Discovery and Follow-up Observations of the Young Type Ia Supernova 2016coj

The Type~Ia supernova (SN~Ia) 2016coj in NGC 4125 (redshift $z=0.004523$) was discovered by the Lick Observatory Supernova Search 4.9 days after the fitted first-light time (FFLT; 11.1 days before $B$-band maximum). Our first detection (pre-discovery) is merely $0.6\pm0.5$ day after the FFLT, making SN 2016coj one of the earliest known detections of a SN Ia. A spectrum was taken only 3.7 hr after discovery (5.0 days after the FFLT) and classified as a normal SN Ia. We performed high-quality photometry, low- and high-resolution spectroscopy, and spectropolarimetry, finding that SN 2016coj is a spectroscopically normal SN Ia, but with a high velocity of \ion{Si}{2} $\lambda$6355 ($\sim 12,600$\,\kms\ around peak brightness). The \ion{Si}{2} $\lambda$6355 velocity evolution can be well fit by a broken-power-law function for up to a month after the FFLT. SN 2016coj has a normal peak luminosity ($M_B \approx -18.9 \pm 0.2$ mag), and it reaches a $B$-band maximum \about16.0~d after the FFLT. We estimate there to be low host-galaxy extinction based on the absence of Na~I~D absorption lines in our low- and high-resolution spectra. The spectropolarimetric data exhibit weak polarization in the continuum, but the \ion{Si}{2} line polarization is quite strong ($\sim 0.9\% \pm 0.1\%$) at peak brightness.Comment: Submitte

Identification of genetic variants associated with Huntington's disease progression: a genome-wide association study

Background Huntington's disease is caused by a CAG repeat expansion in the huntingtin gene, HTT. Age at onset has been used as a quantitative phenotype in genetic analysis looking for Huntington's disease modifiers, but is hard to define and not always available. Therefore, we aimed to generate a novel measure of disease progression and to identify genetic markers associated with this progression measure. Methods We generated a progression score on the basis of principal component analysis of prospectively acquired longitudinal changes in motor, cognitive, and imaging measures in the 218 indivduals in the TRACK-HD cohort of Huntington's disease gene mutation carriers (data collected 2008–11). We generated a parallel progression score using data from 1773 previously genotyped participants from the European Huntington's Disease Network REGISTRY study of Huntington's disease mutation carriers (data collected 2003–13). We did a genome-wide association analyses in terms of progression for 216 TRACK-HD participants and 1773 REGISTRY participants, then a meta-analysis of these results was undertaken. Findings Longitudinal motor, cognitive, and imaging scores were correlated with each other in TRACK-HD participants, justifying use of a single, cross-domain measure of disease progression in both studies. The TRACK-HD and REGISTRY progression measures were correlated with each other (r=0·674), and with age at onset (TRACK-HD, r=0·315; REGISTRY, r=0·234). The meta-analysis of progression in TRACK-HD and REGISTRY gave a genome-wide significant signal (p=1·12 × 10−10) on chromosome 5 spanning three genes: MSH3, DHFR, and MTRNR2L2. The genes in this locus were associated with progression in TRACK-HD (MSH3 p=2·94 × 10−8 DHFR p=8·37 × 10−7 MTRNR2L2 p=2·15 × 10−9) and to a lesser extent in REGISTRY (MSH3 p=9·36 × 10−4 DHFR p=8·45 × 10−4 MTRNR2L2 p=1·20 × 10−3). The lead single nucleotide polymorphism (SNP) in TRACK-HD (rs557874766) was genome-wide significant in the meta-analysis (p=1·58 × 10−8), and encodes an aminoacid change (Pro67Ala) in MSH3. In TRACK-HD, each copy of the minor allele at this SNP was associated with a 0·4 units per year (95% CI 0·16–0·66) reduction in the rate of change of the Unified Huntington's Disease Rating Scale (UHDRS) Total Motor Score, and a reduction of 0·12 units per year (95% CI 0·06–0·18) in the rate of change of UHDRS Total Functional Capacity score. These associations remained significant after adjusting for age of onset. Interpretation The multidomain progression measure in TRACK-HD was associated with a functional variant that was genome-wide significant in our meta-analysis. The association in only 216 participants implies that the progression measure is a sensitive reflection of disease burden, that the effect size at this locus is large, or both. Knockout of Msh3 reduces somatic expansion in Huntington's disease mouse models, suggesting this mechanism as an area for future therapeutic investigation

