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Randomized controlled trials - mechanistic studies of testosterone and the cardiovascular system

Asian Journal of Andrology 2018年第2期20卷 120-130页

作者： T Hugh Jones daniel M Kelly Robert Hague Centre for Diabetes and Endocrinology Barnsley Hospital NHS Foundation Trust Barnsley UK Academic Unit of Diabetes Endocrinology and Metabolism Department of Oncology and Metabolism University of Sheffield Medical School Sheffield UK Biomedical Research Centre Sheffield Hallam University Sheffield UK

Testosterone deficiency is common in men with cardiovascular disease （CVD）, and randomized placebo-controlled trials （RCTs） have reported beneficial effects of testosterone therapy on exercise-induced cardiac ischemia in chronic stable angina, functional exercise capacity, maximum oxygen consumption during exercise （VO2m,x） and muscle strength in chronic heart failure （CHF）, shortening of the Q-T interval, and improvement of some cardiovascular risk factors. Testosterone deficiency is associated with an adverse CV risk profile and mortality. Clinical and scientific studies have provided mechanistic evidence to support and explain the findings of the RCTs. Testosterone is a rapid-onset arterial vasodilator within the coronary circulation and other vascular beds including the pulmonary vasculature and can reduce the overall peripheral systemic vascular resistance. Evidence has demonstrated that testosterone mediates this effect on vascular reactivity through calcium channel blockade （l-calcium channel） and stimulates potassium channel opening by direct nongenomic mechanisms. Testosterone also stimulates repolarization of cardiac myocytes by stimulating the ultra-rapid potassium channel-operated current. Testosterone improves cardiac output, functional exercise capacity, VO2m=x and vagally mediated arterial baroreceptor cardiac reflex sensitivity in CHF, and other mechanisms. Independent of the benefit of testosterone on cardiac function, testosterone substitution may also increase skeletal muscle glucose metabolism and enhance muscular strength, both factors that could contribute to the improvement in functional exercise capacity may include improved glucose metabolism and muscle strength. Testosterone improves metabolic CV risk factors including body composition, insulin resistance, and hypercholesterolemia by improving both glucose utilization and lipid metabolism by a combination of genomic and nongenomic actions of glucose uptake and utilization expression of the

关键词： cardiovascular testosterone testosterone replacement

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An evolutionary computational framework for capacity-safety trade-off in an air transportation network

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Chinese Journal of Aeronautics 2019年第4期32卷 999-1010页

作者： Md.Murad HOSSAIN Sameer AlAM daniel DElAHAYE School of Engineering and Information Technology University of New South Wales School of Mechanical and Aerospace Engineering Nanyang Technological University MAIAA laboratory Ecole Nationale de l'Aviation Civile

Airspace safety and airport capacity are two key challenges to sustain the growth in Air Transportation. In this paper, we model the Air Transportation Network as two sub-networks of airspace and airports, such that the safety and capacity of the overall Air Transportation network emerge from the interaction between the two. We propose a safety-capacity trade-off approach,using a computational framework, where the two networks can inter-act and the trade-off between capacity and safety in an Air Transport Network can be established. The framework comprise of an evolutionary computation based air traffic scenario generation using a flow capacity estimation module(for capacity), Collision risk estimation module(for safety) and an air traffic simulation module(for evaluation). The proposed methodology to evolve air traffic scenarios such that it minimizes collision risk for given capacity estimation was tested on two different air transport network topologies(random and small-world) with the same number of airports. Experimental results indicate that though airspace collision risk increases almost linearly with the increasing flow(flow intensity) in the corresponding airport network, the critical flow depend on the underlying network configuration. It was also found that, in general, the capacity upper bound depends not only on the connectivity among airports and their individual performances but also the configuration of waypoints and mid-air interactions among conflicts. Results also show that airport network can accommodate more traffic in terms of capacity but the corresponding airspace network cannot accommodate the resulting traffic flow due to the bounds on collision risk.

