Structural determinants in the bulk heterojunction

A multiscale approach is used to characterize essential morphological features of the bulk heterojunction

High-Performance Drug Discovery: Computational Screening by Combining Docking and Molecular Dynamics Simulations

Virtual compound screening using molecular docking is widely used in the discovery of new lead compounds for drug design. However, this method is not completely reliable and therefore unsatisfactory. In this study, we used massive molecular dynamics simulations of protein-ligand conformations obtained by molecular docking in order to improve the enrichment performance of molecular docking. Our screening approach employed the molecular mechanics/Poisson-Boltzmann and surface area method to estimate the binding free energies. For the top-ranking 1,000 compounds obtained by docking to a target protein, approximately 6,000 molecular dynamics simulations were performed using multiple docking poses in about a week. As a result, the enrichment performance of the top 100 compounds by our approach was improved by 1.6–4.0 times that of the enrichment performance of molecular dockings. This result indicates that the application of molecular dynamics simulations to virtual screening for lead discovery is both effective and practical. However, further optimization of the computational protocols is required for screening various target proteins

Petascale turbulence simulation using a highly parallel fast multipole method on GPUs

This paper reports large-scale direct numerical simulations of homogeneous-isotropic fluid turbulence, achieving sustained performance of 1.08 petaflop/s on gpu hardware using single precision. The simulations use a vortex particle method to solve the Navier-Stokes equations, with a highly parallel fast multipole method (FMM) as numerical engine, and match the current record in mesh size for this application, a cube of 4096^3 computational points solved with a spectral method. The standard numerical approach used in this field is the pseudo-spectral method, relying on the FFT algorithm as numerical engine. The particle-based simulations presented in this paper quantitatively match the kinetic energy spectrum obtained with a pseudo-spectral method, using a trusted code. In terms of parallel performance, weak scaling results show the fmm-based vortex method achieving 74% parallel efficiency on 4096 processes (one gpu per mpi process, 3 gpus per node of the TSUBAME-2.0 system). The FFT-based spectral method is able to achieve just 14% parallel efficiency on the same number of mpi processes (using only cpu cores), due to the all-to-all communication pattern of the FFT algorithm. The calculation time for one time step was 108 seconds for the vortex method and 154 seconds for the spectral method, under these conditions. Computing with 69 billion particles, this work exceeds by an order of magnitude the largest vortex method calculations to date

Plasmacytoid DCs help lymph node DCs to induce anti-HSV CTLs

Antiviral cell–mediated immunity is initiated by the dendritic cell (DC) network in lymph nodes (LNs). Plasmacytoid DCs (pDCs) are known to migrate to inflamed LNs and produce interferon (IFN)-α, but their other roles in antiviral T cell immunity are unclear. We report that LN-recruited pDCs are activated to create local immune fields that generate antiviral cytotoxic T lymphocytes (CTLs) in association with LNDCs, in a model of cutaneous herpes simplex virus (HSV) infection. Although pDCs alone failed to induce CTLs, in vivo depletion of pDCs impaired CTL-mediated virus eradication. LNDCs from pDC-depleted mice showed impaired cluster formation with T cells and antigen presentation to prime CTLs. Transferring circulating pDC precursors from wild-type, but not CXCR3-deficient, mice to pDC-depleted mice restored CTL induction by impaired LNDCs. In vitro co-culture experiments revealed that pDCs provided help signals that recovered impaired LNDCs in a CD2- and CD40L-dependent manner. pDC-derived IFN-α further stimulated the recovered LNDCs to induce CTLs. Therefore, the help provided by pDCs for LNDCs in primary immune responses seems to be pivotal to optimally inducing anti-HSV CTLs

FPGAを用いた論理回路設計実験のための遠隔実験システムの作成と評価

本研究では，本学学内における対面での利用のみを想定して作成されていた実験システムを，やむを得ない理由で遠隔対応させ使用した結果，教育にどのような影響を及ぼしたかを調査した．対象となる実験システムは，本学3年生の実験科目の中のFPGA（Field Programmable Gate Array）を用いて初歩的な論理回路を設計する課題で用いられている．作成した回路の動作確認に実機の物理的な操作をともなうため，例年，受講生は機器の設置された計算機室に一堂に介して課題に取り組んできた．2020年度は新型コロナウイルス感染症対策として入構禁止措置がとられたため，学外から機器を操作する仕組みを導入し実験を遂行した．とくに致命的なトラブルもなく実験を行うことはできたが成績の低下がみられた．遠隔対応とすることで学生の望むタイミングで課題に取り組めたことが見出されたものの，対面であれば容易に行える学生の理解度チェックがオンラインでは難しいことも分かり，ひいてはそれが成績低下の一因であることが示唆された．In this study, we investigated the impacts on education as a result of using an experimental system that was originally designed for face-to-face use only, but was adapted for remote use. The target experimental system is used in the third-year undergraduate laboratory course of our university, where students are required to design elementary logic circuits using an FPGA (Field Programmable Gate Array). To assure correctness of circuits, they must operate the actual equipment physically. In past years, students have worked on their assignments together in a computer room where the equipment is lined up. But in FY2020, the campus entry was banned as a measure against COVID-19, so we added some functions to the existing equipment and created a GUI application from scratch to control the equipment from outside the campus. Although we were able to complete the experiment without any fatal problems, but the grades declined. It was found that the students were able to work on the assignments at their preferred timing in remote work. However, it was also found that it was difficult to check students\u27 understanding online, which is easy to do in person. This difficulty was suggested to be one of the reasons for the decline in grades

