Refine
Year of publication
Document Type
- Preprint (719)
- Article (581)
- Conference Proceeding (5)
- Report (1)
- Working Paper (1)
Has Fulltext
- yes (1307)
Is part of the Bibliography
- no (1307)
Keywords
- Heavy Ion Experiments (21)
- Hadron-Hadron Scattering (11)
- Hadron-Hadron scattering (experiments) (11)
- LHC (9)
- Heavy-ion collision (6)
- SARS-CoV-2 (6)
- ALICE experiment (4)
- COVID-19 (4)
- COVID19-NMR (4)
- Collective Flow (4)
- Jets (4)
- Quark-Gluon Plasma (4)
- Solution NMR spectroscopy (4)
- 5′-UTR (3)
- ALICE (3)
- Heavy Ions (3)
- Heavy Quark Production (3)
- Jets and Jet Substructure (3)
- anal cancer (3)
- chemoradiotherapy (3)
- p53 (3)
- pp collisions (3)
- risk factors (3)
- Beauty production (2)
- Biochemistry (2)
- C-reactive protein (2)
- Charm physics (2)
- Collectivity (2)
- Correlation (2)
- Diffraction (2)
- Elastic scattering (2)
- Elliptic flow (2)
- Experimental nuclear physics (2)
- Experimental particle physics (2)
- HIV (2)
- Head and neck cancer (2)
- Heavy-ion collisions (2)
- Lepton-Nucleon Scattering (experiments) (2)
- Particle Correlations and Fluctuations (2)
- Particle and resonance production (2)
- Particle correlations and fluctuations (2)
- Patterns of care (2)
- Pb–Pb collisions (2)
- Postoperative radiochemotherapy (2)
- Precipitation inhibition (2)
- QCD (2)
- Quarkonium (2)
- RNA (2)
- Radiotherapy (2)
- Relativistic heavy-ion collisions (2)
- Shear viscosity (2)
- Single electrons (2)
- Supersaturation (2)
- Target validation (2)
- Treatment (2)
- albumin (2)
- biomarker (2)
- cervical cancer (2)
- chemotherapy (2)
- clinically important restrictions and symptoms (2)
- drug resistance (2)
- inflammation (2)
- local control (2)
- nutlin-3 (2)
- observational study (2)
- portal hypertension (2)
- rare disease (2)
- supersaturation (2)
- 19F (1)
- 5'-UTR (1)
- 5_SL4 (1)
- 900 GeV (1)
- ACLF (1)
- ADHD (1)
- AIDS (1)
- ALICE detector (1)
- Adolescents (1)
- Advanced stage (1)
- Anal cancer (1)
- Anti-kaon–nucleon physics (1)
- Anti-nuclei (1)
- Archaeogeophysics (1)
- Atomic and molecular interactions with photons (1)
- Attention-Deficit/Hyperactivity Disorder (ADHD) (1)
- Azores Archipelago (1)
- B-slope (1)
- Biochemistry and chemical biology (1)
- Biodiversity (1)
- Bioenabling formulations (1)
- Biomarker (1)
- Blood sample handling (1)
- Boosted Jets (1)
- CAR (1)
- CD8 (1)
- CD8+ tumor infiltrating lymphocytes (1)
- CNS toxicity (1)
- COVID (1)
- COVID‐19 (1)
- CRT (1)
- CXCR4 (1)
- Cancer genomics (1)
- Centrality Class (1)
- Centrality Selection (1)
- Charge fluctuations (1)
- Charged-particle multiplicity (1)
- Charm quark spatial diffusion coefficient (1)
- Chemical composition (1)
- Chemical physics (1)
- Chemoradiotherapy (1)
- Coalescence (1)
- Cold nuclear matter effects (1)
- Collective Flow, (1)
- Comparative genomics (1)
- Comparison with QCD (1)
- Complicated stage (1)
- Conduct disorder (1)
- Conformational trapping (1)
- Contingent Negative Variation, CNV (1)
- Continuous Performance Test, CPT (1)
- Costs (1)
- Covid19-nmr (1)
- Critical point (1)
- Cue-P3 (1)
- DKTK-ROG (1)
- DNA-PAINT (1)
- Data management (1)
- Data sharing (1)
- Demolition emissions (1)
- Depression (1)
- Deuteron production (1)
- Di-hadron correlations (1)
- Direct oral anticoagulation (1)
- Direct reactions (1)
- Disease Activity (1)
- E. colo (1)
- EP300 (1)
- EWSR1 (1)
- Early Rheumatoid Arthritis (1)
- Ecosystems (1)
- Electron-pion identification (1)
- Electronic structure of atoms and molecules (1)
- Electroweak interaction (1)
- Emotion regulation (1)
- Endocannabinoids (1)
- Enthalpy (1)
- Environment (1)
- Epilepsy (1)
- Ethics Committees/Consultation (1)
- European distribution (1)
- Event related potentials (1)
- Evolution (1)
- FBS (1)
- FOXO1 (1)
- Family Physician (1)
- Females (1)
- Femtoscopy (1)
- Fibre/foam sandwich radiator (1)
- First-line regimen (1)
- Forschung (1)
- Full waveform (1)
- Fungi (1)
- G protein-coupled receptor (GPCR) (1)
- Gene expression profiling (1)
- Gene fusion (1)
- Glioblastoma survival (1)
- Groomed jet radius (1)
- HBT (1)
- HNO (1)
- HNSCC (1)
- HPV (1)
- Hadron production (1)
- Hadron-Hadron Scattering Heavy (1)
- Hadron-hadron interactions (1)
- Hals-Nasen-Ohren-Heilkunde (1)
- Hard Scattering (1)
- Health information (1)
- Health-seeking behaviour (1)
- Heavy Ion Experiment (1)
- Heavy flavor production (1)
- Heavy flavour production (1)
- Heavy ions (1)
- Heavy-Ion Collision (1)
- Heavy-flavor decay electron (1)
- Heavy-flavour decay muons (1)
- Heavy-flavour production (1)
- Helpline (1)
- High-throughput screening (1)
- Higher moments (1)
- HoLEP (1)
- Holmium laser enucleation (1)
- Hsp70 (1)
- ICON model (1)
- IHC (1)
- Imrt (1)
- In vitro selection (1)
