1,390 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
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
Remarks on Brill–Noether divisors and Hilbert schemes
No full textAbstractLet Mg,dr be the sublocus of Mg, whose points correspond to smooth curves possessing gdr. If the Brill–Noether number ρ(g,r,d)=−1, it is known that Mg,dr is irreducible. In this paper, we prove that if g is odd, and r,s,d,e (r≠s) are positive integers satisfying ρ(g,r,d)=ρ(g,s,e)=−1 and e≠2g−2−d, then the supports of Mg,dr and Mg,es are distinct. As an application, we show that in the case d>g there is a unique irreducible component Dd,g,r of Hd,g,r dominating Mg,dr and that a general member C∈Dd,g,r has no (d−e)-secant (r−s−1)-plane for ρ(g,s,e)=−1,e≠2g−2−d
A Perfect Tidal Storm: HD 104067 Planetary Architecture Creating an Incandescent World
No full textThe discovery of planetary systems beyond the solar system has revealed a diversity of architectures, most of which differ significantly from our system. The initial detection of an exoplanet is often followed by subsequent discoveries within the same system as observations continue, measurement precision is improved, or additional techniques are employed. The HD 104067 system is known to consist of a bright K-dwarf host star and a giant planet in a ?55 days period eccentric orbit. Here we report the discovery of an additional planet within the HD 104067 system, detected through the combined analysis of radial velocity (RV) data from the High Resolution Echelle Spectrometer and High Accuracy Radial velocity Planet Searcher instruments. The new planet has a mass similar to Uranus and is in an eccentric ?14 days orbit. Our injection-recovery analysis of the RV data exclude Saturn-mass and Jupiter-mass planets out to 3 au and 8 au, respectively. We further present Transiting Exoplanet Survey Satellite observations that reveal a terrestrial planet candidate (R p = 1.30 ± 0.12 R ?) in a ?2.2 days period orbit. Our dynamical analysis of the three planet model shows that the two outer planets produce significant eccentricity excitation of the inner planet, resulting in tidally induced surface temperatures as high as ?2600 K for an emissivity of unity. The terrestrial planet candidate may therefore be caught in a tidal storm, potentially resulting in its surface radiating at optical wavelengths. © 2024. The Author(s). Published by the American Astronomical Society
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No full textIn this paper, this author proved that always has
the integral solutions for Then we conjecture the equation always has the integral solutions
Polarized disk emission from Herbig AE/BE stars observed using Gemini planet imager: HD 144432, HD 150193, HD 163296, and HD 169142
No full textThis is the author accepted manuscript. The final version is available from the publisher via the DOI in this record.In order to look for signs of on-going planet formation in young disks, we carried out the first J-band polarized emission imaging of the Herbig Ae/Be stars HD 150193, HD 163296, and HD 169142 using
the Gemini Planet Imager (GPI), along with new H band observations of HD 144432. We confirm the complex “double ring” structure for the nearly face-on system HD 169142 first seen in H-band, finding
the outer ring to be substantially redder than the inner one in polarized intensity. Using radiative transfer modeling, we developed a physical model that explains the full spectral energy distribution (SED) and J- and H-band surface brightness profiles, suggesting that the di↵erential color of the two rings could come from reddened starlight traversing the inner wall and may not require di↵erences in grain properties. In addition, we clearly detect an elongated, o↵-center ring in HD 163296 (MWC 275), locating the scattering surface to be 18 AU above the midplane at a radial distance of 77 AU, cospatial with a ring seen at 1.3mm by ALMA linked to the CO snow line. Lastly, we report a weak tentative detection of scattered light for HD 150193 (MWC 863) and a non-detection for HD 144432; the stellar companion known for each of these targets has likely disrupted the material in the outer disk of the primary star. For HD 163296 and HD 169142, the prominent outer rings we detect could be evidence for giant planet formation in the outer disk or a manifestation of large-scale dust growth processes possibly related to snow-line chemistry.Exeter’s STFC Consolidated Grant (ST/J001627/1). SK acknowledges support from an STFC Rutherford Fellowship
(ST/J004030/1) and a European Research Council (ERC) Starting Grant (Grant agreement No 639889).
