L-DOPA Neurotoxicity Is Mediated by Up-Regulation of DMT1−IRE Expression

2008-2009 > Academic research: refereed > Publication in refereed journalpublished_fina

An Intronic Variant in the GRP78, a Stress-Associated Gene, Improves Prediction for Liver Cirrhosis in Persistent HBV Carriers

Background: Our previous study indicated that a common variant (rs430397 G>A) in the intron 5 of glucose-regulated protein 78 (GRP78) gene was associated with risk and prognosis of primary hepatocellular carcinoma (HCC), including HBV- and cirrhosis-related HCC. rs430397 polymorphism may be a contributing factor or biomarker of HBV infection or HBV-related cirrhosis. Methodology/Principal Findings: 539 non-HBV-infected individuals, 205 self-limited infection and 496 persistent HBV infection were recruited between January 2001 and April 2005 from the hospitals in Southern China. Genomic DNA was genotyped for rs430397. The associations between the variation and susceptibility to liver cirrhosis (LC) in persistent HBV infection were examined. We observed that individuals carrying allele rs430397A were more likely to become HBV-related LC. When persistently infected patients were divided into four subgroups, patients with phase IV had an increased allele A and genotype AG compared with phase I and/or phase III. Decreased serum albumin and prolonged plasma prothrombin time (PT) were showed in LC patients carrying genotype AA. Furthermore, rs430397 genotype had an increased susceptibility to LC with dose-dependent manners (P-trend = 0.005), and the genotype did constitute a risk factor for the development of advanced LC (Child-Pugh classification C and B, P-trend = 0.021). Conclusions/Significance: rs430397 polymorphism may be a contributing factor to LC in persistent HBV carriers. © 2011 Zhu et al.published_or_final_versio

Arsenic trioxide exerts synergistic effects with cisplatin on non-small cell lung cancer cells via apoptosis induction

<p>Abstract</p> <p>Background</p> <p>Despite multidisciplinary treatment, lung cancer remains a highly lethal disease due to poor response to chemotherapy. The identification of therapeutic agents with synergistic effects with traditional drugs is an alternative for lung cancer therapy. In this study, the synergistic effects of arsenic trioxide (As₂O₃) with cisplatin (DDP) on A549 and H460 non-small cell lung cancer (NSCLC) cells were explored.</p> <p>Methods</p> <p>A549 and H460 human lung cancer cells were treated with As₂O₃and/or DDP. Cell growth curves, cell proliferation, cell cycle, and apoptosis of human cancer cell lines were determined by the 3-(4,5)-dimethylthiahiazo (-z-y1)-3,5-di-phenytetrazoliumromide (MTT) method, clonogenic assay, and flow cytometry (FCM). Apoptosis was further assessed by TUNEL staining. Cell cycle and apoptosis related protein p21, cyclin D1, Bcl-2, bax, clusterin, and caspase-3 were detected by western blot.</p> <p>Results</p> <p>MTT and clonogenic assay showed As₂O₃within 10^-2μM to 10 μM exerted inhibition on the proliferation of NSCLC cells, and 2.5 μM As₂O₃exerted synergistic inhibition on proliferation with 3 μg/ml DDP. The combination indices (CI) for A549 and H460 were 0.5 and 0.6, respectively, as confirmed by the synergism of As₂O₃with DDP. FCM showed As₂O₃did not affect the cell cycle. The G0/G1 fraction ranged from 57% to 62% for controlled A549 cells and cells treated with As₂O₃and/or DDP. The G0/G1 fraction ranged from 37% to 42% for controlled H460 cells and cells treated with As₂O₃and/or DDP. FCM and TUNEL staining illustrated that the combination of As₂O₃and DDP provoked synergistic effects on apoptosis induction based on the analysis of the apoptosis index. Western blotting revealed that the expression of cell cycle related protein p21 and cyclin D1 were not affected by the treatments, whereas apoptosis related protein bax, Bcl-2, and clusterin were significantly regulated by As₂O₃and/or DDP treatments compared with controls. The expression of caspase-3 in cells treated with the combination of As₂O₃and DDP did not differ from that in cells treated with a single agent.</p> <p>Conclusion</p> <p>As₂O₃exerted synergistic effects with DDP on NSCLC cells, and the synergistic effects were partly due to the induction of caspase-independent apoptosis.</p

