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

A Wind Tunnel Experimental Study of Icing on NACA0012 Aircraft Airfoil with Silicon Compounds Modified Polyurethane Coatings

Ice formation on the aerodynamic surfaces of an aircraft is regarded as a major problem in the aerospace industry. Ice accumulation may damage parts, sensors and controllers and alter the aerodynamics of the airplane, leading to a range of undesired consequences, including flight delays, emergency landings, damaged parts and increased energy consumption. There are various approaches to reducing ice accretion, one of them being the application of icephobic coatings. In this work, commercially available polyurethane-based coatings were modified and deposited on NACA 0012 aircraft airfoils. A hybrid modification of polyurethane (PUR) topcoats was adopted by the addition of nanosilica and three-functional spherosilicates (a variety of silsesqioxane compound), which owe their unique properties to the presence of three different groups. The ice accretion on the manufactured nanocomposites was determined in an icing wind tunnel. The tests were performed under three different icing conditions: glaze ice, rime ice and mixed ice. Furthermore, the surface topography and wetting behavior (static contact angle and contact angle hysteresis) were investigated. It was found that the anti-icing properties of polyurethane nanocomposite coatings strongly depend on the icing conditions under which they are tested. Moreover, the addition of nanosilica and spherosilicates enabled the reduction of accreted ice by 65% in comparison to the neat topcoat

Synchronization between computation and acquisition parts in the GEM detector-based measurement system

The presented system is used for monitoring of the plasma impurities in the tokamak. It is done by measuring radiation in Soft X-Ray range with the use of a GEM-based detector. Acquired data is transferred through the whole system with low latency. Presented system can be divided into many parts - detector, analog electronics, FPGA, PCIe transmission line and computer system with high-performance CPU. This work will concentrate on synchronization between FPGA, which write data to the memory on the CPU side and computational part, which is executed in the computer. In long-running measurements, there is a synchronization problems which can arise. There is a difference in variables based on which the execution time of both parts is dependent. Working on measurements of radiation of plasma impurities requires limits in terms of latency. This paper presents reasons, descriptions and solutions for such problems

Search for the rare hadronic decay Bs0→ppˉB_s^0\to p \bar{p}

A search for the rare hadronic decay Bs0→pp¯ is performed using proton-proton collision data recorded by the LHCb experiment at a center-of-mass energy of 13 TeV, corresponding to an integrated luminosity of 6  fb-1. No evidence of the decay is found and an upper limit on its branching fraction is set at B(Bs0→pp¯)&lt;4.4(5.1)×10-9 at 90% (95%) confidence level; this is currently the world’s best upper limit. The decay mode B0→pp¯ is measured with very large significance, confirming the first observation by the LHCb experiment in 2017. The branching fraction is determined to be B(B0→pp¯)=(1.27±0.15±0.05±0.04)×10-8, where the first uncertainty is statistical, the second is systematic and the third is due to the external branching fraction of the normalization channel B0→K+π-. The combination of the two LHCb measurements of the B0→pp¯ branching fraction yields B(B0→pp¯)=(1.27±0.13±0.05±0.03)×10-8.A search for the rare hadronic decay $B_s^0\to p \bar{p}$ is performed using proton-proton collision data recorded by the LHCb experiment at a center-of-mass energy of 13 TeV, corresponding to an integrated luminosity of 6 fb$^{-1}$. No evidence of the decay is found and an upper limit on its branching fraction is set at ${\cal B}(B_s^0\to p \bar{p}) < 4.4~(5.1) \times 10^{-9}$ at 90% (95%) confidence level; this is currently the world's best upper limit. The decay mode $B^0\to p \bar{p}$ is measured with very large significance, confirming the first observation by the LHCb experiment in 2017. The branching fraction is determined to be ${\cal B}(B^0\to p \bar{p}) = \rm (1.27 \pm 0.15 \pm 0.05 \pm 0.04) \times 10^{-8}$, where the first uncertainty is statistical, the second is systematic and the third is due to the external branching fraction of the normalization channel $B^0\to K^+\pi^-$. The combination of the two LHCb measurements of the $B^0\to p \bar{p}$ branching fraction yields ${\cal B}(B^0\to p \bar{p}) = \rm (1.27 \pm 0.13 \pm 0.05 \pm 0.03) \times 10^{-8}$

