Accelerating the pace of protein functional annotation with intel xeon phi coprocessors

© 2002-2011 IEEE. Intel Xeon Phi is a new addition to the family of powerful parallel accelerators. The range of its potential applications in computationally driven research is broad; however, at present, the repository of scientific codes is still relatively limited. In this study, we describe the development and benchmarking of a parallel version of {\mmb e}FindSite, a structural bioinformatics algorithm for the prediction of ligand-binding sites in proteins. Implemented for the Intel Xeon Phi platform, the parallelization of the structure alignment portion of {\mmb e}FindSite using pragma-based OpenMP brings about the desired performance improvements, which scale well with the number of computing cores. Compared to a serial version, the parallel code runs 11.8 and 10.1 times faster on the CPU and the coprocessor, respectively; when both resources are utilized simultaneously, the speedup is 17.6. For example, ligand-binding predictions for 501 benchmarking proteins are completed in 2.1 hours on a single Stampede node equipped with the Intel Xeon Phi card compared to 3.1 hours without the accelerator and 36.8 hours required by a serial version. In addition to the satisfactory parallel performance, porting existing scientific codes to the Intel Xeon Phi architecture is relatively straightforward with a short development time due to the support of common parallel programming models by the coprocessor. The parallel version of {\mmb e}FindSite is freely available to the academic community at www.brylinski.org/efindsite

GeauxDock: A novel approach for mixed-resolution ligand docking using a descriptor-based force field

© 2015 Wiley Periodicals, Inc. Molecular docking is an important component of computer-aided drug discovery. In this communication, we describe GeauxDock, a new docking approach that builds on the ideas of ligand homology modeling. GeauxDock features a descriptor-based scoring function integrating evolutionary constraints with physics-based energy terms, a mixed-resolution molecular representation of protein-ligand complexes, and an efficient Monte Carlo sampling protocol. To drive docking simulations toward experimental conformations, the scoring function was carefully optimized to produce a correlation between the total pseudoenergy and the native-likeness of binding poses. Indeed, benchmarking calculations demonstrate that GeauxDock has a strong capacity to identify near-native conformations across docking trajectories with the area under receiver operating characteristics of 0.85. By excluding closely related templates, we show that GeauxDock maintains its accuracy at lower levels of homology through the increased contribution from physics-based energy terms compensating for weak evolutionary constraints. GeauxDock is available at http://www.institute.Loni.org/lasigma/package/dock/

Tragic choices in intensive care during the COVID-19 pandemic: on fairness, consistency and community

Tragic choices arise during the COVID-19 pandemic when the limited resources made available in acute medical settings cannot be accessed by all patients who need them. In these circumstances, healthcare rationing is unavoidable. It is important in any healthcare rationing process that the interests of the community are recognised, and that decision-making upholds these interests through a fair and consistent process of decision-making. Responding to recent calls (1) to safeguard individuals’ legal rights in decision-making in intensive care, and (2) for new authoritative national guidance for decision-making, this paper seeks to clarify what consistency and fairness demand in healthcare rationing during the COVID-19 pandemic, from both a legal and ethical standpoint. The paper begins with a brief review of UK law concerning healthcare resource allocation, considering how community interests and individual rights have been marshalled in judicial deliberation about the use of limited health resources within the National Health Service (NHS). It is then argued that an important distinction needs to be drawn between procedural and outcome consistency, and that a procedurally consistent decision-making process ought to be favoured. Congruent with the position that UK courts have adopted for resource allocation decision-making in the NHS more generally, specific requirements for a procedural framework and substantive triage criteria to be applied within that framework during the COVID-19 pandemic are considered in detail

Fanning the flames: How the European Union is fuelling a new arms race - Executive Summary

At the time of writing in March 2022, a war has broken out in eastern Europe following the illegal invasion of Ukraine by Russian troops. Towards the end of 2021 unrest in the Balkans came close to boiling point. Tensions in the South China Sea continue to simmer and threaten regional and global stability. Wars and violence continue in Afghanistan, in Central Africa, Iraq, several countries across the Sahel, Syria, and Yemen among other countries and regions experiencing constant violence and consequent displacement. Some of the world's most powerful nations are sabre-rattling, drafting and deploying troops, stockpiling military materiel, and actively preparing for war – including the European Union (EU) and some of its member states. Contrary to the EU's founding principle of promoting peace, it too has been charting a course to establish itself as a global military power. History has shown, however, that far from contributing to stability and peace, militarism fuels tension, instability, destruction and devastation.In a 'watershed moment', in response to the war in Ukraine, the EU announced that it would, for the first time, fund and supply lethal weapons to a country under attack through the European Peace Facility (EPF). While this move is unprecedented, it is not unexpected. The EU has been pursuing a military path since the entry in to force of the Lisbon Treaty in 2009, which provides the legal underpinning to create a common security and defence policy. Less than a decade later, in a new point of departure, the EU created specific budget lines to allocate funding to military-related projects. This decision firmly set the EU on a new and deeply worrying trajectory, where international political and social problems were to be addressed not only through dialogue and diplomacy, but also through the threat of military solutions

