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Application of nonclinical assays in screening drug candidates for hepatotoxicity

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Application of nonclinical assays in screening drug candidat...

Evaluation of the thyroid toxicity of an oral drug candidate for neuropathic pain through in vitro methods,animal studies,and clinical trials

中国毒理学会第九次全国毒理学大会

作者： Edward Chow William Chang Josh Rowe allergan plc

＜正＞More than 900 drugs have been implicated in causing liver injury, and it is not surprising that hepatotoxicity is the most frequent single cause of safety-related drug marketing withdrawals over the last few decades. Tremendous effort has been made over the last decade to improve the understanding of the mechanisms underlying drug induced hepatotoxicity, including both the idiosyncratic type(causing

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Evaluation of the thyroid toxicity of an oral drug candidate...

Stopping or reducing dietary fiber intake reduces constipation and its associated symptoms

中国毒理学会第七次全国毒理学大会暨第八届湖北科技论坛

作者： Edward Chow Research Investigator Department of ToxicologyAllerganPLC

Clinical evaluation of AGN-203818,an imidazole compound,as an oral agent for the treatment of neuropathic pain was initiated with supportive nonclinical studies showing reversible thyroid follicular epithelial hypertrophy,along with increased thyroid weight,and higher mitotic activity in rats at 30 mg/kg/day(AUC = 38,200ng-hr/mL) after one month of daily oral dosing but not in dogs administered the same dose for the same *** appearance of these rat thyroid changes is characteristic of increased thyrotrophic action by thyroid stimulating hormone(TSH).Thyroid hypertrophic change in the rat is often associated with direct or indirect effects of xenobiotics on thyroxine(T) synthesis and/or metabolism,which could be a rat-specific ***,a subsequent 3-month monkey study revealed thyroid follicular cell hypertrophy at ≥30 mg/kg/day(minimal;AUC = 19,400(ng-hr/mL),thyroid follicular cell hyperplasia at ≥100 mg/kg/day,and an increased hypertrophy of basophils in the pituitary at≥100 mg/kg/*** thyroid-pituitary axis changes were associated with increases in serum T4 and TSH at ≥100mg/kg/day and lower serum triiodothyronine(T) at 300 mg/kg/*** of thyroid peroxidase was determined to be the primary mechanism for these effects by in vitro assays as well as in vivo studies,including radioactive I and I thyroid uptake studies in dogs and *** humans,thyroid hormone perturbations such as T3 decreases and TSH increases were noted only at oral dose levels ≥200 mg BID for 6 days,a dose several-fold above the therapeutic *** data are consistent with the hypothesis that low T/T levels were the trigger for TSH elevation due to a reduction in the feedback inhibition of the hypothalamus and *** low to moderate dose levels of AGN-203818,a new steady state is achieved for the thyroid-pituitary axis in animals and humans with repeated dosing and further clinical development at or below these dose levels is considered safe.

关键词： thyroid toxicity imidazole thyroid hormone animal model for thyroid

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World Journal of Gastroenterology 2012年第33期18卷 4593-4596页

作者： Kok-Sun Ho Charmaine You Mei Tan Muhd Ashik Mohd Daud Francis Seow-Choen Seow-Choen Colorectal Surgery plc Singapore 238859 Singapore

AIM: To investigate the effect of reducing dietary fiber on patients with idiopathic constipation. METHODS: Sixty-three cases of idiopathic constipation presenting between May 2008 and May 2010 were enrolled into the study after colonoscopy excluded an organic cause of the constipation. Patients with previous colon surgery or a medical cause of their constipation were excluded. All patients were given an explanation on the role of fiber in the gastrointestinal tract. They were then asked to go on a no fiber diet for 2 wk. Thereafter, they were asked to reduce the amount of dietary fiber intake to a level that they found acceptable. Dietary fiber intake, symptoms of constipation, difficulty in evacuation of stools, anal bleeding, abdominal bloating or abdominal pain were recorded at 1 and 6 mo. RESULTS: The median age of the patients (16 male, 47 female) was 47 years (range, 20-80 years). At 6 mo, 41 patients remained on a no fiber diet, 16 on a reduced fiber diet, and 6 resumed their high fiber diet for religious or personal reasons. Patients who stopped or reduced dietary fiber had significant improvement in their symp-toms while those who continued on a high fiber diet had no change. Of those who stopped fiber completely, the bowel frequency increased from one motion in 3.75 d (± 1.59 d) to one motion in 1.0 d (± 0.0 d) (P < 0.001); those with reduced fiber intake had increased bowel frequency from a mean of one motion per 4.19 d (± 2.09 d) to one motion per 1.9 d (± 1.21 d) on a reduced fiber diet (P < 0.001); those who remained on a high fiber diet continued to have a mean of one motion per 6.83 d (± 1.03 d) before and after consultation. For no fiber, reduced fiber and high fiber groups, respectively, symptoms of bloating were present in 0%, 31.3% and 100% (P < 0.001) and straining to pass stools occurred in 0%, 43.8% and 100% (P < 0.001). CONCLUSION: Idiopathic constipation and its associated symptoms can be effectively reduced by stopping or even lowering the