关键词： Airport network Airspace capacity Airspace safety Collision risk Flow intensity

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Helicobacter pylori and autoimmune disease:Cause or bystander

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World Journal of Gastroenterology 2014年第3期20卷 613-629页

作者： daniel S Smyk Andreas l Koutsoumpas Maria G Myt-ilinaiou Eirini I Rigopoulou lazaros I Sakkas Dimitrios P Bogdanos Institute of liver Studies Division of Transplantation Immunology and Mucosal BiologyKing's College HospitalSchool of MedicineKing's College London Department of Medicine Faculty of MedicineSchool of Health SciencesUniversity of Thessaly Department of Rheumatology Faculty of MedicineSchool of Health SciencesUniversity of Thessaly Cellular Immunotherapy and Molecular Immunodiagnostics Biomedical SectionCEntre for REsearch and TEchnology Hellas (CE.R.T.H.)/Institute for REsearch and Technology-THessaly (I.RE.TE.TH)

Helicobacter pylori (H. pylori) is the main cause of chronic gastritis and a major risk factor for gastric cancer. This pathogen has also been considered a potential trigger of gastric autoimmunity, and in particular of autoimmune gastritis. However, a considerable number of reports have attempted to link H. pylori infection with the development of extra-gastrointestinal autoimmune disorders, affecting organs not immediately relevant to the stomach. This review discusses the current evidence in support or against the role of H. pylori as a potential trigger of autoimmune rheumatic and skin diseases, as well as organ specific autoimmune diseases. We discuss epidemiological, serological, immunological and experimental evidence associating this pathogen with autoimmune diseases. Although over one hundred autoimmune diseases have been investigated in relation to H. pylori, we discuss a select number of papers with a larger literature base, and include Sjögrens syndrome, rheumatoid arthritis, systemic lupus erythematosus, vasculitides, autoimmune skin conditions, idiopathic thrombocytopenic purpura, autoimmune thyroid disease, multiple sclerosis, neuromyelitis optica and autoimmune liver diseases. Specific mention is given to those studies reporting an association of anti-H. pylori antibodies with the presence of autoimmune disease-specific clinical parameters, as well as those failing to find such associations. We also provide helpful hints for future research.

关键词： Autoimmunity Helicobacter pylori Infection Gastritis Mimicry Rheumatology

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Ultrathin Acoustic Parity-Time Symmetric Metasurface Cloak

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Research 2019年第1期2019卷 671-677页

作者： Hao-xiang li Mar-a Rosendo-lópez Yi-fan Zhu Xu-dong Fan daniel Torrent Bin liang Jian-chun Cheng Johan Christensen Key laboratory of Modern Acoustics MOEInstitute of AcousticsDepartment of PhysicsCollaborative Innovation Center of Advanced MicrostructuresNanjing UniversityNanjing 210093China Department of Physics Universidad Carlos III de Madrid28916 LeganesMadridSpain GROC UJIInstitut de Noves Tecnologies de la Imatge(INIT)Universitat Jaume I12080 Castell`eSpain

Invisibility or unhearability cloaks have been made possible by using metamaterials enabling light or sound to fow around obstacle without the trace of refections or *** are known for being fexible building units that can mimic a host of unusual and extreme material responses,which are essential when engineering artifcial material properties to realize a coordinate transforming *** and stretching the coordinate grid in space require stringent material parameters;therefore,small inaccuracies and inevitable material losses become sources for unwanted scattering that are decremental to the desired *** obstacles further limit the possibility of achieving a robust concealment of sizeable objects from either radar or sonar *** using an elaborate arrangement of gain and lossy acoustic media respecting parity-time symmetry,we built a one-way unhearability cloak able to hide objects seven times larger than the acoustic *** speaking,our approach has no limits in terms of working frequency,shape,or size,specifcally though we demonstrate how,in principle,an object of the size of a human can be hidden from audible sound.

关键词： coordinate stretching arrangement

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Coating independent cytotoxicity of citrate-and PEG-coated silver nanoparticles on a human hepatoma cell line

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Journal of Environmental Sciences 2017年第1期29卷 191-201页

作者： Veronica Bastos Jose M.P.Ferreira-de-Oliveira Joana Carrola Ana l.daniel-da-Silva Iola F.Duarte Conceicao Santos Helena Oliveira CESAM&laboratory of Biotechnology and Cytomics Department of BiologyUniversity of Aveiro3810-193 AveiroPortugal CICECO-Aveiro Institute of Materials Department of ChemistryUniversity of Aveiro3810-193 AveiroPortugal Department of Biology Faculty of SciencesUniversity of Porto4169-007 PortoPortugal

