Background The relationship between plasma concentrations of betaine and choline metabolism and major cardiovascular disease (CVD) end points remains unclear. We have evaluated the association between metabolites from the choline pathway and risk of incident CVD and the potential modifying effect of Mediterranean diet interventions. Methods and Results We designed a case‐cohort study nested within the PREDIMED (Prevention With Mediterranean Diet) trial, including 229 incident CVD cases and 751 randomly selected participants at baseline, followed up for 4.8 years. We used liquid chromatography–tandem mass spectrometry to measure, at baseline and at 1 year of follow‐up, plasma concentrations of 5 metabolites in the choline pathway: trimethylamine N‐oxide, betaine, choline, phosphocholine, and α‐glycerophosphocholine. We have calculated a choline metabolite score using a weighted sum of these 5 metabolites. We used weighted Cox regression models to estimate CVD risk. The multivariable hazard ratios (95% confidence intervals) per 1‐ SD increase in choline and α‐glycerophosphocholine metabolites were 1.24 (1.05–1.46) and 1.24 (1.03–1.50), respectively. The baseline betaine/choline ratio was inversely associated with CVD . The baseline choline metabolite score was associated with a 2.21‐fold higher risk of CVD across extreme quartiles (95% confidence interval, 1.36–3.59; P <0.001 for trend) and a 2.27‐fold higher risk of stroke (95% confidence interval, 1.24–4.16; P <0.001 for trend). Participants in the higher quartiles of the score who were randomly assigned to the control group had a higher risk of CVD compared with participants in the lower quartile and assigned to the Mediterranean diet groups ( P =0.05 for interaction). No significant associations were observed for 1‐year changes in individual plasma metabolites and CVD . Conclusions A metabolite score combining plasma metabolites from the choline pathway was associated with an increased risk of CVD in a Mediterranean population at high cardiovascular risk. Clinical Trial Registration URL : http://www.controlled-trials.com . Unique identifier: ISRCTN 35739639.
No abstract is provided for this article.
Drainage channels are essential components of englacial and subglacial hydrologic systems. Here, we use the M integral, a path-independent integral of the equations of continuum mechanics for a class of media, to unify descriptions of creep closure under a variety of stress states surrounding drainage channels. The advantage of this approach is that the M integral around the hydrologic channels is identical to same integral evaluated in the far field. In this way, the creep closure on the channel wall can be determined as a function of the far-field loading, e.g., involving antiplane shear as well as overburden pressure. We start by analyzing the axisymmetric case and show that the Nye solution for the creep closure of the channels is implied by the path independence of the M integral. We then examine the effects of superimposing antiplane shear. We show that the creep closure of the channels acts as a perturbation in the far field, which we explore analytically and numerically. In this way, the creep closure of channels can be succinctly written in terms of the path-independent M integral, and understanding the variation with applied shear is useful for glacial hydrology models.
There is some controversy over the analysis of the peel test when there is significant plastic deformation. To resolve this controversy a round robin on it
This report describes a method for patterning ligands onto mixed SAMs of alkanethiolates on gold by microcontact printing (μCP). The mixed SAMs were made from thiols presenting terminal tri(ethylene glycol) groups (HS(CH2)11(OCH2CH2)3OH, 1) and terminal hexa(ethylene glycol)−CH2CO2H groups (HS(CH2)11(OCH2CH2)6OCH2CO2H, 2). Ligands were printed using a two-step procedure. The carboxylic acid groups of 2 were first converted to reactive pentafluorophenyl esters. A freshly oxidized PDMS stamp, inked with a ligand derivatized with a primary amine, was then brought into contact with the activated SAM; in the areas of contact, the amine reacted with the activated ester and formed an amide. Two ligands, biotin and benzenesulfonamide, were printed onto these SAMs. The formation of patterned SAMs presenting biotin ligands was detected by fluorescence microscopy of substrates that were incubated with a solution of fluorescently labeled antibiotin antibody. The formation of patterned biotin was also detected using a sandwich experiment; in this experiment, the SAM was incubated sequentially in solutions of streptavidin, protein G-biotin conjugate, and fluorescently labeled goat antirabbit IgG. The smallest features resolved in images obtained by these methods were squares with a 5 μm side. Using surface plasmon resonance (SPR) to detect binding of antibiotin antibody to SAMs presenting biotin groups, the yield of coupling by μCP was estimated to be ∼90% of that obtained by immersion. Printing of the benzenesulfonamide ligand was detected by binding of carbonic anhydrase (CA) to the sulfonamide-derivatized SAMs; the yield of coupling, as estimated by SPR, was ∼ 75% of that obtained by immersion. For both ligands, oxidation of the PDMS stamp before inking was found to be critical for good coupling yields.
The deformation in thin ductile metal layers bonding elastic adherends is constrained. This constraint produces stress distribution with a large component of hydrostatic tension, such that the normal stress on the interfaces can greatly exceed the tensile flow strength of the layer material. The interaction of such stress fields with small incipient interface cracks is studied in this paper. Three models are analyzed: (a) pre-existing stationary cracks, (b) cracks which “nucleate” on a pre-loaded interface, and (c) cracks which grow along the pre-stressed interface, shielded by a thin plasticity-free region. A striking feature is a highly selective size dependence of the cracking process. A crack having a diameter roughly one half the layer thickness experiences significantly higher loading intensity than either larger or smaller cracks. This feature is related to recent experimental observations on interface debonding at thin ductile layers.
Abstract Enzymes have great potential as catalysts for use in synthetic organic chemistry. Applications of enzymes in synthesis have so far been limited to a relatively small number of largescale hydrolytic processes used in industry, and to a large number of small‐scale syntheses of materials used in analytical procedures and in research. Changes in the technology for production of enzymes (in part attributable to improved methods from classical microbiology, and in part to the promise of genetic engineering) and for their stabilization and manipulation now make these catalysts practical for wider use in large‐scale synthetic organic chemistry. This paper reviews the status of the rapidly developing field of enzyme‐catalyzed organic synthesis, and outlines both present opportunities and probable future developments in this field.
