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Drug targets beyond HMG-CoA reductase:Why venture beyond the statins?

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Frontiers in Biology 2011年第3期6卷 197-205页

作者： Ingrid C.GELISSEN andrew j.brown Faculty of Pharmacy The University of SydneySydney NSW 2006Australia BABS School of Biotechnology and Biomolecular SciencesThe University of New South WalesSydney NSW 2052Australia

In this review,we aim to convey a brief,select history of the development of cholesterol-lowering *** focus particularly on the highly successful statins as well as setbacks that should serve as cautionary *** go on to preview recent developments that may complement,if not one day replace,the *** focus is on pharmacological interventions,particularly those targeting the cholesterol biosynthetic ***,we examine therapies under current investigation that target the assembly of atherogenic lipoproteins(via apolipoprotein B or microsomal triglyceride transfer protein),the stability of the low-density lipoprotein-receptor(via PCSK9,proprotein convertase subtilisin kexin 9),or are designed to increase high-density lipoprotein-cholesterol(via inhibition of cholesteryl ester transfer protein).

关键词： statins cholesterol-lowering drugs side-effects adverse reactions cholesterol synthesis

Regulated protein degradation and lipid sensing:Lessons from a key cholesterol synthesis enzyme

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Regulated protein degradation and lipid sensing:Lessons from...

A review of public health guidelines for postpartum physical activity and sedentary behavior from around the world

第三届中国生物物理学会代谢生物学分会学术研讨会

作者： Ngee Kiat Chua andrew j.brown From the School of Biotechnology and Biomolecular Sciences UNSW Sydney

＜正＞Squalene monooxygenase （SM） is a rate-limiting enzyme in cholesterol *** region comprising the first 100 amino acids,termed SM N100,represents the shortest cholesterol-responsive degron and enables SM to sense excess cholesterol in the endoplasmic reticulum （ER） *** accelerates the ubiquitination of SM by membrane-associated ring-CH-type finger 6 （MARCH6）,a key E3 ubiquitin ligase involved in

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journal of Sport and Health Science 2024年第4期13卷 472-483,F0003页

作者： Kelly R.Evenson Wendy j.brown Alison K.Brinson Emily Budzynski-Seymour Melanie Hayman Department of Epidemiology Gillings School of Global Public HealthUniversity of North Carolina at Chapel HillChapel HillNC 27599-8050USA Faculty of Health Sciences and Medicine Bond UniversityGold CoastQLD 4226Australia School of Human Movement and Nutrition Sciences The University of QueenslandBrisbaneQLD 4072Australia Department of Anthropology University of North Carolina at Chapel HillChapel HillNC 27599-3115USA Carolina Population Center University of North Carolina at Chapel HillChapel HillNC 27599-8120USA Faculty of Sport Health and Social SciencesSolent UniversitySouthamptonSO140YNUK Appleton Institute School of HealthMedical and Applied SciencesCentral Queensland UniversityRockhamptonQLD 4701Australia

Background:The period following pregnancy is a critical time window when future habits with respect to physical activity(PA) and sedentary behavior(SB) are established;therefore,it warrants *** purpose of this scoping review was to summarize public health-oriented country-specific postpartum PA and SB guidelines ***:To identity guidelines published since 2010,we performed a(a) systematic search of 4 databases(CINAHL,Global Health,PubMed,and SPORTDiscus),(b) structured repeatable web-based search separately for 194 countries,and(c) separate web-based *** the most recent guideline was included for each ***:We identified 22 countries with public health-oriented postpartum guidelines for PA and 11 countries with SB *** continents with guidelines included Europe(n=12),Asia(n=5),Oceania(n=2),Africa(n=1),North America(n=1),and South America(n=1).The most common benefits recorded for PA included weight control/management(n=10),reducing the risk of postpartum depression or depressive symptoms(n=9),and improving mood/well-being(n=8).Postpartum guidelines specified exercises to engage in,including pelvic floor exercises(n=17);muscle strengthening,weight training,or resistance exercises(n=13);aerobics/general aerobic activity(n=13);walking(n=11);cycling(n=9);and swimming(n=9).Eleven guidelines remarked on the interaction between PA and breastfeeding;several guidelines stated that PA did not impact breast milk quantity(n=7),breast milk quality(n=6),or infant growth(n=3).For SB,suggestions included limiting long-term sitting and interrupting sitting with ***:Country-specific postpartum guidelines for PA and SB can help promote healthy behaviors using a culturally appropriate context while providing specific guidance to public health practitioners.

