Quasi-Lagrangian Systems of Newton Equations

Systems of Newton equations of the form $\ddot{q}=-{1/2}A^{-1}(q)\nabla k$ with an integral of motion quadratic in velocities are studied. These equations generalize the potential case (when A=I, the identity matrix) and they admit a curious quasi-Lagrangian formulation which differs from the standard Lagrange equations by the plus sign between terms. A theory of such quasi-Lagrangian Newton (qLN) systems having two functionally independent integrals of motion is developed with focus on two-dimensional systems. Such systems admit a bi-Hamiltonian formulation and are proved to be completely integrable by embedding into five-dimensional integrable systems. They are characterized by a linear, second-order PDE which we call the fundamental equation. Fundamental equations are classified through linear pencils of matrices associated with qLN systems. The theory is illustrated by two classes of systems: separable potential systems and driven systems. New separation variables for driven systems are found. These variables are based on sets of non-confocal conics. An effective criterion for existence of a qLN formulation of a given system is formulated and applied to dynamical systems of the Henon-Heiles type.Comment: 50 pages including 9 figures. Uses epsfig package. To appear in J. Math. Phy

An economical biorefinery process for propionic acid production from glycerol and potato juice using high cell density fermentation.

An economically sustainable process was developed for propionic acid production by fermentation of glycerol using Propionibacterium acidipropionici and potato juice, a by-product of starch processing, as a nitrogen/vitamin source. The fermentation was done as high-cell-density sequential batches with cell recycle. Propionic acid production and glycerol consumption rates were dependent on initial biomass concentration, and reached a maximum of 1.42 and 2.30gL(-1)h(-1), respectively, from 50gL(-1) glycerol at initial cell density of 23.7g(CDW)L(-1). Halving the concentration of nitrogen/vitamin source resulted in reduction of acetic and succinic acids yields by ∼39% each. At glycerol concentrations of 85 and 120gL(-1), respectively, 43.8 and 50.8gL(-1) propionic acid were obtained at a rate of 0.88 and 0.29gL(-1)h(-1) and yield of 84 and 78mol%. Succinic acid was 13g% of propionic acid and could represent a potential co-product covering the cost of nitrogen/vitamin source

Production of glycidyl ethers by chemo-enzymatic epoxidation of allyl ethers

Production of glycidyl ethers is industrially carried Out by reacting alcohols with epichlorhydrin, a potentially carcinogenic compound. This paper investigates a less hazardous alternative-that of a chemo-enzymatic process in which Candida antarctica lipase B catalysed generation of peracid from a carboxylic acid is followed by a Prileshajev epoxidation of the corresponding allyl ether. Trimethylolpropane monoallyl ether (TMPME) was used as a model substrate. A maximal epoxide product yield of 77% was achieved through the optimization of temperature. acid concentration and hydrogen peroxide concentration. Peracid formation was considerably faster than the subsequent epoxidation step, and accumulation of the peracid was Found to be important to drive the epoxidation forward. (C) 2008 Elsevier B.V. All rights reserved

Constrained Simulations of the Real Universe: the Local Supercluster

We present cosmological simulations which closely mimic the real Universe within 100Mpc of the Local Group. The simulations, called Constrained Simulations, reproduce the large-scale density field with major nearby structures, including the Local Group, the Coma and Virgo clusters, the Great Attractor, the Perseus-Pices, and the Local Supercluster, in approximately correct locations. The MARK III survey of peculiar velocities of the observed structures inside 80Mpc/h sphere is used to constrain the initial conditions. Fourier modes on scales larger then 5Mpc/h are dominated by the constraints, while small scale waves are random. The main aim of this paper is the structure of the Local Supercluster (LSC; 30Mpc/h around the Virgo cluster) and the Local Group environment. We find that at the current epoch most of the mass (7.5e14Msun/h) of the LSC is located in a filament roughly centered on the Virgo cluster and extending over 40Mpc/h. The simulated Local Group (LG) is located in an adjacent smaller filament, which is not a part of the main body of the LSC, and has a peculiar velocity of 250kms toward the Virgo cluster. The peculiar velocity field in the LSC region is complicated and is drastically different from the field assumed in the Virgocentric infall models. The peculiar velocity flow in the vicinity of the LG in the simulation is ``cold'': the peculiar line-of-sight velocity dispersion within 7Mpc/h of the LG is less than 60km/s, comparable to the observed velocity dispersion of nearby galaxies.Comment: 22 pages, 9 figures, submitted to ApJ, high resolution version is available at http://astro.nmsu.edu/~aklypin/HOFFMA

Genomic correlates of glatiramer acetate adverse cardiovascular effects lead to a novel locus mediating coronary risk

