Metabolomic Characterization of Human Model of Liver Rejection Identifies Aberrancies Linked to Cyclooxygenase (COX) and Nitric Oxide Synthase (NOS)

BACKGROUND Acute liver rejection (ALR), a significant complication of liver transplantation, burdens patients, healthcare payers, and the healthcare providers due to an increase in morbidity, cost, and resources. Despite clinical resolution, ALR is associated with an increased risk of graft loss. A unique protocol of delayed immunosuppression used in our institute provided a model to characterize metabolomic profiles in human ALR. MATERIAL AND METHODS Twenty liver allograft biopsies obtained 48 hours after liver transplantation in the absence of immunosuppression were studied. Hepatic metabolites were quantitated in these biopsies by liquid chromatography and mass spectroscopy (LC/MS). Metabolite profiles were compared among: 1) biopsies with reperfusion injury but no histological evidence of rejection (n=7), 2) biopsies with histological evidence of moderate or severe rejection (n=5), and 3) biopsies with histological evidence of mild rejection (n=8). RESULTS There were 133 metabolites consistently detected by LC/MS and these were prioritized using variable importance to projection (VIP) analysis, comparing moderate or severe rejection vs. no rejection or mild rejection using partial least squares discriminant statistical analysis (PLS-DA). Twenty metabolites were identified as progressively different. Further PLS-DA using these metabolites identified 3 metabolites (linoleic acid, γ-linolenic acid, and citrulline) which are associated with either cyclooxygenase or nitric oxide synthase functionality. CONCLUSIONS Hepatic metabolic aberrancies associated with cyclooxygenase and nitric oxide synthase function occur contemporaneous with ALR. Additional studies are required to better characterize the role of these metabolic pathways to enhance utility of the metabolomics approach in diagnosis and outcomes of ALR

A Linear First-Order Functional Intermediate Language for Verified Compilers

We present the linear first-order intermediate language IL for verified compilers. IL is a functional language with calls to a nondeterministic environment. We give IL terms a second, imperative semantic interpretation and obtain a register transfer language. For the imperative interpretation we establish a notion of live variables. Based on live variables, we formulate a decidable property called coherence ensuring that the functional and the imperative interpretation of a term coincide. We formulate a register assignment algorithm for IL and prove its correctness. The algorithm translates a functional IL program into an equivalent imperative IL program. Correctness follows from the fact that the algorithm reaches a coherent program after consistently renaming local variables. We prove that the maximal number of live variables in the initial program bounds the number of different variables in the final coherent program. The entire development is formalized in Coq.Comment: Addressed comments from reviewers (ITP 2015): (1) Added discussion of a paper in related work (2) Added definition of renamed-apart in appendix (3) Formulation changes in a coupe of place

A dependent nominal type theory

Nominal abstract syntax is an approach to representing names and binding pioneered by Gabbay and Pitts. So far nominal techniques have mostly been studied using classical logic or model theory, not type theory. Nominal extensions to simple, dependent and ML-like polymorphic languages have been studied, but decidability and normalization results have only been established for simple nominal type theories. We present a LF-style dependent type theory extended with name-abstraction types, prove soundness and decidability of beta-eta-equivalence checking, discuss adequacy and canonical forms via an example, and discuss extensions such as dependently-typed recursion and induction principles

Maternal plasma docosahexaenoic acid (DHA) concentrations increase at the critical time of neural tube closure

No abstract available

Lambda-lifting and CPS conversion in an imperative language

This paper is a companion technical report to the article "Continuation-Passing C: from threads to events through continuations". It contains the complete version of the proofs of correctness of lambda-lifting and CPS-conversion presented in the article.Comment: arXiv admin note: substantial text overlap with arXiv:1011.455

Self-oscillations in an Alpha Stirling Engine: a bifurcation analysis

We study a thermo-mechanical system comprised of an alpha Stirling engine and a flywheel from the perspective of dynamical systems theory. Thermodynamics establish a static relation between the flywheel's angle and the forces exerted by the two power pistons that constitute the engine. Mechanics, in turn, provide a dynamic relation between the forces and the angle, ultimately leading to a closed dynamical model. We are interested in the different behaviors that the engine displays as parameters are varied. The temperature of the hot piston and the mechanical phase between both pistons constitute our bifurcation parameters. Considering that energy conversion in the engine can only take place through cyclic motions, we are particularly interested in the appearance of limit cycles.Comment: To be submitte

CRANKITE: a fast polypeptide backbone conformation sampler

Background: CRANKITE is a suite of programs for simulating backbone conformations of polypeptides and proteins. The core of the suite is an efficient Metropolis Monte Carlo sampler of backbone conformations in continuous three-dimensional space in atomic details. Methods: In contrast to other programs relying on local Metropolis moves in the space of dihedral angles, our sampler utilizes local crankshaft rotations of rigid peptide bonds in Cartesian space. Results: The sampler allows fast simulation and analysis of secondary structure formation and conformational changes for proteins of average length

Regularization modeling for large-eddy simulation of diffusion flames

We analyze the evolution of a diffusion flame in a turbulent mixing layer using large-eddy simulation. The large-eddy simulation includes Leray regularization of the convective transport and approximate inverse filtering to represent the chemical source terms. The Leray model is compared to the more conventional dynamic mixed model. The location of the flame-center is defined by the 'stoichiometric' interface. Geometrical properties such as its surface-area and wrinkling are characterized using an accurate numerical level-set quadrature method. This allows to quantify flame-properties as well as turbulence modulation effects due to coupling between combustion and turbulent transport. We determine the active flame-region that is responsible for the main part of the chemical conversion in the flame and compare direct and large-eddy simulation predictions