Infection with the hepatitis C virus causes viral genotype-specific differences in cholesterol metabolism and hepatic steatosis

Background: Lipids play essential roles in the hepatitis C virus (HCV) life cycle and patients with chronic HCV infection display disordered lipid metabolism which resolves following successful anti-viral therapy. It has been proposed that HCV genotype 3 (HCV-G3) infection is an independent risk factor for hepatocellular carcinoma and evidence suggests lipogenic proteins are involved in hepatocarcinogenesis. Aims: We aimed to characterise variation in host lipid metabolism between participants chronically infected with HCV genotype 1 (HCV-G1) and HCV-G3 to identify likely genotype-specific differences in lipid metabolism. Methods: We combined several lipidomic approaches: analysis was performed between participants infected with HCV-G1 and HCV-G3, both in the fasting and non-fasting states, and after sustained virological response (SVR) to treatment. Sera were obtained from 112 fasting patients (25% with cirrhosis). Serum lipids were measured using standard enzymatic methods. Lathosterol and desmosterol were measured by gas-chromatography mass spectrometry (MS). For further metabolic insight on lipid metabolism, ultra-performance liquid chromatography MS was performed on all samples. A subgroup of 13 participants had whole body fat distribution determined using in vivo magnetic resonance imaging and spectroscopy. A second cohort of (non-fasting) sera were obtained from HCV Research UK for comparative analyses: 150 treatment naïve patients and 100 non-viraemic patients post-SVR. Results: HCV-G3 patients had significantly decreased serum apoB, non-HDL cholesterol concentrations, and more hepatic steatosis than those with HCV-G1. HCV-G3 patients also had significantly decreased serum levels of lathosterol, without significant reductions in desmosterol. Lipidomic analysis showed lipid species associated with reverse cholesterol transport pathway in HCV-G3. Conclusions: We demonstrated that compared to HCV-G1, HCV-G3 infection is characterised by low LDL cholesterol levels, with preferential suppression of cholesterol synthesis via lathosterol, associated with increasing hepatic steatosis. The genotype-specific lipid disturbances may shed light on genotypic variations in liver disease progression and promotion of hepatocellular cancer in HCV-G3

Infection with the hepatitis C virus causes viral genotype-specific differences in cholesterol metabolism and hepatic steatosis

Lipids play essential roles in the hepatitis C virus (HCV) life cycle and patients with chronic HCV infection display disordered lipid metabolism which resolves following successful anti-viral therapy. It has been proposed that HCV genotype 3 (HCV-G3) infection is an independent risk factor for hepatocellular carcinoma and evidence suggests lipogenic proteins are involved in hepatocarcinogenesis. We aimed to characterise variation in host lipid metabolism between participants chronically infected with HCV genotype 1 (HCV-G1) and HCV-G3 to identify likely genotype-specific differences in lipid metabolism. We combined several lipidomic approaches: analysis was performed between participants infected with HCV-G1 and HCV-G3, both in the fasting and non-fasting states, and after sustained virological response (SVR) to treatment. Sera were obtained from 112 fasting patients (25% with cirrhosis). Serum lipids were measured using standard enzymatic methods. Lathosterol and desmosterol were measured by gas-chromatography mass spectrometry (MS). For further metabolic insight on lipid metabolism, ultra-performance liquid chromatography MS was performed on all samples. A subgroup of 13 participants had whole body fat distribution determined using in vivo magnetic resonance imaging and spectroscopy. A second cohort of (non-fasting) sera were obtained from HCV Research UK for comparative analyses: 150 treatment naïve patients and 100 non-viraemic patients post-SVR. HCV-G3 patients had significantly decreased serum apoB, non-HDL cholesterol concentrations, and more hepatic steatosis than those with HCV-G1. HCV-G3 patients also had significantly decreased serum levels of lathosterol, without significant reductions in desmosterol. Lipidomic analysis showed lipid species associated with reverse cholesterol transport pathway in HCV-G3. We demonstrated that compared to HCV-G1, HCV-G3 infection is characterised by low LDL cholesterol levels, with preferential suppression of cholesterol synthesis via lathosterol, associated with increasing hepatic steatosis. The genotype-specific lipid disturbances may shed light on genotypic variations in liver disease progression and promotion of hepatocellular cancer in HCV-G3

Zero temperature string breaking in lattice quantum chromodynamics

The separation of a heavy quark and antiquark pair leads to the formation of a tube of flux, or "string", which should break in the presence of light quark-antiquark pairs. This expected zero-temperature phenomenon has proven elusive in simulations of lattice QCD. We study mixing between the string state and the two-meson decay channel in QCD with two flavors of dynamical sea quarks. We confirm that mixing is weak and find that it decreases at level crossing. While our study does not show direct effects of internal quark loops, our results, combined with unitarity, give clear confirmation of string breaking.Comment: 20 pages, 7 figures. With small clarifications and two additions to references. Submitted to Phys. Rev.

