Effects of turbulence-chemistry interactions on auto-ignition and flame structure for n-dodecane spray combustion

The Engine Combustion Network (ECN) spray A under diesel engine conditions is investigated with a non-adiabatic 5D Flamelet Generated Manifolds (FGM) model with the consideration of detailed chemical kinetic mechanisms. The enthalpy deficit due to droplet vapourisation is considered by employing an additional controlling parameter in the FGM library. In this FGM model, ß-PDF is used for the PDF integration over the control variable space. Validation results in non-reacting conditions indicate relatively good agreement between the predicted and experimental data in terms of liquid and vapour penetrations and mixture fraction spatial distribution. In reacting conditions, the effects of variance of mixture fraction and progress variable were examined. The ignition delay time and the quasi-steady flame structure are both affected by the variances. The variance of mixture fraction delays the ignition process and the variance of progress variable accelerates it. For mixture fraction, the ignition process is quicker at any stage in the case of neglecting variance. While things are more complex for progress variable, the ignition process is advanced in the case of neglecting variance at early times, but surpassed by the case of ß-PDF later and until auto-ignition. When variance of mixture fraction is considered, the OH mass fraction shows a wide spatial distribution. While if not, a very thin flame is observed with a higher peak in OH, and a very large lift-off length. The variance of progress variable has little impact on the global flame structure, but makes the flame lift-off length much shorter. This study confirms the general observation, that the variance of mixture fraction is of higher importance in high temperature non-premixed combustion, however, we found that the variance of progress variable is far from negligible.This work was supported by Major Research Plan of the National Natural Sci-ence Foundation of China (No. 91541205); National Natural Science Foundation of China [grant numbers 51876140]; the project of National Key R&D Program of China (2017YFE0102800); This project has also received funding from the European Union’s Horizon 2020 research and innovation programme under the Marie Sk lodowska-Curie grant agreement No. 713673. Ambrus Both has received financial support through the ”la Caixa” INPhINIT Fellowship Grant for Doctoral studies at Spanish Research Centres of Excellence, ”la Caixa” Banking Foundation, Barcelona, Spain.Peer ReviewedPostprint (author's final draft

A novel 4-(1,3,4-thiadiazole-2-ylthio)pyrimidine derivative inhibits cell proliferation by suppressing the MEK/ERK signaling pathway in colorectal cancer

Colorectal cancer (CRC) is one of the most common types of malignant cancers worldwide. Although molecularly targeted therapies have significantly improved treatment outcomes, most of these target inhibitors are resistant. Novel inhibitors as potential anti-cancer drug candidates are still needed to be discovered. Therefore, in the present study, we synthesized a novel 4-(1,3,4-thiadiazole-2-ylthio)pyrimidine derivative (compound 4) using fragment- and structure-based techniques and then investigated the anti-cancer effect and underlying mechanism of anti-CRC. The results revealed that compound 4 significantly inhibited HCT116 cell proliferation with IC50 values of 8.04 ± 0.94 µmol L–1 after 48 h and 5.52 ± 0.42 µmol L–1 after 72 h, respectively. Compound 4 also inhibited colony formation, migration, and invasion of HCT116 cells in a dose-dependent manner, as well as inducing cell apoptosis and arresting the cell cycle in the G2/M phase. In addition, compound 4 was able to inhibit the activation of the MEK/ERK signaling in HCT116 cells. And compound 4 yielded the same effects as the MEK inhibitor U0126 on cell apoptosis and MEK/ERK-related proteins. These findings suggested that compound 4 inhibited cell proliferation and growth, and induced cell apoptosis, indicating its use as e a novel and potent anti-cancer agent against CRC via the MEK/ERK signaling pathway

SMAUG: End-to-End Full-Stack Simulation Infrastructure for Deep Learning Workloads

In recent years, there has been tremendous advances in hardware acceleration of deep neural networks. However, most of the research has focused on optimizing accelerator microarchitecture for higher performance and energy efficiency on a per-layer basis. We find that for overall single-batch inference latency, the accelerator may only make up 25-40%, with the rest spent on data movement and in the deep learning software framework. Thus far, it has been very difficult to study end-to-end DNN performance during early stage design (before RTL is available) because there are no existing DNN frameworks that support end-to-end simulation with easy custom hardware accelerator integration. To address this gap in research infrastructure, we present SMAUG, the first DNN framework that is purpose-built for simulation of end-to-end deep learning applications. SMAUG offers researchers a wide range of capabilities for evaluating DNN workloads, from diverse network topologies to easy accelerator modeling and SoC integration. To demonstrate the power and value of SMAUG, we present case studies that show how we can optimize overall performance and energy efficiency for up to 1.8-5x speedup over a baseline system, without changing any part of the accelerator microarchitecture, as well as show how SMAUG can tune an SoC for a camera-powered deep learning pipeline.Comment: 14 pages, 20 figure

