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Novel Mechanistic Interplay between Products of Oxidative Stress and Components of the Complement System in AMD Pathogenesis

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Open Journal of Ophthalmology 2016年第1期6卷 43-50页

作者： Hongjun Du Xu Xiao Travis Stiles Christopher Douglas Daisy Ho peter X. shaw Department of Ophthalmology Xijing Hospital Xi’an China Department of Ophthalmology and Shiley Eye Institute University of California San Diego San Diego USA Sichuan Provincial People’s Hospital Chengdu China

Age-related macular degeneration (AMD) is a leading cause of vision loss affecting tens of millions of elderly worldwide. Early AMD includes soft drusen and pigmentary changes in the retinal pigment epithelium (RPE). As people age, such soft confluent drusen can progress into two forms of advanced AMD, geographic atrophy (GA, or dry AMD) or choroidal neovascularization (CNV, or wet AMD) and result in the loss of central vision. The exact mechanism for developing early AMD and progressing to advanced stage of disease is still largely unknown. However, significant evidence exists demonstrating a complex interplay of genetic and environmental factors as the cause of AMD progression. Together, complement factor H (CFH) and HTRA1/ARMS polymorphisms contribute to more than 50% of the genetic risk for AMD. Environmentally, oxidative stress from activities such as smoking has also demonstrated a powerful contribution to AMD progression. To extend our previous finding that genetic polymorphisms in CFH results in OxPLs and the risk-form of CFH (CFH Y402H) has reduced affinity for oxidized phospholipids, and subsequent diminished capacity which subsequently diminishes the capability to attenuate the inflammatory effects of these molecules, we compared the binding properties of CFH and CFH related protein 1 (CFHR1), which is also associated with disease risk, to OxPLs and their effects on modulating inflammation and lipids uptake. As both CFH-402H and CFHR1 are associated with increased risk to AMD, we hypothesized that like CFH-402H, CFHR1 contribution to AMD risk may also be due to its diminished affinity for OxPLs. Interestingly, we found that association of CFHR1 with OxPLs was not statistically different than CFH. However, binding of CFHR1 did not elicit the same protective benefits as CFH in that both inflammation and lipid uptake are unaffected by CFHR1 association with OxPLs. These findings demonstrate a novel and interesting complexity to the potential interplay betwee

关键词： Age-Related Macular Degeneration Oxidative Stress Complement Factor H Inflammation

Enhancing pedestrian mobility in Smart Cities using Big Data

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Journal of Management Analytics 2020年第2期7卷 173-188页

作者： Ebony Carter Patrick Adam Deon Tsakis Stephanie shaw Richard Watson peter Ryan Faculty of Business and Law Swinburne UniversityHawthornAustralia Swinburne University of Technology Defence Science&Technology Group MelbourneAustralia

Smart City is an emerging concept in global urban development.A Smart City applies ICT technologies to provide greater efficiencies for its urban areas and civilian *** of the key requirements for a Smart City is to exploit data from its ICT infrastructure(such as Internet of Things connected sensors)to improve city services and features such as accessibility and *** address this requirement,the City of Melbourne(COM)Smart City office maintains several hundred data sets relating to urban activity and *** datasets address parking,mobility,land use,3D data,statistics,environment,and major city developments such as rail *** promising dataset relates to pedestrian *** are obtained from sensors and updated on the COM website(City of Melbourne Open Data Platform:https://***/.)at regular *** data include the number of pedestrians passing 53 specific locations in the central business district and also their times and directions of *** a 24 h period,over 650,000 pedestrians were counted passing all *** rates of several thousand pedestrians per minute are regularly recorded during city rush hours at hotspots making the data amenable to Big Data analysis *** are obtained in graphical format as heatmaps and charts of city pedestrian traffic using both Microsoft Excel^(■)for static analysis and PowerBI^(■)for more advanced interactive visualisation and *** findings can identify pedestrian hotspots and inform future locations of traffic lights and street configurations to make the city more pedestrian ***,the experience gained can be used to examine other data sets such as bicycle traffic that can be analysed to inform city infrastructure *** work is suggested that could link these pedestrian flow data with social media data from smartphones and potentially wearable devices such as fitness monitors to correlate pedestrian s

关键词： Internet of Things Smart Cities Big Data analytics

Janus kinase inhibitors are potential therapeutics for amyotrophic lateral sclerosis

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Translational Neurodegeneration 2023年第1期12卷 225-241页