关键词： Dietary fiber Constipation Chronic idiopathic constipation Abdominal bloating

Bibliometric analysis of glaucoma-related literature based on SCIE database:a 10-year literature analysis from 2009 to 2018

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International Journal of Ophthalmology(English edition) 2020年第12期13卷 1998-2006页

作者： Yun-Xiao Sun Ying-Na Liu Ying Han Fan-Qi Kong Yue Zhang Siloka Arthur Labisi Kai Cao Beijing Ophthalmology and Visual Sciences Key Laboratory Beijing Tongren Eye CenterBeijing Tongren HospitalCapital Medical UniversityBeijingChina Beijing Institute of Ophthalmology Beijing Tongren HospitalCapital Medical UniversityBeijingChina Department of Ophthalmology University of California San FranciscoSan FranciscoCA 94143USA allergan plc ShanghaiChina

AIM:To explore the global trends and focus of glaucoma research from 2009 to ***:Searching for glaucoma-related articles published in Science Citation Index Expanded(SCIE)database during 2009-2018,and describing the distribution of the published year,countries,authors,institutions,funding agencies,journals,impact factor,citation and hot research topic of articles by using bibliometric ***,we compared some of these indicators over two five-year periods,from 2009 to 2013 and from 2014 to ***:A total of 19609 glaucoma-related articles were retrieved and the global SCIE articles have increased yearly from 2009 to *** USA was the pioneer which has made great *** kept the second place and the number of publications has increased rapidly between 2014 and *** author with the highest number of publications was Weinreb,***-occurrence maps were built amongst the top 50 authors or the top 50 institutions with the most articles,which visualize the closer collaboration of international authors or *** journal Investigative Ophthalmology&Visual Science has published the most *** literature with an impact factor of 3-5 points accounted for the largest proportion(28.96%).The most frequently cited paper had 798 *** top three hot areas on glaucoma were intraocular pressure,optical coherence tomography(OCT)and retinal ganglion *** trabecular meshwork,primary angle-closure glaucoma and Spectral-domain OCT have become new hot research topics in recent five years during ***:Bibliometric analysis is an effective method to describe the global literature on *** a 10-year literature survey from 2009 to 2018,global glaucoma research has developed in a balanced manner,and the cooperation between various institutions and teams has become ***-related pathogenesis research,imaging examinations of OCT and surgery therapy have attracted most attention.

关键词： bibliometric analysis Science Citation Index Expanded glaucoma ocular hypertension

Experimental study of the effect of wear parameters on the wear behavior of A356 alloy/cow horn particulate composites

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Defence Technology（防务技术） 2018年第1期14卷 77-82页

作者： B.Q.Ochieze C.C.Nwobi-Okoye P.N.Atamuo Lafarge Africa plc Mfamosing Plant Department of Mechanical Engineering Chukwuemeka Odumegwu Ojukwu University

Experimental study of the effect of wear parameters on the wear behaviour of A356 alloy reinforced with cow horn particles(CHp) produced by spark plasma sintering was investigated. Experiments were conducted based on the plan of experiments generated through Taguchi's(L9) technique. Tribometer was used for the wear test and Scanning electron microscope was used to analyse the worn scar of the samples. The results shows that, A356 alloy reinforced with CHp exhibited better dry sliding wear resistance than the unreinforced alloy. Wear rate decreased as the amount of CHp reinforcement increased in the matrix. It was found that, the optimum level of the factors with minimized the wear loss were obtained at: wt%CHp(20%), applied load(10 N), sliding velocity(3 m/s) and sliding distance(2000 m). It can be seen that the wear track of the sample are(D ? 0.81 and L = 42.85 mm) and(D ? 0.54 and L= 27.03 mm) for A356 alloy and composites at optimum condition respectively. The results showed that the addition of cow horn particles as reinforcing materials in A356 alloy composites increased the wear resistance of the composites greatly.

