Maximizing resource usage in multifold molecular dynamics with rCUDA

[EN] The full-understanding of the dynamics of molecular systems at the atomic scale is of great relevance in the fields of chemistry, physics, materials science, and drug discovery just to name a few. Molecular dynamics (MD) is a widely used computer tool for simulating the dynamical behavior of molecules. However, the computational horsepower required by MD simulations is too high to obtain conclusive results in real-world scenarios. This is mainly motivated by two factors: (1) the long execution time required by each MD simulation (usually in the nanoseconds and microseconds scale, and beyond) and (2) the large number of simulations required in drug discovery to study the interactions between a large library of compounds and a given protein target. To deal with the former, graphics processing units (GPUs) have come up into the scene. The latter has been traditionally approached by launching large amounts of simulations in computing clusters that may contain several GPUs on each node. However, GPUs are targeted as a single node that only runs one MD instance at a time, which translates into low GPU occupancy ratios and therefore low throughput. In this work, we propose a strategy to increase the overall throughput of MD simulations by increasing the GPU occupancy through virtualized GPUs. We use the remote CUDA (rCUDA) middleware as a tool to decouple GPUs from CPUs, and thus enabling multi-tenancy of the virtual GPUs. As a working test in the drug discovery field, we studied the binding process of a novel flavonol to DNA with the GROningen MAchine for Chemical Simulations (GROMACS) MD package. Our results show that the use of rCUDA provides with a 1.21x speed-up factor compared to the CUDA counterpart version while requiring a similar power budget.The author(s) disclosed receipt of the following financial support for the research, authorship, and/or publication of this article: This work was jointly supported by the Fundación Séneca (Agencia Regional de Ciencia y Tecnología, Región de Murcia) under grants (20524/PDC/18, 20813/PI/ 18, and 20988/PI/18) and by the Spanish MEC and Eur-opean Commission FEDER under grants TIN2015-66972-C5-3-R, TIN2016-78799-P, and CTQ2017-87974-R (AEI/FEDER, UE). Researchers from the Universitat Politècnica de València are supported by the Generalitat Valenciana under grant PROMETEO/2017/077.Prades, J.; Imbernon, B.; Reaño González, C.; Peña-García, J.; Cerón-Carrasco, JP.; Silla Jiménez, F.; Pérez-Sánchez, H. (2020). Maximizing resource usage in multifold molecular dynamics with rCUDA. 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Molecular-Level Insight into Charge Carrier Transport and Speciation in Solid Polymer Electrolytes by Chemically Tuning Both Polymer and Lithium Salt

The advent of Li-metal batteries has seen progress toward studies focused on the chemical modification of solid polymer electrolytes, involving tuning either polymer or Li salt properties to enhance the overall cell performance. This study encompasses chemically modifying simultaneously both polymer matrix and lithium salt by assessing ion coordination environments, ion transport mechanisms, and molecular speciation. First, commercially used lithium bis(trifluoromethanesulfonyl)imide (LiTFSI) salt is taken as a reference, where F atoms become partially substituted by one or two H atoms in the −CF3 moieties of LiTFSI. These substitutions lead to the formation of lithium(difluoromethanesulfonyl)(trifluoromethanesulfonyl)imide (LiDFTFSI) and lithium bis(difluoromethanesulfonyl)imide (LiDFSI) salts. Both lithium salts promote anion immobilization and increase the lithium transference number. Second, we show that exchanging archetypal poly(ethylene oxide) (PEO) with poly(ε-caprolactone) (PCL) significantly changes charge carrier speciation. Studying the ionic structures of these polymer/Li salt combinations (LiTFSI, LiDFTFSI or LiDFSI with PEO or PCL) by combining molecular dynamics simulations and a range of experimental techniques, we provide atomistic insights to understand the solvation structure and synergistic effects that impact macroscopic properties, such as Li+ conductivity and transference number.The authors acknowledge support from the European Commission grant for Erasmus Mundus Joint Master’s Degree MESC+ under Framework Agreement Number 2018-1424/001-001-EMJMD, the EU Marie Sklodowska-Curie COFUND DESTINY project under Grant Agreement No. 945357, and the Basque Government PhD Grant. H.M. acknowledges funding from the “Departamento de Educación, Política Lingüística y Cultura del Gobierno Vasco” (Grant IT1358-22). They also thank SGI/IZO-SGIker UPV/EHU for supercomputing resources

The Gaia spectrophotometric standard stars survey - IV. Results of the absolute photometry campaign

