System Structure Risk Metric Method Based on Information Flow

Part 5: Modelling and SimulationInternational audienceThe measurement of structure risk aims to analysis and evaluate the not occurred, potential, and the objectively exist risk in system structure. It is an essential way to validate system function and system quality. This paper proposes the risk metric model and algorithm based on information flow and analysis risk trend between traditional tree structure and network-centric structure

Describing coevolution of business and IS alignment via agent-based modeling

The coevolution of business and IS alignment is a growing concern for researchers and practitioners alike. Extant literature on describing and modeling the coevolution is still in infancy, which makes it hard to capture the complexity and to offer reasonable decisions in the evolution of organizations. This paper focuses on the actors’ behaviors, and explores their emergent effects on the holistic alignment. We build an agent-based model to describe the complex alignment landscape and to improve the coevolution governance. The model embraces the emergent behaviors shaped by the interactions of business and IS agents, and guides the coevolution of alignment driven by the external changes. The development of this model forms a necessary step towards suggesting guidance how to analyze and implement coevolution in companies. The paper also shows the capability of an agent-based model to capture some of the emergent behaviors that emerge from bottom-level behaviors

Numerical Simulation on Dispersal Character of Fuel by Central HE

A fuel-air explosive (FAE) device consists of a shell (top-end cover, bottom-end cover, shell-side wall), a mixed fuel, a central pipe and a burst high-explosive (HE) charged in the central pipe.The mixed fuel is filled in a column structure and dispersed by the explosion drive of central burstHE in the central pipe. The dispersed fuel mixes with air, which produces combustible cloudwhich can be detonated. That is the fuel-air explosive (FAE). The height and ignition positionof the central HE charged column affect the fuel dispersal process. The initial stage of fueldispersal was simulated by numerical computation. The simulation result indicated that thedistribution of fuel dispersal velocity, when the central HE is ignited at the end, is not the sameas that when the central HE is ignited on the axis of the central HE simultaneously. When theratio of the column height of the central HE and that of the FAE device is 0.64~0.73, the distributionof fuel dispersal velocity has little difference when the central HE is ignited at the end of column.But, when the ratio of the column height of the central HE and that of the FAE device is 0.89,the fuel axial dispersal velocity is obviously more than that when the ratio of the column heightof the central HE and that of the FAE device is 0.64~0.73

NCOA5 Haploinsufficiency in Myeloid-Lineage Cells Sufficiently Causes Nonalcoholic Steatohepatitis and Hepatocellular Carcinoma

BACKGROUND & AIMS: The nuclear receptor coactivator 5 (NCOA5) is a putative type 2 diabetes susceptibility gene. NCOA5 haploinsufficiency results in the spontaneous development of nonalcoholic fatty liver disease (NAFLD), insulin resistance, and hepatocellular carcinoma (HCC) in male mice; however, the cell-specific effect of NCOA5 haploinsufficiency in various types of cells, including macrophages, on the development of NAFLD and HCC remains unknown. METHODS: Control and myeloid-lineage-specific Ncoa5 deletion (Ncoa5(ΔM/+)) mice fed a normal diet were examined for the development of NAFLD, non-alcoholic steatohepatitis (NASH), and HCC. Altered genes and signaling pathways in the intrahepatic macrophages of Ncoa5(ΔM/+) male mice were analyzed and compared with that of obese human individuals. The role of platelet factor 4 (PF4) in macrophages and the underlying mechanism by which PF4 affects NAFLD/NASH were explored in vitro and in vivo. PF4 expression in HCC patient specimens and prognosis was examined. RESULTS: Myeloid-lineage-specific Ncoa5 deletion sufficiently causes spontaneous NASH and HCC development in male mice fed a normal diet. PF4 overexpression in Ncoa5(ΔM/+) intrahepatic macrophages is identified as a potent mediator to trigger lipid accumulation in hepatocytes by inducing lipogenesis-promoting gene expression. The transcriptome of intrahepatic macrophages from Ncoa5(ΔM/+) male mice resembles that of obese human individuals. High PF4 expression correlated with poor prognosis of HCC patients and increased infiltrations of M2 macrophages, regulatory T cells (Tregs), and myeloid-derived suppressor cells (MDSCs) in HCCs. CONCLUSIONS: Our findings reveal a novel mechanism for the onset of NAFLD/NASH and HCC initiated by NCOA5-deficient macrophages, suggesting the NCOA5-PF4 axis in macrophages as a potential target for developing preventive and therapeutic interventions against NAFLD/NASH and HCC

