28 research outputs found

    Effects of Gamification Elements on Crowdsourcing Participation: The Mediating Role of Justice Perceptions

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    Justice perceptions have been regarded as an important influencing factor for solvers’ (i.e., users who solve tasks on the crowdsourcing platforms) continued participation in crowdsourcing. However, researchers and practitioners still lack of sufficient understanding on the design of crowdsourcing platform that can effectively foster solvers’ justice perceptions. By synthesizing theory of organizational justice and the literature on gamification, we examine the effects of solvers’ gamification element perceptions on their crowdsourcing participation through justice perceptions. Specifically, we propose a research model to explain the effects of three gamification element perceptions (i.e., point, feedback, social network) on solvers’ distributive, interactional, and informational justice perceptions which, in turn, foster their crowdsourcing participation. By collecting survey data from 295 solvers and analyzing the data with the partial least squares-structural equation modeling (PLS-SEM) approach, our study finds that point fosters crowdsourcing participation through distributive and interactional justice. Feedback enhances participation through distributive, interactional and informational justice. While social network strengthens participation via interactional and informational justice. Our study offers significant theoretical contributions and practical implications for the gamified crowdsourcing and organizational justice literatures

    CD24-p53 axis suppresses diethylnitrosamine-induced hepatocellular carcinogenesis by sustaining intrahepatic macrophages

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    It is generally assumed that inflammation following diethylnitrosamine (DEN) treatment promotes development of hepatocellular carcinoma (HCC) through the activity of intrahepatic macrophages. However, the tumor-promoting function of macrophages in the model has not been confirmed by either macrophage depletion or selective gene depletion in macrophages. Here we show that targeted mutation of Cd24 dramatically increased HCC burden while reducing intrahepatic macrophages and DEN-induced hepatocyte apoptosis. Depletion of macrophages also increased HCC burden and reduced hepatocyte apoptosis, thus establishing macrophages as an innate effector recognizing DEN-induced damaged hepatocytes. Mechanistically, Cd24 deficiency increased the levels of p53 in macrophages, resulting in their depletion in Cd24 -/- mice following DEN treatment. These data demonstrate that the Cd24-p53 axis maintains intrahepatic macrophages, which can remove hepatocytes with DNA damage. Our data establish a critical role for macrophages in suppressing HCC development and call for an appraisal of the current dogma that intrahepatic macrophages promote HCC development

    Intracellular CD24 disrupts the ARF–NPM interaction and enables mutational and viral oncogene-mediated p53 inactivation

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    CD24 is overexpressed in nearly 70% human cancers, whereas TP53 is the most frequently mutated tumour-suppressor gene that functions in a context-dependent manner. Here we show that both targeted mutation and short hairpin RNA (shRNA) silencing of CD24 retard the growth, progression and metastasis of prostate cancer. CD24 competitively inhibits ARF binding to NPM, resulting in decreased ARF, increase MDM2 and decrease levels of p53 and the p53 target p21/CDKN1A. CD24 silencing prevents functional inactivation of p53 by both somatic mutation and viral oncogenes, including the SV40 large T antigen and human papilloma virus 16 E6-antigen. In support of the functional interaction between CD24 and p53, in silico analyses reveal that TP53 mutates at a higher rate among glioma and prostate cancer samples with higher CD24 mRNA levels. These data provide a general mechanism for functional inactivation of ARF and reveal an important cellular context for genetic and viral inactivation of TP53. P53 is a tumour suppressor that is frequently mutated or downregulated in cancer. Here, Wang et al. show that CD24, a molecule frequently overexpressed in cancer, promotes p53 degradation by disrupting a regulatory ARF–MDM2 interaction, and silencing CD24 prevents the downregulation of p53

    Paradoxical CD4 Lymphopenia in Autoimmune Lymphoproliferative Syndrome (ALPS)

