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新英格兰地区的隐形杂货巨头

商业周刊（中文版） 2013年第17期 51-52页

作者： brendan coffey Zohair Siraj 杨飞(译)

理查德·科恩凭借利润率很低的杂货业务累积起了庞大的财富“c＆S是一家没有人听说过的大公司”

关键词：新英格兰杂货隐形大公司利润率理查德财富

Evolving concepts in bone infection: redefining “biofilm”,“acute vs. chronic osteomyelitis”, “the immune proteome” and “local antibiotic therapy”

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Bone Research 2019年第3期7卷 225-242页

作者： Elysia A. Masters Ryan P. Trombetta Karen L. de Mesy Bentley brendan F Boyce Ann Lindley Gill Steven R. Gill Kohei Nishitani Masahiro Ishikawa Yugo Morita Hiromu Ito Sheila N. Bello-Irizarry Mark Ninomiya James D. Brodell Jr. charles c. Lee Stephanie P. Hao Irvin Oh chao Xie Hani A. Awad John L. Daiss John R. Owen Stephen L. Kates Edward M. Schwarz Gowrishankar Muthukrishnan center for Musculoskeletal Research University of Rochester Medical Center Rochester NY USA Department of Biomedical Engineering University of Rochester Medical Center Rochester NY USA Department of Pathology and Laboratory Medicine University of Rochester Medical Center Rochester NY USA Department of Orthopaedics University of Rochester Medical Center Rochester NY USA Department of Microbiology & Immunology University of Rochester Medical Center Rochester NY USA Department of Orthopaedic Surgery Kyoto University Kyoto Japan Department of Orthopaedic Surgery Virginia Commonwealth University Medical Center Richmond VA USA

Osteomyelitis is a devastating disease caused by microbial infection of bone. While the frequency of infection following elective orthopedic surgery is low, rates of reinfection are disturbingly high. Staphylococcus aureus is responsible for the majority of chronic osteomyelitis cases and is often considered to be incurable due to bacterial persistence deep within bone. Unfortunately, there is no consensus on clinical classifications of osteomyelitis and the ensuing treatment algorithm. Given the high patient morbidity,mortality, and economic burden caused by osteomyelitis, it is important to elucidate mechanisms of bone infection to inform novel strategies for prevention and curative treatment. Recent discoveries in this field have identified three distinct reservoirs of bacterial biofilm including: Staphylococcal abscess communities in the local soft tissue and bone marrow, glycocalyx formation on implant hardware and necrotic tissue, and colonization of the osteocyte-lacuno canalicular network(OLcN) of cortical bone. In contrast, *** intracellular persistence in bone cells has not been substantiated in vivo, which challenges this mode of chronic osteomyelitis. There have also been major advances in our understanding of the immune proteome against S. aureus, from clinical studies of serum antibodies and media enriched for newly synthesized antibodies(MENSA), which may provide new opportunities for osteomyelitis diagnosis, prognosis, and vaccine development. Finally, novel therapies such as antimicrobial implant coatings and antibiotic impregnated 3D-printed scaffolds represent promising strategies for preventing and managing this devastating disease. Here, we review these recent advances and highlight translational opportunities towards a cure.

关键词： disease caused by soft tissue necrotic tissuel

Sieving characteristics of cytokine-and peroxide-induced epithelial barrier leak:Inhibition by berberine

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World Journal of Gastrointestinal Pathophysiology 2016年第2期7卷 223-234页

作者： Katherine M DiGuilio christina M Mercogliano Jillian Born brendan Ferraro Julie To Brittany Mixson Allison Smith Mary carmen Valenzano James M Mullin Lankenau Institute for Medical Research Lankenau Medical Center Departments of Biology and Biomedical Engineering Drexel University

