Refine
Year of publication
Document Type
- Preprint (690)
- Article (589)
- Working Paper (10)
- Conference Proceeding (3)
- Part of Periodical (2)
- Part of a Book (1)
- Report (1)
Has Fulltext
- yes (1296)
Is part of the Bibliography
- no (1296)
Keywords
- Heavy Ion Experiments (20)
- Hadron-Hadron Scattering (11)
- Hadron-Hadron scattering (experiments) (11)
- LHC (9)
- Heavy-ion collision (6)
- ALICE experiment (4)
- Collective Flow (4)
- Hepatocellular carcinoma (4)
- Jets (4)
- Quark-Gluon Plasma (4)
- ALICE (3)
- COVID-19 (3)
- Cirrhosis (3)
- Gene expression (3)
- HIV (3)
- Heavy Ions (3)
- Immunology (3)
- Inflammation (3)
- Jets and Jet Substructure (3)
- Liver diseases (3)
- cancer (3)
- child (3)
- pp collisions (3)
- Antitrust (2)
- Beauty production (2)
- Bone density (2)
- Charm physics (2)
- Consumer Welfare (2)
- Diagnostic markers (2)
- Ewing sarcoma (2)
- Experimental nuclear physics (2)
- Experimental particle physics (2)
- HCC (2)
- Heavy Quark Production (2)
- Lepton-Nucleon Scattering (experiments) (2)
- Literaturtheorie (2)
- MLL (2)
- Mouse models (2)
- Oncology (2)
- Osteoporosis (2)
- Particle Correlations and Fluctuations (2)
- Particle and resonance production (2)
- Particle correlations and fluctuations (2)
- Pb–Pb collisions (2)
- Psychiatric disorders (2)
- QCD (2)
- Relativistic heavy-ion collisions (2)
- SARS-CoV-2 (2)
- Single electrons (2)
- Sustainability (2)
- aortic stenosis (2)
- biomarker (2)
- children (2)
- habitat destruction (2)
- hematopoietic stem cell transplantation (2)
- invasive fungal disease (2)
- lung cancer (2)
- proteomics (2)
- soft tissue sarcoma (2)
- sphingolipids (2)
- web archiving (2)
- 15-PGDH (1)
- 900 GeV (1)
- ACURATE neo (1)
- AKI (1)
- ALICE detector (1)
- ALK-rearranged NSCLC (1)
- ALL (1)
- AML (1)
- APRI (1)
- Accelerators & Beams (1)
- Accelerators & storage rings (1)
- Actin (1)
- Active middle ear implants (1)
- Acute coronary syndrome (1)
- Acute myeloid leukemia (1)
- Adenylyl cyclase (1)
- Amino acid analysis (1)
- Anandamide (1)
- Angiogenesis (1)
- Animal models (1)
- Anti-nuclei (1)
- Antibiotic steward-ship (1)
- Antibiotic therapy (1)
- Antibiotics (1)
- Antiretroviral therapy (1)
- Antiretrovirals (1)
- Antiviral therapy (1)
- Apoptosis (1)
- Artificial Intelligence (1)
- Ataxia-telangiectasia (1)
- Atomic & molecular beams (1)
- Atomic, Molecular & Optical (1)
- Atoms (1)
- Atrial fibrillation (1)
- Auditory system (1)
- Autologous stem cell transplantation (1)
- Autorschaft (1)
- BFIS (1)
- BRAF (1)
- Backscattering (1)
- Beam loss (1)
- Biodiversity Data (1)
- Biomarker (1)
- Biomarkers (1)
- Biomass monitoring (1)
- Biomonitoring (1)
- Bioprocess automation (1)
- Bipolar disorder (1)
- Blood plasma (1)
- Bone conduction devices (1)
- Bone diseases, Metabolic (1)
- Boosted Jets (1)
- Botanical Collections (1)
- Breast cancer (1)
- Breast tumors (1)
- Buprestidae (1)
- C6 ceramide (1)
- CCL2 (1)
- CEP68 (1)
- COMT (1)
- COVID 19 (1)
- CRISPR/Cas (1)
- CT (1)
- CT dual-energy computed tomography (1)
- CVID (1)
- Cancer (1)
- Cancer chemotherapy (1)
- Cancer detection and diagnosis (1)
- Cancer treatment (1)
- Canopy height model (1)
- Cardiac hypertrophy (1)
- Cardiac surgery (1)
- Cardiac troponin (1)
- Cardiology (1)
- Cardiovascular biology (1)
- Cardiovascular disease risk (1)
- Cardiovascular diseases (1)
- Cell binding (1)
- Cell membranes (1)
- Cell staining (1)
- Centrality Class (1)
- Centrality Selection (1)
- Cerambycidae (1)
- Charge fluctuations (1)
- Charge-transfer collisions (1)
- Checkpoint inhibitor (1)
- Chronic hepatitis C (1)
- Circular accelerators (1)
- Cleanliness level (1)
- Clinical Trials and Observations (1)
- Clinical genetics (1)
- Collective Flow, (1)
- Colon capsule endoscopy (1)
- Colorectal cancer (1)
- Comparison with QCD (1)
- Complementation rate (1)
- Computer-aided drug design (1)
- Congenital anomalies (1)
- Consensus statement (1)
- Conservation (1)
- CuveWaters (1)
- C‐reactive protein (1)
- DNA sequence analysis (1)
- DST (1)
- Data sharing (1)
- Denervation (1)
- Diauxic effects (1)
- Differentiation (1)
- Digestive system procedures (1)
- Digitization (1)
- Dilated cardiomyopathy (1)
- Direct Acting Antivirals (DAA) (1)
- Drug susceptibility testing (1)
- Dual-energy computed tomography (1)
- ESBL (1)
- ESG (1)
- ETP-ALL (1)
- Early goal-directed therapy (1)
- Eicosanoids (1)
- Electroantennography (1)
- Electron-pion identification (1)
- Electronic transitions (1)
- Electroweak interaction (1)
- Elliptic flow (1)
- Embryos (1)
- Empirische Ästhetik (1)
- European Society for Immunodeficiencies (ESID) (1)
- Extended donor criteria (1)
- F508del homozygous (1)
- FDM (1)
- FGFR (1)
- FIB-4 (1)
- FLT3 (1)
- Fatty acids (1)
- Fatty liver (1)
- Femtoscopy (1)
- Fibre/foam sandwich radiator (1)
- Fibrosis (1)
- Fibrotest (1)
- Filovirus cell entry; attachment factors redundancy; SH-SY5Y cell line; host–pathogen interactions (1)
- Flow cytometry (1)
- Forschung (1)
- Forschungsdatenmanagement (1)
- Functional clustering (1)
- G-protein-coupled receptors (1)
- GWAS (1)
- Gastric cancer (1)
- Genetic causes of cancer (1)
- Genetic testing (1)
- Genetics (1)
- Genome editing (1)
- German PID-NET registry (1)
