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Acta Pharmaceutica Sinica B 2021年第6期11卷 1446-1468页

作者： Michael A.Serwetnyk brian S.j.Blagg Department of Chemistry and Biochemistry Warren Family Research Center for Drug Discovery and DevelopmentUniversity of Notre DameIN 46556USA

The 90-kilo Dalton(kD) heat shock protein(Hsp90) is a ubiquitous,ATP-dependent molecular chaperone whose primary function is to ensure the proper folding of several hundred client protein *** many of these clients are overexpressed or become mutated during cancer progression,Hsp90 inhibition has been pursued as a potential strategy for cancer as one can target multiple oncoproteins and signaling pathways *** first discovered Hsp90 inhibitors,geldanamycin and radicicol,function by competitively binding to Hsp90’s N-terminal binding site and inhibiting its ATPase ***,most of these N-terminal inhibitors exhibited detrimental activities during clinical evaluation due to induction of the pro-survival heat shock response as well as poor selectivity amongst the four ***,alternative approaches to Hsp90 inhibition have been pursued and include C-terminal inhibition,isoform-selective inhibition,and the disruption of Hsp90 protein-protein *** the Hsp90 protein folding cycle requires the assembly of Hsp90 into a large heteroprotein complex,along with various co-chaperones and immunophilins,the development of small molecules that prevent assembly of the complex offers an alternative method of Hsp90 inhibition.

关键词： Hsp90 Protein-protein interactions Disruptors Natural products Small molecules Peptidomimetics

Establishment of Withania somnifera Hairy Root Cultures for the Production of Withanolide A

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j.urnal of Integrative Plant Biology 2008年第8期50卷 975-981页

作者： Hosakatte N. Murthy Camelia Dij.stra Paul Anthony Daniel A. White Mike R. Davey j. brian Power Eun j. Hahn Kee Y. Paek Plant Sciences Division School of Biosciences University of Nottingham Sutton Bonington Campus Loughborough LE12 5RD UK Department of Botany Karnatak University Dharwad 580 003 India Research Center for the Development of Advanced Horticultural Technology Chungbuk National University Cheongju 361-763 Korea Department of Botany Karnatak University Dharwad 580 003 India Food Sciences Division School of Biosciences University of Nottingham Sutton Bonington Campus Loughborough LE12 5RD UK Research Center for the Development of Advanced Horticultural Technology Chungbuk National University Cheongju 361-763 Korea

Withania sominifera （Indian ginseng） was transformed by Agrobacterium rhizogenes. Explants from seedling roots, stems, hypocotyls, cotyledonary nodal segments, cotyledons and young leaves were inoculated with A. rhizogenes strain R1601. Hairy （transformed） roots were induced from cotyledons and leaf explants. The transgenic status of hairy roots was confirmed by polymerase chain reaction using nptll and rolB specific primers and, subsequently, by Southern analysis for the presence of nptll and rolB genes in the genomes of transformed roots. Four clones of hairy roots were established; these differed in their morphology. The doubling time of faster growing cultures was 8-14 d with a fivefold increase in biomass after 28 d compared with cultured, non-transformed seedling roots. MS-based liquid medium was superior for the growth of transformed roots compared with other culture media evaluated （SH, LS and N6）, with MS-based medium supplemented with 40 g/L sucrose being optimal for biomass production. Cultured hairy roots synthesized withanolide A, a steroidal lactone of medicinal and therapeutic value. The concentration of withanolide A in transformed roots （157.4 μg/g dry weight） was 2.7-fold more than in non-transformed cultured roots （57.9 μg/g dry weight）.

