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Selective androgen receptor modulators for the treatment of late onset male hypogonadism

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Asian Journal of Andrology 2014年第2期16卷 256-261,I0009页

作者： Christopher C Coss Amanda Jones michael l hancock Mitchell S Steiner James T Dalton GTx Inc. Memphis Tennessee USA.

Several testosterone preparations are used in the treatment of hypogonadism in the ageing male. These therapies differ in their convenience, flexibility, regional availability and expense but share their pharmacokinetic basis of approval and dearth of long-term safety data. The brevity and relatively reduced cost of pharmacokinetic based registration trials provides little commercial incentive to develop improved novel therapies for the treatment of late onset male hypogonadism. Selective androgen receptor modulators （SARMs） have been shown to provide anabolic benefit in the absence of androgenic effects on prostate, hair and skin. Current clinical development for SARMs is focused on acute muscle wasting conditions with defined clinical endpoints of physical function and lean body mass. Similar regulatory clarity concerning clinical deficits in men with hypogonadism is required before the beneficial pharmacology and desirable pharmacokinetics of SARMs can be employed in the treatment of late onset male hypogonadism.

关键词： hypogonadism late onset hypogonadism selective androgen receptor modulators testosterone

lKB1 depletion-mediated epithelial-mesenchymal transition induces fibroblast activation in lung fibrosis

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Genes & Diseases 2024年第3期11卷 417-426页

作者： Zijian Xu Elizabeth R.Davies liudi Yao Yilu Zhou Juanjuan li Aiman Alzetani Ben G.Marshall David hancock Tim Wallis Julian Downward Rob M.Ewing Donna E.Davies Mark G.Jones Yihua Wang Biological Sciences Faculty of Environmental and Life SciencesUniversity of SouthamptonSouthampton SO171BJUK clinical and Experimental Sciences Faculty of MedicineUniversity of SouthamptonSouthampton SO166YDUK Institute for life Sciences University of SouthamptonSouthampton SO171BJUK NIHR Southampton Biomedical Research Centre University Hospital SouthamptonSouthampton SO166YDUK University Hospital Southampton Southampton SO166YDUK Oncogene Biology The Francis Crick InstituteLondon NW11ATUK

The factors that determine fibrosis progression or normal tissue repair are largely *** previously demonstrated that autophagy inhibition-mediated epithelial-mesenchymal transition(EMT)in human alveolar epithelial type Il(ATIl)cells augments local myofibroblast differentiation in pulmonary fibrosis by paracrine ***,we report that liver kinase B1(lKB1)inactivation in ATIl cells inhibits autophagy and induces EMT as a *** IPF lungs,this is caused by the down-regulation of CAB39l,a key subunit within the lKB1 complex.3D co-cultures of ATIl cells and MRC5 lung fibroblasts coupled with RNA sequencing(RNA-seq)confirmed that paracrine signaling between lKB1-depleted ATIl cells and fibroblasts augmented myofibroblast ***,these data suggest that reduced autophagy caused by lKB1 inhibition can induce EMT in ATIl cells and contribute to fibrosis via aberrant epithelial-fibroblast crosstalk.

关键词： CAB39l Crosstalk EMT lKB1 Pulmonary fibrosis

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与“个体”概念有关的一些问题

自然辩证法研究 1993年第7期 34-36页

作者： R.l.hancock,许良兰州大学中国理论生物研究所兰州大学哲学系

本文指出了生物个体概念的各种模糊性,并通过一些真实的和理论上的异常脑所表现出的潜在精神这一事实,指出了个体概念的成问题的背景。所谓个体,或许就是各种可能状态中最为可能的—种状态。最后,从全息生物学和系统论的观点对问题提出... 详细信息

本文指出了生物个体概念的各种模糊性,并通过一些真实的和理论上的异常脑所表现出的潜在精神这一事实,指出了个体概念的成问题的背景。所谓个体,或许就是各种可能状态中最为可能的—种状态。最后,从全息生物学和系统论的观点对问题提出了有益的见解。

