1,497 research outputs found
Wiskott-Aldrich syndrome. A model for defective actin reorganization, cell trafficking and synapse formation
No full textPhorbol ester causes down-regulation of CD11/CD18-independent neutrophil adherence to endothelium.
No full textCD11/CD18-independent neutrophil adherence to inducible endothelial-leucocyte adhesion molecules (E-LAM) in vitro.
No full textShort-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
HEPATITIS-C VIRUS TRANSMISSION BY INTRAVENOUS IMMUNOGLOBULIN
No full textThe polymerase chain reaction was used to detect hepatitis C virus infection in patients who had previously been reported to have developed non-A, non-B hepatitis after intravenous immunoglobulin infusion. Of the 33 patients with intravenous immunoglobulin associated non-A, non-B hepatitis studied, HCV RNA could be detected in 15 out of 17 patients (88%) who were HCV RNA negative prior to the development of non-A, non-B hepatitis after implicated intravenous immunoglobulin batches. Similarly, eight out of nine patients (89%) in whom no sample was available for polymerase chain reaction testing prior to intravenous immunoglobulin therapy, had detectable HCV RNA after intravenous immunoglobulin therapy with intravenous immunoglobulin batches implicated in non-A, non-B hepatitis transmission. Two of the three intravenous immunoglobulin preparations implicated in non-A, non-B hepatitis transmissions that were available for polymerase chain reaction testing also had detectable HCV RNA, confirming that hepatitis C virus is the implicated virus in intravenous immunoglobulin-associated non-A, non-B hepatitis
WASP confers selective advantage for specific hematopoietic cell populations and serves a unique role in marginal zone B-cell homeostasis and function
No full textAnonymous 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
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