关键词： Agrobacterium rhizogenes hairy (transformed) roots Indian ginseng transformation withanolide A

Strategies to improve fiber utilization in swine

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j.urnal of Animal Science and Biotechnology 2013年第2期4卷 112-123页

作者： brian j.Kerr Gerald C Shurson USDA-ARS-National Laboratory for Agriculture and the Environment University of Minnesota

Application of feed processing methods and use of exogenous feed additives in an effort to improve nutrient digestibility of plant-based feed ingredients for swine has been studied for decades. The following review will discuss several of these topics, including： fiber characterization, impact of dietary fiber on gastrointestinal physiology, energy, and nutrient digestibility, mechanical processing of feed on fiber and energy digestibility, and the use of exogenous enzymes in diets fed to growing pigs. Taken together, the diversity and concentration of chemical characteristics that exists among plant-based feed ingredients, as well as interactions among constituents within feed ingredients and diets, suggests that improvements in nutrient digestibility and pig performance from mechanical processing or adding exogenous enzymes to diets fed to swine depends on a better understanding of these characteristics, but also relating enzyme activity to targeted substrates. It may be that an enzyme must not only match a target substrate（s）, but there may also need to be a ＇cocktail＇ of enzymes to effectively breakdown the complex matrixes of fibrous carbohydrates, such that the negative impact of these compounds on nutrient digestibility or voluntary feed intake are alleviated. With the inverse relationship between fiber content and energy digestibility being well described for several feed ingredients, it is only logical that development of processing techniques or enzymes that degrade fiber, and thereby improve energy digestibility or voluntary feed intake, will be both metabolically and economically beneficial to pork production.

关键词： Energy Enzymes Fiber Growing-finishing pigs Nutrient digestibility Processing

Circumcision reduces prostate cancer risk

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Asian j.urnal of Andrology 2012年第5期14卷 661-662页

作者： brian j.Morris lake H Waskett School of Medical Sciences University of SydneySydney NSW 2006 Australia CircumcisionIndependent Reference and Commentary Service Manchester M26 1JR UK

There is a strong negative correlation between prostate cancer and circumcision rate across 181 countries （P〈0.0001）. Adding to the large protective effect of cir- cumcision seen in small studies over the past six decades, a recent large study in Seattle has shown a smaller protective effect. If verified by other large studies else- where, the finding would add to the wide array of benefits conferred by this safe, sim- ple procedure that is best performed in infancy.

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Evaluating the quality of feed fats and oils and their effects on pig growth performance

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j.urnal of Animal Science and Biotechnology 2016年第3期7卷 330-340页

作者： Gerald C Shurson brian j.Kerr Andrea R Hanson Department of Animal Science University of MinnesotaStPaulMN 55018USA usda-ars-national laboratory for agriculture and the environment Ames IA 50011USA svc-research St PeterMN 56082USA

Feed fats and oils provide significant amounts of energy to swine diets, but there is large variation in composition,quality, feeding value, and price among sources. Common measures of lipid quality include moisture, insolubles,and unsaponifiables（MIU）, titer, and free fatty acid content, but provide limited information regarding their feeding value. Lipid peroxidation is an important quality factor related to animal growth performance and health, but maximum tolerable limits in various lipids have not been established. Several indicative assays can be used to detect the presence of various peroxidation compounds, but due to the complexity and numerous compounds produced and degraded during peroxidation process, no single method can adequately determine the extent of peroxidation. Until further information is available, using a combination of peroxide value, thiobarbituric acid reactive substances（TBARS）, and anisidine value appear to provide a reasonable assessment of the extent of peroxidation in a lipid at a reasonable cost. However, fatty acid composition of the lipid being evaluated should be considered when selecting specific assays. Predictive tests can also be used to estimate the stability or susceptibility of lipids to peroxidation and include active oxygen method, oil stability index, and oxygen bomb method. A review of 16 published studies with pigs has shown an average decrease of 11.4% in growth rate, 8.8% feed intake fed isocaloric diets containing peroxidized lipids compared to diets containing unperoxidized lipids of the same ***, serum vitamin E content was generally reduced and serum TBARS content was increased when peroxidized lipids were fed in these studies, suggesting that feeding peroxidized lipids negatively affects metabolic oxidative status of pigs. However, it is unclear if antioxidants are useful additions to lipids to maintain optimal nutritional value, or if their addition to swine diets is beneficial in overcoming a met

关键词： Growth Indicative tests Lipids Metabolic oxidation Peroxidation Pigs

The practice of mine ventilation engineering

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International j.urnal of Mining Science and Technology 2015年第2期25卷 165-169页

作者： Wallace Keith Prosser brian Stinnette j.Daniel Mine Ventilation Services Inc.

