17 research outputs found

    Balanced Sparsity for Efficient DNN Inference on GPU

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    In trained deep neural networks, unstructured pruning can reduce redundant weights to lower storage cost. However, it requires the customization of hardwares to speed up practical inference. Another trend accelerates sparse model inference on general-purpose hardwares by adopting coarse-grained sparsity to prune or regularize consecutive weights for efficient computation. But this method often sacrifices model accuracy. In this paper, we propose a novel fine-grained sparsity approach, balanced sparsity, to achieve high model accuracy with commercial hardwares efficiently. Our approach adapts to high parallelism property of GPU, showing incredible potential for sparsity in the widely deployment of deep learning services. Experiment results show that balanced sparsity achieves up to 3.1x practical speedup for model inference on GPU, while retains the same high model accuracy as fine-grained sparsity

    Endogenous relapse and exogenous reinfection in recurrent pulmonary tuberculosis: A retrospective study revealed by whole genome sequencing

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    BackgroundTuberculosis may reoccur due to reinfection or relapse after initially successful treatment. Distinguishing the cause of TB recurrence is crucial to guide TB control and treatment. This study aimed to investigate the source of TB recurrence and risk factors related to relapse in Hunan province, a high TB burden region in southern China.MethodsA population-based retrospective study was conducted on all culture-positive TB cases in Hunan province, China from 2013 to 2020. Phenotypic drug susceptibility testing and whole-genome sequencing were used to detect drug resistance and distinguish between relapse and reinfection. Pearson chi-square test and Fisher exact test were applied to compare differences in categorical variables between relapse and reinfection. The Kaplan–Meier curve was generated in R studio (4.0.4) to describe and compare the time to recurrence between different groups. p < 0.05 was considered statistically significant.ResultsOf 36 recurrent events, 27 (75.0%, 27/36) paired isolates were caused by relapse, and reinfection accounted for 25.0% (9/36) of recurrent cases. No significant difference in characteristics was observed between relapse and reinfection (all p > 0.05). In addition, TB relapse occurs earlier in patients of Tu ethnicity compared to patients of Han ethnicity (p < 0.0001), whereas no significant differences in the time interval to relapse were noted in other groups. Moreover, 83.3% (30/36) of TB recurrence occurred within 3 years. Overall, these recurrent TB isolates were predominantly pan-susceptible strains (71.0%, 49/69), followed by DR-TB (17.4%, 12/69) and MDR-TB (11.6%, 8/69), with mutations mainly in codon 450 of the rpoB gene and codon 315 of the katG gene. 11.1% (3/27) of relapse cases had acquired new resistance during treatment, with fluoroquinolone resistance occurring most frequently (7.4%, 2/27), both with mutations in codon 94 of gyrA.ConclusionEndogenous relapse is the main mechanism leading to TB recurrences in Hunan province. Given that TB recurrences can occur more than 4 years after treatment completion, it is necessary to extend the post-treatment follow-up period to achieve better management of TB patients. Moreover, the relatively high frequency of fluoroquinolone resistance in the second episode of relapse suggests that fluoroquinolones should be used with caution when treating TB cases with relapse, preferably guided by DST results

    What are the risks of financial management under the digital transformation of enterprises? Evidence from systems engineering

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    Digitalization is rewriting the track of economic development and becoming a new driving force for economic growth. It is of great significance for enterprises to better complete digital transformation to scientifically and rationally understand the key indicators and their interrelationships in financial management risks. This paper constructs the index system of enterprise financial management risk under the background of digital transformation, uses the interpretative structural model (ISM) to calculate and analyze the adjacency matrix, obtains the hierarchical division of influencing factors, summarizes the internal pointing relationship between the index factors at all levels, and then uses the cross influence matrix multiplication (MICMAC) to calculate the driving-dependence relationship of each factor to judge its attribute category. This paper summarizes a relatively complete and comprehensive financial management risk impact path with the help of ISM-MICMAC method, and provides a scientific and reasonable countermeasure for enterprises that are about to or undergoing digital transformation to better avoid financial management risks