AIM: To study whether the inflammatory bowel disease (IBD) colon which exhibits varying severity and cytokine levels across its mucosa create varying types of transepithelial leak. METHODS: We examined the effects of tumor necrosis factor-α (TNF-α), interferon-γ (IFN-γ), interleukin-1-β (IL1β) and hydrogen peroxide (H2O2) - singly and in combinations - on barrier function of cAcO-2 cell layers. Our focus was on the type (not simply the magnitude) of transepithelial leak generated by these agents as measured by transepithelial electrical resistance (TER) and transepithelial flux of 14c-D-mannitol, 3H-Lactulose and 14c-Polyethylene glycol as radiolabeled probe molecules. The isoquinoline alkaloid, berberine, was then examined for its ability to reduce specific types of transepithelial leak. RESULTS: Exposure to TNF-α alone (200 ng/mL; 48 h) induced a 50% decrease in TER, i.e., increased leak of Na+ and cl- - with only a marginal but statistically significant increase in transepithelial leak of 14c-mannitol (Jm). Exposure to TNF-α + IFN-γ (200 ng/mL; 48 h) + IL1β (50 ng/mL; 48 h) did not increase the TER change (from TNF-α alone), but there was now a 100% increase in Jm. There however was no increase in transepithelial leak of two larger probe molecules, 3H-lactulose and 14c-polyethylene glycol (PEG). However, exposure to TNF-α + IFN-γ + IL1β followed by a 5 h exposure to 2 mmol/L H2O2 resulted in a 500% increase in 14c-PEG leak as well as leak to the luminal mitogen, epidermal growth factor. cONcLUSION: This model of graded transepithelial leak is useful in evaluating therapeutic agents reducing IBD morbidity by reducing barrier leak to various luminal substances.

关键词： Intestine crohn’s disease Tight junction Ulcerative colitis cAcO-2 Berberine Micronutrient cytokine

剖宫产术后皮下连续输注布比卡因对切口处IL-10、P物质浓度的影响

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麻醉与镇痛 2012年第2期8卷 64-72页

作者： brendan carvalho David J. clark David c. Yeomans Martin S. Angst 何欣（译）刘晓（译）郭曲练（校） Department of Anesthesia Stanford University School of Medicine Stanford VA Palo Alto Health care System Palo Alto California

背景最新的证据表明，局部给予局麻药可能产生组织损伤效应。例如，关节腔内注射局麻药可导致软骨溶解。炎症应答可能是这种组织毒性反应的机制之一。在本研究中，我们观察了剖宫产术后局部持续输注局麻药对皮肤切口处炎性介质和疼痛介... 详细信息

背景最新的证据表明，局部给予局麻药可能产生组织损伤效应。例如，关节腔内注射局麻药可导致软骨溶解。炎症应答可能是这种组织毒性反应的机制之一。在本研究中，我们观察了剖宫产术后局部持续输注局麻药对皮肤切口处炎性介质和疼痛介质释放的影响。方法本研究纳入38例蛛网膜下隙麻醉下行剖宫产的健康女性。剖宫产术后24小时内，随机在手术切口处以2ml/h的速度持续皮下输注5mg／ml的布比卡因或生理盐水。通过皮下g1流管分别在术后第1小时、3小时、5小时、7小时和24小时取伤口渗出物为标本，采用多样Bio-Plex（Bio-Rad，Hercules，cA）和酶联免疫吸附法检测细胞因子、炎症趋化因子、P物质、前列腺素E2和神经生长因子的含量。结果与生理盐水相比，输注布比卡因可导致切口处IL-10降低，P物质增高（24小时的浓度．时间曲线下面积；P〈0．001）。而其他细胞因子、神经生长因子和前列腺素E2未发现显著的统计学差异。结论本研究表明，在切口处持续输注临床剂量的布比卡因会影响切口局部创伤调节物质的组成。研究中所观察到的IL-10变化与抗炎机制的破坏是一致的。这种与促炎症介质P物质释放相关联的调节活动是否会引起伤口的全面促炎反应还有待进一步的研究。

关键词：剖宫产术后皮下连续输注 IL-10 布比卡因物质浓度切口处神经生长因子前列腺素E2

Vulnerability of Kenya’s Water Towers to Future climate change: An Assessment to Inform Decision Making in Watershed Management

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American Journal of climate change 2020年第3期9卷 317-353页

作者： Kenneth Kemucie Mwangi Anthony M. Musili Viola A. Otieno Hussen S. Endris Geoffrey Sabiiti Mohammed A. Hassan Abebe Tadege Tsehayu Artan Guleid Zachary Atheru Alphonce c. Guzha Thomas De Meo Nikola Smith dickson Lubanga Makanji John Kerkering Brehan Doud Enock Kanyanya IGAD climate Prediction and Applications centre Nairobi Kenya USDA Forest Service International Programs c/o African Wildlife Foundation (AWF) Karen Kenya USDA Forest Service Pacific Northwest Region Portland OR USA Egerton University Njoro Kenya USDA Forest Service International Programs Washington DC USA USDA Forest Service International Programs Seattle USA USAID Kenya and East Africa Nairobi Kenya