- Incidental prostate cancer (1)
- Inclusive spectra (1)
- Intensity interferometry (1)
- Interference fragmentation function (1)
- Interpretation (1)
- Invariant Mass Distribution (1)
- Inversion (1)
- Ionisation energy loss (1)
- J/ψ suppression (1)
- Jet Physics (1)
- Jet Substructure (1)
- Jet substructure (1)
- KCGS (1)
- Kaonic nuclei (1)
- Ki-67/MIB1 (1)
- LEOSS (1)
- Lehre (1)
- Loimia (1)
- Low energy QCD (1)
- Low-molecular-weight heparin (1)
- Lymphocytes (1)
- Lymphoid tissues (1)
- MDM2 (1)
- MRI (1)
- Machine learning (1)
- Massive Online Open Course (1)
- Material budget (1)
- Mechanistic (1)
- Medication Appropriateness Index (1)
- Medicinal chemistry (1)
- Membrane protein (1)
- Mesoporous silica (1)
- Mid-rapidity (1)
- Minimum Bias (1)
- Molecular diagnostics (1)
- Molecular modelling (1)
- Monte Carlo (1)
- Multi-Parton Interactions (1)
- Multi-strange baryons (1)
- Multi-wire proportional drift chamber (1)
- Multiple parton interactions (1)
- Myocarditis (1)
- NK cells (1)
- NMR spectroscopy (1)
- NSCLC (1)
- Nanobody (1)
- Nek1 (1)
- Neural network (1)
- Neuroepithelial tumor (1)
- Neurofeedback (1)
- Nuclear modification factor (1)
- Nuclear reactions (1)
- Nuclear structure & decays (1)
- Nucleon induced nuclear reactions (1)
- ORL (1)
- Observation (1)
- Oncology (1)
- Oppositional defiant disorder (1)
- Otorhinolaryngology (1)
- Outcomes research (1)
- PCV (1)
- PD-L1 (1)
- PLAGL1 (1)
- PM10 (1)
- PYTHIA (1)
- Partial wave analysis (1)
- Particle and Resonance Production (1)
- Pb–Pb (1)
- Phage display (1)
- Pharmacology (1)
- Plant symbiosis (1)
- Plasma (1)
- Pneumocystis jirovecii (1)
- Pneumonia (1)
- Point of care (1)
- Polo-like kinase 3 (1)
- Pre-analytics (1)
- Predictive model (1)
- Primary Care Health Centre (1)
- Production Cross Section (1)
- Prognostic (1)
- Properties of Hadrons (1)
- Prostate cancer (1)
- Proteins (1)
- Proton-proton collisions (1)
- Proton–proton (1)
- Proton–proton collisions (1)
- Pulmonary embolism (1)
- QGP (1)
- Quality of life (1)
- Quark Deconfinement (1)
- Quark Gluon Plasma (1)
- Quark Production (1)
- Quark gluon plasma (1)
- RHIC (1)
- RITA (1)
- RNA Biology (1)
- RNA genome (1)
- RNASolution-state NMR (1)
- Randomised controlled trial (1)
- Randomized Controlled Trial (1)
- Rapidity Range (1)
- Rare diseases (1)
- Relativistic heavy ion physics (1)
- Research (1)
- Research Ethics (1)
- Residency (1)
- Residential care (1)
- Resolution Parameter (1)
- Response control (1)
- Rheumatoid Arthritis (1)
- Ribosome display (1)
- SARS-CoV‑2 pandemic (1)
- SARS-CoV‑2-Pandemie (1)
- SCCHN (1)
- SDF-1 (1)
- SEDDS (1)
- SL1 (1)
- SL5a (1)
- SL5b (1)
- SL5b + c (1)
- SL5c (1)
- SMAD (1)
- SMEDDS (1)
- SNEDDS (1)
- SPSS (1)
- Salivary gland cancer (1)
- Salivary gland carcinoma (1)
- Scientific Research (1)
- Screening (1)
- Seizure (1)
- Serum (1)
- Shell model (1)
- Single muons (1)
- Size distribution (1)
- Skills training (1)
- Slow Cortical Potentials, SCP (1)
- Small molecules (1)
- Social Control of Human Experimentation (1)
- Social Control of Science/Technology (1)
- Socio-ecology (1)
- SoftDrop (1)
- Solid dispersion (1)
- Sonography (1)
- Spanish National Health System (1)
- Specialist training (1)
- Spectroscopic factors & electromagnetic moments (1)
- Splitting function (1)
- Ste2p (1)
- Stereotactic ablative body radiotherapy (1)
- Structural biology and molecular biophysics (1)
- Supratentorial (1)
- Surgery (1)
- Survey (1)
- Sustained attention (1)
- Systematic Uncertainty (1)
- Systemic therapy (1)
- TGFβ (1)
- TR (1)
- TTFields (1)
- TUR-P (1)
- Teaching (1)
- Techniques and instrumentation (1)
- Telemedicine (1)
- Therapeutic anticoagulation (1)
- Thermal model (1)
- Time Projection Chamber (1)
- Tomography (1)
- Tools and ressources (1)
- Topology (1)
- Tracking (1)
- Transition radiation detector (1)
- Transurethral resection of the prostate (1)
- Transverse momentum (1)
- Transversity (1)
- Treatment modification (1)
- Trigger (1)
- Ultrafine particles (1)
- University hospitals (1)
- Universitätskliniken (1)
- Urban aerosol (1)
- Vaccination (1)
- Vector Boson Production (1)
- Weiterbildung (1)
- X-rays (1)
- Xenon-based gas mixture (1)
- accident (1)
- acoustic radiation force impulse (1)
- acute decompensation (1)
- acute-on-chronic liver failure (1)
- aggression (1)
- aging (1)
- algal evolution (1)
- amorphous stability (1)
- anal carcinoma (1)
- antiviral therapy (1)
- archeological modeling (1)
- artifacts (1)
- attention-deficit/hyperactivity disorder (ADHD) (1)
- biogeographic legaciese (1)
- brain cancer (1)
- cART (1)
- cBioPortal (1)
- cancer (1)
- cancer-specific survival (1)
- caspase 8 (1)
- caspase-8 (1)
- chemogenomic set (1)
- chemoresistance (1)
- chromalveolate (1)
