Concordance rate between copy number variants detected using either high- or medium-density single nucleotide polymorphism genotype panels and the potential of imputing copy number variants from flanking high density single nucleotide polymorphism haplotypes in cattle

peer-reviewedBackground The trading of individual animal genotype information often involves only the exchange of the called genotypes and not necessarily the additional information required to effectively call structural variants. The main aim here was to determine if it is possible to impute copy number variants (CNVs) using the flanking single nucleotide polymorphism (SNP) haplotype structure in cattle. While this objective was achieved using high-density genotype panels (i.e., 713,162 SNPs), a secondary objective investigated the concordance of CNVs called with this high-density genotype panel compared to CNVs called from a medium-density panel (i.e., 45,677 SNPs in the present study). This is the first study to compare CNVs called from high-density and medium-density SNP genotypes from the same animals. High (and medium-density) genotypes were available on 991 Holstein-Friesian, 1015 Charolais, and 1394 Limousin bulls. The concordance between CNVs called from the medium-density and high-density genotypes were calculated separately for each animal. A subset of CNVs which were called from the high-density genotypes was selected for imputation. Imputation was carried out separately for each breed using a set of high-density SNPs flanking the midpoint of each CNV. A CNV was deemed to be imputed correctly when the called copy number matched the imputed copy number. Results For 97.0% of CNVs called from the high-density genotypes, the corresponding genomic position on the medium-density of the animal did not contain a called CNV. The average accuracy of imputation for CNV deletions was 0.281, with a standard deviation of 0.286. The average accuracy of imputation of the CNV normal state, i.e. the absence of a CNV, was 0.982 with a standard deviation of 0.022. Two CNV duplications were imputed in the Charolais, a single CNV duplication in the Limousins, and a single CNV duplication in the Holstein-Friesians; in all cases the CNV duplications were incorrectly imputed. Conclusion The vast majority of CNVs called from the high-density genotypes were not detected using the medium-density genotypes. Furthermore, CNVs cannot be accurately predicted from flanking SNP haplotypes, at least based on the imputation algorithms routinely used in cattle, and using the SNPs currently available on the high-density genotype panel

Adaptive homodyne measurement of optical phase

We present an experimental demonstration of the power of real-time feedback in quantum metrology, confirming a theoretical prediction by Wiseman regarding the superior performance of an adaptive homodyne technique for single-shot measurement of optical phase. For phase measurements performed on weak coherent states with no prior knowledge of the signal phase, we show that the variance of adaptive homodyne estimation approaches closer to the fundamental quantum uncertainty limit than any previously demonstrated technique. Our results underscore the importance of real-time feedback for reaching quantum performance limits in coherent telecommunication, precision measurement and information processing.Comment: RevTex4, color PDF figures (separate files), submitted to PR

Initial Survey of Engineering Technology Capstone Courses and TeamworkBuilding Using CATME

This paper represents a first step in what is to become a multi –institutional initiative focused on identifying best practices for developing and improving teamwork skills within the Capstone experiences of engineering, technology and computing programs. Teamwork in this paper is defined and measured as the dimensions measured by the CATME Peer Review [1], which is currently used by thousands of technology and engineering instructors and institutions worldwide. The CATME Peer Review measurement tool is used to collect self and peer evaluations of team members’ contributions on five different teamwork dimensions [2]. These teamwork dimensions are 1) pose the knowledge, skills, and abilities to help the team; 2) expect quality work from the team; 3) keep the team on schedule; 4) positive interactions between teammates to help the team; and 5) all team members contribute to the team\u27s work and success. Pung and Farris[3] used CATME in a one semester junior level design class and reported a “significant improvement” in student behavior when compared to the old system of peer review. A workshop was developed to assemble all the participants, and develop a systematic method of evaluating teamwork building using CATME. All the participating schools and faculty will be testing changes in their Capstone courses and sharing the results of this analysis, in teamwork skills, with their colleagues

