OpenMM 8: Molecular Dynamics Simulation with Machine Learning Potentials

Machine learning plays an important and growing role in molecular simulation. The newest version of the OpenMM molecular dynamics toolkit introduces new features to support the use of machine learning potentials. Arbitrary PyTorch models can be added to a simulation and used to compute forces and energy. A higher-level interface allows users to easily model their molecules of interest with general purpose, pretrained potential functions. A collection of optimized CUDA kernels and custom PyTorch operations greatly improves the speed of simulations. We demonstrate these features on simulations of cyclin-dependent kinase 8 (CDK8) and the green fluorescent protein (GFP) chromophore in water. Taken together, these features make it practical to use machine learning to improve the accuracy of simulations at only a modest increase in cost.Comment: 16 pages, 5 figure

OpenMM 8:Molecular Dynamics Simulation with Machine Learning Potentials

Machine learning plays an important and growing role in molecular simulation. The newest version of the OpenMM molecular dynamics toolkit introduces new features to support the use of machine learning potentials. Arbitrary PyTorch models can be added to a simulation and used to compute forces and energy. A higher-level interface allows users to easily model their molecules of interest with general purpose, pretrained potential functions. A collection of optimized CUDA kernels and custom PyTorch operations greatly improves the speed of simulations. We demonstrate these features in simulations of cyclin-dependent kinase 8 (CDK8) and the green fluorescent protein chromophore in water. Taken together, these features make it practical to use machine learning to improve the accuracy of simulations with only a modest increase in cost.</p

Bioactive characterization of Persea americana Mill. by-products: A rich source of inherent antioxidants

[EN] Avocado (Persea americana Mill.) is a worldwide consumed fruit, with great interest for cosmetic and pharmaceutical industries; however, 30% of avocado fruits are bio-wastes (peels and kernels), converting them into a potential source of bioactive compounds, such as phenolic compounds. Therefore, the hydroethanolic extracts of peels and kernels of Persea america Mill. var. Hass were analysed regarding their individual phenolic profile by HPLC-DAD/ESI-MS and correlated with their antioxidant, antimicrobial and cytotoxic activities. Avocado by-products presented a very distinct phenolic profile, presenting higher concentration in peels (227.9 mg/g of extract for total phenolic content), mainly in (epi)catechin derivatives (175 mg/g of extract), followed by chlorogenic derivatives (42.9 mg/g of extract). In this study hydrophilic and lipophilic antioxidant assays were performed together for the first time in P. americana by-products, and although kernels showed a great antioxidant potential (EC50 values ranging from 18.1 to 276 mu g/mL), peels presented the highest potential (EC50 ranging from 11.7 to 152 mu g/mL), mainly due to the presence of phenolic compounds, and an overall better performance in the antibacterial assays. Further studies needs to be conducted to better understand the correlation between the presence of phenolic compounds and bioactivities, however, the main objective is to implement these biocompounds in different products and industries, due to results obtained, P. americana peels could be a great alternative in the substitution of synthetic antioxidants.The authors are grateful to the Foundation for Science and Technology(FCT, Portugal) and FEDER under Program PT2020 for financial support to CIMO (UID/AGR/00690/2013) and L. Barros contract. The authors would like to thank the Interreg Espana-Portugal for financial support through the project 0377_Iberphenol_6_E. B. Melgar thanks CONACyT for his grant (No. 329930). The authors are also grateful to the Serbian Ministry of Education, Science and Technological Development, grant number 173032 for financial support.Melgar-Castañeda, B.; Dias, MI.; Ciric, A.; Sokovic, M.; Garcia-Castello, EM.; Rodríguez López, AD.; Barros, L.... (2018). Bioactive characterization of Persea americana Mill. by-products: A rich source of inherent antioxidants. Industrial Crops and Products. 111:212-218. https://doi.org/10.1016/j.indcrop.2017.10.024S21221811

Two photons into \pi^0\pi^0

We perform a theoretical study based on dispersion relations of the reaction \gamma\gamma\to \pi^0\pi^0 emphasizing the low energy region. We discuss how the f_0(980) signal emerges in \gamma\gamma\to \pi\pi within the dispersive approach and how this fixes to a large extent the phase of the isoscalar S-wave \gamma\gamma\to \pi\pi amplitude above the K\bar{K} threshold. This allows us to make sharper predictions for the cross section at lower energies and our results could then be used to distinguish between different \pi\pi isoscalar S-wave parameterizations with the advent of new precise data on \gamma\gamma\to\pi^0\pi^0. We compare our dispersive approach with an updated calculation employing Unitary Chiral Perturbation Theory (U\chiPT). We also pay special attention to the role played by the \sigma resonance in \gamma\gamma\to\pi\pi and calculate its coupling and width to gamma\gamma, for which we obtain \Gamma(\sigma\to\gamma\gamma)=(1.68\pm 0.15) KeV.Comment: 31 pages, 9 figure