- chronic hepatitis C (1)
- cirrhosis (1)
- clinical (1)
- clinical practice (1)
- colorectal cancer (1)
- comorbidities (1)
- complex plastid (1)
- computational biology (1)
- computed tomography (1)
- computer-assisted (1)
- congenital duodenal obstruction (1)
- consensus (1)
- corneas (1)
- corticosteroids (1)
- critically ill patients (1)
- crystal structure determination (1)
- dE/dx (1)
- data quality (1)
- decision making (1)
- decision support systems (1)
- deep neural network models (1)
- deswelling (1)
- detector (1)
- dexamethasone (1)
- diffuse low-grade glioma (1)
- diffusion-weighted magnetic resonance imaging (1)
- direct-acting antiviral (DAA) treatment (1)
- disease-free survival (1)
- drug discovery (1)
- druggable genome (1)
- ectosomes (1)
- electroencephalography (EEG) (1)
- eltrombopag (1)
- emiliania huxleyi (1)
- epilepsy (1)
- excitation (1)
- exosomes (1)
- experimental results (1)
- extracellular vesicles (1)
- fMRI (1)
- fMRI/EEG (1)
- fluorine (1)
- forest classification (1)
- forest functional similarity (1)
- fractionation (1)
- fragment screening (1)
- fragment-based screening (1)
- freshwater ecosystems (1)
- gastrointestinal stromal tumours (1)
- gene signature (1)
- glass forming ability (1)
- glioblastoma survival (1)
- glioma (1)
- global change (1)
- guidelines (1)
- habitat destruction (1)
- head and neck squamous cell carcinoma (1)
- health-related quality of life (1)
- health-relatedquality of life (1)
- heavy ion experiments (1)
- hepatic encephalopathy (1)
- highly-charged ions (1)
- hotmelt extrusion (1)
- hotspot loci (1)
- human (1)
- human cytomegalovirus (1)
- human–environment interaction (1)
- hydrate (1)
- hypothesis (1)
- immune microenvironment (1)
- immunotherapy (1)
- in silico tools (1)
- injury (1)
- insect abundance (1)
- interscalene brachial plexus block (1)
- intraspecific morphological variability (1)
- iron chelation (1)
- keratoplasty (1)
- kinase inhibitor (1)
- land use (1)
- lasso regression (1)
- leukocytosis (1)
- leukopenia (1)
- lipid based formulation (1)
- lipid suspension (1)
- liver (1)
- liver cirrhosis (1)
- local anesthetic (1)
- lockdown (1)
- logistic models (1)
- long-term research (1)
- lung cancer (1)
- mRNA and protein expression (1)
- machine learning (1)
- maternal care (1)
- membrane protein (1)
- merkel cell carcinoma (1)
- mesoporous silica (1)
- metabolic syndromes (1)
- microdeletions (1)
- microkeratome (1)
- microparticles (1)
- microvesicles (1)
- minimal information requirements (1)
- molecular tumor board (1)
- multicenter study (1)
- multiplexed immunofluorescence (1)
- multivariate pattern analysis (1)
- myeloperoxidase (1)
- neoadjuvant chemoradiotherapy (1)
- neoplasms (1)
- neurodegeneration (1)
- neurodevelopmental (1)
- neurological outcome (1)
- neuroscience (1)
- neutrophils (1)
- nomogram (1)
- nuclear magnetic resonance (NMR) (1)
- open science (1)
- oral cavity cancer (1)
- organic pigment (1)
- organic thin films (1)
- outcome (1)
- ovarian cancer (1)
- overall survival (1)
- p+p collisions (1)
- p16 (1)
- p53 activator (1)
- paleoclimate modeling (1)
- paleoenvironment modeling (1)
- paleoenvironment reconstruction (1)
- parameterization development (1)
- pediatric intensive care (1)
- pediatric surgery (1)
- peri-implantitis (1)
- phenotypic screening (1)
- phylogenetic community distance (1)
- plastid protein import (1)
- polo-like kinase 1 (1)
- polo-like kinase 3 (1)
- polymers (1)
- polyomavirus (MCPyV) (1)
- portosystemic shunt (1)
- postnatal care (1)
- postoperative radiochemotherapy (1)
- postoperative radiotherapy (1)
- ppK − (1)
- precipitation inhibitor (1)
- precision medicine (1)
- predictive (1)
- predictive biomarker (1)
- prenatal diagnostic (1)
- prognosis (1)
- prognostic (1)
- prognostic biomarker (1)
- prognostic marker (1)
- propensity score matching (1)
- protein folding (1)
- protein kinase (1)
- proteins (1)
- pulmonary embolism (1)
- quark gluon plasma (1)
- radiation (1)
- radioimmunotherpay (1)
- radiosensitization (1)
- real-world structure (1)
- recurrence pattern (1)
- relativistic collisions (1)
- reproducibility (1)
- requirements analysis (1)
- resilience (1)
- retrospective trial (1)
- rigor (1)
- sarcoma (1)
- sarcopenia (1)
- scene representation (1)
- secondary endosymbiosis (1)
- selenolates (1)
- self-assembled monolayers (1)
- short molecular distance (1)
- single-column mode (1)
- small molecules (1)
- solvate (1)
- spectra (1)
- spontaneous portosystemic shunt (1)
- standardization (1)
- storage rings (1)
- structural biology (1)
- super-SMEDDS (1)
- super-SNEDDS (1)
- supersaturating drug delivery systems (1)
- survival (1)
- temozolomide (1)
- therapeutic anticoagulation (1)
- thiolates (1)
- threats (1)