Polycrystalline Crusts in Accreting Neutron Stars

The crust of accreting neutron stars plays a central role in many different observational phenomena. In these stars, heavy elements produced by H-He burning in the rapid proton capture (rp-) process continually freeze to form new crust. In this paper, we explore the expected composition of the solid phase. We first demonstrate using molecular dynamics that two distinct types of chemical separation occur, depending on the composition of the rp-process ashes. We then calculate phase diagrams for three-component mixtures and use them to determine the allowed crust compositions. We show that, for the large range of atomic numbers produced in the rp-process ($Z\sim 10$--$50$), the solid that forms has only a small number of available compositions. We conclude that accreting neutron star crusts should be polycrystalline, with domains of distinct composition. Our results motivate further work on the size of the compositional domains, and have implications for crust physics and accreting neutron star phenomenology.Comment: 8 pages, 4 figures, Submitted to ApJ, this article supersedes arXiv:1709.0926

A combined Fourier transform infrared and Cr K-edge X-ray absorption near-edge structure spectroscopy study of the substitution and diffusion of H in Cr-doped forsterite

International audienceSingle crystals of synthetic Cr-doped forsterite (Cr:Mg2SiO4) containing both Cr3+ and Cr4+ were partially hydroxylated in piston-cylinder apparatuses at 750-1300 degrees C and pressures from 0.5 to 2.5 GPa, with P(H2O) approximate to P-total. The oxygen fugacity (fO(2)) was buffered by graphite-water, Ni-NiO, Re-ReO2, Fe2O3-Fe3O4 or Ag-Ag2O, and the silica activity (a SiO2) was buffered by powdered forsterite plus either enstatite (Mg2Si2O6), periclase (MgO) or zircon-baddeleyite (ZrSiO4-ZrO2). Profiles of OH content versus distance from the crystal edge were determined using Fourier transform infrared (FTIR) spectroscopy, and profiles of the oxidation state and coordination geometry of Cr were obtained, at the same positions, using K-edge X-ray absorption near-edge structure (XANES) spectroscopy. The techniques are complementary - FTIR spectroscopy images the concentration and nature of O-H bonds, where Cr K-edge XANES spectroscopy shows the effect of the added H on the speciation of Cr already present in the lattice. Profiles of defect-specific absorbance derived from FTIR spectra were fitted to solutions of Fick's second law to derive diffusion coefficients, which yield the Arrhenius relationship for H diffusion in forsterite: log(10)(D) over tilde ([001]) = -2.5 +/- 0.6 + -(224 +/- 12 + 4.0 +/- 2.0 P)/2.303 RT , where (D) over tilde is the measured diffusion coefficient in m(2) s(-1), valid for diffusion parallel to [001] and calibrated between 1000 and 750 degrees C, P and T are in GPa and K, and R is 0.008314 kJK(-1) mol(-1). Diffusivity parallel to [100] is around 1 order of magnitude lower. This is consistent with previous determinations of H diffusion associated with M-site vacancies. The FTIR spectra represent a variety of Cr-bearing hydrous defects, along with defects associated with the pure Mg-Si-O-H system. It is proposed that all of the defects can form by interaction between the dry lattice, including Cr3+ and Cr4+, and fully hydroxylated M-site vacancies. The initial diffusive wave of hydroxylation is associated with neither reduction nor oxidation of Cr but with Cr4+ changing from tetrahedral to octahedral coordination. Superimposed on the H diffusion and concomitant change in Cr4+ site occupancy, but at a slower rate, producing shorter profiles, is reduction of Cr4+ to Cr3+ and potentially of Cr4+ and Cr3+ to Cr2+. In addition, by comparing FTIR data to trace element contents measured by laser ablation inductively coupled plasma mass spectrometry (LA-ICP-MS), constraints can be placed on absorption coefficients used for converting absorbance to H2O contents - our data support either wavenumber- or defect-dependent values of absorption coefficients. We estimate absorption coefficients of between 60 200 and 68 200 L mol(-1) cm(-1) for OH- associated with octahedral Cr3+ and an M-site vacancy and 18 700 to 24 900 L mol(-1) cm(-1) for two OH- associated with octahedrally coordinated Cr4+ and a Si vacancy (i.e. a clinohumite-type point defect)

Safety of guidewire-based measurement of fractional flow reserve and the index of microvascular resistance using intravenous adenosine in patients with acute or recent myocardial infarction

