Obesity and type-2 diabetes arise from the complex interplay of both genetic and environmental factors. In the past several years, we have seen considerable progress in the use of genomics and metabolomics in investigating the role of diet and nutrition in the etiology of obesity and diabetes. Recent work suggests that the adverse effect of several obesity loci especially FTO may be modified by dietary factors. In a recent study (Qi et al. NEJM 2012), we found a significant interaction between consumption of Sugar-Sweetened Beverages (SSBs) and genetic variants related to Body Mass Index (BMI) in three cohort studies. A genetic-predisposition score was calculated on the basis of 32 BMI-associated loci. We found that the genetic association with BMI was more pronounced among participants with higher intake of SSBs than among those with lower intake. In the combined cohorts, the increases in BMI per increment of 10 risk alleles were 1.00 unit for an intake of < 1 serving/month, 1.12 for 1-4 servings/month, 1.38 for 2-6 servings/week, and 1.78 for ≥ 1 servings/day (P<0.001 for interaction). This analysis suggests that the genetic association with adiposity is amplified by greater intakes of SSBs. In the area of nutrition and metabolomics, several recent epidemiological studies have found that plasma concentrations of metabolites especially Branched-Chain Amino Acids (BCAAs) are associated with increased risk of type-2 diabetes. Other novel metabolite classes have also been linked to diabetes, such as short- and medium-chain acylcarnitines, the specific lipid classes of sphingomyelins (SMs), lysophosphatidylcholines, phosphatidylcholines (PCs), and lysophosphatidylethanolamines. Metabolomics has also been used to characterize the complex human metabolic effects of specific foods, nutrients, and dietary patterns in both intervention and epidemiological studies. Our preliminary analysis found that urinary levels of gut flora metabolites derived from dietary intakes of polyphenols were significantly associated with risk of diabetes. In summary, both nutrigenomics and metabolomics studies have provided new insights to the etiology of obesity and diabetes and individual differences in response to diet. Continued technological advances in sensitive high-throughput methods and enhanced bioinformatics and analytical tools in combination with carefully conducted population-based studies will enable more widespread use of these technologies in nutrition and metabolic disease research, which will eventually help to achieve the goal of personalized nutrition for prevention and treatment of chronic diseases.
Previous chapters have frequently pointed out that certain aspects of fracture inmultilayers require complete solutions for stress distributions close to the crack tip. Important examples include mode mix, channeling/tunneling cracks, crack kinking and features with finite length (such as edge cracks or ligaments). While analytical solutions have been presented for a few important cases, a numerical approach is often needed even for relatively simple geometries.
Consider solving a PDE on a domain D using a domain decomposition or Schwarz splitting approach. We decompose D several times, with each level having a finer (more accurate) decomposition than the preceding one. Iterative methods are initiated on each level so long as the higher level iterations have not converged. This is implemented in a parallel computing environment (such as a hypercube machine). The passing of information between levels is asynchronous. Parameters of such a method are (1) number of levels and number of domains per level, (2) number of processors per level, (3) choice of method on the subdomains of each level (and their convergence rates), and (4) the tolerances used to terminate higher level iterations. We report on both analytic and experimental studies of the effectiveness of such methods and of good values for the parameters.
Oxidation of low-density polyethylene film with chromic acid/sulfur acid at 72 C generates a material (PE-CO2H) having a high density of carboxylic acid and ketone functionalities in a thin surface layer on the polymer. Similar oxidation of low density polyethylene powder (powder PE-CO2H) and ultrahigh molecular weight polyethylene (UHMW-CO2H) generate materials having only slightly different properties. This paper determines extent of the ionization of the surface and near-surface carboxylic acis groups of these materials in contact with water as a function of pH using three experimental techniques: measurement of attenuated total reflectance infrared (ATR-IR) spectra, measurement of contact angles, and direct potentiometric titration. The first and third techniques measure the concentrations of carboxylic acid and carboxylate groups throughout the polymer surface and near-surface region. The second technique relies on differences in the hydrophilicity of carboxylic acid and carboxylate groups to produce differences in the polymer-water interfacial free energy. This technique is sensitive primarily to surface functionality. On the basis of correlations between results obtained using these three techniques, we propose an equation (eq 6) relating the contact angel of an aqueous solution having a given value of pH on PE-CO2H and UHMW-CO2H and the extent of ionization of those carboxylic acid groups which are directly exposed to the solution.