- thrombopenia (1)
- thrombopietin receptor agonist (1)
- toxic hemisphere syndrome (1)
- toxicity (1)
- transient elastography (1)
- translational investigation (1)
- trauma (1)
- triptycene (1)
- tropical forests (1)
- tumor microenvironment (1)
- tumor-infiltrating-lymphocytes (1)
- tyrosine kinase inhibitors (1)
- understudied kinase (1)
- validation (1)
- venetoclax (1)
- ventral striatum (1)
- visual perception (1)
- xenograft (1)
- √sN N = 2.76 TeV (1)
Institute
- Physik (1129)
- Frankfurt Institute for Advanced Studies (FIAS) (992)
- Informatik (921)
- Medizin (88)
- Geowissenschaften (16)
- Biochemie, Chemie und Pharmazie (14)
- Biowissenschaften (11)
- Zentrum für Biomolekulare Magnetische Resonanz (BMRZ) (8)
- Biochemie und Chemie (7)
- Institut für Ökologie, Evolution und Diversität (5)
Introduction: Merkel cell carcinoma (MCC) is linked to the presence of clonally integrated Merkel cell polyomavirus (MCPyV) in up to 80% of the cases. The aim of the study was to determine the prognostic value of baseline MCPyV viral load and lymphocytic infiltration.
Methods: MCPyV DNA prevalence, integration status and viral load were determined by specific quantitative real-time PCR in surgical specimens obtained from 49 patients with MCC treated with (n = 22, 45%) or without postoperative radiotherapy (RT). CD8+ tumor infiltrating lymphocytes (TILs) and programmed death ligand 1 (PD-L1) status were assessed using immunohistochemistry. MCPyV characteristics and immune marker expression were correlated with clinicopathological factors and overall survival (OS).
Results: Median age at diagnosis was 74 (range, 42–100); 51% of the patients were female. One-, three, and five-year OS rates were 83.8, 58.6, and 47.1%, respectively. A positive MCPyV status was associated with female gender (p = 0.042). Tumor localization (head/arms vs. trunk) positively correlated with PD-L1 status (p = 0.011) and combined CD8/PD-L1 expression (p = 0.038). Overall CD8+ infiltration was inversely associated with N-stage (p = 0.048). Stromal TILs correlated significantly with both PD-L1 expression (p = 0.010) and N-stage (p = 0.037). A high viral load (>median) was significantly associated with worse OS (p = 0.029) and high intratumoral CD8+ infiltration with improved OS for the entire cohort (p = 0.045).
Conclusion: These data provide important insight on the role of MCPy DNA viral load and TILs in the context of PD-L1 in patients with Merkel cell carcinoma. Future clinical studies should aim to explore the effect of PD-1/PD-L1 immune-checkpoint inhibitors in combination with existing radiotherapy approaches.
SARS-CoV-2 and stroke characteristics: a report from the Multinational COVID-19 Stroke Study Group
(2020)
Background: Stroke is reported as a consequence of SARS-CoV-2 infection. However, there is a lack of regarding comprehensive stroke phenotype and characteristics
Methods: We conducted a multinational observational study on features of consecutive acute ischemic stroke (AIS), intracranial hemorrhage (ICH), and cerebral venous or sinus thrombosis (CVST) among SARS-CoV-2 infected patients. We further investigated the association of demographics, clinical data, geographical regions, and countries’ health expenditure among AIS patients with the risk of large vessel occlusion (LVO), stroke severity as measured by National Institute of Health stroke scale (NIHSS), and stroke subtype as measured by the TOAST criteria. Additionally, we applied unsupervised machine learning algorithms to uncover possible similarities among stroke patients.
Results: Among the 136 tertiary centers of 32 countries who participated in this study, 71 centers from 17 countries had at least one eligible stroke patient. Out of 432 patients included, 323(74.8%) had AIS, 91(21.1%) ICH, and 18(4.2%) CVST. Among 23 patients with subarachnoid hemorrhage, 16(69.5%) had no evidence of aneurysm. A total of 183(42.4%) patients were women, 104(24.1%) patients were younger than 55 years, and 105(24.4%) patients had no identifiable vascular risk factors. Among 380 patients who had known interval onset of the SARS-CoV-2 and stroke, 144(37.8%) presented to the hospital with chief complaints of stroke-related symptoms, with asymptomatic or undiagnosed SARS-CoV-2 infection. Among AIS patients 44.5% had LVO; 10% had small artery occlusion according to the TOAST criteria. We observed a lower median NIHSS (8[3-17], versus 11 [5-17]; p=0.02) and higher rate of mechanical thrombectomy (12.4% versus 2%; p<0.001) in countries with middle to high-health expenditure when compared to countries with lower health expenditure. The unsupervised machine learning identified 4 subgroups, with a relatively large group with no or limited comorbidities.
