292 research outputs found

    Algorithm-Directed Crash Consistence in Non-Volatile Memory for HPC

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    Fault tolerance is one of the major design goals for HPC. The emergence of non-volatile memories (NVM) provides a solution to build fault tolerant HPC. Data in NVM-based main memory are not lost when the system crashes because of the non-volatility nature of NVM. However, because of volatile caches, data must be logged and explicitly flushed from caches into NVM to ensure consistence and correctness before crashes, which can cause large runtime overhead. In this paper, we introduce an algorithm-based method to establish crash consistence in NVM for HPC applications. We slightly extend application data structures or sparsely flush cache blocks, which introduce ignorable runtime overhead. Such extension or cache flushing allows us to use algorithm knowledge to \textit{reason} data consistence or correct inconsistent data when the application crashes. We demonstrate the effectiveness of our method for three algorithms, including an iterative solver, dense matrix multiplication, and Monte-Carlo simulation. Based on comprehensive performance evaluation on a variety of test environments, we demonstrate that our approach has very small runtime overhead (at most 8.2\% and less than 3\% in most cases), much smaller than that of traditional checkpoint, while having the same or less recomputation cost.Comment: 12 page

    Quantitative Proteomic and Transcriptomic Analyses of Metabolic Regulation of Adult Reproductive Diapause in Drosophila suzukii (Diptera: Drosophilidae) Females

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    Diapause is a form of dormancy used by many insects to survive adverse environmental conditions, which can occur in specific developmental stages in different species. Drosophila suzukii is a serious economic pest and we determined the conditions for adult reproductive diapause by the females in our previous studies. In this study, we combined RNA-Seq transcriptomic and quantitative proteomic analyses to identify adult reproductive diapause-related genes and proteins. According to the transcriptomic analysis, among 242 annotated differentially expressed genes in non-diapause and diapause females, 129 and 113 genes were up- and down-regulated, respectively. In addition, among the 2,375 proteins quantified, 39 and 23 proteins were up- and down-regulated, respectively. The gene expression patterns in diapause- and non-diapause were confirmed by qRT-PCR or western blot analysis. The overall analysis of robustly regulated genes at the protein and mRNA levels found four genes that overlapped in the up-regulated group and six genes in the down-regulated group, and thus these proteins/genes may regulate adult reproductive diapause. These differentially expressed proteins/genes act in the citrate cycle, insulin signaling pathway, PI3K-Akt signaling pathway, and amino acid biosynthesis pathways. These results provide the basis for further studies of the molecular regulation of reproductive diapause in this species

    Curcumin-loaded nanostructured lipid carrier induced apoptosis in human HepG2 cells through activation of DR5/caspases-mediated extrinsic apoptosis pathway

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    Curcumin is a lipophilic anti-cancer compound extracted from turmeric. Our previous study demonstrated that the curcumin-loaded nanostructured lipid carrier (Cur-NLC) exhibits superior anti-cancer activity in inhibiting proliferation as well as inducing apoptosis of human HepG2 cells compared to native curcumin. This study aims to unveil the mechanisms underlying the pro-apoptotic effect of Cur-NLC on HepG2 cells. Evidence indicates that low expression of death receptors (DRs) on cancer cell membranes leads to attenuated apoptosis signaling. This study showed that Cur-NLC significantly increased total expression of DR5 protein while simultaneously upregulated cell membrane expression of DR5. Cur-NLC significantly increased caspase-8 and caspase-3 activities, accompanied by increased apoptosis. Furthermore, enhanced apoptosis was inhibited in the presence of a pan-caspase inhibitor, Z-VAD-FMK. Therefore, Cur-NLC induced activation of the extrinsic apoptosis pathway via modulating the DR5/caspase-8/-3 mediated apoptosis pathway in HepG2 cells, suggesting that Cur-NLC is a promising therapeutic agent or supplement for the treatment of hepatocellular carcinoma

    Fork head transcription factor is required for ovarian mature in the brown planthopper, Nilaparvata lugens (Stål)

