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The Interface of Toxicology with Drug Discovery

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The Interface of Toxicology with Drug Discovery

药物非临床安全性研究学术研讨会

作者： carl l．McMillian Investigative Toxicology and Pathology lilly Research laboratories Division of Eli lilly and Company Ph.D Director

Involvement of Toxicology in the Discovery to launch Continuum ...Target to FHD

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毒理学与发现药物的相互关系

毒理学与发现药物的相互关系

药物非临床安全性研究学术研讨会

作者： carl l．McMillian 礼来公司礼来研究实验室

毒理学参与从研发到投放市场的连续过程…目标是首次人的给药剂量(FHD)

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复杂蒸馏的最小回流比

化学工程 1992年第1期20卷 73-76页

作者： carl l Yaw 张立奎江西工业大学

本文提出的直接计算方法不仅适用于多股进料的蒸馏塔,而且也适于有多股侧线抽出的情况。

关键词：蒸馏塔蒸馏回流比

The AlFAlFA Entomology Pest Identification System

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Journal of Computer Science and Technology 1988年第4期3卷 251-262页

作者：洪家荣 carl Uhrik Harbin Institute of Technology Department of Computer Science University of Illinois Urbana USA

Rule groups with preconditions,posteonditions,and termination conditions were added tothe ADVISE Meta-Expert ***,varying goals are also an attribute of the new *** treating the data collection process as separating from the rule inference engine,techniques for enhanced data acquisition were developed using semantic networks to describerelations among variables and to restructure value sets for variables *** thusextended the ADVISE tools,an automated key to alfalfa field pest identification was selected as atest application and found to be particularly well suited by the new features.A need fordisjunctive(“OR”)constructs in the right hand side of rules is discussed,and directions forfuture applications are given.

关键词： The AlFAlFA Entomology Pest Identification System

Temporal and elevation trends in rainfall erosivity on a 149 km2watershed in a semi-arid region of the American Southwest

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International Soil and Water Conservation Research 2015年第2期3卷 77-85页

作者： Mark A.Nearingn carl l.Unkrich Dave C.Goodrich Mary H.Nichols Tim O.Keefer USDA-ARS Southwest Watershed Research Center 2000 E Allen RoadTucsonAZ 85719USA

Temporal changes in rainfall erosivity can be expected to occur with changing climate and because rainfall amounts areknown to bein pait of afunction of elevation erosivity can be expected to be influenced by elevation as *** is particularly truein mountainous regions such as are found over much of the westem United *** objective of this study was to identify temporal and elevation trends in rainfall erosivity on a 149km^(2)(58 miles)watershed in a semi-arid region of southeastem Arizona Data from 84 rain gages forthe years 19602012 at elevations ranging from 1231 to 1644 m(40385394 ft)were used in the *** average annual erosivity over the watershed as a whole was 1104 MJ mm ha^(-1)h^(-1)yr^(-1)(65 hundreds of foot ton inch acrei h^(-1)yr^(-1)),and ranged from approximately 950 to 1225 MJ mm ha^(-1)h^(-1)yr^(-1)(56-72 hundreds of foot ton inch acre^(-1)h^(-1)yr^(-1)),with a statistical trend showing greater erosivity af the higher elevations No statistically significant temporal changes in annual or summer erosivities were *** result stands in contrast to fecent modeling studies of runoff and erosion in the area based on downscaled GCM information that project significant levels of erosivity changes over coming *** results are consistent with known orographic rainfall effects,but contrast with recent studies that presented projections of significant trends of increasing erosivity in the future based on downscaled GCM outputs for the area The results illustiate the need for testing and developing improved techniques to evaluate future erosion scenarios for purposes of making targeted soil conservation decisions Production and Hosting by Elsevier B.V on behalf of International Research and Training Center on Erosion and Sedimentation and China Water and Power Press This is anopen access article under theCCBY-NC-ND licens(http://***/licenses/by-ncnd/4.0/).