Conclusions: We observed a relatively high number of young, and asymptomatic SARS-CoV-2 infections among stroke patients. Traditional vascular risk factors were absent among a relatively large cohort of patients. Among hospitalized patients, the stroke severity was lower and rate of mechanical thrombectomy was higher among countries with middle to high-health expenditure.
The concept of using precipitation inhibitors (PIs) to sustain supersaturation is well established for amorphous formulations but less in the case of lipid-based formulations (LBF). This study applied a systematic in silico–in vitro–in vivo approach to assess the merits of incorporating PIs in supersaturated LBFs (sLBF) using the model drug venetoclax. sLBFs containing hydroxypropyl methylcellulose (HPMC), hydroxypropyl methylcellulose acetate succinate (HPMCAS), polyvinylpyrrolidone (PVP), PVP-co-vinyl acetate (PVP/VA), Pluronic F108, and Eudragit EPO were assessed in silico calculating a drug–excipient mixing enthalpy, in vitro using a PI solvent shift test, and finally, bioavailability was assessed in vivo in landrace pigs. The estimation of pure interaction enthalpies of the drug and the excipient was deemed useful in determining the most promising PIs for venetoclax. The sLBF alone (i.e., no PI present) displayed a high initial drug concentration in the aqueous phase during in vitro screening. sLBF with Pluronic F108 displayed the highest venetoclax concentration in the aqueous phase and sLBF with Eudragit EPO the lowest. In vivo, the sLBF alone showed the highest bioavailability of 26.3 ± 14.2%. Interestingly, a trend toward a decreasing bioavailability was observed for sLBF containing PIs, with PVP/VA being significantly lower compared to sLBF alone. In conclusion, the ability of a sLBF to generate supersaturated concentrations of venetoclax in vitro was translated into increased absorption in vivo. While in silico and in vitro PI screening suggested benefits in terms of prolonged supersaturation, the addition of a PI did not increase in vivo bioavailability. The findings of this study are of particular relevance to pre-clinical drug development, where the high in vivo exposure of venetoclax was achieved using a sLBF approach, and despite the perceived risk of drug precipitation from a sLBF, including a PI may not be merited in all cases.
Long-term effects on cirrhosis and portal hypertension of direct antiviral agent (DAA)-based eradication of hepatitis C virus (HCV) are still under debate. We analysed dynamics of liver and spleen elastography to assess potential regression of cirrhosis and portal hypertension 3 years post-treatment. Fifty-four patients with HCV-associated cirrhosis and DAA-induced SVR were included. Liver and spleen stiffness were measured at baseline (BL), end of treatment (EOT), 24 weeks after EOT (FU24) and 1, 2 and 3 (FU144) years post-treatment by transient liver elastography (L-TE) and point shear wave elastography (pSWE) using acoustic radiation force impulse (ARFI) of the liver (L-ARFI) and spleen (S-ARFI). Biochemical, virological and clinical data were also obtained. Liver stiffness assessed by L-TE decreased between BL [median (range), 32.5(9.1–75) kPa] and EOT [21.3(6.7–73.5) kPa; p < .0001] and EOT and FU144 [16(4.1–75) kPa; p = .006]. L-ARFI values improved between EOT [2.5(1.2–4.1) m/s] and FU144 [1.7(0.9–4.1) m/s; p = .001], while spleen stiffness remained unchanged. Overall, L-TE improved in 38 of 54 (70.4%) patients at EOT and 29 of 38 (76.3%) declined further until FU144, whereas L-ARFI values decreased in 30/54 (55.6%) patients at EOT and continued to decrease in 28/30 (93.3%) patients at FU144. Low bilirubin and high albumin levels at BL were associated with improved L-ARFI values (p = .048) at EOT or regression of cirrhosis (<12.5 kPa) by L-TE at FU144 (p = .005), respectively. Liver stiffness, but not spleen stiffness, continued to decline in a considerable proportion of patients with advanced liver disease after HCV eradication.
Abstract: Neurophysiological measures of preparation and attention are often atypical in ADHD. Still, replicated findings that these measures predict which patients improve after Neurofeedback (NF), reveal neurophysiological specificity, and reflect ADHD-severity are limited. Methods: We analyzed children’s preparatory (CNV) and attentional (Cue-P3) brain activity and behavioral performance during a cued Continuous Performance Task (CPT) before and after slow cortical potential (SCP)-NF or semi-active control treatment (electromyogram biofeedback). Mixed-effects models were performed with 103 participants at baseline and 77 were assessed for pre-post comparisons focusing on clinical outcome prediction, specific neurophysiological effects of NF, and associations with ADHD-severity. Results: Attentional and preparatory brain activity and performance were non-specifically reduced after treatment. Preparatory activity in the SCP-NF group increased with clinical improvement. Several performance and brain activity measures predicted non-specific treatment outcome. Conclusion: Specific neurophysiological effects after SCP-NF were limited to increased neural preparation associated with improvement on ADHD-subscales, but several performance and neurophysiological measures of attention predicted treatment outcome and reflected symptom severity in ADHD. The results may help to optimize treatment.
System size and centrality dependence of the balance function in A + A collisions at √sNN = 17.2 GeV
(2004)
Electric charge correlations were studied for p+p, C+C, Si+Si and centrality selected Pb+Pb collisions at sqrt s_NN = 17.2$ GeV with the NA49 large acceptance detector at the CERN-SPS. In particular, long range pseudo-rapidity correlations of oppositely charged particles were measured using the Balance Function method. The width of the Balance Function decreases with increasing system size and centrality of the reactions. This decrease could be related to an increasing delay of hadronization in central Pb+Pb collisions.