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    <p>Abstract</p> <p>Background</p> <p>The brown planthopper (BPH), <it>Nilaparvata lugens</it>, is the most devastating rice pest in many areas throughout Asia. The reproductive system of female <it>N. lugens </it>consists of a pair of ovaries with 24-33 ovarioles per ovary in most individuals which determine its fecundity. The fork head (Fox) is a transcriptional regulatory molecule, which regulates and controls many physiological processes in eukaryotes. The Fox family has several subclasses and members, and several Fox factors have been reported to be involved in regulating fecundity.</p> <p>Results</p> <p>We have cloned a fork head gene in <it>N. lugens</it>. The full-length cDNA of <it>Nl</it>FoxA is 1789 bp and has an open reading frame of 1143 bp, encoding a protein of 380 amino acids. Quantitative real-time PCR (RT-qPCR) and Reverse Transcription- PCR (RT-PCR) analysis revealed that <it>NlFoxA </it>mRNA was mainly expressed in the fat body, midgut, cuticle and Malpighian tube, and was expressed continuously with little change during all the developmental stages. <it>Nl</it>FoxA belongs to the FoxA subfamily of the Fox transcription factors. Knockdown of <it>NlFoxA </it>expression by RNAi using artificial diet containing double-stranded RNA (dsRNA) significantly decreased the number of offspring and impacted the development of ovaries. ELISA and Western blot analyses showed that feeding-based RNAi of <it>NlFoxA </it>gene also resulted in decreased expression of vitellogenin (Vg) protein.</p> <p>Conclusion</p> <p><it>Nl</it>FoxA plays an important role in regulation of fecundity and development of ovaries in the BPH via regulating vitellogenin expression.</p

    Poly[(μ-1H-benzimidazole-5,6-dicarboxyl­ato)lead(II)]

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    The crystal structure of the two-dimensional polymeric title compound, [Pb(C9H4N2O4)]n, comprises one crystallo­graphic­ally independent PbII atom and one fully deprotonated 1H-benzimidazole-5,6-dicarboxyl­ate (H2 L) ligand. The PbII atom is seven-coordinated by six O atoms and one N atom from the H2 L ligands, giving a capped octa­hedral coordination geometry. The structure is a layered two-dimensional coordination polymer extending parallel to (100) with N—H⋯O hydrogen bonds inter­actions between the layers, stabilizing the crystal structure

    Anomalous extensive landfast sea ice in the vicinity of Inexpressible Island, Antarctica

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    On 10 December 2017, a Chinese research vessel R/V Xuelong encountered an extensive area of landfast ice offshore Inexpressible Island (Antarctica) near the location where the fifth Chinese Antarctic research station is to be built. Using multi-source satellite images and weather data, we analyzed the ice conditions during the event season and reconstructed the development of landfast ice. Two stages in late September and early October were identified as contributing to the final ice extent. These two events are highly related to local- and large-scale weather conditions. Satellite images from 2003 to 2017 showed that four in fifteen years experienced severe landfast ice conditions, suggesting that it is not a rare phenomenon

    GLM-130B: An Open Bilingual Pre-trained Model

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    We introduce GLM-130B, a bilingual (English and Chinese) pre-trained language model with 130 billion parameters. It is an attempt to open-source a 100B-scale model at least as good as GPT-3 (davinci) and unveil how models of such a scale can be successfully pre-trained. Over the course of this effort, we face numerous unexpected technical and engineering challenges, particularly on loss spikes and divergence. In this paper, we introduce the training process of GLM-130B including its design choices, training strategies for both efficiency and stability, and engineering efforts. The resultant GLM-130B model offers significant outperformance over GPT-3 175B (davinci) on a wide range of popular English benchmarks while the performance advantage is not observed in OPT-175B and BLOOM-176B. It also consistently and significantly outperforms ERNIE TITAN 3.0 260B -- the largest Chinese language model -- across related benchmarks. Finally, we leverage a unique scaling property of GLM-130B to reach INT4 quantization without post training, with almost no performance loss, making it the first among 100B-scale models and more importantly, allowing its effective inference on 4×\timesRTX 3090 (24G) or 8×\timesRTX 2080 Ti (11G) GPUs, the most affordable GPUs required for using 100B-scale models. The GLM-130B model weights are publicly accessible and its code, training logs, related toolkit, and lessons learned are open-sourced at \url{https://github.com/THUDM/GLM-130B/}.Comment: Accepted to ICLR 202