关键词： Climate change R-factor RUSlE Semiarid Soil erosion Walnut Gulch

In vivo and ex vivo confocal endomicroscopy of pancreatic cystic lesions: A prospective study

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World Journal of Gastroenterology 2017年第18期23卷 3338-3348页

作者： Somashekar G Krishna Rohan M Modi Amrit K Kamboj Benjamin J Swanson Phil A Hart Mary E Dillhoff Andrei Manilchuk carl R Schmidt Darwin l Conwell Division of Gastroenterology Hepatology and NutritionThe Ohio State University Wexner Medical Center Department of Internal Medicine The Ohio State University Wexner Medical Center College of Medicine The Ohio State University Wexner Medical Center Department of Pathology The Ohio State University Wexner Medical Center Division of Surgical Oncology The Ohio State University Wexner Medical Center Deparment of General Surgery The Ohio State University Wexner Medical Center

AIM To investigate the reproducibility of the in vivo endoscopic ultrasound(EUS)-guided needle based confocal endomicroscopy(n ClE) image patterns in an ex vivo setting and compare these to surgical histopathology for characterizing pancreatic cystic lesions(PCls). METHODS In a prospective study evaluating EUS-nC lE for evaluation of PCls, 10 subjects underwent an in vivo nC lE(AQFlex nC lE miniprobe; Cellvizio, MaunaK ea, Paris, France) during EUS and ex vivo probe based ClE(pC lE) of the PCl(Gastroflex ultrahigh definition probe, Cellvizio) after surgical resection. Biopsies were obtained from ex vivo ClE-imaged areas for comparative histopathology. All subjects received intravenous fluorescein prior to EUS and pancreatic surgery for in vivo and ex vivo ClE imaging respectively. RESUlTS A total of 10 subjects(mean age 53 ± 12 years; 5 female) with a mean PCl size of 34.8 ± 14.3 mm were enrolled. Surgical histopathology confirmed 2 intraductal papillary mucinous neoplasms(IPMNs), 3 mucinous cystic neoplasms(MCNs), 2 cystic neuroendocrine tumors(cystic-NETs), 1 serous cystadenoma(SCA), and 2 squamous lined PCls. Characteristic in vivo nC lE image patterns included papillary projections for IPMNs, horizon-type epithelial bands for MCNs, nests and trabeculae of cells for cystic-NETs, and a "fern pattern" of vascularity for SCA. Identical image patterns were observed during ex vivo pC lE imaging of the surgically resected PCls. Both in vivo and ex vivo ClE imaging findings correlated with surgical *** In vivo n ClE patterns are reproducible in ex vivo p ClE for all major neoplastic PCls. These findings add further support the application of EUS-nC lE as an imaging biomarker in the diagnosis of PCls.

关键词：共焦的激光 endomicroscopy 浆液的 cystadenoma 胰腺的 neuroendocrine 肿瘤 Intraductal 乳突的 mucinous 瘤胰腺的膀胱的瘤

The modifying influence of HlA classⅡDQB1^(*)06:02 on the Streptococcus and clinical phenotype correlation among anti-Ro+mothers of children with neonatal lupus

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Genes & Diseases 2023年第4期10卷 1169-1171页

作者： Robert M.Clancy carla J.Guthridge Miranda C.Marion Joel Guthridge Timothy D.Howard Peter M.Izmirly Mala Masson Jill P.Buyon Judith A.James carl D.langefeld Department of Medicine Division of RheumatologyNYU Grossman School of MedicineNew YorkNY 10016USA Arthritis and Clinical Immunology Oklahoma Medical Research FoundationOklahoma CityOK 73104USA Department of Biostatistics and Data Science Wake Forest School of MedicineWinstone SalemNC 27101USA Center for Precision Medicine Wake Forest School of MedicineWinstoneSalemNC 27101USA Department of Biochemistry Wake Forest School of MedicineWinstoneSalemNC 27101USA

The genus Streptococcus,a gram-positive bacterium,con-tains species associated with immune activation at morbid outcomes,including scarlet fever,endocarditis,meningitis,and rheumatic *** both stool and saliva,there is a pos-itive correlation between Streptococcus abundance and Sjogren’s syndrome(SS)and systemic lupus erythematosus(SlE).

