol (1)
- 25-hydroxycholesterol 7 alpha-hydroxylase (1)
- 2D material (1)
- 3-coordinate organoboron compounds (1)
- 3D Bioprinting (1)
- 3D Modell (1)
- 3D Point Cloud Processing (1)
- 3D Tumormodell (1)
- 3D cultures (1)
- 3D model (1)
- 3D remote sensing (1)
- 3D tumour model (1)
- 3D-Modell (1)
- 3 T (1)
- 4-HNE (1)
- 4D flow (1)
- 68Ga-DOTANOC (1)
- 68Ga-DOTATATE (1)
- 68Ga-DOTATOC (1)
- A-D-A dyes (1)
- A-priori-Wissen (1)
- A. abbreviatus (1)
- A. likoko (1)
- ABP1 (1)
- ADHD (1)
- AHRR (1)
- ALAN (1)
- AMP-activated kinases (1)
- AMP‐activated protein kinase (1)
- APOBEC3G (1)
- APRI (1)
- ARCI (1)
- ARCI EM type III (1)
- ATP generation (1)
- AUX1 (1)
- Abfallbehandlung (1)
- Abfallwirtschaft (1)
- Absorbed Doses (1)
- Abszision (1)
- Accurate (1)
- Acids (1)
- Ackerschmalwand (1)
- Actin (1)
- Actin-bindende Proteine (1)
- Activation (1)
- Active Galactic Nuclei (1)
- Active disease (1)
- Acute myeloid leukemia (AML) (1)
- AdS-CFT Correspondence (1)
- AdS-CFT-Korrespondenz (1)
- AdS/CFT correspondence (1)
- Adaptation (1)
- Adherens junction (1)
- Adhesion GPCR (1)
- Adipositas (1)
- Administered Activities (1)
- Adolescent (1)
- Adult (1)
- Advanced Analytics (1)
- Affekt (1)
- African Trypanosomiasis (1)
- Akt (1)
- Akt/PKB (1)
- Aktionsforschung (1)
- Alcohol dependence (1)
- Algorithm (1)
- Alkaloid (1)
- Allogeneic transplantation (1)
- Alpine habitats (1)
- Alzheimer's disease (1)
- Aminerge Nervenzelle (1)
- Amygdala (1)
- Andalusian varieties (1)
- Angiogenese (1)
- Angstverarbeitung (1)
- Animales Nervensystem (1)
- Anisotropic Magnetoresistance (1)
- Anomalous magnetic-moment (1)
- Anreize (1)
- Antarctica (1)
- Anthropocene (1)
- Anti-infective (1)
- Antibiotikum (1)
- Antigen CD19 (1)
- Antigen CD28 (1)
- Antigenrezeptor (1)
- Antikörper (1)
- Antimalariamittel (1)
- Antioxidants (1)
- Antizipation (1)
- Aortic arch (1)
- Apidae (1)
- Apis mellifera (1)
- Aplastic anemia (1)
- Apoptosis (1)
- Applied physics (1)
- Arabidopsis thaliana (1)
- Arbeitsmobilität (1)
- Archaeology (1)
- Aromatically annulated triquinacenes (1)
- Aromatisch anellierte Triquinacene (1)
- Arylborylene Complexes (1)
- Arzneimittel (1)
- Ascaris lumbricoides (1)
- Aspergillus (1)
- Aspergillus fumigalus (1)
- Assistenzbedarf (1)
- Associative learning (1)
- Astronomie (1)
- Astrophysical neutrino sources (1)
- Astroteilchenphysik (1)
- Atacama (1)
- Atmospheric muons (1)
- Atomic and molecular interactions with photons (1)
- Atrial fibrillation (1)
- Attitude Determination and Control (1)
- Attitude Dynamics (1)
- Audit Quality (1)
- Audit sampling (1)
- Aufsichtsrat (1)
- Autoaggressionskrankheit (1)
- Autologous hematopoietic stem cell transplantation (1)
- Autoproteolysis (1)
- Auxine (1)
- Außenhandel (1)
- B cell malignancies (1)
- B cells (1)
- B,N-heterocylcles (1)
- B-B bond activation (1)
- B7-H1 (1)
- BAL (1)
- BCG (1)
- BMI (1)
- BRAF mutation (1)
- BRAF-mutant (1)
- BRAF-mutiert (1)
- BRCA1 (1)
- BaBiO3 (1)
- Bank (1)
- Banking (1)
- Barrier (1)
- Behaviour (1)
- Behavioural ecology (1)
- Benchmarking (1)
- Benutzeroberfläche (1)
- Benzimidazole (1)
- Berberine (1)
- Berechnung (1)
- Berufsbildung (1)
- Bevacizumab (1)
- Bhabha Scattering (1)
- Big Data (1)
- Bildbearbeitung (1)
- Bildgebung intakten Knochens (1)
- Bildungswesen (1)
- Binge drinking (1)
- Biofabrication (1)
- Biofabrikation (1)
- Biofilm (1)
- Biofilmarchitektur (1)
- Bioink (1)
- Biokinetics (1)
- Biologika (1)
- Biomarke (1)
- Biomedicine (1)
- Biophysics (1)
- Bioreaktor (1)
- Biotinten (1)
- Bioverfügbarkeit (1)
- Bipolar disorder (1)
- Biradikal (1)
- Bistability (1)
- Black Holes in String Theory (1)
- Black holes (1)
- Black-hole (1)
- Blazar (1)
- Blood (1)
- Body schema (1)
- Boson (1)
- Bosons (1)
- Brain cancer (1)
- Brain diseases (1)
- Brain endothelial cells (1)
- Branching fractions (1)
- Bronchopulmonary dysplasia (1)
- Brustkrebs (1)
- Business Process Management (1)
- Business Process Modeling (1)
- By-Light Scattering (1)
- B−H activation (1)
- C-60 fullerene (1)
- C-C coupling (1)
- C/EBP (1)
- C3a (1)
- C3aR (1)
- C5a (1)
- C5aR1 (1)
- C5aR2 (1)
- C60 fullerene (1)
- CAR T cells (1)
- CCI (1)
- CD274 (1)
- CD4+ T cells (1)
- CD8+ T cells (1)
- CD95 (1)
- CDC42 (1)
- CERN (1)
- CIDP (1)
- CMV (1)
- CO sensing (1)
- CO‐releasing molecules (CORMs) (1)
- CRH1 (1)
- CRMO (1)
- CXCL5 (1)
- CXCL8 (1)
- CXCR2 (1)
- CYP1B1 (1)
- C\(_{60}\) fullerene (1)
- Cadherine (1)
- Caenorhabditis elegans (1)
- Calcium (1)
- Calciumphosphat (1)
- Calciumphosphate (1)
- Calciumphosphatzemente (1)
- Callyspongia siphonella (1)
- Cancer Cell (1)
- Cancer genetics (1)
- Capicua transcriptional repressor (1)
- Capillary Electrophoresis (1)
- Cardiac ventricles (1)
- Cardiovascular diseases (1)
- Cardiovascular risk factors (1)
- Cardiovascular risk prediction (1)
- Carotid intima-media thickness (CIMT) (1)
- Carotid segment (1)
- Carotid ultrasound (1)
- Carotisstenose (1)
- Caspase (1)
- Cataglyphis (1)
- Cdh13 (1)
- Cell migration (1)
- Cell stainin (1)
- Central Asia (1)
- Central nervous system (1)
- Ceramic polymer composite (1)
- Chambers (1)
- Channelrhodopsin-2 (1)
- Characterization and analytical techniques (1)
- Charge carrier recombination (1)
- Charge-transfer-Komplexe (1)
- Chelatbildner (1)
- Chemical Structure (1)
- Chemical composition (1)
- Chemical stability (1)
- Chemische Synthese (1)
- Cherenkov underwater neutrino telescope (1)
- Children (1)
- Chile (1)
- Chili RNA Aptamer (1)
- Chimeric Antigen Receptor (1)
- Chimärer Antigenrezeptor (1)
- China (1)
- Chiral spin liquids (1)
- Chirale Spinflússigkeiten (1)
- Choice Behavior/physiology (1)
- Chondrogenesis (1)
- Chromatographie (1)
- Chronische Nierenerkrankung (1)
- Chronobiology (1)
- Circinella (1)
- Circular dichroism (1)
- Click Chemie (1)
- Clinical Data Warehouse (1)
- Clinically silent stroke (1)
- CoQ10 (1)
- Code Examples (1)
- Codon (1)
- Cognitive behavior (1)
- Cognitive neuroscience (1)
- Coherent Multidimensional Spectroscopy (1)
- Community-acquired methicillin-resistant Staphylococcus aureus (1)
- Commuting (1)
- Complexity (1)
- Computational Chemistry (1)
- Computational and Systems Biology (1)
- Computed axial tomography (1)
- Computer modelling (1)
- Computersimulation (1)
- Conditioning regimen (1)
- Confidence intervals (1)
- Confocal microscopy (1)
- Conformal Metrics (1)
- Congolese Ancistrocladus plants (1)
- Conical Intersections (1)
- Conifers (1)
- Conservation (1)
- Consistent partial least squares (1)
- Construct Modeling (1)
- Controlling (1)
- Corporate Governance (1)
- Corporate Social Responsibility (1)
- Correlated Electron Materials (1)
- Correlated Fermions (1)
- Corticosteroids (1)
- Cosmic-rays (1)
- Couplings (1)
- CpG (1)
- Cranial sutures (1)
- Cross-section (1)
- Curvature Equation (1)
- Cushing-Syndrom (1)
- Cushing’s disease (1)
- Cutaneous lymphoma (1)
- Cysteinproteasen (1)
- Cystic fibrosis (1)
- Cytochrome P 450 pathway (1)
- Cytokine (1)
- Cytologie (1)
- Cytosol (1)
- DC gate (1)
- DCAF17 (1)
- DEM (1)
- DFT mechanism (1)
- DLS and AFM measurements (1)
- DNA electronic transport (1)
- DNA methyltransferases (1)
- DNA repair (1)
- DNA weight (1)
- DNA-Schäden (1)
- DNA-repair (1)
- DNA-repair genes (1)
- DPP IV (1)
- DRG (1)
- DROSHA (1)
- DSB focus substructure (1)
- DSM (1)
- Dark-Matter (1)
- Dark-matter (1)
- Data Analytics (1)
- Data Warehouse (1)
- Data acquisition (1)
- Data-Warehouse-Konzept (1)
- Decision Support (1)
- Declarative Performance Engineering (1)
- Deep Inelastic-scattering (1)
- Delbruck Scattering (1)
- Demokratische Republik Kongo (1)
- Dendritic cell (1)
- Dendritische Zelle (1)
- Densovirus (1)
- Dental Phobia (1)
- Depression (1)
- Design (1)
- Development (1)
- Developmental biology (1)
- Dezellularisierung (1)
- Diabetes mellitus (1)
- Diagnostic Imaging Exams (1)
- Diagnostic medicine (1)
- Dickdarmtumor (1)
- Diffusion tensor imaging (1)
- Dihydroboranes (1)
- Disease severity (1)
- Dopamin (1)
- Dopamine (1)
- Dosimetry (1)
- Dosis (1)
- Dotierung (1)
- Double-Beta Decay (1)
- Doxorubicin (1)
- Drug delivery platforms (1)
- Drug discovery (1)
- Drug resistance (1)
- Drug testing (1)
- Dual setting system (1)
- Dynamical Systems (1)
- Dynamical system (1)
- Dynamics (1)
- Dünne Schicht (1)
- Dünnschichten (1)
- E(+)E(-) collicions (1)
- E-Learning (1)
- E2 conjugating enzyme (1)
- E3 ligating enzyme (1)
- E8 symmetry (1)
- ER-Stress (1)
- ERK (1)
- ERK signaling (1)
- ERK1/2 (1)
- ESAT‐6‐like secretion system (1)
- ESS (1)
- EUROASPIRE (1)
- EWAS (1)
- Earnings Management (1)
- Earnings Quality (1)
- Earnings management (1)
- Earth observation (1)
- Echinococcosis (1)
- Echinococcus (1)
- Efficiency (1)
- Efficiency Gains (1)
- Effizienzsteigerung (1)
- Efflux transport (1)
- Eierstockkrebs (1)
- Eigenvectors (1)
- Einkommensverteilung (1)
- Einwandige Kohlenstoff-Nanoröhre (1)
- Einzelmolekülmikroskopie (1)
- Elderly (1)
- Electrical impedance tomography (1)
- Electromagnetic signals (1)
- Electromagnon (1)
- Electron (1)
- Electrophysiology (1)
- Electrospinning (1)
- Electroweak Measurements (1)
- Electroweak Phase-Transition (1)
- Electroweak interaction (1)
- Elektrizitätsverbrauch (1)
- Elektromagnon (1)
- Elektron-Phonon-Wechselwirkung (1)
- Elektronentransfer (1)
- Elektrospinnen (1)
- Elissen-Palm flux (1)
- Embryonic induction (1)
- Embryos (1)
- Emergence (1)
- Emotionales Verhalten (1)
- Empirical Analysis (1)
- Enantiomerentrennung (1)
- Endogene Rhythmik (1)
- Endoplasmic-Reticulum Stress (1)
- Endothel (1)
- Energieeffizienz (1)
- Energy (1)
- Energy Efficiency (1)
- Enhancer elements (1)
- Entanglement (1)
- Entscheidungsunterstützung (1)
- Entscheidungsunterstützungssystem (1)
- Entwicklung (1)
- Entzündung (1)
- Environmental impact (1)
- Epidemiology (1)
- Epigenetic (1)
- Epigenetic regulation (1)
- Epitaxy (1)
- Epstein-Barr virus-induced gene 2 (1)
- Equipment (1)
- Erfolgsplanung (1)
- EsaA (1)
- Escherichia coli (1)
- European Organization for Nuclear Research. ATLAS Collaboration (1)
- European Spanish (1)
- European group (1)
- Event builder (1)
- Events GW150914 (1)
- Evolutionary developmental biology (1)
- Evolutionary emergence (1)
- Excited state dynamics (1)
- Exciton (1)
- Exciton coupling (1)
- Exciton localization dynamics (1)
- Exercise testing (1)
- Experimental Studies (1)
- Experimentelle Psychologie (1)
- Expiry date (1)
- Explosives (1)
- Explosivstoff (1)
- Extensions of gauge sector (1)
- Extracellular matrix (1)
- Extracellular volume (1)
- Extramedullary disease (1)
- Extrazelluläre Matrix (1)
- Extreme flows (1)
- Exziton-Polariton (1)
- Exzitonenkopplung (1)
- Eye Movements/physiology (1)
- Eye development (1)
- FIB-4 (1)
- Face Voice Matching (1)
- Fahrerassistenzsystem (1)
- Fak regulation (1)
- Familial Beckwith-Wiedemann syndrome (1)
- Farbstoff (1)
- FasL (1)
- Fatigue (1)
- Fats (1)
- Fear Generalization (1)
- Fear Learning (1)
- Fear conditioning (1)
- Female (1)
- Fertigarzneimittel (1)
- Festkörperphysik (1)
- Fgf-signalling (1)
- Fibroblastenwachstumsfaktor (1)
- Finite support distributions (1)
- Flavor Violation (1)
- Fliegenkippen (1)
- Flowering plants (1)
- Flowers (1)
- Fludarabine (1)
- Fludarabine-treosulfan (FT) (1)
- Fluorescence spectroscopy (1)
- Fluoreszenzspektroskopie (1)
- Fluorine (1)
- Fluorverbindungen (1)
- Flüssigkristall (1)
- Forces (1)
- Forests (1)
- Fotochemie (1)
- Fotophysik (1)
- Fourier-Spektroskopie (1)
- Fractional cover analysis (1)
- Fractional quantum Hall effect (1)
- Fraktionaler Quanten-Hall-Effekt (1)
- Full body ownership illusion (1)
- Functional Connectivity (1)
- Funktionalisierung <Chemie> (1)
- Funktionalisierung von elektrogesponnenen Fasern (1)
- Funktionelle Konnektivität (1)
- Furchkonditionierung (1)
- Furcht (1)
- Furchtgeneralisierung (1)
- Fusarium (1)
- G Protein-coupled receptor (1)
- G-2 (1)
- G-Protein gekoppelte Rezeptor (1)
- G-quadruplex (1)
- GABAA (1)
- GAD1 (1)
- GRP78 (1)
- GSV (1)
- GVHD (1)
- Ga-68-labelled Peptides (1)
- Galactic sources (1)
- Gallensalze (1)
- Gas chromatography (1)
- Gaseous detectors (1)
- Gauge bosons (1)
- Gauge-gravity correspondence (1)
- Gauge/Gravity Duality (1)
- Gaussian approximation (1)
- Gelatine (1)
- Gen-Umwelt Interaktion (1)
- Gene by Environment (1)
- Gene expression analysis (1)
- Gene silencing (1)
- General anaesthesia (1)
- Generalisierung (1)
- Generalisierung <Kartografie> (1)
- Generation (1)
- Genetik (1)
- Genmutation (1)
- Genom (1)
- Genome (1)
- Genome Annotation (1)
- Genomics (1)
- Genotype (1)
- Geriatric care (1)
- Geriatrics (1)
- Germany (1)
- Germline (1)
- Gesicht (1)
- Gestational diabetes (1)
- Gestationsdiabetes (1)
- Getz Ice Shelf (1)
- Gitterdynamik (1)
- Gliazelle (1)
- Glioblastoma (1)
- Glutathione (1)
- Glycidol (1)
- Glycoengineering (1)
- Glykane (1)
- Glykosylierung (1)
- Google Earth Engine (1)
- Governance (1)
- Graft versus host disease (1)
- Graph (1)
- Gravitons (1)
- Greenland ice sheet (1)
- Grenzfläche (1)
- Grenzflächenleitfähigkeit (1)
- Group B Streptococcus (1)
- Grundlagenforschung (1)
- Gruppo-italiano (1)
- GvHD (1)
- Gyrasehemmer (1)
- H-infinity (1)
- HARPES (1)
- HCV (1)
- HDAC (1)
- HEMA (1)
- HNE (1)
- HNSCC (1)
- HPA axis (1)
- HPLC (1)
- HRQOL (1)
- Hadron-Hadron scattering (experiments) (1)
- Hadron-hadron interactions (1)
- Haemophilus influenzae (1)
- Hard X-ray Angle Resolved Photoemission (1)
- Haut (1)
- Health (1)
- Heart (1)
- Heart failure (1)
- Helicasen (1)
- Hematopoietic Stem (1)
- Hematopoietic cell transplant (1)
- Heme-regulated inhibitor (1)
- Hemipelvectomy (1)
- Herzmuskelzelle (1)
- Heterosolarzelle (1)
- Heterostruktur (1)
- Hfq (1)
- Higgy-Boson (1)
- High grade glioma (1)
- High-Energies (1)
- High-Z Oxides (1)
- High-energy astrophysics (1)
- Hindbrain (1)
- Hippo pathway (1)
- Hippocampus (1)
- Histone deacetylase (1)
- Hochauflösende Fluoreszenzmikroskopie (1)
- Hodgkin lymphoma (1)
- Holstein model (1)
- Holstein-Modell (1)
- Honey bees (1)
- Hordeum vulgare (1)
- Hormontransport (1)
- Host Genome Integrity (1)
- Host-parasite interaction (1)
- Human Body Weight (1)
- Human Herpesvirus 6 (1)
- Human Muse Cells (1)
- Human behaviour (1)
- Human-Computer Interaction (1)
- Humanes Herpesvirus 6 (1)
- Humangenetik (1)
- Humans (1)
- Hunsrueck (1)
- Hurwitz theorem (1)
- Hyaluronic Acid (1)
- Hyaluronsäure (1)
- Hybrid Dynamical Systems (1)
- Hybridsystem (1)
- Hydrocarbon radicals (1)
- Hydrocarbons (1)
- Hydrogen (1)
- Hyperosmotic Stress (1)
- Hypothalamus (1)
- Hypothetical gauge bosons (1)
- Hypoxia (1)
- Hypoxie (1)
- IFN (1)
- IL-10 (1)
- IP3 (1)
- Icecube (1)
- Ideomotor Theory (1)
- Ideomotorik (1)
- Image Processing (1)
- Imatinib (1)
- Immune system (1)
- Immune-related adverse event (1)
- Immunologe (1)
- Immunology (1)
- Immunoprecipitation (1)
- Immuntherapie (1)
- Imo Bundesstaat (1)
- Imo State - Nigeria (1)
- Impella (1)
- Implicit and explicit reward learning (1)
- InSAR (1)
- InSAR height (1)
- Incontinentia pigmenti (1)
- Individualität (1)
- Induced apoptosis (1)
- Inducible Clindamycin Resistance (1)
- Induzierte pluripotente Stammzelle (1)
- Infectious disease (1)
- Inflammatio (1)
- Inflammatory Pain (1)
- Inflammatory diseases (1)
- Inflammatory pain (1)
- Information (1)
- Information Extraction (1)
- Information System (1)
- Information seeking and sharing (1)
- Information system (1)
- Informationsverarbeitung (1)
- Inhibition (1)
- Innovation (1)
- Input-Output-Tabelle (1)
- Insect flight (1)
- Insulin (1)
- Insulin-like Growth Factor I (1)
- Insulin-like growth factor-I (1)
- Integrine (1)
- Intention (1)
- Intentional Nonaction (1)
- Intentionale Nichthandlung (1)
- Interaction Design (1)
- Interactions (1)
- Interconnection (1)
- Interface Conductivity (1)
- Interfaces (1)
- Intergenerational income mobility (1)
- Intergenerationenmobilität (1)
- Intergenerative Einkommensmobilität (1)
- Interleukin-10 (1)
- Interleukin-6 (1)
- Invasion (1)
- Inverse Gaschromatographie (1)
- Invertebrate herbivory (1)
- Ionenkanal (1)
- Ionenleitfähigkeit (1)
- Ionic Liquid (1)
- Ionische Flüssigkeit (1)
- Ipilimumab (1)
- Iridate (1)
- Ischemic stroke (1)
- Isocyanate (1)
- Isolation (1)
- J-Aggregate (1)
- JAK2 (1)
- K-RAS (1)
- KIF (1)
- KIF11 (1)
- KM3NeT (1)
- KTaO3 (1)
- Kapillarelektrophorese (1)
- Kilombero (1)
- Kinect (1)
- Kinetic Self-assembly (1)
- Kleinsatellit (1)
- Klinisches Experiment (1)
- Knee (1)
- Knochenimplantat (1)
- Knochenkleber (1)
- Knochenregeneration (1)
- Knochenwachs (1)
- Knorpelbildung (1)
- Kohärente Multidimensionale Spektroskopie (1)
- Kokristallisation (1)
- Kollektive Invasion (1)
- Komplexität (1)
- Komponentenanalyse (1)
- Konditionierung (1)
- Konfidenzintervall (1)
- Konfokale Mikroskopie (1)
- Konforme Metrik (1)
- Kongo (1)
- Konische Durchschneidung (1)
- Korrelierte Fermionen (1)
- Krebs (1)
- Krebs <Medizin> (1)
- Kreditgenossenschaft (1)
- Kristallfeld (1)
- Körpergewicht (1)
- L1 reading comprehension (1)
- L2 reading comprehension (1)
- L2 reading motivation (1)
- LATE DEATHS (1)
- LC-HRESIMS (1)
- LC3-associated phagocytosis (1)
- LCD Pulse Shaper (1)
- LCD Pulsformer (1)
- LHC (1)
- LMICS (1)
- LSD1 (1)
- LST (1)
- La gestion des déchets (1)
- LaAlO3/SrTiO3 (1)
- Ladungstrennung (1)
- Ladungsträger (1)
- Ladungsträgerlokalisation (1)
- Lageregelung (1)
- Land Change Modeler (1)
- Landnutzungskartierung (1)
- Landsat time series (1)
- Lantana camara (1)
- Lanthantitanate (1)
- Laparoscopy (1)
- Large Hadron Collider (1)
- Laser Pulse Shaping (1)
- Laserpulsformung (1)
- Late mortality (1)
- Latin America (1)
- Latrophilin (1)
- Leaf traits (1)
- Learning and memory (1)
- Learning walk (1)
- Learning/physiology (1)
- Lebende Polymerisation (1)
- Lee Smolin (1)
- Leptonic (1)
- Lernen (1)
- Lernverhalten (1)
- Leseverstehen (1)
- Lewis-base adducts (1)
- Library Screening (1)
- Lichtabsorption (1)
- Lichtblattmikroskopie (1)
- Lichtheimia (1)
- Lichtscheibenmikroskopie (1)
- Lichtstreuung (1)
- Lidschlag (1)
- Lifetime spectroscopy (1)
- Ligand <Biochemie> (1)
- Light sheet microscopy (1)
- Limb development (1)
- Limb salvage (1)
- Limestone (1)
- Liquid Crystal (1)
- Liquid Crystals (1)
- Living Polymerisation (1)
- Llullaillaco Volcano (1)
- Lokalisation (1)
- Low energy electron microscopy LEEM (1)
- Low risk alcohol use (1)
- Low-income Countries (1)
- Lung (1)
- Lung disease, (1)
- Lunge (1)
- Lyapunov Stability (1)
- Lymph nodes (1)
- Lysine-specific methylase (1)
- Löslichkeit (1)
- M14 carboxypeptidasses (1)
- MASS (1)
- MCP1 (1)
- MDSC (1)
- MGMT promoter methylation (1)
- MI-RADS (1)
- MIBG (1)
- MLST (1)
- MMB (1)
- MMB complex (1)
- MODIS (1)
- MOF (1)
- MOLLI (1)
- MRI (1)
- MRI spectroscopy (1)
- MRSA (1)
- Maculinea butterfly (1)
- Magnesiumphosphate (1)
- Magnetic Resonance Imaging (1)
- Magnetic resonance imaging (1)
- Magnetische Eigenschaft (1)
- Magnetismus (1)
- Magnetit (1)
- Magnetometry (1)
- Magnetoresistance (1)
- Magnetowiderstand (1)
- Magnon (1)
- Makrokolonie (1)
- Male (1)
- Mamma carcinoma (1)
- Mammakarzinom (1)
- Management (1)
- Managementinformationssystem (1)
- Manganese Carbonyl ligands (1)
- Mangansilicide (1)
- Manöverintention (1)
- Masern-Virus (1)
- Masticatory mucosa (1)
- Mastoid process (1)
- Mathematik (1)
- Matter (1)
- Mc4r (1)
- Measles virus (1)
- Measurement error correlation (1)
- Measurement-based Analysis (1)
- Meat (1)
- Mechanisms (1)
- Mechanisms of Social Attention (1)
- Mechanismus (1)
- Mechanosensation (1)
- Media Psychology (1)
- Medical research (1)
- Medienkonsum (1)
- Megakaryopoese (1)
- Megakaryozytopoese (1)
- Melanom (1)
- Melt Electrowriting (1)
- Memory B cells (1)
- Meniskus (1)
- Meniskusimplantat (1)
- Mensch-Maschine-Kommunikation (1)
- Merger-specific Efficiency Gains (1)
- Mergers (1)
- Mergers and Acquisitions (1)
- Merocyanine dyes (1)
- Mesenchymal stem/stromal cells (1)
- Messenger-RNAs (1)
- Messung (1)
- Metadynamik (1)
- Metal clusters (1)
- Metall-Isolator-Phasenumwandlung (1)
- Metallorganisches Netzwerk (1)
- Methicillin-resistant Staphylococcus aureus (1)
- Methodology (1)
- Metrics (1)
- Metrologie (1)
- Mfn2 KO mice (1)
- Microbiology and Infectious Disease (1)
- Midollo-Osseo (1)
- Migration (1)
- Mikroskopie (1)
- Mikrotubulus (1)
- Minimal change disease (1)
- Minimally invasive surgery (1)
- Missing Energy (1)
- Mitochondria (1)
- MnSi (1)
- Mobile genetic element (1)
- Model specification (1)
- Model-based Performance Prediction (1)
- Modell (1)
- Modifikation von Biokeramiken (1)
- Modular Hamiltonian (1)
- Modularer Hamiltonoperator (1)
- Molekulardynamik (1)
- Molekularstrahlepitaxie (1)
- Molekülsystem (1)
- Monoschicht (1)
- Monte Carlo simulation (1)
- Monte-Carlo-Simulation (1)
- Moral Hazard (1)
- Motivation (1)
- Motor behaviour (1)
- Mott Transistion (1)
- Mott-Isolator (1)
- Mott-Übergang (1)
- Mouse (1)
- Movement behavior (1)
- Mucor (1)
- Mucorales (1)
- Multi-Messenger (1)
- Multiferroics (1)
- Multiferroika (1)
- Multiphotonenmikroskopie (1)
- Multiple (1)
- Multiple myeloma (1)
- Multiple-Scattering (1)
- Multiplex PCR (1)
- Multiwavelength Astronomy (1)
- Muon spectrometers (1)
- Muscle function (1)
- Muscle power (1)
- Muster (1)
- Mutation (1)
- Myb-MuvB (1)
- Myrmecology (1)
- Myrmica ant non-equilibrium dynamics (1)
- N-heterocyclic olefins (1)
- NAFLD (1)
- NASH (1)
- NCH93 (1)
- NCI-H295R (1)
- NCO-sP(EO-stat-PO) (1)
- NF-Kappa-B (1)
- NF-κB/NFAT reporter cells (1)
- NFκB (1)
- NHCs (1)
- NH\(_{3}\) (1)
- NIPAL4 (1)
- NIQs (1)
- NIR OLED (1)
- NLO Computations (1)
- NMR spectroscopy (1)
- NMR-Spektroskopie (1)
- Nachhaltigkeit (1)
- Nahfeldoptik (1)
- Nahrungserwerb (1)
- Nanoparticles (1)
- Nanostruktur (1)
- Naphthylisoquinoline (1)
