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Background Eukaryotic gene expression is controlled by cis-regulatory elements (CREs) including promoters and enhancers which are bound by transcription factors (TFs). Differential expression of TFs and their putative binding sites on CREs cause tissue and developmental-specific transcriptional activity. Consolidating genomic data sets can offer further insights into the accessibility of CREs, TF activity, and thus gene regulation. However, the integration and analysis of multi-modal data sets are hampered by considerable technical challenges. While methods for highlighting differential TF activity from combined ChIP-seq and RNA-seq data exist, they do not offer good usability, have limited support for large-scale data processing, and provide only minimal functionality for visual result interpretation.
Results We developed TF-Prioritizer, an automated java pipeline to prioritize condition-specific TFs derived from multi-modal data. TF-Prioritizer creates an interactive, feature-rich, and user-friendly web report of its results. To showcase the potential of TF-Prioritizer, we identified known active TFs (e.g., Stat5, Elf5, Nfib, Esr1), their target genes (e.g., milk proteins and cell-cycle genes), and newly classified lactating mammary gland TFs (e.g., Creb1, Arnt).
Conclusion TF-Prioritizer accepts ChIP-seq and RNA-seq data, as input and suggests TFs with differential activity, thus offering an understanding of genome-wide gene regulation, potential pathogenesis, and therapeutic targets in biomedical research.
Purpose: The PELICAN trial evaluates for the first time efficacy and safety of pegylated liposomal doxorubicin (PLD) versus capecitabine as first-line treatment of metastatic breast cancer (MBC).
Methods: This randomized, phase III, open-label, multicenter trial enrolled first-line MBC patients who were ineligible for endocrine or trastuzumab therapy. Cumulative adjuvant anthracyclines of 360 mg/m2 doxorubicin or equivalent were allowed. Left ventricular ejection fraction of >50 % was required. Patients received PLD 50 mg/m2 every 28 days or capecitabine 1250 mg/m2 twice daily for 14 days every 21 days. The primary endpoint was time-to-disease progression (TTP).
Results: 210 patients were randomized (n = 105, PLD and n = 105, capecitabine). Adjuvant anthracyclines were given to 37 % (PLD) and 36 % (capecitabine) of patients. No significant difference was observed in TTP [HR = 1.21 (95 % confidence interval, 0.838–1.750)]. Median TTP was 6.0 months for both PLD and capecitabine. Comparing patients with or without prior anthracyclines, no significant difference in TTP was observed in the PLD arm (log-rank P = 0.64). For PLD versus capecitabine, respectively, overall survival (median, 23.3 months vs. 26.8 months) and time-to-treatment failure (median, 4.6 months vs. 3.7 months) were not statistically significantly different. Compared to PLD, patients on capecitabine experienced more serious adverse events (P = 0.015) and more cardiac events among patients who had prior anthracycline exposure (18 vs. 8 %; P = 0.31).
Conclusion: Both PLD and capecitabine are effective first-line agents for MBC.
The production of Σ0 baryons in the nuclear reaction p (3.5 GeV) + Nb (corresponding to sNN=3.18 GeV) is studied with the detector set-up HADES at GSI, Darmstadt. Σ0s were identified via the decay Σ0→Λγ with subsequent decays Λ→pπ− in coincidence with a e+e− pair from either external (γ→e+e−) or internal (Dalitz decay γ⁎→e+e−) gamma conversions. The differential Σ0 cross section integrated over the detector acceptance, i.e. the rapidity interval 0.5<y<1.1, has been extracted as ΔσΣ0=2.3±(0.2)stat±(−0.6+0.6)sys±(0.2)norm mb, yielding the inclusive production cross section in full phase space σΣ0total=5.8±(0.5)stat±(−1.4+1.4)sys±(0.6)norm±(1.7)extrapol mb by averaging over different extrapolation methods. The Λall/Σ0 ratio within the HADES acceptance is equal to 2.3±(0.2)stat±(−0.6+0.6)sys. The obtained rapidity and momentum distributions are compared to transport model calculations. The Σ0 yield agrees with the statistical model of particle production in nuclear reactions. Keywords: Hyperons, Strangeness, Proton, Nucleus.