Glatiramer acetate is used therapeutically in multiple sclerosis but also known for adverse effects including elevated coronary artery disease (CAD) risk. The mechanisms underlying the cardiovascular side effects of the medication are unclear. Here, we made use of the chromosomal variation in the genes that are known to be affected by glatiramer treatment. Focusing on genes and gene products reported by drug-gene interaction database to interact with glatiramer acetate we explored a large meta-analysis on CAD genome-wide association studies aiming firstly, to investigate whether variants in these genes also affect cardiovascular risk and secondly, to identify new CAD risk genes. We traced association signals in a 200-kb region around genomic positions of genes interacting with glatiramer in up to 60 801 CAD cases and 123 504 controls. We validated the identified association in additional 21 934 CAD cases and 76 087 controls. We identified three new CAD risk alleles within the TGFB1 region on chromosome 19 that independently affect CAD risk. The lead SNP rs12459996 was genome-wide significantly associated with CAD in the extended meta-analysis (odds ratio 1.09, p = 1.58×10-12). The other two SNPs at the locus were not in linkage disequilibrium with the lead SNP and by a conditional analysis showed p-values of 4.05 × 10-10 and 2.21 × 10-6. Thus, studying genes reported to interact with glatiramer acetate we identified genetic variants that concordantly with the drug increase the risk of CAD. Of these, TGFB1 displayed signal for association. Indeed, the gene has been associated with CAD previously in both in vivo and in vitro studies. Here we establish genome-wide significant association with CAD in large human samples.This work was supported by grants from the Fondation Leducq (CADgenomics: Understanding CAD Genes, 12CVD02), the German Federal Ministry of Education and Research (BMBF) within the framework of the e:Med research and funding concept (e:AtheroSysMed, grant 01ZX1313A-2014 and SysInflame, grant 01ZX1306A), and the European Union Seventh Framework Programme FP7/2007-2013 under grant agreement no HEALTH-F2-2013-601456 (CVgenes-at-target). Further grants were received from the DFG as part of the Sonderforschungsbereich CRC 1123 (B2). T.K. was supported by a DZHK Rotation Grant. I.B. was supported by the Deutsche Forschungsgemeinschaft (DFG) cluster of excellence ‘Inflammation at Interfaces’. F.W.A. is supported by a Dekker scholarship-Junior Staff Member 2014T001 - Netherlands Heart Foundation and UCL Hospitals NIHR Biomedical Research Centre

New genetic loci link adipose and insulin biology to body fat distribution.

Body fat distribution is a heritable trait and a well-established predictor of adverse metabolic outcomes, independent of overall adiposity. To increase our understanding of the genetic basis of body fat distribution and its molecular links to cardiometabolic traits, here we conduct genome-wide association meta-analyses of traits related to waist and hip circumferences in up to 224,459 individuals. We identify 49 loci (33 new) associated with waist-to-hip ratio adjusted for body mass index (BMI), and an additional 19 loci newly associated with related waist and hip circumference measures (P < 5 × 10(-8)). In total, 20 of the 49 waist-to-hip ratio adjusted for BMI loci show significant sexual dimorphism, 19 of which display a stronger effect in women. The identified loci were enriched for genes expressed in adipose tissue and for putative regulatory elements in adipocytes. Pathway analyses implicated adipogenesis, angiogenesis, transcriptional regulation and insulin resistance as processes affecting fat distribution, providing insight into potential pathophysiological mechanisms

Causal effect of plasminogen activator inhibitor type 1 on coronary heart disease

Background--Plasminogen activator inhibitor type 1 (PAI-1) plays an essential role in the fibrinolysis system and thrombosis. Population studies have reported that blood PAI-1 levels are associated with increased risk of coronary heart disease (CHD). However, it is unclear whether the association reflects a causal influence of PAI-1 on CHD risk. Methods and Results--To evaluate the association between PAI-1 and CHD, we applied a 3-step strategy. First, we investigated the observational association between PAI-1 and CHD incidence using a systematic review based on a literature search for PAI-1 and CHD studies. Second, we explored the causal association between PAI-1 and CHD using a Mendelian randomization approach using summary statistics from large genome-wide association studies. Finally, we explored the causal effect of PAI-1 on cardiovascular risk factors including metabolic and subclinical atherosclerosis measures. In the systematic meta-analysis, the highest quantile of blood PAI-1 level was associated with higher CHD risk comparing with the lowest quantile (odds ratio=2.17; 95% CI: 1.53, 3.07) in an age- and sex-adjusted model. The effect size was reduced in studies using a multivariable-adjusted model (odds ratio=1.46; 95% CI: 1.13, 1.88). The Mendelian randomization analyses suggested a causal effect of increased PAI-1 level on CHD risk (odds ratio=1.22 per unit increase of log-transformed PAI-1; 95% CI: 1.01, 1.47). In addition, we also detected a causal effect of PAI-1 on elevating blood glucose and high-density lipoprotein cholesterol. Conclusions--Our study indicates a causal effect of elevated PAI-1 level on CHD risk, which may be mediated by glucose dysfunction