Multi-TGDR, a multi-class regularization method, identifies the metabolic profiles of hepatocellular carcinoma and cirrhosis infected with hepatitis B or hepatitis C virus

BACKGROUND: Over the last decade, metabolomics has evolved into a mainstream enterprise utilized by many laboratories globally. Like other “omics” data, metabolomics data has the characteristics of a smaller sample size compared to the number of features evaluated. Thus the selection of an optimal subset of features with a supervised classifier is imperative. We extended an existing feature selection algorithm, threshold gradient descent regularization (TGDR), to handle multi-class classification of “omics” data, and proposed two such extensions referred to as multi-TGDR. Both multi-TGDR frameworks were used to analyze a metabolomics dataset that compares the metabolic profiles of hepatocellular carcinoma (HCC) infected with hepatitis B (HBV) or C virus (HCV) with that of cirrhosis induced by HBV/HCV infection; the goal was to improve early-stage diagnosis of HCC. RESULTS: We applied two multi-TGDR frameworks to the HCC metabolomics data that determined TGDR thresholds either globally across classes, or locally for each class. Multi-TGDR global model selected 45 metabolites with a 0% misclassification rate (the error rate on the training data) and had a 3.82% 5-fold cross-validation (CV-5) predictive error rate. Multi-TGDR local selected 48 metabolites with a 0% misclassification rate and a 5.34% CV-5 error rate. CONCLUSIONS: One important advantage of multi-TGDR local is that it allows inference for determining which feature is related specifically to the class/classes. Thus, we recommend multi-TGDR local be used because it has similar predictive performance and requires the same computing time as multi-TGDR global, but may provide class-specific inference

Insurance Crisis, Legal Environment, and the Sustainability of Professional Liability Insurance Market in the Construction Industry: Based on the US Market

PLI (professional liability insurance) is currently the main method used to control construction practice risk and is an important economic measure of construction industry governance. Few literatures have analyzed the sustainability of the liability insurance market. In particular, the research on the sustainability of the PLI market in the construction industry is still blank. The sustainability of the market can be identified with the equilibrium of the system over a certain period of time. From the perspective of cooperation benefits, this paper adopts evolutionary game theory (EGT) to analyze the evolutionary trends of stakeholders’ behaviors and their evolutionarily stable strategy (ESS) in the PLI market of the construction industry. A case study from the history of the US PLI market evolution over nearly 100 years is taken to illustrate the stakeholder game and interpret the market evolution path, and several typical stages of the development of the US PLI market are explored. Some factors that can cause a shift in equilibrium are found. The results show that the change in the legal environment will directly affect the payoffs of the stakeholders, cause market imbalance, and trigger crisis. These findings will help out the government to regulate the market in a timely manner by improving external factors, such as by building a sound credit system and ensuring the stability of the legal system. In an equilibrium state, competitive markets can eliminate individuals with high accident rates and companies with high operating costs. Moreover, these findings will also set a base for future researches to investigate the role of insurance market and legal environment in depth while providing the intensive critical factors towards sustainable construction industry

Spatiotemporal variations and its driving factors of soil conservation services in the Three Gorges Reservoir area in China

Soil conservation services play a vital role in regulating ecosystem services to prevent soil erosion and ensure regional ecological security. Therefore, effective evaluation and quantification of soil conservation services in the Three Gorges Reservoir Area (TGRA) are conducive to sustainable management under future global change. In this study, based on a basic database, including land use/cover data, soil data, topographic data, meteorological data, and NDVI (Normalized Difference Vegetation Index) data as the basic databases, to evaluate the temporal and spatial changes of soil conservation services in the TGRA from 1990 to 2015 at a regional-scale level using the general soil loss equation. The results showed that forest ecosystems (including coniferous and broad-leaved mixed forests, coniferous forests, shrub forests, and broad-leaved forests) made a greater contribution (69%) to regulating soil conservation in TGRA, followed by farmland ecosystems (29%). In total TGRA, large spatial variation in soil conservation, such as the highest appeared in the northern hinterland, whereas the lowest was mostly shown in the northwest with relatively frequent human activities and developed industry and agriculture. In general, soil conservation in the TGRA ecosystem gradually increased from 1990 to 2015, with a total increase of 6%. In this period, with the effective implementation of ecological projects, such as the conversion of farmland to forest and natural forest protection, the distributed proportion of forest land area in total TGRA showed a significant increase. In the meantime, the increase of vegetation coverage also helps the restoration of ecosystem structure and function and the improvement of soil conservation services. Our findings will aid our knowledge regarding the ecosystem services of the TGRA and provide implications for future sustainable land management and ecological protection