Identification of BC005512 as a DNA Damage Responsive Murine Endogenous Retrovirus of GLN Family Involved in Cell Growth Regulation

Genotoxicity assessment is of great significance in drug safety evaluation, and microarray is a useful tool widely used to identify genotoxic stress responsive genes. In the present work, by using oligonucleotide microarray in an in vivo model, we identified an unknown gene BC005512 (abbreviated as BC, official full name: cDNA sequence BC005512), whose expression in mouse liver was specifically induced by seven well-known genotoxins (GTXs), but not by non-genotoxins (NGTXs). Bioinformatics revealed that BC was a member of the GLN family of murine endogenous retrovirus (ERV). However, the relationship to genotoxicity and the cellular function of GLN are largely unknown. Using NIH/3T3 cells as an in vitro model system and quantitative real-time PCR, BC expression was specifically induced by another seven GTXs, covering diverse genotoxicity mechanisms. Additionally, dose-response and linear regression analysis showed that expression level of BC in NIH/3T3 cells strongly correlated with DNA damage, measured using the alkaline comet assay,. While in p53 deficient L5178Y cells, GTXs could not induce BC expression. Further functional studies using RNA interference revealed that down-regulation of BC expression induced G1/S phase arrest, inhibited cell proliferation and thus suppressed cell growth in NIH/3T3 cells. Together, our results provide the first evidence that BC005512, a member from GLN family of murine ERV, was responsive to DNA damage and involved in cell growth regulation. These findings could be of great value in genotoxicity predictions and contribute to a deeper understanding of GLN biological functions

The complete chloroplast genome sequence of Hordeum distichon (Poales: Poaceae)

Hordeum distichon (H. distichon) is a two-row cultivated barley used as food and as a feed crop. Chloroplast genome is an excellent way to study the genetic structure and evolutionary process of natural population of plant species in recent years. In this study, the complete chloroplast genome of H. distichon was sequenced and analyzed: the size of the chloroplast genome is 136,462 bp in length, including a large single copy region (LSC) of 80,597 bp, a small single copy region (SSC) of 12,701 bp, and a pair of inverted repeated regions (IR) of 21,582 bp; the H. distichon chloroplast genome encodes 129 genes, including 83 protein-coding genes, 38 tRNA genes, and eight rRNA genes; the overall GC-content of the chloroplast genome was 38.32%, with the LSC, SSC, and IR regions being 36.31%, 32.33%, and 43.83%, respectively. Phylogenetic analysis based on 32 species with the maximum likelihood (ML) method indicated that H. distichon was closely related to Hordeum vulgare

Identification and functional analysis of the HvWRKY1 gene associated with Qingke (Hordeum vulgare L. var. nudum Hook. f.) leaf stripe disease

To explore the role of WRKY transcription factors (TFs) in the resistance process of Qingke (Hordeum vulgare L. var. nudum Hook. f.), leaves of the leaf stripe disease-resistant variety Kunlun 14 and the susceptible variety Z1141 were sequenced by transcriptome sequencing (RNA-seq). A differentially expressed gene HvnWKRY1 was identified, and its disease-resistance function was preliminarily analysed. The result showed that the open reading frame (ORF) of the gene was 1 062 bp and encoded 354 amino acids. It contained the conserved WRKY domain (273-351) and belonged to the WRKY protein family. The phylogenetic tree results showed that HvWRKY1 was most closely related to Hordeum vulgare L. The WRKY family of Qingke, barley, maize and rice were divided into categories I, II, and III, among which HvWRKY1 was located in group III. Results of the quantitative real-time fluorescence PCR (qRT-PCR) showed that the expression of HvWRKY1 was significantly (P < 0.01) higher in leaf stripe infected leaves of Kunlun 14 than that of Z1141. In Arabidopsis thaliana transformed with HvWRKY1, resistance to Botrytis cinerea was enhanced. The RNA-seq analysis showed there were 824 differentially expressed genes (DEGs). Data of the Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment indicated, that a plant-pathogen interaction pathway was enriched. This study is expected to provide a theoretical basis for further studies of functioning of  the Qingke gene HvWRKY1 in resistance to the leaf stripe disease

Causal effects between atrial fibrillation and heart failure: evidence from a bidirectional Mendelian randomization study