The practice of ventilation is continually evolving with new technological advances developed in the mining *** recent years the advances in diesel engine technologies,ventilation modeling software,and ventilation management capacities have redefined the historical methods used to evaluate *** advances re-evaluate previous methods used to calculate the airflow requirements for the dilution of diesel exhaust *** software has become an integral part of planning and developing ventilation systems in partnership with graphical mine design software packages to generate realistic representations of the *** advances in ventilation control strategies through remote sensors and monitoring capabilities have been developed to results in cost *** there has been much advancement in mine ventilation technology,the practices and basic ventilation principals enacted through the ventilation engineer cannot be placated with technological advances only.

关键词： Modern ventilation Ventilation on demand Diesel Airflow evaluation Monitoring system

Variable retention harvesting in Great Lakes mixed-pine forests: emulating a natural model in managed ecosystems

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Ecological Processes 2019年第1期8卷 210-224页

作者： brian j.Palik Anthony W.D’Amato USDA Forest Service Northern Research StationGrand RapidsMN 55744USA Rubenstein School of Environment and Natural Resources University of VermontBurlingtonVT 05095USA.

Variable retention harvesting(VRH)systems have gained wide use in many different forest types across the globe,but largely have been implemented in forests characterized by severe,infrequent disturbance *** has been less attention given to developing VRH approaches in forests that are characterized as having a mixed-severity disturbance regime that often results in only partial mortality of canopy trees in spatially heterogeneous *** example of such a forest type is red pine(Pinus resinosa Ait.)-dominated ecosystem of the western Great Lakes region of North *** purpose of this review is to provide a conceptual foundation for developing VRH approaches in red pine ecosystems that are based on a mixed-severity disturbance *** contention is that red pine forests managed following a natural model are more resilient to disturbances and external threats such as climate *** the red pine ecosystem,VRH application should reflect the often severe,but partial canopy removal from natural disturbance that is characteristic of this ecosystem and that results in more than trivial numbers of surviving overstory trees across a range of spatial configurations in regenerating *** live trees should span a range of diameters,but favor the larger end of the diameter distribution,as this reflects the likely pattern of survival after natural disturbance and is often a key structural element lacking from managed *** should be applied in ways that vary the spatial pattern of legacy trees in and among stands,but largely in ways that reflect the pattern of spatially patchy canopy structure,with large openings surrounded by a less disturbed matrix,as occurs with a natural disturbance *** trees and deadwood structures should reflect the composition of the pre-disturbance forest,including species in addition to dominant red ***,retained structures should be viewed as dynamic entities that grow,die,and decay and that need

关键词： Red pine Mixed-severity Variable retention Natural disturbance

An Assessment of Burs Designed to Cut Zirconia

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Open j.urnal of Stomatology 2017年第5期7卷 277-282页

作者： brian j. Millar Restorative Dentistry King’s College London Dental Institute London UK

Obj.ctive: Zirconia is increasingly being used in restorative dentistry but its removal is often a difficult procedure due to its resistance to cutting with conventional diamond burs. Zirconia cutting burs have been developed and this study aims to compare 4 such burs. Methods: 35 experienced restorative dentists selected from our Practice Based Network (PBN) were asked to evaluate the cutting of a 1 mm groove into zirconia using 4 burs A (Meisinger), B (ZR2-1 experimental bur from DIATECH), C (Komet) & D (DIATECH Z-Rex, a bur designed with enhanced bonding of diamond grit to bur shank). Responses regarding cutting time, performance and wear were recorded. Results: For best cutting times and also overall performance D performed best and C the worst, with little difference between burs A and B. Bur C also performed least well for wear on the bur. Conclusion: The newly designed zirconia cutting bur DIATECH Z-Rex with enhanced bonding of diamond grit performed best in the analysis by the 35 dentists.

