Intergenerational Metabolomic Analysis of Mothers with a History of Gestational Diabetes Mellitus and Their Offspring

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.     

Effects of category prototypes on performance-rating accuracy.

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)     

Expanding the MOS: Development and Psychometric Evaluation of the MOS-R and MOS-X

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.     

Error-free 10 Gbit/s transmission using individual Fabry-Perot modes of low-noise quantum-dot laser

A comb-generating laser suitable for DWDM application is demonstrated on the basis of a multimode quantum-dot laser. Bit error rate < 10^-13 at 10 Gbit/s external modulation was measured for 10 longitudinal modes owing to low (<0.3% over 0.001-10 GHz) relative intensity noise of each individual mode.     

Development of Covalent Chitosan-Polyethylenimine Derivatives as Gene Delivery Vehicle: Synthesis,Characterization, and Evaluation

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; M_W 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.     

Interleukin 6 and Aneurysmal Subarachnoid Hemorrhage. A Narrative Review

Interleukin 6 (IL-6) is a prominent proinflammatory cytokine. Neuroinflammation in general, and IL-6 signaling in particular, appear to play a major role in the pathobiology and pathophysiology of aneurysm formation and aneurysmal subarachnoid hemorrhage (SAH). Most importantly, elevated IL-6 CSF (rather than serum) levels appear to correlate with delayed cerebral ischemia (DCI, “vasospasm”) and secondary (“vasospastic”) infarctions. IL-6 CSF levels may also reflect other forms of injury to the brain following SAH, i.e., early brain damage and septic complications of SAH and aneurysm treatment. This would explain why many researchers have found an association between IL-6 levels and patient outcomes. These findings clearly suggest CSF IL-6 as a candidate biomarker in SAH patients. However, at this point, discrepant findings in variable study settings, as well as timing and other issues, e.g., defining proper clinical endpoints (i.e., secondary clinical deterioration vs. angiographic vasospasm vs. secondary vasospastic infarct) do not allow for its routine use. It is also tempting to speculate about potential therapeutic measures targeting elevated IL-6 CSF levels and neuroinflammation in SAH patients. Corticosteroids and anti-platelet drugs are indeed used in many SAH cases (not necessarily with the intention to interfere with detrimental inflammatory signaling), however, no convincing benefit has been demonstrated yet. The lack of a robust clinical perspective against the background of a relatively large body of data linking IL-6 and neuroinflammation with the pathophysiology of SAH is somewhat disappointing. One underlying reason might be that most relevant studies only report correlative data. The specific molecular pathways behind elevated IL-6 levels in SAH patients and their various interactions still remain to be delineated. We are optimistic that future research in this field will result in a better understanding of the role of neuroinflammation in the pathophysiology of SAH, which in turn, will translate into the identification of suitable biomarkers and even potential therapeutic targets.     

Distortion Engineering - Identification of Causes for Dimensional and Form Deviations of Bearing Rings

Distortion of power transmission parts after heat treatment is influenced by each step of the process chain, ranging from material production to hard-machining. However, an experimental analysis for each production step in the manufacture of bearing rings has shown that distortion is significantly influenced by turning before heat treatment. Elastic ring deformation caused by fixing the workpiece in the chuck leads to a variation of the depth of cut and polygonal form deviations occur after machining. In addition the cutting process induces locally varying residual stresses which also contribute to dimensional and form deviations of machined rings. In this paper results from experimental investigations of the principle physical causes for the distortion of bearing rings are presented and discussed. Finally, strategies for the minimization of distortion are derived.     

Protein design to understand peptide ligand recognition by tetratricopeptide repeat proteins

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.     

Hydrogenation of 3,4-epoxy-1-butene over Cu–Pd/SiO2 catalysts prepared by electroless deposition

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.     

The mechanism of CO oxidation over Cu(110): Effect of CO gas energy

The effect of the temperature of gas phase CO upon the kinetics of the oxygen titration reaction: CO_g +O_a CO_2,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.