Learning controllers from data via kernel-based interpolation

We propose a data-driven control design method for nonlinear systems that builds on kernel-based interpolation. Under some assumptions on the system dynamics, kernel-based functions are built from data and a model of the system, along with deterministic model error bounds, is determined. Then, we derive a controller design method that aims at stabilizing the closed-loop system by cancelling out the system nonlinearities. The proposed method can be implemented using semidefinite programming and returns positively invariant sets for the closed-loop system

The lithospheric lager and block velocity structure and motion of Substance for Tibetan plateau

Abstract HKT-ISTP 2013 A

Molecular Dynamic Simulation to Explore the Molecular Basis of Btk-PH Domain Interaction with Ins(1,3,4,5)P4

Bruton’s tyrosine kinase contains a pleckstrin homology domain, and it specifically binds inositol 1,3,4,5-tetrakisphosphate (Ins(1,3,4,5)P4), which is involved in the maturation of B cells. In this paper, we studied 12 systems including the wild type and 11 mutants, K12R, S14F, K19E, R28C/H, E41K, L11P, F25S, Y40N, and K12R-R28C/H, to investigate any change in the ligand binding site of each mutant. Molecular dynamics simulations combined with the method of molecular mechanics/Poisson-Boltzmann solvent-accessible surface area have been applied to the twelve systems, and reasonable mutant structures and their binding free energies have been obtained as criteria in the final classification. As a result, five structures, K12R, K19E, R28C/H, and E41K mutants, were classified as “functional mutations,” whereas L11P, S14F, F25S, and Y40N were grouped into “folding mutations.” This rigorous study of the binding affinity of each of the mutants and their classification provides some new insights into the biological function of the Btk-PH domain and related mutation-causing diseases

Panoramic insights into microevolution and macroevolution of a Prevotella copri-containing lineage in primate guts

Prevotella copri and its related taxa are widely detected in mammalian gut microbiomes and have been linked with an enterotype in humans. However, their microevolution and macroevolution among hosts are poorly characterized. In this study, extensively collected marker genes and genomes were analyzed to trace their evolutionary history, host specificity, and biogeographic distribution. Investigations based on marker genes and genomes suggest that a P. copri-containing lineage (PCL) harbors diverse species in higher primates. Firstly, P. copri in the human gut consisted of multiple groups exhibiting high genomic divergence and conspicuous but non-strict biogeographic patterns. Most African strains with high genomic divergence from other strains were phylogenetically located at the root of the species, indicating the co-evolutionary history of P. copri and Homo sapiens. Secondly, although long-term co-evolution between PCL and higher primates was revealed, sporadic signals of co-speciation and extensive host jumping of PCL members were suggested among higher primates. Metagenomic and phylogenetic analyses indicated that P. copri and other PCL species found in domesticated mammals had been recently transmitted from humans. Thirdly, strong evidence was found on the extensively horizontal transfer of genes (e.g., genes encoding carbohydrate-active enzymes) among sympatric P. copri groups and PCL species in the same primate host. Our study provides panoramic insights into the combined effects of vertical and horizontal transmission, as well as potential niche adaptation, on the microevolutionary and macroevolutionary history for an enterotype-representative lineage

Risk assessment of malaria in land border regions of China in the context of malaria elimination

BACKGROUND:Cross-border malaria transmission poses a challenge for countries to achieve and maintain malaria elimination. Because of a dramatic increase of cross-border population movement between China and 14 neighbouring countries, the malaria epidemic risk in China's land border regions needs to be understood.METHODS: In this study, individual case-based epidemiological data on malaria in the 136 counties of China with international land borders, from 2011 to 2014, were extracted from the National Infectious Disease Information System. The Plasmodium species, seasonality, spatiotemporal distribution and changing features of imported and indigenous cases were analysed using descriptive spatial and temporal methods.RESULTS:A total of 1948 malaria cases were reported, with 1406 (72.2%) imported cases and 542 (27.8%) indigenous cases. Plasmodium vivax is the predominant species, with 1536 malaria cases occurrence (78.9%), following by Plasmodium falciparum (361 cases, 18.5%), and the others (51 cases, 2.6%). The magnitude and geographic distribution of malaria in land border counties shrunk sharply during the elimination period. Imported malaria cases were with a peak of 546 cases in 2011, decreasing yearly in the following years. The number of counties with imported cases decreased from 28 counties in 2011 to 26 counties in 2014. Indigenous malaria cases presented a markedly decreasing trend, with 319 indigenous cases in 2011 reducing to only 33 indigenous cases in 2014. The number of counties with indigenous cases reduced from 26 counties in 2011 to 10 counties in 2014. However, several bordering counties of Yunnan province adjacent to Myanmar reported indigenous malaria cases in the four consecutive years from 2011 to 2014.CONCLUSIONS:The scale and extent of malaria occurrence in the international land border counties of China decreased dramatically during the elimination period. However, several high-risk counties, especially along the China-Myanmar border, still face a persistent risk of malaria introduction and transmission. The study emphasizes the importance and urgency of cross-border cooperation between neighbouring countries to jointly face malaria threats to elimination goals