We present Johnson-Kron-Cousins BVRI photometry of 228 candidate spectrophotometric standard stars for the external (absolute) flux calibration of Gaia data. The data were gathered as part of a 10-yr observing campaign with the goal of building the external grid of flux standards for Gaia and we obtained absolute photometry, relative photometry for constancy monitoring, and spectrophotometry. Preliminary releases of the flux tables were used to calibrate the first two Gaia releases. This paper focuses on the imaging frames observed in good sky conditions (about 9100). The photometry will be used to validate the ground-based flux tables of the Gaia spectrophotometric standard stars and to correct the spectra obtained in non-perfectly photometric observing conditions for small zero-point variations. The absolute photometry presented here is tied to the Landolt standard stars system to ≃1 per cent or better, depending on the photometric band. Extensive comparisons with various literature sources show an overall ≃1 per cent agreement, which appears to be the current limit in the accuracy of flux calibrations across various samples and techniques in the literature. The Gaia photometric precision is presently of the order of 0.1 per cent or better, thus various ideas for the improvement of photometric calibration accuracy are discussed.This work was supported by the MINECO (Spanish Ministry of Economy and Competitiveness) through grant RTI2018-095076-B-C21 (MINECO/FEDER- Fondo Europeo de Desarrollo Regional, UE). APV acknowledges FAPESP (Fundação de Amparo à Pesquisa do Estado de São Paulo) for the postdoctoral fellowship No. 2017/15893-1 and the DGAPA (Dirección General de Asuntos del Personal Académico) PAPIIT grant IG100319

Gemini GMOS--IFU spectroscopy of the compact HII galaxies Tol 0104-388 and Tol 2146-391: The dependence on the properties of the interstellar medium

Using GMOS--IFU spectroscopic observations of the compact HII/BCD galaxies Tol 0104-388 and Tol 2146-391, we study the spatial distribution of emission lines, equivalent width EW(Hb), extinction c(Hb), ionization ratios ([OIII]5007/Hb, [SII]6717,6731/Ha and [NII]6584/Ha), kinematics, and the chemical pattern (O/H, N/H and N/O) of the warm interstellar medium in these galaxies. We also investigate a possible dependence of these properties on the I(HeII4686)/I(Hb) ratio and find no significant correlation between these variables. In fact, the oxygen abundances appear to be uniform in the regions where the HeII4686 emission line was measured. It can be interpreted in the sense that these correlations are related to global properties of the galaxies and not with small patches of the interstellar medium. Although a possible weak N/H gradient is observed in Tol 2146-391, the available data suggest that the metals from previous star-formation events are well mixed and homogeneously distributed through the optical extent of these galaxies. The spatial constancy of the N/O ratio might be attributed to efficient transport and mixing of metals by starburst-driven super-shells, powered by a plethora of unresolved star cluster in the inner part of the galaxies. This scenario agrees with the idea that most of the observed HeII4686 emission line, in our sample of galaxies, is produced by radiative shocks.Comment: 16 pages, 18 figures, 5 tables, accepted for publication in MNRA

Nivolumab and sunitinib combination in advanced soft tissue sarcomas : A multicenter, single-arm, phase Ib/II trial

Sarcomas exhibit low expression of factors related to immune response, which could explain the modest activity of PD-1 inhibitors. A potential strategy to convert a cold into an inflamed microenvironment lies on a combination therapy. As tumor angiogenesis promotes immunosuppression, we designed a phase Ib/II trial to test the double inhibition of angiogenesis (sunitinib) and PD-1/PD-L1 axis (nivolumab). This single-arm, phase Ib/II trial enrolled adult patients with selected subtypes of sarcoma. Phase Ib established two dose levels: level 0 with sunitinib 37.5 mg daily from day 1, plus nivolumab 3 mg/kg intravenously on day 15, and then every 2 weeks; and level-1 with sunitinib 37.5 mg on the first 14 days (induction) and then 25 mg per day plus nivolumab on the same schedule. The primary endpoint was to determine the recommended dose for phase II (phase I) and the 6-month progression-free survival rate, according to Response Evaluation Criteria in Solid Tumors 1.1 (phase II). From May 2017 to April 2019, 68 patients were enrolled: 16 in phase Ib and 52 in phase II. The recommended dose of sunitinib for phase II was 37.5 mg as induction and then 25 mg in combination with nivolumab. After a median follow-up of 17 months (4-26), the 6-month progression-free survival rate was 48% (95% CI 41% to 55%). The most common grade 3-4 adverse events included transaminitis (17.3%) and neutropenia (11.5%). Sunitinib plus nivolumab is an active scheme with manageable toxicity in the treatment of selected patients with advanced soft tissue sarcoma, with almost half of patients free of progression at 6 months

A Precision Treatment Model for Internet-Delivered Cognitive Behavioral Therapy for Anxiety and Depression among University Students:A Secondary Analysis of a Randomized Clinical Trial

