Filtern
Erscheinungsjahr
Dokumenttyp
- Wissenschaftlicher Artikel (32)
- Preprint (5)
- Konferenzveröffentlichung (1)
Volltext vorhanden
- ja (38)
Gehört zur Bibliographie
- nein (38)
Schlagworte
- ATO (1)
- Actin (1)
- Alzheimer’s dementia (1)
- Amyloid-beta 42 (1)
- Anti-kaon–nucleon physics (1)
- B cell receptor (1)
- Baryonic resonances (1)
- Bevacizumab (1)
- Biomarkers (1)
- COVID-19 (1)
Institut
- Physik (23)
- Medizin (12)
- Frankfurt Institute for Advanced Studies (FIAS) (6)
- Informatik (6)
- ELEMENTS (1)
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.
The first measurement of ϕ-meson production in p-Pb collisions at a nucleon-nucleon centre-of-mass energy sNN−−−√ = 5.02 TeV has been performed with the ALICE apparatus at the LHC. The ϕ-mesons have been identified in the dimuon decay channel in the transverse momentum (pT) range 1<pT<7 GeV/c, both in the p-going (2.03<y<3.53) and the Pb-going (−4.46<y<−2.96) directions, where y stands for the rapidity in the nucleon-nucleon centre-of-mass. Differential cross sections as a function of transverse momentum and rapidity are presented. The forward-backward asymmetry for ϕ-meson production is measured for 2.96<|y|<3.53, resulting in a factor ∼0.5 with no significant pT dependence within the uncertainties. The pT dependence of the ϕ nuclear modification factor RpPb exhibits an enhancement up to a factor 1.6 at pT = 3-4 GeV/c in the Pb-going direction. The pT dependence of the ϕ-meson cross section in pp collisions at s√ = 2.76 TeV, which is used to determine a reference for the p-Pb results, is also presented here for 1<pT<5 GeV/c and 2.5<y<4.
We report on results obtained with the Event Shape Engineering technique applied to Pb-Pb collisions at sNN−−−√=2.76 TeV. By selecting events in the same centrality interval, but with very different average flow, different initial state conditions can be studied. We find the effect of the event-shape selection on the elliptic flow coefficient v2 to be almost independent of transverse momentum pT, as expected if this effect is due to fluctuations in the initial geometry of the system. Charged hadron, pion, kaon, and proton transverse momentum distributions are found to be harder in events with higher-than-average elliptic flow, indicating an interplay between radial and elliptic flow.
Transverse momentum (pT) spectra of pions, kaons, and protons up to pT=20 GeV/c have been measured in Pb-Pb collisions at sNN−−−√=2.76 TeV using the ALICE detector for six different centrality classes covering 0-80%. The proton-to-pion and the kaon-to-pion ratios both show a distinct peak at pT≈3 GeV/c in central Pb-Pb collisions that decreases towards more peripheral collisions. For pT>10 GeV/c, the nuclear modification factor is found to be the same for all three particle species in each centrality interval within systematic uncertainties of 10-20%. This suggests there is no direct interplay between the energy loss in the medium and the particle species composition in the hard core of the quenched jet. For pT<10 GeV/c, the data provide important constraints for models aimed at describing the transition from soft to hard physics.
Observation of enhanced subthreshold K+ production in central collisions between heavy nuclei
(1994)
In the very heavy collision system 197Au+197Au the K+ production process was studied as a function of impact parameter at 1 GeV/nucleon, a beam energy well below the free N-N threshold. The K+ multiplicity increases more than linearly with the number of participant nucleons and the K+/ pi + ratio rises significantly when going from peripheral to central collisions. The measured K+ double differential cross section is enhanced by a factor of 6 compared to microscopic transport calculations if secondary processes (Delta N-->K Lambda N and Delta Delta -->K Lambda N) are ignored.
Der Langstielige Mannsschild (Androsace elongata) gehört zu den auch früher schon sehr seltenen Pflanzenarten Hessens und wurde erstmals Anfang des 19. Jahrhunderts nachgewiesen. Weitere Nachweise gelangen danach erst ab etwa 1950. Seither wurde die Art im Raum Münzenberg in der nördlichen Wetterau kontinuierlich bestätigt. Im Rahmen der 2008 durchgeführten Untersuchungen konnten zwei weitere Wuchsorte aufgefunden werden. Keines dieser Vorkommen unterliegt bislang gesetzlichem Schutz. Die wenigen Pflanzen an stärker geneigten Böschungen sind durch Sukzession hochgradig bedroht und auf den geringer geneigten Wuchsflächen können die individuenreicheren Bestände bei Ausbleiben oder Änderung der derzeitigen Nutzung rasch zusammenbrechen. Als geeignete Maßnahme zur Erhaltung bietet sich die Einbeziehung aller Flächen in die auf anderen Magerrasen der Umgebung schon praktizierte Huteschäferei an.
