Publications

Increasing cereal fiber in the diet may be an effective means of reducing the risk of type 2 diabetes, a disease that has reached epidemic proportions in black women.

Particles, bubbles, and drops carried by a fluid in a confined environment such as a pipe can be subjected to hydrodynamic lift forces, i.e., forces that are perpendicular to the direction of the flow. We investigated the positioning effect of lift forces acting on buoyant drops and bubbles suspended in a carrier fluid and flowing in a horizontal microchannel. We report experiments on drops of water in fluorocarbon liquid, and on bubbles of nitrogen in hydrocarbon liquid and silicone oil, inside microchannels with widths on the order of 0.1-1 mm. Despite their buoyancy, drops and bubbles could travel without contacting with the walls of channels; the most important parameters for reaching this flow regime in our experiments were the viscosity and the velocity of the carrier fluid, and the sizes of drops and bubbles. The dependencies of the transverse position of drops and bubbles on these parameters were investigated. At steady state, the trajectories of drops and bubbles approached the center of the channel for drops and bubbles almost as large as the channel, carried by rapidly flowing viscous liquids; among our experiments, these flow conditions were characterized by larger capillary numbers and smaller Reynolds numbers. Analytical models of lift forces developed for the flow of drops much smaller than the width of the channel failed to predict their transverse position, while computational fluid dynamic simulations of the experiments agreed better with the experimental measurements. The degrees of success of these predictions indicate the importance of confinement on generating strong hydrodynamic lift forces. We conclude that, inside microfluidic channels, it is possible to support and position buoyant drops and bubbles simply by flowing a single-stream (i.e., "sheathless") carrier liquid that has appropriate velocity and hydrodynamic properties.

Background: The association between monounsaturated fat (MUFA) intake and coronary heart disease (CHD) risk remains unclear. We aimed to investigate whether MUFA from plant foods (MUFA-P) and animal foods (MUFA-A) show different associations with CHD risk in two large prospective studies of U.S. men and women. Method: We calculated MUFA-P and MUFA-A among 60,931 women in the Nurses’ Health Study (1990-2012), and 28,445 men in the Health Professionals Follow-Up Study (1990-2010). Diet was assessed by validated food-frequency questionnaire every 4 years. CHD incidence was self-reported and confirmed by review of medical records or death certificates. Result: MUFA-A (median intake: 5.8-6.1% energy) was highly correlated with saturated fat (SFA; spearman correlation [ r ] =0.81-0.83) but not polyunsaturated fat (PUFA, r =0.04 -0.19), whereas MUFA-P intake (median: 5.3-5.4.9% energy) was strongly correlated with PUFA(r=0.61 for both cohorts) but not SFA ( r =0.20-0.21; All P<0.001). In multivariate models adjusted for demographic, lifestyle, and dietary factors, hazard ratios of CHD (HR, 95% confidence interval[95%CI]) from low to high total MUFA quintiles were 1 (reference), 0.92 (0.83, 1.02), 1.03 (0.93, 1.05), 0.89 (0.79,1.00). 0.95(0.873, 1.08; P trend =0.42). For MUFA P these were 1(reference), 0.98 (0.89, 1.07), 0.90 (0.82, 0.99), 0.85 (0.77, 0.93), and 0.86 (0.78, 0.94; P trend <0.001) and for MUFA-A 1(reference), 1.09 (0.99, 1.20), 1.22 (1.11, 1.35), 1.26 (1.13, 1.39), and 1.33 (1.19, 1.48; P trend <0.001). In the energy-density model, CHD risk was lower when MUFA-P iso-calorically replaced 1% energy from total SFA (HR [95%CI]: 0.96[0.92, 1.00]; P=0.03), with no significant changes when MUFA-A replacing SFA (HR [95%CI]: 1.01[0.95, 1.07]; P=0.76). When grouping fat intake as the sum of animal MUFA plus saturated fat and the sum of plant MUFA plus PUFA, the HR (95%CI) of CHD was 0.96 (0.95, 0.98; P<0.001) for replacing 1% energy from the former with the latter. Conclusion: Because MUFA compositions of animal and plant origins are largely similar, our data suggested other components in plant and animal foods may lead to the observed different associations of MUFA-P and MUFA-A with CHD risk. These findings provided a possible explanation on current controversies regarding MUFA intake and CHD risk, and further support health benefit of MUFA intake.

Abstract The timing of puberty is a highly polygenic childhood trait that is epidemiologically associated with various adult diseases. Here, we analyse 1000-Genome reference panel imputed genotype data on up to ~370,000 women and identify 389 independent signals (all P<5×10 −8 ) for age at menarche, a notable milestone in female pubertal development. In Icelandic data from deCODE, these signals explain ~7.4% of the population variance in age at menarche, corresponding to one quarter of the estimated heritability. We implicate over 250 genes via coding variation or associated gene expression, and demonstrate enrichment across genes active in neural tissues. We identify multiple rare variants near the imprinted genes MKRN3 and DLK1 that exhibit large effects on menarche only when paternally inherited. Disproportionate effects of variants on early or late puberty timing are observed: single variant and heritability estimates are larger for early than late puberty timing in females. The opposite pattern is seen in males, with larger estimates for late than early puberty timing. Mendelian randomization analyses indicate causal inverse associations, independent of BMI, between puberty timing and risks for breast and endometrial cancers in women, and prostate cancer in men. In aggregate, our findings reveal new complexity in the genetic regulation of puberty timing and support new causal links with adult cancer risks.

This letter describes the fabrication of functional GaAs/AlGaAs field effect transistors using micromolding in capillaries—a representative soft lithographic technique. The fabrication process involved three soft lithographic steps and two registration steps. Room temperature characteristics of these transistors resemble those of field effect transistors fabricated by photolithography. The fabrication of functional microelectronic devices using multilayer soft lithography establishes the compatibility of these techniques with the processing methods used in device fabrication, and opens the door for their development as a technique in this area.

Large-scale genome-wide association studies (GWAS) have identified over 40 genomic regions significantly associated with type 2 diabetes mellitus. However, GWAS results are not always straightforward to interpret, and linking these loci to meaningful disease etiology is often difficult without extensive follow-up studies. The authors expanded on previously reported type 2 diabetes mellitus GWAS from the nested case-control studies of 2 prospective US cohorts by incorporating expression single nucleotide polymorphism (SNP) information and applying SNP set enrichment analysis to identify sets of SNPs associated with genes that could provide further biologic insight to traditional genome-wide analysis. Using data collected between 1989 and 1994 in these previous studies to form a nested case-control study, the authors found that 3 of the most significantly associated SNPs to type 2 diabetes mellitus in their study are expression SNPs to the lymphocyte antigen 75 gene (LY75), the ubiquitin-specific peptidase 36 gene (USP36), and the phosphatidylinositol transfer protein, cytoplasmic 1 gene (PITPNC1). SNP set enrichment analysis of the GWAS results identified enrichment for expression SNPs to the macrophage-enriched module and the Gene Ontology (GO) biologic process fat cell differentiation human, which includes the transcription factor 7-like 2 gene (TCF7L2), as well as other type 2 diabetes mellitus-associated genes. Integrating genome-wide association, gene expression, and gene set analysis may provide valuable biologic support for potential type 2 diabetes mellitus susceptibility loci and may be useful in identifying new targets or pathways of interest for the treatment and prevention of type 2 diabetes mellitus.