Refine
Year of publication
Document Type
- Preprint (660)
- Article (442)
- Book (1)
- Conference Proceeding (1)
- Contribution to a Periodical (1)
- Review (1)
- Working Paper (1)
Has Fulltext
- yes (1107)
Is part of the Bibliography
- no (1107)
Keywords
- Heavy Ion Experiments (20)
- Hadron-Hadron Scattering (11)
- Hadron-Hadron scattering (experiments) (11)
- LHC (9)
- SARS-CoV-2 (8)
- Heavy-ion collision (6)
- COVID19-NMR (5)
- ALICE experiment (4)
- Collective Flow (4)
- Jets (4)
- Quark-Gluon Plasma (4)
- Solution NMR spectroscopy (4)
- 5′-UTR (3)
- ALICE (3)
- Heavy Ions (3)
- Jets and Jet Substructure (3)
- RNA (3)
- pp collisions (3)
- ACLF (2)
- BCR/ABL (2)
- Beauty production (2)
- Charm physics (2)
- Epilepsy (2)
- Experimental nuclear physics (2)
- Experimental particle physics (2)
- Heavy Quark Production (2)
- Lepton-Nucleon Scattering (experiments) (2)
- NMR spectroscopy (2)
- Non-structural protein (2)
- Particle Correlations and Fluctuations (2)
- Particle and resonance production (2)
- Particle correlations and fluctuations (2)
- Pb–Pb collisions (2)
- Philadelphia chromosome (2)
- QCD (2)
- Seizure (2)
- Single electrons (2)
- Solution NMR-spectroscopy (2)
- acute-on-chronic liver failure (2)
- glioblastoma (2)
- proteomics (2)
- radiotherapy (2)
- 19F (1)
- 2-deoxyglucose (2-DG) (1)
- 5'-UTR (1)
- 5_SL4 (1)
- 900 GeV (1)
- ALICE detector (1)
- ALK-rearranged NSCLC (1)
- Abl kinase inhibitors (1)
- Active middle ear implants (1)
- Allosteric inhibition (1)
- Alternating Phase Focusing (1)
- Angiomyolipoma (1)
- Anti-nuclei (1)
- Anti-seizure medication (1)
- Anticonvulsant (1)
- Auditory system (1)
- Autologous stem cell transplantation (1)
- B cell receptor (1)
- B. subtilis (1)
- Bartonella grahamii (1)
- Bartonella henselae (1)
- Bartonella schoenbuchensis (1)
- Beam dynamics simulation (1)
- Beskid Niski Mts (1)
- Biogeochemistry (1)
- Biomarker (1)
- Bone conduction devices (1)
- Boosted Jets (1)
- Brain tumor (1)
- Business strategy in drug development (1)
- CAKUT (1)
- CLIF-C ACLF score (1)
- CLIF-C ACLF-R score (1)
- COVID-19 (1)
- CPTAC (1)
- CRC65 (1)
- Carbon cycle (1)
- Cementation (1)
- Centrality Class (1)
- Centrality Selection (1)
- Ceramic (1)
- Chemical communication (1)
- Chocó rainforest (1)
- Chronic disease (1)
- Collective Flow, (1)
- Communication center (1)
- Comparative genomics (1)
- Comparison with QCD (1)
- Consensus statement (1)
- Continuous wave (1)
- Core marking (1)
- Costs (1)
- Covid19-NMR (1)
- Covid19-nmr (1)
- DNA-PAINT (1)
- Data sharing (1)
- Depression (1)
- Diagnostic imaging (1)
- Drug screens (1)
- Drug therapy (1)
- E. coli (1)
- Ecosystem ecology (1)
- Ecuador (1)
- Electron-pion identification (1)
- Electroweak interaction (1)
- Elliptic flow (1)
- Everolimus (1)
- Evolution (1)
- FBS (1)
- Femtoscopy (1)
- Fibre/foam sandwich radiator (1)
- Forest ecology (1)
- Functionally-impaired elderly (1)
- Fungi (1)
- Gene expression profiling (1)
- General practice (1)
- Genetics (1)
- Glioma (1)
- HBT (1)
- HOD (1)
- Hadron production (1)
- Hadron-Hadron Scattering Heavy (1)
- Hadron-hadron interactions (1)
- Hard Scattering (1)
- Health policy (1)
- Heavy Ion Experiment (1)
- Heavy flavor production (1)
- Heavy flavour production (1)
- Heavy ion (1)
- Heavy ions (1)
- Heavy-flavour decay muons (1)
- Heavy-flavour production (1)
- Heavy-ion collisions (1)
- Hematology (1)
