Novel genotyping algorithms for rare variants significantly improve the accuracy of Applied Biosystems™ Axiom™ array genotyping calls: Retrospective evaluation of UK Biobank array data.

The UK Biobank genotyped about 500k participants using Applied Biosystems Axiom microarrays. Participants were subsequently sequenced by the UK Biobank Exome Sequencing Consortium. Axiom genotyping was highly accurate in comparison to sequencing results, for almost 100,000 variants both directly genotyped on the UK Biobank Axiom array and via whole exome sequencing.

Electronically steered metasurface antenna.

Mobile devices, climate science, and autonomous vehicles all require advanced microwave antennas for imaging, radar, and wireless communications. We propose a waveguide-fed metasurface antenna architecture that enables electronic beamsteering from a lightweight circuit board with varactor-tuned elements. Our approach uses a unique feed structure and layout that enables spatial sampling at the Nyquist limit of half a wavelength.

Development and validation of a universal blood donor genotyping platform: a multinational prospective study.

Each year, blood transfusions save millions of lives. However, under current blood-matching practices, sensitization to non-self-antigens is an unavoidable adverse side effect of transfusion. We describe a universal donor typing platform that could be adopted by blood services worldwide to facilitate a universal extended blood-matching policy and reduce sensitization rates.

Dynamic Metasurface Aperture as Smart Around-the-Corner Motion Detector.

Detecting and analysing motion is a key feature of Smart Homes and the connected sensor vision they embrace. At present, most motion sensors operate in line-of-sight Doppler shift schemes. Here, we propose an alternative approach suitable for indoor environments, which effectively constitute disordered cavities for radio frequency (RF) waves; we exploit the fundamental sensitivity of modes of such cavities to perturbations, caused here by moving objects.

Computational polarimetric microwave imaging.

We propose a polarimetric microwave imaging technique that exploits recent advances in computational imaging. We utilize a frequency-diverse cavity-backed metasurface, allowing us to demonstrate high-resolution polarimetric imaging using a single transceiver and frequency sweep over the operational microwave bandwidth. The frequency-diverse metasurface imager greatly simplifies the system architecture compared with active arrays and other conventional microwave imaging approaches.

Millimeter-wave spotlight imager using dynamic holographic metasurface antennas.

Computational imaging systems leverage generalized measurements to produce high-fidelity images, enabling novel and often lower cost hardware platforms at the expense of increased processing. However, obtaining full resolution images across a large field-of-view (FOV) can lead to slow reconstruction times, limiting system performance where faster frame rates are desired. In many imaging scenarios, the highest resolution is needed only in smaller subdomains of interest within a scene, suggesting an aperture supporting multiple modalities of image capture with different resolutions can provide a path to system optimization.

Large Metasurface Aperture for Millimeter Wave Computational Imaging at the Human-Scale.

We demonstrate a low-profile holographic imaging system at millimeter wavelengths based on an aperture composed of frequency-diverse metasurfaces. Utilizing measurements of spatially-diverse field patterns, diffraction-limited images of human-sized subjects are reconstructed. The system is driven by a single microwave source swept over a band of frequencies (17.

Phaseless computational imaging with a radiating metasurface.

Computational imaging modalities support a simplification of the active architectures required in an imaging system and these approaches have been validated across the electromagnetic spectrum. Recent implementations have utilized pseudo-orthogonal radiation patterns to illuminate an object of interest-notably, frequency-diverse metasurfaces have been exploited as fast and low-cost alternative to conventional coherent imaging systems. However, accurately measuring the complex-valued signals in the frequency domain can be burdensome, particularly for sub-centimeter wavelengths.

Spatially resolving antenna arrays using frequency diversity.

Radio imaging devices and synthetic aperture radar typically use either mechanical scanning or phased arrays to illuminate a target with spatially varying radiation patterns. Mechanical scanning is unsuitable for many high-speed imaging applications, and phased arrays contain many active components and are technologically and cost prohibitive at millimeter and terahertz frequencies. We show that antennas deliberately designed to produce many different radiation patterns as the frequency is varied can reduce the number of active components necessary while still capturing high-quality images.