System size dependence of multiplicity fluctuations of charged particles produced in nuclear collisions at 158 A GeV was studied in the NA49 CERN experiment. Results indicate a non-monotonic dependence of the scaled variance of the multiplicity distribution with a maximum for semi-peripheral Pb+Pb interactions with number of projectile participants of about 35. This effect is not observed in a string-hadronic model of nuclear collision HIJING.
Vaccination represents one of the fundamentals in the fight against SARS-CoV-2. Myocarditis has been reported as a rare but possible adverse consequence of different vaccines, and its clinical presentation can range from mild symptoms to acute heart failure. We report a case of a 29-year-old man who presented with fever and retrosternal pain after receiving SARS-CoV-2 vaccine. Cardiac magnetic resonance imaging and laboratory data revealed typical findings of acute myocarditis.
Despite the implementation of consolidative immune checkpoint inhibition after definitive chemoradiotherapy (CRT), the prognosis for locally advanced non-small-cell lung cancer (NSCLC) remains poor. We assessed the impact of the C-reactive protein (CRP) to albumin ratio (CAR) as an inflammation-based prognostic score in patients with locally advanced NSCLC treated with CRT. We retrospectively identified and analyzed 52 patients with primary unresectable NSCLC (UICC Stage III) treated with definitive/neoadjuvant CRT between 2014 and 2019. CAR was calculated by dividing baseline CRP by baseline albumin levels and correlated with clinicopathologic parameters to evaluate prognostic impact. After dichotomizing patients by the median, univariate and multivariate Cox regression analyses were performed. An increased CAR was associated with advanced T-stage (p = 0.018) and poor performance status (p = 0.004). Patients with pre-therapeutic elevated CAR had significantly lower hemoglobin and higher leukocyte levels (hemoglobin p = 0.001, leukocytes p = 0.018). High baseline CAR was shown to be associated with worse local control (LPFS, p = 0.006), shorter progression-free survival (PFS, p = 0.038) and overall survival (OS, p = 0.022), but not distant metastasis-free survival (DMFS). Multivariate analysis confirmed an impaired outcome in patients with high CAR (LPFS: HR 3.562, 95% CI 1.294–9.802, p = 0.011). CAR is an easily available and independent prognostic marker after CRT in locally advanced NSCLC. CAR may be a useful biomarker for patient stratification to individualize treatment concepts.
The design, construction, and commissioning of the ALICE Time-Projection Chamber (TPC) is described. It is the main device for pattern recognition, tracking, and identification of charged particles in the ALICE experiment at the CERN LHC. The TPC is cylindrical in shape with a volume close to 90 m3 and is operated in a 0.5 T solenoidal magnetic field parallel to its axis.
In this paper we describe in detail the design considerations for this detector for operation in the extreme multiplicity environment of central Pb–Pb collisions at LHC energy. The implementation of the resulting requirements into hardware (field cage, read-out chambers, electronics), infrastructure (gas and cooling system, laser-calibration system), and software led to many technical innovations which are described along with a presentation of all the major components of the detector, as currently realized. We also report on the performance achieved after completion of the first round of stand-alone calibration runs and demonstrate results close to those specified in the TPC Technical Design Report.
SR proteins function in nuclear pre-mRNA processing, mRNA export, and translation. To investigate their cellular dynamics, we developed a quantitative assay, which detects differences in nucleocytoplasmic shuttling among seven canonical SR protein family members. As expected, SRSF2 and SRSF5 shuttle poorly in HeLa cells but surprisingly display considerable shuttling in pluripotent murine P19 cells. Combining individual-resolution cross-linking and immunoprecipitation (iCLIP) and mass spectrometry, we show that elevated arginine methylation of SRSF5 and lower phosphorylation levels of cobound SRSF2 enhance shuttling of SRSF5 in P19 cells by modulating protein-protein and protein-RNA interactions. Moreover, SRSF5 is bound to pluripotency-specific transcripts such as Lin28a and Pou5f1/Oct4 in the cytoplasm. SRSF5 depletion reduces and overexpression increases their cytoplasmic mRNA levels, suggesting that enhanced mRNA export by SRSF5 is required for the expression of pluripotency factors. Remarkably, neural differentiation of P19 cells leads to dramatically reduced SRSF5 shuttling. Our findings indicate that posttranslational modification of SR proteins underlies the regulation of their mRNA export activities and distinguishes pluripotent from differentiated cells.
Targeted redox inhibition of protein phosphatase 1 by Nox4 regulates eIF2α‐mediated stress signaling
(2016)
Phosphorylation of translation initiation factor 2α (eIF2α) attenuates global protein synthesis but enhances translation of activating transcription factor 4 (ATF4) and is a crucial evolutionarily conserved adaptive pathway during cellular stresses. The serine–threonine protein phosphatase 1 (PP1) deactivates this pathway whereas prolonging eIF2α phosphorylation enhances cell survival. Here, we show that the reactive oxygen species‐generating NADPH oxidase‐4 (Nox4) is induced downstream of ATF4, binds to a PP1‐targeting subunit GADD34 at the endoplasmic reticulum, and inhibits PP1 activity to increase eIF2α phosphorylation and ATF4 levels. Other PP1 targets distant from the endoplasmic reticulum are unaffected, indicating a spatially confined inhibition of the phosphatase. PP1 inhibition involves metal center oxidation rather than the thiol oxidation that underlies redox inhibition of protein tyrosine phosphatases. We show that this Nox4‐regulated pathway robustly enhances cell survival and has a physiologic role in heart ischemia–reperfusion and acute kidney injury. This work uncovers a novel redox signaling pathway, involving Nox4–GADD34 interaction and a targeted oxidative inactivation of the PP1 metal center, that sustains eIF2α phosphorylation to protect tissues under stress.