- Naphthylisoquinoline alkaloids (1)
- Nasal Carriage (1)
- Necrotizing enterocolitis (1)
- Nectin‐2 (1)
- Neisseria gonorrhoeae (1)
- Neolithic period (1)
- Nephroblastom (1)
- Nephrogenese (1)
- Netherlands (1)
- Netzwerk (1)
- Neural Differentiation (1)
- Neural circuits (1)
- Neuroanatomie (1)
- Neurodevelopmental Disorder (1)
- Neuroimaging (1)
- Neuroinflammation (1)
- Neuroscience (1)
- Neutrino Detectors and Telescopes (experiments) (1)
- Neutrino Mass (1)
- Neutrinos (1)
- Nfatc1 (1)
- Nicht-kleinzelliges Bronchialkarzinom (1)
- Nigeria (1)
- Nivolumab (1)
- Nociceptor (1)
- Non-coding RNA (1)
- Non-smooth optimal control (1)
- Nonlinear Dynamics (1)
- Non‐ischaemic cardiogenic shock (1)
- Nuclear Medicine (1)
- Nucleus subthalamicus (1)
- Numerical Cognition (1)
- Nursing homes (1)
- OSCC (1)
- OSI (1)
- Oberflächenfunktionalisierung (1)
- Oberflächenphonon (1)
- Oberflächenphysik (1)
- Oberflächenplasmon (1)
- Object recognition (1)
- Oculomotor Muscles/physiology (1)
- Oncology (1)
- Operations Management (1)
- Optical spectroscopy (1)
- Optik (1)
- Optimal foraging (1)
- Optimale Kontrolle (1)
- Optogenetics (1)
- Oral anticoagulation (1)
- Ordered metal adsorbates on semiconductor surfaces (1)
- Ordinal Categorical Indictators (1)
- Organic and hybrid semiconductors (1)
- Organische Chemie (1)
- Oscillation (1)
- Outer membrane proteins (1)
- Overstatement models (1)
- OxPL (1)
- Oxide Heterostructure (1)
- Oxidized Phospholipids (1)
- Oxidized phospholipids (1)
- P(P) over-bar collisions (1)
- P-glycoprotein (1)
- P-gp (1)
- PA-flexed view (1)
- PALS (1)
- PCR (1)
- PD-1 (1)
- PD-L1 (1)
- PDF neurons (1)
- PET/CT (1)
- PKD1 (1)
- PP collisions (1)
- PRKACA (1)
- PROMISE (1)
- PSMA (1)
- PSMA-RADS (1)
- PTEN (1)
- Parametric inference (1)
- Parkinson’s disease (1)
- Partial Least Squares Path Modeling (1)
- Particle accelerators (1)
- Particle tracking detectors (Gaseous detectors) (1)
- Particle-acceleration (1)
- Parvovirus (1)
- Paternal age and BMI effects (1)
- Pathogenesis (1)
- Pathogens (1)
- Patterns and drivers of invertebrate herbivory (1)
- Patterns and drivers of species diversity of phytophagous beetles (1)
- Patterns and drivers of species richness and community biomass of large mammals (1)
- Pavlovian-to-instrumental transfer (1)
- Pediatric Nuclear Medicine (1)
- Pediatric Patients (1)
- Peierls-Übergang (1)
- Pendeln (1)
- Pentixafor (1)
- Perception (1)
- Perowskit (1)
- Personalized medicine (1)
- Perturbative/Functional Renormalization Group (1)
- Perturbative/Funktionale Renormierungsgruppe (1)
- Perylenbisdicarboximide <Perylen-3,4:9,10-bis(dicarboximide)> (1)
- Perylenbisimide (1)
- Perylenbisimides (1)
- Perylene Bisimide (1)
- Perylene Bisimides (1)
- Pfadintegral (1)
- Pflanzen (1)
- Pflanzenhormone (1)
- Phagozytose (1)
- Pharmakokinetik (1)
- Pharmakotherapie (1)
- Phase- (1)
- Phenols (1)
- Phobie (1)
- Phosphatasen (1)
- Phosphoglykolat-Phosphatase (1)
- Phosphoglykolatphosphatase (1)
- Phospholipide (1)
- Phosphorylation (1)
- Photic (1)
- Photoelectron Spectroscopy (1)
- Photoelektronenspektroskopie (1)
- Photoemission electron microscopy PEEM (1)
- Photoluminescence (1)
- Photolumineszenz (1)
- Photoreceptor (1)
- Physical activity (1)
- Physiologie (1)
- Phytochemical investigations of a Congolese Ancistrocladus Liana (1)
- Phytochemie (1)
- Pigmentdispergierender Faktor (1)
- Plant signalling (1)
- Plants (1)
- Plasmaantrieb (1)
- Plasmamembranorganisation (1)
- Plasmon (1)
- Platzierungsalgorithmen (1)
- Poly(2-oxazolin)e (1)
- Polyethylenglykole (1)
- Polygonum cuspidatum (1)
- Polymer-drug interaction (1)
- Polymere (1)
- Polymers (1)
- Polynomial Factor Models (1)
- Polyphenole (1)
- Polysaccharide (1)
- Poplars (1)
- Positron annihilation spectroscopy (1)
- Positron-Emission Tomography (1)
- Postoperative complications (1)
- Preconcentration (1)
- Predictive Analytics (1)
- Prefrontal cortex (1)
- Premna (1)
- Prescriptive Analytics (1)
- Preterm birth (1)
- Prevalence (1)
- Prior information (1)
- Privatsphäre (1)
- ProQ (1)
- Probability theory (1)
- Prognostic markers (1)
- Prognostic scoring system (1)
- Prospektives Gedächtnis (1)
- Protease-sensitive release (1)
- Protein (1)
- Protein Kinase D (1)
- Protein Kinase D 1 (1)
- Protein folding (1)
- Protein kinase D3 (PKD3) (1)
- Proteinkinase A (1)
- Proteinkinase D (1)
- Proteomics Analysis of Complexes (1)
- Proteotype (1)
- Proteus vulgaris (1)
- Proton-Proton Collisions (1)
- Präsenz (1)
- Präzisionsmessung (1)
- Psychiatric disorders (1)
- Psychiatrie (1)
- Psychologie (1)
- Psychology (1)
- Psychometrie (1)
- Psychomotor Performance/physiology (1)
- Pulmonary function tests (1)
- Pulsed laser deposition (1)
- Punktwolke (1)
- Quality assessment of antimalarial medicines from the Congo (1)
- Quality ccontrol (1)
- Quality-control (1)
- Qualität der Abschlussprüfung (1)
- Qualität der Rechnungslegung (1)
- Qualitätskontrolle (1)
- Quanten-Hall-Effekt (1)
- Quanten-Monte-Carlo (1)
- Quanteninformation (1)
- Quantenpunkt (1)
- Quantifizierung (1)
- Quantitative Mikroskopie (1)
- Quantum Hall effect (1)
- Quantum electrodynamics (1)
- Quinolone amides (1)
- R package (1)
- RADS (1)
- RAS Evaluation (1)
- RCT (1)
- REDD1 (1)
- RFID (1)
- RNA Sequencing (1)
- RNA expression (1)
- RNA metabolism (1)
- RNA protein interactions (1)
- RNA secondary structures (1)
- RNA-Seq (1)
- RNA-seq transcriptome (1)
- RNAi (1)
- RNAlater (1)
- RNS (1)
- ROR1 (1)
- ROS (1)
- RSV-A ON1 (1)
- RT-qPCR (1)
- Radiation (1)
- Radiation Protection (1)
- Radiation exposure (1)
- Radiation-associated Cancer Risk (1)
- Radiographs (1)
- Radiotherapy (1)
- Raphe (1)
- RapidEye (1)
- Raumwahrnehmung (1)
- Regelbasiertes Modell (1)
- Regimes (1)
- Regional trade (1)
- Regionaler Arbeitsmarkt (1)
- Regionaler Handel (1)
- Regionalpolitik (1)
- Regionalwirtschaft (1)
- Regulierung (1)
- Reiz (1)
- Relativistic heavy-ion collisions (1)
- Reminder e-mails (1)
- Remnant RX J1713.7-3946 (1)
- Remote Sensing (1)
- Reporter Cells (1)
- Reporterzellen (1)
- Rescue behaviour (1)
- Research Article (1)
- Respiratory tract infection (1)
- Retinopathy (1)
- Rhizomucor (1)
- Rhizopus (1)
- RhoA (1)
- Rhodopsin (1)
- Ribozyme-catalyzed RNA labeling (1)
- Ringöffnungspolymerisation (1)
- Risk (1)
- Risk Assessment (1)
- Roboter (1)
- Robotics (1)
- Runge-type Theorems (1)
- Ruthenium (1)
- Ruxolitinib (1)
- Röntgenastronomie (1)
- Röntgendiffraktometrie (1)
- S. aureus (1)
- SASHA (1)
- SB332235 (1)
- SIX1 (1)
- SPOT-6 (1)
- SR/mitochondria metabolic feedback (1)
- SREBP (1)
- SSR42 (1)
- SSTR (1)
- SSTR-RADS (1)
- ST 772 (1)
- ST18 (1)
- SWAT (1)
- SWAT model (1)
- Saccades/physiology (1)
- Salmo trutta fario (1)
- Satellit (1)
- Scarabaeidae (1)
- Scattering (1)
- Scenario analysis (1)
- Scheme for solving optimal control problems (1)
- Schlichte Funktion (1)
- Schmerzforschung (1)
- Schmerztherapie (1)
- Secondary stroke prevention (1)
- Sediment (1)
- Segmentation (1)
- Sekundärprävention (1)
- Selbstassemblierung (1)
- Self-assembly (1)
- Self-navigation (1)
- Self-renewal (1)
- Semantics (1)
- Semantik (1)
- Sense of Agency (1)
- Sensor Fusion (1)
- Sentinel-2 (1)
- Septine (1)
- Sequential quadratic Hamiltonian scheme (1)
- Serine proteases (1)
- Server (1)
- Sex chromosome (1)
- Sex determination (1)
- Sexual development and function (1)
- ShMOLLI (1)
- Shelf-life (1)
- Shell (1)
- Sibling donor (MSD) (1)
- Silver (1)
- Single Molecule Localization Microscopy (SMLM) (1)
- Single-Photon (1)
- Situationsbewusstsein (1)
- Skin (1)
- Skull (1)
- Small RNA (1)
- Small interfering RNAs (1)
- Small-Gain Theorem (1)
- Smoking (1)
- Social Cognition (1)
- Social Cueing (1)
- Social Web (1)
- Societe Francaise (1)
- Soft tissues (1)
- Software (1)
- Software Defined Networking (1)
- Software Performance Engineering (1)
- Software-defined Networking (1)
- Softwarisierte Netze (1)
- Solid tumors (1)
- Somites (1)
- Soziale Aufmerksamkeit (1)
- Soziale Mobilität (1)
- Soziale Software (1)
- Spatial Cognition (1)
- Spatially resolved 2D spectroscopy (1)
- Species delimitation (1)
- Species richness (1)
- Specific Phobia (1)
- Specimen grinding (1)
- Speckle tracking (1)
- Spezifische Phobien (1)
- Spezifische Wärme (1)
- Sphingosine-1-phosphate (1)
- Sphingosine-1-phosphats (1)
- Spin flip (1)
- Spin-Bahn-Kopplung (1)
- Spin-Orbit interaction (1)
- Spin-Phonon Kopplung (1)
- Spin-chemistry (1)
- Spin-phonon coupling (1)
- Spinflüssigkeit (1)
- Stability (1)
- Stabilität (1)
- Stammzelle (1)
- Standardmodell <Elementarteilchenphysik> (1)
- Staphylococcus aureus USA300 (1)
- Starke Kopplung (1)
- Stechameisen (1)
- Stem cell (1)
- Stem-cell biotechnology (1)
- Stenosis degree (1)
- Stenosis length (1)
- Stereochemistry (1)
- Sternpolymere (1)
- Stigmatisierung (1)
- Stimme (1)
- Stimmverarbeitung (1)
- Stimulation (1)
- Stoffwechsel (1)
- Stokes-shifted fluorescence emission (1)
- Strains (1)
- Strange Baryon Production (1)
- Strategisches Management (1)
- Stratigraphy (1)
- Streptococcus agalactiae (1)
- Stroke (1)
- Stroke unit (1)
- Stromal cells (1)
- Strontiumtitanat (1)
- Strontiumvanadate (1)
- Structural Equation Modeling (1)
- Structural elucidation (1)
- Structural equation modelling (1)
- Structure elucidation (1)
- Struktur-Aktivitäts-Beziehung (1)
- Strukturgleichungsmodell (1)
- Sub-Saharan Africa (1)
- Subject (1)
- Subtercola vilae (1)
- Success Factors (1)
- Supernova (1)
- Supportive therapy (1)
- Supramolecular Block Copolymers (1)
- Supramolecular aggregates (1)
- Supramolekulare Aggregate (1)
- Supramolekulare Struktur (1)
- Surface Plasmon (1)
- Surface Raman spectroscopy (1)
- Surgical and invasive medical procedures (1)
- Surgical oncology (1)
- Survey (1)
- Suspensionskultur (1)
- Swine (1)
- Syap1 knockout (1)
- Symmetry (1)
- Systemic sclerosis (1)
- T cell (1)
- T cell receptor (1)
- T cell suppression (1)
- T cells (1)
- T-cell lymphoma (1)
- T1 mapping (1)
- TDDFT (1)
- TDMT (1)
- TEV (1)
- TFP (1)
- TGFβ/BMP signaling (1)
- TLR2 (1)
- TLR3 (1)
- TLR4 (1)
- TMEM16F (1)
- TNF (1)
- TNF-alpha (1)
- TNFR family costimulatory receptors (1)
- TNFR2 (1)
- TNFR2 agonists (1)
- TNFR2 antagonism (1)
- TNFα (1)
- TNNI3 (1)
- TP53 (1)
- TPCA1 (1)
- TRAF1 (1)
- TRAF2 (1)
- TRAILR1 (1)
- TRAILR2 (1)
- TRPA1 channel (1)
- TWEAK (1)
- Tagesrhythmus (1)
- Tamoxifen (1)
- TanDEM-X (1)
- Tc-99m-MAG3 Scans (1)
- TeV energies (1)
- Telemedizin (1)
- Temozolomide (1)
- Terramechanics (1)
- Theoretische Chemie (1)
- Therapeutisches System (1)
- Therapie (1)
- Therapiesimulation (1)
- Thermodynamik (1)
- Thin Films (1)
- Thin intermetallic films (1)
- Thiotepa-busulfan-fludarabine (TBF) (1)
- Thrombo-inflammation (1)
- Thrombosis (1)
- Thrombozytopenie (1)
- Thrust Vector Control (1)
- Tiermodell (1)
- Time resolved measurements (1)
- Time-resolved photoemission electron microscopy (1)
- Time-resolved photoluminescence (1)
- Tissue engineering (1)
- Toddler (1)
- Top quark (1)
- Topological insulators (1)
- Topologische Isolatoren (1)
- Topologischer Isolator (1)
- Torque (1)
- Total Factor Productivity (1)
- Tourenplanung (1)
- Tractography (1)
- Transcription (1)
- Transcription factor NRF1 (1)
- Transcriptomic (1)
- Translation (1)
- Translation Initiation (1)
- Translational research (1)
- Transplantat-Wirt-Reaktion (1)
- Transposable element (1)
- Transverse-Momentum (1)
- Trees (1)
- Tregs (regulatory T cells) (1)
- Triquinacenderivate (1)
- Triticeae (1)
- Triticum aestivum (1)
- Trousseau's syndrome (1)
- Trypanosomiase (1)
- Tryptophan hydroxylase (1)
- Tubulin (1)
- Tumor (1)
- Tumorzelle (1)
- Twin Domains (1)
- Twin Suppression (1)
- Two-color pump-probe spectroscopy (1)
- U-Net (1)
- USA (1)
- UV-VIS-Spektroskopie (1)
- UV/Vis spectroscopy (1)
- UV–Vis (1)
- Ultrakurzzeitspektroskopie (1)
- Ultrarelativistic Heavy-Ion (1)
- Ultrashort echo time - UTE (1)
- Umwelt (1)
- Unconventional/Topological superconductivity (1)
- Universal Functions (1)
- Unkonventionelle/Topologische Supraleitung (1)
- Unnötige Warnung (1)
- Unrelated donor (UD) (1)
- Unternehmensverfassung (1)
- User Behavior (1)
- User-Guidelines (1)
- Ustilago maydis (1)
- V-ATPase (1)
- VLBW (1)
- VMAT (1)
- Vakuole (1)
- Valentine Leukocidin Genes (1)
- Valgus osteoarthritis (1)
- Value at Risk (1)
- Vascularized (1)
- Vaskularisation (1)
- Vcsels (1)
- Verarbeitende Industrie (1)
- Verbundwerkstoff (1)
- Verkehrspsychologie (1)
- View (1)
- Virtuelle Realität (1)
- Visuelle Aufmerksamkeit (1)
- Visuo-tactile congruency (1)
- Voice Processing (1)
- W & Z bosons (1)
- W-Boson (1)
- WSS (1)
- Wahrscheinlichkeitstheorie (1)
- Warnung (1)
- Waste management (1)
- Weak-Interactions (1)
- WebGIS (1)
- Wechselwirkungen (1)
- Wheel (1)
- White matter lesions (1)
- Wide-gap-Halbleiter (1)
- Wilms tumor (1)
- Wilms-Tumor (1)
- Winkelaufgelöste Photoemission mit harten Röntgenstrahlen (1)
- Wire chambers (MWPC, Thin-gap chambers, drift chambers, drift tubes, proportional chambers etc) (1)
- Wirkstoff (1)
- Wirkstofftestung (1)
- Wirtschaftliche Integration (1)
- Wirtschaftsinformatik (1)
- Woodhouse-Sakati Syndrom (1)
- Woodhouse-Sakati sydrome (1)
- Wundheilung (1)
- X-ray radiography (1)
- XRD (1)
- YAP (1)
- Yoga (1)
- Young Adult (1)
- ZF1 degradation assay (1)
- ZFAND1 (1)
- Zahnbehandlungsphobie (1)
- Zebrafish (1)
- Zell Migration (1)
- Zelloberfläche (1)
- Zentralasien (1)
- Zinc (1)
- Zinkselenid (1)
- ZnO-NP (1)
- Zusammenstoß (1)
- Zwillingsbildung (1)
- [68Ga]Pentixafor (1)
- \(^{177}\)Lu-OPS201 (1)
- abdominal surgery (1)
- absolute bioavailability (1)
- accessory medulla (1)
- accidents (1)
- accumulation (1)
- accuracy (1)
- acetate (1)
- acid ceramidase (1)
- acid ceramidase inhibitor ceranib-2 (1)
- acoustic radiation force impulse imaging (1)
- acrophobia (1)
- actin (1)
- actin cytoskeleton (1)
- actin-binding proteins (1)
- action control (1)
- activated delayes flourescence (1)
- activation (1)
- active galactic nuclei (1)
- active ingredients (1)
- acute kidney injury (1)
- acute lymphoblastic leukemia (1)
- adalimumab (1)
- additive manufacturing (1)
- adenoma (1)
- adenotonsillectromy (1)
- adipocyte (1)
- adipose (1)
- adiposity (1)
- administrative boundary (1)
- adrenocortical carcinoma (1)
- adult attention deficit/hyperactivity disorder (adult ADHD) (1)
- advanced breast cancer (1)
- aerobic fitness (1)
- affect bursts (1)
- age at onset (1)
- age groups (1)
- age-related macular degeneration (1)
- agriculture (1)
- airway management (1)
- alkaloids-Quinoid (1)
- alkynes (1)
- alternative splicing (1)
- altitudinal gradients (1)
- alveolar epithelium (1)
- amine borane dehydrocoupling (1)
- aminergic neurons (1)
- amodiaquine (1)
- amorphous solid dispersion (1)
- amphiphilic block copolymer (1)
- amsacrine (1)
- amyloidoma (1)
- amyotrophic lateral sclerosis (ALS) (1)
- anakinra (1)
- analysis of variance (1)
- animal research (1)
- anime (1)
- anomaly detection (1)
- anorexia nervosa (1)
- anti-contactin-1 (1)
- anti-depressant drug (1)
- antibacterial (1)
- antibacterial activity (1)
- antibiofilm (1)
- antibiotic resistance (1)
- anticancer (1)
- anticipation (1)
- antifungal (1)
- antitrypanosomal (1)
- anti‐aging (1)
- anxiety generalization (1)
- anxiolytics (1)
- aortocaval fistula model (1)
- appraisal theory of emotion expression (1)
- arctic greening (1)
- arenes (1)
- artemether - lumefantrine (1)
- artifacts (1)
- artificial intelligence (1)
- artificial light at night (1)
- aspergillosis (1)
- asylum seekers (1)
- asylum status (1)
- atmospheric waves (1)
- atrial fibrillation (1)
- auto-planning (1)
- autoantibody (1)
- autobiography (1)
- autoimmune disease (1)
- autophagy (1)
- autosomal recessive (1)
- auxin (1)
- axillary dissection (1)
- back reaction (1)
- bacterial pathogen (1)
- baghdadite (1)
- balancing trade-offs (1)
- bank mergers (1)
- bariatric surgery (1)
- behavior (1)
- behavioral plasticity (1)
- beige adipocytes (1)
- bench press (1)
- bending strength (1)
- benige tumor (1)
- beta-lactam antibiotics (1)
- biceps tendinitis (1)
- biceps tendon (1)
- big earth data (1)
- bilateral internal carotid artery stenosis (1)
- binary species (1)
- bioavailability (1)
- bioceramics (1)
- biofabricated vascular graft (1)
- biofilm architecture (1)
- bioinformatics tool (1)
- bioink (1)
- bioinks (1)
- biokinetics (1)
- biological rhythm (1)
- biological scaffolds (1)
- biomarker (1)
- biomarker signature (1)
- biomaterial ink (1)
- biomaterials (1)
- biomechanics (1)
- biomolecular processes (1)
- bioreactor (1)
- biotic interaction (1)
- bispecific antobodies (1)
- bisulfite pyrosequencing (1)
- black trout syndrome (1)
- bladder (1)
- blazars (1)
- blinatumoman (1)
- blinking (1)
- blocking phagocytosis (1)
- blood (1)
- blood brain barrier (1)
- blood cerebrospinal fluid barrier (1)
- blood-cerebrospinal fluid barrier (1)
- bohrbar (1)
- bone critical size defect (1)
- bone graft substitutes (1)
- bone marrow stromal cells (1)
- bone wax (1)
- boolean modeling (1)
- boreholes (1)
- borohydrides (1)
- boronate (1)
- boronic acid (1)
- borylenes (1)
- bottom-up processing (1)
- brain (1)
- brain activity (1)
- brain development (1)
- brain disorders (1)
- brain endothelial cell (1)
- brain endothelial cells (1)
- brain networks (1)
- brain plasticity (1)
- brain tumor (1)
- breast cancer (1)
- bridge-to-transplant (1)
- bronchoalveolar lavage fluid (1)
- bronchopulmonary dysplasia (1)
- brown trout (1)
- building (1)
- bullae (1)
- burn severity (1)
- burnt-wood (1)
- calcium (1)
- calcium phosphate (1)
- calnexin (1)
- calving front (1)
- cancer immunotherapy (1)
- capillary zone electrophoresis (1)
- carabid beetles (1)
- carbenes (1)
- carbon (1)
- carbon monoxide (1)
- cardiac metabolism (1)
- cardiac remodelling (1)
- cardiac surgery (1)
- cardiac tissue (1)
- cardiolipin (1)
- cardiomyocytes (1)
- cardiopulmonary bypass (1)
- cardiovascular genetics (1)
- cardiovascular risk factors (1)
- care (1)
- cartilage repair (1)
- catalysis (1)
- catchment (1)
- catheterization (1)
- catheters (1)
- caveolin-1 (Cav-1) (1)
- cefotiam (1)
- cell differentiation (1)
- cell migration (1)
- cell therapy and immunotherapy (1)
- cellular model (1)
- ceramide (1)
- cerebral microbleeds (1)
- cerebrospinal fluid (1)
- cervical dystonia (1)
- channelrhodopsins (1)
- charge carrier localization (1)
- charge recombination (1)
- charge separation (1)
- chemical crosslinking (1)
- chemokine (1)
- chemokine receptor (1)
- child behavior (1)
- chimeric antigen receptor (1)
- chirality (1)
- chirality-induced spin selectivity (1)
- chlamydia (1)
- chlorophyll fluorescence imaging (1)
- cholesterol (1)
- cholesterol 25 hydroxylase (1)
- cholesteryl ester (1)
- chondrocyte (1)
- chondrogenesis (1)
- chronic kidney disease (1)
- chronic kidney disease (CKD) (1)
- chronic non-bacterial osteomyelitis (1)
- circRNA (1)
- circadian clock (1)
- circadian rhythm (1)
- circadian rhythms (1)
- circular transcriptome sequencing (1)
- cisplatin (1)
- claudin-5 (1)
- click chemistry (1)
- climate extremes (1)
- clinical characteristics (1)
- clinical imaging (1)
- clinical outcome (1)
- clinical pharmacy (1)
- clinical trial (1)
- closed-loop systems (1)
- cluster analysis (1)
- co-culture (1)
- coastline (1)
- cocrystal (1)
- cognitive control (1)
- coherence (1)
- coherent risk measures (1)
- cold adaptation (1)
- collagen sponge (1)
- collective invasion (1)
- collimator (1)
- collodion baby (1)
- collybistin (1)
- colonization (1)
- commission error (1)
- common diseases (1)
- comparative genomics (1)
- comparison (1)
- competition (1)
- complement deposition (1)
- complement factor H (1)
- complex DNA damage (1)
- composite material (1)
- composition (1)
- computer-mediated communication (1)
- concealed information test (1)
- conditioning (1)
- congruency sequences (1)
- conjugation (1)
- consensus (1)
- conservation (1)
- constructed trade-offs (1)
- context-based teaching (1)
- contextual fear conditioning (1)
- continuous theta burst stimulation (cTBS) (1)
- continuum limit (1)
- control levels (1)
- convolutional neural network (1)
- copeptin (1)
- coping (1)
- copy number variation (1)
- coronary heart disease (1)
- correspondence (1)
- cortical excitability (1)
- cortical silent period (1)
- cosmology (1)
- count time series (1)
- covalent and site-specific RNA labeling (1)
- cristal engeneering (1)
- crop statistics (1)
- cross-coupling (1)
- cross-sectional study (1)
- cryosphere (1)
- cryostructured scaffolds (1)
- crystal growth (1)
- crystallization (1)
- crystallography (1)
- curcumin (1)
- curvature (1)
- curved hydrocarbons (1)
- cuticular permeability (1)
- cyclase-associated protein (1)
- cyclase-associated protein 2 (1)
- cyclic compounds (1)
- cyclophosphamide (FLAMSA) (1)
- cytokinesis (1)
- cytoskeleton (1)
- cytotoxic (1)
- daratumumab (1)
- data structure (1)
- data warehouse (1)
- dead-wood enrichment (1)
- decay (1)
- decellularization (1)
- deception (1)
- deep learning (1)
- default-interventionist framework (1)
- definition (1)
- dehydrocoupling (1)
- dehydrogenaticve borylation (1)
- democracy (1)
- democracy profiles (1)
- dendritic cell (1)
- depth dose curves (1)
- designer cell (1)
- desk-based (1)
- desmin (1)
- desmin-related myopathy (1)
- desminopathy (1)
- desmoglein (1)
- desmoplastic small round cell tumor (1)
- desmosome (1)
- deubiquitinases (1)
- developmental forms (1)
- dexamethasone (1)
- diabetes (1)
- diacylglycerol (1)
- diacylglycerol (DAG) (1)
- dialysis adequacy (1)
- diazadiborinines (1)
- diborane(6) (1)
- diboranes (1)
- diboration (1)
- diborene (1)
- diborenes (1)
- diborynes (1)
- differentiation potential (1)
- diffuse large B-cell lymphoma (1)