- High-dose chemotherapy (1)
- High-throughput screening (1)
- Holmes tremor (1)
- Hyperons (1)
- Immunology (1)
- Inclusive spectra (1)
- Intensity interferometry (1)
- Invariant Mass Distribution (1)
- Invertebrates (1)
- Ionisation energy loss (1)
- Ixodes ricinus (1)
- Jet Physics (1)
- Jet Substructure (1)
- Lenalidomide (1)
- Leukemias (1)
- Linear accelerator (1)
- Localized defecation (1)
- MTOR inhibitor (1)
- Macrodomain (1)
- Magnetic resonance imaging (1)
- Material budget (1)
- Meriç River (1)
- Microplastic (1)
- Mid-rapidity (1)
- Minimal invasive (1)
- Minimum Bias (1)
- Mixed hearing loss (1)
- Mixture toxicity (1)
- Molecular biology (1)
- Molecular matched therapy (1)
- Molecular medicine (1)
- Molecular modelling (1)
- Molecular profiling (1)
- Molecular therapy (1)
- Mollusks (1)
- Monolithic crown (1)
- Monte Carlo (1)
- Multi-Parton Interactions (1)
- Multi-stakeholder approach (1)
- Multi-strange baryons (1)
- Multi-wire proportional drift chamber (1)
- Multiple myeloma (1)
- Multiple stressors (1)
- NAFL (1)
- NASH (1)
- Neural network (1)
- Neuroscience (1)
- Non-small cell lung cancer (1)
- Nonlinear beam dynamics (1)
- Nuclear modification factor (1)
- Nucleus (1)
- Oncology (1)
- Osimertinib (1)
- PYTHIA (1)
- Pain (1)
- Particle and Resonance Production (1)
- Patient-Reported Outcomes Version of the Common Terminology Criteria for Adverse Events (1)
- Pb–Pb (1)
- Physiology (1)
- Plant symbiosis (1)
- Pond snail (1)
- Positron emission tomography (1)
- Production Cross Section (1)
- Properties of Hadrons (1)
- Protein drugability (1)
- Proteins (1)
- Proton (1)
- Proton–proton (1)
- Psychiatric disorders (1)
- Quality of life (1)
- Quark Deconfinement (1)
- Quark Gluon Plasma (1)
- Quark Production (1)
- Quark gluon plasma (1)
- Quarkonium (1)
- RNA genome (1)
- RNASolution-state NMR (1)
- RSL curve (1)
- Rapidity Range (1)
- Rehabilitation (1)
- Relapse (1)
- Relativistic heavy ion physics (1)
- Relativistic heavy-ion collisions (1)
- Resolution Parameter (1)
- Rhabdomyoma (1)
- SL1 (1)
- SL5a (1)
- SL5b (1)
- SL5b + c (1)
- SL5c (1)
- SLC20A1 (1)
- SPSS (1)
- Second-line treatment (1)
- Self-assessment (1)
- Single muons (1)
- Sociodemographic characteristics (1)
- Strangeness (1)
- Subependymal giant cell astrocytoma (1)
- Surgery (1)
- Systematic Uncertainty (1)
- TP53 mutation status (1)
- TR (1)
- TSC (1)
- Target validation (1)
- Targeted therapy (1)
- Technical data (1)
- Tet-inducible system (1)
- Time Projection Chamber (1)
- Tracking (1)
- Transition radiation detector (1)
- Transverse momentum (1)
- Trigger (1)
- Urban ecology (1)
- Vasculitis (1)
- Vector Boson Production (1)
- Warburg effect (1)
- Xenon-based gas mixture (1)
- Zirconia (1)
- aboveground biomass (1)
- accessory proteins (1)
- acute coronary syndrome (1)
- acute decompensation (1)
- acute lymphatic leukemia (1)
- adult (1)
- aegean (1)
- aging (1)
- allosteric inhibition (1)
- amplicon sequencing (1)
- antisynthetase antibodies (1)
- antisynthetase syndrome (1)
- archeological sea-level limiting points (1)
- arthritis (1)
- artifacts (1)
- artificial feeding (1)
- attention-deficit/hyperactivity disorder (ADHD) (1)
- biochemistry (1)
- biodiversity (1)
- biophysics (1)
- bipartite networks (1)
- bladder exstrophy-epispadias complex (1)
- cancer (1)
- cannabidiol (1)
- cannabinoids (1)
- cannabis (1)
- cell-free protein synthesis (1)