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    Autoimmune lymphoproliferative syndrome (ALPS) is caused by germline or somatic loss of function FAS mutations resulting in impaired apoptosis and consequent expansion of T-lymphocytes causing organomegaly and autoimmune anemia, neutropenia and thrombocytopenia. Herein, we report on a case of disseminated varicella zoster infection after post-partum vaccination in a patient found to have CD4 lymphopenia and eventually diagnosed with ALPS caused by a novel germline missense mutation in FAS death-domain. A subsequent retrospective analysis of 169 patients of the NIH ALPS-FAS cohort, revealed that CD4-T-cells lymphopenia (< 300 cells/μl) may occur in 5% of ALPS-FAS patients irrespectively of the underlying genetic defect, organomegaly or immunosuppressive treatment. Although immunophenotyping did not show depletion of specific CD4-T-cells subpopulations, CD4-lymphopenic ALPS-FAS subjects had an expansion of a subset of circulating T-follicular-helper (cTfh) cells, associated with autoantibody production (CCR7lowPD-1high). Furthermore, autoantibodies binding on CD4-T-cells were detected in 50% of the CD4-lymphopenic ALPS-FAS patients and caused cytotoxicity in a natural killer (NK)-mediated antibody-dependent-cellular cytotoxicity assay. Such autoantibodies can therefore be associated with CD4-T-cell death, impaired activation induced proliferation or impaired trafficking. The expansion of autoreactive T-cells in ALPS-FAS is known to be associated with autoimmune clinical manifestations, however our study reveals that ALPS-FAS can also be associated with a paradoxical depletion of CD4-T-cells due to the presence of autoantibodies on the surface of CD4-T-cells which can in turn result in increased susceptibility to opportunistic infections. These novel findings have implications for the diagnosis, clinical monitoring, and management of patients with ALPS-FAS

    New mechanistic insights, novel treatment paradigms, and clinical progress in cerebrovascular diseases

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    The past decade has brought tremendous progress in diagnostic and therapeutic options for cerebrovascular diseases as exemplified by the advent of thrombectomy in ischemic stroke, benefitting a steeply increasing number of stroke patients and potentially paving the way for a renaissance of neuroprotectants. Progress in basic science has been equally impressive. Based on a deeper understanding of pathomechanisms underlying cerebrovascular diseases, new therapeutic targets have been identified and novel treatment strategies such as pre- and post-conditioning methods were developed. Moreover, translationally relevant aspects are increasingly recognized in basic science studies, which is believed to increase their predictive value and the relevance of obtained findings for clinical application.This review reports key results from some of the most remarkable and encouraging achievements in neurovascular research that have been reported at the 10th International Symposium on Neuroprotection and Neurorepair. Basic science topics discussed herein focus on aspects such as neuroinflammation, extracellular vesicles, and the role of sex and age on stroke recovery. Translational reports highlighted endovascular techniques and targeted delivery methods, neurorehabilitation, advanced functional testing approaches for experimental studies, pre-and post-conditioning approaches as well as novel imaging and treatment strategies. Beyond ischemic stroke, particular emphasis was given on activities in the fields of traumatic brain injury and cerebral hemorrhage in which promising preclinical and clinical results have been reported. Although the number of neutral outcomes in clinical trials is still remarkably high when targeting cerebrovascular diseases, we begin to evidence stepwise but continuous progress towards novel treatment options. Advances in preclinical and translational research as reported herein are believed to have formed a solid foundation for this progress

    Simulation of the Evolution of Thermal Dynamics during Selective Laser Melting and Experimental Verification Using Online Monitoring

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    The process parameters of selective laser melting (SLM) significantly influence molten pool formation. A comprehensive understanding and analysis, from a macroscopic viewpoint, of the mechanisms underlying these technological parameters and how they affect the evolution of molten pools are presently lacking. In this study, we established a dynamic finite element simulation method for the process of molten pool formation by SLM using a dynamic moving heat source. The molten pool was generated, and the dynamic growth process of the molten pool belt and the evolution process of the thermal field of the SLM molten pool were simulated. Then, a deposition experiment that implemented a new measurement method for online monitoring involving laser supplementary light was conducted using the same process parameters as the simulation, in which high-speed images of the molten pool were acquired, including images of the pool surface and cross-section images of the deposited samples. The obtained experimental results show a good agreement with the simulation results, demonstrating the effectiveness of the proposed algorithm

