83 research outputs found
Gaze-dependent topography in human posterior parietal cortex.
The brain must convert retinal coordinates into those required for directing an effector. One prominent theory holds that, through a combination of visual and motor/proprioceptive information, head-/body-centered representations are computed within the posterior parietal cortex (PPC). An alternative theory, supported by recent visual and saccade functional magnetic resonance imaging (fMRI) topographic mapping studies, suggests that PPC neurons provide a retinal/eye-centered coordinate system, in which the coding of a visual stimulus location and/or intended saccade endpoints should remain unaffected by changes in gaze position. To distinguish between a retinal/eye-centered and a head-/body-centered coordinate system, we measured how gaze direction affected the representation of visual space in the parietal cortex using fMRI. Subjects performed memory-guided saccades from a central starting point to locations āaround the clock.ā Starting points varied between left, central, and right gaze relative to the head-/body midline. We found that memory-guided saccadotopic maps throughout the PPC showed spatial reorganization with very subtle changes in starting gaze position, despite constant retinal input and eye movement metrics. Such a systematic shift is inconsistent with models arguing for a retinal/eye-centered coordinate system in the PPC, but it is consistent with head-/body-centered coordinate representations
SensorWeb 3G: Extending On-Orbit Sensor Capabilities to Enable Near Realtime User Configurability
This research effort prototypes an implementation of a standard interface, Web Coverage Processing Service (WCPS), which is an Open Geospatial Consortium(OGC) standard, to enable users to define, test, upload and execute algorithms for on-orbit sensor systems. The user is able to customize on-orbit data products that result from raw data streaming from an instrument. This extends the SensorWeb 2.0 concept that was developed under a previous Advanced Information System Technology (AIST) effort in which web services wrap sensors and a standardized Extensible Markup Language (XML) based scripting workflow language orchestrates processing steps across multiple domains. SensorWeb 3G extends the concept by providing the user controls into the flight software modules associated with on-orbit sensor and thus provides a degree of flexibility which does not presently exist. The successful demonstrations to date will be presented, which includes a realistic HyspIRI decadal mission testbed. Furthermore, benchmarks that were run will also be presented along with future demonstration and benchmark tests planned. Finally, we conclude with implications for the future and how this concept dovetails into efforts to develop "cloud computing" methods and standards
Bronchus-associated lymphoid tissueāresident Foxp3+ T lymphocytes prevent antibody-mediated lung rejection
A simplified quantitative real-time PCR assay for monitoring SARS-CoV-2 growth in cell culture
Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has infected millions within just a few months, causing severe respiratory disease and mortality. Assays to monitor SARS-CoV-2 growt
Effect of the Breakup Context on Unwanted Pursuit Behavior Perpetration Between Former Partners*
Find Them Home or Abroad? The Relative Contribution of International Technology In-licensing to āIndigenous Innovationā in China
Corrigendum: Phase I trial outcome of amnion cell therapy in patients with ischemic stroke (I-ACT)
Pre-clinical evaluation of CYP 2D6 dependent drugādrug interactions between primaquine and SSRI/SNRI antidepressants
Global, regional, and national burden of tuberculosis, 1990ā2016: results from the Global Burden of Diseases, Injuries, and Risk Factors 2016 Study
Background
Although a preventable and treatable disease, tuberculosis causes more than a million deaths each year. As countries work towards achieving the Sustainable Development Goal (SDG) target to end the tuberculosis epidemic by 2030, robust assessments of the levels and trends of the burden of tuberculosis are crucial to inform policy and programme decision making. We assessed the levels and trends in the fatal and non-fatal burden of tuberculosis by drug resistance and HIV status for 195 countries and territories from 1990 to 2016.
Methods
We analysed 15ā943 site-years of vital registration data, 1710 site-years of verbal autopsy data, 764 site-years of sample-based vital registration data, and 361 site-years of mortality surveillance data to estimate mortality due to tuberculosis using the Cause of Death Ensemble model. We analysed all available data sources, including annual case notifications, prevalence surveys, population-based tuberculin surveys, and estimated tuberculosis cause-specific mortality to generate internally consistent estimates of incidence, prevalence, and mortality using DisMod-MR 2.1, a Bayesian meta-regression tool. We assessed how the burden of tuberculosis differed from the burden predicted by the Socio-demographic Index (SDI), a composite indicator of income per capita, average years of schooling, and total fertility rate.
Findings
Globally in 2016, among HIV-negative individuals, the number of incident cases of tuberculosis was 9Ā·02 million (95% uncertainty interval [UI] 8Ā·05ā10Ā·16) and the number of tuberculosis deaths was 1Ā·21 million (1Ā·16ā1Ā·27). Among HIV-positive individuals, the number of incident cases was 1Ā·40 million (1Ā·01ā1Ā·89) and the number of tuberculosis deaths was 0Ā·24 million (0Ā·16ā0Ā·31). Globally, among HIV-negative individuals the age-standardised incidence of tuberculosis decreased annually at a slower rate (ā1Ā·3% [ā1Ā·5 to ā1Ā·2]) than mortality did (ā4Ā·5% [ā5Ā·0 to ā4Ā·1]) from 2006 to 2016. Among HIV-positive individuals during the same period, the rate of change in annualised age-standardised incidence was ā4Ā·0% (ā4Ā·5 to ā3Ā·7) and mortality was ā8Ā·9% (ā9Ā·5 to ā8Ā·4). Several regions had higher rates of age-standardised incidence and mortality than expected on the basis of their SDI levels in 2016. For drug-susceptible tuberculosis, the highest observed-to-expected ratios were in southern sub-Saharan Africa (13Ā·7 for incidence and 14Ā·9 for mortality), and the lowest ratios were in high-income North America (0Ā·4 for incidence) and Oceania (0Ā·3 for mortality). For multidrug-resistant tuberculosis, eastern Europe had the highest observed-to-expected ratios (67Ā·3 for incidence and 73Ā·0 for mortality), and high-income North America had the lowest ratios (0Ā·4 for incidence and 0Ā·5 for mortality).
Interpretation
If current trends in tuberculosis incidence continue, few countries are likely to meet the SDG target to end the tuberculosis epidemic by 2030. Progress needs to be accelerated by improving the quality of and access to tuberculosis diagnosis and care, by developing new tools, scaling up interventions to prevent risk factors for tuberculosis, and integrating control programmes for tuberculosis and HIV
AI is a viable alternative to high throughput screening: a 318-target study
: High throughput screening (HTS) is routinely used to identify bioactive small molecules. This requires physical compounds, which limits coverage of accessible chemical space. Computational approaches combined with vast on-demand chemical libraries can access far greater chemical space, provided that the predictive accuracy is sufficient to identify useful molecules. Through the largest and most diverse virtual HTS campaign reported to date, comprising 318 individual projects, we demonstrate that our AtomNetĀ® convolutional neural network successfully finds novel hits across every major therapeutic area and protein class. We address historical limitations of computational screening by demonstrating success for target proteins without known binders, high-quality X-ray crystal structures, or manual cherry-picking of compounds. We show that the molecules selected by the AtomNetĀ® model are novel drug-like scaffolds rather than minor modifications to known bioactive compounds. Our empirical results suggest that computational methods can substantially replace HTS as the first step of small-molecule drug discovery
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