5,550 research outputs found
Short-interval observational data to inform clinical trial design in Huntington's disease.
No full textOBJECTIVES: To evaluate candidate outcomes for disease-modifying trials in Huntington's disease (HD) over 6-month, 9-month and 15-month intervals, across multiple domains. To present guidelines on rapid efficacy readouts for disease-modifying trials. METHODS: 40 controls and 61 patients with HD, recruited from four EU sites, underwent 3 T MRI and standard clinical and cognitive assessments at baseline, 6 and 15 months. Neuroimaging analysis included global and regional change in macrostructure (atrophy and cortical thinning), and microstructure (diffusion metrics). The main outcome was longitudinal effect size (ES) for each outcome. Such ESs can be used to calculate sample-size requirements for clinical trials for hypothesised treatment efficacies. RESULTS: Longitudinal changes in macrostructural neuroimaging measures such as caudate atrophy and ventricular expansion were significantly larger in HD than controls, giving rise to consistently large ES over the 6-month, 9-month and 15-month intervals. Analogous ESs for cortical metrics were smaller with wide CIs. Microstructural (diffusion) neuroimaging metrics ESs were also typically smaller over the shorter intervals, although caudate diffusivity metrics performed strongly over 9 and 15 months. Clinical and cognitive outcomes exhibited small longitudinal ESs, particularly over 6-month and 9-month intervals, with wide CIs, indicating a lack of precision. CONCLUSIONS: To exploit the potential power of specific neuroimaging measures such as caudate atrophy in disease-modifying trials, we propose their use as (1) initial short-term readouts in early phase/proof-of-concept studies over 6 or 9 months, and (2) secondary end points in efficacy studies over longer periods such as 15 months
A new HgMn star HD 196821
No full textIn this study, we present the chemical abundance analysis of HD 196821. The spectra of HD 196821 was obtained at the TUBITAK National Observatory using the Coude Echelle spectrograph attached to the 1.5 m telescope. We determined the atmospheric parameters of HD 196821: T-eff=10600K, log g=3.6, nu(mic)=0 km/s, and [Fe/H]=0.16 dex. HD 196821 shows an overabundance of 85 times solar for Mn and 208,930 times solar for Hg. This strongly suggests that the star should be classified as an HgMn star
A Spectroscopic Analysis of HD 134439 and HD 134440
No full textWe analyze elemental abundances of the common proper motion pair HD 134439 and HD 134440 to understand their formation history. This pair of metal-poor ([Fe/H]) halo dwarfs are known, from previous studies, to exhibit abnormally low [/Fe] ratios compared to typical Galactic halo stars. Some have attributed this to planetesimal accretion; others believe these stars formed in the dusty part of a dwarf spheroidal galaxy and were later captured by our Galaxy. To investigate this anomaly, we measure carbon, nitrogen, and oxygen abundances for HD 134439 and HD 134440 from near-UV molecular features using high-resolution spectra obtained with Keck HIRES spectrograph. The [C, N, O/Fe] ratios range from to dex. We confirm a previously suggested correlation between the elemental abundances and condensation temperature at the 5\% confidence level. A comparison of HD 134439 and HD 134440 with stars of similar metallicity in the Galactic halo suggests very different formation histories; though, the abundances of dwarf spheroidal stars seems less different from our stars. Chemical yields of low mass Type II supernovae provide an explanation for most of the abundance patterns observed for the common proper motion pair. Finally, the peculiar abundances of neutron-capture elements (Y, Ag, Ba, Eu) are put in context with various nucleosynthetic sources
Anonymous HD video streaming
No full textNo scalable privacy-enhancing technologies exists that is capable of anonymous HD video streaming. Our paper discusses the new anonymizer built into Tribler, a social content-sharing client. With anonymous HD-video streaming as the main objective requirements as at least 10 Mbit/s throughput, user bandwidth donations and NAT-traversal are defined. Using the Tribler API and related tools as Dispersy the ProxyCommunity is designed. This community of proxies provides peer discovery, onion routing and multi-tunnel proxying. Our system evolved through various stages. From the initial standalone routing prototype, to the first Tribler version. This was followed by profiling to achieve performance improvements. Finally the version with libtorrent and cryptography-readyness was implemented. Our performance evaluation shows that the proxy community is able to discover others on the network effectively and built circuits with them. Over these circuits the required 10 Mbit/s throughput for HD streaming has been achieved. Preliminary real-world testing shows that the system works in the wild. However more testing needs to be done and important work on our security model remains.Parallel and Distributed SystemsElectrical Engineering, Mathematics and Computer Scienc
Haploinsufficiency of the ESCRT Component HD-PTP Predisposes to Cancer
No full textSummaryEndosomal sorting complexes required for transport (ESCRT) drive cell surface receptor degradation resulting in attenuation of oncogenic signaling and pointing to a tumor suppressor function. Here, we show that loss of function of an ESCRT protein (HD-PTP encoded by the PTPN23 gene, located on the tumor suppressor gene cluster 3p21.3) drives tumorigenesis in vivo. Indeed, Ptpn23+/− loss predisposes mice to sporadic lung adenoma, B cell lymphoma, and promotes Myc-driven lymphoma onset, dissemination, and aggressiveness. Ptpn23+/−-derived tumors exhibit an unaltered remaining allele and maintain 50% of HD-PTP expression. Consistent with the role of HD-PTP in attenuation of integrin recycling, cell migration, and invasion, hemizygous Ptpn23+/− loss increases integrin β1-dependent B cell lymphoma survival and dissemination. Finally, we reveal frequent PTPN23 deletion and downregulation in human tumors that correlates with poor survival. Altogether, we establish HD-PTP/PTPN23 as a prominent haploinsufficient tumor suppressor gene preventing tumor progression through control of integrin trafficking
Chromosomal locations of soybean HD-Zip genes.
No full text<p>Colored boxes ahead of the gene names represent the classes to which each HD-Zip gene belongs (HD-Zip I, red; HD-Zip II, green; HD-Zip III, pink; HD-Zip IV, blue). The 88 HD-Zip genes were mapped to the 20 chromosomes, while only one gene (<i>Gmhdz1</i>) resides on unassembled scaffolds. The data used to generate the schematic diagram of the genome-wide chromosome organization were obtained from the SoyBase browser. Only segmental duplicated blocks including HD-Zip genes are indicated with the same colors. Small boxes connected by colored line (two types) indicate corresponding sister gene pairs, of which the genes connected by solid lines are located in the homologous duplicated blocks, while genes connected by the dashed line were observed in the duplicated blocks shown with different colors. Tandemly duplicated genes are indicated with red boxes. The scale represents the length of the chromosome.</p
Infrared spectroscopy of endohedral HD and D2 in C60
No full textWe report on the dynamics of two hydrogen isotopomers, D2 and HD, trapped in the molecular cages of a fullerene C60 molecule. We measured the infrared spectra and analyzed them using a spherical potential for a vibrating rotor. The potential, vibration-rotation Hamiltonian, and dipole moment parameters are compared with previously studied H2@C 60 parameters [M. Ge, U. Nagel, D. Hvonen, T. Rm, S. Mamone, M. H. Levitt, M. Carravetta, Y. Murata, K. Komatsu, J. Y.-C. Chen, and N. J. Turro, J. Chem. Phys. 134, 054507 (2011)10.1063/1.3535598]. The isotropic part of the potential is similar for all three isotopomers. In HD@C60, we observe mixing of the rotational states and an interference effect of the dipole moment terms due to the displacement of the HD rotation center from the fullerene cage center. © 2011 American Institute of Physics
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