Measurement of CP asymmetries in D(s)+→ηπ+ {D}_{(s)}^{+}\to \eta {\pi}^{+} and D(s)+→η′π+ {D}_{(s)}^{+}\to {\eta}^{\prime }{\pi}^{+} decays

Searches for CP violation in the decays ${D}_{(s)}^{+}\to \eta {\pi}^{+}$ and ${D}_{(s)}^{+}\to {\eta}^{\prime }{\pi}^{+}$ are performed using pp collision data corresponding to 6 fb$^{−1}$ of integrated luminosity collected by the LHCb experiment. The calibration channels ${D}_{(s)}^{+}\to \phi {\pi}^{+}$ are used to remove production and detection asymmetries. The resulting CP-violating asymmetries are${\displaystyle \begin{array}{l}{\mathcal{A}}^{CP}=\left({D}^{+}\to \eta {\pi}^{+}\right)=\left(0.34\pm 0.66\pm 0.16\pm 0.05\right)\%,\\ {}{\mathcal{A}}^{CP}=\left({D}_s^{+}\to \eta {\pi}^{+}\right)=\left(0.32\pm 0.51\pm 0.12\right)\%,\\ {}\begin{array}{l}{\mathcal{A}}^{CP}=\left({D}^{+}\to {\eta}^{\prime }{\pi}^{+}\right)=\left(0.49\pm 0.18\pm 0.06\pm 0.05\right)\%,\\ {}{\mathcal{A}}^{CP}=\left({D}_s^{+}\to {\eta}^{\prime }{\pi}^{+}\right)=\left(0.01\pm 0.12\pm 0.08\right)\%,\end{array}\end{array}}$where the first uncertainty is statistical, the second is systematic and the third, relevant for the D$^{+}$ channels, is due to the uncertainty on ${\mathcal{A}}^{CP}=\left({D}^{+}\to \phi {\pi}^{+}\right)$. These measurements, currently the most precise for three of the four channels considered, are consistent with the absence of CP violation. A combination of these results with previous LHCb measurements is presented.[graphic not available: see fulltext]Searches for $CP$ violation in the decays $D^+_{(s)}\rightarrow \eta \pi^+$ and $D^+_{(s)}\rightarrow \eta^{\prime} \pi^+$ are performed using $pp$ collision data corresponding to 6 fb$^{-1}$ of integrated luminosity collected by the LHCb experiment. The calibration channels $D^+_{(s)}\rightarrow \phi \pi^+$ are used to remove production and detection asymmetries. The resulting $CP$-violating asymmetries are $A^{CP}(D^+ \rightarrow \eta \pi^+) = (0.34 \pm 0.66 \pm 0.16 \pm 0.05)\%$, $A^{CP}(D^+_s \rightarrow \eta \pi^+) = (0.32 \pm 0.51 \pm 0.12)\%$, $A^{CP}(D^+ \rightarrow \eta^{\prime} \pi^+) = (0.49 \pm 0.18 \pm 0.06 \pm 0.05)\%$, $A^{CP}(D^+_s \rightarrow \eta^{\prime} \pi^+) = (0.01 \pm 0.12 \pm 0.08)\%$, where the first uncertainty is statistical, the second is systematic and the third, relevant for the $D^+$ channels, is due to the uncertainty on $A^{CP}(D^+ \to \phi \pi^+)$. These measurements, currently the most precise for three of the four channels considered, are consistent with the absence of $CP$ violation. A combination of these results with previous LHCb measurements is presented