A comment on multiple vacua, particle production and the time dependent AdS/CFT correspondence

We give an explicit formulation of the time dependent AdS/CFT correspondence when there are multiple vacua present in Lorentzian signature. By computing sample two point functions we show how different amplitudes are related by cosmological particle production. We illustrate our methods in two example spacetimes: (a) a ``bubble of nothing'' in AdS space, and (b) an asymptotically locally AdS spacetime with a bubble of nothing on the boundary. In both cases the alpha vacua of de Sitter space make an interesting appearance.Comment: 9 page

Observing the First Stars and Black Holes

The high sensitivity of JWST will open a new window on the end of the cosmological dark ages. Small stellar clusters, with a stellar mass of several 10^6 M_sun, and low-mass black holes (BHs), with a mass of several 10^5 M_sun should be directly detectable out to redshift z=10, and individual supernovae (SNe) and gamma ray burst (GRB) afterglows are bright enough to be visible beyond this redshift. Dense primordial gas, in the process of collapsing from large scales to form protogalaxies, may also be possible to image through diffuse recombination line emission, possibly even before stars or BHs are formed. In this article, I discuss the key physical processes that are expected to have determined the sizes of the first star-clusters and black holes, and the prospect of studying these objects by direct detections with JWST and with other instruments. The direct light emitted by the very first stellar clusters and intermediate-mass black holes at z>10 will likely fall below JWST's detection threshold. However, JWST could reveal a decline at the faint-end of the high-redshift luminosity function, and thereby shed light on radiative and other feedback effects that operate at these early epochs. JWST will also have the sensitivity to detect individual SNe from beyond z=10. In a dedicated survey lasting for several weeks, thousands of SNe could be detected at z>6, with a redshift distribution extending to the formation of the very first stars at z>15. Using these SNe as tracers may be the only method to map out the earliest stages of the cosmic star-formation history. Finally, we point out that studying the earliest objects at high redshift will also offer a new window on the primordial power spectrum, on 100 times smaller scales than probed by current large-scale structure data.Comment: Invited contribution to "Astrophysics in the Next Decade: JWST and Concurrent Facilities", Astrophysics & Space Science Library, Eds. H. Thronson, A. Tielens, M. Stiavelli, Springer: Dordrecht (2008

Measurements of long-range near-side angular correlations in sNN=5\sqrt{s_{\text{NN}}}=5TeV proton-lead collisions in the forward region

Two-particle angular correlations are studied in proton-lead collisions at a nucleon-nucleon centre-of-mass energy of $\sqrt{s_{\text{NN}}}=5$TeV, collected with the LHCb detector at the LHC. The analysis is based on data recorded in two beam configurations, in which either the direction of the proton or that of the lead ion is analysed. The correlations are measured in the laboratory system as a function of relative pseudorapidity, $\Delta\eta$, and relative azimuthal angle, $\Delta\phi$, for events in different classes of event activity and for different bins of particle transverse momentum. In high-activity events a long-range correlation on the near side, $\Delta\phi \approx 0$, is observed in the pseudorapidity range $2.0<\eta<4.9$. This measurement of long-range correlations on the near side in proton-lead collisions extends previous observations into the forward region up to $\eta=4.9$. The correlation increases with growing event activity and is found to be more pronounced in the direction of the lead beam. However, the correlation in the direction of the lead and proton beams are found to be compatible when comparing events with similar absolute activity in the direction analysed.Comment: All figures and tables, along with any supplementary material and additional information, are available at https://lhcbproject.web.cern.ch/lhcbproject/Publications/LHCbProjectPublic/LHCb-PAPER-2015-040.htm

Study of the production of Λb0\Lambda_b^0 and B‾0\overline{B}^0 hadrons in pppp collisions and first measurement of the Λb0→J/ψpK−\Lambda_b^0\rightarrow J/\psi pK^- branching fraction