Slip-Flow and Heat Transfer of a Non-Newtonian Nanofluid in a Microtube

The slip-flow and heat transfer of a non-Newtonian nanofluid in a microtube is theoretically studied. The power-law rheology is adopted to describe the non-Newtonian characteristics of the flow, in which the fluid consistency coefficient and the flow behavior index depend on the nanoparticle volume fraction. The velocity profile, volumetric flow rate and local Nusselt number are calculated for different values of nanoparticle volume fraction and slip length. The results show that the influence of nanoparticle volume fraction on the flow of the nanofluid depends on the pressure gradient, which is quite different from that of the Newtonian nanofluid. Increase of the nanoparticle volume fraction has the effect to impede the flow at a small pressure gradient, but it changes to facilitate the flow when the pressure gradient is large enough. This remarkable phenomenon is observed when the tube radius shrinks to micrometer scale. On the other hand, we find that increase of the slip length always results in larger flow rate of the nanofluid. Furthermore, the heat transfer rate of the nanofluid in the microtube can be enhanced due to the non-Newtonian rheology and slip boundary effects. The thermally fully developed heat transfer rate under constant wall temperature and constant heat flux boundary conditions is also compared

Search for New Physics in e mu X Data at D0 Using Sleuth: A Quasi-Model-Independent Search Strategy for New Physics

We present a quasi-model-independent search for the physics responsible for electroweak symmetry breaking. We define final states to be studied, and construct a rule that identifies a set of relevant variables for any particular final state. A new algorithm ("Sleuth") searches for regions of excess in those variables and quantifies the significance of any detected excess. After demonstrating the sensitivity of the method, we apply it to the semi-inclusive channel e mu X collected in 108 pb^-1 of ppbar collisions at sqrt(s) = 1.8 TeV at the D0 experiment during 1992-1996 at the Fermilab Tevatron. We find no evidence of new high p_T physics in this sample.Comment: 23 pages, 12 figures. Submitted to Physical Review

Search for Charged Higgs Bosons in e+e- Collisions at \sqrt{s} = 189 GeV

A search for pair-produced charged Higgs bosons is performed with the L3 detector at LEP using data collected at a centre-of-mass energy of 188.6 GeV, corresponding to an integrated luminosity of 176.4 pb^-1. Higgs decays into a charm and a strange quark or into a tau lepton and its associated neutrino are considered. The observed events are consistent with the expectations from Standard Model background processes. A lower limit of 65.5 GeV on the charged Higgs mass is derived at 95 % confidence level, independent of the decay branching ratio Br(H^{+/-} -> tau nu)

Search for new phenomena in final states with an energetic jet and large missing transverse momentum in pp collisions at √ s = 8 TeV with the ATLAS detector

Results of a search for new phenomena in final states with an energetic jet and large missing transverse momentum are reported. The search uses 20.3 fb−1 of √ s = 8 TeV data collected in 2012 with the ATLAS detector at the LHC. Events are required to have at least one jet with pT > 120 GeV and no leptons. Nine signal regions are considered with increasing missing transverse momentum requirements between Emiss T > 150 GeV and Emiss T > 700 GeV. Good agreement is observed between the number of events in data and Standard Model expectations. The results are translated into exclusion limits on models with either large extra spatial dimensions, pair production of weakly interacting dark matter candidates, or production of very light gravitinos in a gauge-mediated supersymmetric model. In addition, limits on the production of an invisibly decaying Higgs-like boson leading to similar topologies in the final state are presente