- Gomphus flavipes (1)
- Guanine nucleotide exchange factors (1)
- Guanosine triphosphatase (1)
- Gαq/11 (1)
- HBT (1)
- HBV (1)
- HCV (1)
- HDAC4 (1)
- HIF1α (1)
- HIPPO signalling (1)
- HIV-1 (1)
- HNO (1)
- Hadron production (1)
- Hadron-Hadron Scattering Heavy (1)
- Hadron-hadron interactions (1)
- Hals-Nasen-Ohren-Heilkunde (1)
- Haploidentical stem cell transplantation (1)
- Hard Scattering (1)
- Health policy (1)
- Heart (1)
- Heavy Ion Experiment (1)
- Heavy flavor production (1)
- Heavy flavour production (1)
- Heavy ions (1)
- Heavy-flavour decay muons (1)
- Heavy-flavour production (1)
- Heavy-ion collisions (1)
- Hepatitis B virus (1)
- Hepatitis C (1)
- Hepatitis C virus (1)
- Hepatotoxicity (1)
- Herbaria (1)
- High-dose chemotherapy (1)
- Histology (1)
- Homeostasis (1)
- Hsp70 (1)
- Human genetics (1)
- Hypertension (1)
- Hypoxic responses (1)
- IHC (1)
- IWRM (1)
- Icelandic Family Sagas (1)
- IgG substitution therapy (1)
- Immunogenetics (1)
- Inclusive spectra (1)
- Incomplete colonoscopy (1)
- Infection (1)
- Intensity interferometry (1)
- Intensive care unit (1)
- International Law (1)
- Internationales Recht (1)
- Interventional oncological treatment (1)
- Intravenous injections (1)
- Invariant Mass Distribution (1)
- Ionisation energy loss (1)
- Ions (1)
- Jet Physics (1)
- Jet Substructure (1)
- KDIGO (1)
- KIR (1)
- Konstitutionalismus (1)
- Kupffer cells (1)
- LCH (1)
- Landesinitiative (1)
- Landesinitiative für Forschungsdatenmanagement (1)
- Langerhans cell histiocytosis (1)
- Laser interstitial thermal therapy (1)
- Lehre (1)
- Lenalidomide (1)
- Libellen (1)
- Library screening (1)
- Literarischer Stil (1)
- Literaturwissenschaft (1)
- Liver (1)
- Liver cancer (1)
- Liver cirrhosis (1)
- Liver enzymes (1)
- Liver fibrosis (1)
- Liver transplantation (1)
- Long non-coding RNAs (1)
- Low & intermediate-energy accelerators (1)
- Low volume prep (1)
- Luciferase (1)
- Lymphoid Neoplasia (1)
- Lyrik (1)
- M. Intracellulare (1)
- M. avium (1)
- M. avium complex (1)
- M. chimaera (1)
- MALAT1 (1)
- MRP4 (1)
- Macrophages (1)
- Marker genes (1)
- Material budget (1)
- Mechanisms of disease (1)
- Mena/VASP (1)
- Mesenchymal stem cells (1)
- Metabolic shift (1)
- Metabolism (1)
- Microbiology and Infectious Disease (1)
- Microglial cells (1)
- Microwave ablation (1)
- Mid-rapidity (1)
- Minimal residual disease (1)
- Minimum Bias (1)
- Mixed hearing loss (1)
- Mongolia (1)
- Monochamus galloprovincialis (1)
- Monte Carlo (1)
- Mortality (1)
- Moviprep (1)
- Multi-Parton Interactions (1)
- Multi-nucleated cardiomyocytes (1)
- Multi-stakeholder approach (1)
- Multi-strange baryons (1)
- Multi-wire proportional drift chamber (1)
- Multidrug-resistant organisms (1)
- Multiple myeloma (1)
- Multivariate analysis (1)
- Muscle atrophy (1)
- Musikästhetik (1)
- Mutation databases (1)
- Myocardial infarction (1)
- NCoR1 (1)
- NFDI (1)
- NK cells (1)
- NMR spectroscopy (1)
- NOTCH1 (1)
- NTM (1)
- Nachhaltigkeit (1)
- Namibia (1)
- Nationale Forschungsdateninfrastruktur (1)
- Neural network (1)
- Neurons (1)
- Neuroästhetik (1)
- Non-tuberculous mycobacteria (1)
- Nuclear astrophysics (1)
- Nuclear modification factor (1)
- Nuclear physics of explosive environments (1)
- Nuclear reactions (1)
- Nucleus accumbens (1)
- ORL (1)
- Oncogenes (1)
- Online monitoring (1)
- Ophiogomphus cecilia (1)
- Optogenetics (1)
- Organ allocation (1)
- Orphan disease (1)
- Osteoporotic fractures (1)
- Otorhinolaryngology (1)
- Ovarian cancer (1)
- PD-L1 (1)
- PGE2 (1)
- PID prevalence (1)
- PKA (1)
- PKD (1)
- PKD/IC (1)
- PRRT2 (1)
- PYTHIA (1)
- Pancreas transplantation (1)
- Parallelisation (1)
- Particle and Resonance Production (1)
- Pb–Pb (1)
- Periodontal disease (1)
- Periodontal therapy (1)
- Perturbative methods (1)
- Phaenops cyanea (1)
- Phantoms (imaging) (1)
- Phospho-soda (1)
- Phosphorylation (1)
- Photon counting (1)
- PillCamColon2 (1)
- Plasminogen (1)
- Platelets (1)
- Polyps (1)
- Portal veins (1)
- Production Cross Section (1)
- Properties of Hadrons (1)
- Prostaglandin (1)
- Proton–proton (1)
- Pulsed SILAC (1)
- QGP (1)
- Quark Deconfinement (1)
- Quark Gluon Plasma (1)
- Quark Production (1)
- Quark gluon plasma (1)
- Quarkonium (1)
- RDM (1)
- RNA (1)
- RNA, long noncoding (1)
- RNA-binding proteins (1)
- Radiative capture (1)
- Random forest (1)
- Rapidity Range (1)
- Regression analysis (1)
- Rehabilitation (1)
- Rejection (1)
- Relapse (1)
- Relativistic heavy ion physics (1)
- Renal cell carcinoma (1)
- Research (1)
- Research Article (1)
- Research Data Management (1)
- Research Infrastructure (1)
- Residency (1)
- Resolution Parameter (1)
- Riftia pachyptila (1)
- S. cerevisiae (1)
- SARS CoV 2 (1)
- SARS-CoV‑2 pandemic (1)
- SARS-CoV‑2-Pandemie (1)
- SCCHN (1)
- SENP (1)
- SKI II (1)
- STED superresolution (1)
- SUMO (1)
- SVR (1)
- Safety (1)
- Sarcopenia (1)
- Scattering of atoms, molecules, clusters & ions (1)
- Scattering theory (1)
- Second-line treatment (1)
- Semantics (1)
- Sepsis-bundle (1)
- Sequence (1)
- Shake flask (1)
- Single muons (1)
- Single-cell RNA-sequencing (1)
- Small molecules (1)
- Specialist training (1)
- Spectrin (1)
- Sphingolipids (1)
- Stem cells (1)
- Surgery (1)
