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1.
Shared metabolomic patterns at delivery have been suggested to underlie the mother-to-child transmission of adverse metabolic health. This study aimed to investigate whether mothers with gestational diabetes mellitus (GDM) and their offspring show similar metabolomic patterns several years postpartum. Targeted metabolomics (including 137 metabolites) was performed in plasma samples obtained during an oral glucose tolerance test from 48 mothers with GDM and their offspring at a cross-sectional study visit 8 years after delivery. Partial Pearson’s correlations between the area under the curve (AUC) of maternal and offspring metabolites were calculated, yielding so-called Gaussian graphical models. Spearman’s correlations were applied to investigate correlations of body mass index (BMI), Matsuda insulin sensitivity index (ISI-M), dietary intake, and physical activity between generations, and correlations of metabolite AUCs with lifestyle variables. This study revealed that BMI, ISI-M, and the AUC of six metabolites (carnitine, taurine, proline, SM(-OH) C14:1, creatinine, and PC ae C34:3) were significantly correlated between mothers and offspring several years postpartum. Intergenerational metabolite correlations were independent of shared BMI, ISI-M, age, sex, and all other metabolites. Furthermore, creatinine was correlated with physical activity in mothers. This study suggests that there is long-term metabolic programming in the offspring of mothers with GDM and informs us about targets that could be addressed by future intervention studies.  相似文献   
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This paper describes an approach, conceptual framework, and software architecture for dynamic reconfiguration of the order picking system. The research and development project was sponsored by the Material Handling Research Center (MHRC), a National Science Foundation sponsored Cooperative Industry/University Research Center. The storage configuration is assumed to be an in-the-aisle order picking system in which stockkeeping units (SKUs) can occupy variable capacity storage locations and stock-splitting is allowed among zones (clusters). The product mix may include multiple product families with different life cycles, correlated demand within families and commonality of demand across families.  相似文献   
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Two studies examined whether the accessibility of performance prototypes influences performance appraisals. Pilot studies revealed students used performance prototypes when rating instructor performance. Study 1 manipulated the accessibility of these prototypes and the time delay of performance ratings. Results showed no effect of the prime on rating error and accuracy; however, discrimination accuracy decreased over time and recognition bias became more conservative. Study 2 manipulated prototype accessibility and type of rating stimuli (videotape vs. vignette). Rating accuracy and recall were higher for vignette than videotape stimuli, and only those participants exposed to the vignette exhibited priming effects. Results supported transfer-appropriate processing and implied that cognitive primes may have a stronger effect on performance ratings based on "paper-people" than videotaped stimuli. (PsycINFO Database Record (c) 2010 APA, all rights reserved)  相似文献   
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The Mean Opinion Scale (MOS) is a questionnaire used to obtain listeners' subjective assessments of synthetic speech. This paper documents the motivation, method, and results of six experiments conducted from 1999 to 2002 that investigated the psychometric properties of the MOS and expanded the range of speech characteristics it evaluates. Our initial experiments documented the reliability, validity, sensitivity, and factor structure of the P.L. Salza et al. (Acta Acustica, Vol. 82, pp. 650–656, 1996) MOS and used psychometric principles to revise and improve the scale. This work resulted in the MOS-Revised (MOS-R). Four subsequent experiments expanded the MOS-R beyond its previous focus on Intelligibility and Naturalness, to include measurement of the Prosody and Social Impression of synthetic voices. As a result of this work, we created the MOS-Expanded (MOS-X), a rating scale shown to be reliable, valid, and sensitive for high-quality evaluation of synthetic speech in applied industrial settings.  相似文献   
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There is an increasing interest in cationic polymers as important constituents of non-viral gene delivery vectors. In the present study, we developed a versatile synthetic route for the production of covalent polymeric conjugates consisting of water-soluble depolymerized chitosan (dCS; MW 6–9 kDa) and low molecular weight polyethylenimine (PEI; 2.5 kDa linear, 1.8 kDa branched). dCS-PEI derivatives were evaluated based on their physicochemical properties, including purity, covalent bonding, solubility in aqueous media, ability for DNA condensation, and colloidal stability of the resulting polyplexes. They were complexed with non-integrating DNA vectors coding for reporter genes by simple admixing and assessed in vitro using liver-derived HuH-7 cells for their transfection efficiency and cytotoxicity. Using a rational screening cascade, a lead compound was selected (dCS-Suc-LPEI-14) displaying the best balance of biocompatibility, cytotoxicity, and transfection efficiency. Scale-up and in vivo evaluation in wild-type mice allowed for a direct comparison with a commercially available non-viral delivery vector (in vivo-jetPEI). Hepatic expression of the reporter gene luciferase resulted in liver-specific bioluminescence, upon intrabiliary infusion of the chitosan-based polyplexes, which exceeded the signal of the in vivo jetPEI reference formulation by a factor of 10. We conclude that the novel chitosan-derivative dCS-Suc-LPEI-14 shows promise and potential as an efficient polymeric conjugate for non-viral in vivo gene therapy.  相似文献   
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Protein design aims to understand the fundamentals of protein structure by creating novel proteins with pre-specified folds. An equally important goal is to understand protein function by creating novel proteins with pre-specified activities. Here we describe the design and characterization of a tetratricopeptide (TPR) protein, which binds to the C-terminal peptide of the eukaryotic chaperone Hsp90. The design emphasizes the importance of both direct, short-range protein-peptide interactions and of long-range electrostatic optimization. We demonstrate that the designed protein binds specifically to the desired peptide and discriminates between it and the similar C-terminal peptide of Hsp70.  相似文献   
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Electroless deposition has been used to prepare Cu–Pd/SiO2 bimetallic catalysts wherein initial Cu coverages are limited only to the pre-existing Pd surface. Cu loading on the Pd surface can be systematically varied by modification of deposition kinetic parameters. In this case deposition time was used as the kinetic variable for the preparation of a series of Cu–Pd catalysts. These materials have been characterized using atomic absorption, CO chemisorption, and FT-IR (adsorption of CO), and then evaluated for the hydrogenation of 3,4-epoxy-1-butene, a functionalized olefin having many potential reaction pathways. Catalyst performance and characterization results suggest that Cu is not distributed in a monodisperse manner on the Pd surface, indicating the existence of autocatalytic deposition of Cu on Cu sites. The FT-IR results suggest that although CO adsorption on all sites is suppressed by Cu addition, initial Cu deposition occurs more readily on certain sites. The bimetallic Cu–Pd sites that are formed exhibit unusually high activity for EpB conversion and formation of unsaturated alcohols and aldehydes. This bimetallic effect on catalyst activity and selectivity is best explained, not by the existence of either ligand or ensemble effects, but rather by the bifunctional nature of the Cu–Pd sites present on the surface of these catalysts.  相似文献   
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The effect of the temperature of gas phase CO upon the kinetics of the oxygen titration reaction: COg +Oa CO2,g, has been studied. It is found that the reaction's rate is independant of CO gas temperature between 300 and 623 K. The activation energy (6.5 kcal/mole), dependence upon CO pressure (first-order), and independence upon oxygen coverage for 0.1 o 0.4 are all independant of the CO gas phase temperature. This result rules out any Eley-Rideal type mechanism whereby CO reacts directly from the gas phase with an oxygen adatom without first being accommodated to the surface temperature in an absorbed state. The result is instead interpretable in terms of a Langmuir-Hinshelwood mechanism.Camille and Henry Dreyfus Foundation Teacher-Scholar Fellowship.  相似文献   
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