关键词：记忆程度功能大脑半球概念思维形式

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脆性微观构造学:原理和实践

地震地质译丛

地震地质译丛 1986年第1期 1-9页

作者： P.l.hancock 王焕金

脆性微观构造学研究的目的是运用中型断裂分析技术来阐明构造问题。术语"中型"(Mesoscale)系沿用Turner和Weiss(1963)的定义,即指尺度从不足一厘米到数厘米的构造,同时它们可以在单个不连续的露头上分辨出来。本文涉及的构造包括中型断... 详细信息

脆性微观构造学研究的目的是运用中型断裂分析技术来阐明构造问题。术语"中型"(Mesoscale)系沿用Turner和Weiss(1963)的定义,即指尺度从不足一厘米到数厘米的构造,同时它们可以在单个不连续的露头上分辨出来。本文涉及的构造包括中型断裂、剪切带、雁形裂隙、扭折带、裂缝、岩脉以及压溶条纹

关键词：节理迹线共扼节理面断层带断裂带张节理沉积岩层剪节理节理组褶皱带地槽带构造带运动学标志压溶剪切带剪切破裂带

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津巴布韦几种经济上重要的实蝇

植物检疫 1985年第3期 51-53页

作者： D.l hancock 梁广勤

双翅目实蝇科包括若干对园艺具有重要性的种类。这类实蝇为害的作物范围很广,从落叶果树,亚热带果树和柑桔类果树,到咖啡浆果、蔬菜类和花类。也有一些种是有益的,感染杂草的种子,例如五星梅(lant-ana)和黑皮橡树中的一些品种。

关键词：实蝇科东部地区翅斑高地草原胸部斑蝇总科躯干南瓜实蝇果实蝇南罗得西亚津巴布韦

英国婴儿痉挛研究中心进行的多中心随机对照试验:用药14d时氨己烯酸与去氢氢化可的松和替可克肽的药效对比

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世界核心医学期刊文摘（儿科学分册） 2005年第4期1卷 6-7页

作者： lux A.l. Edwards hancock E. J.P.Osborne 李开 Roy.U.Hosp.Bath NHS Trust Sch. H. University of BathBathUnited Kingdom

研究背景:婴儿痉挛症为婴儿的一种严重癫痫性疾病,死亡率高且难治疗。既往几十年中,激素疗法(促肾上腺皮质激素和去氢氢化可的松)已成为主要的治疗方法,但却很少有证据支持此疗法。据记载,氨己烯酸对此病有效。目的:氨己烯酸与去氢化可... 详细信息

研究背景:婴儿痉挛症为婴儿的一种严重癫痫性疾病,死亡率高且难治疗。既往几十年中,激素疗法(促肾上腺皮质激素和去氢氢化可的松)已成为主要的治疗方法,但却很少有证据支持此疗法。据记载,氨己烯酸对此病有效。目的:氨己烯酸与去氢化可的松和替可克肽均可治疗婴儿痉挛症,本文对比分析两类药物的治疗效果。方法:本研究为多中心随机对照试验,在英国150所医院进行,由英国婴儿痉挛研究中心评测结果。以用药第13和14天时痉挛停止作为有效治疗结果指标。

关键词：氨己烯酸婴儿痉挛随机对照试验癫痫性研究中心去氢激素疗法癫痛 seizure 结果指标

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爱琴地区新构造正断层带的构造非均匀性

地壳构造与地壳应力 1992年第5期 40-53页

作者： I.S.Stewart P.l.hancock 马保启吴卫民

一、引言本文是对爱琴张性构造区新构造正断层带为期五年的野外调查结果所作的综台与分析(图1)．着重介绍爱琴地区的三个地带．(1)希腊大陆的科林斯地区(图1a)．(2)西土耳其的伊密兹尔地区(图1b)．(3)柯雷特的中部及西部(图1c)．在这... 详细信息

一、引言本文是对爱琴张性构造区新构造正断层带为期五年的野外调查结果所作的综台与分析(图1)．着重介绍爱琴地区的三个地带．(1)希腊大陆的科林斯地区(图1a)．(2)西土耳其的伊密兹尔地区(图1b)．(3)柯雷特的中部及西部(图1c)．在这三个地带正断层使中生代碳酸岩同第四纪沉积物直接相接，