Importance: Guided internet-delivered cognitive behavioral therapy (i-CBT) is a low-cost way to address high unmet need for anxiety and depression treatment. Scalability could be increased if some patients were helped as much by self-guided i-CBT as guided i-CBT. Objective: To develop an individualized treatment rule using machine learning methods for guided i-CBT vs self-guided i-CBT based on a rich set of baseline predictors. Design, Setting, and Participants: This prespecified secondary analysis of an assessor-blinded, multisite randomized clinical trial of guided i-CBT, self-guided i-CBT, and treatment as usual included students in Colombia and Mexico who were seeking treatment for anxiety (defined as a 7-item Generalized Anxiety Disorder [GAD-7] score of ≥10) and/or depression (defined as a 9-item Patient Health Questionnaire [PHQ-9] score of ≥10). Study recruitment was from March 1 to October 26, 2021. Initial data analysis was conducted from May 23 to October 26, 2022. Interventions: Participants were randomized to a culturally adapted transdiagnostic i-CBT that was guided (n = 445), self-guided (n = 439), or treatment as usual (n = 435). Main Outcomes and Measures: Remission of anxiety (GAD-7 scores of ≤4) and depression (PHQ-9 scores of ≤4) 3 months after baseline. Results: The study included 1319 participants (mean [SD] age, 21.4 [3.2] years; 1038 women [78.7%]; 725 participants [55.0%] came from Mexico). A total of 1210 participants (91.7%) had significantly higher mean (SE) probabilities of joint remission of anxiety and depression with guided i-CBT (51.8% [3.0%]) than with self-guided i-CBT (37.8% [3.0%]; P =.003) or treatment as usual (40.0% [2.7%]; P =.001). The remaining 109 participants (8.3%) had low mean (SE) probabilities of joint remission of anxiety and depression across all groups (guided i-CBT: 24.5% [9.1%]; P =.007; self-guided i-CBT: 25.4% [8.8%]; P =.004; treatment as usual: 31.0% [9.4%]; P =.001). All participants with baseline anxiety had nonsignificantly higher mean (SE) probabilities of anxiety remission with guided i-CBT (62.7% [5.9%]) than the other 2 groups (self-guided i-CBT: 50.2% [6.2%]; P =.14; treatment as usual: 53.0% [6.0%]; P =.25). A total of 841 of 1177 participants (71.5%) with baseline depression had significantly higher mean (SE) probabilities of depression remission with guided i-CBT (61.5% [3.6%]) than the other 2 groups (self-guided i-CBT: 44.3% [3.7%]; P =.001; treatment as usual: 41.8% [3.2%]; P &lt;.001). The other 336 participants (28.5%) with baseline depression had nonsignificantly higher mean (SE) probabilities of depression remission with self-guided i-CBT (54.4% [6.0%]) than guided i-CBT (39.8% [5.4%]; P =.07). Conclusions and Relevance: Guided i-CBT yielded the highest probabilities of remission of anxiety and depression for most participants; however, these differences were nonsignificant for anxiety. Some participants had the highest probabilities of remission of depression with self-guided i-CBT. Information about this variation could be used to optimize allocation of guided and self-guided i-CBT in resource-constrained settings. Trial Registration: ClinicalTrials.gov Identifier: NCT04780542.</p

Health care utilization in the elderly Mexican population: Expenditures and determinants

<p>Abstract</p> <p>Background</p> <p>Worldwide population aging has been considered one of the most important demographic phenomena, and is frequently referred as a determinant of health costs and expenditures. These costs are an effect either of the aging process itself (social) or because of the increase that comes with older age (individual).</p> <p>Objective</p> <p>To analyze health expenditures and its determinants in a sample of Mexican population, for three dimensions acute morbidity, ambulatory care and hospitalization focusing on different age groups, particularly the elderly.</p> <p>Methods</p> <p>A secondary analysis of the Mexican National Health and Nutrition Survey (ENSANUT), 2006 was conducted. A descriptive analysis was performed to establish a health profile by socio-demographic characteristics. Logistic regression models were estimated to determine the relation between acute morbidity, ambulatory care, hospitalization and age group; to establish the determinants of hospitalization among the population 60 years and older; and to determine hospitalization expenditures by age.</p> <p>Results</p> <p>Higher proportion of elderly reporting health problems was found. Average expenditures of hospitalization in households were $240.6 am dlls, whereas in households exclusively with elderly the expenditure was$308.9 am dlls, the highest among the considered age groups. The multivariate analysis showed higher probability of being hospitalized among the elderly, but not for risks for acute morbidity and ambulatory care. Among the elderly, older age, being male or living in a city or in a metro area implied a higher probability of hospitalization during the last year, with chronic diseases playing a key role in hospitalization.</p> <p>Conclusions</p> <p>The conditions associated with age, such as chronic diseases, have higher weight than age itself; therefore, they are responsible for the higher expenditures reported. Conclusions point towards a differentiated use and intensity of health services depending on age. The projected increase in hospitalization and health care needs for this group requires immediate attention.</p