Heavy Ion Collisions and the Density Dependence of the Local Mean Field

We study the effect of the density dependence of the scalar and the vector part of the nucleonic self-energy in Relativistic Quantum Molecular Dynamics (RQMD) on observables like the transversal flow and the rapidity distribution. The stability of nuclei in RQMD is greatly improved if the density dependence is included in the self-energies compared to a calculation assuming always saturation density of nuclear matter. Different approaches are studied: The main results are calculated with self-energies extracted from a Dirac-Br\"uckner-Hartree-Fock G-matrix of a one boson exchange model, i.e. the Bonn potential. These results are compared with those obtained by a generalization of static Skyrme force, with calculations in the simple linear Walecka model and results of the Br\"uckner-Hartree-Fock G-matrix of the Reid soft core potential. The transversal flow is very sensitive to these different approaches. A comparison with the data is given.Comment: LaTex-file, 13 pages, 5 figures (available upon request), submitted to Nuclear Physics

Influence of the pion-nucleon interaction on the collective pion flow in heavy ion reactions

We investigate the influence of the real part of the in-medium pion optical potential on the pion dynamics in intermediate energy heavy ion reactions at 1 GeV/A. For different models, i.e. a phenomenological model and the $\Delta$--hole model, a pionic potential is extracted from the dispersion relation and used in Quantum Molecular Dynamics calculations. In addition with the inelastic scattering processes we thus take care of both, real and imaginary part of the pion optical potential. A strong influence of the real pionic potential on the pion in-plane flow is observed. In general such a potential has the tendency to reduce the anticorrelation of pion and nucleon flow in non-central collisions.Comment: 12 pages Latex, 4 PS-figure

Influence of the in-medium pion dispersion relation in heavy ion collisions

We investigate the influence of medium corrections to the pion dispersion relation on the pion dynamics in intermediate energy heavy ion collisions. To do so a pion potential is extracted from the in-medium dispersion relation and used in QMD calculations and thus we take care of both, real and imaginary part of the pion optical potential. The potentials are determined from different sources, i.e. from the $\Delta$--hole model and from phenomenological approaches. Depending on the strength of the potential a reduction of the anti-correlation of pion and nucleon flow in non-central collisions is observed as well as an enhancement of the high energetic yield in transverse pion spectra. A comparison to experiments, in particular to $p_t$-spectra for the reaction Ca+Ca at 1 GeV/nucleon and the pion in-plane flow in Ne+Pb collisions at 800 MeV/nucleon, generally favours a weak potential.Comment: 25 pages, using REVTeX, 6 postscript figures; replaced by published versio

Medium effects in high energy heavy-ion collisions

The change of hadron properties in dense matter based on various theoretical approaches are reviewed. Incorporating these medium effects in the relativistic transport model, which treats consistently the change of hadron masses and energies in dense matter via the scalar and vector fields, heavy-ion collisions at energies available from SIS/GSI, AGS/BNL, and SPS/CERN are studied. This model is seen to provide satisfactory explanations for the observed enhancement of kaon, antikaon, and antiproton yields as well as soft pions in the transverse direction from the SIS experiments. In the AGS heavy-ion experiments, it can account for the enhanced $K^+/\pi^+$ ratio, the difference in the slope parameters of the $K^+$ and $K^-$ transverse kinetic energy spectra, and the lower apparent temperature of antiprotons than that of protons. This model also provides possible explanations for the observed enhancement of low-mass dileptons, phi mesons, and antilambdas in heavy-ion collisions at SPS energies. Furthermore, the change of hadron properties in hot dense matter leads to new signatures of the quark-gluon plasma to hadronic matter transition in future ultrarelativistic heavy-ion collisions at RHIC/BNL.Comment: RevTeX, 65 pages, including 25 postscript figures, invited topical review for Journal of Physics G: Nuclear and Particle Physic

Phosphodiesterase-5 inhibitors have distinct effects on the hemodynamics of the liver

<p>Abstract</p> <p>Background</p> <p>The NO - cGMP system plays a key role in the regulation of sinusoidal tonus and liver blood flow with phosphodiesterase-5 (PDE-5) terminating the dilatory action of cGMP. We, therefore, investigated the effects of PDE-5 inhibitors on hepatic and systemic hemodynamics in rats.</p> <p>Methods</p> <p>Hemodynamic parameters were monitored for 60 min. after intravenous injection of sildenafil and vardenafil [1, 10 and 100 μg/kg (sil1, sil10, sil100, var1, var10, var100)] in anesthetized rats.</p> <p>Results</p> <p>Cardiac output and heart rate remained constant. After a short dip, mean arterial blood pressure again increased. Systemic vascular resistance transiently decreased slightly. Changes in hepatic hemodynamic parameters started after few minutes and continued for at least 60 min. Portal (var10 -31%, sil10 -34%) and hepatic arterial resistance (var10 -30%, sil10 -32%) decreased significantly (p < 0.05). At the same time portal venous (var10 +29%, sil10 +24%), hepatic arterial (var10 +34%, sil10 +48%), and hepatic parenchymal blood flow (var10 +15%, sil10 +15%) increased significantly (p < 0.05). The fractional liver blood flow (total liver flow/cardiac output) increased significantly (var10 26%, sil10 23%). Portal pressure remained constant or tended to decrease. 10 μg/kg was the most effective dose for both PDE-5 inhibitors.</p> <p>Conclusion</p> <p>Low doses of phosphodiesterase-5 inhibitors have distinct effects on hepatic hemodynamic parameters. Their therapeutic use in portal hypertension should therefore be evaluated.</p

