Delay-dependent stabilization of stochastic interval delay systems with nonlinear disturbances

This is the post print version of the article. The official published version can be obtained from the link below - Copyright 2007 Elsevier Ltd.In this paper, a delay-dependent approach is developed to deal with the robust stabilization problem for a class of stochastic time-delay interval systems with nonlinear disturbances. The system matrices are assumed to be uncertain within given intervals, the time delays appear in both the system states and the nonlinear disturbances, and the stochastic perturbation is in the form of a Brownian motion. The purpose of the addressed stochastic stabilization problem is to design a memoryless state feedback controller such that, for all admissible interval uncertainties and nonlinear disturbances, the closed-loop system is asymptotically stable in the mean square, where the stability criteria are dependent on the length of the time delay and therefore less conservative. By using Itô's differential formula and the Lyapunov stability theory, sufficient conditions are first derived for ensuring the stability of the stochastic interval delay systems. Then, the controller gain is characterized in terms of the solution to a delay-dependent linear matrix inequality (LMI), which can be easily solved by using available software packages. A numerical example is exploited to demonstrate the effectiveness of the proposed design procedure.This work was supported in part by the Engineering and Physical Sciences Research Council (EPSRC) of the UK under Grant GR/S27658/01, the Nuffield Foundation of the UK under Grant NAL/00630/G, and the Alexander von Humboldt Foundation of Germany

Robust stability for stochastic Hopfield neural networks with time delays

This is the post print version of the article. The official published version can be obtained from the link below - Copyright 2006 Elsevier Ltd.In this paper, the asymptotic stability analysis problem is considered for a class of uncertain stochastic neural networks with time delays and parameter uncertainties. The delays are time-invariant, and the uncertainties are norm-bounded that enter into all the network parameters. The aim of this paper is to establish easily verifiable conditions under which the delayed neural network is robustly asymptotically stable in the mean square for all admissible parameter uncertainties. By employing a Lyapunov–Krasovskii functional and conducting the stochastic analysis, a linear matrix inequality (LMI) approach is developed to derive the stability criteria. The proposed criteria can be checked readily by using some standard numerical packages, and no tuning of parameters is required. Examples are provided to demonstrate the effectiveness and applicability of the proposed criteria.This work was supported in part by the Engineering and Physical Sciences Research Council (EPSRC) of the UK under Grant GR/S27658/01, the Nuffield Foundation of the UK under Grant NAL/00630/G, and the Alexander von Humboldt Foundation of German

Emergently Alteration of Procedural Strategy During Transcatheter Aortic Valve Replacement to Prevent Coronary Occlusion: A Case Report

BackgroundCoronary occlusion is an uncommon but fatal complication of transcatheter aortic valve replacement (TAVR) with a poor prognosis.Case PresentationA patient with symptomatic severe bicuspid aortic valve stenosis was admitted to a high-volume center specializing in transfemoral TAVR with self-expanding valves. No anatomical risk factors of coronary occlusion were identified on pre-procedural computed tomography analysis. The patient was scheduled for a transfemoral TAVR with a self-expanding valve. Balloon pre-dilatation prior to prosthesis implantation was routinely used for assessing the supra-annular structure and assessing the risk of coronary occlusion. Immediately after the tubular balloon inflation, fluoroscopy revealed that the right coronary artery was not visible, and the flow in the left coronary artery was reduced. The patient would be at high-risk of coronary occlusion if a long stent self-expanding valve was implanted. Therefore, our heart team decided to suspend the ongoing procedure. A transapical TAVR with a 23 mm J-valve was performed 3 days later. The prosthesis was deployed at a proper position without blocking the coronary ostia and the final fluoroscopy showed normal flow in bilateral coronary arteries with the same filling as preoperatively.DiscussionOur successful case highlights the importance of a comprehensive assessment of coronary risk and a thorough understanding of the TAVR procedure for the heart team. A short-stent prosthesis is feasible for patients at high risk of coronary occlusion. Most importantly TAVR should be called off even if the catheter has been introduced when an extremely high risk of coronary obstruction is identified during the procedure and no solution can be found