- Surgical and invasive medical procedures (1)
- Surgical oncology (1)
- Survival (1)
- Sustained virological response (SVR) (1)
- Systematic Uncertainty (1)
- Systemic treatment (1)
- T-ALL (1)
- TACE (1)
- TAVR (1)
- TGF-beta (1)
- TOR signalling (1)
- TP53 mutation status (1)
- TR (1)
- Targeted therapy (1)
- Taxonomy (1)
- Teaching (1)
- Technical data (1)
- Thrombosis (1)
- Thromboxane (1)
- Time Projection Chamber (1)
- Tomography (x-ray computed) (1)
- Tracking (1)
- Transarterial chemoembolization (1)
- Transcriptome analysis (1)
- Transferases (1)
- Transient elastography (1)
- Transition radiation detector (1)
- Transverse momentum (1)
- Trigger (1)
- Trousseau’s syndrome (1)
- Type 2 diabetes (1)
- Tyrosine kinase inhibitor mTOR inhibition (1)
- UAV (1)
- Ubiquitination (1)
- University hospitals (1)
- Universitätskliniken (1)
- VRE (1)
- Vector Boson Production (1)
- Veins (1)
- Vesicles (1)
- Viral load (1)
- Weiterbildung (1)
- Wettbewerbsrecht (1)
- X-ray crystallography (1)
- Xenon-based gas mixture (1)
- Yellow fluorescent protein (1)
- a-induced reactions (1)
- accessory proteins (1)
- acoustic radiation force impulse imaging (1)
- activation (1)
- acute coronary syndrome (1)
- acute leukemia (1)
- acute lymphoblastic leukemia (1)
- adenocarcinoma (1)
- adenosine receptors (1)
- aesthetic reward (1)
- age (1)
- agriculture (1)
- alcoholic hepatitis (1)
- allogeneic stem cell transplantation (1)
- amino acids (1)
- angiopoietin-like 3 (ANGPTL3) (1)
- anti-EGFR therapy (1)
- antibiotic therapy (1)
- antibodies (1)
- antiepileptic drugs (1)
- antifungal combination therapy (1)
- antifungal therapy (1)
- antimicrobial stewardship (1)
- antiviral therapy (1)
- arachidonate 12/15-lipoxygenase (Alox12/15) (1)
- architecture (1)
- ascites (1)
- atherosclerosis (1)
- atrial fibrillation (1)
- atrophy (1)
- autophagy (1)
- b-cell lymphomas (1)
- bacteremia (1)
- bendamustine (1)
- blood (1)
- bone marrow metastasis (1)
- bone metastasis (1)
- cAMP (1)
- cART (1)
- cancer surveillance (1)
- carbapenem resistance (1)
- cardiac I/R injury (1)
- cardiac remodeling (1)
- cell differentiation (1)
- cell heterogeneity (1)
- cell-free protein synthesis (1)
- centrosome (1)
- centrosome linker (1)
- ceramides (1)
- chemoembolization (1)
- chemorefractory metastatic colorectal cancer (1)
- chemotherapy regimen (1)
- children and adolescents (1)
- chills (1)
- chimeric antigen receptor t-cell therapy (1)
- chimeric antigen receptors (1)
- cholestasis (1)
- chromosomal translocations (1)
- chronic kidney disease (1)
- chronic viral hepatitis (1)
- cirrhosis (1)
- co-infection (1)
- cohort study (1)
- computed tomography (1)
- confidence interval (1)
- confirmatory factor analysis (1)
- constitutionalisation (1)
- constitutionalism (1)
- coronary disease (1)
- critical care unit (1)
- critical ill patients (1)
- cutaneous T cell lymphoma (1)
- cystic fibrosis (1)
- dE/dx (1)
- damage detection (1)
- decision aids (1)
- demand-responsive approach (1)
- desmoplastic small round cell tumor (1)
- detector (1)
- dihydroceramide (1)
- dihydroceramides (1)
- direct-acting antivirals (1)
- disease progression (1)
- drone (1)
- eNPP2 (1)
- enrichment (1)
- entity and event extraction (1)
- epigenomics (1)
- experimental results (1)
- extraskeletal (1)
- familial infantile epilepsy (1)
- fatigue testing (1)
- fibrocytes (1)
- fibrosis (1)
- fibrotest (1)
- fine spatial resolution remote sensing (1)
- first-time shoulder dislocation (1)
- fixed-links modeling (1)
- fluid intelligence (1)
- fumonisin B1 (1)
- gap junction protein alpha 4-genotype (1)
- genetic generalized epilepsy (1)
- germ cell tumors (1)
- glass fiber reinforced materials (1)
- glioblastoma (1)
- global change (1)
- graft rejection (1)
- head-and-neck cancer (1)
- heart failure (1)
- heavy ion experiments (1)
- hematopoietic cell transplantation (1)
- hemiplegic migraine (1)
- hepatic fibrosis (1)
- hepatic tumor (1)
- hepatitis C (1)
- hepatitis C virus (1)
- hepatitis c (1)
- herbarium (1)
- high-dose chemotherapy (1)
- histology (1)
- homoarginine (1)
- host-microbe interaction (1)
- human knockout model (1)
- hypertension, pulmonary (1)
- idiopathic pulmonary fibrosis (1)
- immobilization in external rotation and abduction (1)
- immune checkpoint inhibitor (ICI) (1)
- immunohistochemistry (1)
- immunoprecipitation (1)
- immunotherapy (1)
- infection (1)
- infection control (1)
- infections (1)
- inflammatory markers (1)
- insulin resistance (1)
- interferon regulatory factor 9 (IRF9) (1)
- international legal theory (1)
- intraperitoneal therapy (1)
- intrinsically disordered region (1)
- ischemic type biliary lesions (1)
- knockout mouse (1)
- lamotrigine (1)
- land use (1)
- leukapheresis (1)
- leukemia (1)
- levetiracetam (1)
- lipoxin A4 (1)
- liver (1)
- liver abscess (1)
- liver cirrhosis (1)
- liver transplantation (1)
- long non-coding RNA (1)
- lung disease phenotype (1)
- lung function (1)
- lymphoma (1)
- l‐arginine:glycine amidinotransferase (1)
- maintenance therapy (1)
- malignancy (1)
- mass spectrometry (1)
- metastasis (1)
- methyltransferases (1)
- molecular characteristics (1)
- multi-resources mix (1)
- multidrug resistance (1)
- naturalization (1)