The antibacterial potential of silver nanoparticles（AgNPs） resulted in their increasing incorporation into consumer,industrial and biomedical ***,human and environmental exposure to AgNPs（either as an engineered product or a contaminant）supports the emergent research on the features conferring them different toxicity *** this study,30 ran AgNPs coated with citrate or poly（ethylene glycol）（PEG） were used to assess the influence of coating on the effects produced on a human hepatoma cell line（HepG2）,namely in terms of viability,apoptosis,apoptotic related genes,cell cycle and cyclins gene *** types of coated AgNPs decreased cell proliferation and viability with a similar toxicity *** the concentrations used（11 and 5 μg/ml corresponding to IC50 and-IC10 levels,respectively） the amount of cells undergoing apoptosis was not significant and the apoptotic related genes BCl2（anti-apoptotic gene）and BAX（pro-apoptotic gene） were both ***,both AgNPs affected HepG2 cell cycle progression at the higher concentration（11 μg/ml） by increasing the percentage of cells in S（synthesis phase） and G2（Gap 2 phase） *** the cell-cycle related genes,the expression of cyclin B1 and cyclin E1 genes were ***,this work has shown that citrate- and PEG-coated AgNPs impact on HepG2 apoptotic gene expression,cell cycle dynamics and cyclin regulation in a similar *** research is needed to determine the properties that confer AgNPs at lower toxicity,since their use has proved helpful in several industrial and biomedical contexts.

关键词： Silver nanoparticles(AgNPs) Citrate Polyethylene glycol)(PEG) HepG2 cells Cytotoxicity Nanotoxicology

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Deep learning-based analysis of macaque corneal sub-basal nerve fibers in confocal microscopy images

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Eye and Vision 2020年第1期7卷 255-265页

作者： Jonathan D.Oakley daniel B.Russakoff Megan E.McCarron Rachel l.Weinberg Jessica M.Izzi Stuti l.Misra Charles N.McGhee Joseph l.Mankowski Voxeleron llC San FranciscoCAUSA Department of Molecular and Comparative Pathobiology Johns Hopkins University School of MedicineBaltimoreMDUSA Department of Ophthalmology Faculty of Medical and Health SciencesNew Zealand National Eye CentreUniversity of AucklandAucklandNew Zealand

Background:To develop and validate a deep learning-based approach to the fully-automated analysis of macaque corneal sub-basal nerves using in vivo confocal microscopy(IVCM).Methods:IVCM was used to collect 108 images from 35 macaques.58 of the images from 22 macaques were used to evaluate different deep convolutional neural network(CNN)architectures for the automatic analysis of sub-basal nerves relative to manual *** remaining images were used to independently assess correlations and interobserver performance relative to three ***:Correlation scores using the coefficient of determination between readers and the best CNN averaged *** inter-observer comparison,inter-correlation coefficients(ICCs)between the three expert readers and the automated approach were 0.75,0.85 and *** ICC between all four observers was 0.84,the same as the average between the CNN and individual ***:Deep learning-based segmentation of sub-basal nerves in IVCM images shows high to very high correlation to manual segmentations in macaque data and is indistinguishable across *** quantitative measurements of corneal sub-basal nerves are important biomarkers for disease screening and management,the reported work offers utility to a variety of research and clinical studies using IVCM.

关键词： Cornea Sensory nerves Macaque Deep learning In vivo confocal microscopy

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Synthesis of Pyrrole-Imidazole Polyamide

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Chinese Chemical letters 2000年第3期11卷 207-208页

作者： Jun Hua XIAO Gu YUAN Wei Qiang HUANG Fei li TANG Albert S.C.CHAN K.l.daniel lEE Bioorganic Molecular Engineering laboratory Department of ChemistryPeking UniversityBeijing 100871 Department of Applied Biology and Chemical Technology The Hong Kong Polytechnic UniversityHK

One simple and versatile method is established far the synthesis of DNA recognition molecules-polyamides containing alternating N-methylpyrrole and N-methylimidazole without necessitating NH2- group protection.

关键词： polyamides DNA recognition molecules pyrroles and imidazoles

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Towards intermediate-band photovoltaic absorbers:theoretical insights on the incorporation of Ti and Nb in In_(2)S_(3)

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npj Computational Materials 2020年第1期6卷 705-713页

作者： Elaheh Ghorbani daniel Barragan-Yani Karsten Albe Fachgebiet Materialmodellierung Institut für MaterialwissenschaftTU DarmstadtOtto-Berndt-Straße 3D-64287 DarmstadtGermany Physics and Materials Science Research Unit University of LuxembourgL-1511 LuxembourgLuxembourg

Creation of a partially filled intermediate band in a photovoltaic absorber material is an appealing concept for increasing the quantum efficiency of solar ***,we showed that formation of a partially filled intermediate band through doping a host semiconductor with a transition metal dopant is hindered by the strongly correlated nature of d-electrons and the antecedent Jahn–Teller distortion,as we have previously *** present work,we take a step forward and study the delocalization of a filled(valence-like)intermediate band throughout the lattice:a case study of Ti-and Nb-doped In_(2)S_(3).By means of hybrid density functional calculations,we present extensive analysis on structural properties and interactions leading to electronic characteristics of Ti-and Nb-doped In_(2)S_(3).