Immersion freezing is the most relevant heterogeneous ice nucleation mechanism through which ice crystals are formed in mixed-phase clouds. In recent years, an increasing number of laboratory experiments utilizing a variety of instruments have examined immersion freezing activity of atmospherically relevant ice nucleating particles (INPs). However, an inter-comparison of these laboratory results is a difficult task because investigators have used different ice nucleation (IN) measurement methods to produce these results. A remaining challenge is to explore the sensitivity and accuracy of these techniques and to understand how the IN results are potentially influenced or biased by experimental parameters associated with these techniques.
Within the framework of INUIT (Ice Nucleation research UnIT), we distributed an illite rich sample (illite NX) as a representative surrogate for atmospheric mineral dust particles to investigators to perform immersion freezing experiments using different IN measurement methods and to obtain IN data as a function of particle concentration, temperature (T), cooling rate and nucleation time. Seventeen measurement methods were involved in the data inter-comparison. Experiments with seven instruments started with the test sample pre-suspended in water before cooling, while ten other instruments employed water vapor condensation onto dry-dispersed particles followed by immersion freezing. The resulting comprehensive immersion freezing dataset was evaluated using the ice nucleation active surface-site density (ns) to develop a representative ns(T) spectrum that spans a wide temperature range (−37 °C < T < −11 °C) and covers nine orders of magnitude in ns.
Our inter-comparison results revealed a discrepancy between suspension and dry-dispersed particle measurements for this mineral dust. While the agreement was good below ~ −26 °C, the ice nucleation activity, expressed in ns, was smaller for the wet suspended samples and higher for the dry-dispersed aerosol samples between about −26 and −18 °C. Only instruments making measurement techniques with wet suspended samples were able to measure ice nucleation above −18 °C. A possible explanation for the deviation between −26 and −18 °C is discussed. In general, the seventeen immersion freezing measurement techniques deviate, within the range of about 7 °C in terms of temperature, by three orders of magnitude with respect to ns. In addition, we show evidence that the immersion freezing efficiency (i.e., ns) of illite NX particles is relatively independent on droplet size, particle mass in suspension, particle size and cooling rate during freezing. A strong temperature-dependence and weak time- and size-dependence of immersion freezing efficiency of illite-rich clay mineral particles enabled the ns parameterization solely as a function of temperature. We also characterized the ns (T) spectra, and identified a section with a steep slope between −20 and −27 °C, where a large fraction of active sites of our test dust may trigger immersion freezing. This slope was followed by a region with a gentler slope at temperatures below −27 °C. A multiple exponential distribution fit is expressed as ns(T) = exp(23.82 × exp(−exp(0.16 × (T + 17.49))) + 1.39) based on the specific surface area and ns(T) = exp(25.75 × exp(−exp(0.13 × (T + 17.17))) + 3.34) based on the geometric area (ns and T in m−2 and °C, respectively). These new fits, constrained by using an identical reference samples, will help to compare IN measurement methods that are not included in the present study and, thereby, IN data from future IN instruments.
Immersion freezing is the most relevant heterogeneous ice nucleation mechanism through which ice crystals are formed in mixed-phase clouds. In recent years, an increasing number of laboratory experiments utilizing a variety of instruments have examined immersion freezing activity of atmospherically relevant ice-nucleating particles. However, an intercomparison of these laboratory results is a difficult task because investigators have used different ice nucleation (IN) measurement methods to produce these results. A remaining challenge is to explore the sensitivity and accuracy of these techniques and to understand how the IN results are potentially influenced or biased by experimental parameters associated with these techniques.
Within the framework of INUIT (Ice Nuclei Research Unit), we distributed an illite-rich sample (illite NX) as a representative surrogate for atmospheric mineral dust particles to investigators to perform immersion freezing experiments using different IN measurement methods and to obtain IN data as a function of particle concentration, temperature (T), cooling rate and nucleation time. A total of 17 measurement methods were involved in the data intercomparison. Experiments with seven instruments started with the test sample pre-suspended in water before cooling, while 10 other instruments employed water vapor condensation onto dry-dispersed particles followed by immersion freezing. The resulting comprehensive immersion freezing data set was evaluated using the ice nucleation active surface-site density, ns, to develop a representative ns(T) spectrum that spans a wide temperature range (−37 °C < T < −11 °C) and covers 9 orders of magnitude in ns.
In general, the 17 immersion freezing measurement techniques deviate, within a range of about 8 °C in terms of temperature, by 3 orders of magnitude with respect to ns. In addition, we show evidence that the immersion freezing efficiency expressed in ns of illite NX particles is relatively independent of droplet size, particle mass in suspension, particle size and cooling rate during freezing. A strong temperature dependence and weak time and size dependence of the immersion freezing efficiency of illite-rich clay mineral particles enabled the ns parameterization solely as a function of temperature. We also characterized the ns(T) spectra and identified a section with a steep slope between −20 and −27 °C, where a large fraction of active sites of our test dust may trigger immersion freezing. This slope was followed by a region with a gentler slope at temperatures below −27 °C. While the agreement between different instruments was reasonable below ~ −27 °C, there seemed to be a different trend in the temperature-dependent ice nucleation activity from the suspension and dry-dispersed particle measurements for this mineral dust, in particular at higher temperatures. For instance, the ice nucleation activity expressed in ns was smaller for the average of the wet suspended samples and higher for the average of the dry-dispersed aerosol samples between about −27 and −18 °C. Only instruments making measurements with wet suspended samples were able to measure ice nucleation above −18 °C. A possible explanation for the deviation between −27 and −18 °C is discussed. Multiple exponential distribution fits in both linear and log space for both specific surface area-based ns(T) and geometric surface area-based ns(T) are provided. These new fits, constrained by using identical reference samples, will help to compare IN measurement methods that are not included in the present study and IN data from future IN instruments.