Effect of Aged Wuyi Rock Tea on Relieving Dextran Sulfate Sodium-Induced Colitis and Regulating the Gut Microbiota in Mice

This research was performed in order to investigate the alleviative effect of aged Wuyi rock tea on dextran sulfate sodium (DSS)-induced colitis in mice. Fifty C57BL/6JGpt female mice were randomly and equally divided into five groups: control, DSS, DSS + infusion of 20-year-old Wuyi rock tea (DSS + OT01), DSS + infusion of 10-year-old Wuyi rock tea (DSS + OT11) and DSS + infusion of fresh Wuyi rock tea (DSS + OT20). The physiological and histopathological conditions of mice after Wuyi rock tea interventions, and the changes of serum inflammatory factors and cecal microbiota were analyzed. The results showed that aged Wuyi rock tea could significantly alleviate the symptoms of body mass loss, diarrhea, bloody stool, and colon length shortening, reduce inflammatory cell infiltration, and significantly inhibit the secretion of pro-inflammatory cytokines. In addition, aged Wuyi rock tea could alleviate the disorder of the gut microbiota, significantly down-regulate the relative abundance of Proteobacteria, Enterobacteriaceae and Escherichia, and up-regulate the relative abundance of Verrucomicrobia and Akkermansia. In summary, aged Wuyi rock tea can alleviate DSS-induced colitis in mice, and the tea produced in 2011 is more effective than that produced in 2001, which may be due to proper oxidation of catechins such as epigallocatechin gallate to produce thearubigins, with better anti-inflammatory and antioxidant properties. In addition, aged Wuyi rock tea is able to maintain intestinal homeostasis by regulating the relative abundance of Escherichia and Akkermansia in the intestine, which in turn alleviates the symptoms of DSS-induced colitis in mice such as body mass loss, diarrhea, bloody stool, colon length shortening, mucosal and crypt damage, inflammatory cell infiltration, and serum inflammatory factor overexpression

Integrated metabolome and transcriptome analyses provide insight into the effect of red and blue LEDs on the quality of sweet potato leaves

Red and blue light-emitting diodes (LEDs) affect the quality of sweet potato leaves and their nutritional profile. Vines cultivated under blue LEDs had higher soluble protein contents, total phenolic compounds, flavonoids, and total antioxidant activity. Conversely, chlorophyll, soluble sugar, protein, and vitamin C contents were higher in leaves grown under red LEDs. Red and blue light increased the accumulation of 77 and 18 metabolites, respectively. Alpha-linoleic and linolenic acid metabolism were the most significantly enriched pathways based on Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway analyses. A total of 615 genes were differentially expressed between sweet potato leaves exposed to red and blue LEDs. Among these, 510 differentially expressed genes were upregulated in leaves grown under blue light compared with those grown under red light, while the remaining 105 genes were expressed at higher levels in the latter than in the former. Among the KEGG enrichment pathways, blue light significantly induced anthocyanin and carotenoid biosynthesis structural genes. This study provides a scientific reference basis for using light to alter metabolites to improve the quality of edible sweet potato leaves