n this paper we report on the investigation of baryonic resonance production in proton-proton collisions at the kinetic energies of 1.25 GeV and 3.5 GeV, based on data measured with HADES. Exclusive channels npπ+ and ppπ0 as well as ppe+e− were studied simultaneously in the framework of a one-boson exchange model. The resonance cross sections were determined from the one-pion channels for Δ(1232) and N(1440) (1.25 GeV) as well as further Δ and N* resonances up to 2 GeV/c2 for the 3.5 GeV data. The data at 1.25 GeV energy were also analysed within the framework of the partial wave analysis together with the set of several other measurements at lower energies. The obtained solutions provided the evolution of resonance production with the beam energy, showing a sizeable non-resonant contribution but with still dominating contribution of Δ(1232)P33. In the case of 3.5 GeV data, the study of the ppe+e− channel gave the insight on the Dalitz decays of the baryon resonances and, in particular, on the electromagnetic transition form-factors in the time-like region. We show that the assumption of a constant electromagnetic transition form-factors leads to underestimation of the yield in the dielectron invariant mass spectrum below the vector mesons pole. On the other hand, a comparison with various transport models shows the important role of intermediate ρ production, though with a large model dependency. The exclusive channels analysis done by the HADES collaboration provides new stringent restrictions on the parameterizations used in the models.
his contribution aims to give a basic overview of the latest results regarding the production of resonances in different collision systems. The results were extracted from experimental data collected with HADES that is a multipurpose detector located at the GSI Helmholtzzentrum, Darmstadt. The main points discussed here are: the properties of the strange resonances Λ(1405) and Σ(1385), the role of Δ’s as a source of pions in the final state, the production dynamics reflected in form of differential cross sections, and the role of the ϕ meson as a source for K− particles.
We present the results of two-pion production in tagged quasi-free np collisions at a deutron incident beam energy of 1.25 GeV/c measured with the High-Acceptance Di-Electron Spectrometer (HADES) installed at GSI. The specific acceptance of HADES allowed for the first time to obtain high-precision data on π+π− and π−π0 production in np collisions in a region corresponding to large transverse momenta of the secondary particles. The obtained differential cross section data provide strong constraints on the production mechanisms and on the various baryon resonance contributions (∆∆, N(1440), N(1520), ∆(1600)). The invariant mass and angular distributions from the np → npπ+π −and np → ppπ−π0 reactions are compared with different theoretical model predictions.
The toolbox for imaging molecules is well-equipped today. Some techniques visualize the geometrical structure, others the electron density or electron orbitals. Molecules are many-body systems for which the correlation between the constituents is decisive and the spatial and the momentum distribution of one electron depends on those of the other electrons and the nuclei. Such correlations have escaped direct observation by imaging techniques so far. Here, we implement an imaging scheme which visualizes correlations between electrons by coincident detection of the reaction fragments after high energy photofragmentation. With this technique, we examine the H2 two-electron wave function in which electron–electron correlation beyond the mean-field level is prominent. We visualize the dependence of the wave function on the internuclear distance. High energy photoelectrons are shown to be a powerful tool for molecular imaging. Our study paves the way for future time resolved correlation imaging at FELs and laser based X-ray sources.
How long does it take to emit an electron from an atom? This question has intrigued scientists for decades. As such emission times are in the attosecond regime, the advent of attosecond metrology using ultrashort and intense lasers has re-triggered strong interest on the topic from an experimental standpoint. Here, we present an approach to measure such emission delays, which does not require attosecond light pulses, and works without the presence of superimposed infrared laser fields. We instead extract the emission delay from the interference pattern generated as the emitted photoelectron is diffracted by the parent ion’s potential. Targeting core electrons in CO, we measured a 2d map of photoelectron emission delays in the molecular frame over a wide range of electron energies. The emission times depend drastically on the photoelectrons’ emission directions in the molecular frame and exhibit characteristic changes along the shape resonance of the molecule.