Recently significant advances have been made in the collection, detection, and characterization of ice nucleating particles (INP). Ice nuclei are particles that facilitate the heterogeneous formation of ice within the atmospheric aerosol by lowering the free energy barrier to spontaneous nucleation and growth of ice from atmospheric water and/or vapor. The Frankfurt isostatic diiffusion chamber (FRIDGE) is an INP collection and offline detection system that has become widely deployed and shows additional potential for ambient measurements. Since its initial development FRIDGE has gone through several iterations and improvements. Here we describe improvements that have been made in the collection and analysis techniques. We detail the uncertainties inherent in the measurement method, and suggest a systematic method of error analysis for FRIDGE measurements. Thus what is presented herein should serve as a foundation for the dissemination of all current and future measurements using FRIDGE instrumentation.
Ice nucleating particles over the eastern mediterranean measured by unmanned aircraft systems
(2017)
During an intensive field campaign on aerosol, clouds, and ice nucleation in the Eastern Mediterranean in April 2016, we measured the abundance of ice nucleating particles (INPs) in the lower troposphere from unmanned aircraft systems (UASs). Aerosol samples were collected by miniaturized electrostatic precipitators onboard the UASs at altitudes up to 2.5 km. The number of INPs in these samples, which are active in the deposition and condensation modes at temperatures from −20 to −30 °C, were analyzed immediately after collection on site using the ice nucleus counter FRIDGE (FRankfurt Ice nucleation Deposition freezinG Experiment). During the 1-month campaign, we encountered a series of Saharan dust plumes that traveled at several kilometers' altitude. Here we present INP data from 42 individual flights, together with aerosol number concentrations, observations of lidar backscattering, dust concentrations derived by the dust transport model DREAM (Dust Regional Atmospheric Model), and results from scanning electron microscopy. The effect of the dust plumes is reflected by the coincidence of INPs with the particulate matter (PM), the lidar signal, and the predicted dust mass of the model. This suggests that mineral dust or a constituent related to dust was a major contributor to the ice nucleating properties of the aerosol. Peak concentrations of above 100 INPs std L−1 were measured at −30 °C. The INP concentration in elevated plumes was on average a factor of 10 higher than at ground level. Since desert dust is transported for long distances over wide areas of the globe predominantly at several kilometers' altitude, we conclude that INP measurements at ground level may be of limited significance for the situation at the level of cloud formation.
Ice nucleating particles over the Eastern Mediterranean measured by unmanned aircraft systems
(2016)
During an intensive field campaign on aerosol, clouds and ice nucleation in the Eastern Mediterranean in April 2016, we have measured the abundance of ice nucleating particles (INP) in the lower troposphere from unmanned aircraft systems (UAS). Aerosol samples were collected by miniaturized electrostatic precipitators onboard the UAS at altitudes up to 2.5 km. The number of INP in these samples, which are active in the deposition and condensation modes at temperatures from −20 to −30 ◦C, were analyzed immediately after collection on site using the ice nucleus counter FRIDGE. During the one month campaign we encountered a series of Saharan dust plumes that traveled at several kilometers altitude. Here we present INP data from 42 individual flights, together with aerosol number concentrations, observations of lidar backscattering, dust concentrations derived by the dust transport model DREAM (Dust Regional Atmospheric Model), and results from scanning electron microscopy. The effect of the dust plumes is reflected by the coincidence of INP with the particulate mass (PM), the lidar signal and with the predicted dust mass of the model. This suggests that mineral dust or a constituent related to dust was a major contributor to the ice nucleating properties of the aerosol. Peak concentrations of above 100 INP std.l -1 were measured at −30 ◦C. The INP concentration in elevated plumes was on average a factor of 10 higher than at ground level. Since desert dust is transported for long distances over wide areas of the globe predominantly at several km altitude we conclude that INP measurements at ground level may be of limited significance for the situation at the level of cloud formation.
Recently significant advances have been made in the collection, detection and characterization of ice nucleating particles (INPs). Ice nuclei are particles that facilitate the heterogeneous formation of ice within the atmospheric aerosol by lowering the free energy barrier to spontaneous nucleation and growth of ice from atmospheric water and/or vapor. The Frankfurt isostatic diffusion chamber (FRankfurt Ice nucleation Deposition freezinG Experiment: FRIDGE) is an INP collection and offline detection system that has become widely deployed and shows additional potential for ambient measurements. Since its initial development FRIDGE has gone through several iterations and improvements. Here we describe improvements that have been made in the collection and analysis techniques. We detail the uncertainties inherent in the measurement method and suggest a systematic method of error analysis for FRIDGE measurements. Thus what is presented herein should serve as a foundation for the dissemination of all current and future measurements using FRIDGE instrumentation.
In this report, we present the contributions, outcomes, ideas, discussions and conclusions obtained at the PaleoMaps Workshop 2019, that took place at the Institute of Geography of the University of Cologne on 23 and 24 September 2019. The twofold aim of the workshop was: (1) to provide an overview of approaches and methods that are presently used to incorporate paleoenvironmental information in human–environment interaction modeling applications, and building thereon; (2) to devise new approaches and solutions that might be used to enhance the reconstruction of past human–environmental interconnections. This report first outlines the presented papers, and then provides a joint protocol of the often extensive discussions that came up following the presentations or else during the refreshment intervals. It concludes by adressing the open points to be resolved in future research avenues, e.g., implementation of open science practices, new procedures for reviewing of publications, and future concepts for quality assurance of the often complex paleoenvironmental data. This report may serve as an overview of the state of the art in paleoenvironment mapping and modeling. It includes an extensive compilation of the basic literature, as provided by the workshop attendants, which will itself facilitate the necessary future research.