An Introduction to the Chandra Carina Complex Project

The Great Nebula in Carina provides an exceptional view into the violent massive star formation and feedback that typifies giant HII regions and starburst galaxies. We have mapped the Carina star-forming complex in X-rays, using archival Chandra data and a mosaic of 20 new 60ks pointings using the Chandra X-ray Observatory's Advanced CCD Imaging Spectrometer, as a testbed for understanding recent and ongoing star formation and to probe Carina's regions of bright diffuse X-ray emission. This study has yielded a catalog of properties of >14,000 X-ray point sources; >9800 of them have multiwavelength counterparts. Using Chandra's unsurpassed X-ray spatial resolution, we have separated these point sources from the extensive, spatially-complex diffuse emission that pervades the region; X-ray properties of this diffuse emission suggest that it traces feedback from Carina's massive stars. In this introductory paper, we motivate the survey design, describe the Chandra observations, and present some simple results, providing a foundation for the 15 papers that follow in this Special Issue and that present detailed catalogs, methods, and science results.Comment: Accepted for the ApJS Special Issue on the Chandra Carina Complex Project (CCCP), scheduled for publication in May 2011. All 16 CCCP Special Issue papers are available at http://cochise.astro.psu.edu/Carina_public/special_issue.html through 2011 at least. 43 pages; 18 figure

Feasibility of 68Ga-labeled Siglec-9 peptide for the imaging of acute lung inflammation: a pilot study in a porcine model of acute respiratory distress syndrome

There is an unmet need for noninvasive, specific and quantitative imaging of inherent inflammatory activity. Vascular adhesion protein-1 (VAP-1) translocates to the luminal surface of endothelial cells upon inflammatory challenge. We hypothesized that in a porcine model of acute respiratory distress syndrome (ARDS), positron emission tomography (PET) with sialic acid-binding immunoglobulin-like lectin 9 (Siglec-9) based imaging agent targeting VAP-1 would allow quantification of regional pulmonary inflammation. ARDS was induced by lung lavages and injurious mechanical ventilation. Hemodynamics, respiratory system compliance (Crs) and blood gases were monitored. Dynamic examination using [15O]water PET-CT (10 min) was followed by dynamic (90 min) and whole-body examination using VAP-1 targeting 68Ga-labeled 1,4,7,10-tetraaza cyclododecane-1,4,7-tris-acetic acid-10-ethylene glycol-conjugated Siglec-9 motif peptide ([68Ga]Ga-DOTA-Siglec-9). The animals received an anti-VAP-1 antibody for post-mortem immunohistochemistry assay of VAP-1 receptors. Tissue samples were collected post-mortem for the radioactivity uptake, histology and immunohistochemistry assessment. Marked reduction of oxygenation and Crs, and higher degree of inflammation were observed in ARDS animals. [68Ga]Ga-DOTA-Siglec-9 PET showed significant uptake in lungs, kidneys and urinary bladder. Normalization of the net uptake rate (Ki) for the tissue perfusion resulted in 4-fold higher uptake rate of [68Ga]Ga-DOTA-Siglec-9 in the ARDS lungs. Immunohistochemistry showed positive VAP-1 signal in the injured lungs. Detection of pulmonary inflammation associated with a porcine model of ARDS was possible with [68Ga]Ga-DOTA-Siglec-9 PET when using kinetic modeling and normalization for tissue perfusion.</p

The Impact of Critical Thinking Disposition on Learning Using Business Simulations

This research seeks to determine the relationship between students’ critical thinking disposition and their learning while engaging in a business simulation at a UK higher education institution (HEI). The research informs educators making decisions about the use of simulations as to the value of considering critical thinking dispositions. Previous research has found that simulations are an effective way for students to engage actively in learning, bridging the gap between theory and practice. It has also been found that such simulations can develop students’ critical thinking skills. However, hitherto no research has been undertaken into the role that existing critical thinking disposition has on the learning of students, as measured by the degree to which students perceived that they met the module’s intended learning outcomes. This research offers insights into the role and importance of critical thinking disposition and its component dimensions and how this impacts student learning. The results indicate that the level of critical thinking disposition is positively related to the students’ learning. The implications of the research suggest educators should target business simulations at specific cohorts of students. The relative importance of the critical thinking disposition constructs and the practical educational implications of these findings are discussed

