Genetic variants in novel pathways influence blood pressure and cardiovascular disease risk.

Blood pressure is a heritable trait influenced by several biological pathways and responsive to environmental stimuli. Over one billion people worldwide have hypertension (≥140 mm Hg systolic blood pressure or  ≥90 mm Hg diastolic blood pressure). Even small increments in blood pressure are associated with an increased risk of cardiovascular events. This genome-wide association study of systolic and diastolic blood pressure, which used a multi-stage design in 200,000 individuals of European descent, identified sixteen novel loci: six of these loci contain genes previously known or suspected to regulate blood pressure (GUCY1A3-GUCY1B3, NPR3-C5orf23, ADM, FURIN-FES, GOSR2, GNAS-EDN3); the other ten provide new clues to blood pressure physiology. A genetic risk score based on 29 genome-wide significant variants was associated with hypertension, left ventricular wall thickness, stroke and coronary artery disease, but not kidney disease or kidney function. We also observed associations with blood pressure in East Asian, South Asian and African ancestry individuals. Our findings provide new insights into the genetics and biology of blood pressure, and suggest potential novel therapeutic pathways for cardiovascular disease prevention

Genome-wide association study identifies six new loci influencing pulse pressure and mean arterial pressure.

Numerous genetic loci have been associated with systolic blood pressure (SBP) and diastolic blood pressure (DBP) in Europeans. We now report genome-wide association studies of pulse pressure (PP) and mean arterial pressure (MAP). In discovery (N = 74,064) and follow-up studies (N = 48,607), we identified at genome-wide significance (P = 2.7 × 10(-8) to P = 2.3 × 10(-13)) four new PP loci (at 4q12 near CHIC2, 7q22.3 near PIK3CG, 8q24.12 in NOV and 11q24.3 near ADAMTS8), two new MAP loci (3p21.31 in MAP4 and 10q25.3 near ADRB1) and one locus associated with both of these traits (2q24.3 near FIGN) that has also recently been associated with SBP in east Asians. For three of the new PP loci, the estimated effect for SBP was opposite of that for DBP, in contrast to the majority of common SBP- and DBP-associated variants, which show concordant effects on both traits. These findings suggest new genetic pathways underlying blood pressure variation, some of which may differentially influence SBP and DBP

Piezoelectric structural sensor technology for extreme environments

High temperature sensors are desired for down-hole well monitoring, future propulsion components, as well as improving performance and maintainability of power production facilities and other rotary combustion engines. Recently discovered high temperature oxyborate crystals showed stable piezoelectric properties and high resistivity at temperatures close to its melting point (∼ 1500°C, or 2730°F), which is very promising for high temperature sensor applications. In this paper the feasibility of using oxyborate based high temperature piezoelectric crystal (HTPC) for high temperature piezoelectric sensor applications is demonstrated. Oxyborate HTPC with various crystal cuts and vibration modes were investigated to obtain high temperature resistivity, dielectric, piezoelectric and thermal expansion properties. YCa 4O(BO3)3 crystals (YCOB) showed excellent piezoelectricity, low dielectric loss and high resistivity at temperatures up to 1000°C (\u3e 1800°F). The measured thermal expansion coefficients of YCOB are about ∼3-8 ppm/K, depending on different orientations. High temperature accelerometers were demonstrated using YCOB HTPC at temperatures up to 1000°C with sensitivity remaining steady (∼ 2.4 pC/g) across the temperature range of 20°C - 1000°C

Single-Shot Characterization of Enzymatic Reaction Constants <i>K</i>_m and <i>k</i>_cat by an Acoustic-Driven, Bubble-Based Fast Micromixer

In this work we present an acoustofluidic approach for rapid, single-shot characterization of enzymatic reaction constants <i>K</i>_m and <i>k</i>_cat. The acoustofluidic design involves a bubble anchored in a horseshoe structure which can be stimulated by a piezoelectric transducer to generate vortices in the fluid. The enzyme and substrate can thus be mixed rapidly, within 100 ms, by the vortices to yield the product. Enzymatic reaction constants <i>K</i>_m and <i>k</i>_cat can then be obtained from the reaction rate curves for different concentrations of substrate while holding the enzyme concentration constant. We studied the enzymatic reaction for β-galactosidase and its substrate (resorufin-β-D-galactopyranoside) and found <i>K</i>_m and <i>k</i>_cat to be 333 ± 130 μM and 64 ± 8 s^–1, respectively, which are in agreement with published data. Our approach is valuable for studying the kinetics of high-speed enzymatic reactions and other chemical reactions

An integrated, multiparametric flow cytometry chip using “microfluidic drifting” based three-dimensional hydrodynamic focusing

In this work, we demonstrate an integrated, single-layer, miniature flow cytometry device that is capable of multi-parametric particle analysis. The device integrates both particle focusing and detection components on-chip, including a “microfluidic drifting” based three-dimensional (3D) hydrodynamic focusing component and a series of optical fibers integrated into the microfluidic architecture to facilitate on-chip detection. With this design, multiple optical signals (i.e., forward scatter, side scatter, and fluorescence) from individual particles can be simultaneously detected. Experimental results indicate that the performance of our flow cytometry chip is comparable to its bulky, expensive desktop counterpart. The integration of on-chip 3D particle focusing with on-chip multi-parametric optical detection in a single-layer, mass-producible microfluidic device presents a major step towards low-cost flow cytometry chips for point-of-care clinical diagnostics

An On-Chip, Multichannel Droplet Sorter Using Standing Surface Acoustic Waves

The emerging field of droplet microfluidics requires effective on-chip handling and sorting of droplets. In this work, we demonstrate a microfluidic device that is capable of sorting picoliter water-in-oil droplets into multiple outputs using standing surface acoustic waves (SSAW). This device integrates a single-layer microfluidic channel with interdigital transducers (IDTs) to achieve on-chip droplet generation and sorting. Within the SSAW field, water-in-oil droplets experience an acoustic radiation force and are pushed toward the acoustic pressure node. As a result, by tuning the frequency of the SSAW excitation, the position of the pressure nodes can be changed and droplets can be sorted to different outlets at rates up to 222 droplets s^–1. With its advantages in simplicity, controllability, versatility, noninvasiveness, and capability to be integrated with other on-chip components such as droplet manipulation and optical detection units, the technique presented here could be valuable for the development of droplet-based micro total analysis systems (μTAS)