关键词： Breastfeeding Caesarean section Guidelines Postnatal Recommendations

Gene therapy for spinal muscular atrophy:perspectives on the possibility of optimizing SMN1 delivery to correct all neurological and systemic perturbations

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Neural Regeneration Research 2025年第7期20卷 2011-2012页

作者： Sharon j.brown Rafael j.Yáñez-Muñoz Heidi R.Fuller School of Pharmacy and Bioengineering Keele UniversityKeeleUK Wolfson Center for Inherited Neuromuscular Disease TORCH BuildingRJAH Orthopaedic HospitalOswestryUK *** Center of Gene and Cell TherapyDepartment of Biological SciencesSchool of Life Sciences and the EnvironmentRoyal Holloway University of LondonEghamUK

Spinal muscular atrophy(SMA)is a genetic condition that results in selective lower motor neuron loss with concomitant muscle weakness and *** genetic cause of SMA was understood in 1995 when loss or impairment of the survival motor neuron 1(SMN1)gene was identified as the main contributing factor(Lefebvre et al.,1995).This,in combination with the discovery that humans have a“back-up”gene,SMN2,which can produce low levels(approximately 10%)of the full-length functional SMN protein,has led to the generation of SMA-specific gene *** was traditionally classified according to age of symptom onset and developmental milestones achieved,with life expectancy and severity varying between ***,SMN2 copy number is used as a proxy for the prediction of disease severity,with higher SMN2 copy number typically being associated with reduced severity of SMA,although this relationship is not absolute:some individuals with low SMN2 copy number have less severe SMA phenotypes and vice ***,the etiology of SMA is further complicated by other factors,such as non-typical nucleotide variants and SMN2-independent modifiers of disease severity.

关键词： atrophy traditionally absolute

Older Adult Compendium of Physical Activities:Energy costs of human activities in adults aged 60 and older

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journal of Sport and Health Science 2024年第1期13卷 13-17,F0003页

作者： Erik A.Willis Stephen D.Herrmann Mary Hastert Chelsea L.Kracht Tiago V.Barreira john M.Schuna jr. Zhenghua Cai Minghui Quan Scott A.Conger Wendy j.brown Barbara E.Ainsworth Center for Health Promotion and Disease Prevention University of North Carolina at Chapel HillChapel HillNC 27599USA Kansas Center for Metabolism and Obesity Research The University of Kansas Medical CenterKansas CityKS 66160USA Division of Physical Activity and Weight Management Department of Internal MedicineUniversity of Kansas Medical CenterKansas CityKS 66160USA Clinical Science Division Pennington Biomedical Research CenterBaton RougeLA 70808USA Exercise Science Department Syracuse UniversitySyracuseNY 13244USA School of Exercise&Sport Science Oregon State UniversityCorvallisOR 97331USA School of Exercise and Health Shanghai University of SportShanghai 200438China Department of Kinesiology Boise State UniversityBoiseID 83725USA School of Human Movement and Nutrition Sciences The University of QueenslandSt.LuciaQLD 4072Australia Faculty of Health Sciences and Medicine Bond UniversityGold CoastQLD 4229Australia College of Health Solutions Arizona State UniversityPhoenixAZ 85003USA

Purpose:To describe the development of a Compendium for estimating the energy costs of activities in adults>60 years(OA Compendium).Methods:Physical activities(PAs)and their metabolic equivalent of task(MET)values were obtained from a systematic search of studies published in 4 sport and exercise databases(PubMed,Embase,SPORTDiscus(EBSCOhost),and Scopus)and a review of articles included in the 2011 Adult Compendium that measured PA in older *** values were computed as the oxygen cost(VO_(2),mL/kg/min)during PA divided by 2.7 m L/kg/min(MET_(60+))to account for the lower resting metabolic rate in older ***:We identified 68 articles and extracted energy expenditure data on 427 *** these,we derived 99 unique Specific Activity codes with corresponding MET_(60+)values for older *** developed a website to present the OA Compendium MET_(60+)values:https://***:The OA Compendium uses data collected from adults>60 years for more accurate estimation of the energy cost of PAs in older *** is an accessible resource that will allow researchers,educators,and practitioners to find MET_(60+)values for older adults for use in PA research and practice.