Using non-invasive biomarkers to identify hepatic fibrosis in people with type 2 diabetes mellitus: the Edinburgh type 2 diabetes study

BACKGROUND & AIMS: It is difficult to determine the different stages of non-alcoholic fatty liver disease without the use of invasive liver biopsy. In this study we investigated five non-invasive biomarkers used previously to detect hepatic fibrosis and determined the level of agreement between them in order to inform future research. METHODS: In the Edinburgh Type 2 Diabetes Study, a population-based cohort aged 60-74 years with type 2 diabetes, 831 participants underwent ultrasound assessment for fatty liver and had serum aspartate aminotransferase to alanine aminotransferase ratio (AST/ALT), aspartate to platelet ratio index (APRI), European Liver Fibrosis panel (ELF), Fibrosis-4 Score (FIB4) and liver stiffness measurement (LSM) measured. RESULTS: Literature based cut-offs yielded marked differences in the proportions of the cohort with probable liver fibrosis in the full cohort. Agreement between the top 5% of the distribution for each biomarker pair was poor. APRI and FIB4 had the best positive agreement at 76.4%, but agreement for all of the other serum biomarker pairs was between 18% and 34%. Agreement with LSM was poor (9-16%). CONCLUSIONS: We found poor correlation between the five biomarkers of liver fibrosis studied. Using the top 5% of each biomarker resulted in good agreement on the absence of advanced liver disease but poor agreement on the presence of advanced disease. Further work is required to validate these markers against liver biopsy and to determine their predictive value for clinical liver-related endpoints, in a range of different low and high risk population groups

Multidisciplinary treatment for functional neurological symptoms: a prospective study.

Although functional neurological symptoms are often very disabling there is limited information on outcome after treatment. Here we prospectively assessed the short- and long-term efficacy of an inpatient multidisciplinary programme for patients with FNS. We also sought to determine predictors of good outcome by assessing the responsiveness of different scales administered at admission, discharge and follow-up. Sixty-six consecutive patients were included. Assessments at admission, discharge and at 1 year follow-up (55%) included: the Health of the Nation Outcome Scale, the Hospital Anxiety and Depression Scale, the Patient Health Questionnaire-15, the Revised Illness Perception Questionnaire, the Common Neurological Symptom Questionnaire, the Fear Questionnaire and the Canadian Occupational Performance Measure. At discharge and at 1 year follow-up patients were also asked to complete five-point self-rated scales of improvement. There were significant improvements in clinician-rated mental health and functional ability. In addition, patients reported that their levels of mood and anxiety had improved and that they were less bothered by somatic symptoms in general and neurological symptoms in particular. Two-thirds of patients rated their general health such as "better" or "much better" at discharge and this improvement was maintained over the following year. Change in HoNOS score was the only measure that successfully predicted patient-rated improvement. Our data suggest that a specialized multidisciplinary inpatient programme for FNS can provide long-lasting benefits in the majority of patients. Good outcome at discharge was exclusively predicted by improvement in the HoNOS which continued to improve over the 1 year following discharge

Sequential, successive, and simultaneous decoders for entanglement-assisted classical communication

Bennett et al. showed that allowing shared entanglement between a sender and receiver before communication begins dramatically simplifies the theory of quantum channels, and these results suggest that it would be worthwhile to study other scenarios for entanglement-assisted classical communication. In this vein, the present paper makes several contributions to the theory of entanglement-assisted classical communication. First, we rephrase the Giovannetti-Lloyd-Maccone sequential decoding argument as a more general "packing lemma" and show that it gives an alternate way of achieving the entanglement-assisted classical capacity. Next, we show that a similar sequential decoder can achieve the Hsieh-Devetak-Winter region for entanglement-assisted classical communication over a multiple access channel. Third, we prove the existence of a quantum simultaneous decoder for entanglement-assisted classical communication over a multiple access channel with two senders. This result implies a solution of the quantum simultaneous decoding conjecture for unassisted classical communication over quantum multiple access channels with two senders, but the three-sender case still remains open (Sen recently and independently solved this unassisted two-sender case with a different technique). We then leverage this result to recover the known regions for unassisted and assisted quantum communication over a quantum multiple access channel, though our proof exploits a coherent quantum simultaneous decoder. Finally, we determine an achievable rate region for communication over an entanglement-assisted bosonic multiple access channel and compare it with the Yen-Shapiro outer bound for unassisted communication over the same channel.Comment: 33 pages, 2 figures; v2 contains a proof of the quantum simultaneous decoding conjecture for two-sender quantum multiple access channels; v3 shows how to recover the known unassisted and assisted quantum communication regions with a coherent quantum simultaneous decode