- cerebrospinal fluid (1)
- chemotherapy (1)
- chronosequence (1)
- cirrhosis (1)
- clinical trial (1)
- cloacal malformation (1)
- coastal geomorphology (1)
- computed tomography (1)
- copeptin (1)
- dE/dx (1)
- data quality (1)
- deadwood (1)
- decomposition (1)
- detector (1)
- diffusion-weighted magnetic resonance imaging (1)
- doxycycline (1)
- drug response (1)
- dysbiosis (1)
- ectosomes (1)
- electrical resistivity tomography (1)
- electroencephalography (EEG) (1)
- exosomes (1)
- experimental results (1)
- extracellular vesicles (1)
- females (1)
- fluorine (1)
- folding (1)
- foraminifera (1)
- foraminifers (1)
- fragment screening (1)
- fragment-based screening (1)
- functional genetics (1)
- geophysical prospections (1)
- global change (1)
- glycolysis (1)
- guidelines (1)
- habitat destruction (1)
- head-and-neck cancer (1)
- healthy subjects (1)
- heavy ion experiments (1)
- hepatic encephalopathy (1)
- hypoxia-induced cell death (1)
- immunotherapy (1)
- inducible gene expression (1)
- inflammation (1)
- interferon gamma (1)
- interstitial lung disease (1)
- intrinsically disordered region (1)
- isocaloric ketogenic diet (1)
- kidney formation (1)
- kinetics (1)
- land use (1)
- lichen diversity (1)
- lichenized fungi (1)
- liver (1)
- lung cancer (1)
- mTOR inhibitor (1)
- magnetic gradiometry (1)
- magnetic resonance imaging (1)
- mechanical ventilation (1)
- medulloblastoma (1)
- medulloblastoma resection (1)
- meta-stable structures (1)
- metabolic cancer therapy (1)
- metabolic syndromes (1)
- metastasis (1)
- microbes (1)
- microbiome (1)
- micropalaeontology (1)
- microparticles (1)
- microvesicles (1)
- minimal information requirements (1)
- mitochondria (1)
- model psychosis (1)
- modularity (1)
- molecular therapy (1)
- mortality (1)
- multicenter study (1)
- multiplexed immunofluorescence (1)
- myocardial infarction (1)
- myositis (1)
- myxomycete (1)
- neoadjuvant chemoradiotherapy (1)
- neoepitopes (1)
- neurodegeneration (1)
- new records (1)
- newly diagnosed glioblastoma (1)
- nivolumab (1)
- nonstructural proteins (1)
- nymphs (1)
- oral cavity cancer (1)
- palatal tremor (1)
- patient stratification (1)
- portal hypertension (1)
- portosystemic shunt (1)
- posterior fossa masses (1)
- predictive biomarker (1)
- proteins (1)
- pulmonary failure (1)
- quark gluon plasma (1)
- randomized (1)
- rare species (1)
- rct (1)
- reassembly (1)
- registry (1)
- reproducibility (1)
- resilience (1)
- resistance (1)
- respiratory failure (1)
- riboswitches (1)
- rigor (1)
- saprotrophic fungi (1)
- sea-level indicator (1)
- sequential ALK-inhibitor therapy (1)
- specialization (1)
- spectra (1)
- spontaneous portosystemic shunt (1)
- standardization (1)
- structural biology (1)
- structural proteins (1)
- subgrouping (1)
- targeted therapy (1)
- temozolomide (1)
- tetracycline (1)
- tetrahydrocannabinol (1)
- transcription (1)
- transovarial transmission (1)
- transstadial transmission (1)
- trees (1)
- troponin (1)
- tumor metabolism (1)
- tumor-infiltrating lymphocytes (1)
- unmethylated MGMT (1)
- urinary tract development (1)
- vector (1)
- zebrafish development (1)
- “gatekeeper” mutation T315I (1)
- √sN N = 2.76 TeV (1)
Institute
- Physik (1024)
- Frankfurt Institute for Advanced Studies (FIAS) (947)
- Informatik (914)
- Medizin (49)
- Biowissenschaften (12)
- Biochemie, Chemie und Pharmazie (10)