- diffusion weighted mri (1)
- digital health (1)
- diluted magnetic Semiconductor (1)
- dimeric peptide (1)
- direct muss spectrometric profiling (1)
- discrete systems (1)
- disease modelling (1)
- dissolution rates (1)
- distractor-response binding (1)
- distributed control (1)
- distributed learning (1)
- distributions (1)
- diversity gradients (1)
- document analysis (1)
- domain-specific language (1)
- donor (1)
- donor-acceptor systems (1)
- dorsal root ganglion (1)
- dose individualization (1)
- dosimetry (1)
- double arc (1)
- doxorubicin (1)
- drillable (1)
- drivers and patterns of diversity and herbivory (1)
- driving simulation (1)
- drought (1)
- drug release (1)
- drug resistance evolution (1)
- dual abbindend (1)
- dual setting (1)
- dual setting system (1)
- dualsteric (1)
- duchenne muscular dystrophy (1)
- duplication-deficiency (1)
- dyads (1)
- dyes (1)
- dynamic facial emotion expression (1)
- dystonia (1)
- e(+)e(-) Collisions (1)
- e-learning (1)
- early brain injury (1)
- early-life stress (1)
- earlywood (1)
- eccentric hypertrophy (1)
- echocardiography (1)
- ecosystem service (1)
- education system (1)
- effective point of measurement (1)
- efficient intervention points (1)
- eindimensionale Systeme (1)
- electrical resistivity tomography (1)
- electrochemistry (1)
- electron-precise diborates (1)
- electrospun fibers (1)
- elementary body (1)
- eletrhydrodynamic (1)
- emission (1)
- emotion (1)
- emotion enactment (1)
- emotion processing (1)
- emotion recognition (1)
- emotional behavior (1)
- emotions (1)
- emulsions oil-in-water (1)
- en bloc transfer (1)
- enantiomers (1)
- enbrel (1)
- end-stage renal disease (1)
- endocytosis (1)
- endothelial cells (1)
- endothelin-1 (1)
- endurance (1)
- enercy-richness hypothesis (1)
- energy homeostasis (1)
- enhancer (1)
- environmental justice (1)
- environmental sustainability (1)
- enzyme mechanism (1)
- epidural block (1)
- epithelial-mesenchymal transition (1)
- error estimation (1)
- estimation error (1)
- etanercept (1)
- ethics (1)
- eugenol (1)
- evapotranspiration (1)
- exciton (1)
- exciton dynamics (1)
- exciton-polariton (1)
- exercise intervention (1)
- expansion microscopy (1)
- expected value of control (1)
- external stimuli (1)
- extinction (1)
- extinction dynamics (1)
- extracellular domain (1)
- extramedullary hematopoiesis (1)
- extreme phenotypes (1)
- eye movement (1)
- eye movements (1)
- eye-tracking (1)
- fMRI (1)
- fMRT (1)
- face (1)
- face-voice integration (1)
- faces (1)
- fan culture (1)
- fatigue (1)
- fault detection (1)
- fear (1)
- fear learning (1)
- febrile seizures (1)
- feminist rap (1)
- femoral head (1)
- fertility (1)
- fibre length (1)
- fibromyalgia (1)
- fibrotest (1)
- field-induced surface hopping (1)
- fission (1)
- flash freezing (1)
- fliegende Toilette (1)
- flora (1)
- flourescence quantum yield (1)
- flu-like symptoms (1)
- fluerescence (1)
- fluorenscence (1)
- fluorescence microscopy (1)
- fluorescent probes (1)
- fluorine (1)
- fluoroarene (1)
- fluorogen-activating RNA aptamer (FLAP) (1)
- fluoroquinolone (1)
- fluxosome (1)
- fly-tipping (1)
- flying toilet (1)
- folda-dimer (1)
- food colorings (1)
- food resources (1)
- foraging patterns (1)
- forensic sample (1)
- forest ecology (1)
- forest fire (1)
- forest management (1)
- forest resources inventory (1)
- formation control (1)
- fractional variability (1)
- fracture (1)
- fragmentation functions (1)
- free choice (1)
- free movement (1)
- free radical polymerization (1)
- friut fly behaviour (1)
- full arc (1)
- fully convolutional neural networks (1)
- function (1)
- functional MRI (1)
- functional analysis (1)
- functional connectivity (1)
- functional training (1)
- fungal molecular diagnostics (1)
- fungal rhodopsins (1)
- funktionale Präpolymere (1)
- games (1)
- gangliosides and lipid rafts (1)
- gastric-bypass surgery (1)
- gastrointestinal cancer (1)
- gastrointestinal tract (1)
- gauge/gravity duality (1)
- gaze control (1)
- gekrümmte Kohlenwasserstoffe (1)
- gem-bisboronates (1)
- gene alleles (1)
- gene expression analysis (1)
- gene family evolution (1)
- gene network (1)
- gene regulation (1)
- genetic codon expansion (1)
- genetic recombination (1)
- genome (1)
- genome analysis (1)
- genomic imprinting (1)
- genotoxicity (1)
- glacier front (1)
- glacier terminus (1)
- glia cells (1)
- glioblastoma multiforme (GBM) (1)
- glioma (1)
- global (1)
- global change (1)
- glucose transporter (1)
- glycine transporter 2 (1)
- glycoprotein Ibα (1)
- glycoprotein VI (1)
- glyvine uptake (1)
- graft vs. host disease (1)
- graft-versus host (1)
- graft-versus-host-disease (1)
- granules (1)
- gravitational waves (1)
- green fluorescence protein (GFP) (1)
- ground penetrating radar (1)
- ground-dwelling predators (1)
- growth (1)
- growth patterns (1)
- growth ring width (1)
- guanylyl cyclase (GC) (1)
- guided bone regeneration (1)
- guideline adherent treatment (1)
- guidelines (1)
- gut–liver axis (1)
- hA<sub>3</sub>AR (1)
- habit (1)
- habit strength (1)
- hadronic Recoil (1)
- hadronischer Rückstoß (1)
- haematopoietic stem cell (1)
- halogens (1)
- hard x-ray photoemission (1)
- head and neck squamous cell carcinoma (1)
- heart-to-mediastinum ratio (1)
- heat wave (1)
- helical molecules (1)
- helicenes (1)
- hematopoietic stem cell transplantation (1)
- heme oxygenase-1 (1)
- hemicraniectomy (1)
- hemodiafiltration (1)
- hemodialysis (1)
- hemophagocytosis (1)
- hemorrhagic (1)
- hemostasis (1)
- henoch-schönlein purpura (1)
- hepatitis B virus (1)
- hereditary breast and ovarian cancer (1)
- heterocycles (1)
- heterotypic scaffold design (1)
- heuristics (1)
- hiPSC aggregation (1)
- high LET irradiation (1)
- high efficiency (1)
- high risk (1)
- high-resolution tandem mass spectrometry (1)
- hip fracture (1)
- hippocampus (1)
- histological subtype (1)
- histone H2AX (1)
- historical document analysis (1)
- historical printings (1)
- homogeneous catalysis (1)
- homogenization (1)
- honeybee (1)
- honeybees (1)
- hospital exemption (1)
- hospital-acquired methicillin-resistant Staphylococcus aureus (1)
- human adipose-derived stromal cells (1)
- human cerebral endothelial cells (1)
- human plasma (1)
- human xenografted mouse models (1)
- hybrid fabrication (1)
- hybrid materials (1)
- hydrogels (1)
- hydrological regime (1)
- hydroxyapatite (1)
- hydroxylation (1)
- hyperosmolality (1)
- hyperpersonal communication (1)
- hypertension (1)
- hypothermia (1)
- iGC (1)
- iPSC (1)
- ichthyosis (1)
- identification (1)
- iliac crest (1)
- illness-death model (1)
- imaging (1)
- imaging PAM (1)
- immediate-early gene (1)
- immune evasion (1)
- immunity (1)
- immunocompetent skin (1)
- immunotherapy of cancer (1)
- implant (1)
- impurity profiling (1)
- in situ microscopy (1)
- in vitro model (1)
- in vitro models (1)
- in vitro selection from a structured RNA library (1)
- incidence (1)
- individualization (1)
- indole-3-acetic acid (1)
- indolylpyrimidylpiperazines (1)
- induced pluripotent stem cells (1)
- infection biology (1)
- infections (1)
- infectious diseases (1)
- inflammatory gene (1)
- inflation (1)
- information retrieval (1)
- information sharing (1)
- inherited cardiomyopathies (1)
- inherited macrothrombocytopenia (1)
- inhibition (1)
- inhibitor (1)
- injection site reactions (1)
- injury (1)
- inmates (1)
- innate immune evasions (1)
- insect abundance (1)
- insect collection (1)
- insurance medicine (1)
- intact bone imaging (1)
- integrative management strategy (1)
- integrin α2 (1)
- integrins (1)
- interactions (1)
- intercomparison (1)
- interface (1)
- interface conductivity (1)
- interferon beta (1)
- interleukin (1)
- interleukin-6 (1)
- intermediate dose Ara-C (1)
- intermediate filaments (1)
- intermittent exercise (1)
- intermolecular applications of ribozymes (1)
- internal carotid artery stenosis (1)
- intersession experiences (1)
- intersession processes (1)
- interval training (1)
- intervention point analyzing (1)
- intestine (1)
- intracellular bacterial pathogens (1)
- intracranial bleeding (1)
- invasive aspergillosis (1)
- inventory (1)
- iodine (1)
- ionization chambers (1)
- ionization energy (1)
- ionization potential (1)
- iron metabolism (1)
- ischemia reperfusion injury (1)
- ischemia time (1)
- isotropic hyper fine coupling (1)
- jet shapes (1)
- jet stream (1)
- jets (1)
- keratinocytes (1)
- key structure - fluorescence activation relationships (SFARs) (1)
- kidney (1)
- kidney development (1)
- kinesin (1)
- kinesthesia (1)
- kolorektales Karzinom (1)
- koronare Herzerkrankung (1)
- la durabilité environnementale (1)
- labour market (1)
- lag effect (1)
- land sharing (1)
- land surface (1)
- land use (1)
- land-cover area (1)
- language in media (1)
- late onset sepsis (1)
- late positive potential (1)
- lateral process of the talus (1)
- latewood (1)
- lattice forces (1)
- leaf width (1)
- learner characteristics (1)
- learning (1)
- les toilettes volantes (1)
- library screening (1)
- lichen planus (1)
- lifestyle (1)
- ligand binding (1)
- ligand exchange (1)
- ligand-receptor promiscuity (1)
- light-emitting-diodes (1)
- light-matter interaction (1)
- lightsheet microscopy (1)
- lignan (1)
- lineage-specific genes (1)
- linear conversion (1)
- linguistic cues (1)
- linguistic politics (1)
- lipid metabolism (1)
- liponeurocytoma (1)
- liquid biopsy (1)
- liver (1)
- liver metastases (1)
- local field potentials (1)
- localization microscopy (1)
- logical trade-offs (1)
- long head of biceps tendon (1)
- long-term potentiation (1)
- loss of function (1)
- low-cost photometer (1)
- low-valent compounds (1)
- low-valent main group chemistry (1)
- low-valent main-group species (1)
- lowland beech forests (1)
- luminescence (1)
- lung cancer (1)
- lung metastases (1)
- lying (1)
- lymph nodes (1)
- lymphohistiocytosis (1)
- lyso-phospholipids (1)
- mAb engineering (1)
- mRNA (1)
- mTOR (1)
- macrocolony (1)
- macrophage polarization (1)
- magnesium phosphate cement (1)
- magnetic field effect (1)
- maintenance therapy (1)
- major river basins (1)
- management (1)
- manga (1)
- manoeuvre intention (1)
- match load (1)
- maternal separation (1)
- mating (1)
- mating preference (1)
- mebendazole (1)
- mechanical performance (1)
- mechanistic modelling (1)
- medaka (1)
- medical rehabilitation (1)
- medication extraction (1)
- medicinal plant (1)
- medicine (1)
- medieval manuscripts (1)
- medulloblastoma (1)
- megakaryocyte (1)
- melatonin (1)
- melt electrowriting (MEW) (1)
- memory (1)
- meningioma (1)
- meningococcal disease (1)
- meningococcus (1)
- meniscus implant (1)
- merocyanines (1)
- mesenchymal stem cell (1)
- mesenchymal stem cells (1)
- mesenchymal stromal cell (1)
- mesentery (1)
- meta-analysis (1)
- metabolic flux (1)
- metabolic modeling (1)
- metabolic modelling (1)
- metabolic switch (1)
- metabolism (1)
- metabolism of infected and uninfected host cells (1)
- metabolite profiling (1)
- metabolomic (1)
- metabolomic profiling (1)
- metacognition (1)
- metal complexenes (1)
- metallo-supramolecular polymer (1)
- metaproteomics (1)
- metastasis (1)
- metastasis-associated in colon cancer 1 (MACC1) (1)
- methods (1)
- methylation array (1)
- methylprednisolone (1)
- miR-221-5p (1)
- micelles (1)
- micro processor complex (1)
- micro-chambers (1)
- microRNA (1)
- microbial rhodopsins (1)
- microbial surface component recognising adhesive matrix molecules (1)
- microbiota (1)
- microfilament (1)
- microtubules (1)
- midbody remnant (1)
- migrant (1)
- minerals (1)
- minimal residual disease (1)
- minipig (1)
- minocycline (1)
- mitochondrial genome (1)
- mitochondrial mRyR1 (1)
- mitofusin 2 (1)
- mitosis (1)
- mitotic gene expression (1)
- mitotic genes (1)
- mixed methods (1)
- mobile app (1)
- mobile health intervention (1)
- model-based diagnosis (1)
- molecular biology (1)
- molecular imaging (1)
- molecular signature (1)
- molecular structures (1)
- molecular subtypes (1)
- monitoring (1)
- monocyte-derived DC (1)
- monotoring (1)
- moonlighting (1)
- morphing (1)
- motility (1)
- motor-evoked potentials (MEP) (1)
- mouse feeding model (1)
- movement (1)
- mucormycosis (1)
- multi-photon microscopy (1)
- multi-spectral (1)
- multiphoton microscopy (1)
- multiresistance (1)
- murine (1)
- muscarinic receptors (1)
- mutants (1)
- mycophenolic acid (1)
- myelination (1)
- myeloid-derived suppressor cell (MDSC) (1)
- n-Halbleiter (1)
- n-type semiconductors (1)
- nano-satellite (1)
- nanocomplex (1)
- nanoparticles (1)
- naphthylisoquinoline alkaloids (1)
- nasal mucosal barrier function (1)
- native populations (1)
- natural pest control (1)
- naturalistic scenes (1)
- naïve B cells (1)
- near-IR chromophores (1)
- necroptosis (1)
- need for assistance (1)
- negation detection (1)
- neonatal outcome (1)
- neonates (1)
- nerve injury (1)
- nervous system (1)
- nest microbiota (1)
- neume notation (1)
- neurocytoma (1)
- neurodegenerative disease (1)
- neuroendocrine neoplasia (1)
- neuroendocrine tumors (1)
- neuromuscular disease (1)
- neuronal (1)
- neuronal apoptosis (1)
- neurooncology (1)
- neuropathic pain (1)
- neurovascular unit (1)
- neutral sphingomyelinase-2 (1)
- neutrinos (1)
- next-generation sequencing (1)
- next-generation-sequencing (1)
- niche (1)
- nicknames (1)
- non-invasive fibrosis assessment (1)
- non-smooth optimization (1)
- nonalcoholic fatty liver disease (1)
- noncoding RNA (1)
- nonconvex optimization (1)
- noncovalent complex (1)
- noncovalent nanocomplex (1)
- normal distribution (1)
- nu SVR (1)
- nuclear envelope (1)
- nuclear export (1)
- null-aggregate (1)
- number of (1)
- obesity (1)
- object segmentation (1)
- obstructive sleep apnoea (1)
- office environment (1)
- office-workers (1)
- oligodendrocyte (1)
- oncolysis (1)
- oncolytic vaccinia virus (1)
- one-dimensional systems (1)
- online dating (1)
- online survey (1)
- ontology (1)
- open waste burning (1)
- optical antenna (1)
- optical character recognition (1)
- optical music recognition (1)
- optimal drug targeting (1)
- optimal pharmacological modulation (1)
- optimal treatment strategies (1)
- optimization (1)
- organic solar cells (1)
- orthoreovirus (1)
- oscillations (1)
- osteochondral defect (1)
- otakuism (1)
- outcome devaluation (1)
- ovarian cancer (1)
- overuse injury (1)
- oxidative DNA damage (1)
- oxidative stress (1)
- oxide heterostructure (1)
- oxidische Heterostruktur (1)
- oxindole alkaloids (1)
- oxygen vacancies (1)
- p-block element (1)
- p21-activated kinase Mbt/PAK4 (1)
- paediatrics (1)
- pain generator (1)
- panel sequencing (1)
- panic disorder (1)
- panniculitis (1)
- paranodopathy (1)
- parasexual recombination (1)
- parent-child relationship (1)
- parental perception (1)
- partial agonists (1)
- partial arc (1)
- passive transfer (1)
- patch-clamp (1)
- pathogenesis (1)
- pathogenic bacteria (1)
- pathogens (1)
- peatland (1)
- pediatrics (1)
- peer review (1)
- pefloxacin (1)
- peginterferon bet-1a (1)
- pemphigus (1)
- penetration bias (1)
- penumbra (1)
- peptide inhibitor design (1)
- peptidomoics (1)
- performativity (1)
- pericytes (1)
- permeability (1)
- persistence (1)
- person identity processing (1)
- personality development (1)
- personality judgments (1)
- personalized medicine (1)
- perylene bisimide (1)
- perylene bisimide dimers (1)
- perylene bisimides (1)
- pesicicles (1)
- pharmacokinetics (1)
- pharmacophore map (1)
- phenolic compounds (1)
- phosphorescence (1)
- phosphorescene spectra (1)
- photoconductive interlayer (1)
- photodynamic chemotherapy (1)
- photoelectron spectroscopy (1)
- photoluminescence spectroscopy (1)
- photolysis (1)
- photophysical prosperties (1)
- photophysics (1)
- physical activity (1)
- physical activity promotion (1)
- physical saliency (1)
- phytic acid (1)
- pi-conjugation (1)
- piRNA (1)
- piscine orthoreovirus (1)
- pit membrane diameter (1)
- pkd (1)
- placebo and nocebo effects (1)
- plan comparison (1)
- plant reproduction (1)
- plant-derived metabolites (1)
- plants (1)
- plant–microbe–pollinator triangle (1)
- plant–pathogen interaction (1)
- plaque cross-sectional area (1)
- plasma membrane (1)
- plasma membrane depolarization (1)
- plasma membrane organization (1)
- plasminogen (1)
- platelet (1)
- platelet degranulation (1)
- podosome formation (1)
- point shear wave elastography (1)
- pointing task (1)
- pol(2-oxazoline) (1)
- polarimetery (1)
- polarization (1)
- pollination (1)
- pollination network (1)
- poly(2-oxazine) (1)
- poly(2-oxazoline) (1)
- poly(2-oxazoline)s (1)
- poly(glycidol) (1)
- polycaprolactone (1)
- polyglycerol sulfates (1)
- polynomials (1)
- polyphenols (1)
- population genetics (1)
- position estimation (1)
- positron (1)
- positron annihilation lifetime spectroscopy (1)
- post-fire management (1)
- post-translational modification (1)
- posttranscriptional control (1)
- powerlifting (1)
- precision medicine (1)
- predictive performance (1)
- premature aging (1)
- premixed (1)
- presynaptic hyperekplexia (1)
- preterm infants (1)
- primary endpoint (1)
- primary healthcare (1)
- primary outcome (1)
- primary vascular smooth muscle‐like cells (vSMCs) (1)
- probe-based real-time PCR (1)
- production machines (1)
- prognosis (1)
- prognostic marker (1)
- proliferation (1)
- proliferative darkening syndrome (1)
- prospective memory (1)
- prostate-specific membrane antigen (1)
- protected forests (1)
- protein binding (1)
- protein kinase D1 (1)
- protein processing (1)
- protein transport (1)
- protein-bound uremic toxins (1)
- protein-protein interaction (PPI) (1)
- proteomics (1)
- präfabriziert (1)
- psychiatric disorders (1)
- psychological pain modulation (1)
- psychometrics (1)
- psychosocial adaptation (1)
- psychosocial stress (1)
- psychotherapy (1)
- puberty (1)
- pyrolysis (1)
- quality assurance (1)
- quality of democracy (1)
- quality of life (QoL) (1)
- quantile forecasts (1)
- quantitative analysis (1)
- quantum Monte Carlo (1)
- quantum dot (1)
- quantum gravity (1)
- quantum optics (1)
- questionnaires (1)
- radiation (1)
- radiation sensitivity (1)
- radical (1)
- radical ion pair (1)
- radiopacity (1)
- radiotherapy (1)
- ray (1)
- reaction times (1)
- reactive intermediates (1)
- real life setting (1)
- real world evidence (1)
- reciprocal translocation (1)
- recombinant tissue-type plasminogen activator (1)
- reconstructive surgery (1)
- recording methods (1)
- rectum (1)
- refractory aGvHD (1)
- regulatory T cells (Treg) (1)
- regulatory capital (1)
- regulatory dendritic cells (1)
- reliability (1)
- renal imaging (1)
- repeated sprint (1)
- reprogamming of host cell metabolism (1)
- required hydrophilic–lipophilic balance (1)
- rereading (1)
- resettlement refugees (1)
- resistance (1)
- resonance theory (1)
- restriction factors (1)
- restrictive cardiomyopathy (1)
- resveratrol biosynthesis (1)
- retention interval (1)
- reticulate body (1)
- retinal pigment epithelium (1)
- retrospective (1)
- review (1)
- rhBMP–2 (1)
- ring-expansion reactions (1)
- ring-opening polymerization (1)
- ripk1 (1)
- ripk3 (1)
- risk factors (1)
- risk society (1)
- risk stratification (1)
- robust control (1)
- rulebased analysis (1)
- ruthenium (1)
- sPEG (1)
- saccades (1)
- sacha inchi oil (1)
- sample storage (1)
- saproxylic organisms (1)
- sarcomere (1)
- satellite formation flying (1)
- satellite remote sensing (1)
- scaffold (1)
- search (1)
- seco-NIQs-Naphthylisoindolinone (1)
- secreted effectors (1)
- segmental progeria (1)
- self-determination theory (1)
- semantic segmentation (1)
- semileptonic & radiative decays (1)
- sensor data (1)
- sensor supports (1)
- sentinel (1)
- sentinel prey (1)
- sepsis (1)
- sequence analysis (1)
- sequential addition (1)
- serotonin (1)
- serotonin deficiency (1)
- setting reaction (1)
- sex robots (1)
- short neuropeptide F (1)
- short-range JCT-coupling (1)
- short-range order (1)
- shoulder (1)
- shoulder pain (1)
- shyness (1)
- sigma boranes (1)
- signal specification (1)
- signalling (1)
- silica supraparticles (1)
- simple (1)
- simulation and modeling (1)
- simultaneous presentation paradigm (1)
- single arc (1)
- single cell anatomy (1)
- single photon (1)
- single-molecule tracking (1)
- sirolimus (1)
- site-specific protein modification (1)
- situation awareness (1)
- skeletal progenitor cells (1)
- skewness (1)
- skin model (1)
- sleep (1)
- slope bogs (1)
- small RNA (1)
- small intestinal submucosa scaffold (1)
- small-molecule activation (1)
- smart surfaces (1)
- snowboarder's ankle (1)
- snowboarder's fracture (1)
- soccer (football) (1)
- social anxiety disorder (1)
- sociophonetics (1)
- sodium (1)
- soft tissue sarcoma (1)
- soft x-ray photoemission (1)
- soil fauna (1)
- solar cells (1)
- solid tumors (1)
- solid-state NMR spectroscopy (1)
- solid-state emitters (1)
- solitary bees (1)
- solubility (1)
- solubility enhancement (1)
- solvent-dependent fluorescence yield (1)
- somatic mutations (1)
- somatosensory evoked potential (1)
- somatosensory temporal discrimination (1)
- somatostatin receptor (1)
- spa typing (1)
- spacer-controlled self-assembly (1)
- spacing effect (1)
- spatial analyses (1)
- spatial heterogeneity (1)
- spatial scale (1)
- species richness (1)
- species‐area hypothesis (1)
- specific heat (1)
- sphingomyelinase (1)
- sphingosine kinase (1)
- sphingosine kinase inhibitor SKI-II (1)
- sphingosine-1-phosphate (1)
- spin polarization (1)
- spin relaxation (1)
- spin transport (1)
- spinal muscular atrophy (1)
- spleen (1)
- split renal function (1)
- sporidia (1)
- standardized reporting (1)
- standing (1)
- starPEG (1)
- starPEG hydrogel (1)
- startle response (1)
- static vs. dynamic faces (1)