Frequency-diverse microwave imaging using planar Mills-Cross cavity apertures.

We demonstrate a frequency diverse, multistatic microwave imaging system based on a set of transmit and receive, radiating, planar cavity apertures. The cavities consist of double-sided, copper-clad circuit boards, with a series of circular radiating irises patterned into the upper conducting plate. The iris arrangement is such that for any given transmitting and receiving aperture pair, a Mills-Cross pattern is formed from the overlapped patterns.

Comprehensive simulation platform for a metamaterial imaging system.

Recently, a frequency-diverse, metamaterial-based aperture has been introduced in the context of microwave and millimeter wave imaging. The generic form of the aperture is that of a parallel plate waveguide, in which complementary metamaterial elements patterned into the upper plate couple energy from the waveguide mode to the scene. To reliably predict the imaging performance of such an aperture prior to fabrication and experiments, it is necessary to have an accurate forward model that predicts radiation from the aperture, a model for scattering from an arbitrary target in the scene, and a set of image reconstruction approaches that allow scene estimation from an arbitrary set of measurements.

Genotyping Informatics and Quality Control for 100,000 Subjects in the Genetic Epidemiology Research on Adult Health and Aging (GERA) Cohort.

The Kaiser Permanente (KP) Research Program on Genes, Environment and Health (RPGEH), in collaboration with the University of California-San Francisco, undertook genome-wide genotyping of >100,000 subjects that constitute the Genetic Epidemiology Research on Adult Health and Aging (GERA) cohort. The project, which generated >70 billion genotypes, represents the first large-scale use of the Affymetrix Axiom Genotyping Solution. Because genotyping took place over a short 14-month period, creating a near-real-time analysis pipeline for experimental assay quality control and final optimized analyses was critical.

Flagellar kinematics and swimming of algal cells in viscoelastic fluids.

The motility of microorganisms is influenced greatly by their hydrodynamic interactions with the fluidic environment they inhabit. We show by direct experimental observation of the bi-flagellated alga Chlamydomonas reinhardtii that fluid elasticity and viscosity strongly influence the beating pattern - the gait - and thereby control the propulsion speed. The beating frequency and the wave speed characterizing the cyclical bending are both enhanced by fluid elasticity.

Tunable capillary-induced attraction between vertical cylinders.

Deformation of a fluid interface caused by the presence of objects at the interface can lead to large lateral forces between objects. We explore these fluid-mediated attractive force between partially submerged vertical cylinders. Forces are experimentally measured by slowly separating cylinder pairs and cylinder triplets after capillary rise is initially established for cylinders in contact.

Metamaterial microwave holographic imaging system.

We demonstrate a microwave imaging system that combines advances in metamaterial aperture design with emerging computational imaging techniques. The flexibility inherent to guided-wave, complementary metamaterials enables the design of a planar antenna that illuminates a scene with dramatically varying radiation patterns as a function of frequency. As frequency is swept over the K-band (17.

MicroRNA polymorphisms and risk of colorectal cancer.

Background: miRNAs act as post-transcriptional regulators of gene expression. Genetic variation in miRNA-encoding sequences or their corresponding binding sites may affect the fidelity of the miRNA-mRNA interaction and subsequently alter the risk of cancer development.

Methods: This study expanded the search for miRNA-related polymorphisms contributing to the etiology of colorectal cancer across the genome using a novel platform, the Axiom miRNA Target Site Genotyping Array (237,858 markers).

Rheology of soft colloids across the onset of rigidity: scaling behavior, thermal, and non-thermal responses.

We study the rheological behavior of colloidal suspensions composed of soft sub-micron-size hydrogel particles across the liquid-solid transition. The measured stress and strain-rate data, when normalized by thermal stress and time scales, suggest our systems reside in a regime wherein thermal effects are important. In a different vein, critical point scaling predictions for the jamming transition, typical in athermal systems, are tested.

Flagellar waveform dynamics of freely swimming algal cells.