    The association between time-mean serum uric acid levels and the incidence of chronic kidney disease in the general population: a retrospective study

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    Abstract Background Investigations on the role of the time-mean serum uric acid (SUA) value in determining the risk of chronic kidney disease (CKD) are limited. We investigated whether the time-mean SUA value indicates the risk of CKD, and explored associations of the baseline and time-mean SUA levels with kidney function decline and incident CKD in a healthy population. Methods We initiated an inhabitant-based cohort study between January 2011 and December 2016. All participants completed a yearly medical check-up at the Zhejiang Province People’s Hospital and had baseline estimated glomerular filtration rates (eGFR) > 60 ml/min/1.73m2. The SUA level and eGFR were assessed every year in the follow-up period. A multivariate adjusted binary logistic regression analysis and Cox proportional hazards models were used to evaluate the risk of newly-developed CKD among different stratified groups. Results During the 6-year follow-up period, 227 (4.4%) participants developed CKD. In multivariable-adjusted analyses, the odds ratio (OR) for new-onset CKD increased, with higher time-mean SUA levels than at baseline (OR: 1.00 [reference], 2.709 [95% confidence interval: 1.836–5.293], 3.754 [1.898–7.428], and 7.462 [3.694–15.073]). After adjustment for potential cofounders, a multivariate Cox proportional hazard model showed that a higher SUA increased the risk of developing CKD (the adjusted hazard ratios of the highest and lowest quartiles for the baseline and time-mean SUA levels were 1.689 [1.058–2.696] and 6.320 [3.285–12.159], respectively). Conclusion An increased time-mean and single SUA value were independently associated with an increased likelihood of eGFR decline and development of new-onset CKD in the general population

    Coupling Analysis on Microstructure and Residual Stress in Selective Laser Melting (SLM) with Varying Key Process Parameters

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    With the application of Selective Laser Melting (SLM) technology becoming more and more widespread, it is important to note the process parameters that have a very important effect on the forming quality. Key process parameters such as laser power (P), scan speed (s), and scanning strategy (μ) were investigated by determining the correlation between the microstructure and residual stress in this paper. A total of 10 group 316L specimens were fabricated using SLM for comprehensive analysis. The results show that the key process parameters directly affect the morphology and size of the molten pool in the SLM deposition, and the big molten pool width has a direct effect on the larger grain size and crystal orientation distribution. In addition, the larger grain size and misorientation angle also affect the size of the residual stress. Therefore, better additive manufacturing grain crystallization can be obtained by reasonably adjusting the process parameter combinations. The transfer energy density can synthesize the influence of four key process parameters (P, v, the hatching distance (δ), and the layer thickness (h)). In this study, it is proposed that the accepted energy density will reflect the influence of five key process parameters, including the scanning trajectory (μ), which can reflect the comprehensive effect of process parameters more accurately

    Microstructure and Corrosion Behavior of Laser-Cladding CeO2-Doped Ni-Based Composite Coatings on TC4

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    Laser-cladding CeO2-doped Ni-based composite coatings were prepared on the surface of a titanium alloy, and the effects of CeO2 addition on the microstructure, microhardness, and corrosion resistance of the prepared coatings were studied. The results showed that TiC, NiTi, Ni3Ti, and Ti2Ni phases were formed on the prepared coatings. Moreover, the addition of CeO2 in laser-cladding coatings effectively refined the microstructure and reduced the number of cracks generated in the laser-cladding process. When the amount of CeO2 was 2%, the number of cracks in the laser-cladding coating was significantly reduced compared with that of 0%. When the content of CeO2 was 2% or 3%, the microhardness of laser-cladding coatings reached the maximum value. At the same time, it was found that the appropriate addition of CeO2 was helpful to improve the corrosion resistance of the laser-cladding coating. However, excessive CeO2 addition could reduce the corrosion resistance of the laser-cladding coating
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