- statistical distributions (1)
- statistical models (1)
- steering (1)
- stem Cells (1)
- stem cell transplantation (1)
- stereospecific sythesis (1)
- stereotactic body radiation therapy (1)
- stereotactic irradiation (1)
- steric effects (1)
- steroid-resistant aGvHD (1)
- stigma (1)
- storage-pool diseases (1)
- strain rate (1)
- strength training (1)
- stress (1)
- stress fiber (1)
- stress tolerance (1)
- stromal vascular fraction (1)
- strong coupling (1)
- strong light matter coupling (1)
- structural disruption (1)
- structural restriction (1)
- structure-activity (1)
- structure-activity relationship (1)
- structure-activity relationships (1)
- structured illumination microscopy (1)
- subadditivity (1)
- subarachnoid hemorrhage (1)
- submicroscopic chromosome rearrangement (1)
- subsarcolemmal mitochondria (1)
- substandard and falsified medicines from the Congo (1)
- substituent (1)
- subsurface hydrology (1)
- sulfoimines (1)
- sulfur (1)
- super resolution microscopy (1)
- super-resolution fluorescence microscopy (1)
- super-resolution microscopy (1)
- superresolution (1)
- suppressor cells (1)
- suppressor mutation (1)
- surface functionalization (1)
- surface plasmon (1)
- surface transport (1)
- surface water (1)
- surgical and invasive medical procedures (1)
- surgical site infection (1)
- survival analysis (1)
- synapses (1)
- synchrotron radiation (1)
- synchrotron radiatoren (1)
- synergistic effect (1)
- synthetic biology (1)
- systematic affiliation (1)
- systematic drug targeting (1)
- targeted bisulfite sequencing (1)
- taxonomy (1)
- telemedicine (1)
- temozolomide (1)
- temperature‐mediated resource exploitation hypothesis (1)
- temperature‐richness hypothesis (1)
- temporal discrimination threshold (1)
- temporal lobe epilepsy (1)
- tendon-derived stem cell (1)
- terrestrial LiDAR (1)
- theranostics (1)
- therapy (1)
- therapy response (1)
- therapy simulation (1)
- thermal remote sensing (1)
- thiol-ene (1)
- thrombo-inflammation (1)
- thrombosis (1)
- tight junctions (1)
- time lag (1)
- time series (1)
- time-resolved photoelectron spectroscopy (1)
- time-resolved spectroscopy (1)
- tisindoline (1)
- top-down processing (1)
- topminnow (1)
- total body irradiation/busulfan (1)
- toxicity (1)
- trans-acting 2'-5' adenylyl transferase ribozymes (1)
- transcranial magnetic simulation (TMS) (1)
- transcription (1)
- transcription deficiency (1)
- transcriptome (1)
- transfer hydrogenation (1)
- transient absorption (1)
- transient dynamics (1)
- transient elastography (1)
- transient ischemic attack (1)
- transient middle cerebral artery occlusion (1)
- transition metal (1)
- transition metall dichalcogenide monolayer (1)
- transmission (1)
- transplantation (1)
- transposable elements (1)
- tree cavities (1)
- triacylglycerides (1)
- triarylboranes (1)
- triple bonds (1)
- triquinacene derivatives (1)
- trivalent boron (1)
- trypanosomes (1)
- tryptophan hydroxylase 2 (1)
- tumor burden (1)
- tumor control probability (1)
- tumor heterogeneity (1)
- tumor suppressor miRNA (1)
- tumour (1)
- two-component (1)
- two-photon absorption (1)
- tyloses (1)
- type VII secretion system (1)
- ubiquitin ligase (1)
- ubiquitylation (ubiquitination) (1)
- uncanny valley (1)
- uncertainties (1)
- uncertainty (1)
- uneven-aged mountainous (1)
- unmanaged broadleaved forests (1)
- unnecessary alarm (1)
- unsaturated fatty acids (1)
- upconversion (1)
- uptake (1)
- urban environments (1)
- uremic toxins (1)
- urinary tract infections (1)
- vaccinia (1)
- variability (1)
- vascularization (1)
- vasculitis (1)
- verdünnt magnetische Halbleiter (1)
- vertebral body (1)
- vertical and radial variation (1)
- very high energies (VHE) (1)
- very long-chain aliphatic compounds (1)
- vessel lumen diameter (1)
- vessel wall resident stem cells (1)
- vestibular schwannoma (1)
- viability (1)
- video laryngoscopy (1)
- virotherapy (1)
- virtual isocenter (1)
- virus (1)
- viruses (1)
- visual orientation (1)
- visual perception (1)
- visual realism (1)
- vitamin D (1)
- vitamins (1)
- vocational education (1)
- voice-face matching (1)
- volume overload (1)
- walking (1)
- waste sorting (1)
- water balance (1)
- watershed (1)
- weightlifting (1)
- well-being (1)
- white matter lesions (1)
- whole-genome duplication (1)
- whole-genome sequencing (1)
- wild bees (1)
- wood anatomy (1)
- work (1)
- work capacity evaluation (1)
- work engagement (1)
- work performance (1)
- youth (1)
- zeitaufgelöste Spektroskopie (1)
- zielgerichtete Behandlung (1)
- zinc oxide (1)
- zinc oxide nanoparticles (1)
- zonal construct (1)
- zooming (1)
- État d'Imo (1)
- β3 adrenergic receptor (1)
Institute
- Theodor-Boveri-Institut für Biowissenschaften (84)
- Graduate School of Life Sciences (51)
- Physikalisches Institut (38)
- Institut für Psychologie (28)
- Institut für Anorganische Chemie (27)
- Institut für Organische Chemie (27)
- Institut für deutsche Philologie (24)
- Neuphilologisches Institut - Moderne Fremdsprachen (24)
- Neurologische Klinik und Poliklinik (24)
- Medizinische Klinik und Poliklinik II (23)
Schriftenreihe
Sonstige beteiligte Institutionen
- VolkswagenStiftung (24)
- Johns Hopkins School of Medicine (2)
- Bio-Imaging Center Würzburg (1)
- CAPES - Coordenação de Aperfeiçoamento de Pessoal de Nível Superior - the development agency of the Brazilian Federal Government (1)
- Center for Nanosystems Chemistry (CNC), Universität Würzburg (1)
- DAAD - Deutscher Akademischer Austauschdienst (1)
- Department of Hematology and Oncology, Sana Hospital Hof, Hof, Germany (1)
- Department of Laboratory Medicine and Medicine Huddinge, Karolinska Institutet and University Hospital, Stockholm, Sweden (1)
- Department of Medicine A, University Hospital of Münster, Münster, Germany (1)
- Ernst Strüngmann Institute for Neuroscience in Cooperation with Max Planck Society (ESI) (1)
ResearcherID
- B-4606-2017 (1)
Defeat of the antibiotic resistance of pathogenic bacteria is one great challenge today and for the future. In the last century many classes of effective antibacterials have been developed, so that upcoming resistances could be met with novel drugs of various compound classes. Meanwhile, there is a certain lack of research of the pharmaceutical companies, and thus there are missing developments of novel antibiotics. Gram-positive bacteria are the most important cause of clinical infections. The number of novel antibacterials in clinical trials is strongly restricted. There is an urgent need to find novel antibacterials. We used synthetic chemistry to build completely novel hybrid molecules of substituted indoles and benzothiophene. In a simple one-pot reaction, two novel types of thienocarbazoles were yielded. Both indole substituted compound classes have been evaluated as completely novel antibacterials against the Staphylococcus and Enterococcus species. The evaluated partly promising activities depend on the indole substituent type. First lead compounds have been evaluated within in vivo studies. They confirmed the in vitro results for the new classes of small-molecule antibacterials.
Background: Cancer patients are increasingly treated with alpha-particle-emitting radiopharmaceuticals. At the subcellular level, alpha particles induce densely spaced ionizations and molecular damage. Induction of DNA lesions, especially clustered DNA double-strand breaks (DSBs), threatens a cell's survival. Currently, it is under debate to what extent the spatial topology of the damaged chromatin regions and the repair protein arrangements are contributing. Methods: Super-resolution light microscopy (SMLM) in combination with cluster analysis of single molecule signal-point density regions of DSB repair markers was applied to investigate the nano-structure of DNA damage foci tracks of Ra-223 in-solution irradiated leukocytes. Results: Alpha-damaged chromatin tracks were efficiently outlined by γ-H2AX that formed large (super) foci composed of numerous 60–80 nm-sized nano-foci. Alpha damage tracks contained 60–70% of all γ-H2AX point signals in a nucleus, while less than 30% of 53BP1, MRE11 or p-ATM signals were located inside γ-H2AX damage tracks. MRE11 and p-ATM protein fluorescent tags formed focal nano-clusters of about 20 nm peak size. There were, on average, 12 (±9) MRE11 nanoclusters in a typical γ-H2AX-marked alpha track, suggesting a minimal number of MRE11-processed DSBs per track. Our SMLM data suggest regularly arranged nano-structures during DNA repair in the damaged chromatin domain.
Approaches to mimic the complexity of the skeletal mesenchymal stem/stromal cell niche in vitro
(2019)
Mesenchymal stem/stromal cells (MSCs) are an essential element of most modern tissue engineering and regenerative medicine approaches due to their multipotency and immunoregulatory functions. Despite the prospective value of MSCs for the clinics, the stem cells community is questioning their developmental origin, in vivo localization, identification, and regenerative potential after several years of far-reaching research in the field. Although several major progresses have been made in mimicking the complexity of the MSC niche in vitro, there is need for comprehensive studies of fundamental mechanisms triggered by microenvironmental cues before moving to regenerative medicine cell therapy applications. The present comprehensive review extensively discusses the microenvironmental cues that influence MSC phenotype and function in health and disease – including cellular, chemical and physical interactions. The most recent and relevant illustrative examples of novel bioengineering approaches to mimic biological, chemical, and mechanical microenvironmental signals present in the native MSC niche are summarized, with special emphasis on the forefront techniques to achieve bio-chemical complexity and dynamic cultures. In particular, the skeletal MSC niche and applications focusing on the bone regenerative potential of MSC are addressed. The aim of the review was to recognize the limitations of the current MSC niche in vitro models and to identify potential opportunities to fill the bridge between fundamental science and clinical application of MSCs.
Background
Limited data is available to guide the choice of the conditioning regimen for patients with acute myeloid leukemia (AML) undergoing transplant with persistent disease.
Methods
We retrospectively compared outcome of fludarabine-treosulfan (FT), thiotepa-busulfan-fludarabine (TBF), and sequential fludarabine, intermediate dose Ara-C, amsacrine, total body irradiation/busulfan, cyclophosphamide (FLAMSA) conditioning in patients with refractory or relapsed AML.
Results
Complete remission rates at day 100 were 92%, 80%, and 88% for FT, TBF, and FLAMSA, respectively (p=0.13). Non-relapse mortality, incidence of relapse, acute (a) and chronic (c) graft-versus-host disease (GVHD) rates did not differ between the three groups. Overall survival at 2years was 37% for FT, 24% for TBF, and 34% for FLAMSA (p=0.10). Independent prognostic factors for survival were Karnofsky performance score and patient CMV serology (p=0.01; p=0.02), while survival was not affected by age at transplant. The use of anti-thymocyte globulin (ATG) was associated with reduced risk of grade III-IV aGVHD (p=0.02) and cGVHD (p=0.006), with no influence on relapse.
Conclusions
In conclusion, FT, TBF, and FLAMSA regimens provided similar outcome in patients undergoing transplant with active AML. Survival was determined by patient characteristics as Karnofsky performance score and CMV serology, however was not affected by age at transplant. ATG appears able to reduce the incidence of acute and chronic GVHD without influencing relapse risk.
Background
Causality between hepatitis B virus (HBV) infection and diffuse large B-cell lymphoma (DLBCL) was reported in various studies. However, the implication of different virological serum markers of HBV infection in patients with both HBV infection and DLBCL is not fully understood. The aim of this study was to investigate the impact of HBV markers on overall survival (OS) and progression-free survival (PFS) in patients with both HBV infection and DLBCL.
Methods
In this study, patients (n = 40) diagnosed with both HBV infection and DLBCL were identified between 2000 and 2017. Six patients with hepatitis C virus (HCV) and/or human immunodeficiency virus (HIV) co-infection were excluded from this study. We retrospectively analyzed patients’ demographic characteristics, treatment, and the prognostic impact of different HBV markers at first diagnosis of DLBCL (HBsAg, anti-HBs, HBeAg, anti-HBe, and HBV-DNA) on OS and PFS.
Results
The majority of patients (n = 21, 62%) had advanced disease stage (III/IV) at diagnosis. In the first-line therapy, 24 patients (70%) were treated with R-CHOP regimen (rituximab, cyclophosphamide, hydroxydaunorubicin, vincristine, and prednisolone). HBeAg positive patients had a trend toward inferior OS and PFS compared with HBeAg negative patients. Anti-HBe positive patients had a statistically significant better OS and PFS compared with anti-HBe negative group (both P < .0001). Viremia with HBV-DNA ≥ 2 × 107 IU/L had a significant negative impact on OS and PFS (both P < .0001).
Conclusion
High activity of viral replication is associated with a poor survival outcome of patients with both HBV infection and DLBCL.
The identification of biomarker signatures is important for cancer diagnosis and prognosis. However, the detection of clinical reliable signatures is influenced by limited data availability, which may restrict statistical power. Moreover, methods for integration of large sample cohorts and signature identification are limited. We present a step-by-step computational protocol for functional gene expression analysis and the identification of diagnostic and prognostic signatures by combining meta-analysis with machine learning and survival analysis. The novelty of the toolbox lies in its all-in-one functionality, generic design, and modularity. It is exemplified for lung cancer, including a comprehensive evaluation using different validation strategies. However, the protocol is not restricted to specific disease types and can therefore be used by a broad community. The accompanying R package vignette runs in ~1 h and describes the workflow in detail for use by researchers with limited bioinformatics training.
The gastrointestinal tract is abundantly colonized by microbes, yet the translocation of oral species to the intestine is considered a rare aberrant event, and a hallmark of disease. By studying salivary and fecal microbial strain populations of 310 species in 470 individuals from five countries, we found that transmission to, and subsequent colonization of, the large intestine by oral microbes is common and extensive among healthy individuals. We found evidence for a vast majority of oral species to be transferable, with increased levels of transmission in colorectal cancer and rheumatoid arthritis patients and, more generally, for species described as opportunistic pathogens. This establishes the oral cavity as an endogenous reservoir for gut microbial strains, and oral-fecal transmission as an important process that shapes the gastrointestinal microbiome in health and disease.
Biofabrication aims to fabricate biologically functional products through bioprinting or bioassembly (Groll et al 2016 Biofabrication 8 013001). In biofabrication processes, cells are positioned at defined coordinates in three-dimensional space using automated and computer controlled techniques (Moroni et al 2018 Trends Biotechnol. 36 384–402), usually with the aid of biomaterials that are either (i) directly processed with the cells as suspensions/dispersions, (ii) deposited simultaneously in a separate printing process, or (iii) used as a transient support material. Materials that are suited for biofabrication are often referred to as bioinks and have become an important area of research within the field. In view of this special issue on bioinks, we aim herein to briefly summarize the historic evolution of this term within the field of biofabrication. Furthermore, we propose a simple but general definition of bioinks, and clarify its distinction from biomaterial inks.
Two different chromophores, namely a dipolar and an octupolar system, were prepared and their linear and nonlinear optical properties as well as their bioimaging capabilities were compared. Both contain triphenylamine as the donor and a triarylborane as the acceptor, the latter modified with cationic trimethylammonio groups to provide solubility in aqueous media. The octupolar system exhibits a much higher two‐photon brightness, and also better cell viability and enhanced selectivity for lysosomes compared with the dipolar chromophore. Furthermore, both dyes were applied in two‐photon excited fluorescence (TPEF) live‐cell imaging.
Cyclic (amino)(aryl)carbenes (cAArCs) based on the isoindoline core were successfully generated in situ by α‐elimination of 3‐alkoxyisoindolines at high temperatures or by deprotonation of isoindol‐2‐ium chlorides with sodium or copper(I) acetates at low temperatures. 3‐Alkoxy‐isoindolines 2 a,b‐OR (R=Me, Et, iPr) have been prepared in high yields by the addition of a solution of 2‐aryl‐1,1‐diphenylisoindol‐2‐ium triflate (1 a,b‐OTf; a: aryl=Dipp=2,6‐diisopropylphenyl; b: Mesityl‐, Mes=2,4,6‐trimethylphenyl) to the corresponding alcohol (ROH) with NEt3 at room temperature. Furthermore, the reaction of 2 a,b‐OMe in diethyl ether with a tenfold excess of hydrochloric acid led to the isolation of the isoindol‐2‐ium chlorides 1 a,b‐Cl in high yields. The thermally generated cAArC reacts with sulfur to form the thioamide 3 a. Without any additional trapping reagent, in situ generation of 1,1‐diphenylisoidolin‐3‐ylidenes does not lead to the isolation of these compounds, but to the reaction products of the insertion of the carbene carbon atom into an ortho C−H bond of a phenyl substituent, followed by ring‐expansion reaction; namely, anthracene derivatives 9‐N(H)aryl‐10‐Ph‐C14H8 4 a,b (a: Dipp; b: Mes). These compounds are conveniently synthesized by deprotonation of the isoindol‐2‐ium chlorides with sodium acetate in high yields. Deprotonation of 1 a‐Cl with copper(I) acetate at low temperatures afforded a mixture of 4 a and the corresponding cAArC copper(I) chloride 5 a, and allowed the isolation and structural characterization of the first example of a cAArC copper complex of general formula [(cAArC)CuCl].
Nodular lymphocyte predominant Hodgkin lymphoma (NLPHL) can present with different histopathological growth patterns. The impact of these histopathological growth patterns on relapse characteristics is unknown. We therefore analyzed paired biopsies obtained at initial diagnosis and relapse from 33 NLPHL patients who had received first‐line treatment within German Hodgkin Study Group (GHSG) trial protocols, and from a second cohort of 41 relapsed NLPHL patients who had been treated outside GHSG studies. Among the 33 GHSG patients, 21 patients presented with a typical growth pattern at initial diagnosis, whereas 12 patients had a variant histology. The histopathological growth patterns at initial diagnosis and at relapse were consistent in 67% of cases. A variant histology at initial diagnosis was associated with a shorter median time to lymphoma recurrence (2.8 vs 5.2 years; P = .0219). A similar tendency towards a shorter median time to lymphoma recurrence was observed for patients presenting with a variant histology at relapse, irrespective of the growth pattern at initial diagnosis. Results obtained from the 41 NLPHL patients who had been treated outside GHSG studies were comparable (median time to lymphoma recurrence for variant histology vs typical growth pattern at initial diagnosis: 1.5 vs 7.0 years). In conclusion, the histopathological growth pattern remains consistent at relapse in the majority of NLPHL cases, and has major impact on the time of relapse.
Nonalcoholic steatohepatitis (NASH), a primary cause of liver disease, leads to complications such as fibrosis, cirrhosis, and carcinoma, but the pathophysiology of NASH is incompletely understood. Epstein-Barr virus-induced G protein-coupled receptor 2 (EBI2) and its oxysterol ligand 7 alpha,25-dihydroxycholesterol (7 alpha,25-diHC) are recently discovered immune regulators. Several lines of evidence suggest a role of oxysterols in NASH pathogenesis, but rigorous testing has not been performed. We measured oxysterol levels in the livers of NASH patients by LC-MS and tested the role of the EBI2-7 alpha,25-diHC system in a murine feeding model of NASH. Free oxysterol profiling in livers from NASH patients revealed a pronounced increase in 24- and 7-hydroxylated oxysterols in NASH compared with controls. Levels of 24- and 7-hydroxylated oxysterols correlated with histological NASH activity. Histological analysis of murine liver samples demonstrated ballooning and liver inflammation. No significant genotype-related differences were observed in Ebi2(-/-) mice and mice with defects in the 7 alpha,25-diHC synthesizing enzymes CH25H and CYP7B1 compared with wild-type littermate controls, arguing against an essential role of these genes in NASH pathogenesis. Elevated 24- and 7-hydroxylated oxysterol levels were confirmed in murine NASH liver samples. Our results suggest increased bile acid synthesis in NASH samples, as judged by the enhanced level of 7 alpha-hydroxycholest-4-en-3-one and impaired 24S-hydroxycholesterol metabolism as characteristic biochemical changes in livers affected by NASH.