Total area of spontaneous portosystemic shunts independently predicts hepatic encephalopathy and mortality in liver cirrhosis

BACKGROUND: Spontaneous portosystemic shunts (SPSS) frequently develop in liver cirrhosis. Recent data suggested that presence of a single large SPSS is associated with complications, especially overt hepatic encephalopathy (oHE). However, presence of >1 SPSS is common. This study evaluates the impact of total cross-sectional SPSS area (TSA) on outcome of patients with liver cirrhosis. METHODS: In this retrospective international multicentric study, computed tomography (CT) scans of 908 cirrhotic patients with SPSS were evaluated for TSA. Clinical and laboratory data were recorded. Each detected SPSS radius was measured and TSA calculated. 1-year survival was primary and acute decompensation (oHE, variceal bleeding, ascites) secondary endpoint. RESULTS: 301 patients (169 male) were included in the training cohort. 30% of all patients presented >1 SPSS. TSA cut-off of 83 mm2 was determined to classify patients with small or large TSA (S-/L-TSA). L-TSA patients presented higher MELD (11 vs. 14) and more commonly history of oHE (12% vs. 21%, p83mm2 increases the risk for oHE and mortality in liver cirrhosis. Our results may have impact on clinical use of TSA/SPSS for risk stratification and clinical decision-making considering management of SPSS

Epigenomic Profiling of Human CD4+ T Cells Supports a Linear Differentiation Model and Highlights Molecular Regulators of Memory Development

SummaryThe impact of epigenetics on the differentiation of memory T (Tmem) cells is poorly defined. We generated deep epigenomes comprising genome-wide profiles of DNA methylation, histone modifications, DNA accessibility, and coding and non-coding RNA expression in naive, central-, effector-, and terminally differentiated CD45RA+ CD4+ Tmem cells from blood and CD69+ Tmem cells from bone marrow (BM-Tmem). We observed a progressive and proliferation-associated global loss of DNA methylation in heterochromatic parts of the genome during Tmem cell differentiation. Furthermore, distinct gradually changing signatures in the epigenome and the transcriptome supported a linear model of memory development in circulating T cells, while tissue-resident BM-Tmem branched off with a unique epigenetic profile. Integrative analyses identified candidate master regulators of Tmem cell differentiation, including the transcription factor FOXP1. This study highlights the importance of epigenomic changes for Tmem cell biology and demonstrates the value of epigenetic data for the identification of lineage regulators

microRNA-Mediated Messenger RNA Deadenylation Contributes to Translational Repression in Mammalian Cells

Animal microRNAs (miRNAs) typically regulate gene expression by binding to partially complementary target sites in the 3′ untranslated region (UTR) of messenger RNA (mRNA) reducing its translation and stability. They also commonly induce shortening of the mRNA 3′ poly(A) tail, which contributes to their mRNA decay promoting function. The relationship between miRNA-mediated deadenylation and translational repression has been less clear. Using transfection of reporter constructs carrying three imperfectly matching let-7 target sites in the 3′ UTR into mammalian cells we observe rapid target mRNA deadenylation that precedes measureable translational repression by endogenous let-7 miRNA. Depleting cells of the argonaute co-factors RCK or TNRC6A can impair let-7-mediated repression despite ongoing mRNA deadenylation, indicating that deadenylation alone is not sufficient to effect full repression. Nevertheless, the magnitude of translational repression by let-7 is diminished when the target reporter lacks a poly(A) tail. Employing an antisense strategy to block deadenylation of target mRNA with poly(A) tail also partially impairs translational repression. On the one hand, these experiments confirm that tail removal by deadenylation is not strictly required for translational repression. On the other hand they show directly that deadenylation can augment miRNA-mediated translational repression in mammalian cells beyond stimulating mRNA decay. Taken together with published work, these results suggest a dual role of deadenylation in miRNA function: it contributes to translational repression as well as mRNA decay and is thus critically involved in establishing the quantitatively appropriate physiological response to miRNAs

Mathematical modeling of microRNA-mediated mechanisms of translation repression

MicroRNAs can affect the protein translation using nine mechanistically different mechanisms, including repression of initiation and degradation of the transcript. There is a hot debate in the current literature about which mechanism and in which situations has a dominant role in living cells. The worst, same experimental systems dealing with the same pairs of mRNA and miRNA can provide ambiguous evidences about which is the actual mechanism of translation repression observed in the experiment. We start with reviewing the current knowledge of various mechanisms of miRNA action and suggest that mathematical modeling can help resolving some of the controversial interpretations. We describe three simple mathematical models of miRNA translation that can be used as tools in interpreting the experimental data on the dynamics of protein synthesis. The most complex model developed by us includes all known mechanisms of miRNA action. It allowed us to study possible dynamical patterns corresponding to different miRNA-mediated mechanisms of translation repression and to suggest concrete recipes on determining the dominant mechanism of miRNA action in the form of kinetic signatures. Using computational experiments and systematizing existing evidences from the literature, we justify a hypothesis about co-existence of distinct miRNA-mediated mechanisms of translation repression. The actually observed mechanism will be that acting on or changing the limiting "place" of the translation process. The limiting place can vary from one experimental setting to another. This model explains the majority of existing controversies reported.Comment: 40 pages, 9 figures, 4 tables, 91 cited reference. The analysis of kinetic signatures is updated according to the new model of coupled transcription, translation and degradation, and of miRNA-based regulation of this process published recently (arXiv:1204.5941). arXiv admin note: text overlap with arXiv:0911.179