Recent trends show that in the coming decades, Kenya’s natural resources will continue to face significant pressure due to both anthropogenic and natural stressors, and this will have greater negative impacts on socio-economic development including food security and livelihoods. Understanding the impacts of these stressors is an important step to developing coping and adaptation strategies at every level. The Water Towers of Kenya play a critical role in supplying ecosystems services such as water supply, timber and non-timber forest products and regulating services such as climate and water quantity and quality. To assess the vulnerability of the Water Towers to climate change, the study adopted the IPcc AR4 framework that defines vulnerability as a function of exposure, sensitivity, and adaptive capacity. The historical trends in rainfall indicate that the three Water Towers show a declining rainfall trend during the March-April-May (MAM) main rainy season, while the October-November-December (OND) short rainy season shows an increase. The temperature patterns are consistent with the domain having a common rising trend with a rate in the range of 0.3°c to 0.5°c per decade. Projection analysis considered three emissions scenarios: low-emission (mitigation) scenario (RcP2.6), a medium-level emission scenario (RcP4.5), and a high-emission (business as usual) scenario (RcP8.5). The results of the high-emission scenario show that the annual temperature over the Water Towers could rise by 3.0°c to 3.5color

关键词： Kenya Water Towers climate change Vulnerability Exposure Sensitivity Adaptive capacity

在K/T界线的全球微量元素生物地球化学——对假想的陨石碰撞的海洋和生物的响应

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宝石和宝石学杂志(中英文) 1989年第2期 55-58页

作者： David J.EricksonⅢ Stephen M.dickson 汪东波

对于与假想的一直径10km的c1球粒陨石有关海洋的微量元素通量计算表明,陨星中包含的某些元素的质量,如Fe,co,Mn,Al,Zn,Ni,Ge,cr,Sn,cd,Pb,Ag,cu,Hg和Se,相当于或大于世界海洋的储量.所以,在一个大的陨石碰撞后。以大气雾微粒形式的陨石... 详细信息

对于与假想的一直径10km的c1球粒陨石有关海洋的微量元素通量计算表明,陨星中包含的某些元素的质量,如Fe,co,Mn,Al,Zn,Ni,Ge,cr,Sn,cd,Pb,Ag,cu,Hg和Se,相当于或大于世界海洋的储量.所以,在一个大的陨石碰撞后。以大气雾微粒形式的陨石元素进入到表层海洋,同时各种特定元素的溶解性能,能迅速改变一些海洋微量元素的地球化学平衡.我们确信这种假想的微量元素涌入量足以扰乱66.4Ma前,即陨石可能的碰撞时间的生物地球化学循环、通过直接暴露和生物堆积,这些陨石元素将对海洋食物链的很多营养水平产生不利的影响。这些生存于表层海洋的生物将暴露在有毒元素的长期高浓度下。当海洋中微量元素含量较高时,由于不同种属对高含量的微量元素忍耐程度不同,就可能发生选择性的灭绝。K/T界线处与火山作用有联系的微量元素雾的通量对世界海洋的微量元素高含量也作出了贡献。微量元素中毒说推测这一机制在中生代末海洋生物选择性灭绝的事件中起了作用。

关键词：陨石天空石 K/T 微量元素痕量元素界线

类似卵巢性索肿瘤的子宫肿瘤:一种以复发性NcOA2/3基因融合为特征的独特肿瘤实体

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临床与实验病理学杂志 2019年第7期35卷 819-819页

作者： dickson B c childs T J colgan T J 赵芳(摘译) 魏建国(审校) 不详浙江省绍兴市中心医院妇产科绍兴312030 浙江省绍兴市人民医院病理科绍兴312000

类似卵巢性索肿瘤的子宫肿瘤(UTROScT)是一类组织学发生尚不清楚、恶性潜能未定的罕见肿瘤,其形态学类似卵巢性索-间质肿瘤,具有多向分化的免疫表型,分子致病机制尚不清楚.