关键词： Energy expenditure Exercise MET Older adults

Physical activity volume,frequency,and intensity:Associations with hypertension and obesity over 21 years in Australian women

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journal of Sport and Health Science 2024年第5期13卷 631-641页

作者： Gregore I.Mielke Ding Ding Shelley E.Keating Bruno P.Nunes Ruth Brady Wendy j.brown School of Public Health The University of QueenslandBrisbaneQLD 4006Australia Sydney School of Public Health Faculty of Medicine and HealthThe University of SydneySydneyNSW 2006Australia The Charles Perkins Centre The University of SydneySydneyNSW 2006Australia School of Human Movement and Nutrition Sciences The University of QueenslandBrisbaneQLD 4072Australia School of Nursing Federal University of PelotasPelotasRio Grande do Sul 96010-610Brazil Faculty of Health Sciences and Medicine Bond UniversityGold CoastQLD 4226Australia

Background:Optimal patterns of accrual of recommended levels of physical activity(PA)for prevention of hypertension and obesity are not *** overall aim of this study was to investigate whether different patterns of accumulation of PA are differentially associated with hypertension and obesity in Australian women over 21 ***,we investigated whether,for the same weekly volume of PA,the number of sessions(frequency)and vigorousness of PA(intensity)were associated with a reduction in the occurrence of hypertension and obesity in ***:Data from the 1973-1978 and 1946-1951 cohorts of the Australian Longitudinal Study on Women's Health were analyzed(n=20,588;12%-16%with a Bachelor's or higher degree).Self-reported PA,hypertension,height,and weight were collected using mail surveys every 3 years from 1998/2000 to 2019/*** Estimating Equation models with a 3-year lag model were used to investigate the association of PA volume(metabolic equivalent min/week)(none;33-499;500-999;≥1000,weekly frequency(none;1-2 times;3-4times;5-7 times;≥8 times),and the proportion of vigorous PA to total volume of PA(none;0%;1%-33%;34%-66%;67%-100%)with odds of hypertension and obesity from 2000 to ***:The cumulative incidence of hypertension was 6%in the 1973-1978 and 23%in the 1946-1951 cohort;27%of women in the 1973-1978;and 15%in the 1946-1951 cohort developed obesity over the ***,a higher volume of PA was associated with reduced odds of hypertension and *** the volume of PA was considered,the odds of hypertension did not vary according to the frequency or intensity of ***,increased proportion of vigorous PA to the total volume of PA was associated with a small additional reduction in the risk of obe ***:PA volume appears to be more important than the pattern of accumulation for the prevention of hypertension and *** more sessions,particularly of vigorous-intensity PA,may provide extr

关键词： Physical activity Frequency Intensity Incidences Epidemiology Women

Development process for a higher capacity Propsetter~ system

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International journal of Mining Science and Technology 2018年第1期28卷 121-126页

作者： Christopher j.brown Product Development-Strata Worldwide LLC

As longwall tailgate support technologies continue to be developed and improved, strata worldwide has worked to design and manufacture a revised Propsetter to provide additional support capacity and enable applications at greater mine *** support is targeted for tailgate applications, however, it can also be utilized for roof support in various types of mining *** paper describes the design changes for enhancing the support capacity of the Propsetter to more closely align its performance with other support technologies currently being employed in longwall *** changes to each design aspect of the Propsetter was key to successfully improving the roof support's load capacity while maintaining controlled *** the load capacity would allow a mine to improve support efficiency with a smaller, less intrusive support compared to support alternatives and reduce the cost per foot of supported *** target support capacity was 711–890 k N at 50 mm of deformation to more closely match the performance of competing tailgate supports such as the 610 mm-diameter CAN~.To achieve this goal, changes were made to all design aspects of the Propsetter: diameter, wedge cut depth and angle, pod size, and confinement *** results from the NIOSH Mine Roof Simulator verified that these design changes were successful in increasing the capacity of the Propsetter to the 711–890 k N range at fifty mms of deformation.

