Modeling of corticosteroid pharmacogenomics in rat liver using gene microarrays."

ABSTRACT Corticosteroid (CS) pharmacogenomics was studied using gene microarrays in rat liver. Methylprednisolone (MPL) was administered intravenously at 50 mg/kg. Rats were sacrificed and liver excised at 17 time points over 72 h. RNAs from individual livers were used to query Affymetrix GeneChips that contain sequences for 8000 genes. Cluster analysis revealed six temporal patterns consisting of 197 CS-responsive probes representing 143 genes. Based on our fifth-generation model of CS pharmacokinetics/pharmacodynamics (PK/PD), mechanistic models were developed to describe the time pattern for each CS-responsive gene. Two clusters showed increased expression with different effect duration. PK/PD models assuming CS stimulation of mRNA synthesis were applied. Another two clusters showed an initial decline followed by delayed increase, suggesting two mechanisms might be involved jointly. The initial suppression was captured by CS inhibition of mRNA synthesis or stimulation of degradation. CS may also stimulate the production of a biosignal (transcription factors or other hormones), which can cause secondary induction of the target mRNA. One cluster showed a very abrupt increase in message followed by rapid decrease. These genes were lymphocytic in origin and were modeled combining the fast gene induction effect of CS in lymphoid cells and its direct lymphocyte trafficking effect. Another cluster showed reduction persisting for 18 h, which was described by CS inhibition of mRNA synthesis. Our results reveal the marked diversity of genes regulated by CS via a limited array of mechanisms. These PK/PD models provide quantitation of CS pharmacogenomics and new hypotheses regarding understanding of diverse mechanisms of CS receptor-gene mediated action

Strangeness enhancements at central rapidity in 40 A GeV/c Pb-Pb collisions

Results are presented on neutral kaon, hyperon and antihyperon production in Pb-Pb and p-Be interactions at 40 GeV/c per nucleon. The enhancement pattern follows the same hierarchy as seen in the higher energy data - the enhancement increases with the strangeness content of the hyperons and with the centrality of collision. The centrality dependence of the Pb-Pb yields and enhancements is steeper at 40 than at 158 A GeV/c. The energy dependence of strangeness enhancements at mid-rapidity is discussed.Comment: 15 pages, 10 figures and 3 tables. Presented at International Conference on Strangeness in Quark Matter (SQM2009), Buzios, Rio de Janeiro, Brazil, 27 Sept - 2 Oct 2009. Submitted to J.Phys.G: Nucl.Part.Phys, one reference adde

Expansion dynamics of Pb-Pb collisions at 40 A GeV/c viewed by negatively charged hadrons

In this paper we present results on transverse mass spectra and Hanbury-Brown and Twiss correlation functions of negatively charged hadrons, which are expected to be mostly negative pions, measured in Pb-Pb collisions at 40 A GeV/c beam momentum. Based on these data, the collision dynamics and the space-time extent of the system at the thermal freeze-out are studied over a centrality range corresponding to the most central 53% of the Pb--Pb inelastic cross section. Comparisons with freeze-out conditions of strange particles and HBT results from other experiments are discussed.Comment: 29 pages, 18 figure

Using geologic conditions and multiattribute decision analysis to determine the relative favorability of selected areas for siting a high-level radioactive waste repository

A method is presented for determining the relative favorability of geologically complex areas for isolating high-level radioactive wastes. In applying the method to the northeastern region of the United States, seismicity and tectonic activity were the screening criteria used to divide the region into three areas of increasing seismotectonic risk. Criteria were then used to subdivide the area of lowest seismotectonic risk into six geologically distinct subareas including characteristics, surface-water and groundwater hydrology, potential human intrusion, site geometry, surface characteristics, and tectonic environment. Decision analysis was then used to identify the subareas most favorable from a geologic standpoint for further investigation, with a view to selecting a site for a repository. Three subareas (parts of northeastern Vermont, northern New Hampshire, and western Maine) were found to be the most favorable, using this method and existing data. However, because this study assessed relative geologic favorability, no conclusions should be drawn concerning the absolute suitability of individual subareas for high-level radioactive waste isolation. 34 refs., 7 figs., 20 tabs

Rapidity distributions around mid-rapidity of strange particles in Pb-Pb collisions at 158 AA GeV/c

The production at central rapidity of K0s, Lambda, Xi and Omega particles in Pb-Pb collisions at 158 A GeV/c has been measured by the NA57 experiment over a centrality range corresponding to the most central 53% of the inelastic Pb-Pb cross section. In this paper we present the rapidity distribution of each particle in the central rapidity unit as a function of the event centrality. The distributions are analyzed based on hydrodynamical models of the collisions.Comment: 15 pages, 10 figure

Strange particle production in 158 and 40 AA GeV/cc Pb-Pb and p-Be collisions

Results on strange particle production in Pb-Pb collisions at 158 and 40 $A$ GeV/$c$ beam momentum from the NA57 experiment at CERN SPS are presented. Particle yields and ratios are compared with those measured at RHIC. Strangeness enhancements with respect to p-Be reactions at the same beam momenta have been also measured: results about their dependence on centrality and collision energy are reported and discussed.Comment: Contribution to the proceedings of the "Hot Quarks 2004" Conference, July 18-24 2004, New Mexico, USA, submitted to Journal of Physics G 7 pages, 5 figure

Maternal DDT Exposures in Relation to Fetal and 5-Year Growth

Dichlorodiphenyltrichloroethane (DDT) is an organo-chlorine pesticide still used in areas of the world where malaria vector control is needed. Few studies have examined in utero exposures to DDT in relation to fetal and early childhood growth in populations with substantial exposure to DDT. Furthermore, only a portion of these studies have investigated in utero exposures and growth during childhood

New results from the NA57 experiment

We report results from the experiment NA57 at CERN SPS on hyperon production at midrapidity in Pb-Pb collisions at 158 $A$ GeV/$c$ and 40 $A$ GeV/$c$. $\Lambda$, $\Xi$ and $\Omega$ yields are compared with those from the STAR experiment at the higher energy of the BNL RHIC. $\Lambda$, $\Xi$, $\Omega$\ and preliminary $K_S^0$ transverse mass spectra are presented and interpreted within the framework of a hydro-dynamical blast wave model.Comment: 8 pages, 3 figures, contribution to the proceedings of The XXXVIIIth Rencontres de Moriond "QCD and High Energy Hadronic Interactions