- Zentrum für Biomolekulare Magnetische Resonanz (BMRZ) (9)
- Geowissenschaften (4)
- Biodiversität und Klima Forschungszentrum (BiK-F) (3)
- Georg-Speyer-Haus (3)
ABSTRACT: BACKGROUND: Philadelphia positive leukemias are characterized by the presence of Bcr-Abl fusion protein which exhibits an abnormal kinase activity. Selective Abl kinase inhibitors have been successfully established for the treatment of Ph (+) leukemias. Despite high rates of clinical response, Ph (+) patients can develop resistance against these kinase inhibitors mainly due to point mutations within the Abl protein. Of special interest is the 'gatekeeper' T315I mutation, which confers complete resistance to Abl kinase inhibitors. Recently, GNF-2, Abl allosteric kinase inhibitor, was demonstrated to possess cellular activity against Bcr-Abl transformed cells. Similarly to Abl kinase inhibitors (AKIs), GNF-2 failed to inhibit activity of mutated Bcr-Abl carrying the T315I mutation.
METHODS: Ba/F3 cells harboring native or T315I mutated Bcr-Abl constructs were treated with GNF-2 and AKIs. We monitored the effect of GNF-2 with AKIs on the proliferation and clonigenicity of the different Ba/F3 cells. In addition, we monitored the auto-phosphorylation activity of Bcr-Abl and JAK2 in cells treated with GNF-2 and AKIs.
RESULTS: In this study, we report a cooperation between AKIs and GNF-2 in inhibiting proliferation and clonigenicity of Ba/F3 cells carrying T315I mutated Bcr-Abl. Interestingly, cooperation was most evident between Dasatinib and GNF-2. Furthermore, we showed that GNF-2 was moderately active in inhibiting the activity of JAK2 kinase, and presence of AKIs augmented GNF-2 activity.
CONCLUSIONS: Our data illustrated the ability of allosteric inhibitors such as GNF-2 to cooperate with AKIs to overcome T315I mutation by Bcr-Abl-independent mechanisms, providing a possibility of enhancing AKIs efficacy and overcoming resistance in Ph+ leukemia cells.
Background: Chronic myelogenous leukemia (CML) and Philadelphia chromosome-positive (Ph+) acute lymphatic leukemia (Ph + ALL) are caused by the t(9;22), which fuses BCR to ABL resulting in deregulated ABL-tyrosine kinase activity. The constitutively activated BCR/ABL-kinase "escapes" the auto-inhibition mechanisms of c-ABL, such as allosteric inhibition. The ABL-kinase inhibitors (AKIs) Imatinib, Nilotinib or Dasatinib, which target the ATP-binding site, are effective in Ph + leukemia. Another molecular therapy approach targeting BCR/ABL restores allosteric inhibition. Given the fact that all AKIs fail to inhibit BCR/ABL harboring the 'gatekeeper' mutation T315I, we investigated the effects of AKIs in combination with the allosteric inhibitor GNF2 in Ph + leukemia.
Methods: The efficacy of this approach on the leukemogenic potential of BCR/ABL was studied in Ba/F3 cells, primary murine bone marrow cells, and untransformed Rat-1 fibroblasts expressing BCR/ABL or BCR/ABL-T315I as well as in patient-derived long-term cultures (PDLTC) from Ph + ALL-patients.
Results: Here, we show that GNF-2 increased the effects of AKIs on unmutated BCR/ABL. Interestingly, the combination of Dasatinib and GNF-2 overcame resistance of BCR/ABL-T315I in all models used in a synergistic manner.
Conclusions: Our observations establish a new approach for the molecular targeting of BCR/ABL and its resistant mutants using a combination of AKIs and allosteric inhibitors.