关键词： Propsetter Can Longwall mining Tailgate roof support Controlled deformation

Effects of different organic fertilizers on nitrous oxide and methane emissions from double-cropping rice fields

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Pedosphere 2024年第1期34卷 52-62页

作者： Mingcheng HU andrew j.WADE Weishou SHEN Zhenfang ZHONG Chongwen QIU Xiangui LIN jiangsu Key Laboratory of Atmospheric Environment Monitoring and Pollution Control Collaborative Innovation Center of Atmospheric Environment and Equipment TechnologySchool of Environmental Science and EngineeringNanjing University of Information Science&TechnologyNanjing 210044China Department of Geography and Environmental Science University of ReadingReading RG66 DWUK Haina Research Institute of Guangdong Haina Agricultural Co. Ltd.Huizhou 516000China State Key Laboratory of Soil and Sustainable Agriculture Institute of Soil ScienceChinese Academy of SciencesNanjing 210008China

Rice fields are a major source of greenhouse gases,such as nitrous oxide (N_(2)O) and methane (CH_(4)).Organic fertilizers may potentially replace inorganic fertilizers to meet the nitrogen requirement for rice growth;however,the simultaneous effects of organic fertilizers on N_(2)O and CH_(4)emissions and crop yield in paddy fields remain poorly understood and *** this study,experimental plots were established in conventional double-cropping paddy fields in the Pearl River Delta,China,including an unfertilized control and five fertilizer treatments with fresh organic fertilizer (FOF),successively composted organic fertilizer (SOF),chemically composted organic fertilizer (COF),COF supplemented with inorganic fertilizer (COIF),and chemical fertilizers (CFs)(TFOF,TSOF,TCOF,TCOIF,and TCF,respectively).Paddy field soils behaved simultaneously as an N_(2)O sink (cumulative N_(2)O emission:-196 to-381 g N ha^(-1)) and as a CH_(4)source (cumulative CH_(4)emission:719 to 2 178 kg ha^(-1)).Compared to CFs,the effects of organic fertilizers on N_(2)O emission were not *** contrast,total annual CH_(4)emission increased by 157%,132%,125%,and 37%in TFOF,TCOF,TSOF,and TCOIF,respectively,compared to *** TCOIF,rice yield was maintained,while CH_(4)emission was not significantly increased from the paddy fields characterized by a prolonged flood *** important next step is to extend these field-based measurements to larger rice cultivation areas to quantify the regional and national-scale impacts on greenhouse gas emissions and to help determine the optimum practice for fertilizer use.

关键词： crop production global warming potential greenhouse gases manure paddy sustainable agriculture

PREPARATION OF ASYMMETRIC POLYETHERKETONE FLAT AND HOLLOW FIBER MEMBRANES FOR GAS SEPARATION USING ACETIC ACID BASED COAGULANTS

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Chinese journal of Polymer Science 2008年第3期26卷 263-273页

作者：杨继萍 Philip j.brown School of Material Science and Engineering Beihang UniversityBeijing 100083China School of Materials Science and Engineering Clemson UniversitySC29634USA

Membranes for gas separation have developed significantly in the last twenty years,however,there is still a need for high temperature and chemically resistant membranes that exhibit good selectivity and gas *** study examines the fundamental properties of polyetherketone (PEK,a thermally stable and chemically resistant polymer) membranes prepared using concentrated sulphuric acid (98% H_2SO_4) as the ***-solvents used in the work included acetic acid,ethanol,methanol,glycerol,and water....

关键词： Polyetherketones Membranes Gas permeation Internal coagulant effect Morphology