Comprehensive analysis of REST corepressors (RCORs) in pan-cancer

REST corepressors (RCORs) are the core component of the LSD1/CoREST/HDACs transcriptional repressor complex, which have been revealed differently expressed in various cancers, but the therapeutic and prognostic mechanisms in cancer are still poorly understood. In this study, we analyzed expression, prognostic value, molecular subtypes, genetic alteration, immunotherapy response and drug sensitivity of RCORs in pan-cancer. Clinical correlation, stemness index, immune infiltration and regulatory networks of RCORs in hepatocellular carcinoma (HCC) were detected through TCGA and GSCA database. In-vitro experiments were conducted to explore the role of RCOR1 in HCC cells. The expression of RCORs varied among different cancers, and have prognostic values in several cancers. Cancer subtypes were categorized according to the expression of RCORs with clinical information. RCORs were significantly correlated with immunotherapy response, MSI, drug sensitivity and genetic alteration in pan-cancer. In HCC, RCORs were considered as potential predictor of stemness and also had association with immune infiltration. The ceRNA-TF-kinase regulatory networks of RCORs were constructed. Besides, RCOR1 acts as an oncogene in HCC and promotes the proliferation of HCC cells by inhibiting cell cycle arrest and cell apoptosis. Taken together, our study revealed the potential molecular mechanisms of RCORs in pan-cancer, offering a benchmark for disease-related research

Diabetes risk among US adults with different socioeconomic status and behavioral lifestyles: evidence from the National Health and Nutrition Examination Survey

BackgroundDiabetes disproportionately affects minorities and those with low socioeconomic status (SES) in the United States, and differences in behavioral lifestyles are largely responsible for the unequal distribution of diabetes among different groups.MethodsWith data of 9,969 participants collected in the 2007–2008 and 2009–2010 cycles of the US National Health and Nutrition Examination Survey (NHANES), this study examined several mediators and their mediating effects in the connection between SES and the risk of diabetes. The SES is assessed by the income-to-poverty ratio (IPR), education level, and employment status. For the mediation analysis, we used health-related behaviors as mediators (smoking, alcohol use, consumption of green vegetables and fruits, physical activity and sedentary time, health insurance, and healthcare). In this study, the structural equation model was utilized to evaluate the mediating effects of behavioral lifestyle as a mediator in the relationship between SES and diabetes.ResultsA total of 9,969 participants were included in this study. We found a negative nonlinear association between IPR and diabetes risk (Poverall < 0.001; Pnon-linear = 0.46), which was independent of the majority of known or suspected risk factors and confounding variables (gender, age, race). Participants with lower SES had higher risk of diabetes compared with those with higher SES. In mediating analysis, we found alcohol intake (OR = 0.996), physical activity (OR = 0.993), health insurance (OR = 0.998), and healthcare (OR = 1.002) mediated the IPR-diabetes association. But in the relationship between education status and diabetes, the mediation effect of alcohol intake (OR = 0.995), physical activity (OR = 0.991), and health care (OR = 1.008) were obvious. Likewise, alcohol intake (OR = 0.996), fruit intake (OR = 0.998), and health care (OR = 0.975) were important mediators in the association between employment status and diabetes.ConclusionThis study provides critical insights on the link between SES and diabetes. Our results highlight that poor health-related behaviors and limited access to healthcare are important pathways for increased diabetes risk related to those with low SES, particularly among Mexican Americans and males. They should be top priorities for agencies and healthcare providers to develop behavior-related interventions to reduce inequalities in diabetes risk

Hyperpolarization-activated cyclic nucleotide-gated cation channel 3 promotes HCC development in a female-biased manner

Sex differences in hepatocellular carcinoma (HCC) development are regulated by sex and non-sex chromosomes, sex hormones, and environmental factors. We previously reported that Ncoa5(+/-) mice develop HCC in a male-biased manner. Here we show that NCOA5 expression is reduced in male patient HCCs while the expression of an NCOA5-interacting tumor suppressor, TIP30, is lower in female HCCs. Tip30 heterozygous deletion does not change HCC incidence in Ncoa5(+/-) male mice but dramatically increases HCC incidence in Ncoa5(+/-) female mice, accompanied by hepatic hyperpolarization-activated cyclic nucleotide-gated cation channel 3 (HCN3) overexpression. HCN3 overexpression cooperates with MYC to promote mouse HCC development, whereas Hcn3 knockout preferentially hinders HCC development in female mice. Furthermore, HCN3 amplification and overexpression occur in human HCCs and correlate with a poorer prognosis of patients in a female-biased manner. Our results suggest that TIP30 and NCOA5 protect against female liver oncogenesis and that HCN3 is a female-biased HCC driver

Triarylamine polymers by microwave-assisted polycondensation for use in organic field-effect transistors †

Triarylamine polymers can be rapidly assembled by microwave-assisted amination of aryldibromides. A series of polymers are reported with backbones containing 4,4 0 -biphenyl, 2.9-fluorene and 3,6-carbazole repeating units