Study of the fluid mechanics of aerodynamic microparticle sampling

Thesis (Ph.D.)--University of Washington, 2020It is no secret that there is significant room for improvement when it comes to security at airports and other secure locations. One area with considerable room for improvement is in the passenger screening for the presence of illicit materials. Traditional swabbing methods used for sampling can be inconvenient and ineffective. Non-contact sampling can offer improvements over traditional sampling methods by increasing speed and effectiveness. Aerodynamic sampling uses a combination of impinging jets to remove particles from the surface of interest and suction to direct the removed particles onto a collection substrate or directly to a detector of choice. This offers improvements over swabbing as there is less room for contamination of the sampling substrate, removes user bias, and allows for sampling of larger areas in less time. To design an effective non-contact surface sampler, one must characterize several distinct phenomena; the flow field of impinging jets, the necessary flow conditions for the removal of micro-particles resting on a surface, and the aerodynamic forces experienced by particles under these conditions. This dissertation focuses on (i) characterization of wall shear stress from axisymmetric underexpanded impinging jets, (ii) development of equations for the wall jet velocity profile and wall shear stress of planar underexpanded impinging jets, (ii) development of a method for calculating the adhesion force of spherical microparticles, and (iv) formulations of aerodynamic forces on non-spherical particles in a boundary layer

Model for Wall Shear Stress from Obliquely Impinging Planar Underexpanded Jets

Though inclined under-expanded planar jets are used in many practical applications, the wall stress resulting from their impingement has not been adequately characterized. Reduced-order models for wall shear as a function of jet parameters have not been reported. This work uses computational fluid dynamics to determine wall shear stress as a function of the nozzle parameters and jet angle. The simulations of the impinging jet are validated against the experimental data and direct numerical simulation; then, the jet parameters are varied to formulate an empirical relationship for maximum wall shear stress as a function of a nozzle pressure ratio, standoff distance, jet Reynolds number, and impingement angle. The global expression for shear stress agrees with the numerical results within a mean deviation of 3%. The relationship can be used for applications where shear stress information is required to design or assess the performance of practical systems, such as surface cleaning, particle resuspension from the surface, and surface cooling

Model for Wall Shear Stress from Obliquely Impinging Planar Underexpanded Jets

Though inclined under-expanded planar jets are used in many practical applications, the wall stress resulting from their impingement has not been adequately characterized. Reduced-order models for wall shear as a function of jet parameters have not been reported. This work uses computational fluid dynamics to determine wall shear stress as a function of the nozzle parameters and jet angle. The simulations of the impinging jet are validated against the experimental data and direct numerical simulation; then, the jet parameters are varied to formulate an empirical relationship for maximum wall shear stress as a function of a nozzle pressure ratio, standoff distance, jet Reynolds number, and impingement angle. The global expression for shear stress agrees with the numerical results within a mean deviation of 3%. The relationship can be used for applications where shear stress information is required to design or assess the performance of practical systems, such as surface cleaning, particle resuspension from the surface, and surface cooling

The integrin binding site 2 (IBS2) in the talin rod domain is essential for linking integrin beta subunits to the cytoskeleton.

Talin1 is a large cytoskeletal protein that links integrins to actin filaments through two distinct integrin binding sites, one present in the talin head domain (IBS1) necessary for integrin activation and a second (IBS2) that we have previously mapped to talin residues 1984-2113 (fragment J) of the talin rod domain (1 Tremuth, L. Kreis, S. Melchior, C. Hoebeke, J. Ronde, P. Plancon, S. Takeda, K. and Kieffer, N. (2004) J. Biol. Chem. 279, 22258-22266), but whose functional role is still elusive. Using a bioinformatics and cell biology approach, we have determined the minimal structure of IBS2 and show that this integrin binding site corresponds to 23 residues located in alpha helix 50 of the talin rod domain (residues 2077-2099). Alanine mutation of 2 highly conserved residues (L2094A/I2095A) within this alpha helix, which disrupted the alpha-helical structure of IBS2 as demonstrated by infrared spectroscopy and limited trypsin proteolysis, was sufficient to prevent in vivo talin fragment J targeting to alphaIIbbeta3 integrin in focal adhesions and to inhibit in vitro this association as shown by an alphaIIbbeta3 pulldown assay. Moreover, expression of a full-length mouse green fluorescent protein-talin LI/AA mutant in mouse talin1(-/-) cells was unable to rescue the inability of these cells to assemble focal adhesions (in contrast to green fluorescent protein-talin wild type) despite the presence of IBS1. Our data provide the first direct evidence that IBS2 in the talin rod is essential to link integrins to the cytoskeleton.Journal ArticleResearch Support, Non-U.S. Gov'tinfo:eu-repo/semantics/publishe