关键词：卵巢性索-间质肿瘤子宫肿瘤性索肿瘤肿瘤实体基因融合复发性组织学发生罕见肿瘤

Rationally designed mariner vectors for functional genomic analysis of Actinobacillus pleuropneumoniae and other Pasteurellaceae species by transposon-directed insertion-site sequencing (TraDIS)

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Animal Diseases 2021年第4期1卷 249-261页

作者： Janine T.Bossé Yanwen Li Leon G.Leanse Liqing Zhou Roy R.chaudhuri Sarah E.Peters Jinhong Wang Gareth A.Maglennon Matthew T.G.Holden Duncan J.Maskell Alexander W.Tucker brendan W.Wren Andrew N.Rycroft Paul R.Langford on behalf of the BRaDPT consortium Section of Paediatric Infectious Disease Department of Infectious DiseaseImperial College LondonSt.Mary’s CampusLondonUK Wellman center for Photomedicine Harvard Medical SchoolBostonUSA The Applied Diagnostic Research and Evaluation Unit St George’s University of LondonLondonUK Department of Veterinary Medicine University of CambridgeCambridgeUK Department of Molecular Biology and Biotechnology University of SheffieldSheffieldUK Department of Pathology and Pathogen Biology The Royal Veterinary CollegeHatfieldUK The Wellcome Trust Sanger Institute CambridgeUK School of Medicine University of St AndrewsSt AndrewsUK The University of Melbourne ParkvilleVictoriaAustralia s Faculty of Infectious&Tropical Diseases London School of Hygiene&Tropical MedicineLondonUK

comprehensive identification of conditionally essential genes requires efficient tools for generating high-density transposon libraries that, ideally, can be analysed using next-generation sequencing methods such as Transposon Directed Insertion-site Sequencing (TraDIS). The Himar1 (mariner) transposon is ideal for generating near-saturating mutant libraries, especially in AT-rich chromosomes, as the requirement for integration is a TA dinucleotide, and this transposon has been used for mutagenesis of a wide variety of bacteria. However, plasmids for mariner delivery do not necessarily work well in all bacteria. In particular, there are limited tools for functional genomic analysis of Pasteurellaceae species of major veterinary importance, such as swine and cattle pathogens, Actinobacillus pleuropneumoniae and Pasteurella multocida, respectively. Here, we developed plasmids, pTsodcPc9 and pTlacPc9 (differing only in the promoter driving expression of the transposase gene), that allow delivery of mariner into both these pathogens, but which should also be applicable to a wider range of bacteria. Using the pTlacPc9 vector, we have generated, for the first time, saturating mariner mutant libraries in both A. pleuropneumoniae and P. multocida that showed a near random distribution of insertions around the respective chromosomes as detected by TraDIS. A preliminary screen of 5000 mutants each identified 8 and 14 genes, respectively, that are required for growth under anaerobic conditions. Future high-throughput screening of the generated libraries will facilitate identification of mutants required for growth under different conditions, including in vivo, highlighting key virulence factors and pathways that can be exploited for development of novel therapeutics and vaccines.

关键词： Mariner Transposon TraDIS Pasteurellaceae Actinobacillus pleuropneumoniae Pasteurella multocida

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帷集星座——集丝坊品牌集合店

中国建筑装饰装修 2020年第5期 34-39页

作者：郭锡恩胡如珊 Federico Saralvo 冯立星 brendan Kellogg callum Holgate Nicolas Fardet 如恩设计研究室如恩设计研究室、设计共和哈佛大学设计研究生院 John c.Portman建筑设计

由郭锡恩先生和胡如珊女士于2004年共同创立的如恩设计研究室(Neri&Hu),是一家立足于中国上海的多元化建筑设计研究室。如恩设计提供国际化的建筑、室内、整体规划、平面以及产品设计服务。公司目前的项目分布在很多不同的国家,拥有来... 详细信息

由郭锡恩先生和胡如珊女士于2004年共同创立的如恩设计研究室(Neri&Hu),是一家立足于中国上海的多元化建筑设计研究室。如恩设计提供国际化的建筑、室内、整体规划、平面以及产品设计服务。公司目前的项目分布在很多不同的国家,拥有来自全世界各地的员工,使用超过30种语言。不同文化背景组成了如恩的设计团队,正是团队的差异独特性增强了其设计理念:以全球化的观念结合多元、重叠的设计理念来创造一个新的建筑范例。

关键词：建筑设计整体规划产品设计设计理念设计团队国际化多元化全球化