作者： peter J.Richardson Daniel P.Smith Alex de Giorgio Xenia Snetkov Joshua Almond-Thynne Sara Cronin Richard J.Mead Christopher J.McDermott Pamela J.shaw BenevolentAI 4-8 Maple StreetLondon W1T 5HDUK BenevolentAI 15 MetroTech Centre8th FLBrooklynNY 11201USA Sheffield Institute for Translational Neuroscience Faculty of MedicineDentistry and HealthUniversity of SheffieldSheffieldUK NIHR Sheffield Biomedical Research Centre University of Sheffield and Sheffield Teaching Hospitals NHS Foundation TrustSheffieldUK

Amyotrophic lateral sclerosis(ALS)is a poorly treated multifactorial neurodegenerative disease associated with multiple cell types and subcellular *** with other multifactorial diseases,it is likely that drugs will need to target multiple disease processes and cell types to be *** review here the role of Janus kinase(JAK)/Signal transducer and activator of transcription(STAT)signalling in ALS,confirm the association of this signalling with fundamental ALS disease processes using the BenevolentAI Knowledge Graph,and demonstrate that inhibitors of this pathway could reduce the ALS pathophysiology in neurons,glia,muscle fibres,and blood ***,we suggest that inhibition of the JAK enzymes by approved inhibitors known as Jakinibs could reduce STAT3 activation and modify the progress of this *** of the Jakinibs highlights baricitinib as a suitable candidate due to its ability to penetrate the central nervous system and exert beneficial effects on the immune ***,we recommend that this drug be tested in appropriately designed clinical trials for ALS.

关键词： Janus kinase STAT3 Amyotrophic lateral sclerosis

Maintaining biodiversity will define our long-term success

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Plant Diversity 2020年第4期42卷 211-220页

作者： peter Raven Mathis Wackernagel Missouri Botanical Garden 4344 Shaw BlvdSt.LouisMO63110USA Global Footprint Network 1528 Webster StreetSuite 11OaklandCA94612USA

Human beings are not only a part of our planet's ecosystems,but also,they are massively overusing *** makes ecosystem protection,including biodiversity preservation,vital for humanity's *** speed and scale of the threat are unprecedented in human *** long arch of evolution has been confronted with such a high level of human impact,that we are now facing the sixth mass extinction event,66 million years after the last *** threat heightens the imperative for bold human *** paper identifies three strategies for such an ***,and possibly most challenging,human demand needs to be curbed so it fits within the bounds of what Earth's ecosystems can *** meeting this quantitative goal,biodiversity preservation efforts will not be able to get ***,in the transition time,we must focus on those locations and areas where most biodiversity is *** a focus on‘hotspots’will help safeguard the largest portion of biodiversity with least ***,to direct biodiversity preservation strategies,we need to much better document the existence and distribution of biodiversity around the *** information technologies could help with this critical *** conclusion,biodiversity preservation is no longer just a concern for specialized biologist but is becoming a societal necessity if humanity wants to have a stable future.

关键词： Biodiversity Hotspots Biocapacity Conservation strategy

Astrocyte Function and Role in Motor Neuron Disease:A Future Therapeutic Target?

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神经损伤与功能重建 2009年第5期4卷 351-362页

作者： DANIEL BLACKBURN SIRANUSH SARGSYAN peter N.MONK PAMELA J.shaw Academic Neurology Unit Sheffield Care and Research Centre for Motor Neuron DisordersUniversity of Sheffield

星形胶质细胞是中枢神经系统中数量最多的细胞,从引导轴突、突触支持到控制血-脑脊液屏障及脑血流,发挥多种作用。发挥这些作用需要通过大量不同类型的星形胶质细胞进行。本文对星形胶质细胞的功能,尤其是保持突触平衡、调节神经元信号... 详细信息

星形胶质细胞是中枢神经系统中数量最多的细胞,从引导轴突、突触支持到控制血-脑脊液屏障及脑血流,发挥多种作用。发挥这些作用需要通过大量不同类型的星形胶质细胞进行。本文对星形胶质细胞的功能,尤其是保持突触平衡、调节神经元信号传导、保护氧化损伤下的神经元和决定内源性神经前体细胞分化方面的作用进行综述。本文还重点讨论近年星形胶质细胞在运动神经元病(MND)中的作用方面的研究,强调其在细胞替代治疗中作为治疗靶标和治疗剂的潜能。在20%家族性MND中涉及到的铜锌超氧化物歧化酶(SOD1)基因,其必须表达在胶质细胞和运动神经元中来诱导小鼠疾病模型的疾病状态。在星形胶质细胞中选择性减少突变SOD1(mSOD1)不会影响疾病发作,可延缓疾病进展;但减少运动神经元中的mSOD1可推迟疾病发作,延缓早期病程,对寿命无影响。这提示胶质细胞在MND中可作为潜在的治疗靶标。然而,对星形胶质细胞特异性标志物、前体细胞、亚型的认识缺乏意味着对其发育/分化、应对损伤的了解落后于对其功能的认识。只有深入理解这些问题才能有效运用星形胶质细胞靶向或替代治疗慢性中枢神经系统疾病,如MND。