    Eutectoid Transformation Kinetics of FeO under N2 and Air Atmospheres

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    The effect of different oxygen content on eutectoid transformation kinetics in FeO were studied in this paper. Thermogravimetric analysis was employed to investigate the eutectoid reaction in the oxide formed on pure Fe after being exposed to air at 900 °C for 10 min. The oxidized specimens were held isothermally in N2 and air from 100 s to 10,000 s in the temperature range of 350 to 550 °C, and the morphologies in FeO were observed by electron probe microanalysis. The results of the eutectoid transformation are statistically analyzed, and the dynamic model of the FeO eutectoid transformation is established based on the Johnson-Mehl-Avrami-Kolmogorov equation. Combined with the measured values and the calculation results, the time of eutectoid reaction in air is earlier than that in N2. Under the experimental conditions, the formation of Fe3O4 seams can occur at the interface of the FeO-substrate after the eutectoid reaction has begun, which means the eutectoid reaction is more determined by local ion concentration changes. At the Fe3O4-FeO interface, there is a high concentration enrichment of Fe ions, giving priority to the formation of Fe-rich FeO, which makes the eutectoid phase transition time earlier than in N2 conditions

    Outcome Reporting Variability in Trials of Chinese Medicine for Hyperlipidemia: A Systematic Review for Developing a Core Outcome Set

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    Introduction. Hyperlipidemia is an underlying process behind cardiovascular disease. Chinese medicine (CM) may be effective in treating hyperlipidemia, but there is a lack of studies with high methodological quality. A major reason for this is heterogeneity in outcome reporting. Therefore, this study explores the degree of outcome reporting variation in CM trials for hyperlipidemia. It then generates a list of potentially important outcomes for developing a core outcome set (COS). Methods. A systematic review of literature focusing on studies of CM for hyperlipidemia was conducted. Outcomes were listed verbatim and grouped into 8 domains. Outcome frequency and definition uniformity were analyzed. Results. 3,702 studies and 452 individual outcomes were identified. These outcomes were reported 27,328 times, of which 1.6% were reported as primary outcomes, and 13.3% were defined. The most frequent outcome was total triglyceride, represented in 86.7% of the studies, followed by total cholesterol (86.0%), total effective rate (75.1%), high-density lipoprotein cholesterol (73.2%), and low-density lipoprotein cholesterol (60.5%). However, 43.6% of outcomes were reported only once. The largest outcome domain was “pathological or pathophysiological outcomes,” which included 67.0% of outcomes. Of the “response rate related outcomes” domain, total effective rate was the most frequently reported outcome (n = 2,780), and 95.3% of the studies gave a clear definition. However, these definitions were often contradictory. Only 10 papers reported cardiovascular events, 3 of which referred to them as primary outcomes. Moreover, ten patient-reported outcomes were reported in the retrieved literature 19 times in total. The majority of the outcomes did not report measurement instruments (MIs) (269/453, 59.4%). MIs of the surrogate outcomes were reported more frequently. Conclusion. Outcome reporting in CM trials for hyperlipidemia is inconsistent and ill-defined, creating barriers to data synthesis and comparison. Thus, we propose and are developing a COS for CM trials for hyperlipidemia

    Effects of Texture and Grain Size on the Yield Strength of ZK61 Alloy Rods Processed by Cyclic Extrusion and Compression

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    The ZK61 alloy rods with different grain sizes and crystallographic texture were successfully fabricated by cyclic extrusion and compression (CEC). Their room-temperature tension & compression yield strength displayed a significant dependence on grain size and texture, essentially attributed to {10-12} twinning. The texture variations were characterized by the angle θ between the c-axis of the grain and the extrusion direction (ED) during the process. The contour map of room-temperature yield strength as a function of grain size and the angle θ was obtained. It showed that both the tension yield strength and the compression yield strength of ZK61 alloy were fully consistent with the Hall-Patch relationship at a certain texture, but the change trends of the tension yield strength and the compression yield strength were completely opposite at the same grain size while texture altered. The friction stresses of different deformation modes calculated based on the texture confirmed the tension yield strength of the CECed ZK61 alloy rods, which was determined by both the basal slip and the tension twinning slip during the tension deformation at room temperature, while the compression yield strength was mainly determined by the basal slip during the compression deformation

    ATR inhibitor AZD6738 enhances the antitumor activity of radiotherapy and immune checkpoint inhibitors by potentiating the tumor immune microenvironment in hepatocellular carcinoma