Genome-wide associations for birth weight and correlations with adult disease

Birth weight (BW) has been shown to be influenced by both fetal and maternal factors and in observational studies is reproducibly associated with future risk of adult metabolic diseases including type 2 diabetes (T2D) and cardiovascular disease. These life-course associations have often been attributed to the impact of an adverse early life environment. Here, we performed a multi-ancestry genome-wide association study (GWAS) meta-analysis of BW in 153,781 individuals, identifying 60 loci where fetal genotype was associated with BW ($\textit{P}$  < 5 × 10$^{-8}$). Overall, approximately 15% of variance in BW was captured by assays of fetal genetic variation. Using genetic association alone, we found strong inverse genetic correlations between BW and systolic blood pressure ($\textit{R}$ $_{g}$ = -0.22, $\textit{P}$  = 5.5 × 10$^{-13}$), T2D ($\textit{R}$ $_{g}$ = -0.27, $\textit{P}$  = 1.1 × 10$^{-6}$) and coronary artery disease ($\textit{R}$ $_{g}$ = -0.30, $\textit{P}$  = 6.5 × 10$^{-9}$). In addition, using large -cohort datasets, we demonstrated that genetic factors were the major contributor to the negative covariance between BW and future cardiometabolic risk. Pathway analyses indicated that the protein products of genes within BW-associated regions were enriched for diverse processes including insulin signalling, glucose homeostasis, glycogen biosynthesis and chromatin remodelling. There was also enrichment of associations with BW in known imprinted regions ($\textit{P}$ = 1.9 × 10$^{-4}$). We demonstrate that life-course associations between early growth phenotypes and adult cardiometabolic disease are in part the result of shared genetic effects and identify some of the pathways through which these causal genetic effects are mediated.For a full list of the funders pelase visit the publisher's website and look at the supplemetary material provided. Some of the funders are: British Heart Foundation, Cancer Research UK, Medical Research Council, National Institutes of Health, Royal Society and Wellcome Trust

A Meta-analysis of Gene Expression Signatures of Blood Pressure and Hypertension

Genome-wide association studies (GWAS) have uncovered numerous genetic variants (SNPs) that are associated with blood pressure (BP). Genetic variants may lead to BP changes by acting on intermediate molecular phenotypes such as coded protein sequence or gene expression, which in turn affect BP variability. Therefore, characterizing genes whose expression is associated with BP may reveal cellular processes involved in BP regulation and uncover how transcripts mediate genetic and environmental effects on BP variability. A meta-analysis of results from six studies of global gene expression profiles of BP and hypertension in whole blood was performed in 7017 individuals who were not receiving antihypertensive drug treatment. We identified 34 genes that were differentially expressed in relation to BP (Bonferroni-corrected p&lt;0.05). Among these genes, FOS and PTGS2 have been previously reported to be involved in BP-related processes; the others are novel. The top BP signature genes in aggregate explain 5%–9% of inter-individual variance in BP. Of note, rs3184504 in SH2B3, which was also reported in GWAS to be associated with BP, was found to be a trans regulator of the expression of 6 of the transcripts we found to be associated with BP (FOS, MYADM, PP1R15A, TAGAP, S100A10, and FGBP2). Gene set enrichment analysis suggested that the BP-related global gene expression changes include genes involved in inflammatory response and apoptosis pathways. Our study provides new insights into molecular mechanisms underlying BP regulation, and suggests novel transcriptomic markers for the treatment and prevention of hypertension

Genetic drivers of heterogeneity in type 2 diabetes pathophysiology

Type 2 diabetes (T2D) is a heterogeneous disease that develops through diverse pathophysiological processes1,2 and molecular mechanisms that are often specific to cell type3,4. Here, to characterize the genetic contribution to these processes across ancestry groups, we aggregate genome-wide association study data from 2,535,601 individuals (39.7% not of European ancestry), including 428,452 cases of T2D. We identify 1,289 independent association signals at genome-wide significance (P &lt; 5 × 10-8) that map to 611 loci, of which 145 loci are, to our knowledge, previously unreported. We define eight non-overlapping clusters of T2D signals that are characterized by distinct profiles of cardiometabolic trait associations. These clusters are differentially enriched for cell-type-specific regions of open chromatin, including pancreatic islets, adipocytes, endothelial cells and enteroendocrine cells. We build cluster-specific partitioned polygenic scores5 in a further 279,552 individuals of diverse ancestry, including 30,288 cases of T2D, and test their association with T2D-related vascular outcomes. Cluster-specific partitioned polygenic scores are associated with coronary artery disease, peripheral artery disease and end-stage diabetic nephropathy across ancestry groups, highlighting the importance of obesity-related processes in the development of vascular outcomes. Our findings show the value of integrating multi-ancestry genome-wide association study data with single-cell epigenomics to disentangle the aetiological heterogeneity that drives the development and progression of T2D. This might offer a route to optimize global access to genetically informed diabetes care.</p