Aims: Coronary guidewire-based diagnostic assessments with hyperemia may cause iatrogenic complications. We assessed the safety of guidewire-based measurement of coronary physiology, using intravenous adenosine, in patients with an acute coronary syndrome. Methods: We prospectively enrolled invasively managed STEMI and NSTEMI patients in two simultaneously conducted studies in 6 centers (NCT01764334; NCT02072850). All of the participants underwent a diagnostic coronary guidewire study using intravenous adenosine (140 μg/kg/min) infusion for 1–2 min. The patients were prospectively assessed for the occurrence of serious adverse events (SAEs) and symptoms and invasively measured hemodynamics were also recorded. Results: 648 patients (n = 298 STEMI patients in 1 hospital; mean time to reperfusion 253 min; n = 350 NSTEMI in 6 hospitals; median time to angiography from index chest pain episode 3 (2, 5) days) were included between March 2011 and May 2013. Two NSTEMI patients (0.03% overall) experienced a coronary dissection related to the guidewire. No guidewire dissections occurred in the STEMI patients. Chest symptoms were reported in the majority (86%) of patient's symptoms during the adenosine infusion. No serious adverse events occurred during infusion of adenosine and all of the symptoms resolved after the infusion ceased. Conclusions: In this multicenter analysis, guidewire-based measurement of FFR and IMR using intravenous adenosine was safe in patients following STEMI or NSTEMI. Self-limiting symptoms were common but not associated with serious adverse events. Finally, coronary dissection in STEMI and NSTEMI patients was noted to be a rare phenomenon

Large-area epitaxial growth of curvature-stabilized ABC trilayer graphene.

The properties of van der Waals (vdW) materials often vary dramatically with the atomic stacking order between layers, but this order can be difficult to control. Trilayer graphene (TLG) stacks in either a semimetallic ABA or a semiconducting ABC configuration with a gate-tunable band gap, but the latter has only been produced by exfoliation. Here we present a chemical vapor deposition approach to TLG growth that yields greatly enhanced fraction and size of ABC domains. The key insight is that substrate curvature can stabilize ABC domains. Controllable ABC yields ~59% were achieved by tailoring substrate curvature levels. ABC fractions remained high after transfer to device substrates, as confirmed by transport measurements revealing the expected tunable ABC band gap. Substrate topography engineering provides a path to large-scale synthesis of epitaxial ABC-TLG and other vdW materials

Boundary Layer Transition Results From STS-114

The tool for predicting the onset of boundary layer transition from damage to and/or repair of the thermal protection system developed in support of Shuttle Return to Flight is compared to the STS-114 flight results. The Boundary Layer Transition (BLT) Tool is part of a suite of tools that analyze the aerothermodynamic environment of the local thermal protection system to allow informed disposition of damage for making recommendations to fly as is or to repair. Using mission specific trajectory information and details of each damage site or repair, the expected time of transition onset is predicted to help determine the proper aerothermodynamic environment to use in the subsequent thermal and stress analysis of the local structure. The boundary layer transition criteria utilized for the tool was developed from ground-based measurements to account for the effect of both protuberances and cavities and has been calibrated against flight data. Computed local boundary layer edge conditions provided the means to correlate the experimental results and then to extrapolate to flight. During STS-114, the BLT Tool was utilized and was part of the decision making process to perform an extravehicular activity to remove the large gap fillers. The role of the BLT Tool during this mission, along with the supporting information that was acquired for the on-orbit analysis, is reviewed. Once the large gap fillers were removed, all remaining damage sites were cleared for reentry as is. Post-flight analysis of the transition onset time revealed excellent agreement with BLT Tool predictions

Second-generation nitazoxanide derivatives: thiazolides are effective inhibitors of the influenza A virus

Aim: The only small molecule drugs currently available for treatment of influenza A virus (IAV) are M2 ion channel blockers and sialidase inhibitors. The prototype thiazolide, nitazoxanide, has successfully completed Phase III clinical trials against acute uncomplicated influenza. Results: We report the activity of seventeen thiazolide analogs against A/PuertoRico/8/1934(H1N1), a laboratory-adapted strain of the H1N1 subtype of IAV, in a cell culture-based assay. A total of eight analogs showed IC50s in the range of 0.14–5.0 μM. Additionally a quantitative structure–property relationship study showed high correlation between experimental and predicted activity based on a molecular descriptor set. Conclusion: A range of thiazolides show useful activity against an H1N1 strain of IAV. Further evaluation of these molecules as potential new small molecule therapies is justified