We present quantitative measurements of time-dependent flagellar waveforms for freely swimming biflagellated algal cells, for both synchronous and asynchronous beating. We use the waveforms in conjunction with resistive force theory as well as a singularity method to predict a cell's time-dependent velocity for comparison with experiments. While net propulsion is thought to arise from asymmetry between the power and recovery strokes, we show that hydrodynamic interactions between the flagella and cell body on the return stroke make an important contribution to enhance net forward motion.

Light localization, photon sorting, and enhanced absorption in subwavelength cavity arrays.

A periodically patterned metal-dielectric composite material is designed, fabricated and characterized that spatially splits incoming microwave radiation into two spectral ranges, individually channeling the separate spectral bands to different cavities within each spatially repeating unit cell. Further, the target spectral bands are absorbed within each associated set of cavities. The photon sorting mechanism, the design methodology, and experimental methods used are all described in detail.

Genome-wide maps of circulating miRNA biomarkers for ulcerative colitis.

Inflammatory Bowel Disease--comprised of Crohn's Disease and Ulcerative Colitis (UC)--is a complex, multi-factorial inflammatory disorder of the gastrointestinal tract. In this study we have explored the utility of naturally occurring circulating miRNAs as potential blood-based biomarkers for non-invasive prediction of UC incidences. Whole genome maps of circulating miRNAs in micro-vesicles, Peripheral Blood Mononuclear Cells and platelets have been constructed from a cohort of 20 UC patients and 20 normal individuals.

Dynamical heterogeneity in soft-particle suspensions under shear.

We present experimental measurements of dynamical heterogeneities in a dense system of microgel spheres, sheared at different rates and at different packing fractions in a microfluidic channel, and visualized with high-speed digital video microscopy. A four-point dynamic susceptibility is deduced from video correlations, and is found to exhibit a peak that grows in height and shifts to longer times as the jamming transition is approached from two different directions. In particular, the time for particle-size root-mean square relative displacements is found to scale as τ*∼(γΔφ4)(-1), where γ is the strain rate and Δφ = |φ - φ(c)| is the distance from the random close-packing volume fraction.

Design and coverage of high throughput genotyping arrays optimized for individuals of East Asian, African American, and Latino race/ethnicity using imputation and a novel hybrid SNP selection algorithm.

Four custom Axiom genotyping arrays were designed for a genome-wide association (GWA) study of 100,000 participants from the Kaiser Permanente Research Program on Genes, Environment and Health. The array optimized for individuals of European race/ethnicity was previously described. Here we detail the development of three additional microarrays optimized for individuals of East Asian, African American, and Latino race/ethnicity.

Impact of cellular miRNAs on circulating miRNA biomarker signatures.

Effective diagnosis and surveillance of complex multi-factorial disorders such as cancer can be improved by screening of easily accessible biomarkers. Highly stable cell free Circulating Nucleic Acids (CNA) present as both RNA and DNA species have been discovered in the blood and plasma of humans. Correlations between tumor-associated genomic/epigenetic/transcriptional changes and alterations in CNA levels are strong predictors of the utility of this biomarker class as promising clinical indicators.

Enhancement of biomixing by swimming algal cells in two-dimensional films.

Fluid mixing in active suspensions of microorganisms is important to ecological phenomena and presents a fascinating stochastic process. We investigate the mixing produced by swimming unicellular algal cells (Chlamydomonas) in quasi-two-dimensional liquid films by simultaneously tracking the motion of the cells and that of microscopic passive tracer particles advected by the fluid. The reduced spatial dimension of the system leads to long-range flows and a surprisingly strong dependence of tracer transport on the concentration of swimmers, which is explored over a wide range.

Next generation genome-wide association tool: design and coverage of a high-throughput European-optimized SNP array.

The success of genome-wide association studies has paralleled the development of efficient genotyping technologies. We describe the development of a next-generation microarray based on the new highly-efficient Affymetrix Axiom genotyping technology that we are using to genotype individuals of European ancestry from the Kaiser Permanente Research Program on Genes, Environment and Health (RPGEH). The array contains 674,517 SNPs, and provides excellent genome-wide as well as gene-based and candidate-SNP coverage.