Background: The t(9;22) translocation leads to the formation of the chimeric breakpoint cluster region/c-abl oncogene 1 (BCR/ABL) fusion gene on der22, the Philadelphia chromosome. The p185(BCR/ABL) or the p210(BCR/ABL) fusion proteins are encoded as a result of the translocation, depending on whether a "minor" or "major" breakpoint occurs, respectively. Both p185(BCR/ABL) and p210(BCR/ABL) exhibit constitutively activated ABL kinase activity. Through fusion to BCR the ABL kinase in p185(BCR/ABL) and p210(BCR/ABL) "escapes" the auto-inhibition mechanisms of c-ABL, such as allosteric inhibition. A novel class of compounds including GNF-2 restores allosteric inhibition of the kinase activity and the transformation potential of BCR/ABL. Here we investigated whether there are differences between p185(BCR/ABL) and p210(BCR/ABL) regarding their sensitivity towards allosteric inhibition by GNF-2 in models of Philadelphia chromosome-positive acute lymphatic leukemia.
Design and methods: We investigated the anti-proliferative activity of GNF-2 in different Philadelphia chromosome-positive acute lymphatic leukemia models, such as cell lines, patient-derived long-term cultures and factor-dependent lymphatic Ba/F3 cells expressing either p185(BCR/ABL) or p210(BCR/ABL) and their resistance mutants.
Results: The inhibitory effects of GNF-2 differed constantly between p185(BCR/ABL) and p210(BCR/ABL) expressing cells. In all three Philadelphia chromosome-positive acute lymphatic leukemia models, p210(BCR/ABL)-transformed cells were more sensitive to GNF-2 than were p185BCR/ABL-positive cells. Similar results were obtained for p185(BCR/ABL) and the p210(BCR/ABL) harboring resistance mutations.
Conclusions: Our data provide the first evidence of a differential response of p185(BCR/ABL)- and p210(BCR/ABL)- transformed cells to allosteric inhibition by GNF-2, which is of importance for the treatment of patients with Philadelphia chromosome-positive acute lymphatic leukemia.
We present measurements of exclusive ensuremathπ+,0 and η production in pp reactions at 1.25GeV and 2.2GeV beam kinetic energy in hadron and dielectron channels. In the case of π+ and π0 , high-statistics invariant-mass and angular distributions are obtained within the HADES acceptance as well as acceptance-corrected distributions, which are compared to a resonance model. The sensitivity of the data to the yield and production angular distribution of Δ (1232) and higher-lying baryon resonances is shown, and an improved parameterization is proposed. The extracted cross-sections are of special interest in the case of pp → pp η , since controversial data exist at 2.0GeV; we find \ensuremathσ=0.142±0.022 mb. Using the dielectron channels, the π0 and η Dalitz decay signals are reconstructed with yields fully consistent with the hadronic channels. The electron invariant masses and acceptance-corrected helicity angle distributions are found in good agreement with model predictions.
We have sampled atmospheric ice nuclei (IN) and aerosol in Germany and in Israel during spring 2010. IN were analyzed by the static vapor diffusion chamber FRIDGE, as well as by electron microscopy. During the Eyjafjallajökull volcanic eruption of April 2010 we have measured the highest ice nucleus number concentrations (>600 l−1) in our record of 2 yr of daily IN measurements in central Germany. Even in Israel, located about 5000 km away from Iceland, IN were as high as otherwise only during desert dust storms. The fraction of aerosol activated as ice nuclei at −18 °C and 119% rhice and the corresponding area density of ice-active sites per aerosol surface were considerably higher than what we observed during an intense outbreak of Saharan dust over Europe in May 2008.
Pure volcanic ash accounts for at least 53–68% of the 239 individual ice nucleating particles that we collected in aerosol samples from the event and analyzed by electron microscopy. Volcanic ash samples that had been collected close to the eruption site were aerosolized in the laboratory and measured by FRIDGE. Our analysis confirms the relatively poor ice nucleating efficiency (at −18 °C and 119% ice-saturation) of such "fresh" volcanic ash, as it had recently been found by other workers. We find that both the fraction of the aerosol that is active as ice nuclei as well as the density of ice-active sites on the aerosol surface are three orders of magnitude larger in the samples collected from ambient air during the volcanic peaks than in the aerosolized samples from the ash collected close to the eruption site. From this we conclude that the ice-nucleating properties of volcanic ash may be altered substantially by aging and processing during long-range transport in the atmosphere, and that global volcanism deserves further attention as a potential source of atmospheric ice nuclei.