The product of the $\Lambda_b^0$ ($\overline{B}^0$) differential production cross-section and the branching fraction of the decay $\Lambda_b^0\rightarrow J/\psi pK^-$ ($\overline{B}^0\rightarrow J/\psi\overline{K}^*(892)^0$) is measured as a function of the beauty hadron transverse momentum, $p_{\rm T}$, and rapidity, $y$. The kinematic region of the measurements is $p_{\rm T}<20~{\rm GeV}/c$ and $2.0<y<4.5$. The measurements use a data sample corresponding to an integrated luminosity of $3~{\rm fb}^{-1}$ collected by the LHCb detector in $pp$ collisions at centre-of-mass energies $\sqrt{s}=7~{\rm TeV}$ in 2011 and $\sqrt{s}=8~{\rm TeV}$ in 2012. Based on previous LHCb results of the fragmentation fraction ratio, $f_{\Lambda_B^0}/f_d$, the branching fraction of the decay $\Lambda_b^0\rightarrow J/\psi pK^-$ is measured to be \begin{equation*} \mathcal{B}(\Lambda_b^0\rightarrow J/\psi pK^-)= (3.17\pm0.04\pm0.07\pm0.34^{+0.45}_{-0.28})\times10^{-4}, \end{equation*} where the first uncertainty is statistical, the second is systematic, the third is due to the uncertainty on the branching fraction of the decay $\overline{B}^0\rightarrow J/\psi\overline{K}^*(892)^0$, and the fourth is due to the knowledge of $f_{\Lambda_b^0}/f_d$. The sum of the asymmetries in the production and decay between $\Lambda_b^0$ and $\overline{\Lambda}_b^0$ is also measured as a function of $p_{\rm T}$ and $y$. The previously published branching fraction of $\Lambda_b^0\rightarrow J/\psi p\pi^-$, relative to that of $\Lambda_b^0\rightarrow J/\psi pK^-$, is updated. The branching fractions of $\Lambda_b^0\rightarrow P_c^+(\rightarrow J/\psi p)K^-$ are determined.Comment: 29 pages, 19figures. All figures and tables, along with any supplementary material and additional information, are available at https://lhcbproject.web.cern.ch/lhcbproject/Publications/LHCbProjectPublic/LHCb-PAPER-2015-032.htm

Evidence for the strangeness-changing weak decay Ξb−→Λb0π−\Xi_b^-\to\Lambda_b^0\pi^-

Using a $pp$ collision data sample corresponding to an integrated luminosity of 3.0~fb$^{-1}$, collected by the LHCb detector, we present the first search for the strangeness-changing weak decay $\Xi_b^-\to\Lambda_b^0\pi^-$. No $b$ hadron decay of this type has been seen before. A signal for this decay, corresponding to a significance of 3.2 standard deviations, is reported. The relative rate is measured to be ${{f_{\Xi_b^-}}\over{f_{\Lambda_b^0}}}{\cal{B}}(\Xi_b^-\to\Lambda_b^0\pi^-) = (5.7\pm1.8^{+0.8}_{-0.9})\times10^{-4}$, where $f_{\Xi_b^-}$ and $f_{\Lambda_b^0}$ are the $b\to\Xi_b^-$ and $b\to\Lambda_b^0$ fragmentation fractions, and ${\cal{B}}(\Xi_b^-\to\Lambda_b^0\pi^-)$ is the branching fraction. Assuming $f_{\Xi_b^-}/f_{\Lambda_b^0}$ is bounded between 0.1 and 0.3, the branching fraction ${\cal{B}}(\Xi_b^-\to\Lambda_b^0\pi^-)$ would lie in the range from $(0.57\pm0.21)\%$ to $(0.19\pm0.07)\%$.Comment: 7 pages, 2 figures, All figures and tables, along with any supplementary material and additional information, are available at https://lhcbproject.web.cern.ch/lhcbproject/Publications/LHCbProjectPublic/LHCb-PAPER-2015-047.htm

BB flavour tagging using charm decays at the LHCb experiment

An algorithm is described for tagging the flavour content at production of neutral $B$ mesons in the LHCb experiment. The algorithm exploits the correlation of the flavour of a $B$ meson with the charge of a reconstructed secondary charm hadron from the decay of the other $b$ hadron produced in the proton-proton collision. Charm hadron candidates are identified in a number of fully or partially reconstructed Cabibbo-favoured decay modes. The algorithm is calibrated on the self-tagged decay modes $B^+ \to J/\psi \, K^+$ and $B^0 \to J/\psi \, K^{*0}$ using $3.0\mathrm{\,fb}^{-1}$ of data collected by the LHCb experiment at $pp$ centre-of-mass energies of $7\mathrm{\,TeV}$ and $8\mathrm{\,TeV}$. Its tagging power on these samples of $B \to J/\psi \, X$ decays is $(0.30 \pm 0.01 \pm 0.01) \%$.Comment: All figures and tables, along with any supplementary material and additional information, are available at http://lhcbproject.web.cern.ch/lhcbproject/Publications/LHCbProjectPublic/LHCb-PAPER-2015-027.htm