关键词：星形胶质细胞星形胶质细胞增生胶质纤维酸性蛋白运动神经元病

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电视人才争夺加剧好莱坞出手回击

商业周刊（中文版） 2018年第19期 16-17页

作者： Lucas shaw 许诺(译)

好莱坞传统电视制作公司迫于奈飞高价挖角，纷纷下血本对抗挖角。彼得·罗斯（peter Roth）知道，现在是该掏出支票簿的时候了。罗斯是华纳兄弟娱乐公司（Warner ***）电视制作业务的掌门人。

关键词：电视制作公司好莱坞人才争夺娱乐公司罗斯支票

Promise and pitfalls of modeling grassland soil moisture in a free-air CO_(2) enrichment experiment(BioCON)using the shaw model

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Pedosphere 2021年第5期31卷 783-795页

作者： Raquel H.FLINKER M.Bayani CARDENAS Todd G.CALDWELL Gerald N.FLERCHINGER Roy RICH peter B.REICH Department of Geological Sciences The University of Texas at AustinAustin 78712(USA) Bureau of Economic Geology The University of Texas at AustinAustin 78713(USA) Agricultural Research Service United States Department of AgricultureBoise 83712(USA) Smithsonian Environmental Research Center Edgewater 20137(USA) Department of Forest Resources University of MinnesotaSt.Paul 55108(USA) Hawkesbury Institute for the Environment Western Sydney UniversitySydney 2753(Australia)

Free-air carbon dioxide(CO_(2))enrichment(FACE)experiments provide an opportunity to test models of heat and water flow under novel,controlled situations and eventually allow use of these models for hypothesis *** study assesses whether the United States Department of Agriculture shaw(Simultaneous Heat and Water)numerical model of vertical one-dimensional soil water flow across the soil-plant-atmosphere continuum is able to adequately represent and explain the effects of increasing atmospheric CO_(2) on soil moisture dynamics in temperate *** in a FACE experiment,the Bio CON(Biodiversity,CO_(2),and Nitrogen)experiment,in Minnesota,USA,were compared with results of vertical soil moisture *** scenarios represented by different plots were assessed:bare,vegetated with ambient CO_(2),and similarly vegetated with high CO_(2).From the simulations,the bare plot soil was generally the wettest,followed by a drier high-CO_(2) vegetated plot,and the ambient CO_(2) plot was the *** shaw simulations adequately reproduced the expected behavior and showed that vegetation and atmospheric CO_(2) concentration significantly affected soil moisture *** differences in modeled soil moisture amongst the plots were largely due to transpiration,which was low with high CO_(2).However,the modeled soil moisture only modestly reproduced the ***,while shaw is able to replicate and help broadly explain soil moisture dynamics in a FACE experiment,its application for point-and time-specific simulations of soil moisture needs further *** typical design of a FACE experiment makes the experimental observations challenging to model with a one-dimensional distributed *** addition,FACE instrumentation and monitoring will need improvement in order to be a useful platform for robust model *** after this can we recommend that models such as shaw are adequate for process interpretation of datasets from FACE exp

关键词： carbon dioxide FACE experiment soil water flow vadose zone vegetation

Mobilizing Crop Biodiversity

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Molecular Plant 2020年第10期13卷 1341-1344页