The pT-differential inclusive production cross section of the prompt charm-strange meson Ds+ in the rapidity range |y|<0.5 was measured in proton–proton collisions at s=7 TeV at the LHC using the ALICE detector. The analysis was performed on a data sample of 2.98×108 events collected with a minimum-bias trigger. The corresponding integrated luminosity is Lint=4.8 nb−1. Reconstructing the decay Ds+→ϕπ+, with ϕ→K−K+, and its charge conjugate, about 480 Ds± mesons were counted, after selection cuts, in the transverse momentum range 2<pT<12 GeV/c. The results are compared with predictions from models based on perturbative QCD. The ratios of the cross sections of four D meson species (namely D0, D+, D⁎+ and Ds+) were determined both as a function of pT and integrated over pT after extrapolating to full pT range, together with the strangeness suppression factor in charm fragmentation. The obtained values are found to be compatible within uncertainties with those measured by other experiments in e+e−, ep and pp interactions at various centre-of-mass energies.
he first measurements of the invariant differential cross sections of inclusive π0 and η meson production at mid-rapidity in proton–proton collisions at s=0.9 TeV and s=7 TeV are reported. The π0 measurement covers the ranges 0.4<pT<7 GeV/c and 0.3<pT<25 GeV/c for these two energies, respectively. The production of η mesons was measured at s=√7 TeV in the range 0.4<pT<15 GeV/c. Next-to-Leading Order perturbative QCD calculations, which are consistent with the π0 spectrum at s=0.9 TeV, overestimate those of π0 and η mesons at s=√7 TeV, but agree with the measured η/π0 ratio at s=√7 TeV.
The ALICE Collaboration has measured inclusive J/ψ production in pp collisions at a center-of-mass energy √s=2.76 TeV at the LHC. The results presented in this Letter refer to the rapidity ranges |y|<0.9 and 2.5<y<4 and have been obtained by measuring the electron and muon pair decay channels, respectively. The integrated luminosities for the two channels are Linte=1.1 nb−1 and Lintμ=19.9 nb−1, and the corresponding signal statistics are NJ/ψe+e−=59±14 and NJ/ψμ+μ−=1364±53. We present dσJ/ψ/dy for the two rapidity regions under study and, for the forward-y range, d2σJ/ψ/dydpt in the transverse momentum domain 0<pt<8 GeV/c. The results are compared with previously published results at s=7 TeV and with theoretical calculations.
The ALICE experiment has measured low-mass dimuon production in pp collisions at √s=7 TeV in the dimuon rapidity region 2.5<y<4. The observed dimuon mass spectrum is described as a superposition of resonance decays (η,ρ,ω,η′,ϕ) into muons and semi-leptonic decays of charmed mesons. The measured production cross sections for ω and ϕ are σω(1<pt<5 GeV/c,2.5<y<4)=5.28±0.54(stat)±0.49(syst) mb and σϕ(1<pt<5 GeV/c,2.5<y<4)=0.940±0.084(stat)±0.076(syst) mb. The differential cross sections d2σ/dydpt are extracted as a function of pt for ω and ϕ. The ratio between the ρ and ω cross section is obtained. Results for the ϕ are compared with other measurements at the same energy and with predictions by models.
Identical neutral kaon pair correlations are measured in √s=7 TeV pp collisions in the ALICE experiment. One-dimensional Ks0Ks0 correlation functions in terms of the invariant momentum difference of kaon pairs are formed in two multiplicity and two transverse momentum ranges. The femtoscopic parameters for the radius and correlation strength of the kaon source are extracted. The fit includes quantum statistics and final-state interactions of the a0/f0 resonance. Ks0Ks0 correlations show an increase in radius for increasing multiplicity and a slight decrease in radius for increasing transverse mass, mT, as seen in ππ correlations in pp collisions and in heavy-ion collisions. Transverse mass scaling is observed between the Ks0Ks0 and ππ radii. Also, the first observation is made of the decay of the f2′(1525) meson into the Ks0Ks0 channel in pp collisions.