Understanding the mechanisms of early invasion and epithelial defense in opportunistic mold infections is crucial for the evaluation of diagnostic biomarkers and novel treatment strategies. Recent studies revealed unique characteristics of the immunopathology of mucormycoses. We therefore adapted an alveolar Transwell® A549/HPAEC bilayer model for the assessment of epithelial barrier integrity and cytokine response to Rhizopus arrhizus, Rhizomucor pusillus, and Cunninghamella bertholletiae. Hyphal penetration of the alveolar barrier was validated by 18S ribosomal DNA detection in the endothelial compartment. Addition of dendritic cells (moDCs) to the alveolar compartment led to reduced fungal invasion and strongly enhanced pro-inflammatory cytokine response, whereas epithelial CCL2 and CCL5 release was reduced. Despite their phenotypic heterogeneity, the studied Mucorales species elicited the release of similar cytokine patterns by epithelial and dendritic cells. There were significantly elevated lactate dehydrogenase concentrations in the alveolar compartment and epithelial barrier permeability for dextran blue of different molecular weights in Mucorales-infected samples compared to Aspergillus fumigatus infection. Addition of monocyte-derived dendritic cells further aggravated LDH release and epithelial barrier permeability, highlighting the influence of the inflammatory response in mucormycosis-associated tissue damage. An important focus of this study was the evaluation of the reproducibility of readout parameters in independent experimental runs. Our results revealed consistently low coefficients of variation for cytokine concentrations and transcriptional levels of cytokine genes and cell integrity markers. As additional means of model validation, we confirmed that our bilayer model captures key principles of Mucorales biology such as accelerated growth in a hyperglycemic or ketoacidotic environment or reduced epithelial barrier invasion upon epithelial growth factor receptor blockade by gefitinib. Our findings indicate that the Transwell® bilayer model provides a reliable and reproducible tool for assessing host response in mucormycosis.
Translation efficiency can be affected by mRNA stability and secondary structures, including G-quadruplex structures (G4s). The highly conserved DEAH-box helicase DHX36/RHAU resolves G4s on DNA and RNA in vitro, however a systems-wide analysis of DHX36 targets and function is lacking. We map globally DHX36 binding to RNA in human cell lines and find it preferentially interacting with G-rich and G4-forming sequences on more than 4500 mRNAs. While DHX36 knockout (KO) results in a significant increase in target mRNA abundance, ribosome occupancy and protein output from these targets decrease, suggesting that they were rendered translationally incompetent. Considering that DHX36 targets, harboring G4s, preferentially localize in stress granules, and that DHX36 KO results in increased SG formation and protein kinase R (PKR/EIF2AK2) phosphorylation, we speculate that DHX36 is involved in resolution of rG4 induced cellular stress.
Animals, just like humans, can freely move. They do so for various important reasons, such as finding food and escaping predators. Observing these behaviors can inform us about the underlying cognitive processes. In addition, while humans can convey complicated information easily through speaking, animals need to move their bodies to communicate. This has prompted many creative solutions by animal neuroscientists to enable studying the brain during movement. In this review, we first summarize how animal researchers record from the brain while an animal is moving, by describing the most common neural recording techniques in animals and how they were adapted to record during movement. We further discuss the challenge of controlling or monitoring sensory input during free movement.
However, not only is free movement a necessity to reflect the outcome of certain internal cognitive processes in animals, it is also a fascinating field of research since certain crucial behavioral patterns can only be observed and studied during free movement. Therefore, in a second part of the review, we focus on some key findings in animal research that specifically address the interaction between free movement and brain activity. First, focusing on walking as a fundamental form of free movement, we discuss how important such intentional movements are for understanding processes as diverse as spatial navigation, active sensing, and complex motor planning. Second, we propose the idea of regarding free movement as the expression of a behavioral state. This view can help to understand the general influence of movement on brain function.
Together, the technological advancements towards recording from the brain during movement, and the scientific questions asked about the brain engaged in movement, make animal research highly valuable to research into the human “moving brain”.
Hepatic activation of protein kinase C (PKC) isoforms by diacylglycerol (DAG) promotes insulin resistance and contributes to the development of type 2 diabetes (T2D). The closely related protein kinase D (PKD) isoforms act as effectors for DAG and PKC. Here, we showed that PKD3 was the predominant PKD isoform expressed in hepatocytes and was activated by lipid overload. PKD3 suppressed the activity of downstream insulin effectors including the kinase AKT and mechanistic target of rapamycin complex 1 and 2 (mTORC1 and mTORC2). Hepatic deletion of PKD3 in mice improved insulin-induced glucose tolerance. However, increased insulin signaling in the absence of PKD3 promoted lipogenesis mediated by SREBP (sterol regulatory element-binding protein) and consequently increased triglyceride and cholesterol content in the livers of PKD3-deficient mice fed a high-fat diet. Conversely, hepatic-specific overexpression of a constitutively active PKD3 mutant suppressed insulin-induced signaling and caused insulin resistance. Our results indicate that PKD3 provides feedback on hepatic lipid production and suppresses insulin signaling. Therefore, manipulation of PKD3 activity could be used to decrease hepatic lipid content or improve hepatic insulin sensitivity.
Background
To evaluate optimal therapy and potential risk factors.
Methods
Data of DSRCT patients <40 years treated in prospective CWS trials 1997-2015 were analyzed.
Results
Median age of 60 patients was 14.5 years. Male:female ratio was 4:1. Tumors were abdominal/retroperitoneal in 56/60 (93%). 6/60 (10%) presented with a localized mass, 16/60 (27%) regionally disseminated nodes, and 38/60 (63%) with extraperitoneal metastases. At diagnosis, 23/60 (38%) patients had effusions, 4/60 (7%) a thrombosis, and 37/54 (69%) elevated CRP. 40/60 (67%) patients underwent tumor resection, 21/60 (35%) macroscopically complete. 37/60 (62%) received chemotherapy according to CEVAIE (ifosfamide, vincristine, actinomycin D, carboplatin, epirubicin, etoposide), 15/60 (25%) VAIA (ifosfamide, vincristine, adriamycin, actinomycin D) and, 5/60 (8%) P6 (cyclophosphamide, doxorubicin, vincristine, ifosfamide, etoposide). Nine received high-dose chemotherapy, 6 received regional hyperthermia, and 20 received radiotherapy. Among 25 patients achieving complete remission, 18 (72%) received metronomic therapies. Three-year event-free (EFS) and overall survival (OS) were 11% (±8 confidence interval [CI] 95%) and 30% (±12 CI 95%), respectively, for all patients and 26.7% (±18.0 CI 95%) and 56.9% (±20.4 CI 95%) for 25 patients achieving remission. Extra-abdominal site, localized disease, no effusion or ascites only, absence of thrombosis, normal CRP, complete tumor resection, and chemotherapy with VAIA correlated with EFS in univariate analysis. In multivariate analysis, significant factors were no thrombosis and chemotherapy with VAIA. In patients achieving complete remission, metronomic therapy with cyclophosphamide/vinblastine correlated with prolonged time to relapse.
Conclusion
Pleural effusions, venous thrombosis, and CRP elevation were identified as potential risk factors. The VAIA scheme showed best outcome. Maintenance therapy should be investigated further.
Aim: European temperate forests have lost dead wood and the associated biodiversity owing to intensive management over centuries. Nowadays, some of these forests are being restored by enrichment with dead wood, but mostly only at stand scales. Here, we investigated effects of a seminal dead-wood enrichment strategy on saproxylic organisms at the landscape scale.
Location: Temperate European beech forest in southern Germany.
Methods: In a before-after control-impact design, we compared assemblages and gamma diversities of saproxylic organisms in strictly protected old-growth forest areas (reserves) and historically moderately and intensively managed forest areas before and a decade after starting a landscape-wide strategy of dead-wood enrichment.
Results: Before enrichment with dead wood, the gamma diversity of saproxylic organisms in historically intensively managed forest stands was significantly lower than in reserves and historically moderately managed forest stands; this difference disappeared after 10 years of dead-wood enrichment. The species composition of beetles in forest stands of the three historical management intensities differed before the enrichment strategy, but a decade thereafter, the species compositions of previously intensively logged and forest reserve plots were similar. However, the differences in fungal species composition between historical management categories before and after 10 years of enrichment persisted.
Main conclusions: Our results demonstrate that intentional enrichment of dead wood at the landscape scale is a powerful tool for rapidly restoring saproxylic beetle communities and for restoring wood-inhabiting fungal communities, which need longer than a decade for complete restoration. We propose that a strategy of area-wide active restoration combined with some permanent strict refuges is a promising means of promoting the biodiversity of age-long intensively managed Central European beech forests.
Kinesins play an important role in many physiological functions including intracellular vesicle transport and mitosis. The emerging role of kinesins in different cancers led us to investigate the expression and functional role of kinesins in meningioma. Therefore, we re-analyzed our previous microarray dataset of benign, atypical, and anaplastic meningiomas (n = 62) and got evidence for differential expression of five kinesins (KIFC1, KIF4A, KIF11, KIF14 and KIF20A). Further validation in an extended study sample (n = 208) revealed a significant upregulation of these genes in WHO°I to °III meningiomas (WHO°I n = 61, WHO°II n = 88, and WHO°III n = 59), which was most pronounced in clinically more aggressive tumors of the same WHO grade. Immunohistochemical staining confirmed a WHO grade-associated upregulated protein expression in meningioma tissues. Furthermore, high mRNA expression levels of KIFC1, KIF11, KIF14 and KIF20A were associated with shorter progression-free survival. On a functional level, knockdown of kinesins in Ben-Men-1 cells and in the newly established anaplastic meningioma cell line NCH93 resulted in a significantly inhibited tumor cell proliferation upon siRNA-mediated downregulation of KIF11 in both cell lines by up to 95% and 71%, respectively. Taken together, in this study we were able to identify the prognostic and functional role of several kinesin family members of which KIF11 exhibits the most promising properties as a novel prognostic marker and therapeutic target, which may offer new treatment options for aggressive meningiomas.
The functional role of the respiratory epithelium is to generate a physical barrier. In addition, the epithelium supports the innate and acquired immune system through various cytokines and chemokines. However, epithelial cells are also involved in the pathogenesis of various respiratory diseases, some of which are mediated by increased permeability of the mucosal membrane or disturbed mucociliary transport. In addition, it has been shown that epithelial cells are involved in the development of inflammatory respiratory diseases. The following review article focuses on the aspects of epithelial mis-differentiation, in particular with respect to nasal mucosal barrier function, epithelial immunogenicity, nasal epithelial-mesenchymal transition and nasal microbiome.
Combining Distributed Consensus with Robust H-infinity-Control for Satellite Formation Flying
(2019)
Control methods that guarantee stability in the presence of uncertainties are mandatory in space applications. Further, distributed control approaches are beneficial in terms of scalability and to achieve common goals, especially in multi-agent setups like formation control. This paper presents a combination of robust H-infinity control and distributed control using the consensus approach by deriving a distributed consensus-based generalized plant description that can be used in H-infinity synthesis. Special focus was set towards space applications, namely satellite formation flying. The presented results show the applicability of the developed distributed robust control method to a simple, though realistic space scenario, namely a spaceborne distributed telescope. By using this approach, an arbitrary number of satellites/agents can be controlled towards an arbitrary formation geometry. Because of the combination with robust H-infinity control, the presented method satisfies the high stability and robustness demands as found e.g., in space applications.
Chimeric Antigen Receptor Library Screening Using a Novel NF-kappa B/NFAT Reporter Cell Platform
(2019)
Chimeric antigen receptor (CAR)-T cell immunotherapy is under intense preclinical and clinical investigation, and it involves a rapidly increasing portfolio of novel target antigens and CAR designs. We established a platform that enables rapid and high-throughput CAR-screening campaigns with reporter cells derived from the T cell lymphoma line Jurkat. Reporter cells were equipped with nuclear factor kappa B (NF kappa B) and nuclear factor of activated T cells (NFAT) reporter genes that generate a duplex output of enhanced CFP (ECFP) and EGFP, respectively. As a proof of concept, we modified reporter cells with CD19-specific and ROR1-specific CARs, and we detected high-level reporter signals that allowed distinguishing functional from non-functional CAR constructs. The reporter data were highly reproducible, and the time required for completing each testing campaign was substantially shorter with reporter cells (6 days) compared to primary CAR-T cells (21 days). We challenged the reporter platform to a large-scale screening campaign on a ROR1-CAR library, and we showed that reporter cells retrieved a functional CAR variant that was present with a frequency of only 6 in 1.05 x 10(6). The data illustrate the potential to implement this reporter platform into the preclinical development path of novel CAR-T cell products and to inform and accelerate the selection of lead CAR candidates for clinical translation.
Bulb, leaf, scape and flower samples of British bluebells (Hyacinthoides non-scripta) were collected regularly for one growth period. Methanolic extracts of freeze-dried and ground samples showed antitrypanosomal activity, giving more than 50% inhibition, for 20 out of 41 samples. High-resolution mass spectrometry was used in the dereplication of the methanolic extracts of the different plant parts. The results revealed differences in the chemical profile with bulb samples being distinctly different from all aerial parts. High molecular weight metabolites were more abundant in the flowers, shoots and leaves compared to smaller molecular weight ones in the bulbs. The anti-trypanosomal activity of the extracts was linked to the accumulation of high molecular weight compounds, which were matched with saponin glycosides, while triterpenoids and steroids occurred in the inactive extracts. Dereplication studies were employed to identify the significant metabolites via chemotaxonomic filtration and considering their previously reported bioactivities. Molecular networking was implemented to look for similarities in fragmentation patterns between the isolated saponin glycoside at m/z 1445.64 [M + formic-H](-) equivalent to C64H104O33 and the putatively found active metabolite at m/z 1283.58 [M + formic-H](-) corresponding to scillanoside L-1. A combination of metabolomics and bioactivity-guided approaches resulted in the isolation of a norlanostane-type saponin glycoside with antitrypanosoma I activity of 98.9% inhibition at 20 mu M.
Deregulation of the HECT-type ubiquitin ligase E6AP (UBE3A) is implicated in human papilloma virus-induced cervical tumorigenesis and several neurodevelopmental disorders. Yet the structural underpinnings of activity and specificity in this crucial ligase are incompletely understood. Here, we unravel the determinants of ubiquitin recognition by the catalytic domain of E6AP and assign them to particular steps in the catalytic cycle. We identify a functionally critical interface that is specifically required during the initial formation of a thioester-linked intermediate between the C terminus of ubiquitin and the ligase-active site. This interface resembles the one utilized by NEDD4-type enzymes, indicating that it is widely conserved across HECT ligases, independent of their linkage specificities. Moreover, we uncover surface regions in ubiquitin and E6AP, both in the N- and C-terminal portions of the catalytic domain, that are important for the subsequent reaction step of isopeptide bond formation between two ubiquitin molecules. We decipher key elements of linkage specificity, including the C-terminal tail of E6AP and a hydrophilic surface region of ubiquitin in proximity to the acceptor site Lys-48. Intriguingly, mutation of Glu-51, a single residue within this region, permits formation of alternative chain types, thus pointing to a key role of ubiquitin in conferring linkage specificity to E6AP. We speculate that substrate-assisted catalysis, as described previously for certain RING-associated ubiquitin-conjugating enzymes, constitutes a common principle during linkage-specific ubiquitin chain assembly by diverse classes of ubiquitination enzymes, including HECT ligases.
Graft-versus-host disease (GVHD) is a major cause of transplant-related mortality (TRM) after allogeneic haematopoietic stem cell transplantation (HSCT) and presents a challenge in haploidentical HSCT. GVHD may be prevented by ex vivo graft T-cell depletion or in vivo depletion of proliferating lymphocytes. However, both approaches pose significant risks, particularly infections and relapse, compromising survival. A photodepletion strategy to eliminate alloreactive T cells from mismatched donor lymphocyte infusions (enabling administration without immunosuppression), was used to develop ATIR101, an adjunctive therapy for use after haploidentical HSCT. In this phase I dose-finding study, 19 adults (median age: 54 years) with high-risk haematological malignancies were treated with T-cell-depleted human leucocyte antigen-haploidentical myeloablative HSCT followed by ATIR101 at doses of 1 x 10(4)-5 x 10(6) CD3(+) cells/kg (median 31 days post-transplant). No patient received post-transplant immunosuppression or developed grade III/IV acute GVHD, demonstrating the feasibility of ATIR101 infusion for evaluation in two subsequent phase 2 studies. Additionally, we report long-term follow -up of patients treated with ATIR101 in this study. At 1 year, all 9 patients receiving doses of 0 center dot 3-2 x 10(6) CD3(+) cells/kg ATIR101 remained free of serious infections and after more than 8 years, TRM was 0%, relapse-related mortality was 33% and overall survival was 67% in these patients.
Previous magnetic resonance imaging (MRI) studies revealed structural-functional brain reorganization 12 months after gastric-bypass surgery, encompassing cortical and subcortical regions of all brain lobes as well as the cerebellum. Changes in the mean of cluster-wise gray/white matter density (GMD/WMD) were correlated with the individual loss of body mass index (BMI), rendering the BMI a potential marker of widespread surgery-induced brain plasticity. Here, we investigated voxel-by-voxel associations between surgery-induced changes in adiposity, metabolism and inflammation and markers of functional and structural neural plasticity. We re-visited the data of patients who underwent functional and structural MRI, 6 months (n = 27) and 12 months after surgery (n = 22), and computed voxel-wise regression analyses. Only the surgery-induced weight loss was significantly associated with brain plasticity, and this only for GMD changes. After 6 months, weight loss overlapped with altered GMD in the hypothalamus, the brain's homeostatic control site, the lateral orbitofrontal cortex, assumed to host reward and gustatory processes, as well as abdominal representations in somatosensory cortex. After 12 months, weight loss scaled with GMD changes in right cerebellar lobule VII, involved in language-related/cognitive processes, and, by trend, with the striatum, assumed to underpin (food) reward. These findings suggest time-dependent and weight-loss related gray matter plasticity in brain regions involved in the control of eating, sensory processing and cognitive functioning.
2D electrophysiology is often used to determine the electrical properties of neurons, while in the brain, neurons form extensive 3D networks. Thus, performing electrophysiology in a 3D environment provides a closer situation to the physiological condition and serves as a useful tool for various applications in the field of neuroscience. In this study, we established 3D electrophysiology within a fiber-reinforced matrix to enable fast readouts from transfected cells, which are often used as model systems for 2D electrophysiology. Using melt electrowriting (MEW) of scaffolds to reinforce Matrigel, we performed 3D electrophysiology on a glycine receptor-transfected Ltk-11 mouse fibroblast cell line. The glycine receptor is an inhibitory ion channel associated when mutated with impaired neuromotor behaviour. The average thickness of the MEW scaffold was 141.4 ± 5.7µm, using 9.7 ± 0.2µm diameter fibers, and square pore spacings of 100 µm, 200 µm and 400 µm. We demonstrate, for the first time, the electrophysiological characterization of glycine receptor-transfected cells with respect to agonist efficacy and potency in a 3D matrix. With the MEW scaffold reinforcement not interfering with the electrophysiology measurement, this approach can now be further adapted and developed for different kinds of neuronal cultures to study and understand pathological mechanisms under disease conditions.
Major depressive disorder and the anxiety disorders are highly prevalent, disabling and moderately heritable. Depression and anxiety are also highly comorbid and have a strong genetic correlation (r(g) approximate to 1). Cognitive behavioural therapy is a leading evidence-based treatment but has variable outcomes. Currently, there are no strong predictors of outcome. Therapygenetics research aims to identify genetic predictors of prognosis following therapy. We performed genome-wide association meta-analyses of symptoms following cognitive behavioural therapy in adults with anxiety disorders (n = 972), adults with major depressive disorder (n = 832) and children with anxiety disorders (n = 920; meta-analysis n = 2724). We (h(SNP)(2)) and polygenic scoring was used to examine genetic associations between therapy outcomes and psychopathology, personality and estimated the variance in therapy outcomes that could be explained by common genetic variants learning. No single nucleotide polymorphisms were strongly associated with treatment outcomes. No significant estimate of h(SNP)(2) could be obtained, suggesting the heritability of therapy outcome is smaller than our analysis was powered to detect. Polygenic scoring failed to detect genetic overlap between therapy outcome and psychopathology, personality or learning. This study is the largest therapygenetics study to date. Results are consistent with previous, similarly powered genome-wide association studies of complex traits.
Aims
The aim of this study was to determine whether the Joint European Societies guidelines on secondary cardiovascular prevention are followed in everyday practice.
Design
A cross-sectional ESC-EORP survey (EUROASPIRE V) at 131 centres in 81 regions in 27 countries.
Methods
Patients (<80 years old) with verified coronary artery events or interventions were interviewed and examined ≥6 months later.
Results
A total of 8261 patients (females 26%) were interviewed. Nineteen per cent smoked and 55% of them were persistent smokers, 38% were obese (body mass index ≥30 kg/m2), 59% were centrally obese (waist circumference: men ≥102 cm; women ≥88 cm) while 66% were physically active <30 min 5 times/week. Forty-two per cent had a blood pressure ≥140/90 mmHg (≥140/85 if diabetic), 71% had low-density lipoprotein cholesterol ≥1.8 mmol/L (≥70 mg/dL) and 29% reported having diabetes. Cardioprotective medication was: anti-platelets 93%, beta-blockers 81%, angiotensin-converting enzyme inhibitors/angiotensin receptor blockers 75% and statins 80%.
Conclusion
A large majority of coronary patients have unhealthy lifestyles in terms of smoking, diet and sedentary behaviour, which adversely impacts major cardiovascular risk factors. A majority did not achieve their blood pressure, low-density lipoprotein cholesterol and glucose targets. Cardiovascular prevention requires modern preventive cardiology programmes delivered by interdisciplinary teams of healthcare professionals addressing all aspects of lifestyle and risk factor management, in order to reduce the risk of recurrent cardiovascular events.
Background
The oral mucosa has an important role in maintaining barrier integrity at the gateway to the gastrointestinal and respiratory tracts. Smoking is a strong environmental risk factor for the common oral inflammatory disease periodontitis and oral cancer. Cigarette smoke affects gene methylation and expression in various tissues. This is the first epigenome-wide association study (EWAS) that aimed to identify biologically active methylation marks of the oral masticatory mucosa that are associated with smoking.
Results
Ex vivo biopsies of 18 current smokers and 21 never smokers were analysed with the Infinium Methylation EPICBeadChip and combined with whole transcriptome RNA sequencing (RNA-Seq; 16 mio reads per sample) of the same samples. We analysed the associations of CpG methylation values with cigarette smoking and smoke pack year (SPY) levels in an analysis of covariance (ANCOVA). Nine CpGs were significantly associated with smoking status, with three CpGs mapping to the genetic region of CYP1B1 (cytochrome P450 family 1 subfamily B member 1;best p=5.5x10(-8)) and two mapping to AHRR (aryl-hydrocarbon receptor repressor; best p=5.9x10(-9)). In the SPY analysis, 61 CpG sites at 52 loci showed significant associations of the quantity of smoking with changes in methylation values. Here, the most significant association located to the gene CYP1B1, with p=4.0x10(-10). RNA-Seq data showed significantly increased expression of CYP1B1 in smokers compared to non-smokers (p=2.2x10(-14)), together with 13 significantly upregulated transcripts. Six transcripts were significantly downregulated. No differential expression was observed for AHRR. In vitro studies with gingival fibroblasts showed that cigarette smoke extract directly upregulated the expression of CYP1B1.
Conclusion
This study validated the established role of CYP1B1 and AHRR in xenobiotic metabolism of tobacco smoke and highlights the importance of epigenetic regulation for these genes. For the first time, we give evidence of this role for the oral masticatory mucosa.
Osmotic stimulus or stress results in vasopressin release. Animal and human in vitro studies have shown that inflammatory parameters, such as interle ukin-8 (IL-8) and tumor necrosis factor-alpha (TNF-alpha), increase in parallel in the central nervous system and bronchial, corneal or intestinal epithelial cell lines in response to osmotic stimulus. Whether osmotic stimulus directly causes a systemic inflammatory response in humans is unknown. We therefore investigated the influence of osmotic stimulus on circulatory markers of systemic inflammation in healthy volunteers. In this prospective cohort study, 44 healthy volunteers underwent a standardized test protocol with an osmotic stimulus leading into the hyperosmotic/hypernatremic range (serum sodium >= 150 mmol/L) by hypertonic saline infusion. Copeptin - a marker indicating vasopressin activity - serum sodium and osmolality, plasma IL-8 and TNF-alpha were measured at baseline and directly after osmotic stimulus. Median (range) serum sodium increased from 141 mmol/L (136, 147) to 151 mmol/L (145, 154) (P < 0.01), serum osmolality increased from 295 mmol/L (281, 306) to 315 mmol/L (304, 325) (P < 0.01). Median (range) copeptin increased from 4.3 pg/L (1.1, 21.4) to 28.8 pg/L (19.9, 43.4) (P < 0.01). Median (range) IL-8 levels showed a trend to decrease from 0.79 pg/mL (0.37, 1.6) to 0.7 pg/mL (0.4, 1.9) (P < 0.09) and TNF-alpha levels decreased from 0.53 pg/mL (0.11, 1.1) to 0.45 pg/mL (0.1 2, 0.97) (P < 0.036). Contrary to data obtained in vitro, circulating proinflammatory cytokines tend to or decrease in human plasma after osmotic stimulus. In this study, osmotic stimulus does not increase circulating markers of systemic inflammation.