- neovascularization, physiologic (1)
- neuroaesthetics (1)
- neutralizing antibodies (1)
- neutropenia (1)
- nomadic lifestyles (1)
- non-ST-segment elevation acute coronary syndrome (1)
- non-invasive fibrosis assessment (1)
- non-neutropenic episode (1)
- nonstructural proteins (1)
- odds ratio (1)
- oral narratives (1)
- orthopic liver transplantation (1)
- outcome (1)
- ovary (1)
- p97 (1)
- parliament libraries (1)
- pediatric solid tumors (1)
- performativity (1)
- peritoneal carcinomatosis (1)
- pharmacoresistance (1)
- phenotype/genotype relation (1)
- phenotypic spectrum (1)
- piloerection (1)
- plant diversity (1)
- plant height (1)
- pneumonia (1)
- poetic language (1)
- point shear wave elastography (1)
- precision medicine (1)
- pressurized intraperitoneal aerosol chemotherapy (PIPAC) (1)
- primary biliary cirrhosis (1)
- primary immunodeficiency (1)
- primary immunodeficiency (PID) (1)
- primary sclerosing cholangitis (1)
- prognostic biomarker (1)
- quark gluon plasma (1)
- radar-based structural health monitoring (1)
- radio sensitivity (1)
- rain- and floodwater harvesting (1)
- rangeland ecosystems (1)
- rats (1)
- re-exposure (1)
- rechallenge (1)
- registry for primary immunodeficiency (1)
- reintroduction (1)
- resolution of inflammation (1)
- retrospective trial (1)
- risk assessment (1)
- rituximab (1)
- rootletin (1)
- rural-urban migration (1)
- sanitation (1)
- sarcoma (1)
- screening routine (1)
- semantic content analysis (1)
- sepsis (1)
- sequential ALK-inhibitor therapy (1)
- sex (1)
- short-chain ceramide (1)
- shortening of treatment (1)
- shoulder instability (1)
- shoulder stabilization (1)
- skeletal muscle (1)
- skin (1)
- social Web (1)
- solid tumor (1)
- sorafenib (1)
- specialized pro-resolving lipid mediators (SPMs) (1)
- spectra (1)
- sphinganine 1-phosphate (1)
- sphingolipid (1)
- sphingosine 1-phosphate (1)
- sphingosine kinase (1)
- sphingosine-1-phosphate (1)
- spike protein (1)
- steppe ecosystem (1)
- stopping rule (1)
- structural proteins (1)
- structure-from-motion photogrammetry (1)
- sulfur-oxidizing symbiont (1)
- symbiosis (1)
- tense switches (1)
- testis (1)
- text analysis (1)
- tomography (1)
- topic detection (1)
- transcatheter aortic valve replacement (1)
- transdisciplinarity (1)
- transfemoral (1)
- transient elastography (1)
- translocation partner genes (1)
- transmission (1)
- treatment (1)
- tumor microenvironment (TME) (1)
- type I interferons (IFNs) (1)
- tyrosine kinase inhibitor (TKI) (1)
- upper gastrointestinal cancer (1)
- valproic acid (1)
- variants of concern (1)
- vascular calcification (1)
- vemurafenib (1)
- versican (VCAN) (1)
- web crawler (1)
- whole-genome sequencing (1)
- wildlife mobility (1)
- wind turbine blades (1)
- working memory capacity (1)
- x-ray techniques (1)
- Ästhetik (1)
- γ-spectroscopy (1)
- гепатит С (1)
- правила прекращения лечения (1)
- противовирусные препараты прямого действия (ПППД) (1)
- сокращение лечения (1)
- устойчивый вирусологический ответ (УВО) (1)
- √sN N = 2.76 TeV (1)
Institute
- Physik (1083)
- Frankfurt Institute for Advanced Studies (FIAS) (958)
- Informatik (921)
- Medizin (158)
- Biowissenschaften (7)
- ELEMENTS (7)
- Biochemie, Chemie und Pharmazie (6)
- Sustainable Architecture for Finance in Europe (SAFE) (6)
- Wirtschaftswissenschaften (6)
- Geowissenschaften (5)
Filoviruses infect a wide range of cell types with the exception of lymphocytes. The intracellular proteins cathepsin B and L, two-pore channel 1 and 2, and bona fide receptor Niemann–Pick Disease C1 (NPC1) are essential for the endosomal phase of cell entry. However, earlier steps of filoviral infection remain poorly characterized. Numerous plasma membrane proteins have been implicated in attachment but it is still unclear which ones are sufficient for productive entry. To define a minimal set of host factors required for filoviral glycoprotein-driven cell entry, we screened twelve cell lines and identified the nonlymphocytic cell line SH-SY5Y to be specifically resistant to filovirus infection. Heterokaryons of SH-SY5Y cells fused to susceptible cells were susceptible to filoviruses, indicating that SH-SY5Y cells do not express a restriction factor but lack an enabling factor critical for filovirus entry. However, all tested cell lines expressed functional intracellular factors. Global gene expression profiling of known cell surface entry factors and protein expression levels of analyzed attachment factors did not reveal any correlation between susceptibility and expression of a specific host factor. Using binding assays with recombinant filovirus glycoprotein, we identified cell attachment as the step impaired in filovirus entry in SH-SY5Y cells. Individual overexpression of attachment factors T-cell immunoglobulin and mucin domain 1 (TIM-1), Axl, Mer, or dendritic cell-specific intercellular adhesion molecule-3-grabbing non-integrin (DC-SIGN) rendered SH-SY5Y cells susceptible to filovirus glycoprotein-driven transduction. Our study reveals that a lack of attachment factors limits filovirus entry and provides direct experimental support for a model of filoviral cell attachment where host factor usage at the cell surface is highly promiscuous.