Evaluation of the performance of a dengue outbreak detection tool for China

An outbreak detection and response system, using time series moving percentile method based on historical data, in China has been used for identifying dengue fever outbreaks since 2008. For dengue fever outbreaks reported from 2009 to 2012, this system achieved a sensitivity of 100%, a specificity of 99.8% and a median time to detection of 3 days, which indicated that the system was a useful decision tool for dengue fever control and risk-management programs in China.This work was supported by the grants from Research and Promotion of Key Technology on Health Emergency Preparation and Dispositions (201202006), the National Key Science and Technology Project on Infectious Disease Surveillance Technique Platform of China (2012ZX10004-201) and Development of Early Warning Systems for Dengue Fever Based on Socio-ecological Factors (NHMRC APP1002608)

Identification of Immune-Associated Biomarkers of Diabetes Nephropathy Tubulointerstitial Injury Based on Machine Learning: A Bioinformatics Multi-Chip Integrated Analysis

BACKGROUND: Diabetic nephropathy (DN) is a major microvascular complication of diabetes and has become the leading cause of end-stage renal disease worldwide. A considerable number of DN patients have experienced irreversible end-stage renal disease progression due to the inability to diagnose the disease early. Therefore, reliable biomarkers that are helpful for early diagnosis and treatment are identified. The migration of immune cells to the kidney is considered to be a key step in the progression of DN-related vascular injury. Therefore, finding markers in this process may be more helpful for the early diagnosis and progression prediction of DN. METHODS: The gene chip data were retrieved from the GEO database using the search term \u27 diabetic nephropathy \u27. The \u27 limma \u27 software package was used to identify differentially expressed genes (DEGs) between DN and control samples. Gene set enrichment analysis (GSEA) was performed on genes obtained from the molecular characteristic database (MSigDB. The R package \u27WGCNA\u27 was used to identify gene modules associated with tubulointerstitial injury in DN, and it was crossed with immune-related DEGs to identify target genes. Gene ontology (GO) enrichment analysis and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway analysis were performed on differentially expressed genes using the \u27ClusterProfiler\u27 software package in R. Three methods, least absolute shrinkage and selection operator (LASSO), support vector machine recursive feature elimination (SVM-RFE) and random forest (RF), were used to select immune-related biomarkers for diagnosis. We retrieved the tubulointerstitial dataset from the Nephroseq database to construct an external validation dataset. Unsupervised clustering analysis of the expression levels of immune-related biomarkers was performed using the \u27ConsensusClusterPlus \u27R software package. The urine of patients who visited Dongzhimen Hospital of Beijing University of Chinese Medicine from September 2021 to March 2023 was collected, and Elisa was used to detect the mRNA expression level of immune-related biomarkers in urine. Pearson correlation analysis was used to detect the effect of immune-related biomarker expression on renal function in DN patients. RESULTS: Four microarray datasets from the GEO database are included in the analysis : GSE30122, GSE47185, GSE99340 and GSE104954. These datasets included 63 DN patients and 55 healthy controls. A total of 9415 genes were detected in the data set. We found 153 differentially expressed immune-related genes, of which 112 genes were up-regulated, 41 genes were down-regulated, and 119 overlapping genes were identified. GO analysis showed that they were involved in various biological processes including leukocyte-mediated immunity. KEGG analysis showed that these target genes were mainly involved in the formation of phagosomes in Staphylococcus aureus infection. Among these 119 overlapping genes, machine learning results identified AGR2, CCR2, CEBPD, CISH, CX3CR1, DEFB1 and FSTL1 as potential tubulointerstitial immune-related biomarkers. External validation suggested that the above markers showed diagnostic efficacy in distinguishing DN patients from healthy controls. Clinical studies have shown that the expression of AGR2, CX3CR1 and FSTL1 in urine samples of DN patients is negatively correlated with GFR, the expression of CX3CR1 and FSTL1 in urine samples of DN is positively correlated with serum creatinine, while the expression of DEFB1 in urine samples of DN is negatively correlated with serum creatinine. In addition, the expression of CX3CR1 in DN urine samples was positively correlated with proteinuria, while the expression of DEFB1 in DN urine samples was negatively correlated with proteinuria. Finally, according to the level of proteinuria, DN patients were divided into nephrotic proteinuria group (n = 24) and subrenal proteinuria group. There were significant differences in urinary AGR2, CCR2 and DEFB1 between the two groups by unpaired t test (P \u3c 0.05). CONCLUSIONS: Our study provides new insights into the role of immune-related biomarkers in DN tubulointerstitial injury and provides potential targets for early diagnosis and treatment of DN patients. Seven different genes ( AGR2, CCR2, CEBPD, CISH, CX3CR1, DEFB1, FSTL1 ), as promising sensitive biomarkers, may affect the progression of DN by regulating immune inflammatory response. However, further comprehensive studies are needed to fully understand their exact molecular mechanisms and functional pathways in DN