Targeted panel sequencing in pediatric primary cardiomyopathy supports a critical role of TNNI3
(2019)
The underlying genetic mechanisms and early pathological events of children with primary cardiomyopathy (CMP) are insufficiently characterized. In this study, we aimed to characterize the mutational spectrum of primary CMP in a large cohort of patients ≤18 years referred to a tertiary center. Eighty unrelated index patients with pediatric primary CMP underwent genetic testing with a panel‐based next‐generation sequencing approach of 89 genes. At least one pathogenic or probably pathogenic variant was identified in 30/80 (38%) index patients. In all CMP subgroups, patients carried most frequently variants of interest in sarcomere genes suggesting them as a major contributor in pediatric primary CMP. In MYH7, MYBPC3, and TNNI3, we identified 18 pathogenic/probably pathogenic variants (MYH7 n = 7, MYBPC3 n = 6, TNNI3 n = 5, including one homozygous (TNNI3 c.24+2T>A) truncating variant. Protein and transcript level analysis on heart biopsies from individuals with homozygous mutation of TNNI3 revealed that the TNNI3 protein is absent and associated with upregulation of the fetal isoform TNNI1. The present study further supports the clinical importance of sarcomeric mutation—not only in adult—but also in pediatric primary CMP. TNNI3 is the third most important disease gene in this cohort and complete loss of TNNI3 leads to severe pediatric CMP.
Invasive aspergillosis (IA) is a severe complication in immunocompromised patients. Early diagnosis is crucial to decrease its high mortality, yet the diagnostic gold standard (histopathology and culture) is time‐consuming and cannot offer early confirmation of IA. Detection of IA by polymerase chain reaction (PCR) shows promising potential. Various studies have analysed its diagnostic performance in different clinical settings, especially addressing optimal specimen selection. However, direct comparison of different types of specimens in individual patients though essential, is rarely reported. We systematically assessed the diagnostic performance of an Aspergillus‐specific nested PCR by investigating specimens from the site of infection and comparing it with concurrent blood samples in individual patients (pts) with IA. In a retrospective multicenter analysis PCR was performed on clinical specimens (n = 138) of immunocompromised high‐risk pts (n = 133) from the site of infection together with concurrent blood samples. 38 pts were classified as proven/probable, 67 as possible and 28 as no IA according to 2008 European Organization for Research and Treatment of Cancer/Mycoses Study Group consensus definitions. A considerably superior performance of PCR from the site of infection was observed particularly in pts during antifungal prophylaxis (AFP)/antifungal therapy (AFT). Besides a specificity of 85%, sensitivity varied markedly in BAL (64%), CSF (100%), tissue samples (67%) as opposed to concurrent blood samples (8%). Our results further emphasise the need for investigating clinical samples from the site of infection in case of suspected IA to further establish or rule out the diagnosis.
Aberrant methylation of DNA is supposed to be a major and early driver of colonic adenoma development, which may result in colorectal cancer (CRC). Although gene methylation assays are used already for CRC screening, differential epigenetic alterations of recurring and nonrecurring colorectal adenomas have yet not been systematically investigated. Here, we collected a sample set of formalin‐fixed paraffin‐embedded colorectal low‐grade adenomas (n = 72) consisting of primary adenomas without and with recurrence (n = 59), recurrent adenomas (n = 10), and normal mucosa specimens (n = 3). We aimed to unveil differentially methylated CpG positions (DMPs) across the methylome comparing not only primary adenomas without recurrence vs primary adenomas with recurrence but also primary adenomas vs recurrent adenomas using the Illumina Human Methylation 450K BeadChip array. Unsupervised hierarchical clustering exhibited a significant association of methylation patterns with histological adenoma subtypes. No significant DMPs were identified comparing primary adenomas with and without recurrence. Despite that, a total of 5094 DMPs (false discovery rate <0.05; fold change >10%) were identified in the comparisons of recurrent adenomas vs primary adenomas with recurrence (674; 98% hypermethylated), recurrent adenomas vs primary adenomas with and without recurrence (241; 99% hypermethylated) and colorectal adenomas vs normal mucosa (4179; 46% hypermethylated). DMPs in cytosine‐phosphate‐guanine (CpG) islands were frequently hypermethylated, whereas open sea‐ and shelf‐regions exhibited hypomethylation. Gene ontology analysis revealed enrichment of genes associated with the immune system, inflammatory processes, and cancer pathways. In conclusion, our methylation data could assist in establishing a more robust and reproducible histological adenoma classification, which is a prerequisite for improving surveillance guidelines.
The synthetic compound dendritic polyglycerol sulfate (dPGS) is a pleiotropic acting molecule but shows a high binding affinity to immunological active molecules as L‐/P‐selectin or complement proteins leading to well described anti‐inflammatory properties in various mouse models. In order to make a comprehensive evaluation of the direct effect on the innate immune system, macrophage polarization is analyzed in the presence of dPGS on a phenotypic but also metabolic level. dPGS administered macrophages show a significant increase of MCP1 production paralleled by a reduction of IL‐10 secretion. Metabolic analysis reveals that dPGS could potently enhance the glycolysis and mitochondrial respiration in M0 macrophages as well as decrease the mitochondrial respiration of M2 macrophages. In summary the data indicate that dPGS polarizes macrophages into a pro‐inflammatory phenotype in a metabolic pathway‐dependent manner.
Aims
Volume overload (VO) and pressure overload (PO) induce differential cardiac remodelling responses including distinct signalling pathways. Extracellular signal‐regulated kinases 1 and 2 (ERK1/2), key signalling components in the mitogen‐activated protein kinase (MAPK) pathways, modulate cardiac remodelling during pressure overload (PO). This study aimed to assess their role in VO‐induced cardiac remodelling as this was unknown.
Methods and results
Aortocaval fistula (Shunt) surgery was performed in mice to induce cardiac VO. Two weeks of Shunt caused a significant reduction of cardiac ERK1/2 activation in wild type (WT) mice as indicated by decreased phosphorylation of the TEY (Thr‐Glu‐Tyr) motif (−28% as compared with Sham controls, P < 0.05). Phosphorylation of other MAPKs was unaffected. For further assessment, transgenic mice with cardiomyocyte‐specific ERK2 overexpression (ERK2tg) were studied. At baseline, cardiac ERK1/2 phosphorylation in ERK2tg mice remained unchanged compared with WT littermates, and no overt cardiac phenotype was observed; however, cardiac expression of the atrial natriuretic peptide was increased on messenger RNA (3.6‐fold, P < 0.05) and protein level (3.1‐fold, P < 0.05). Following Shunt, left ventricular dilation and hypertrophy were similar in ERK2tg mice and WT littermates. Left ventricular function was maintained, and changes in gene expression indicated reactivation of the foetal gene program in both genotypes. No differences in cardiac fibrosis and kinase activation was found amongst all experimental groups, whereas apoptosis was similarly increased through Shunt in ERK2tg and WT mice.
Conclusions
VO‐induced eccentric hypertrophy is associated with reduced cardiac ERK1/2 activation in vivo. Cardiomyocyte‐specific overexpression of ERK2, however, does not alter cardiac remodelling during VO. Future studies need to define the pathophysiological relevance of decreased ERK1/2 signalling during VO.
Background
Deep brain stimulation (DBS) is an effective evidence‐based therapy for dystonia. However, no unequivocal predictors of therapy responses exist. We investigated whether patients optimally responding to DBS present distinct brain network organization and structural patterns.
Methods
From a German multicenter cohort of 82 dystonia patients with segmental and generalized dystonia who received DBS implantation in the globus pallidus internus, we classified patients based on the clinical response 3 years after DBS. Patients were assigned to the superior‐outcome group or moderate‐outcome group, depending on whether they had above or below 70% motor improvement, respectively. Fifty‐one patients met MRI‐quality and treatment response requirements (mean age, 51.3 ± 13.2 years; 25 female) and were included in further analysis. From preoperative MRI we assessed cortical thickness and structural covariance, which were then fed into network analysis using graph theory. We designed a support vector machine to classify subjects for the clinical response based on individual gray‐matter fingerprints.
Results
The moderate‐outcome group showed cortical atrophy mainly in the sensorimotor and visuomotor areas and disturbed network topology in these regions. The structural integrity of the cortical mantle explained about 45% of the DBS stimulation amplitude for optimal response in individual subjects. Classification analyses achieved up to 88% of accuracy using individual gray‐matter atrophy patterns to predict DBS outcomes.
Conclusions
The analysis of cortical integrity, informed by group‐level network properties, could be developed into independent predictors to identify dystonia patients who benefit from DBS.
The detection of toxic gases, such as NH\(_{3}\) and CO, in the environment is of high interest in chemical, electronic, and automotive industry as even small amounts can display a health risk for workers. Sensors for the real‐time monitoring of these gases should be simple, robust, reversible, highly sensitive, inexpensive and show a fast response. The indicator supraparticles presented herein can fulfill all of these requirements. They consist of silica nanoparticles, which are assembled to supraparticles upon spray‐drying. Sensing molecules such as Reichardt's dye and a binuclear rhodium complex are loaded onto the microparticles to target NH\(_{3}\) and CO detection, respectively. The spray‐drying technique affords high flexibility in primary nanoparticle size selection and thus, easy adjustment of the porosity and specific surface area of the obtained micrometer‐sized supraparticles. This ultimately enables the fine‐tuning of the sensor sensitivity and response. For the application of the indicator supraparticles in a gas detection device, they can be immobilized on a coating. Due to their microscale size, they are large enough to poke out of thin coating layers, thus guaranteeing their gas accessibility, while being small enough to be applicable to flexible substrates.
This article focuses on selected Latin American female rap artists (Anita Tijoux, Rebeca Lane, and the duo Krudas Cubensi), and the way they perform feminism, autobiography and testimony through their lyrics and performances. The analysis concentrates on the synergies between the texts themselves, the official music videos shared on YouTube and the background music. It aims to demonstrate that only such a synergistic approach to rap allows a profound understanding of its particularities and its contributions to feminist discourses and spaces for feminist testimony in the current rise of both right-wing politics and feminist movements on the continent.
This contribution deals with the phonetic heterogeneity of spoken Spanish in Andalusia in the sector of public auditory media, specifically in the program ¡Anda Levanta! of Canal Fiesta Radio. First, we take into consideration Article 10 of the Statute of the Autonomy of Andalusia, which enhances the protection, promotion, study, and prestige of the Andalusian modalities and its respective variety (cf. Parlamento de Andalucía 2007: 13). Second, we refer to the Libro de Estilo, a mandatory guide for presenters of public audiovisual media in Andalusia since 2014. The results of the qualitative analysis indicate divergences between the presenters and their audience with regard to their use of phonetic characteristics typical of the Andalusian varieties: where the presenters tend to avoid the salient aspects of the varieties, the audience employs a range of phonetic characteristics typical for Andalusian varieties, including some of the characteristics that are considered less prestigious.
The electron‐precise binary boron subhalide species [B\(_2\)X\(_6\)]\(^{2−}\) X=F, Br, I) were synthesized and their structures confirmed by X‐ray crystallography. The existence of the previously claimed [B\(_2\)Cl\(_6\)]\(^{2−}\), which had been questioned, was also confirmed by X‐ray crystallography. The dianions are isoelectronic to hexahaloethanes, are subhalide analogues of the well‐known tetrahaloborate anions (BX\(_4\)\(^−\)), and are rare examples of molecular electron‐precise binary boron species beyond B\(_2\)X\(_4\), BX\(_3\), and [BX\(_4\)]\(^−\).
The membrane protein EsaA is a conserved component of the type VIIb secretion system. Limited proteolysis of purified EsaA from Staphylococcus aureus USA300 identified a stable 48 kDa fragment, which was mapped by fingerprint mass spectrometry to an uncharacterized extracellular segment of EsaA. Analysis by circular dichroism spectroscopy showed that this fragment folds into a single stable domain made of mostly α‐helices with a melting point of 34.5°C. Size‐exclusion chromatography combined with multi‐angle light scattering indicated the formation of a dimer of the purified extracellular domain. Octahedral crystals were grown in 0.2 M ammonium citrate tribasic pH 7.0, 16% PEG 3350 using the hanging‐drop vapor‐diffusion method. Diffraction data were analyzed to 4.0 Å resolution, showing that the crystals belonged to the enantiomorphic tetragonal space groups P41212 or P43212, with unit‐cell parameters a = 197.5, b = 197.5, c = 368.3 Å, α = β = γ = 90°.
Here, we present the unique case of a 51‐year‐old German patient with multiple myeloma excreting Ascaris lumbricoides in his stool five weeks after allogeneic hematopoietic stem cell transplantation. Stool analysis remained negative for the presence of eggs, and there was no eosinophilia in the peripheral blood at any time around stem cell transplantation. The patient was commenced on a three‐day treatment with mebendazole, which was well tolerated. No serious interactions with the concomitant post‐transplant medication or negative effects on the hematopoiesis were observed, and the myeloma still is in complete remission. To our knowledge, this is the first report on excretion of A lumbricoides in the context of allogeneic stem cell transplantation. The case is remarkable with view to the fact that the parasite has supposedly survived all courses of myeloma treatment including autologous and allogeneic conditioning. Parasitosis with A lumbricoides has a worldwide prevalence of about a billion and is extremely rare in northern Europe. Possibly the patient got infected during a trip to Egypt years before multiple myeloma was diagnosed.
Combined MEK‐BRAF inhibition is a well‐established treatment strategy in BRAF‐mutated cancer, most prominently in malignant melanoma with durable responses being achieved through this targeted therapy. However, a subset of patients face primary unresponsiveness despite presence of the activating mutation at position V600E, and others acquire resistance under treatment. Underlying resistance mechanisms are largely unknown, and diagnostic tests to predict tumor response to BRAF‐MEK inhibitor treatment are unavailable.
Multiple myeloma represents the second most common hematologic malignancy, and point mutations in BRAF are detectable in about 10% of patients. Targeted inhibition has been successfully applied, with mixed responses observed in a substantial subset of patients mirroring the widespread spatial heterogeneity in this genomically complex disease. Central nervous system (CNS) involvement is an extremely rare, extramedullary form of multiple myeloma that can be diagnosed in less than 1% of patients. It is considered an ultimate high‐risk feature, associated with unfavorable cytogenetics, and, even with intense treatment applied, survival is short, reaching less than 12 months in most cases. Here we not only describe the first patient with an extramedullary CNS relapse responding to targeted dabrafenib and trametinib treatment, we furthermore provide evidence that a point mutation within the capicua transcriptional repressor (CIC) gene mediated the acquired resistance in this patient.
The steric and electronic properties of aryl substituents in monoaryl borohydrides (Li[ArBH\(_3\)]) and dihydroboranes were systematically varied and their reactions with [Ru(PCy\(_3\))\(_2\)HCl(H\(_2\))] (Cy: cyclohexyl) were studied, resulting in bis(σ)‐borane or terminal borylene complexes of ruthenium. These variations allowed for the investigation of the factors involved in the activation of dihydroboranes in the synthesis of terminal borylene complexes. The complexes were studied by multinuclear NMR spectroscopy, mass spectrometry, X‐ray diffraction analysis, and density functional theory (DFT) calculations. The experimental and computational results suggest that the ortho‐substitution of the aryl groups is necessary for the formation of terminal borylene complexes.
Viruses and intracellular bacterial pathogens (IBPs) have in common the need of suitable host cells for efficient replication and proliferation during infection. In human infections, the cell types which both groups of pathogens are using as hosts are indeed quite similar and include phagocytic immune cells, especially monocytes/macrophages (MOs/MPs) and dendritic cells (DCs), as well as nonprofessional phagocytes, like epithelial cells, fibroblasts and endothelial cells. These terminally differentiated cells are normally in a metabolically quiescent state when they are encountered by these pathogens during infection. This metabolic state of the host cells does not meet the extensive need for nutrients required for efficient intracellular replication of viruses and especially IBPs which, in contrast to the viral pathogens, have to perform their own specific intracellular metabolism to survive and efficiently replicate in their host cell niches. For this goal, viruses and IBPs have to reprogram the host cell metabolism in a pathogen-specific manner to increase the supply of nutrients, energy, and metabolites which have to be provided to the pathogen to allow its replication. In viral infections, this appears to be often achieved by the interaction of specific viral factors with central metabolic regulators, including oncogenes and tumor suppressors, or by the introduction of virus-specific oncogenes. Less is so far known on the mechanisms leading to metabolic reprogramming of the host cell by IBPs. However, the still scant data suggest that similar mechanisms may also determine the reprogramming of the host cell metabolism in IBP infections. In this review, we summarize and compare the present knowledge on this important, yet still poorly understood aspect of pathogenesis of human viral and especially IBP infections.
Sacha inchi oil is a premier raw material with highly nutritional and functional features for the foodstuff, pharmaceutical, beauty, and personal care industries. One of the most important facts about this oil is the huge chemical content of unsaturated and polyunsaturated fatty acids. However, the current available information on the characterization of the triglyceride composition and the advance physicochemical parameters relevant to emulsion development is limited. Therefore, this research focused on providing a detailed description of the lipid composition using high-resolution tandem mass spectrometry and thorough physicochemical characterization to find the value of the required hydrophilic–lipophilic balance (HLB). For this, a study in the interfacial tension was evaluated, followed by the assessment of different parameters such as creaming index, droplet size, viscosity, zeta potential, pH, and electrical conductivity for a series emulsified at thermal stress condition. The results show that fatty acids are arranged into glycerolipids and the required HLB to achieve the maximum physical stability is around 8.
Active Galactic Nuclei emit radiation over the whole electromagnetic spectrum up to TeV energies. Blazars are one subtype with their jets pointing towards the observer. One of their typical features is extreme variability on timescales, from minutes to years. The fractional variability is an often used parameter for investigating the degree of variability of a light curve. Different detection methods and sensitivities of the instruments result in differently binned data and light curves with gaps. As they can influence the physics interpretation of the broadband variability, the effects of these differences on the fractional variability need to be studied. In this paper, we study the systematic effects of completeness in time coverage and the sampling rate. Using public data from instruments monitoring blazars in various energy ranges, we study the variability of the bright TeV blazars Mrk 421 and Mrk 501 over the electromagnetic spectrum, taking into account the systematic effects, and compare our findings with previous results. Especially in the TeV range, the fractional variability is higher than in previous studies, which can be explained by the much longer (seven years compared to few weeks) and more complete data sample.
The photophysical properties (absorption, fluorescence and phosphorescence) of a series of triarylboranes of the form 4-D-C\(_6\)H\(_4\)-B(Ar)\(_2\) (D=\(^t\)Bu or NPh\(_2\); Ar=mesityl (Mes) or 2,4,6-tris(trifluoromethylphenyl (Fmes)) were analyzed theoretically using state-of-the-art DFT and TD-DFT methods. Simulated emission spectra and computed decay rate constants are in very good agreement with the experimental data. Unrestricted electronic computations including vibronic contributions explain the unusual optical behavior of 4-\(^t\)Bu-C\(_6\)H\(_4\)-B(Fmes)\(_2\) 2, which shows both fluorescence and phosphorescence at nearly identical energies (at 77 K in a frozen glass). Analysis of the main normal modes responsible for the phosphorescence vibrational fine structure indicates that the bulky tert-butyl group tethered to the phenyl ring is strongly involved. Interestingly, in THF solvent, the computed energies of the singlet and triplet excited states are very similar for compound 2 only, which may explain why 2 shows phosphorescence in contrast to the other members of the series.
A series of photoactivatable CO‐releasing molecules (PhotoCORMs) was prepared from manganese pentacarbonyl bromide and 1H‐benzimidazol‐2‐ylmethyl‐(N‐phenyl)amine ligands (L) bearing different electron‐donating and electron‐withdrawing groups R = H, 4‐CH\(_3\), 4‐OCH\(_3\), 4‐Cl, 4‐NO\(_2\), 2‐, 3‐, and 4‐COOCH\(_3\) on the phenyl substituent to give octahedral manganese(I) complexes of the general formula [MnBr(CO)\(_3\)(L)]. Aerated DMSO solutions of the compounds are stable in the dark for 16 h with no CO release. However, the compounds rapidly release CO upon illumination at 412–525 nm, depending on the substitution pattern. Its influence on the photophysical and photochemical properties was systematically explored using UV/Vis spectroscopy and CO release measurements with a commercial gas sensor system. In the nitro‐substituted compound, the electronically excited state switched from benzimidazole‐ to phenyl‐centered, leading to a markedly different photochemical behavior of this visible‐light activated PhotoCORM.
It is one of the primary goals of medical care to secure good quality of life (QoL) while prolonging survival. This is a major challenge in severe medical conditions with a prognosis such as amyotrophic lateral sclerosis (ALS). Further, the definition of QoL and the question whether survival in this severe condition is compatible with a good QoL is a matter of subjective and culture-specific debate. Some people without neurodegenerative conditions believe that physical decline is incompatible with satisfactory QoL. Current data provide extensive evidence that psychosocial adaptation in ALS is possible, indicated by a satisfactory QoL. Thus, there is no fatalistic link of loss of QoL when physical health declines. There are intrinsic and extrinsic factors that have been shown to successfully facilitate and secure QoL in ALS which will be reviewed in the following article following the four ethical principles (1) Beneficence, (2) Non-maleficence, (3) Autonomy and (4) Justice, which are regarded as key elements of patient centered medical care according to Beauchamp and Childress. This is a JPND-funded work to summarize findings of the project NEEDSinALS (www.NEEDSinALS.com) which highlights subjective perspectives and preferences in medical decision making in ALS.
The opportunistic fungal pathogen Aspergillus fumigatus can cause severe infections, particularly in immunocompromised individuals. Upon infection, A. fumigatus faces the powerful and directly acting immune defense of the human host. The mechanisms on how A. fumigatus evades innate immune attack and complement are still poorly understood. Here, we identify A. fumigatus enolase, AfEno1, which was also characterized as fungal allergen, as a surface ligand for human plasma complement regulators. AfEno1 binds factor H, factor-H-like protein 1 (FHL-1), C4b binding protein (C4BP), and plasminogen. Factor H attaches to AfEno1 via two regions, via short conserved repeats (SCRs) 6–7 and 19–20, and FHL-1 contacts AfEno1 via SCRs 6–7. Both regulators when bound to AfEno1 retain cofactor activity and assist in C3b inactivation. Similarly, the classical pathway regulator C4BP binds to AfEno1 and bound to AfEno1; C4BP assists in C4b inactivation. Plasminogen which binds to AfEno1 via lysine residues is accessible for the tissue-type plasminogen activator (tPA), and active plasmin cleaves the chromogenic substrate S2251, degrades fibrinogen, and inactivates C3 and C3b. Plasmin attached to swollen A. fumigatus conidia damages human A549 lung epithelial cells, reduces the cellular metabolic activity, and induces cell retraction, which results in exposure of the extracellular matrix. Thus, A. fumigatus AfEno1 is a moonlighting protein and virulence factor which recruits several human regulators. The attached human regulators allow the fungal pathogen to control complement at the level of C3 and to damage endothelial cell layers and tissue components.
Brushite cements have been clinically used for irregular bone defect filling applications, and various strategies have been previously reported to modify and improve their physicochemical properties such as strength and injectability. However, strategies to address other limitations of brushite cements such as low radiopacity or acidity without negatively impacting mechanical strength have not yet been reported. In this study, we report the effect of substituting the beta-tricalcium phosphate reactant in brushite cement with baghdadite (Ca\(_3\)ZrSi\(_2\)O\(_9\)), a bioactive zirconium-doped calcium silicate ceramic, at various concentrations (0, 5, 10, 20, 30, 50, and 100 wt%) on the properties of the final brushite cement product. X-ray diffraction profiles indicate the dissolution of baghdadite during the cement reaction, without affecting the crystal structure of the precipitated brushite. EDX analysis shows that calcium is homogeneously distributed within the cement matrix, while zirconium and silicon form cluster-like aggregates with sizes ranging from few microns to more than 50 µm. X-ray images and µ-CT analysis indicate enhanced radiopacity with increased incorporation of baghdadite into brushite cement, with nearly a doubling of the aluminium equivalent thickness at 50 wt% baghdadite substitution. At the same time, compressive strength of brushite cement increased from 12.9 ± 3.1 MPa to 21.1 ± 4.1 MPa with 10 wt% baghdadite substitution. Culture medium conditioned with powdered brushite cement approached closer to physiological pH values when the cement is incorporated with increasing amounts of baghdadite (pH = 6.47 for pure brushite, pH = 7.02 for brushite with 20 wt% baghdadite substitution). Baghdadite substitution also influenced the ionic content in the culture medium, and subsequently affected the proliferative activity of primary human osteoblasts in vitro. This study indicates that baghdadite is a beneficial additive to enhance the radiopacity, mechanical performance and cytocompatibility of brushite cement
To facilitate true regeneration, a vascular graft should direct the evolution of a neovessel to obtain the function of a native vessel. For this, scaffolds have to permit the formation of an intraluminal endothelial cell monolayer, mimicking the tunica intima. In addition, when attempting to mimic a tunica media‐like outer layer, the stacking and orientation of vascular smooth muscle cells (vSMCs) should be recapitulated. An integral scaffold design that facilitates this has so far remained a challenge. A hybrid fabrication approach is introduced by combining solution electrospinning and melt electrowriting. This allows a tissue‐structure mimetic, hierarchically bilayered tubular scaffold, comprising an inner layer of randomly oriented dense fiber mesh and an outer layer of microfibers with controlled orientation. The scaffold supports the organization of a continuous luminal endothelial monolayer and oriented layers of vSM‐like cells in the media, thus facilitating control over specific and tissue‐mimetic cellular differentiation and support of the phenotypic morphology in the respective layers. Neither soluble factors nor a surface bioactivation of the scaffold is needed with this approach, demonstrating that heterotypic scaffold design can direct physiological tissue‐like cell organization and differentiation.