The 124Xe(p,γ) reaction has been measured for the first time at energies around the Gamow window by using stored ions at the ESR facility. The desired beam energies below 10 MeV/u introduce new experimental challenges like windowless ions detection under UHV conditions, extremely short beam lifetimes and efficient beam deceleration and cooling, all of which have been successfully met.
The electron-capture process was studied for Xe54+ colliding with H2 molecules at the internal gas target of the Experimental Storage Ring (ESR) at GSI, Darmstadt. Cross-section values for electron capture into excited projectile states were deduced from the observed emission cross section of Lyman radiation, being emitted by the hydrogenlike ions subsequent to the capture of a target electron. The ion beam energy range was varied between 5.5 and 30.9 MeV/u by applying the deceleration mode of the ESR. Thus, electron-capture data were recorded at the intermediate and, in particular, the low-collision-energy regime, well below the beam energy necessary to produce bare xenon ions. The obtained data are found to be in reasonable qualitative agreement with theoretical approaches, while a commonly applied empirical formula significantly overestimates the experimental findings.
Background and aims: Clinical trials of therapy against chronic hepatitis C virus (HCV) infection including boceprevir (BOC) or telaprevir (TVR) plus pegylated interferon and ribavirin (PR) have reported considerably higher response rates than those achieved with PR alone. This study sought to evaluate the efficacy and safety of triple therapy including BOC or TVR in combination with PR in HIV/HCV-coinfected patients under real-life conditions.
Methods: In a multicentre study conducted in 24 sites throughout five European countries, all HIV/HCV-coinfected patients who initiated a combination of BOC or TVR plus PR and who had at least 60 weeks of follow-up, were analyzed. Sustained virologic response 12 weeks after the scheduled end of therapy date (SVR12) and the rate of discontinuations due to adverse events (AE) were evaluated.
Results: Of the 159 subjects included, 127 (79.9%) were male, 45 (34.4%) were treatment-naïve for PR and 60 (45.4%) showed cirrhosis. SVR12 was observed in 31/46 (67.4%) patients treated with BOC and 69/113 (61.1%) patients treated with TVR. Overall discontinuations due to AE rates were 8.7% for BOC and 8% for TVR. Grade 3 or 4 hematological abnormalities were frequently observed; anemia 7%, thrombocytopenia 17.2% and neutropenia 16.4%.
Conclusion: The efficacy and safety of triple therapy including BOC or TVR plus PR under real-life conditions of use in the HIV/HCV-coinfected population was similar to what is observed in clinical trials. Hematological side effects are frequent but manageable.
The production of 77,79,85,85mKr and 77Br via the reaction Se(a, x) was investigated between Ea = 11 and 15 MeV using the activation technique. The irradiation of natural selenium targets on aluminum backings was conducted at the Physikalisch-Technische Bundesanstalt (PTB) in Braunschweig, Germany. The spectroscopic analysis of the reaction products was performed using a high-purity germanium detector located at PTB and a low energy photon spectrometer detector at the Goethe University Frankfurt, Germany. Thicktarget yields were determined. The corresponding energy-dependent production cross sections of 77,79,85,85mKr and 77Br were calculated from the thicktarget yields. Good agreement between experimental data and theoretical predictions using the TALYS-1.6 code was found.
Activated SUMOylation restricts MHC class I antigen presentation to confer immune evasion in cancer
(2022)
Activated SUMOylation is a hallmark of cancer. Starting from a targeted screening for SUMO-regulated immune evasion mechanisms, we identified an evolutionarily conserved function of activated SUMOylation, which attenuated the immunogenicity of tumor cells. Activated SUMOylation allowed cancer cells to evade CD8+ T cell–mediated immunosurveillance by suppressing the MHC class I (MHC-I) antigen-processing and presentation machinery (APM). Loss of the MHC-I APM is a frequent cause of resistance to cancer immunotherapies, and the pharmacological inhibition of SUMOylation (SUMOi) resulted in reduced activity of the transcriptional repressor scaffold attachment factor B (SAFB) and induction of the MHC-I APM. Consequently, SUMOi enhanced the presentation of antigens and the susceptibility of tumor cells to CD8+ T cell–mediated killing. Importantly, SUMOi also triggered the activation of CD8+ T cells and thereby drove a feed-forward loop amplifying the specific antitumor immune response. In summary, we showed that activated SUMOylation allowed tumor cells to evade antitumor immunosurveillance, and we have expanded the understanding of SUMOi as a rational therapeutic strategy for enhancing the efficacy of cancer immunotherapies.
