Publications

The fabrication of arrays of Schottky diodes on p-type silicon is described using a representative soft lithographic technique: micromolding in capillaries (MIMIC). It is demonstrated that soft lithography is compatible with multilayer fabrication of electronically functional structures. The characteristics of the diodes were found to be similar to those fabricated by photolithography. The advantages and limitations of MIMIC are outlined, with particular attention being paid to the degree of registration of features that can be achieved.

This paper combines two techniques--mass spectrometry and protein charge ladders--to examine the relationship between the surface charge and hydrophobicity of a representative globular protein (bovine carbonic anhydrase II; BCA II) and its rate of amide hydrogen-deuterium (H/D) exchange. Mass spectrometric analysis indicated that the sequential acetylation of surface lysine-ε-NH3(+) groups--a type of modification that increases the net negative charge and hydrophobicity of the surface of BCA II without affecting its secondary or tertiary structure--resulted in a linear decrease in the aggregate rate of amide H/D exchange at pD 7.4, 15 °C. According to analysis with MS, the acetylation of each additional lysine generated between 1.4 and 0.9 additional hydrogens that are protected from H/D exchange during the 2 h exchange experiment at 15 °C, pD 7.4. NMR spectroscopy demonstrated that none of the hydrogen atoms which became protected upon acetylation were located on the side chain of the acetylated lysine residues (i.e., lys-ε-NHCOCH3) but were instead located on amide NHCO moieties in the backbone. The decrease in rate of exchange associated with acetylation paralleled a decrease in thermostability: the most slowly exchanging rungs of the charge ladder were the least thermostable (as measured by differential scanning calorimetry). This observation--that faster rates of exchange are associated with slower rates of denaturation--is contrary to the usual assumptions in protein chemistry. The fact that the rates of H/D exchange were similar for perbutyrated BCA II (e.g., [lys-ε-NHCO(CH2)2CH3]18) and peracetylated BCA II (e.g., [lys-ε-NHCOCH3]18) suggests that the electrostatic charge is more important than the hydrophobicity of surface groups in determining the rate of H/D exchange. These electrostatic effects on the kinetics of H/D exchange could complicate (or aid) the interpretation of experiments in which H/D exchange methods are used to probe the structural effects of non-isoelectric perturbations to proteins (i.e., phosphorylation, acetylation, or the binding of the protein to an oligonucleotide or to another charged ligand or protein).

respective flavour characteristics being achieved by controlling the wort composition and fermentation conditions.

Introduction The aim of the study was to determine the association of body mass index (BMI), self-reported symptoms or diagnosis of polycystic ovary syndrome (PCOS), and hyperandrogenemia with the occurrence of gestational diabetes mellitus (GDM) through reproductive life. Material and methods A cohort of women born in 1966 were investigated at ages 14, 31 and 46. Women with self-reported PCOS symptoms (presence of both oligo-amenorrhea and hirsutism) at age 31 or with formally diagnosed polycystic ovaries (PCO)/PCOS by age 46 formed the group of self-reported PCOS (srPCOS, n = 222) and were compared with women without self-reported PCOS symptoms or diagnosis (n = 1357). We investigated also the association of hyperandrogenism (hirsutism or biochemical hyperandrogenism) at age 31 with the occurrence of GDM throughout reproductive life. Results Self-reported PCOS alone was not a risk factor for GDM, but combined with overweight at age 31 (odds ratio [OR] 2.43, 95% confidence interval [CI] 1.22-4.86) or 46 (OR 3.04, 95% CI 1.58-5.83) srPCOS was associated with GDM when compared with normal weight controls. The association disappeared when comparing overweight srPCOS women with overweight controls. However, hyperandrogenemia at age 31, but not hirsutism, was associated with GDM even after adjustment for BMI. Conclusions The increased risk of GDM in women with srPCOS was mostly attributed to overweight or obesity. Importantly, normal weight women with srPCOS did not seem to be at increased risk for developing GDM. However, hyperandrogenemia was associated with GDM even after adjustment for BMI. These findings strengthen the importance of weight management in reproductive-age women and suggest a noteworthy role of hyperandrogenemia in the pathophysiology of GDM.