Association of plasma thioredoxin-1 with renal tubular damage and cardiac prognosis in patients with chronic heart failure

AbstractBackgroundThioredoxin-1 (Trx-1) is an abundant 12.5kDa redox protein expressed in almost all eukaryotic cells that protect against the development of heart failure and kidney dysfunction. Plasma Trx-1 levels are considered as a reliable marker for oxidative stress. However, it remains to be determined whether plasma Trx-1 levels can predict cardiac prognosis in patients with chronic heart failure (CHF).Methods and resultsWe measured plasma Trx-1 levels and urinary β2-microglobulin–creatinine ratio (UBCR), a marker for renal tubular damage, in 156 consecutive patients with CHF and 17 control subjects. The patients were prospectively followed for a median follow-up period of 627 days and 46 cardiac events were observed. The patients with cardiac events had significantly higher plasma Trx-1 levels and UBCR levels than the cardiac event-free patients. Multivariate Cox proportional hazard analysis revealed that an elevated Trx-1 level was independently associated with poor outcome in patients with CHF after adjustment for confounding factors (hazard ratio, 1.74; 95% confidence interval, 1.33–2.29; p<0.0001). UBCR was increased with higher plasma Trx-1 levels. Kaplan–Meier analysis demonstrated that the highest Trx-1 tertile was associated with the highest risk of cardiac events.ConclusionPlasma Trx-1 level was associated with renal tubular damage and cardiac prognosis, suggesting that it could be a useful marker to identify patients at high risk for comorbid heart failure and renal tubular damage

High-mobility group box 1-mediated heat shock protein beta 1 expression attenuates mitochondrial dysfunction and apoptosis

AbstractAimsApoptosis of cardiomyocytes is thought to account for doxorubicin cardiotoxicity as it contributes to loss of myocardial tissue and contractile dysfunction. Given that high-mobility group box 1 (HMGB1) is a nuclear DNA-binding protein capable of inhibiting apoptosis, we aimed to clarify the role of HMGB1 in heat shock protein beta 1 (HSPB1) expression during doxorubicin-induced cardiomyopathy.Methods and resultsMitochondrial damage, cardiomyocyte apoptosis, and cardiac dysfunction after doxorubicin administration were significantly attenuated in mice with cardiac-specific overexpression of HMGB1 (HMGB1-Tg) compared with wild type (WT) -mice. HSPB1 levels after doxorubicin administration were significantly higher in HMGB1-Tg mice than in WT mice. Transfection with HMGB1 increased the expression of HSPB1 at both the protein and mRNA levels, and HMGB1 inhibited mitochondrial dysfunction and apoptosis after exposure of cardiomyocytes to doxorubicin. HSPB1 silencing abrogated the inhibitory effect of HMGB1 on cardiomyocyte apoptosis. Doxorubicin increased the binding of HMGB1 to heat shock factor 2 and enhanced heat shock element promoter activity. Moreover, HMGB1 overexpression greatly enhanced heat shock element promoter activity. Silencing of heat shock factor 2 attenuated HMGB1-dependent HSPB1 expression and abrogated the ability of HMGB1 to suppress cleaved caspase-3 accumulation after doxorubicin stimulation.ConclusionsWe report the first in vivo and in vitro evidence that cardiac HMGB1 increases HSPB1 expression and attenuates cardiomyocyte apoptosis associated with doxorubicin-induced cardiomyopathy. Cardiac HMGB1 increases HSPB1 expression in cardiomyocytes in a heat shock factor 2-dependent manner

Estimating Configuration Parameters of Pipelines for Accelerating N-Body Simulations with an FPGA using High-level Synthesis

In the era of the IoT (Internet of Things) and Edge computing, SoC (System on Chip) with an FPGA (Field Programmable Gate Array) is a suitable solution for embedded systems because it supports running rich operating systems on general-purpose CPUs, as well as the FPGA’s acceleration for specific computing. One problem of designing an accelerator on an FPGA is that optimization of the logic for the accelerator is not automatic and much trial and error is needed before attaining peak performance from the SoC. In this paper we propose a method to reduce the development time of the accelerator using N-body simulation as a target application. Based on the hardware resources needed for several pipelines of the accelerator and their performance estimation model, we can estimate how many pipelines can be implemented on an SoC. In addition, the amount of memory each pipeline requires for attaining maximum performance is suggested. Our model agreed with the actual calculation speed for different constraining conditions

分子動力学シミュレ-ション専用計算機の開発

University of Tokyo (東京大学