A systems model of phosphorylation for inflammatory signaling events

published_or_final_versio

Enhancing energy and glucose metabolism by disrupting triglyceride synthesis: Lessons from mice lacking DGAT1

Although the ability to make triglycerides is essential for normal physiology, excess accumulation of triglycerides results in obesity and is associated with insulin resistance. Inhibition of triglyceride synthesis, therefore, may represent a feasible strategy for the treatment of obesity and type 2 diabetes. Acyl CoA:diacylglycerol acyltransferase 1 (DGAT1) is one of two DGAT enzymes that catalyze the final reaction in the known pathways of mammalian triglyceride synthesis. Mice lacking DGAT1 have increased energy expenditure and insulin sensitivity and are protected against diet-induced obesity and glucose intolerance. These metabolic effects of DGAT1 deficiency result in part from the altered secretion of adipocyte-derived factors. Studies of DGAT1-deficient mice have helped to provide insights into the mechanisms by which cellular lipid metabolism modulates systemic carbohydrate and insulin metabolism, and a better understanding of how DGAT1 deficiency enhances energy expenditure and insulin sensitivity may identify additional targets or strategies for the treatment of obesity and type 2 diabetes

Photoproducts of indomethacin exhibit decreased hydroxyl radical scavenging and xanthine oxidase inhibition activities

AbstractIndomethacin (IN) is a widely used nonsteroidal anti-inflammatory drug. In this study, four photoproducts of IN (IN1–IN4) were produced and isolated from photoirradiated IN. This study investigated the abilities of IN and its photoproducts to scavenge hydroxyl radicals and inhibit xanthine oxidase (XO). The hydroxyl radical-scavenging activity was measured in vitro by electron spin resonance spectrometry using 5,5-dimethyl-1-pyrroline-N-oxide as a spin trapping agent. Enzyme activity was measured by continuous monitoring of uric acid formation, using xanthine as a substrate. The results showed that, among all the related products, IN has the strongest hydroxyl radical-scavenging (IC50 = 65 μM) and XO inhibitory (IC50 = 86 μM) effects. To further understand the stereochemistry of the reactions between these IN derivatives and XO, we performed computer-aided molecular modeling. IN was the most potent inhibitor with the most favorable interaction in the reactive site. Various photoproducts exhibited affinity toward XO as a result of the absence of hydrogen bonding with molybdopterin domain

The stau exchange contribution to muon g-2 in the decoupling solution

We study the possibility that the lepton-flavor changing process can induce the suitable magnitude of the muon anomalous magnetic moment (g_\mu -2) in the decoupling solution to the flavor problem in the minimal supersymmetric standard model. Our analyses introduce the flavor mixings of left- and right-handed stau and smuon phenomenologically. It is found that if both the left- and right-handed sleptons have sizable flavor mixings, the correction to g_\mu -2 from the lighter slepton can reach to 10^{-9} while the correction to the branching ratio of \tau \to \mu \gamma satisfies the current experimental bound. On the other hand, when only the left-handed or right-handed sleptons have the large flavor mixing, the suitable magnitude of the correction to g_\mu-2 is not realized owing to the experimental bound of \tau \to \mu \gamma.Comment: 11 pages, latex2e with axodraw.sty, comments and reference adde

Ultrasensitive, high-dynamic-range and broadband strain sensing by time-of-flight detection with femtosecond-laser frequency combs

Ultrahigh-resolution optical strain sensors provide powerful tools in various scientific and engineering fields, ranging from long-baseline interferometers to civil and aerospace industries. Here we demonstrate an ultrahigh-resolution fibre strain sensing method by directly detecting the time-of-flight (TOF) change of the optical pulse train generated from a free-running passively mode-locked laser (MLL) frequency comb. We achieved a local strain resolution of 18 p{\epsilon}/Hz1/2 and 1.9 p{\epsilon}/Hz1/2 at 1 Hz and 3 kHz, respectively, with largedynamic range of >154 dB at 3 kHz. For remote-point sensing at 1-km distance, 80 p{\epsilon}/Hz1/2 (at 1 Hz) and 2.2 p{\epsilon}/Hz1/2 (at 3 kHz) resolution is demonstrated. While attaining both ultrahigh resolution and large dynamic range, the demonstrated method can be readily extended for multiple-point sensing as well by taking advantage of the broad optical comb spectra. These advantages may allow various applications of this sensor in geophysical science, structural health monitoring, and underwater science.Comment: 20 pages, 4 figure

BEHAVIOR OF REGULAR TRIANGULAR JOINTS UNDER CYCLIC SHEARING

ABSTRACT Synthetic regular triangular joints made of gypsum plaster were cyclicly sheared to measure asperity degradation and mathematical behavior of regular triangular joints. Laboratory cyclic shear tests were conducted for three joint types under three different normal stresses. Asperity degradation and shear strength of joints were found to be a function of joint roughness, normal stress, shearing displacement and number of loading cycles. Based on the experimental results, mathematical models were developed for evaluation of shear strength in cyclic loading conditions. Comparison of the test results with that of the proposed model, it was found a good agreement was observed

Proton Driven Plasma Wakefield Acceleration

Plasma wakefield acceleration, either laser driven or electron-bunch driven, has been demonstrated to hold great potential. However, it is not obvious how to scale these approaches to bring particles up to the TeV regime. In this paper, we discuss the possibility of proton-bunch driven plasma wakefield acceleration, and show that high energy electron beams could potentially be produced in a single accelerating stage.Comment: 13 pages, 4 figure