Autosomal recessive congenital ichthyosis (ARCI) belongs to a heterogeneous group of disorders of keratinization. To date, 10 genes have been identified to be causative for ARCI. NIPAL4 (Nipa‐Like Domain‐Containing 4) is the second most commonly mutated gene in ARCI. In this study, we present a large cohort of 101 families affected with ARCI carrying mutations in NIPAL4. We identified 16 novel mutations and increase the total number of pathogenic mutations in NIPAL4 to 34. Ultrastructural analysis of biopsies from six patients showed morphological abnormalities consistent with an ARCI EM type III. One patient with a homozygous splice site mutation, which leads to a loss of NIPAL4 mRNA, showed additional ultrastructural aberrations together with a more severe clinical phenotype. Our study gives insights into the frequency of mutations, a potential hot spot for mutations, and genotype–phenotype correlations.
The reactivity of a diruthenium tetrahydride complex towards three selected dihydroboranes was investigated. The use of [DurBH\(_{2}\)] (Dur=2,3,5,6‐Me\(_{4}\)C\(_{6}\)H) and [(Me\(_{3}\)Si)\(_{2}\)NBH\(_{2}\)] led to the formation of bridging borylene complexes of the form [(Cp\(^{*}\)RuH)\(_{2}\)BR] (Cp\(^{*}\)=C\(_{5}\)Me\(_{5}\); 1 a: R=Dur; 1 b: R=N(SiMe\(_{3}\))\(_{2}\)) through oxidative addition of the B−H bonds with concomitant hydrogen liberation. Employing the more electron‐deficient dihydroborane [3,5‐(CF\(_{3}\))\(_{2}\)‐C\(_{6}\)H\(_{3}\)BH\(_{2}\)] led to the formation of an anionic complex bearing a tetraarylated chain of four boron atoms, namely Li(THF)\(_{4}\)[(Cp\(^{*}\)Ru)\(_{2}\)B\(_{4}\)H\(_{5}\)(3,5‐(CF\(_{3}\))\(_{2}\)C\(_{6}\)H\(_{3}\))\(_{4}\)] (4), through an unusual, incomplete threefold dehydrocoupling process. A comparative theoretical investigation of the bonding in a simplified model of 4 and the analogous complex nido‐[1,2(Cp\(^{*}\)Ru)\(_{2}\)(μ‐H)B\(_{4}\)H\(_{9}\)] (I) indicates that there appear to be no classical σ‐bonds between the boron atoms in complex I, whereas in the case of 4 the B\(_{4}\) chain better resembles a network of three B−B σ bonds, the central bond being significantly weaker than the other two.
Stereospecific Synthesis and Photophysical Properties of Propeller-Shaped C\(_{90}\)H\(_{48}\) PAH
(2019)
Herein, we have synthesized an enantiomerically pure propeller‐shaped PAH, C\(_{90}\)H\(_{48}\), possessing three [7]helicene and three [5]helicene subunits. This compound can be obtained in gram quantities in a straightforward manner. The photophysical and chiroptical properties were investigated using UV/Vis absorption and emission, optical rotation and circular dichroism spectroscopy, supported by DFT calculations. The nonlinear optical properties were investigated by two‐photon absorption measurements using linearly and circularly polarized light. The extremely twisted structure and packing of the homochiral compound were investigated by single‐crystal X‐ray diffraction analysis.
Up to three polychlorinated pyridyldiphenylmethyl radicals bridged by a triphenylamine carrying electron withdrawing (CN), neutral (Me), or donating (OMe) groups were synthesized and analogous radicals bridged by tris(2,6‐dimethylphenyl)borane were prepared for comparison. All compounds were as stable as common closed‐shell organic compounds and showed significant fluorescence upon excitation. Electronic, magnetic, absorption, and emission properties were examined in detail, and experimental results were interpreted using DFT calculations. Oxidation potentials, absorption and emission energies could be tuned depending on the electron density of the bridges. The triphenylamine bridges mediated intramolecular weak antiferromagnetic interactions between the radical spins, and the energy difference between the high spin and low spin states was determined by temperature dependent ESR spectroscopy and DFT calculations. The fluorescent properties of all radicals were examined in detail and revealed no difference for high and low spin states which facilitates application of these dyes in two‐photon absorption spectroscopy and OLED devices.
The reaction products of the picolyl radicals at high temperature were characterized by mass‐selective threshold photoelectron spectroscopy in the gas phase. Aminomethylpyridines were pyrolyzed to initially produce picolyl radicals (m /z =92). At higher temperatures further thermal reaction products are generated in the pyrolysis reactor. All compounds were identified by mass‐selected threshold photoelectron spectroscopy and several hitherto unexplored reactive molecules were characterized. The mechanism for several dissociation pathways was outlined in computations. The spectrum of m /z =91, resulting from hydrogen loss of picolyl, shows four isomers, two ethynyl pyrroles with adiabatic ionization energies (IE\(_{ad}\)) of 7.99 eV (2‐ethynyl‐1H ‐pyrrole) and 8.12 eV (3‐ethynyl‐1H ‐pyrrole), and two cyclopentadiene carbonitriles with IE′s of 9.14 eV (cyclopenta‐1,3‐diene‐1‐carbonitrile) and 9.25 eV (cyclopenta‐1,4‐diene‐1‐carbonitrile). A second consecutive hydrogen loss forms the cyanocyclopentadienyl radical with IE′s of 9.07 eV (T\(_0\)) and 9.21 eV (S\(_1\)). This compound dissociates further to acetylene and the cyanopropynyl radical (IE=9.35 eV). Furthermore, the cyclopentadienyl radical, penta‐1,3‐diyne, cyclopentadiene and propargyl were identified in the spectra. Computations indicate that dissociation of picolyl proceeds initially via a resonance‐stabilized seven‐membered ring.
While polysulfones constitute a class of well‐established, highly valuable applied materials, knowledge about polymers based on the related sulfoximine group is very limited. We have employed functionalized diaryl sulfoximines and a p ‐phenylene bisborane as building blocks for unprecedented BN‐ and BO‐doped alternating inorganic–organic hybrid copolymers. While the former were accessed by a facile silicon/boron exchange protocol, the synthesis of polymers with main‐chain B–O linkages was achieved by salt elimination.
Two different chromophores, namely a dipolar and an octupolar system, were prepared and their linear and nonlinear optical properties as well as their bioimaging capabilities were compared. Both contain triphenylamine as the donor and a triarylborane as the acceptor, the latter modified with cationic trimethylammonio groups to provide solubility in aqueous media. The octupolar system exhibits a much higher two‐photon brightness, and also better cell viability and enhanced selectivity for lysosomes compared with the dipolar chromophore. Furthermore, both dyes were applied in two‐photon excited fluorescence (TPEF) live‐cell imaging.
Research on facial emotion expression has mostly focused on emotion recognition, assuming that a small number of discrete emotions is elicited and expressed via prototypical facial muscle configurations as captured in still photographs. These are expected to be recognized by observers, presumably via template matching. In contrast, appraisal theories of emotion propose a more dynamic approach, suggesting that specific elements of facial expressions are directly produced by the result of certain appraisals and predicting the facial patterns to be expected for certain appraisal configurations. This approach has recently been extended to emotion perception, claiming that observers first infer individual appraisals and only then make categorical emotion judgments based on the estimated appraisal patterns, using inference rules. Here, we report two related studies to empirically investigate the facial action unit configurations that are used by actors to convey specific emotions in short affect bursts and to examine to what extent observers can infer a person's emotions from the predicted facial expression configurations. The results show that (1) professional actors use many of the predicted facial action unit patterns to enact systematically specified appraisal outcomes in a realistic scenario setting, and (2) naïve observers infer the respective emotions based on highly similar facial movement configurations with a degree of accuracy comparable to earlier research findings. Based on estimates of underlying appraisal criteria for the different emotions we conclude that the patterns of facial action units identified in this research correspond largely to prior predictions and encourage further research on appraisal-driven expression and inference.
Research with adults in laboratory settings has shown that distributed rereading is a beneficial learning strategy but its effects depend on time of test. When learning outcomes are measured immediately after rereading, distributed rereading yields no benefits or even detrimental effects on learning, but the beneficial effects emerge two days later. In a preregistered experiment, the effects of distributed rereading were investigated in a classroom setting with school students. Seventh-graders (N = 191) reread a text either immediately or after 1 week. Learning outcomes were measured after 4 min or 1 week. Participants in the distributed rereading condition reread the text more slowly, predicted their learning success to be lower, and reported a lower on-task focus. At the shorter retention interval, massed rereading outperformed distributed rereading in terms of learning outcomes. Contrary to students in the massed condition, students in the distributed condition showed no forgetting from the short to the long retention interval. As a result, they performed equally well as the students in the massed condition at the longer retention interval. Our results indicate that distributed rereading makes learning more demanding and difficult and leads to higher effort during rereading. Its effects on learning depend on time of test, but no beneficial effects were found, not even at the delayed test.
The mold Fusarium is a ubiquitous fungus causing plant, animal and human infections. In humans, Fusarium spp. are the major cause of eye infections in patients wearing contact lenses or after local trauma. Systemic infections by Fusarium spp. mainly occur in immunosuppressed patients and can disseminate throughout the human body. Due to high levels of resistance to antifungals a fast identification of the causative agent is an urgent need. By using a probe-based real-time PCR assay specific for the genus Fusarium we analysed several different clinical specimens detecting Fusarium spp. commonly found in clinical samples in Germany. Also, a large collection of lung fluid samples of haematological patients was analysed (n = 243). In these, two samples (0.8%) were reproducibly positive, but only one could be confirmed by sequencing. For this case of probable invasive fungal disease (IFD) culture was positive for Fusarium species. Here we describe a rapid, probe-based real-time PCR assay to specifically detect DNA from a broad range of Fusarium species and its application to clinically relevant specimens.
Human A3 adenosine receptor hA3AR has been implicated in gastrointestinal cancer, where its cellular expression has been found increased, thus suggesting its potential as a molecular target for novel anticancer compounds. Observation made in our previous work indicated the importance of the carbonyl group of amide in the indolylpyrimidylpiperazine (IPP) for its human A2A adenosine receptor (hA2AAR) subtype binding selectivity over the other AR subtypes. Taking this observation into account, we structurally modified an indolylpyrimidylpiperazine (IPP) scaffold, 1 (a non-selective adenosine receptors’ ligand) into a modified IPP (mIPP) scaffold by switching the position of the carbonyl group, resulting in the formation of both ketone and tertiary amine groups in the new scaffold. Results showed that such modification diminished the A2A activity and instead conferred hA3AR agonistic activity. Among the new mIPP derivatives (3–6), compound 4 showed potential as a hA3AR partial agonist, with an Emax of 30% and EC50 of 2.89 ± 0.55 μM. In the cytotoxicity assays, compound 4 also exhibited higher cytotoxicity against both colorectal and liver cancer cells as compared to normal cells. Overall, this new series of compounds provide a promising starting point for further development of potent and selective hA3AR partial agonists for the treatment of gastrointestinal cancers.
The normal function of the heart relies on a series of complex metabolic processes orchestrating the proper generation and use of energy. In this context, mitochondria serve a crucial role as a platform for energy transduction by supplying ATP to the varying demand of cardiomyocytes, involving an intricate network of pathways regulating the metabolic flux of substrates. The failure of these processes results in structural and functional deficiencies of the cardiac muscle, including inherited cardiomyopathies. These genetic diseases are characterized by cardiac structural and functional anomalies in the absence of abnormal conditions that can explain the observed myocardial abnormality, and are frequently associated with heart failure. Since their original description, major advances have been achieved in the genetic and phenotype knowledge, highlighting the involvement of metabolic abnormalities in their pathogenesis. This review provides a brief overview of the role of mitochondria in the energy metabolism in the heart and focuses on metabolic abnormalities, mitochondrial dysfunction, and storage diseases associated with inherited cardiomyopathies.
Mineral bone cements were actually not developed for their application as bone-bonding agents, but as bone void fillers. In particular, calcium phosphate cements (CPC) are considered to be unsuitable for that application, particularly under moist conditions. Here, we showed the ex vivo ability of different magnesium phosphate cements (MPC) to adhere on bovine cortical bone substrates. The cements were obtained from a mixture of farringtonite (Mg\(_3\)(PO\(_4\))\(_2\)) with different amounts of phytic acid (C\(_6\)H\(_{18}\)O\(_{24}\)P\(_6\), inositol hexaphosphate, IP6), whereas cement setting occurred by a chelation reaction between Mg\(^{2+}\) ions and IP6. We were able to show that cements with 25% IP6 and a powder-to-liquid ratio (PLR) of 2.0 g/mL resulted in shear strengths of 0.81 ± 0.12 MPa on bone even after 7 d storage in aqueous conditions. The samples showed a mixed adhesive–cohesive failure with cement residues on the bone surface as indicated by scanning electron microscopy and energy-dispersive X-ray analysis. The presented material demonstrated appropriate bonding characteristics, which could enable a broadening of the mineral bone cements’ application field to bone adhesives
The limiting behaviour of a one‐dimensional discrete system is studied by means of Γ‐convergence. We consider a toy model of a chain of atoms. The interaction potentials are of Lennard‐Jones type and periodically or stochastically distributed. The energy of the system is considered in the discrete to continuum limit, i.e. as the number of atoms tends to infinity. During that limit, a homogenization process takes place. The limiting functional is discussed, especially with regard to fracture. Secondly, we consider a rescaled version of the problem, which yields a limiting energy of Griffith's type consisting of a quadratic integral term and a jump contribution. The periodic case can be found in [8], the stochastic case in [6,7].
In recent years, the midlatitudes are characterized by more intense heatwaves in summer and sometimes severe cold spells in winter that might emanate from changes in atmospheric circulation, including synoptic‐scale and planetary wave activity in the midlatitudes. In this study, we investigate the heat and momentum exchange between the mean flow and atmospheric waves in the North Atlantic sector and adjacent continents by means of the physically consistent Eliassen–Palm flux diagnostics applied to reanalysis and forced climate model data. In the long‐term mean, momentum is transferred from the mean flow to atmospheric waves in the northwest Atlantic region, where cyclogenesis prevails. Further downstream over Europe, eddy fluxes return momentum to the mean flow, sustaining the jet stream against friction. A global climate model is able to reproduce this pattern with high accuracy. Atmospheric variability related to atmospheric wave activity is much more expressed at the intraseasonal rather than the interannual time‐scale. Over the last 40 years, reanalyses reveal a northward shift of the jet stream and a weakening of intraseasonal weather variability related to synoptic‐scale and planetary wave activity. This pertains to the winter and summer seasons, especially over central Europe, and correlates with changes in the North Atlantic Oscillation as well as regional temperature and precipitation. A very similar phenomenon is found in a climate model simulation with business‐as‐usual scenario, suggesting an anthropogenic trigger in the weakening of intraseasonal weather variability in the midlatitudes.
Detailed insight into the internal structure of drug‐loaded polymeric micelles is scarce, but important for developing optimized delivery systems. We observed that an increase in the curcumin loading of triblock copolymers based on poly(2‐oxazolines) and poly(2‐oxazines) results in poorer dissolution properties. Using solid‐state NMR spectroscopy and complementary tools we propose a loading‐dependent structural model on the molecular level that provides an explanation for these pronounced differences. Changes in the chemical shifts and cross‐peaks in 2D NMR experiments give evidence for the involvement of the hydrophobic polymer block in the curcumin coordination at low loadings, while at higher loadings an increase in the interaction with the hydrophilic polymer blocks is observed. The involvement of the hydrophilic compartment may be critical for ultrahigh‐loaded polymer micelles and can help to rationalize specific polymer modifications to improve the performance of similar drug delivery systems.
A new strategy is demonstrated for the synthesis of warped, negatively curved, all‐sp\(^2\)‐carbon π‐scaffolds. Multifold C−C coupling reactions are used to transform a polyaromatic borinic acid into a saddle‐shaped polyaromatic hydrocarbon (2 ) bearing two heptagonal rings. Notably, this Schwarzite substructure is synthesized in only two steps from an unfunctionalized alkene. A highly warped structure of 2 was revealed by X‐ray crystallographic studies and pronounced flexibility of this π‐scaffold was ascertained by experimental and computational studies. Compound 2 exhibits excellent solubility, visible range absorption and fluorescence, and readily undergoes two reversible one‐electron oxidations at mild potentials.
Adrenocortical carcinoma (ACC) is a rare tumor and prognosis is overall poor but heterogeneous. Mitotane (MT) has been used for treatment of ACC for decades, either alone or in combination with cytotoxic chemotherapy. Even at doses up to 6 g per day, more than half of the patients do not achieve targeted plasma concentration (14–20 mg L\(^{-1}\)) even after many months of treatment due to low water solubility, bioavailability, and unfavorable pharmacokinetic profile. Here a novel MT nanoformulation with very high MT concentrations in physiological aqueous media is reported. The MT‐loaded nanoformulations are characterized by Fourier transform infrared spectroscopy, differential scanning calorimetry, and powder X‐ray diffraction which confirms the amorphous nature of the drug. The polymer itself does not show any cytotoxicity in adrenal and liver cell lines. By using the ACC model cell line NCI‐H295 both in monolayers and tumor cell spheroids, micellar MT is demonstrated to exhibit comparable efficacy to its ethanol solution. It is postulated that this formulation will be suitable for i.v. application and rapid attainment of therapeutic plasma concentrations. In conclusion, the micellar formulation is considered a promising tool to alleviate major drawbacks of current MT treatment while retaining bioactivity toward ACC in vitro.
A convenient and efficient one‐step synthesis of 1,1,1‐triborylalkanes was achieved via sequential dehydrogenative borylation and double hydroborations of terminal alkynes with HBpin (HBpin=pinacolborane) catalyzed by inexpensive and readily available Cu(OAc)\(_2\). This process proceeds under mild conditions, furnishing 1,1,1‐tris(boronates) with wide substrate scope, excellent selectivity, and good functional‐group tolerance, and is applicable to gram‐scale synthesis without loss of yield. The 1,1,1‐triborylalkanes can be used in the preparation of α‐vinylboronates and borylated cyclic compounds, which are valuable but previously rare compounds. Different alkyl groups can be introduced stepwise via base‐mediated deborylative alkylation to produce racemic tertiary alkyl boronates, which can be readily transformed into useful tertiary alcohols.
Artificial light at night (ALAN) is increasing exponentially worldwide, accelerated by the transition to new efficient lighting technologies. However, ALAN and resulting light pollution can cause unintended physiological consequences. In vertebrates, production of melatonin—the “hormone of darkness” and a key player in circadian regulation—can be suppressed by ALAN. In this paper, we provide an overview of research on melatonin and ALAN in vertebrates. We discuss how ALAN disrupts natural photic environments, its effect on melatonin and circadian rhythms, and different photoreceptor systems across vertebrate taxa. We then present the results of a systematic review in which we identified studies on melatonin under typical light-polluted conditions in fishes, amphibians, reptiles, birds, and mammals, including humans. Melatonin is suppressed by extremely low light intensities in many vertebrates, ranging from 0.01–0.03 lx for fishes and rodents to 6 lx for sensitive humans. Even lower, wavelength-dependent intensities are implied by some studies and require rigorous testing in ecological contexts. In many studies, melatonin suppression occurs at the minimum light levels tested, and, in better-studied groups, melatonin suppression is reported to occur at lower light levels. We identify major research gaps and conclude that, for most groups, crucial information is lacking. No studies were identified for amphibians and reptiles and long-term impacts of low-level ALAN exposure are unknown. Given the high sensitivity of vertebrate melatonin production to ALAN and the paucity of available information, it is crucial to research impacts of ALAN further in order to inform effective mitigation strategies for human health and the wellbeing and fitness of vertebrates in natural ecosystems.
Quinolone antibiotics present an attractive oral treatment option in patients with cystic fibrosis (CF). Prior studies have reported comparable clearances and volumes of distribution in patients with CF and healthy volunteers for primarily renally cleared quinolones. We aimed to provide the first pharmacokinetic comparison for pefloxacin as a predominantly nonrenally cleared quinolone and its two metabolites between both subject groups. Eight patients with CF (fat-free mass [FFM]: 36.3 ± 6.9 kg, average ± SD) and ten healthy volunteers (FFM: 51.7 ± 9.9 kg) received 400 mg pefloxacin as a 30 min intravenous infusion and orally in a randomized, two-way crossover study. All plasma and urine data were simultaneously modelled. Bioavailability was complete in both subject groups. Pefloxacin excretion into urine was approximately 74% higher in patients with CF compared to that in healthy volunteers, whereas the urinary excretion of metabolites was only slightly higher in patients with CF. After accounting for body size and composition via allometric scaling by FFM, pharmacokinetic parameter estimates in patients with CF divided by those in healthy volunteers were 0.912 for total clearance, 0.861 for nonrenal clearance, 1.53 for renal clearance, and 0.916 for volume of distribution. Nonrenal clearance accounted for approximately 90% of total pefloxacin clearance. Overall, bioavailability and disposition were comparable between both subject groups.
We aimed to compare the clinical data at first presentation to inpatient treatment of children (<14 years) vs. adolescents (≥14 years) with anorexia nervosa (AN), focusing on duration of illness before hospital admission and body mass index (BMI) at admission and discharge, proven predictors of the outcomes of adolescent AN. Clinical data at first admission and at discharge in 289 inpatients with AN (children: n = 72; adolescents: n = 217) from a German multicenter, web-based registry for consecutively enrolled patients with childhood and adolescent AN were analyzed. Inclusion criteria were a maximum age of 18 years, first inpatient treatment due to AN, and a BMI <10th BMI percentile at admission. Compared to adolescents, children with AN had a shorter duration of illness before admission (median: 6.0 months vs. 8.0 months, p = 0.004) and higher BMI percentiles at admission (median: 0.7 vs. 0.2, p = 0.004) as well as at discharge (median: 19.3 vs. 15.1, p = 0.011). Thus, in our study, children with AN exhibited clinical characteristics that have been associated with better outcomes, including higher admission and discharge BMI percentile. Future studies should examine whether these factors are actually associated with positive long-term outcomes in children.
The present study assessed the short-term effect of 6 min classroom-based micro-sessions of multi-joint functional high-intensity circuit training (FunctionalHIIT) performed by students during regular classes on parameters related to functional strength and cardiorespiratory fitness. In this randomized controlled 4-week study, 17 students (11 male; 6 female; age: 11.6 ± 0.2 years) performed 6 min of FunctionalHIIT (targeting >17 on the Borg scale) 4 days per week during regular school classes and 18 students (11 male; 7 female; age: 11.7 ± 0.3 years) served as control group (CG) without any additional in-class physical activity. The FunctionalHIIT group completed 86% of all planned sessions (mean duration: 6.0 ± 1.5 min) with a mean RPE of 17.3 ± 2.1. Body height, mass and BMI did not differ between the groups at baseline or between pre- and post-testing (p > 0.05; eta2 ≤ 0.218). The performances in lateral jumping (p < 0.000; part eta2 = 0.382; Δ% 4.6 ± 8.6), sit-ups (p < 0.000; part eta2 = 0.485; Δ% 3.1 ± 8.6) and 20-m sprints (p < 0.000; part eta2 = 0.691; Δ% 15.8 ± 5.4) improved in both groups with greater increase following FunctionalHIIT. No baseline differences and no interaction effects occurred in performance of 6 min run, flexibility, push-ups, balance, and long jump. Classroom-based FunctionalHIIT sessions, performed 4 days per week during 4 weeks did not improve variables related to aerobic endurance performance but enhanced certain parameters of functional strength in schoolchildren. As time is limited in the educational system of schools, FunctionalHIIT during regular school classes could offer a new perspective for increasing functional strength in schoolchildren.
Background: Therapy for acute lymphoblastic leukemia (ALL) are currently initially efficient, but even if a high percentage of patients have an initial complete remission (CR), most of them relapse. Recent data shows that immunotherapy with either bispecific T-cell engagers (BiTEs) of chimeric antigen receptor (CAR) T cells can eliminate residual chemotherapy-resistant B-ALL cells.
Objective: The objective of the manuscript is to present improvements in the clinical outcome for chemotherapy-resistant ALL in the real-life setting, by describing Romania's experience with bispecific antibodies for B-cell ALL.
Methods: We present the role of novel therapies for relapsed B-cell ALL, including the drugs under investigation in phase I-III clinical trials, as a potential bridge to transplant. Blinatumomab is presented in a critical review, presenting both the advantages of this drug, as well as its limitations.
Results: Bispecific antibodies are discussed, describing the clinical trials that resulted in its approval by the FDA and EMA. The real-life setting for relapsed B-cell ALL is described and we present the patients treated with blinatumomab in Romania.
Conclusion: In the current manuscript, we present blinatumomab as a therapeutic alternative in the bridge-to-transplant setting for refractory or relapsed ALL, to gain a better understanding of the available therapies and evidence-based data for these patients in 2019.
Zinc oxide nanoparticles (ZnO-NPs) are commonly used for industrial applications. Consequently, there is increasing exposure of humans to them. The in vitro analysis of cytotoxicity and genotoxicity is commonly performed under standard cell culture conditions. Thus, the question arises of how the results of genotoxicity and cytotoxicity experiments would alter if human plasma was used instead of cell culture medium containing of fetal calf serum (FCS). Human mesenchymal stem cells (hMSCs) were cultured in human plasma and exposed to ZnO-NPs. A cultivation in expansion medium made of DMEM consisting 10% FCS (DMEM-EM) served as control. Genotoxic and cytotoxic effects were evaluated with the comet and MTT assay, respectively. hMSC differentiation capacity and ZnO-NP disposition were evaluated by histology and transmission electron microscopy (TEM). The protein concentration and the amount of soluble Zn2+ were measured. The cultivation of hMSCs in plasma leads to an attenuation of genotoxic and cytotoxic effects of ZnO-NPs compared to control. The differentiation capacity of hMSCs was not altered. The TEM showed ZnO-NP persistence in cytoplasm in both groups. The concentrations of protein and Zn2+ were higher in plasma than in DMEM-EM. In conclusion, the cultivation of hMSCs in plasma compared to DMEM-EM leads to an attenuation of cytotoxicity and genotoxicity in vitro.