Role of mTOR signaling in intestinal cell migration

An early signaling event activated by amino acids and growth factors in many cell types is the phosphorylation of the mammalian target of rapamycin (mTOR; FRAP), which is functionally linked to ribosomal protein s6 kinase (p70s6k), a kinase that plays a critical regulatory role in the translation of mRNAs and protein synthesis. We previously showed that intestinal cell migration, the initial event in epithelial restitution, is enhanced by l-arginine (ARG). In this study, we used amino acids as prototypic activators of mTOR and ARG, IGF-1, or serum as recognized stimulators of intestinal cell migration. We found that 1) protein synthesis is required for intestinal cell migration, 2) mTOR/p70s6k pathway inhibitors (rapamycin, wortmannin, and intracellular Ca2+ chelation) inhibit cell migration, 3) ARG activates migration and mTOR/p70s6k (but not ERK-2) in migrating enterocytes, and 4) immunocytochemistry reveals abundant p70s6k staining in cytoplasm, whereas phosphop70s6k is virtually all intranuclear in resting cells but redistributes to the periphery on activation by ARG. We conclude that mTOR/p70s6k signaling is essential to intestinal cell migration, is activated by ARG, involves both nuclear and cytoplasmic events, and may play a role in intestinal repair

Adaptive command-filtered finite-time consensus tracking control for single-link flexible-joint robotic multi-agent systems

This article presents a command-filtered finite-time consensus tracking control strategy for the considered single-link flexible-joint robotic multi-agent systems. First, each agent system considered in this article is a nonlinear nonstrict-feedback system with unknown nonlinearities, so the traditional backstepping method cannot be directly applied to the design controller. However, by applying the unique structure of the Gaussian function in radial basis function neural networks, the challenges in controller design caused by the aforementioned nonstrict-feedback system have been overcome. Second, the problem of unknown nonlinearities in the system is solved by the approximation property of radial basis function neural network technology. In addition, the traditional backstepping approach often leads to an “explosion of complexity” resulting from repeated derivation of virtual control signals. Our design addresses this issue by employing command filtering technology, which simplifies the controller design process. Meanwhile, new compensation signals are designed, which successfully eliminate the error influence posed by the filters. It is seen that the control strategy presented in this article can guarantee the tracking errors converge to a small neighborhood of origin in a finite time, and all signals in the closed-loop systems remain bounded. Eventually, the simulation results show the validity of the acquired control scheme

Angiogenic and Inflammatory Markers of Cardiopulmonary Changes in Children and Adolescents with Sickle Cell Disease

Background: Pulmonary hypertension and left ventricular diastolic dysfunction are complications of sickle cell disease. Pulmonary hypertension is associated with hemolysis and hypoxia, but other unidentified factors are likely involved in pathogenesis as well. Design and Methods: Plasma concentrations of three angiogenic markers (fibroblast growth factor, platelet derived growth factor-BB [PDGF-BB], vascular endothelial growth factor [VEGF]) and seven inflammatory markers implicated in pulmonary hypertension in other settings were determined by Bio-Plex suspension array in 237 children and adolescents with sickle cell disease at steady state and 43 controls. Tricuspid regurgitation velocity (which reflects systolic pulmonary artery pressure), mitral valve E/Edti ratio (which reflects left ventricular diastolic dysfunction), and a hemolytic component derived from four markers of hemolysis and hemoglobin oxygen saturation were also determined. Results: Plasma concentrations of interleukin-8, interleukin-10 and VEGF were elevated in the patients with sickle cell disease compared to controls (P≤0.003). By logistic regression, greater values for PDGF-BB (P = 0.009), interleukin-6 (P = 0.019) and the hemolytic component (P = 0.026) were independently associated with increased odds of elevated tricuspid regurgitation velocity while higher VEGF concentrations were associated with decreased odds (P = 0.005) among the patients with sickle cell disease. These findings, which are consistent with reports that PDGF-BB stimulates and VEGF inhibits vascular smooth muscle cell proliferation, did not apply to E/Etdi. Conclusions: Circulating concentrations of angiogenic and pro-Inflammatory markers are altered in sickle cell disease children and adolescents with elevated tricuspid regurgitation velocity, a subgroup that may be at risk for developing worsening pulmonary hypertension. Further studies to understand the molecular changes in these children are indicated