关键词： Burs Zirconia Removal

Urban Consumer Attitudes to Fresh Produce Safety in China

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j.urnal of Food Science and Engineering 2016年第1期6卷 1-10页

作者： brian j. Revell Harper Adams University Newport Shropshire TF10 8NB United Kingdom

The obj.ctive of this study was to explain the determinants of the fresh vegetables purchase decision by Chinese urban consumers in Beij.ng including awareness and attitudes to food safety, and their willingness to pay （WTP） more for specific safety characteristics when buying fresh vegetables. The research rationale arises out of a history of food safety scares and scandals in China, and a national government response to promote quality assurance and safety through labelling. The primary hypothesis was that an understanding of food safety systems and product labelling, and trust in supply chain integrity would be key determinants in consumer willingness to purchase and pay more for safety assured vegetables. Based on a questionnaire survey of consumers in Beij.ng, the analysis found that the maj.r factors underlying the purchase decision of fresh vegetables were product freshness, convenience and competitive price rather than assured product labelling. The decisions whether to purchase assurance-labelled vegetables and WTP more for chemical residue-free product were analysed by binomial and ordinal multinomial logit modelling respectively. It revealed a WTP moreof between 20% and 40%. Monthly household income was a key determinant of both quality assured product and WTP, together with degree of concern over residues, trust in retailer and assurance labels and place of purchase. The results suggest much still remains to be done to build trust though rigorous monitoring and enforcement of food safety standards to improve supply chain integrity and consumer confidence.

关键词： Food safety fresh produce consumer preferences China logit modelling WTP

Molecular mechanisms of liver ischemia reperfusion inj.ry:Insights from transgenic knockout models

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World j.urnal of Gastroenterology 2013年第11期19卷 1683-1698页

作者： Gourab Datta Barry j.Fuller brian R Davidson Liver Transplantation and Hepatobiliary Unit Division of Surgery and Interventional ScienceRoyal Free CampusUniversity College LondonRoyal Free Hampstead NHS Trust HospitalLondon NW 2QGUnited Kingdom

Ischemia reperfusion inj.ry is a maj.r obstacle in liver resection and liver transplantation *** the mechanisms of liver ischemia reperfusion inj.ry(IRI) and developing strategies to counteract this inj.ry will therefore reduce acute complications in hepatic resection and transplantation,as well as expanding the potential pool of usable donor *** initial liver inj.ry is initiated by reactive oxygen species which cause direct cellular inj.ry and also activate a cascade of molecular mediators leading to microvascular changes,increased apoptosis and acute inflammatory changes with increased hepatocyte *** adaptive pathways are activated during reperfusion that reduce the reperfusion *** involves a complex interplay between neutrophils,natural killer T-cells cells,CD4+ T cell subtypes,cytokines,nitric oxide synthases,haem oxygenase-1,survival kinases such as the signal transducer and activator of transcription,Phosphatidylinositol 3-kinases/Akt and nuclear factor κβ *** animals,particularly genetic knockout models,have become a powerful tool at elucidating mechanisms of liver ischaemia reperfusion inj.ry and are complementary to pharmacological *** disruption of the protein at the genetic level is more specific and maintained than pharmacological inhibitors or stimulants of the same *** article reviews the evidence from knockout models of liver IRI about the cellular and molecular mechanisms underlying liver IRI.

关键词： Liver Ischemia/reperfusion Transgenic Knockout Nitric oxide synthase Haem oxygenase Mitogen-activated protein kinase T cell receptor