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    Background Radioimmunotherapy has a promising antitumor effect in hepatocellular carcinoma (HCC), depending on the regulatory effect of radiotherapy on tumor immune microenvironment. Ionizing radiation (IR)-induced DNA damage repair (DDR) pathway activation leads to the inhibition of immune microenvironment, thus impairing the antitumor effect of radioimmunotherapy. However, it is unclear whether inhibition of the DDR pathway can enhance the effect of radioimmunotherapy. In this study, we aim to explore the role of DDR inhibitor AZD6738 on the combination of radiotherapy and immune checkpoint inhibitors (ICIs) in HCC.Methods C57BL/6 mouse subcutaneous tumor model was used to evaluate the ability of different treatment regimens in tumor growth control and tumor recurrence inhibition. Effects of each treatment regimen on the alterations of immunophenotypes including the quantification, activation, proliferating ability, exhaustion marker expression, and memory status were assessed by flow cytometry.Results AZD6738 further increased radiotherapy-stimulated CD8+ T cell infiltration and activation and reverted the immunosuppressive effect of radiation on the number of Tregs in mice xenografts. Moreover, compared with radioimmunotherapy (radiotherapy plus anti-PD-L1 (Programmed death ligand 1)), the addition of AZD6738 boosted the infiltration, increased cell proliferation, enhanced interferon (IFN)-γ production ability of TIL (tumor-infiltrating lymphocyte) CD8+ T cells, and caused a decreasing trend in the number of TIL Tregs and exhausted T cells in mice xenografts. Thus, the tumor immune microenvironment was significantly improved. Meanwhile, triple therapy (AZD6738 plus radiotherapy plus anti-PD-L1) also induced a better immunophenotype than radioimmunotherapy in mice spleens. As a consequence, triple therapy displayed greater benefit in antitumor efficacy and mice survival than radioimmunotherapy. Mechanism study revealed that the synergistic antitumor effect of AZD6738 with radioimmunotherapy relied on the activation of cyclic GMP–AMP synthase /stimulator of interferon genes (cGAS/STING) signaling pathway. Furthermore, triple therapy led to stronger immunologic memory and lasting antitumor immunity than radioimmunotherapy, thus preventing tumor recurrence in mouse models.Conclusions Our findings indicate that AZD6738 might be a potential synergistic treatment for radioimmunotherapy to control the proliferation of HCC cells, prolong survival, and prevent tumor recurrence in patients with HCC by improving the immune microenvironment

    Double Lock the COVID 19: Inhibit SARS COV 2 Replication and Suppress Inflammation Cytokine Level by the Golden Compounds

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    Our studies implied the golden compounds may be more effective against COVID 19 as they synergy inhibit SARS COV 2 replication and down regulation inflammation cytokine level. Our crystal structure studies firstly revealed Au (I) ions, derived from auranofin (AF) or gold cluster (GA), covalently bind sulfur atom of Cys145 and Cys156 of Mpro of SARS COV 2. The auranofin or gold cluster well inhibit Mpro activity in vitro. Auranofin or gold cluster could well suppress inflammation cytokine level of IL 6, IL 1β, TNF α via down regulation NF κB activation in macrophage. The cell viability and rat toxicity studies show gold cluster is more safety when compared FDA approved auranofin. The rat pharmacokinetic studies of gold cluster revealed its good bioavailability

    Impact of MSMEG5257 Deletion on <i>Mycolicibacterium smegmatis</i> Growth

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    Mycobacterial membrane proteins play a pivotal role in the bacterial invasion of host cells; however, the precise mechanisms underlying certain membrane proteins remain elusive. Mycolicibacterium smegmatis (Ms) msmeg5257 is a hemolysin III family protein that is homologous to Mycobacterium tuberculosis (Mtb) Rv1085c, but it has an unclear function in growth. To address this issue, we utilized the CRISPR/Cas9 gene editor to construct Δmsmeg5257 strains and combined RNA transcription and LC-MS/MS protein profiling to determine the functional role of msmeg5257 in Ms growth. The correlative analysis showed that the deletion of msmeg5257 inhibits ABC transporters in the cytomembrane and inhibits the biosynthesis of amino acids in the cell wall. Corresponding to these results, we confirmed that MSMEG5257 localizes in the cytomembrane via subcellular fractionation and also plays a role in facilitating the transport of iron ions in environments with low iron levels. Our data provide insights that msmeg5257 plays a role in maintaining Ms metabolic homeostasis, and the deletion of msmeg5257 significantly impacts the growth rate of Ms. Furthermore, msmeg5257, a promising drug target, offers a direction for the development of novel therapeutic strategies against mycobacterial diseases
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