关键词： lupus mother fever Streptococcus

Introduction of new techniques and technologies in surgery: Where is transanal total mesorectal excision today?

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World Journal of Gastrointestinal Surgery 2020年第5期12卷 203-207页

作者： Antonio Caycedo-Marulanda Sunil Patel Shaila Merchant carl Brown Department of surgery Queen’s University and Kingston General HospitalKingston K7L 2V7OntarioCanada Department of Surgery University of British Columbia and St.Paul HospitalVancouver V6Z 1Y6British ColumbiaCanada

The introduction of new surgical techniques and technologies has traditionally been *** many settings surgeons frequently adopt novel procedures without following a structured program of implementation or *** appearance of innovative technology played a pivotal role in the advancement of new surgical techniques during the industrial *** has been an essential component of surgical development,which led to contemporary surgical techniques such as minimally invasive *** initiatives have been developed to guide the safe introduction of new surgical techniques and other *** include comprehensive concepts such as the Idea,Development,Exploration,Assessment,long-term study framework,which could be particularly relevant when reflecting on the novel transanal total mesorectal excision(taTME),introduced a decade *** relatively novel and complex procedure promised to overcome some of the major limitations of traditional surgical approaches for rectal *** to the Idea,Development,Exploration,Assessment,long-term study framework,taTME is in the phase of exploration,where there is an existing and increasing number of reports being published as the experience *** current management of rectal cancer is in a state of radical evolution,with multiple options that were not previously *** TME is only one technique amongst many which could be part of a rectal cancer surgeon’s armamentarium;however,it requires further rigorous study and evaluation.

关键词： Rectal cancer New technology Safety Innovation Transanal surgery

Base-Editing-Mediated Artificial Evolution of OsAlS1 In Planta to Develop Novel Herbicide-Tolerant Rice Germplasms

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Molecular Plant 2020年第4期13卷 565-572页

作者： Yongjie Kuang Shaofang li Bin Ren Fang Yan carl Spetz Xiangju li Xueping Zhou Huanbin Zhou State Key laboratory for Biology of Plant Diseases and Insect Pests Institute of Plant ProtectionChinese Academy of Agricultural SciencesBeijing 100193China College of Biological Sciences China Agricultural UniversityBeijing 100193China Scientific Observing and Experimental Station of Crop Pests in Guilin Ministry of Agriculture and Rural AffairsGuilin 541399China Norwegian Institute of Bioeconomy Research 1432 AasNorway State Key laboratory of Rice Biology Institute of BiotechnologyZhejiang UniversityHangzhou 310058China

Recently developed CRISPR-mediated base editors,which enable the generation of num erous nucleotide changes in target genomic regions,have been widely adopted for gene correction and generation of crop germ plasms containing im portant gain-of-function genetic *** ever,to engineer target genes with unknown functional SNPs remains *** address this issue,we present here abase-e diting-mediated gene evolution(BEMGE)m ethod,employing both Cas9n-based cytosine and adenine base editors as well as a single-guide RNA(sgRNA)library tiling the full-length coding region,for developing novel rice germ plasm swith mutations in any endogenous *** this end,OsAlS1 was artificially evolved in rice cells using BEMGE through both Agrobacterium-mediated and particle-bom bardment-mediated transform *** different types of amino acid substitutions in the evolved OsAlS1,derived from two sites that have never been targeted by natural or human selection during rice dom estication,were identified,conferring varying levels of tolerance to the herbicide *** ore,the P171F substitution identified in a strong OsAlS1 allele was quickly introduced into the commercial rice cultivar Nangeng 46 through precise base editing w ith the corresponding base editor and ***,these data indicate great potential of BEMGE in creating important genetic variants of target genes for crop improvement.

关键词： CRISPR base editor gene evolution OsAlS1 herbicide resistance Otyza sativa l