D→K,lνD \rightarrow K, l \nu Semileptonic Decay Scalar Form Factor and ∣Vcs∣|V_{cs}| from Lattice QCD

We present a new study of D semileptonic decays on the lattice which employs the Highly Improved Staggered Quark (HISQ) action for both the charm and the light valence quarks. We work with MILC unquenched $N_f = 2 + 1$ lattices and determine the scalar form factor $f_0(q^2)$ for $D \rightarrow K, l \nu$ semileptonic decays. The form factor is obtained from a scalar current matrix element that does not require any operator matching. We develop a new approach to carrying out chiral/continuum extrapolations of $f_0(q^2)$. The method uses the kinematic "$z$" variable instead of $q^2$ or the kaon energy $E_K$ and is applicable over the entire physical $q^2$ range. We find $f^{D \rightarrow K}_0(0) \equiv f^{D \rightarrow K}_+(0) = 0.747(19)$ in the chiral plus continuum limit and hereby improve the theory error on this quantity by a factor of $\sim$4 compared to previous lattice determinations. Combining the new theory result with recent experimental measurements of the product $f^{D \rightarrow K}_+(0) * |V_{cs}|$ from BaBar and CLEO-c leads to the most precise direct determination of the CKM matrix element $|V_{cs}|$ to date, $|V_{cs}| = 0.961(11)(24)$, where the first error comes from experiment and the second is the lattice QCD theory error. We calculate the ratio $f^{D \rightarrow K}_+(0)/f_{D_s}$ and find $2.986 \pm 0.087$ GeV$^{-1}$ and show that this agrees with experiment.Comment: 23 pages, 31 figures, 11 tables. Added a paragraph in sction VII, and updated with PDG 2010 instead of PDG 200

A Computational Model of Hepatic Energy Metabolism: Understanding Zonated Damage and Steatosis in NAFLD.

In non-alcoholic fatty liver disease (NAFLD), lipid build-up and the resulting damage is known to occur more severely in pericentral cells. Due to the complexity of studying individual regions of the sinusoid, the causes of this zone specificity and its implications on treatment are largely ignored. In this study, a computational model of liver glucose and lipid metabolism is presented which treats the sinusoid as the repeating unit of the liver rather than the single hepatocyte. This allows for inclusion of zonated enzyme expression by splitting the sinusoid into periportal to pericentral compartments. By simulating insulin resistance (IR) and high intake diets leading to the development of steatosis in the model, we identify key differences between periportal and pericentral cells accounting for higher susceptibility to pericentral steatosis. Secondly, variation between individuals is seen in both susceptibility to steatosis and in its development across the sinusoid. Around 25% of obese individuals do not show excess liver fat, whilst 16% of lean individuals develop NAFLD. Furthermore, whilst pericentral cells tend to show higher lipid levels, variation is seen in the predominant location of steatosis from pericentral to pan-sinusoidal or azonal. Sensitivity analysis was used to identify the processes which have the largest effect on both total hepatic triglyceride levels and on the sinusoidal location of steatosis. As is seen in vivo, steatosis occurs when simulating IR in the model, predominantly due to increased uptake, along with an increase in de novo lipogenesis. Additionally, concentrations of glucose intermediates including glycerol-3-phosphate increased when simulating IR due to inhibited glycogen synthesis. Several differences between zones contributed to a higher susceptibility to steatosis in pericentral cells in the model simulations. Firstly, the periportal zonation of both glycogen synthase and the oxidative phosphorylation enzymes meant that the build-up of glucose intermediates was less severe in the periportal hepatocyte compartments. Secondly, the periportal zonation of the enzymes mediating β-oxidation and oxidative phosphorylation resulted in excess fats being metabolised more rapidly in the periportal hepatocyte compartments. Finally, the pericentral expression of de novo lipogenesis contributed to pericentral steatosis when additionally simulating the increase in sterol-regulatory element binding protein 1c (SREBP-1c) seen in NAFLD patients in vivo. The hepatic triglyceride concentration was predicted to be most sensitive to inter-individual variation in the activity of enzymes which, either directly or indirectly, determine the rate of free fatty acid (FFA) oxidation. The concentration was most strongly dependent on the rate constants for β-oxidation and oxidative phosphorylation. It also showed moderate sensitivity to the rate constants for processes which alter the allosteric inhibition of β-oxidation by acetyl-CoA. The predominant sinusoidal location of steatosis meanwhile was most sensitive variations in the zonation of proteins mediating FFA uptake or triglyceride release as very low density lipoproteins (VLDL). Neither the total hepatic concentration nor the location of steatosis showed strong sensitivity to variations in the lipogenic rate constants

Update: Precision D_s decay constant from full lattice QCD using very fine lattices

We update our previous determination of both the decay constant and the mass of the $D_s$ meson using the Highly Improved Staggered Quark formalism. We include additional results at two finer values of the lattice spacing along with improved determinations of the lattice spacing and improved tuning of the charm and strange quark masses. We obtain $m_{D_s}$ = 1.9691(32) GeV, in good agreement with experiment, and $f_{D_s}$ = 0.2480(25) GeV. Our result for $f_{D_s}$ is 1.6$\sigma$ lower than the most recent experimental average determined from the $D_s$ leptonic decay rate and using $V_{cs}$ from CKM unitarity. Combining our $f_{D_s}$ with the experimental rate we obtain a direct determination of $V_{cs} = 1.010(22)$, or alternatively $0.990 {+0.013 \atop -0.016}$ using a probability distribution for statistical errors for this quantity which vanishes above 1. We also include an accurate prediction of the decay constant of the $\eta_c$, $f_{\eta_c}$ = 0.3947(24) GeV, as a calibration point for other lattice calculations.Comment: 24 pages, 20 figures. Updated to include new experimental results from BaBar, new experimental averages from HFAG and consequent discussion of theory/experiment comparison. Other minor typographical changes. Version accepted by Phys. Rev.

A process systems Engineering approach to analysis of fructose consumption in the liver system and consequences for Non-Alcoholic fatty liver disease

Metabolic disturbances to the liver system can induce lipid deposition and subsequently cause non-alcoholic fatty liver disease (NAFLD). Increasing consumption of fructose has been proposed as a crucial risk component in the development of NAFLD. Three potential therapeutic targets in the network were explored using a composite model of liver function. Introducing a fructose enriched diet under insulin resistance conditions was simulated to evaluate the effectiveness of the model in novel therapy design. In vitro experiments were conducted on rat liver samples to assess the robustness of the model predictions. Synergistic application of all three interventional points in silico has been predicted as the most effective treatment to reduce lipid production under both moderate and severe insulin resistance conditions. This study demonstrates how we can use system models together with in vivo experiments to explore the behaviour of the liver system in response to fructose variation and use it to help identify possible drug targets

Fast Fits for Lattice QCD Correlators

We illustrate a technique for fitting lattice QCD correlators to sums of exponentials that is significantly faster than traditional fitting methods --- 10--40 times faster for the realistic examples we present. Our examples are drawn from a recent analysis of the Upsilon spectrum, and another recent analysis of the D -> pi semileptonic form factor. For single correlators, we show how to simplify traditional effective-mass analyses.Comment: 5 pages, 4 figure