<h3>Objective:</h3> To apply genetic analysis of genome-wide association data to study the extent and nature of a shared biological basis between migraine and coronary artery disease (CAD). <h3>Methods:</h3> Four separate methods for cross-phenotype genetic analysis were applied on data from 2 large-scale genome-wide association studies of migraine (19,981 cases, 56,667 controls) and CAD (21,076 cases, 63,014 controls). The first 2 methods quantified the extent of overlapping risk variants and assessed the load of CAD risk loci in migraineurs. Genomic regions of shared risk were then identified by analysis of covariance patterns between the 2 phenotypes and by querying known genome-wide significant loci. <h3>Results:</h3> We found a significant overlap of genetic risk loci for migraine and CAD. When stratified by migraine subtype, this was limited to migraine without aura, and the overlap was protective in that patients with migraine had a lower load of CAD risk alleles than controls. Genes indicated by 16 shared risk loci point to mechanisms with potential roles in migraine pathogenesis and CAD, including endothelial dysfunction (<i>PHACTR1</i>) and insulin homeostasis (<i>GIP</i>). <h3>Conclusions:</h3> The results suggest that shared biological processes contribute to risk of migraine and CAD, but surprisingly this commonality is restricted to migraine without aura and the impact is in opposite directions. Understanding the mechanisms underlying these processes and their opposite relationship to migraine and CAD may improve our understanding of both disorders.

Background and Aims: Low-calorie weight loss diets with different macronutrient compositions have shown to result in clinically meaningful long-term weight loss. We aimed to identify plasma metabolites that significantly changed over two years in an intervention trial of low-calorie weight-loss diets with varying amounts of fats, carbohydrates, and proteins, and to investigate which changes in plasma metabolites are linked to better long-term weight loss. Materials and methods: The present study included participants who were randomly assigned to one of 4 diets in the POUNDS Lost trial. Untargeted plasma metabolomics was performed; changes in 856 metabolites across various metabolic pathways from baseline to the end of the two-year intervention were calculated in 533 participants. Results: We observed 571 metabolites (67%) showing statistically significant changes ( P- FDR &lt; 0.05) following the two-year diet intervention (Figure panel a). We also identified core metabolites that significantly changed across all diet groups as well as specific metabolites that changed only in each of the 4 diet groups (panel b). Of the significantly modified metabolites by diets, 239 were significantly associated with 2-year weight changes, while others were not linked to weight loss (panel c). When stratifying by diet group, we identified 230 metabolites related to weight loss in response to one of the 4 diet interventions, including 22 metabolites within the lactoyl amino acid pathways, which showed the strongest sub-pathway associations with weight changes over two years in all diet groups. Conclusion: Our study identified core and specific metabolic pathways associated with changes in all or each of three macronutrients that contribute to better long-term weight loss.

We evaluated pubertal growth and pubertal timing of participants born preterm compared to those born at term. In the ESTER Preterm Birth Study, we collected growth data and measured final height of men/women born very or moderately preterm (<34 gestational weeks, n = 52/55), late preterm (34–<37 weeks, 94/106), and term (≥37 weeks, 131/151), resulting in median 9 measurements at ≥6 years. Timing of menarche or voice break was self-reported. Peak height velocity (PHV, cm/year) and age at PHV (years) were compared with SuperImposition by Translation And Rotation (SITAR) model (sexes separately). Age at PHV (years) and PHV (cm/year) were similar in all gestational age groups. Compared to term controls, insignificant differences in age at PHV were 0.1 (95% CI: −0.2 to 0.4) years/0.2 (−0.1 to 0.4) for very or moderately/late preterm born men and −0.0 (−0.3 to 0.3)/−0.0 (−0.3 to 0.2) for women, respectively. Being born small for gestational age was not associated with pubertal growth. Age at menarche or voice break was similar in all the gestational age groups. Timing of pubertal growth and age at menarche or voice break were similar in participants born preterm and at term.