Cost-effectiveness analysis of dostarlimab plus carboplatin-paclitaxel as first-line treatment for advanced endometrial cancer

BackgroundA recent phase III clinical trial (NCT03981796) evaluated the efficacy and safety of dostarlimab combined with carboplatin-paclitaxel (DOS-CP) compared to placebo combined with carboplatin-paclitaxel (PLB-CP) as a first-line treatment for advanced endometrial cancer (EC). The NCT03981796 trial demonstrated that DOS-CP significantly improved progression-free survival and overall survival of patients with advanced EC while maintaining an acceptable safety profile. However, DOS-CP is expensive and its cost-effectiveness has not been evaluated. This study aims to evaluate the cost-effectiveness of DOS-CP compared to PLB-CP as a first-line treatment for advanced EC from the perspective of the Chinese healthcare system.MethodsA Markov model with three health states was developed to evaluate the cost-effectiveness of DOS-CP as a first-line treatment for advanced EC. Clinical efficacy data were derived from the NCT03981796 trial, and drug costs were determined based on national tender prices. Other costs and utility values were obtained from published literature. The outcomes assessed included total costs, quality-adjusted life years (QALYs), and incremental cost-effectiveness ratios (ICERs). The robustness of the model was assessed through one-way sensitivity analysis and probabilistic sensitivity analysis.ResultsIn comparison to PLB-CP, the ICER of DOS-CP was $98,276.61/QALY for the overall population,$53,063.61/QALY for the dMMR subgroup, and $124,088.56/QALY for the pMMR subgroup. All of these ICER values were higher than the willingness-to-pay threshold of$38,201 per QALY. The most important variable that affected the results of the model was the discount rate, the cost of dostarlimab, and the utility value for progressive disease.ConclusionFrom the perspective of the Chinese healthcare system, DOS-CP is unlikely to be a cost-effective first-line treatment option for advanced EC

The epidemiology of Plasmodium vivax and Plasmodium falciparum malaria in China, 2004–2012: from intensified control to elimination

BACKGROUND In China, the national malaria elimination programme has been operating since 2010. This study aimed to explore the epidemiological changes in patterns of malaria in China from intensified control to elimination stages. METHODS Data on nationwide malaria cases from 2004 to 2012 were extracted from the Chinese national malaria surveillance system. The secular trend, gender and age features, seasonality, and spatial distribution by Plasmodium species were analysed. RESULTS In total, 238,443 malaria cases were reported, and the proportion of Plasmodium falciparum increased drastically from <10% before 2010 to 55.2% in 2012. From 2004 to 2006, malaria showed a significantly increasing trend and with the highest incidence peak in 2006 (4.6/100,000), while from 2007 onwards, malaria decreased sharply to only 0.18/100,000 in 2012. Males and young age groups became the predominantly affected population. The areas affected by Plasmodium vivax malaria shrunk, while areas affected by P. falciparum malaria expanded from 294 counties in 2004 to 600 counties in 2012. CONCLUSIONS This study demonstrated that malaria has decreased dramatically in the last five years, especially since the Chinese government launched a malaria elimination programme in 2010, and areas with reported falciparum malaria cases have expanded over recent years. These findings suggest that elimination efforts should be improved to meet these changes, so as to achieve the nationwide malaria elimination goal in China in 2020.This study was supported by grants from the Ministry of Science and Technology of China (2012ZX10004-201, 2012ZX10004-220) and the Ministry of Health of China (No. 201202006), and China UK Global Health Support Programme (grant no. GHSP-CS-OP1). S.I.H. is funded by a Senior Research Fellowship from the Wellcome Trust (#095066). S.I.H. also acknowledges funding support from the RAPIDD programme of the Science & Technology Directorate, Department of Homeland Security, and the Fogarty International Center, National Institutes of Health