Effectiveness and safety of first-generation protease inhibitors in clinical practice: Hepatitis C virus patients with advanced fibrosis

AIM: To evaluates the effectiveness and safety of the first generation, NS3/4A protease inhibitors (PIs) in clinical practice against chronic C virus, especially in patients with advanced fibrosis. METHODS: Prospective study and non-experimental analysis of a multicentre cohort of 38 Spanish hospitals that includes patients with chronic hepatitis C genotype 1, treatment-nai¨ve (TN) or treatment-experienced (TE), who underwent triple therapy with the first generation NS3/4A protease inhibitors, boceprevir (BOC) and telaprevir (TVR), in combination with pegylated interferon and ribavirin. The patients were treatment in routine practice settings. Data on the study population and on adverse clinical and virologic effects were compiled during the treatment period and during follow up. RESULTS: One thousand and fifty seven patients were included, 405 (38%) were treated with BOC and 652 (62%) with TVR. Of this total, 30% (n = 319) were TN and the remaining were TE: 28% (n = 298) relapsers, 12% (n = 123) partial responders (PR), 25% (n = 260) null-responders (NR) and for 5% (n = 57) with prior response unknown. The rate of sustained virologic response (SVR) by intention-to-treatment (ITT) was greater in those treated with TVR (65%) than in those treated with BOC (52%) (P < 0.0001), whereas by modified intention-to-treatment (mITT) no were found significant differences. By degree of fibrosis, 56% of patients were F4 and the highest SVR rates were recorded in the non-F4 patients, both TN and TE. In the analysis by groups, the TN patients treated with TVR by ITT showed a higher SVR (P = 0.005). However, by mITT there were no significant differences between BOC and TVR. In the multivariate analysis by mITT, the significant SVR factors were relapsers, IL28B CC and non-F4; the type of treatment (BOC or TVR) was not significant. The lowest SVR values were presented by the F4-NR patients, treated with BOC (46%) or with TVR (45%). 28% of the patients interrupted the treatment, mainly by non-viral response (51%): this outcome was more frequent in the TE than in the TN patients (57% vs 40%, P = 0.01). With respect to severe haematological disorders, neutropaenia was more likely to affect the patients treated with BOC (33% vs 20%, P = 0.0001), and thrombocytopaenia and anaemia, the F4 patients (P = 0.000, P = 0.025, respectively). CONCLUSION: In a real clinical practice setting with a high proportion of patients with advanced fibrosis, effectiveness of first-generation PIs was high except for NR patients, with similar SVR rates being achieved by BOC and TVR

A922 Sequential measurement of 1 hour creatinine clearance (1-CRCL) in critically ill patients at risk of acute kidney injury (AKI)

Meeting abstrac

Evolution of the use of corticosteroids for the treatment of hospitalised COVID-19 patients in Spain between March and November 2020: SEMI-COVID national registry

Objectives: Since the results of the RECOVERY trial, WHO recommendations about the use of corticosteroids (CTs) in COVID-19 have changed. The aim of the study is to analyse the evolutive use of CTs in Spain during the pandemic to assess the potential influence of new recommendations. Material and methods: A retrospective, descriptive, and observational study was conducted on adults hospitalised due to COVID-19 in Spain who were included in the SEMI-COVID- 19 Registry from March to November 2020. Results: CTs were used in 6053 (36.21%) of the included patients. The patients were older (mean (SD)) (69.6 (14.6) vs. 66.0 (16.8) years; p < 0.001), with hypertension (57.0% vs. 47.7%; p < 0.001), obesity (26.4% vs. 19.3%; p < 0.0001), and multimorbidity prevalence (20.6% vs. 16.1%; p < 0.001). These patients had higher values (mean (95% CI)) of C-reactive protein (CRP) (86 (32.7-160) vs. 49.3 (16-109) mg/dL; p < 0.001), ferritin (791 (393-1534) vs. 470 (236- 996) µg/dL; p < 0.001), D dimer (750 (430-1400) vs. 617 (345-1180) µg/dL; p < 0.001), and lower Sp02/Fi02 (266 (91.1) vs. 301 (101); p < 0.001). Since June 2020, there was an increment in the use of CTs (March vs. September; p < 0.001). Overall, 20% did not receive steroids, and 40% received less than 200 mg accumulated prednisone equivalent dose (APED). Severe patients are treated with higher doses. The mortality benefit was observed in patients with oxygen saturation </=90%. Conclusions: Patients with greater comorbidity, severity, and inflammatory markers were those treated with CTs. In severe patients, there is a trend towards the use of higher doses. The mortality benefit was observed in patients with oxygen saturation </=90%