关键词： absorber filled intermediate

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Effects of intestine-specific deletion of fibroblast growth factor 15 on alcoholic liver disease development in mice

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liver Research 2022年第2期6卷 84-92页

作者： Bo Kong Mingxing Huang Rulaiha E.Taylor daniel Rizzolo Katherine D.Otersen Grace l.Guo Department of Pharmacology and Toxicology Ernest Mario School of PharmacyRutgersThe State University of New JerseyPiscatawayNJUSA Department of Infectious Diseases The Fifth Affiliated Hospital of Sun Yat-sen UniversityZhuhaiGuangdongChina Environmental and Occupational Health Sciences Institute RutgersThe State University of New JerseyPiscatawayNJUSA Rutgers Center for lipid Research RutgersThe State University of New JerseyPiscatawayNJUSA VA New Jersey Health Care System Veterans Administration Medical CenterEast OrangeNJUSA

Background and aims:Alcoholic liver disease(AlD)is an important and growing cause for the development of chronic liver diseases in the *** acid(BA)levels are increased in patients with AlD anddysregulation of BA homeostasis worsens *** synthesis is critically regulated by fibroblast growthfactor(FGF)15 in mice and FGF19 in ***15/19 are mainly produced in the ileum and their mainfunction is to suppress BA synthesis in the liver through the activation of fibroblast growth factor receptor 4(FGFR4)on *** effects of intestine-specific Fgf15 deficiency on the development ofAlD were determined in the current ***:Enterocyte-specific Fgf15 knockout mice(Fgf15intint^(-/-))and the established mouse model bychronic and binge ethanol feeding(NIAAA model)were adapted in this ***:The Fgf15intint^(-/-)mice had increased BA pool size,consistent with negative effects of FGF15-FGFR4signaling on BA *** were not obviously physical and hepatic histological abnormalitiespresented in Fgf15intint^(-/-)mice compared to wild-type *** alcohol treatment,the Fgf15intint^(-/-)mice exhibited a higher degree of liver injury,increased hepatic expression of Cd14,a receptor forlipopolysaccharide expressed in the liver,and increased hepatic lipid *** did not observe alterations in the levels of fibrosis in the liver or expression of genes involved in hepatic fibrosis,regardless ofgenotypes or following the alcohol ***:FGF15 may prevent hepatic steatosis in the development of AlD in mice,and maintainingFGF19/FGFR4 signaling may be critical in the prevention and/or treatment of AlD in humans in thefuture.

关键词： Fibroblast growth factor 15(FGF15) Farnesoid X receptor(FXR) Bile acid(BA) Alcoholic fatty liver disease Alcoholic steatohepatitis

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Homocysteine induces production of monocyte chemoattractant protein-1 and interleukin-8 in cultured human whole blood

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Acta Pharmacologica Sinica 2004年第11期 35-41页

作者： daniel G REMICK Ann Arbor Department of Pathology University of Michigan Medical School MI 48109 USA

AIM: To investigate whether increased plasma l-homocysteine (Hcy) level could promote monocyte chemoattractant protein-1 (MCP-1) and interleukin-8 (Il-8) in cultured whole blood. METHODS: Human whole blood or different type of peripheral blood cells from health volunteers were incubated with Hcy and/or the inhibitors. MCP-1 and Il-8 level were measured by ElISA assay. RESUlTS: Hcy 10-1000μmol/l induced production of MCP-1 and Il-8 in cultured human whole blood (Pllular source of these chemokines corned from monocytes. Meanwhile,Hcy also promoted the upregulation of MPO level even at the 10 μmol/l in the cultured whole blood. The intracellular ROS, particular the OH’ radicals, play extremely important role in the Hcy-induced MCP-1 and Il-8 production. CONClUSION: Increased Hcy level in plasma (hyperhomocysteinemia) induced MCP-1 and Il-8 secretion in cultured human whole blood, especially in monocytes via oxidative stress mechanism.

关键词： atherosclerosis monocyte chemoattractant protein-1 interleukin-8 homocysteine monocytes

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