Malignant germ cell tumors (GCT) are the most common malignant tumors in young men between 18 and 40 years. The correct identification of histological subtypes, in difficult cases supported by immunohistochemistry, is essential for therapeutic management. Furthermore, biomarkers may help to understand pathophysiological processes in these tumor types. Two GCT cell lines, TCam-2 with seminoma-like characteristics, and NTERA-2, an embryonal carcinoma-like cell line, were compared by a quantitative proteomic approach using high-resolution mass spectrometry (MS) in combination with stable isotope labelling by amino acid in cell culture (SILAC). We were able to identify 4856 proteins and quantify the expression of 3936. 347 were significantly differentially expressed between the two cell lines. For further validation, CD81, CBX-3, PHF6, and ENSA were analyzed by western blot analysis. The results confirmed the MS results. Immunohistochemical analysis on 59 formalin-fixed and paraffin-embedded (FFPE) normal and GCT tissue samples (normal testis, GCNIS, seminomas, and embryonal carcinomas) of these proteins demonstrated the ability to distinguish different GCT subtypes, especially seminomas and embryonal carcinomas. In addition, siRNA-mediated knockdown of these proteins resulted in an antiproliferative effect in TCam-2, NTERA-2, and an additional embryonal carcinoma-like cell line, NCCIT. In summary, this study represents a proteomic resource for the discrimination of malignant germ cell tumor subtypes and the observed antiproliferative effect after knockdown of selected proteins paves the way for the identification of new potential drug targets.
Loss of neuronal stimulation enhances protein breakdown and reduces protein synthesis, causing rapid loss of muscle mass. To elucidate the pathophysiological adaptations that occur in atrophying muscles, we used stable isotope labelling and mass spectrometry to quantify protein expression changes accurately during denervation-induced atrophy after sciatic nerve section in the mouse gastrocnemius muscle. Additionally, mice were fed a stable isotope labelling of amino acids in cell culture (SILAC) diet containing 13C6-lysine for 4, 7 or 11 days to calculate relative levels of protein synthesis in denervated and control muscles. Ubiquitin remnant peptides (K-ε-GG) were profiled by immunoaffinity enrichment to identify potential substrates of the ubiquitin-proteasomal pathway. Of the 4279 skeletal muscle proteins quantified, 850 were differentially expressed significantly within 2 weeks after denervation compared with control muscles. Moreover, pulse labelling identified Lys6 incorporation in 4786 proteins, of which 43 had differential Lys6 incorporation between control and denervated muscle. Enrichment of diglycine remnants identified 2100 endogenous ubiquitination sites and revealed a metabolic and myofibrillar protein diglycine signature, including myosin heavy chains, myomesins and titin, during denervation. Comparative analysis of these proteomic data sets with known atrogenes using a random forest approach identified 92 proteins subject to atrogene-like regulation that have not previously been associated directly with denervation-induced atrophy. Comparison of protein synthesis and proteomic data indicated that upregulation of specific proteins in response to denervation is mainly achieved by protein stabilization. This study provides the first integrated analysis of protein expression, synthesis and ubiquitin signatures during muscular atrophy in a living animal.
Purpose: Current systemic treatment of targeted therapies, namely the vascular endothelial growth factor-antibody (VEGF-AB), VEGF receptor tyrosine kinase inhibitor (TKI) and mammalian target of rapamycin (mTOR) inhibitors, have improved progression-free survival and replaced non-specific immunotherapy with cytokines in metastatic renal cell carcinoma (mRCC).
Methods: A panel of experts convened to review currently available phase 3 data for mRCC treatment of approved agents, in addition to available EAU guideline data for a collaborative review as the plurality of substances offers different options of first-, second- and third-line treatment with potential sequencing.
Results: Sunitinib and pazopanib are approved treatments in first-line therapy for patients with favorable- or intermediate-risk clear cell RCC (ccRCC). Temsirolimus has proven benefit over interferon-alfa (IFN-α) in patients with non-clear cell RCC (non-ccRCC). In the second-line treatment TKIs or mTOR inhibitors are treatment choices. Therapy options after TKI failure consist of everolimus and axitinib. Available third-line options consist of everolimus and sorafenib. Recently, nivolumab, a programmed death-1 (PD1) checkpoint inhibitor, improved overall survival benefit compared to everolimus after failure of one or two VEGFR-targeted therapies, which is likely to become the first established checkpoint inhibitor in mRCC. Data for the sequencing of agents remain limited.
Conclusions: Despite the high level of evidence for first and second-line treatment in mRCC, data for third-line therapy are limited. Possible sequences include TKI-mTOR-TKI or TKI–TKI-mTOR with the upcoming checkpoint inhibitors in perspective, which might settle a new standard of care after previous TKI therapy.
Poster presentation: Purpose of the study First-line HAART with tenofovir DF (TDF) and FTC in pivotal trials has been associated with high efficacy and good tolerability. However, real-life clinical practice often differs from clinical trials due to co-morbidities, co-infections, and less intensive clinical monitoring. To evaluate efficacy and safety of first-line HAART in a day-to-day setting, this Gilead-sponsored non-interventional cohort was established. Methods Between July 2005 and August 2006, 533 HIV-1 infected antiretroviral-naïve patients from 50 German centres enrolled in this non-interventional cohort. All patients were followed every 3 months for 3 years to monitor efficacy (viral load [VL], CD4), tolerability, renal safety, regimen changes and resistance profile. All patients received TDF+FTC as a single tablet (Truvada, TVD) in combination with either an NNRTI or PI/r as their first antiretroviral regimen. Summary of results As of June 2008, 2 years of therapy have been documented for 330/533 (62%) patients. At treatment initiation, 81% were male; median age was 39 years; clinical AIDS diagnosis was documented in 22%; 47% started therapy with CD4 <200 cells/mm3. TVD was combined with an NNRTI (43%) or a PI/r (57%). After 24 months, in an As-Treated (AT) analysis, 85% patients achieved a VL <50 copies/ml (VL <500 copies/ml: 97%), median CD4 count increased from 217 at baseline to 450 cells/mm3 (IQR: 325–608). Truvada showed a good safety profile; 76 adverse events (AEs) of any grade were reported in 66/533 patients (12%); six of these were judged serious. Fourteen (2.6%) patients discontinued TVD due to AEs. Renal abnormalities of any grade were reported in 10 patients (1.9%). Virological failure was documented in nine patients, of which eight were genotyped; M184V/I was detected in three, K65R in two patients. Conclusion During 2 years of follow-up, the overall safety of TVD was good; renal AEs of any grade were reported in 1.9% of patients. K65R was detected in two patients. First-line HAART with TVD plus an NNRTI or PI/r in clinical practice showed comparable efficacy to that observed in controlled clinical trials.
