80 research outputs found

    GPUVerify: A Verifier for GPU Kernels

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    We present a technique for verifying race- and divergence-freedom of GPU kernels that are written in mainstream ker-nel programming languages such as OpenCL and CUDA. Our approach is founded on a novel formal operational se-mantics for GPU programming termed synchronous, delayed visibility (SDV) semantics. The SDV semantics provides a precise definition of barrier divergence in GPU kernels and allows kernel verification to be reduced to analysis of a sequential program, thereby completely avoiding the need to reason about thread interleavings, and allowing existing modular techniques for program verification to be leveraged. We describe an efficient encoding for data race detection and propose a method for automatically inferring loop invari-ants required for verification. We have implemented these techniques as a practical verification tool, GPUVerify, which can be applied directly to OpenCL and CUDA source code. We evaluate GPUVerify with respect to a set of 163 kernels drawn from public and commercial sources. Our evaluation demonstrates that GPUVerify is capable of efficient, auto-matic verification of a large number of real-world kernels

    Chimpanzee Rights: The Philosophers' Brief

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    In December 2013, the Nonhuman Rights Project (NhRP) filed a petition for a common law writ of habeas corpus in the New York State Supreme Court on behalf of Tommy, a chimpanzee living alone in a cage in a shed in rural New York (Barlow, 2017). Under animal welfare laws, Tommy’s owners, the Laverys, were doing nothing illegal by keeping him in those conditions. Nonetheless, the NhRP argued that given the cognitive, social, and emotional capacities of chimpanzees, Tommy’s confinement constituted a profound wrong that demanded remedy by the courts. Soon thereafter, the NhRP filed habeas corpus petitions on behalf of Kiko, another chimpanzee housed alone in Niagara Falls, and Hercules and Leo, two chimpanzees held in research facilities at Stony Brook University. Thus began the legal struggle to move these chimpanzees from captivity to a sanctuary, an effort that has led the NhRP to argue in multiple courts before multiple judges. The central point of contention has been whether Tommy, Kiko, Hercules, and Leo have legal rights. To date, no judge has been willing to issue a writ of habeas corpus on their behalf. Such a ruling would mean that these chimpanzees have rights that confinement might violate. Instead, the judges have argued that chimpanzees cannot be bearers of legal rights because they are not, and cannot be persons. In this book we argue that chimpanzees are persons because they are autonomous

    A Magnetohydrodynamic enhanced entry system for space transportation: MEESST

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    This paper outlines the initial development of a novel magnetohydrodynamic (MHD) plasma control system which aims at mitigating shock-induced heating and the radio-frequency communication blackout typically encountered during (re-)entry into planetary atmospheres. An international consortium comprising universities, SMEs, research institutions, and industry has been formed in order to develop this technology within the MEESST project. The latter is funded by the Future and Emerging Technologies (FET) program of the European Commission’s Horizon 2020 scheme (grant no. 899298). Atmospheric entry imposes one of the harshest environments which a spacecraft can experience. The combination of hypersonic velocities and the rapid compression of atmospheric particles by the spacecraft leads to high-enthalpy, partially ionised gases forming around the vehicle. This inhibits radio communications and induces high thermal loads on the spacecraft surface. For the former problem, spacecraft can sometimes rely on satellite constellations for communicating through the plasma wake and therefore preventing the blackout. On the other hand, expensive, heavy, and non-reusable thermal protection systems (TPS) are needed to dissipate the severe thermal loads. Such TPS can represent up to 30% of an entry vehicles weight, and especially for manned missions they can reduce the cost- efficiency by sacrificing payload mass. Such systems are also prone to failure, putting the lives of astronauts at risk. The use of electromagnetic fields to exploit MHD principles has long been considered as an attractive solution for tackling the problems described above. By pushing the boundary layer of the ionized gas layer away from the spacecraft, the thermal loads can be reduced, while also opening a magnetic window for radio communications and mitigating the blackout phenomenon. The application of this MHD-enabled system has previously not been demonstrated in realistic conditions due to the required large magnetic fields (on the order of Tesla or more), which for conventional technologies would demand exceptionally heavy and power-hungry electromagnets. High-temperature superconductors (HTS) have reached a level of industrial maturity sufficient for them to act as a key enabling technology for this application. Thanks to superior current densities, HTS coils can offer the necessary low weight and compactness required for space applications, with the ability to generate the strong magnetic fields needed for entry purposes. This paper provides an overview of the MEESST project, including its goals, methodology and some preliminary design considerations