关键词： A356alloy Cow horn particles Microstructure Analysis of variance and wear behaviour

Virtual-reality-based digital twin of office spaces with social distance measurement feature

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Virtual Reality & Intelligent Hardware 2022年第1期4卷 55-75页

作者： Abhishek MUKHOPADHYAY G S Rajshekar REDDY KamalPreet Singh SALUJA Subhankar GHOSH Anasol PEÑA-RIOS Gokul GOPAL Pradipta BISWAS Indian Institute of Science BangaloreIndia BT plc UK

Background Social distancing is an effective way to reduce the spread of the SARS-CoV-2 *** students and researchers have already attempted to use computer vision technology to automatically detect human beings in the field of view of a camera and help enforce social ***,because of the present lockdown measures in several countries,the validation of computer vision systems using large-scale datasets is a *** In this paper,a new method is proposed for generating customized datasets and validating deep-learning-based computer vision models using virtual reality(VR)*** VR,we modeled a digital twin(DT)of an existing office space and used it to create a dataset of individuals in different postures,dresses,and *** test the proposed solution,we implemented a convolutional neural network(CNN)model for detecting people in a limited-sized dataset of real humans and a simulated dataset of humanoid *** We detected the number of persons in both the real and synthetic datasets with more than 90%accuracy,and the actual and measured distances were significantly correlated(r=0.99).Finally,we used intermittent-layer-and heatmap-based data visualization techniques to explain the failure modes of a *** A new application of DTs is proposed to enhance workplace safety by measuring the social distance between *** use of our proposed pipeline along with a DT of the shared space for visualizing both environmental and human behavior aspects preserves the privacy of individuals and improves the latency of such monitoring systems because only the extracted information is streamed.

关键词： Virtual environment Digital twin 3D visualization Convolutional neural network Object detection Social distancing

*** Prensky:The birth of the acupuncture profession in the United States(1969–1979)——the Institute for Taoist Studies and the National Acupuncture Association

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Journal of Integrative Medicine 2016年第1期14卷 5-11页

作者： Arthur Yin Fan McLean Center for Complementary and Alternative Medicine PLC.Vienna

Acupuncture is one important part of traditional Chinese medicine （here after, the author will only use the term ＂acupuncture＂ to denote both acupuncture and Chinese medicine） and is a fast growing profession in recent years. Many patients have benefited from acupuncture therapy because acupuncture is a safe, effective and natural therapy. Several articles and interviews published in recent years have described the history of the establishment of acupuncture and Chinese medicine on the east and west coasts of the United States （U.S.） of America.

关键词： acupuncture United States history of medicine Gim Shek Ju Tin Yau So William Prensky School

Nevada: the first state that fully legalized acupuncture and Chinese medicine in the Unites States——In memory of Arthur Steinberg, Yee Kung Lok and Jim Joyce who made it happen

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Journal of Integrative Medicine 2015年第2期13卷 72-79页

作者： Arthur Yin Fan Mc Lean Center for Complementary and Alternative Medicine PLC.

1 Introduction In the United States, the largest groups of acupuncture or traditional Chinese medicine （TCM） practitioners settled and still remain in California and New York, as these two states historically have the largest, most concentrated Asian populations. The TCM practitioners originally worked in a legal gray-zone, sometimes even being treated as illegal practitioners by the local governments, since TCM licensing laws did not exist until late 1973[1]. The first legal acupuncture clinic was established in Washington, D.C. in 1972[2], but Nevada was the first state that passed a full practicing law for acupuncture and TCM[3]. Under- standing the legal history of acupuncture in the U.S. will help us to see the road ahead more clearly.

关键词： acupuncture Chinese medicine legislation United States Nevada history of medicine ArthurSteinberg Yee Kung Lok Jim Joyce

跻身未来的电力线通信 (九)plc-NET技术体制探讨

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电力系统自动化 2003年第14期27卷 87-90页

作者：李英敏陈启美许成南京大学plc研究组江苏省南京市210093

电力线通信网络 (plc NET)的推广和应用关键在于其技术体制的建立。文中分析比较了plc NET的现有标准 ,并指出其不足之处 ,进而结合我国实情提出了plc NET技术体制的设想 ,其中就plc NET的网络拓扑结构、网络体系结构、传输频段、调制... 详细信息

电力线通信网络 (plc NET)的推广和应用关键在于其技术体制的建立。文中分析比较了plc NET的现有标准 ,并指出其不足之处 ,进而结合我国实情提出了plc NET技术体制的设想 ,其中就plc NET的网络拓扑结构、网络体系结构、传输频段、调制技术、服务速率、信息跨越技术、家电和网络接口等方面提出了规范要求 ,对数据链路层的帧结构、差错控制和应用语言提出了具体建议 ,对收费制式、安全体系及网络管理也提出了相关措施。

关键词：电力线通信电力线通信网络标准化