Abstract Background Observational studies have suggested a close association between atrial fibrillation (AF) and heart failure (HF), yet the causal effect remains uncertain. In this study, we employed a bidirectional Mendelian randomization analysis to investigate the causal effect of one disease on the other. Methods Genetic instrumental variables were obtained from large-scale summary-level genome-wide association studies of AF (n = 1,030,836) and HF(n = 1,665,481), respectively. Two-sample Mendelian randomization was conducted to establish causal inferences. Inverse-variance weighted (IVW) was the primary estimate, while additional analyses including MR Pleiotropy RESidual Sum and Outlier (MR-PRESSO), MR-Egger, and Weighted median were performed to validate robustness and identify pleiotropy. Results After accounting for confounding variables, MR analysis suggested a potential causal relationship between AF and HF. An augmented genetic predisposition to atrial fibrillation was associated with an elevated risk of heart failure (odds ratio (OR) = 1.18, 95% confidence interval (CI):1.14–1.22). Likewise, genetically determined heart failure also increased the risk of heart failure (OR = 1.44, 95%CI:1.23–1.68). The robustness of the findings was corroborated through MR sensitivity analyses, and the causal estimates remained consistent when the instrument P-value threshold was tightened. Conclusions Our bidirectional Mendelian randomization study supports a reciprocal causal relationship between AF and HF. The shared genetic profile of these conditions may provide crucial insights into potential therapeutic targets for the prevention and progression of both disorders. These findings underscore the necessity for further investigation into the underlying molecular mechanisms linking AF and HF, as well as the potential for personalized treatment strategies grounded in genetic profiling

Prognostic significance of the stress hyperglycemia ratio in critically ill patients

Abstract Background The stress hyperglycemia ratio (SHR) has demonstrated a noteworthy association with unfavorable cardiovascular clinical outcomes and heightened in-hospital mortality. Nonetheless, this relationship in critically ill patients remains uncertain. This study aims to elucidate the correlation between SHR and patient prognosis within the critical care setting. Methods A total of 8978 patients admitted in intensive care unit (ICU) were included in this study. We categorized SHR into uniform groups and assessed its relationship with mortality using logistic or Cox regression analysis. Additionally, we employed the restricted cubic spline (RCS) analysis method to further evaluate the correlation between SHR as a continuous variable and mortality. The outcomes of interest in this study were in-hospital and 1-year all-cause mortality. Results In this investigation, a total of 825 (9.2%) patients experienced in-hospital mortality, while 3,130 (34.9%) individuals died within the 1-year follow-up period. After adjusting for confounding variables, we identified a U-shaped correlation between SHR and both in-hospital and 1-year mortality. Specifically, within the SHR range of 0.75–0.99, the incidence of adverse events was minimized. For each 0.25 increase in the SHR level within this range, the risk of in-hospital mortality rose by 1.34-fold (odds ratio [OR]: 1.34, 95% CI: 1.25–1.44), while a 0.25 decrease in SHR within 0.75–0.99 range increased risk by 1.38-fold (OR: 1.38, 95% CI: 1.10–1.75). Conclusion There was a U-shaped association between SHR and short- and long-term mortality in critical ill patients, and the inflection point of SHR for poor prognosis was identified at an SHR value of 0.96

The Effect of Tai Chi Chuan on Emotional Health: Potential Mechanisms and Prefrontal Cortex Hypothesis.

Deep involvement in the negative mood over long periods of time likely results in emotional disturbances/disorders and poor mental health.&nbsp;Tai Chi Chuan (TCC) is regarded as a typical mind-body practice combining aerobic exercise and meditation to prevent and treat negative mood.&nbsp;Although there are an increasing number of TCC studies examining anxiety, depression, and mental stress, the mechanisms underlying these negative emotions are not fully understood.&nbsp;Tis review study examined TCC studies related to emotional health from both clinical patients and healthy individuals.&nbsp;Next, several potential mechanisms from physiological, psychological, and neurological perspectives were evaluated based on direct and indirect research evidence.&nbsp;We reviewed recent functional magnetic resonance imaging studies, which demonstrated changes in brain anatomy and function, mainly in the prefrontal cortex, following TCC practice.&nbsp;Finally, the effects of TCC on emotion/mental health is depicted with a prefrontal cortex hypothesis that proposed an immune system of the mind indicating the role of the prefrontal cortex as a flexible hub in regulating an individual s mental health.&nbsp;Te prefrontal cortex is likely a key biomarker among the multiple complex neural correlates to help an individual manage negative emotions/mental health.&nbsp;Future research is needed to examine TCC effects on mental health by examining the relationship between the executive control system (mainly prefrontal cortex) and limbic network (including amygdala, insula, and hippocampal gyrus).</p