    Genome-wide characterization of SOS1 gene family in potato (Solanum tuberosum) and expression analyses under salt and hormone stress

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    Salt Overly Sensitive 1 (SOS1) is one of the members of the Salt Overly Sensitive (SOS) signaling pathway and plays critical salt tolerance determinant in plants, while the characterization of the SOS1 family in potato (Solanum tuberosum) is lacking. In this study, 37 StSOS1s were identified and found to be unevenly distributed across 10 chromosomes, with most of them located on the plasma membrane. Promoter analysis revealed that the majority of these StSOS1 genes contain abundant cis-elements involved in various abiotic stress responses. Tissue specific expression showed that 21 of the 37 StSOS1s were widely expressed in various tissues or organs of the potato. Molecular interaction network analysis suggests that 25 StSOS1s may interact with other proteins involved in potassium ion transmembrane transport, response to salt stress, and cellular processes. In addition, collinearity analysis showed that 17, 8, 1 and 5 of orthologous StSOS1 genes were paired with those in tomato, pepper, tobacco, and Arabidopsis, respectively. Furthermore, RT-qPCR results revealed that the expression of StSOS1s were significant modulated by various abiotic stresses, in particular salt and abscisic acid stress. Furthermore, subcellular localization in Nicotiana benthamiana suggested that StSOS1-13 was located on the plasma membrane. These results extend the comprehensive overview of the StSOS1 gene family and set the stage for further analysis of the function of genes in SOS and hormone signaling pathways

    Potential drug-drug interaction of olverembatinib (HQP1351) using physiologically based pharmacokinetic models

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    Olverembatinib (HQP1351) is a third-generation BCR-ABL tyrosine kinase inhibitor for the treatment of chronic myeloid leukemia (CML) (including T315I-mutant disease), exhibits drug-drug interaction (DDI) potential through cytochrome P450 (CYP) enzymes CYP3A4, CYP2C9, CYP2C19, CYP1A2, and CYP2B6. A physiologically-based pharmacokinetic (PBPK) model was constructed based on physicochemical and in vitro parameters, as well as clinical data to predict 1) potential DDIs between olverembatinib and CYP3A4 and CYP2C9 inhibitors or inducers 2), effects of olverembatinib on the exposure of CYP1A2, CYP2B6, CYP2C9, CYP2C19, and CYP3A4 substrates, and 3) pharmacokinetics in patients with liver function injury. The PBPK model successfully described observed plasma concentrations of olverembatinib from healthy subjects and patients with CML after a single administration, and predicted olverembatinib exposure increases when co-administered with itraconazole (strong CYP3A4 inhibitor) and decreases with rifampicin (strong CYP3A4 inducer), which were validated by observed data. The predicted results suggest that 1) strong, moderate, and mild CYP3A4 inhibitors (which have some overlap with CYP2C9 inhibitors) may increase olverembatinib exposure by approximately 2.39-, 1.80- to 2.39-, and 1.08-fold, respectively; strong, and moderate CYP3A4 inducers may decrease olverembatinib exposure by approximately 0.29-, and 0.35- to 0.56-fold, respectively 2); olverembatinib, as a “perpetrator,” would have no or limited impact on CYP1A2, CYP2B6, CYP2C9, CYP2C19, and CYP3A4 enzyme activity 3); systemic exposure of olverembatinib in liver function injury with Child-Pugh A, B, C may increase by 1.22-, 1.79-, and 2.13-fold, respectively. These simulations inform DDI risk for olverembatinib as either a “victim” or “perpetrator”
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