作者： Susan McCouch Zahra Katy Navabi Michael Abberton Noelle L.Anglin Rosa Lia Barbieri Michael Baum Kirstin Bett Helen Booker Gerald L.Brown Glenn J.Bryan Luigi Cattivelli David Charest Kellye Eversole Marcelo Freitas Kioumars Ghamkhar Dario Grattipaglia Robert Henry Maria Cleria Valadares Inglis Tofazzal Islam Zakaria Kehel Paul J.Kersey Graham J.King Stephen Kresovich Emily Marden Sean Mayes Marie Noelle Ndjiondjiop Henry T.Nguyen Samuel Rezende Paiva Roberto Papa peter W.B.Phillips Awais Rasheed Christopher Richards Mathieu Flouard Maria Jose Amstalden Sampaio Uwe Scholz Paul D.shaw Brad Sherman S.Evan Staton Nils Stein Jan Svensson Mark Tester Jose Francisco Montenegro Valls Rajeev Varshney Stephen Visscher Eric von Wettberg Robbie Waugh peter Wenzl Loren H.Rieseberg Plant Breeding and Genetics School of Integrated Plant SciencesCornell UniversityIthacaNY14853USA DivSeek Global Institute for Food Security110 Gymnasium PlaceUniversity of SaskatchewanSaskatoonSKS7N 0W9Canada lnternational Institute of Tropical Agriculture(IITA) PMB 5320Oyo RdIbadanNigeria International Potato Center(CIP)1895 Avenida La Molina Lima Peru 12Lima 15023Peru Embrapa Genetic Resources and Biotechnology Parque Estacjao BiologicaFinal Av W5 NorteCaixa Postal 0237270770-917-Brasilia DFBrazil International Center for Agricultural Research in the Dry Areas(I CAR DA) Station Exp.INRA-Quich.Rue Hafiane Cherkaoui.Agdal.Rabat-Instituts10111RabatMorocco Department of Plant Sciences University of Saskatchewan51 Campus Dr.SaskatoonSK S7N 5A8Canada Department of Plant Agriculture University of GuelphRm 316Crop Science Bldg50 Stone Rd EGuelphON N1G 2W1Canada Genome Prairie 111 Research DriveSuite 101SaskatoonSKS7N 3R2Canada The James Hutt on Institute Errol RoadInvergowrieDundeeDD25DAUK CREA Research Centre for Genomics and Bioinformaticsvia San Protaso 302Fiorenzuola d'Arda29017Italy Genome British Columbia 400-575 West 8th AvenueVancouverBCV5Z 0C4Canada International Wheat Genome Sequencing Consortium 2841 NE Marywood CtLee's SummitMO.64086USA Forage Science Grasslands Research CentreAgResearchPalmerston North4410New Zealand Queensla nd Alliance for Agriculture and Food Inn ovation University of QueenslandBrisbaneQLD 4072Australia Institute of Biotechnology and Genetic Engineering(IBGE) Bangabandhu Sheikh Mujibur Rahman Agricultural UniversityGazipur 1706Bangladesh Southern Cross University PO Box 157LismoreNSW 2480Australia Royal Botanic Gardens KewRichmondSurreyTW93AEUK Feed the Future Innovation Lab for Crop Improvement 431 Weill HallCornell UniversityIthacaNY14853USA Department of Botany and Biodiversity Research Centre University of British ColumbiaVancouverBC V6R 2A5Canada Crops For the Future(UK)CIC 76-80 Baddow Road ChelmsfordEs

Over the past 70 years,the world has witnessed extraordinary growth in crop productivity,enabled by a suite of technological advances,including higher yielding crop varieties,improved farm management,synthetic agrochemicals,and agricultural *** this"Green Revolution"intensified crop production,and is credited with reducing famine and malnutrition,its benefits were accompanied by several undesirable collateral effects(Pingali,2012).These include a narrowing of agricultural biodiversity,stemming from increased monoculture and greater reliance on a smaller number of crops and crop varieties for the majority of our *** reduction in diversity has created vulnerabilities to pest and disease epidemics,climate variation,and ultimately to human health(Harlan,1972).

关键词： intensified crops agricultural

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先进的陆地和海底管道涂覆技术

油气储运 2005年第B12期24卷 110-114页

作者： Shiwei William Guan Nick Gritis Adam Jackson peter Singh 加拿大Bredero shaw公司

油气工业的快速发展给诸如在寒冷的气候和深水环境中、具有独特应用地位的管道涂覆技术的革新带来了巨大的挑战和机遇。突出强调了几种独特的、先进的并已经过证实的管道涂覆技术，这些技术适用于陆地和海底管道的保护，包括高效复合涂... 详细信息

油气工业的快速发展给诸如在寒冷的气候和深水环境中、具有独特应用地位的管道涂覆技术的革新带来了巨大的挑战和机遇。突出强调了几种独特的、先进的并已经过证实的管道涂覆技术，这些技术适用于陆地和海底管道的保护，包括高效复合涂层系统（HPCC）、高强度钢粉末涂层低温涂覆技术和Thermotite稳流保证技术。给出了一些案例和收集的技术数据。

关键词：输油气管道 HPCC复合涂层系统低温涂覆技术研究