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Genotype-phenotype association studies often combine phenotype data from multiple studies to increase statistical power. Harmonization of the data usually requires substantial effort due to heterogeneity in phenotype definitions, study design, data collection procedures, and data-set organization. Here we describe a centralized system for phenotype harmonization that includes input from phenotype domain and study experts, quality control, documentation, reproducible results, and data-sharing mechanisms. This system was developed for the National Heart, Lung, and Blood Institute’s Trans-Omics for Precision Medicine (TOPMed) program, which is generating genomic and other -omics data for more than 80 studies with extensive phenotype data. To date, 63 phenotypes have been harmonized across thousands of participants (recruited in 1948–2012) from up to 17 studies per phenotype. Here we discuss challenges in this undertaking and how they were addressed. The harmonized phenotype data and associated documentation have been submitted to National Institutes of Health data repositories for controlled access by the scientific community. We also provide materials to facilitate future harmonization efforts by the community, which include 1) the software code used to generate the 63 harmonized phenotypes, enabling others to reproduce, modify, or extend these harmonizations to additional studies, and 2) the results of labeling thousands of phenotype variables with controlled vocabulary terms., Peer Reviewed, Postprint (published version)

The capacitance system of a hyperboloidal tip and a rough surface is usually encountered in analyzing electrostatic force microscopy images. In this letter, a perturbation approach has been applied to solve for the electric potential of this system, in which the rough surface is treated as perturbation from a flat one. For the first-variation solution, the boundary value problem is represented in the prolate-spheroidal coordinate system and solved in terms of a generalized Fourier series involving conical functions. Based on this solution, the tip-surface Coulombic interaction can be computed. Sample calculations have been applied to sinusoidal surface profiles, Peer Reviewed, Postprint (published version)

Kelvin probe force microscopy KPFM is designed for measuring the tip-sample contact potential differences by probing the sample surface, measuring the electrostatic interaction, and adjusting a feedback circuit. However, for the case of a dielectric insulating sample, the contact potential difference may be ill defined, and the KPFM probe may be sensing electrostatic interactions with a certain distribution of sample trapped charges or dipoles, leading to difficulty in interpreting the images.We have proposed a general framework based on boundary integral equations for simulating the KPFM image based on the knowledge about the sample charge distributions forward problem and a deconvolution algorithm solving for the trapped charges on the surface from an image inverse problem . The forward problem is a classical potential problem, which can be efficiently solved using the boundary element method. Nevertheless, the inverse problem is ill posed due to data incompleteness. For some special cases, we have developed deconvolution algorithms based on the forward problem solution. As an example, this algorithm is applied to process the KPFM image of a gadolinia-doped ceria thin film to solve for its surface charge density, which is a more relevant quantity for samples of this kind than the contact potential difference normally only defined for conductive samples values contained in the raw image., Peer Reviewed, Postprint (published version)

The objective of this project was to establish the theoretical foundations for applying higher order Rayleigh and interface modes to resonators for high stability sensors. Theoretical studies of the characteristics of Rayleigh waves in single and multi-layer structures were carried out for ST-cut Quartz substrates. Specified materials for this study were MgO, Y2O3, AlN, SiOx, Al2O3, and TiO2. Velocity dispersion and coupling to bulk modes were predicted and confirmed by comparison with experimental results for sputtered films. Stoneley (interfacial) waves were investigated as possible candidates for resonator structures because of their inherently stable and low cost geometry without any type of hermetic enclosure or package. A successful search technique was developed which accurately predicts the existence of Stoneley waves in general anisotropic (and piezoelectric) materials. Using this technique, Stoneley waves were for the first time predicted in single crystal quartz. Several useful orientations where Stoneley waves are well bound and piezoelectrically active were found to exist., Prepared in cooperation with Stanford Univ., Palo Alto, CA. Materials Science and Engineering.