Implicating genes, pleiotropy, and sexual dimorphism at blood lipid loci through multi-ancestry meta-analysis

Background: Genetic variants within nearly 1000 loci are known to contribute to modulation of blood lipid levels. However, the biological pathways underlying these associations are frequently unknown, limiting understanding of these findings and hindering downstream translational efforts such as drug target discovery. Results: To expand our understanding of the underlying biological pathways and mechanisms controlling blood lipid levels, we leverage a large multi-ancestry meta-analysis (N = 1,654,960) of blood lipids to prioritize putative causal genes for 2286 lipid associations using six gene prediction approaches. Using phenome-wide association (PheWAS) scans, we identify relationships of genetically predicted lipid levels to other diseases and conditions. We confirm known pleiotropic associations with cardiovascular phenotypes and determine novel associations, notably with cholelithiasis risk. We perform sex-stratified GWAS meta-analysis of lipid levels and show that 3–5% of autosomal lipid-associated loci demonstrate sex-biased effects. Finally, we report 21 novel lipid loci identified on the X chromosome. Many of the sex-biased autosomal and X chromosome lipid loci show pleiotropic associations with sex hormones, emphasizing the role of hormone regulation in lipid metabolism. Conclusions: Taken together, our findings provide insights into the biological mechanisms through which associated variants lead to altered lipid levels and potentially cardiovascular disease risk.GMP, PN, and CW are supported by NHLBI R01HL127564. GMP and PN are supported by R01HL142711. AG acknowledge support from the Wellcome Trust (201543/B/16/Z), European Union Seventh Framework Programme FP7/2007–2013 under grant agreement no. HEALTH-F2-2013–601456 (CVGenes@Target) & the TriPartite Immunometabolism Consortium [TrIC]-Novo Nordisk Foundation’s Grant number NNF15CC0018486. JMM is supported by American Diabetes Association Innovative and Clinical Translational Award 1–19-ICTS-068. SR was supported by the Academy of Finland Center of Excellence in Complex Disease Genetics (Grant No 312062), the Finnish Foundation for Cardiovascular Research, the Sigrid Juselius Foundation, and University of Helsinki HiLIFE Fellow and Grand Challenge grants. EW was supported by the Finnish innovation fund Sitra (EW) and Finska Läkaresällskapet. CNS was supported by American Heart Association Postdoctoral Fellowships 15POST24470131 and 17POST33650016. Charles N Rotimi is supported by Z01HG200362. Zhe Wang, Michael H Preuss, and Ruth JF Loos are supported by R01HL142302. NJT is a Wellcome Trust Investigator (202802/Z/16/Z), is the PI of the Avon Longitudinal Study of Parents and Children (MRC & WT 217065/Z/19/Z), is supported by the University of Bristol NIHR Biomedical Research Centre (BRC-1215–2001) and the MRC Integrative Epidemiology Unit (MC_UU_00011), and works within the CRUK Integrative Cancer Epidemiology Programme (C18281/A19169). Ruth E Mitchell is a member of the MRC Integrative Epidemiology Unit at the University of Bristol funded by the MRC (MC_UU_00011/1). Simon Haworth is supported by the UK National Institute for Health Research Academic Clinical Fellowship. Paul S. de Vries was supported by American Heart Association grant number 18CDA34110116. Julia Ramierz acknowledges support by the People Programme of the European Union’s Seventh Framework Programme grant n° 608765 and Marie Sklodowska-Curie grant n° 786833. Maria Sabater-Lleal is supported by a Miguel Servet contract from the ISCIII Spanish Health Institute (CP17/00142) and co-financed by the European Social Fund. Jian Yang is funded by the Westlake Education Foundation. Olga Giannakopoulou has received funding from the British Heart Foundation (BHF) (FS/14/66/3129). CHARGE Consortium cohorts were supported by R01HL105756. Study-specific acknowledgements are available in the Additional file 32: Supplementary Note. The views expressed in this manuscript are those of the authors and do not necessarily represent the views of the National Heart, Lung, and Blood Institute; the National Institutes of Health; or the U.S. Department of Health and Human Services