The ligand/receptor pair consisting of a synthetic dimeric derivative of vancomycin (V), linked at the C terminus by p-xylylenediamine (V-CONHCH2C6H4CH2NHCO-V), and a dimeric derivative of l-Lys-d-Ala-d-Ala, [CH2CONεH(Nα-Ac)-l-Lys-d-Ala-d-Ala-CO2-]2, provides a new system with which to study the influence of divalency on the strength of binding. A competitive assay using affinity capillary electrophoresis (ACE) has been developed and used to estimate the dissociation constant of the divalent complex (≈ 1.1 nM) and the enhancement in binding (∼103) relative to the corresponding monomeric interaction between unmodified monomeric vancomycin and diacetyl-l-Lys-d-Ala-d-Ala.
: Two parameters are identified for characterizing the deformation in the plastic zone near the tip of a crack when mixed mode conditions prevail. Details of the near-tip stress and strain distributions are presented for hardening materials in which a diffuse plastic zone occurs under plane stress conditions. For small scale yielding the two near-tip parameters are related to the two elastic stress intensity factors for combined Mode I and Mode II. (Author)
Growing evidence has suggested an important role of n-3 polyunsaturated fatty acids in reducing risk of cardiovascular disease in the general population and patients with preexisting heart disease. In particular, several long-term epidemiologic studies have found an inverse association between fish consumption and risk of coronary heart disease or stroke. Two secondary prevention trials have found that increasing fish consumption or fish oil supplementation significantly reduced coronary death among patients with existing myocardial infarction. In addition, epidemiologic and clinical studies have suggested that alpha-linolenic acid (ALA), a short-chain n3-3 fatty acid from plant sources, may have similar cardiac benefits as long-chain n-3 fatty acids from fish. Potential mechanisms through which n-3 polyunsaturated fatty acids protect against CVD include their antiarrhythmic and antithrombotic effects, and improving insulin sensitivity and endothelial function. (c) 2001 Prous Science. All rights reserved.
ADVERTISEMENT RETURN TO ISSUEPREVArticleNEXTMolecular Dynamics Simulations of H2NSO2C6H4CONH(Gly)3OBn Bound to the Active Site of Human Carbonic Anhydrase IIDonovan N. Chin and George M. WhitesidesCite this: J. Am. Chem. Soc. 1995, 117, 23, 6153–6164Publication Date (Print):June 1, 1995Publication History Published online1 May 2002Published inissue 1 June 1995https://pubs.acs.org/doi/10.1021/ja00128a001https://doi.org/10.1021/ja00128a001research-articleACS PublicationsRequest reuse permissionsArticle Views105Altmetric-Citations14LEARN ABOUT THESE METRICSArticle Views are the COUNTER-compliant sum of full text article downloads since November 2008 (both PDF and HTML) across all institutions and individuals. These metrics are regularly updated to reflect usage leading up to the last few days.Citations are the number of other articles citing this article, calculated by Crossref and updated daily. Find more information about Crossref citation counts.The Altmetric Attention Score is a quantitative measure of the attention that a research article has received online. Clicking on the donut icon will load a page at altmetric.com with additional details about the score and the social media presence for the given article. Find more information on the Altmetric Attention Score and how the score is calculated. Share Add toView InAdd Full Text with ReferenceAdd Description ExportRISCitationCitation and abstractCitation and referencesMore Options Share onFacebookTwitterWechatLinked InRedditEmail Other access optionsGet e-AlertscloseSupporting Info (2)»Supporting Information Supporting Information Get e-Alerts