关键词：正断层新构造张性构造第四纪碳酸岩中生代非均匀性引言大陆希腊

Observations of High Nitrate Concentrations in Forage Bermudagrass during Severe to Exceptional Drought Years

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American Journal of Plant Sciences 2016年第4期7卷 695-701页

作者： Dennis W. hancock Uttam K. Saha Jennifer J. Tucker R. lawton Stewart Jr. Department of Crop and Soil Sciences University of Georgia Athens USA Feed and Environmental Water laboratory University of Georgia Athens USA Department of Animal and Dairy Sciences University of Georgia Tifton USA Department of Animal and Dairy Sciences University of Georgia Athens USA

With the prediction of climate change-induced increases in drought frequency and severity in the southeastern USA, it is important to better understand the risks that drought may pose to NO3 accumulation in bermudagrass [Cynodon dactylon (l.) Pers.] forage. This report offers observations of NO3 concentration in Bermudagrass forage samples submitted to the University of Georgia’s Feed and Environmental Water lab (FEWl) during the extreme to exceptional drought of 2007, the severe drought of 2008, and the four preceding seasons when drought stress was minimal or absent. The probability (P) of a sample being at high risk for nitrate toxicosis was the greatest for the extreme to exceptional drought of 2007 (P = 0.160), slightly lower in the severe drought year of 2008 (P = 0.105), and the lowest for samples from the 2003-2006 growing seasons (P = 0.082) when drought stress was minimal or absent.

关键词： Nitrates Drought Bermudagrass

Elucidating the genetic basis of antioxidant status in lettuce (lactuca sativa)

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Horticulture Research 2015年第1期2卷 47-59页

作者： Annabelle Damerum Stacey l Selmes Gaia F Biggi Graham JJ Clarkson Steve D Rothwell Maria JoséTruco Richard W Michelmore Robert D hancock Connie Shellcock Mark A Chapman Gail Taylor Centre for Biological Sciences University of SouthamptonLife SciencesUniversity RoadSouthamptonSO171BJUK Vitacress limited Lower Link FarmSt Mary BourneAndoverSP116DBHampshireUK The Genome Centre and the Department of Plant Sciences University of CaliforniaDavis95616CAUSA The James Hutton Institute InvergowrieDD25DADundeeUK

A diet rich in phytonutrients from fruit and vegetables has been acknowledged to afford protection against a range of human diseases,but many of the most popular vegetables are low in *** relatives of crops may contain allelic variation for genes determining the concentrations of these beneficial phytonutrients,and therefore understanding the genetic basis of this variation is important for breeding efforts to enhance nutritional *** this study,lettuce recombinant inbred lines,generated from a cross between wild and cultivated lettuce(lactuca serriola and lactuca sativa,respectively),were analysed for antioxidant(AO)potential and important phytonutrients including carotenoids,chlorophyll and phenolic *** grown in two environments,96 quantitative trait loci(QTl)were identified for these nutritional traits:4 for AO potential,2 for carotenoid content,3 for total chlorophyll content and 87 for individual phenolic compounds(two per compound on average).Most often,the *** alleles conferred an increase in total AOs and *** genes underlying these QTl were identified by BlASTn searches;in several cases,these had functions suggesting involvement in phytonutrient biosynthetic *** of a QTl on linkage group 3,which accounted for>30%of the variation in AO potential,revealed several candidate genes encoding multiple MYB transcription factors which regulate flavonoid biosynthesis and flavanone 3-hydroxylase,an enzyme involved in the biosynthesis of the flavonoids quercetin and kaempferol,which are known to have powerful AO ***-up quantitative RT-PCR of these candidates revealed that 5 out of 10 genes investigated were significantly differentially expressed between the wild and cultivated parents,providing further evidence of their potential involvement in determining the contrasting *** results offer exciting opportunities to improve the nutritional content and health benefits of lettu

关键词： breeding crops lactuca