This publication makes use of data products from the Two Micron All Sky Survey, which is a joint project of
the University of Massachusetts and the Infrared Processing and Analysis Center/California Institute of Technology,
funded by the National Aeronautics and Space Administration and the National Science Foundation. Based on
observations obtained at the Gemini Observatory (programs GS-2014A-SV-412, GS-2015A-Q-49), which is operated
by the Association of Universities for Research in Astronomy, Inc., under a cooperative agreement with the NSF on
behalf of the Gemini partnership: the National Science Foundation (United States), the National Research Council
(Canada), CONICYT (Chile), Ministerio de Ciencia, Tecnologa e Innovacin Productiva (Argentina), and Ministrio da
Cincia, Tecnologia e Inovao (Brazil)
Physical therapy as an environmental modulator of genetic determinism in HD: The FIT-HD study
No full textAbstract only.HD has long been viewed as the quintessential example of genetic determinism. However, research has demonstrated that environmental factors play a signifi cant role in modulating the disease process, including the age of onset. In transgenic mouse models of HD, co-author Hannan’s laboratory has demonstrated that environmental enrichment (enhanced motor, cognitive and sensory stimulation) delays onset and progression of motor symptoms and neural degeneration. Introducing an exercise wheel to young HD mice delays onset and progression of motor symptoms, and reverses reduction of brain derived neurotrophic factor in the striatum and hippocampus. Such stimulation has also ameliorated defi cits in learning and memory, as well as depressive behaviours in HD mice. Physical activity (PA) has been found to have benefi cial neural effects in older adults, with increases in hippocampal volume and cognition, apparent even when exercise is limited to later life. We have found that PA improved cognitive function in those at risk of Alzheimer’s disease (AD), and are conducting randomized controlled trials (RCT) investigating this PA program in AD patients, older adults at risk of AD with vascular risk factors or sedentary lifestyle, and in older care recipients and carers. The role of exercise as a potential modifi er is receiving increasing attention in HD. Avoiding passivity was found to be a potential benefi cial modulator in HD, and a PA program improved in motor function in HD patients. However, evidence from RCTs is lacking. AIMS of this study are to: 1) examine the feasibility of our PA program in FIT-HD (by measuring adherence, acceptability, benefi ts, risks); 2) improve physical and mental health and quality of life in HD carriers. HYPOTHESES. Participants randomised to the PA program will: 1) increase PA and adhere to the protocol; have 2) improved quality of life and fi tness, 3) improved sleep, 4) less motor and cognitive decline, 5) improved resting brain state, and 6) have less depressive symptoms, as compared to participants randomised to usual care.
Methods: RCT of a validated 24-week PA intervention in HD in Australia. Participants are randomly allocated to an education/usual care group or to a 24-week home-based PA program.
Results: PA should be more promoted in the HD community due to multiple health benefi ts. Should our RCT be completed successfully and our hypotheses supported then this could change clinical care of HD
Severity of AD/HD symptoms and efficiency of attentional resource allocation
No full textThis study investigated the mechanism that underlies the inefficient allocation of attentional resources in Attention-Deficit/Hyperactivity Disorder (AD/HD). The P300 event-related brain potential (ERP) was elicited from 24 healthy adults using a visual three-stimulus oddball paradigm (standard, 70%; target, 15%; non-target, 15%) and the degree of their AD/HD symptoms was assessed by using AD/HD symptom scales. Target stimulus was a circle and standard stimulus was an “X”. Two task conditions were defined according to the non-target stimulus type (typical or novel): a triangle for the typical condition and colored non-repetitive novel stimuli for the novel condition. In both conditions, target and non-target elicited P300s. A ratio of non-target P300 to target P300 amplitude was used to assess the efficiency of attentional resource allocation; low ratio indicates the efficient allocation of attentional resource. The correlation analysis revealed a strong positive correlation between the AD/HD symptom score and the P300 amplitude ratio in the typical condition (r = .80), while only a weak positive correlation was observed in the novel condition (r = .23). The present study found that the commonality of task-relevant and task-irrelevant information, rather than the stimulus novelty of task-irrelevant information, induces the inefficient allocation of attentional resources in AD/HD
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