Ceritinib-induced regression of an insulin-like growth factor-driven neuroepithelial brain tumor
(2019)
The insulin-like growth factor (IGF) pathway plays an important role in several brain tumor entities. However, the lack of inhibitors crossing the blood–brain barrier remains a significant obstacle for clinical translation. Here, we targeted the IGF pathway using ceritinib, an off-target inhibitor of the IGF1 receptor (IGF1R) and insulin receptor (INSR), in a pediatric patient with an unclassified brain tumor and a notch receptor 1 (NOTCH1) germline mutation. Pathway analysis of the tumor revealed activation of the sonic hedgehog (SHH), the wingless and integrated-1 (WNT), the IGF, and the Notch pathway. The proliferation of the patient tumor cells (225ZL) was inhibited by arsenic trioxide (ATO), which is an inhibitor of the SHH pathway, by linsitinib, which is an inhibitor of IGF1R and INSR, and by ceritinib. 225ZL expressed INSR but not IGF1R at the protein level, and ceritinib blocked the phosphorylation of INSR. Our first personalized treatment included ATO, but because of side effects, we switched to ceritinib. After 46 days, we achieved a concentration of 1.70 µM of ceritinib in the plasma, and after 58 days, MRI confirmed that there was a response to the treatment. Ceritinib accumulated in the tumor at a concentration of 2.72 µM. Our data suggest ceritinib as a promising drug for the treatment of IGF-driven brain tumors.
As new generations of targeted therapies emerge and tumor genome sequencing discovers increasingly comprehensive mutation repertoires, the functional relationships of mutations to tumor phenotypes remain largely unknown. Here, we measured ex vivo sensitivity of 246 blood cancers to 63 drugs alongside genome, transcriptome, and DNA methylome analysis to understand determinants of drug response. We assembled a primary blood cancer cell encyclopedia data set that revealed disease-specific sensitivities for each cancer. Within chronic lymphocytic leukemia (CLL), responses to 62% of drugs were associated with 2 or more mutations, and linked the B cell receptor (BCR) pathway to trisomy 12, an important driver of CLL. Based on drug responses, the disease could be organized into phenotypic subgroups characterized by exploitable dependencies on BCR, mTOR, or MEK signaling and associated with mutations, gene expression, and DNA methylation. Fourteen percent of CLLs were driven by mTOR signaling in a non–BCR-dependent manner. Multivariate modeling revealed immunoglobulin heavy chain variable gene (IGHV) mutation status and trisomy 12 as the most important modulators of response to kinase inhibitors in CLL. Ex vivo drug responses were associated with outcome. This study overcomes the perception that most mutations do not influence drug response of cancer, and points to an updated approach to understanding tumor biology, with implications for biomarker discovery and cancer care.
Within the scope of the Wildlife Conservation Programme of the Botanical Society for the Nature Conservation in Hesse, a comprehensive survey was carried out of a comparatively common species, the Common Pasque Flower (Pulsatilla vulgaris). It still occurs in large populations on the nutrient poor chalk meadows of the Vorderhoen and Kuppenhoen. Other populations are known from the Wetterau and the Schluechterner Becken. A few other populations are known, but they only have a few individuals. Altogether 64 populations were recorded, five with more than 1,000 plants. The largest population, with over 50,000 individuals, is in the Weinberg nature reserve, Molzbach (near Huenfeld).
Background: The progression of mild cognitive impairment (MCI) to Alzheimer’s disease (AD) dementia can be predicted by cognitive, neuroimaging, and cerebrospinal fluid (CSF) markers. Since most biomarkers reveal complementary information, a combination of biomarkers may increase the predictive power. We investigated which combination of the Mini-Mental State Examination (MMSE), Clinical Dementia Rating (CDR)-sum-of-boxes, the word list delayed free recall from the Consortium to Establish a Registry of Dementia (CERAD) test battery, hippocampal volume (HCV), amyloid-beta1–42 (Aβ42), amyloid-beta1–40 (Aβ40) levels, the ratio of Aβ42/Aβ40, phosphorylated tau, and total tau (t-Tau) levels in the CSF best predicted a short-term conversion from MCI to AD dementia.
Methods: We used 115 complete datasets from MCI patients of the "Dementia Competence Network", a German multicenter cohort study with annual follow-up up to 3 years. MCI was broadly defined to include amnestic and nonamnestic syndromes. Variables known to predict progression in MCI patients were selected a priori. Nine individual predictors were compared by receiver operating characteristic (ROC) curve analysis. ROC curves of the five best two-, three-, and four-parameter combinations were analyzed for significant superiority by a bootstrapping wrapper around a support vector machine with linear kernel. The incremental value of combinations was tested for statistical significance by comparing the specificities of the different classifiers at a given sensitivity of 85%.
Results: Out of 115 subjects, 28 (24.3%) with MCI progressed to AD dementia within a mean follow-up period of 25.5 months. At baseline, MCI-AD patients were no different from stable MCI in age and gender distribution, but had lower educational attainment. All single biomarkers were significantly different between the two groups at baseline. ROC curves of the individual predictors gave areas under the curve (AUC) between 0.66 and 0.77, and all single predictors were statistically superior to Aβ40. The AUC of the two-parameter combinations ranged from 0.77 to 0.81. The three-parameter combinations ranged from AUC 0.80–0.83, and the four-parameter combination from AUC 0.81–0.82. None of the predictor combinations was significantly superior to the two best single predictors (HCV and t-Tau). When maximizing the AUC differences by fixing sensitivity at 85%, the two- to four-parameter combinations were superior to HCV alone.
Conclusion: A combination of two biomarkers of neurodegeneration (e.g., HCV and t-Tau) is not superior over the single parameters in identifying patients with MCI who are most likely to progress to AD dementia, although there is a gradual increase in the statistical measures across increasing biomarker combinations. This may have implications for clinical diagnosis and for selecting subjects for participation in clinical trials.