Triple therapy of chronic hepatitis C virus (HCV) infection with boceprevir (BOC) or telaprevir (TVR) leads to virologic failure in many patients which is often associated with the selection of resistance-associated variants (RAVs). These resistance profiles are of importance for the selection of potential rescue treatment options. In this study, we sequenced baseline NS3 RAVs population-based and investigated the sensitivity of NS3 phenotypes in an HCV replicon assay together with clinical factors for a prediction of treatment response in a cohort of 165 German and Swiss patients treated with a BOC or TVR-based triple therapy. Overall, the prevalence of baseline RAVs was low, although the frequency of RAVs was higher in patients with virologic failure compared to those who achieved a sustained virologic response (SVR) (7% versus 1%, P = 0.06). The occurrence of RAVs was associated with a resistant NS3 quasispecies phenotype (P<0.001), but the sensitivity of phenotypes was not associated with treatment outcome (P = 0.2). The majority of single viral and host predictors of SVR was only weakly associated with treatment response. In multivariate analyses, low AST levels, female sex and an IFNL4 CC genotype were independently associated with SVR. However, a combined analysis of negative predictors revealed a significantly lower overall number of negative predictors in patients with SVR in comparison to individuals with virologic failure (P<0.0001) and the presence of 2 or less negative predictors was indicative for SVR. These results demonstrate that most single baseline viral and host parameters have a weak influence on the response to triple therapy, whereas the overall number of negative predictors has a high predictive value for SVR.
Investigators in the cognitive neurosciences have turned to Big Data to address persistent replication and reliability issues by increasing sample sizes, statistical power, and representativeness of data. While there is tremendous potential to advance science through open data sharing, these efforts unveil a host of new questions about how to integrate data arising from distinct sources and instruments. We focus on the most frequently assessed area of cognition - memory testing - and demonstrate a process for reliable data harmonization across three common measures. We aggregated raw data from 53 studies from around the world which measured at least one of three distinct verbal learning tasks, totaling N = 10,505 healthy and brain-injured individuals. A mega analysis was conducted using empirical bayes harmonization to isolate and remove site effects, followed by linear models which adjusted for common covariates. After corrections, a continuous item response theory (IRT) model estimated each individual subject’s latent verbal learning ability while accounting for item difficulties. Harmonization significantly reduced inter-site variance by 37% while preserving covariate effects. The effects of age, sex, and education on scores were found to be highly consistent across memory tests. IRT methods for equating scores across AVLTs agreed with held-out data of dually-administered tests, and these tools are made available for free online. This work demonstrates that large-scale data sharing and harmonization initiatives can offer opportunities to address reproducibility and integration challenges across the behavioral sciences.
Infections are an important cause for morbidity and mortality in pediatric acute myeloid leukemia (AML). We therefore characterized infectious complications in children treated according to the trial AML-BFM 2004. Patients with Down syndrome were excluded from the analysis. Data were gathered from the medical records in the hospital where the patients were treated. A total of 405 patients (203 girls; median age 8.4 years) experienced 1326 infections. Fever without identifiable source occurred in 56.1% of the patients and clinically and microbiologically documented infections in 17.5% and 32.4% of the patients, respectively. In all, 240 Gram-positive (112 viridans group streptococci) and 90 Gram-negative isolates were recovered from the bloodstream. Invasive fungal infection was diagnosed in 3% of the patients. Three children each died of Gram-negative bacteremia and invasive aspergillosis, respectively. As compared with the results of AML-BFM 93 with lower dose intensity, infection-related morbidity was slightly higher in AML-BFM 2004 (3.3. versus 2.8 infections per patient), whereas infection-related mortality significantly decreased (1.5% versus 5.4%; P=0.003). Specific anti-infective recommendations included in the treatment protocol, regular training courses for pediatric hematologists and increasing experience may be the reason for reduced infection-related mortality in children with AML. Further studies are needed to decrease infection-related morbidity.
Experiment NA49 at the Cern SPS uses a large acceptance detector for a systematic study of particle yields and correlations in nucleus-nucleus, nucleon-nucleus and nucleon-nucleon collisions. Preliminary results for Pb+Pb collisions at 40, 80 and 158 A*GeV beam energy are shown and compared to measurements at lower and higher energies.
BACKGROUND: Plasminogen deficiency is a rare autosomal recessive disease, which is associated with aggressive periodontitis and gingival enlargement. Previously described treatments of plasminogen deficiency associated periodontitis have shown limited success. This is the first case report indicating a successful therapy approach consisting of a non-surgical supra- and subgingival debridement in combination with an adjunctive systemic antibiotic therapy and a strict supportive periodontal regimen over an observation period of 4 years.
CASE PRESENTATION: The intraoral examination of a 17-year-old Turkish female with severe plasminogen deficiency revealed generalized increased pocket probing depths ranging from 6 to 9 mm, bleeding on probing over 30%, generalized tooth mobility, and gingival hyperplasia. Alveolar bone loss ranged from 30% to 50%. Clinical attachment loss corresponded to pocket probing depths. Aggregatibacter actinomycetemcomitans, Porphyromonas gingivalis, Treponema denticola, Prevotella intermedia, Prevotella nigrescens and Eikenella corrodens have been detected by realtime polymerase chain reaction. Periodontal treatment consisted of full mouth disinfection and adjunctive systemic administration of amoxicillin (500 mg tid) and metronidazole (400 mg tid). A strict supportive periodontal therapy regimen every three month in terms of supra- and subgingival debridement was rendered. The reported therapy has significantly improved periodontal health and arrested disease progression. Intraoral examination at the end of the observation period 3.5 years after non-surgical periodontal therapy showed generalized decreased pocket probing depths ranging from 1 to 6 mm, bleeding on probing lower 30%, and tooth mobility class I and II. Furthermore, microbiological analysis shows the absence of Porphyromonas gingivalis, Prevotella intermedia and Treponema denticola after therapy.
CONCLUSION: Adjunctive antibiotic treatment may alter the oral microbiome and thus, the inflammatory response of periodontal disease associated to plasminogen deficiency and diminishes the risk of pseudomembrane formation and progressive attachment loss. This case report indicates that patients with plasminogen deficiency may benefit from non-surgical periodontal treatment in combination with an adjunctive antibiotic therapy and a strict supportive periodontal therapy regimen.