Infectious diseases are still a significant cause of morbidity and mortality worldwide. Despite the progress in drug development, the occurrence of microbial resistance is still a significant concern. Alternative therapeutic strategies are required for non-responding or relapsing patients. Chimeric antigen receptor (CAR) T cells has revolutionized cancer immunotherapy, providing a potential therapeutic option for patients who are unresponsive to standard treatments. Recently two CAR T cell therapies, Yescarta® (Kite Pharma/Gilead) and Kymriah® (Novartis) were approved by the FDA for the treatments of certain types of non-Hodgkin lymphoma and B-cell precursor acute lymphoblastic leukemia, respectively. The success of adoptive CAR T cell therapy for cancer has inspired researchers to develop CARs for the treatment of infectious diseases. Here, we review the main achievements in CAR T cell therapy targeting viral infections, including Human Immunodeficiency Virus, Hepatitis C Virus, Hepatitis B Virus, Human Cytomegalovirus, and opportunistic fungal infections such as invasive aspergillosis.
(1) Background: Refractory acute graft-versus-host disease (R-aGvHD) remains a leading cause of death after allogeneic stem cell transplantation. Survival rates of 15% after four years are currently achieved; deaths are only in part due to aGvHD itself, but mostly due to adverse effects of R-aGvHD treatment with immunosuppressive agents as these predispose patients to opportunistic infections and loss of graft-versus-leukemia surveillance resulting in relapse. Mesenchymal stromal cells (MSC) from different tissues and those generated by various protocols have been proposed as a remedy for R-aGvHD but the enthusiasm raised by initial reports has not been ubiquitously reproduced. (2) Methods: We previously reported on a unique MSC product, which was generated from pooled bone marrow mononuclear cells of multiple third-party donors. The products showed dose-to-dose equipotency and greater immunosuppressive capacity than individually expanded MSCs from the same donors. This product, MSC-FFM, has entered clinical routine in Germany where it is licensed with a national hospital exemption authorization. We previously reported satisfying initial clinical outcomes, which we are now updating. The data were collected in our post-approval pharmacovigilance program, i.e., this is not a clinical study and the data is high-level and non-monitored. (3) Results: Follow-up for 92 recipients of MSC-FFM was reported, 88 with GvHD ≥°III, one-third only steroid-refractory and two-thirds therapy resistant (refractory to steroids plus ≥2 additional lines of treatment). A median of three doses of MSC-FFM was administered without apparent toxicity. Overall response rates were 82% and 81% at the first and last evaluation, respectively. At six months, the estimated overall survival was 64%, while the cumulative incidence of death from underlying disease was 3%. (4) Conclusions: MSC-FFM promises to be a safe and efficient treatment for severe R-aGvHD.
Bone graft substitutes in orthopedic applications have to fulfill various demanding requirements. Most calcium phosphate (CaP) bone graft substitutes are highly porous to achieve bone regeneration, but typically lack mechanical stability. This study presents a novel approach, in which a scaffold structure with appropriate properties for bone regeneration emerges from the space between specifically shaped granules. The granule types were tetrapods (TEPO) and pyramids (PYRA), which were compared to porous CaP granules (CALC) and morselized bone chips (BC). Bulk materials of the granules were mechanically loaded with a peak pressure of 4 MP; i.e., comparable to the load occurring behind an acetabular cup. Mechanical loading reduced the volume of CALC and BC considerably (89% and 85%, respectively), indicating a collapse of the macroporous structure. Volumes of TEPO and PYRA remained almost constant (94% and 98%, respectively). After loading, the porosity was highest for BC (46%), lowest for CALC (25%) and comparable for TEPO and PYRA (37%). The pore spaces of TEPO and PYRA were highly interconnected in a way that a virtual object with a diameter of 150 µm could access 34% of the TEPO volume and 36% of the PYRA volume. This study shows that a bulk of dense CaP granules in form of tetrapods and pyramids can create a scaffold structure with load capacities suitable for the regeneration of an acetabular bone defect
C60 fullerene as an effective nanoplatform of alkaloid Berberine delivery into leukemic cells
(2019)
A herbal alkaloid Berberine (Ber), used for centuries in Ayurvedic, Chinese, Middle-Eastern, and native American folk medicines, is nowadays proved to function as a safe anticancer agent. Yet, its poor water solubility, stability, and bioavailability hinder clinical application. In this study, we have explored a nanosized carbon nanoparticle—C60 fullerene (C60)—for optimized Ber delivery into leukemic cells. Water dispersions of noncovalent C60-Ber nanocomplexes in the 1:2, 1:1, and 2:1 molar ratios were prepared. UV–Vis spectroscopy, dynamic light scattering (DLS), and atomic force microscopy (AFM) evidenced a complexation of the Ber cation with the negatively charged C60 molecule. The computer simulation showed that π-stacking dominates in Ber and C\(_{60}\) binding in an aqueous solution. Complexation with C\(_{60}\) was found to promote Ber intracellular uptake. By increasing C\(_{60}\) concentration, the C\(_{60}\)-Ber nanocomplexes exhibited higher antiproliferative potential towards CCRF-CEM cells, in accordance with the following order: free Ber < 1:2 < 1:1 < 2:1 (the most toxic). The activation of caspase 3/7 and accumulation in the sub-G1 phase of CCRF-CEM cells treated with C\(_{60}\)-Ber nanocomplexes evidenced apoptosis induction. Thus, this study indicates that the fast and easy noncovalent complexation of alkaloid Ber with C\(_{60}\) improved its in vitro efficiency against cancer cells.
Auxin is a molecule, which controls many aspects of plant development through both transcriptional and non-transcriptional signaling responses. AUXIN BINDING PROTEIN1 (ABP1) is a putative receptor for rapid non-transcriptional auxin-induced changes in plasma membrane depolarization and endocytosis rates. However, the mechanism of ABP1-mediated signaling is poorly understood. Here we show that membrane depolarization and endocytosis inhibition are ABP1-independent responses and that auxin-induced plasma membrane depolarization is instead dependent on the auxin influx carrier AUX1. AUX1 was itself not involved in the regulation of endocytosis. Auxin-dependent depolarization of the plasma membrane was also modulated by the auxin efflux carrier PIN2. These data establish a new connection between auxin transport and non-transcriptional auxin signaling.
Sea level rise contribution from the Antarctic ice sheet is influenced by changes in glacier and ice shelf front position. Still, little is known about seasonal glacier and ice shelf front fluctuations as the manual delineation of calving fronts from remote sensing imagery is very time-consuming. The major challenge of automatic calving front extraction is the low contrast between floating glacier and ice shelf fronts and the surrounding sea ice. Additionally, in previous decades, remote sensing imagery over the often cloud-covered Antarctic coastline was limited. Nowadays, an abundance of Sentinel-1 imagery over the Antarctic coastline exists and could be used for tracking glacier and ice shelf front movement. To exploit the available Sentinel-1 data, we developed a processing chain allowing automatic extraction of the Antarctic coastline from Seninel-1 imagery and the creation of dense time series to assess calving front change. The core of the proposed workflow is a modified version of the deep learning architecture U-Net. This convolutional neural network (CNN) performs a semantic segmentation on dual-pol Sentinel-1 data and the Antarctic TanDEM-X digital elevation model (DEM). The proposed method is tested for four training and test areas along the Antarctic coastline. The automatically extracted fronts deviate on average 78 m in training and 108 m test areas. Spatial and temporal transferability is demonstrated on an automatically extracted 15-month time series along the Getz Ice Shelf. Between May 2017 and July 2018, the fronts along the Getz Ice Shelf show mostly an advancing tendency with the fastest moving front of DeVicq Glacier with 726 ± 20 m/yr.
This study investigates synthetic aperture radar (SAR) time series of the Sentinel-1 mission acquired over the Atacama Desert, Chile, between March 2015 and December 2018. The contribution analyzes temporal and spatial variations of Sentinel-1 interferometric SAR (InSAR) coherence and exemplarily illustrates factors that are responsible for observed signal differences. The analyses are based on long temporal baselines (365–1090 days) and temporally dense time series constructed with short temporal baselines (12–24 days). Results are compared to multispectral data of Sentinel-2, morphometric features of the digital elevation model (DEM) TanDEM-X WorldDEM™, and to a detailed governmental geographic information system (GIS) dataset of the local hydrography. Sentinel-1 datasets are suited for generating extensive, nearly seamless InSAR coherence mosaics covering the entire Atacama Desert (>450 × 1100 km) at a spatial resolution of 20 × 20 meter per pixel. Temporal baselines over several years lead only to very minor decorrelation, indicating a very high signal stability of C-Band in this region, especially in the hyperarid uplands between the Coastal Cordillera and the Central Depression. Signal decorrelation was associated with certain types of surface cover (e.g., water or aeolian deposits) or with actual surface dynamics (e.g., anthropogenic disturbance (mining) or fluvial activity and overland flow). Strong rainfall events and fluvial activity in the periods 2015 to 2016 and 2017 to 2018 caused spatial patterns with significant signal decorrelation; observed linear coherence anomalies matched the reference channel network and indicated actual episodic and sporadic discharge events. In the period 2015–2016, area-wide loss of coherence appeared as strip-like patterns of more than 80 km length that matched the prevailing wind direction. These anomalies, and others observed in that period and in the period 2017–2018, were interpreted to be caused by overland flow of high magnitude, as their spatial location matched well with documented heavy rainfall events that showed cumulative precipitation amounts of more than 20 mm.
Air temperatures in the Arctic have increased substantially over the last decades, which has extensively altered the properties of the land surface. Capturing the state and dynamics of Land Surface Temperatures (LSTs) at high spatial detail is of high interest as LST is dependent on a variety of surficial properties and characterizes the land–atmosphere exchange of energy. Accordingly, this study analyses the influence of different physical surface properties on the long-term mean of the summer LST in the Arctic Mackenzie Delta Region (MDR) using Landsat 30 m-resolution imagery between 1985 and 2018 by taking advantage of the cloud computing capabilities of the Google Earth Engine. Multispectral indices, including the Normalized Difference Vegetation Index (NDVI), Normalized Difference Water Index (NDWI) and Tasseled Cap greenness (TCG), brightness (TCB), and wetness (TCW) as well as topographic features derived from the TanDEM-X digital elevation model are used in correlation and multiple linear regression analyses to reveal their influence on the LST. Furthermore, surface alteration trends of the LST, NDVI, and NDWI are revealed using the Theil-Sen (T-S) regression method. The results indicate that the mean summer LST appears to be mostly influenced by the topographic exposition as well as the prevalent moisture regime where higher evapotranspiration rates increase the latent heat flux and cause a cooling of the surface, as the variance is best explained by the TCW and northness of the terrain. However, fairly diverse model outcomes for different regions of the MDR (R2 from 0.31 to 0.74 and RMSE from 0.51 °C to 1.73 °C) highlight the heterogeneity of the landscape in terms of influential factors and suggests accounting for a broad spectrum of different factors when modeling mean LSTs. The T-S analysis revealed large-scale wetting and greening trends with a mean decadal increase of the NDVI/NDWI of approximately +0.03 between 1985 and 2018, which was mostly accompanied by a cooling of the land surface given the inverse relationship between mean LSTs and vegetation and moisture conditions. Disturbance through wildfires intensifies the surface alterations locally and lead to significantly cooler LSTs in the long-term compared to the undisturbed surroundings.
o build, run, and maintain reliable manufacturing machines, the condition of their components has to be continuously monitored. When following a fine-grained monitoring of these machines, challenges emerge pertaining to the (1) feeding procedure of large amounts of sensor data to downstream processing components and the (2) meaningful analysis of the produced data. Regarding the latter aspect, manifold purposes are addressed by practitioners and researchers. Two analyses of real-world datasets that were generated in production settings are discussed in this paper. More specifically, the analyses had the goals (1) to detect sensor data anomalies for further analyses of a pharma packaging scenario and (2) to predict unfavorable temperature values of a 3D printing machine environment. Based on the results of the analyses, it will be shown that a proper management of machines and their components in industrial manufacturing environments can be efficiently supported by the detection of anomalies. The latter shall help to support the technical evangelists of the production companies more properly.
Aim: While elevational gradients in species richness constitute some of the best depicted patterns in ecology, there is a large uncertainty concerning the role of food resource availability for the establishment of diversity gradients in insects. Here, we
analysed the importance of climate, area, land use and food resources for determining diversity gradients of dung beetles along extensive elevation and land use gradients on Mt. Kilimanjaro, Tanzania.
Location: Mt. Kilimanjaro, Tanzania.
Taxon: Scarabaeidae (Coleoptera).
Methods: Dung beetles were recorded with baited pitfall traps at 66 study plots along a 3.6 km elevational gradient. In order to quantify food resources for the dung beetle community in form of mammal defecation rates, we assessed mammalian diversity and biomass with camera traps. Using a multi‐model inference framework and path analysis, we tested the direct and indirect links between climate, area, land use and mammal defecation rates on the species richness and abundance of dung beetles.
Results: We found that the species richness of dung beetles declined exponentially with increasing elevation. Human land use diminished the species richness of functional groups exhibiting complex behaviour but did not have a significant influence on total species richness. Path analysis suggested that climate, in particular temperature and to a lesser degree precipitation, were the most important predictors of dung beetle species richness while mammal defecation rate was not supported as a predictor variable.
Main conclusions: Along broad climatic gradients, dung beetle diversity is mainly limited by climatic factors rather than by food resources. Our study points to a predominant role of temperature‐driven processes for the maintenance and origination of species diversity of ectothermic organisms, which will consequently be subject to ongoing climatic changes.
By introduction of four hydroxy (HO) groups into the two perylene bisimide (PBI) bay areas, new HO‐PBI ligands were obtained which upon deprotonation can complex ZnII ions and photosensitize semiconductive zinc oxide thin films. Such coordination is beneficial for dispersing PBI photosensitizer molecules evenly into metal oxide films to fabricate organic–inorganic hybrid interlayers for organic solar cells. Supported by the photoconductive effect of the ZnO:HO‐PBI hybrid interlayers, improved electron collection and transportation is achieved in fullerene and non‐fullerene polymer solar cell devices, leading to remarkable power conversion efficiencies of up to 15.95 % for a non‐fullerene based organic solar cell.
The link between multi‐host use and host switching in host–parasite interactions is a continuing area of debate. Lycaenid butterflies in the genus Maculinea, for example, exploit societies of different Myrmica ant species across their ranges, but there is only rare evidence that they simultaneously utilise multiple hosts at a local site, even where alternative hosts are present.
We present a simple population‐genetic model accounting for the proportion of two alternative hosts and the fitness of parasite genotypes on each host. In agreement with standard models, we conclude that simultaneous host use is possible whenever fitness of heterozygotes on alternative hosts is not too low.
We specifically focus on host‐shifting dynamics when the frequency of hosts changes. We find that (i) host shifting may proceed so rapidly that multiple host use is unlikely to be observed, (ii) back and forth transition in host use can exhibit a hysteresis loop, (iii) the parasites' host use may not be proportional to local host frequencies and be restricted to the rarer host under some conditions, and (iv) that a substantial decline in parasite abundance may typically precede a shift in host use.
We conclude that focusing not just on possible equilibrium conditions but also considering the dynamics of host shifting in non‐equilibrium situations may provide added insights into host–parasite systems.
Iodine oxides appear as reactive intermediates in atmospheric chemistry. Here, we investigate IO and HOI by mass‐selective threshold photoelectron spectroscopy (ms‐TPES), using synchrotron radiation. IO and HOI are generated by photolyzing iodine in the presence of ozone. For both molecules, accurate ionization energies are determined, 9.71±0.02 eV for IO and 9.79±0.02 eV for HOI. The strong spin‐spin interaction in the 3Σ− ground state of IO+ leads to an energy splitting into the Ω=0 and Ω=±1 sublevels. Upon ionization, the I−O bond shortens significantly in both molecules; thus, a vibrational progression, assigned to the I−O stretch, is apparent in both spectra.
BACKGROUND: The barrier to diffusion of organic solutes across the plant cuticle is composed of waxes consisting of very long-chain aliphatic (VLCA) and, to varying degrees, cyclic compounds like pentacyclic triterpenoids. The roles of both fractions in controlling cuticular penetration by organic solutes, e.g. the active ingredients (AI) of pesticides, are unknown to date. We studied thepermeabilityof isolated leaf cuticularmembranes from Garcinia xanthochymus andPrunus laurocerasus for lipophilic azoxystrobin and theobromine as model compounds for hydrophilic AIs.
RESULTS: The wax of P. laurocerasus consists of VLCA (12%) and cyclic compounds (88%), whereas VLCAs make up 97% of the wax of G. xanthochymus.We showthat treating isolated cuticles with methanol almost quantitatively releases the cyclic fraction while leaving the VLCA fraction essentially intact. All VLCAs were subsequently removed using chloroform. In both species, the permeance of the two model compounds did not change significantly after methanol treatment, whereas chloroform extraction had a large effect on organic solute permeability.
CONCLUSION: The VLCA wax fractionmakes up the permeability barrier for organic solutes, whereas cyclic compounds even in high amounts have a negligible role. This is of significance when optimizing the foliar uptake of pesticides.
Adenotonsillectomies are commonly performed procedures and sleep‐disordered breathing is becoming increasingly important as an indication for surgery. Because of the higher risks in patients with obstructive sleep apnoea, the required level of postoperative care for these patients is currently under discussion, and better identification of patients at risk may reduce unnecessary postoperative monitoring. To evaluate the influence of obstructive sleep apnoea, and other risk factors, on peri‐operative complications in children requiring adenotonsillectomy, we performed a retrospective case‐control study that included 1995 patients treated between January 2009 and June 2017. In our analysis, young age (OR 3.8, 95%CI 2.1–7.1), low body weight (OR 2.6, 95%CI 1.5–4.4), obstructive sleep apnoea (OR 2.4, 95%CI 1.5–3.8), pre‐existing craniofacial or syndromal disorders (OR 2.3, 95%CI 1.4–3.8) and adenotonsillectomy, compared with adenoidectomy alone, (OR 7.9, 95%CI 4.7–13.1) were identified as risk factors for complications during or after surgery, p < 0.001. All 13 patients suffering from complications more than 3 h postoperatively had obstructive sleep apnoea plus at least one more of these risk factors. Patients at risk of postoperative complications can therefore be identified by several criteria pre‐operatively, and should be monitored postoperatively using pulse oximetry overnight. For all other patients, postoperative observation on a surgical ward without extra monitoring is sufficient. Admission to paediatric intensive care should be reserved for patients suffering serious intra‐operative complications.
Predation on pest organisms is an essential ecosystem function supporting yields in modern agriculture. However, assessing predation rates is intricate, and they can rarely be linked directly to predator densities or functions. We tested whether sentinel prey aphid cards are useful tools to assess predation rates in the field. Therefore, we looked at aphid cards of different sizes on the ground level as well as within the vegetation. Additionally, by trapping ground‐dwelling predators, we examined whether obtained predation rates could be linked to predator densities and traits. Predation rates recorded with aphid cards were independent of aphid card size. However, predation rates on the ground level were three times higher than within the vegetation. We found both predatory carabid activity densities as well as community weighted mean body size to be good predictors for predation rates. Predation rates obtained from aphid cards are stable over card type and related to predator assemblages. Aphid cards, therefore, are a useful, efficient method for rapidly assessing the ecosystem function predation. Their use might especially be recommended for assessments on the ground level and when time and resource limitations rule out more elaborate sentinel prey methods using exclosures with living prey animals.
Protein-like enwrapped perylene bisimide chromophore as bright microcrystalline emitter material
(2019)
Strongly emissive solid‐state materials are mandatory components for many emerging optoelectronic technologies, but fluorescence is often quenched in the solid state owing to strong intermolecular interactions. The design of new organic pigments, which retain their optical properties despite their high tendency to crystallize, could overcome such limitations. Herein, we show a new material with monomer‐like absorption and emission profiles as well as fluorescence quantum yields over 90 % in its crystalline solid state. The material was synthesized by attaching two bulky tris(4‐tert‐butylphenyl)phenoxy substituents at the perylene bisimide bay positions. These substituents direct a packing arrangement with full enwrapping of the chromophore and unidirectional chromophore alignment within the crystal lattice to afford optical properties that resemble those of their natural pigment counterparts, in which chromophores are rigidly embedded in protein environments.
There is a specialized niche for the electrohydrodynamic jetting of melts, from biomedical products to filtration and soft matter applications. The next frontier includes optics, microfluidics, flexible electronic devices, and soft network composites in biomaterial science and soft robotics. The recent emphasis on reproducibly direct‐writing continual molten jets has enabled a spectrum of contemporary microscale 3D objects to be fabricated. One strong suit of melt processing is the capacity for the jet to solidify rapidly into a fiber, thus fixing a particular structure into position. The ability to direct‐write complex and multiscaled architectures and structures has greatly contributed to a large number of recent studies, explicitly, toward fiber–hydrogel composites and fugitive inks, and has expanded into several biomedical applications such as cartilage, skin, periosteum, and cardiovascular tissue engineering. Following the footsteps of a publication that summarized melt electrowriting literature up to 2015, the most recent literature from then until now is reviewed to provide a continuous and comprehensive timeline that demonstrates the latest advances as well as new perspectives for this emerging technology.
A combination of copper iodide and phenanthroline as the ligand is an efficient catalyst for Suzuki‐Miyaura cross‐coupling of highly fluorinated boronate esters (aryl−Bpin) with aryl iodides and bromides to generate fluorinated biaryls in good to excellent yields. This method represents a nice alternative to traditional cross‐coupling methods which require palladium catalysts and stoichiometric amounts of silver oxide. We note that π⋅⋅⋅π stacking interactions dominate the molecular packing in the partly fluorinated biaryl crystals investigated herein. They are present either between the arene and perfluoroarene, or solely between arenes or perfluoroarenes, respectively.
Cyclic (amino)(aryl)carbenes (cAArCs) based on the isoindoline core were successfully generated in situ by α‐elimination of 3‐alkoxyisoindolines at high temperatures or by deprotonation of isoindol‐2‐ium chlorides with sodium or copper(I) acetates at low temperatures. 3‐Alkoxy‐isoindolines 2 a ,b‐OR (R=Me, Et, i Pr) have been prepared in high yields by the addition of a solution of 2‐aryl‐1,1‐diphenylisoindol‐2‐ium triflate (1 a ,b‐OTf ; a : aryl=Dipp=2,6‐diisopropylphenyl; b : Mesityl‐, Mes=2,4,6‐trimethylphenyl) to the corresponding alcohol (ROH) with NEt3 at room temperature. Furthermore, the reaction of 2 a ,b‐OMe in diethyl ether with a tenfold excess of hydrochloric acid led to the isolation of the isoindol‐2‐ium chlorides 1 a ,b‐Cl in high yields. The thermally generated cAArC reacts with sulfur to form the thioamide 3 a . Without any additional trapping reagent, in situ generation of 1,1‐diphenylisoidolin‐3‐ylidenes does not lead to the isolation of these compounds, but to the reaction products of the insertion of the carbene carbon atom into an ortho C−H bond of a phenyl substituent, followed by ring‐expansion reaction; namely, anthracene derivatives 9‐N(H)aryl‐10‐Ph‐C14H8 4 a ,b (a : Dipp; b : Mes). These compounds are conveniently synthesized by deprotonation of the isoindol‐2‐ium chlorides with sodium acetate in high yields. Deprotonation of 1 a‐Cl with copper(I) acetate at low temperatures afforded a mixture of 4 a and the corresponding cAArC copper(I) chloride 5 a , and allowed the isolation and structural characterization of the first example of a cAArC copper complex of general formula [(cAArC)CuCl].
Understanding extinction debts: spatio-temporal scales, mechanisms and a roadmap for future research
(2019)
Extinction debt refers to delayed species extinctions expected as a consequence of ecosystem perturbation. Quantifying such extinctions and investigating long‐term consequences of perturbations has proven challenging, because perturbations are not isolated and occur across various spatial and temporal scales, from local habitat losses to global warming. Additionally, the relative importance of eco‐evolutionary processes varies across scales, because levels of ecological organization, i.e. individuals, (meta)populations and (meta)communities, respond hierarchically to perturbations. To summarize our current knowledge of the scales and mechanisms influencing extinction debts, we reviewed recent empirical, theoretical and methodological studies addressing either the spatio–temporal scales of extinction debts or the eco‐evolutionary mechanisms delaying extinctions. Extinction debts were detected across a range of ecosystems and taxonomic groups, with estimates ranging from 9 to 90% of current species richness. The duration over which debts have been sustained varies from 5 to 570 yr, and projections of the total period required to settle a debt can extend to 1000 yr. Reported causes of delayed extinctions are 1) life‐history traits that prolong individual survival, and 2) population and metapopulation dynamics that maintain populations under deteriorated conditions. Other potential factors that may extend survival time such as microevolutionary dynamics, or delayed extinctions of interaction partners, have rarely been analyzed. Therefore, we propose a roadmap for future research with three key avenues: 1) the microevolutionary dynamics of extinction processes, 2) the disjunctive loss of interacting species and 3) the impact of multiple regimes of perturbation on the payment of debts. For their ability to integrate processes occurring at different levels of ecological organization, we highlight mechanistic simulation models as tools to address these knowledge gaps and to deepen our understanding of extinction dynamics.