    Membrane-Associated RING-CH Proteins Associate with Bap31 and Target CD81 and CD44 to Lysosomes

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    Membrane-associated RING-CH (MARCH) proteins represent a family of transmembrane ubiquitin ligases modulating intracellular trafficking and turnover of transmembrane protein targets. While homologous proteins encoded by gamma-2 herpesviruses and leporipoxviruses have been studied extensively, limited information is available regarding the physiological targets of cellular MARCH proteins. To identify host cell proteins targeted by the human MARCH-VIII ubiquitin ligase we used stable isotope labeling of amino-acids in cell culture (SILAC) to monitor MARCH-dependent changes in the membrane proteomes of human fibroblasts. Unexpectedly, we observed that MARCH-VIII reduced the surface expression of Bap31, a chaperone that predominantly resides in the endoplasmic reticulum (ER). We demonstrate that Bap31 associates with the transmembrane domains of several MARCH proteins and controls intracellular transport of MARCH proteins. In addition, we observed that MARCH-VIII reduced the surface expression of the hyaluronic acid-receptor CD44 and both MARCH-VIII and MARCH-IV sequestered the tetraspanin CD81 in endo-lysosomal vesicles. Moreover, gene knockdown of MARCH-IV increased surface levels of endogenous CD81 suggesting a constitutive involvement of this family of ubiquitin ligases in the turnover of tetraspanins. Our data thus suggest a role of MARCH-VIII and MARCH-IV in the regulated turnover of CD81 and CD44, two ubiquitously expressed, multifunctional proteins

    A Magnetohydrodynamic enhanced entry system for space transportation: MEESST

    Get PDF
    This paper outlines the initial development of a novel magnetohydrodynamic (MHD) plasma control system which aims at mitigating shock-induced heating and the radio-frequency communication blackout typically encountered during (re-)entry into planetary atmospheres. An international consortium comprising universities, SMEs, research institutions, and industry has been formed in order to develop this technology within the MEESST project. The latter is funded by the Future and Emerging Technologies (FET) program of the European Commission’s Horizon 2020 scheme (grant no. 899298). Atmospheric entry imposes one of the harshest environments which a spacecraft can experience. The combination of hypersonic velocities and the rapid compression of atmospheric particles by the spacecraft leads to high-enthalpy, partially ionised gases forming around the vehicle. This inhibits radio communications and induces high thermal loads on the spacecraft surface. For the former problem, spacecraft can sometimes rely on satellite constellations for communicating through the plasma wake and therefore preventing the blackout. On the other hand, expensive, heavy, and non-reusable thermal protection systems (TPS) are needed to dissipate the severe thermal loads. Such TPS can represent up to 30% of an entry vehicles weight, and especially for manned missions they can reduce the cost- efficiency by sacrificing payload mass. Such systems are also prone to failure, putting the lives of astronauts at risk. The use of electromagnetic fields to exploit MHD principles has long been considered as an attractive solution for tackling the problems described above. By pushing the boundary layer of the ionized gas layer away from the spacecraft, the thermal loads can be reduced, while also opening a magnetic window for radio communications and mitigating the blackout phenomenon. The application of this MHD-enabled system has previously not been demonstrated in realistic conditions due to the required large magnetic fields (on the order of Tesla or more), which for conventional technologies would demand exceptionally heavy and power-hungry electromagnets. High-temperature superconductors (HTS) have reached a level of industrial maturity sufficient for them to act as a key enabling technology for this application. Thanks to superior current densities, HTS coils can offer the necessary low weight and compactness required for space applications, with the ability to generate the strong magnetic fields needed for entry purposes. This paper provides an overview of the MEESST project, including its goals, methodology and some preliminary design considerations