Numerous studies reported a strong link between working memory capacity (WMC) and fluid intelligence (Gf), although views differ in respect to how close these two constructs are related to each other. In the present study, we used a WMC task with five levels of task demands to assess the relationship between WMC and Gf by means of a new methodological approach referred to as fixed-links modeling. Fixed-links models belong to the family of confirmatory factor analysis (CFA) and are of particular interest for experimental, repeated-measures designs. With this technique, processes systematically varying across task conditions can be disentangled from processes unaffected by the experimental manipulation. Proceeding from the assumption that experimental manipulation in a WMC task leads to increasing demands on WMC, the processes systematically varying across task conditions can be assumed to be WMC-specific. Processes not varying across task conditions, on the other hand, are probably independent of WMC. Fixed-links models allow for representing these two kinds of processes by two independent latent variables. In contrast to traditional CFA where a common latent variable is derived from the different task conditions, fixed-links models facilitate a more precise or purified representation of the WMC-related processes of interest. By using fixed-links modeling to analyze data of 200 participants, we identified a non-experimental latent variable, representing processes that remained constant irrespective of the WMC task conditions, and an experimental latent variable which reflected processes that varied as a function of experimental manipulation. This latter variable represents the increasing demands on WMC and, hence, was considered a purified measure of WMC controlled for the constant processes. Fixed-links modeling showed that both the purified measure of WMC (β = .48) as well as the constant processes involved in the task (β = .45) were related to Gf. Taken together, these two latent variables explained the same portion of variance of Gf as a single latent variable obtained by traditional CFA (β = .65) indicating that traditional CFA causes an overestimation of the effective relationship between WMC and Gf. Thus, fixed-links modeling provides a feasible method for a more valid investigation of the functional relationship between specific constructs.
Ongoing and predicted global change makes understanding and predicting species’ range shifts an urgent scientific priority. Here, we provide a synthetic perspective on the so far poorly understood effects of interspecific interactions on range expansion rates. We present theoretical foundations for how interspecific interactions may modulate range expansion rates, consider examples from empirical studies of biological invasions and natural range expansions as well as process-based simulations, and discuss how interspecific interactions can be more broadly represented in process-based, spatiotemporally explicit range forecasts. Theory tells us that interspecific interactions affect expansion rates via alteration of local population growth rates and spatial displacement rates, but also via effects on other demographic parameters. The best empirical evidence for interspecific effects on expansion rates comes from studies of biological invasions. Notably, invasion studies indicate that competitive dominance and release from specialized enemies can enhance expansion rates. Studies of natural range expansions especially point to the potential for competition from resident species to reduce expansion rates. Overall, it is clear that interspecific interactions may have important consequences for range dynamics, but also that their effects have received too little attention to robustly generalize on their importance. We then discuss how interspecific interactions effects can be more widely incorporated in dynamic modeling of range expansions. Importantly, models must describe spatiotemporal variation in both local population dynamics and dispersal. Finally, we derive the following guidelines for when it is particularly important to explicitly represent interspecific interactions in dynamic range expansion forecasts: if most interacting species show correlated spatial or temporal trends in their effects on the target species, if the number of interacting species is low, and if the abundance of one or more strongly interacting species is not closely linked to the abundance of the target species.
Objective: Phenotypic (Sensititre Myco, pDST) and genotypic drug susceptibility testing (GenoType NTM DR, gDST) in M. avium complex (MAC) have become available as standardized assays, but comparable data is needed. This study aimed to investigate the phenotypic and genotypic drug susceptibility patterns in MAC clinical isolates.
Methods: Overall, 98 isolates from 85 patients were included. pDST and gDST were performed on all isolates and results compared regarding specificity and sensitivity using pDST as a reference method. The impact of drug instability on pDST results was studied using a biological assay over 14 days. In addition, the evolution of antimicrobial resistance was investigated in sequential isolates of 13 patients.
Results: Macrolide resistance was rare, 1.2% (95% CI 0.7–7.3) of isolates in the base cohort. No aminoglycoside resistances were found, but 14.1% of the studied isolates (95% CI 7.8–23.8) showed intermediate susceptibility. The GenoType NTM DR identified two out of four macrolide-resistant isolates. Antibiotic stability was demonstrated to be poor in rifampicin, rifabutin, and doxycycylin.
Conclusions: pDST results in NTM for unstable antibiotics must be interpreted with care. A combination of pDST and gDST will be useful for the guidance of antimicrobial therapy in MAC-disease.
Tumor progression largely depends on the presence of alternatively polarized (M2) tumor-associated macrophages (TAMs), whereas the classical M1-polarized macrophages can promote anti-tumorigenic immune responses. Thus, selective inhibition of M2-TAMs is a desirable anti-cancer approach in highly resistant tumor entities such as hepatocellular carcinoma (HCC) or breast cancer. We here examined whether a peptide that selectively binds to and is internalized by in vitro-differentiated murine M2 macrophages as compared to M1 macrophages, termed M2pep, could be used to selectively target TAMs in HCC and breast carcinoma. We confirmed selectivity of M2pep for in vitro M2 polarized macrophages. Upon incubation of suspended mixed 4T1 tumor cells with M2pep, high amounts of the TAMs were found to be associated with M2pep, whereas in mixed tumor cell suspensions from two HCC mouse models, M2pep showed only low-degree binding to TAMs. M2pep also showed low-degree targeting of liver macrophages. This indicates that the TAMs in different tumor entities show different targeting of M2pep and that M2pep is a very promising approach to develop selective M2-TAM-targeting in tumor entities containing M2-TAMs with significant amounts of the so far elusive M2pep receptor(s).
The Eastern Steppe of Mongolia is one of the world's largest mostly intact grassland ecosystems and is characterised by a close coupling of societal and natural processes. In this ecosystem, mobility is one of the key characteristics of wildlife and human societies alike. The current economic development of Mongolia is accompanied by extensive societal transformation and changes in nomadic lifestyles, which potentially affects the unique steppe ecosystem and its biodiversity. The changing lifestyles are mainly characterised by rural-urban migration, resulting in reduced mobility of herders and their livestock, and presumably affecting wildlife. The question is how mobility can be fostered under these transformation processes. Time is pressing as a new generation is born which is growing up in urban environments and with new skill sets but a potential loss of the tight connection to nature and the nomadic lifestyle.