    AI is a viable alternative to high throughput screening: a 318-target study

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    : 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 AtomNet® 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 AtomNet® 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

    Impact of opioid-free analgesia on pain severity and patient satisfaction after discharge from surgery: multispecialty, prospective cohort study in 25 countries

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    Background: Balancing opioid stewardship and the need for adequate analgesia following discharge after surgery is challenging. This study aimed to compare the outcomes for patients discharged with opioid versus opioid-free analgesia after common surgical procedures.Methods: This international, multicentre, prospective cohort study collected data from patients undergoing common acute and elective general surgical, urological, gynaecological, and orthopaedic procedures. The primary outcomes were patient-reported time in severe pain measured on a numerical analogue scale from 0 to 100% and patient-reported satisfaction with pain relief during the first week following discharge. Data were collected by in-hospital chart review and patient telephone interview 1 week after discharge.Results: The study recruited 4273 patients from 144 centres in 25 countries; 1311 patients (30.7%) were prescribed opioid analgesia at discharge. Patients reported being in severe pain for 10 (i.q.r. 1-30)% of the first week after discharge and rated satisfaction with analgesia as 90 (i.q.r. 80-100) of 100. After adjustment for confounders, opioid analgesia on discharge was independently associated with increased pain severity (risk ratio 1.52, 95% c.i. 1.31 to 1.76; P < 0.001) and re-presentation to healthcare providers owing to side-effects of medication (OR 2.38, 95% c.i. 1.36 to 4.17; P = 0.004), but not with satisfaction with analgesia (beta coefficient 0.92, 95% c.i. -1.52 to 3.36; P = 0.468) compared with opioid-free analgesia. Although opioid prescribing varied greatly between high-income and low- and middle-income countries, patient-reported outcomes did not.Conclusion: Opioid analgesia prescription on surgical discharge is associated with a higher risk of re-presentation owing to side-effects of medication and increased patient-reported pain, but not with changes in patient-reported satisfaction. Opioid-free discharge analgesia should be adopted routinely

    Medical care in long-term survivors of childhood cancer: A report from the childhood cancer survivor study

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    Purpose: To evaluate whether childhood cancer survivors receive regular medical care focused on the specific morbidities that can arise from their therapy. Patients and Methods: We conducted a cross-sectional survey of health care use in 8,522 participants in the Childhood Cancer Survivor Study, a multi-institutional cohort of childhood cancer survivors. We assessed medical visits in the preceding 2 years, whether these visits were related to the prior cancer, whether survivors received advice about how to reduce their long-term risks, and whether screening tests were discussed or ordered. Completion of echocardiograms and mammograms were assessed in patients at high risk for cardiomyopathy or breast cancer. We examined the relationship between demographics, treatment, health status, chronic medical conditions, and health care use. Results: Median age at cancer diagnosis was 6.8 years (range, 0 to 20.9 years) and at interview was 31.4 years (range, 17.5 to 54.1 years). Although 88.8% of survivors reported receiving some form of medical care, only 31.5% reported care that focused on their prior cancer (survivor-focused care), and 17.8% reported survivor-focused care that included advice about risk reduction or discussion or ordering of screening tests. Among survivors who received medical care, those who were black, older at interview, or uninsured were less likely to have received risk-based, survivor-focused care. Among patients at increased risk for cardiomyopathy or breast cancer, 511 (28.2%) of 1,810 and 169 (40.8%) of 414 had undergone a recommended echocardiogram or mammogram, respectively. Conclusion: Despite a significant risk of late effects after cancer therapy, the majority of childhood cancer survivors do not receive recommended risk-based care. © 2008 by American Society of Clinical Oncology
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