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Bone research 2023年第1期11卷 193-200页

作者： robert Brommage Jeff Liu david r.powell Department of Metabolism research Lexicon PharmaceuticalsThe WoodlandsTX77381USA

Mutations in SFrP4 cause Pyle’s bone disease with wide metaphyses and increased skeletal *** WNT signaling pathway plays important roles in determining skeletal architecture and SFrP4 is a secreted Frizzled decoy receptor that inhibits WNT *** cohorts of male and female Sfrp4 gene knockout mice,examined through 2 years of age,had a normal lifespan but showed cortical and trabecular bone *** human Erlenmeyer flask deformities,bone cross-sectional areas were elevated 2-fold in the distal femur and proximal tibia but only 30%in femur and tibia *** cortical bone thickness was observed in the vertebral body,midshaft femur and distal *** trabecular bone mass and numbers were observed in the vertebral body,distal femur metaphysis and proximal tibia *** femurs retained extensive trabecular bone through 2 years of *** bodies had increased compressive strength,but femur shafts had reduced bending ***,but not cortical,bone parameters in heterozygous Sfrp4mice were modestly *** resulted in similar declines in both cortical and trabecular bone mass in wild-type and Sfrp4 KO ***4 is critical for metaphyseal bone modeling involved in determining bone ***4 KO mice show similar skeletal architecture and bone fragility deficits observed in patients with Pyle’s disease with SFrP4 mutations.

关键词： SFrP4 skeletal elevated

NOTUM inhibition increases endocortical bone formation and bone strength

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Bone research 2019年第1期7卷 54-65页

作者： robert Brommage Jeff Liu Peter Voge Faika Mseeh Andrea Y.Thompson david G.Potter Melanie K.Shadoan Gwenn M.Hansen Sabrina Jeter-Jones Jie Cui Dawn Bright Jennifer P.Bardenhagen Deon D.Doree Sofia Moverare-Skrtic Karin H.Nilsson Petra Henning Ulf H.Lerner Claes Ohlsson Arthur T.Sands James E.Tarver david r.powell Brian Zambrowicz Qingyun Liu Lexicon Pharmaceuticals The WoodlandsTXUSA Wntrix HoustonTXUSA PrA Health Sciences RaleighNCUSA University of Pennsylvania PhiladelphiaPAUSA regeneron Pharmaceuticals TarrytownNYUSA University of Texas HoustonTXUSA Centre for Bone and Arthritis research Institute of MedicineThe Sahlgrenska Academy at University of GothenburgGothenburgSweden Centre for Bone and Arthritis research University of GothenburgGothenburgSweden Biogen CambridgeMAUSA St.Jude Children’s research Hospital MemphisTNUSA MD Anderson Cancer Center HoustonTXUSA Bethyl Laboratories MontgomeryTXUSA Merck RahwayNJUSA Nurix San FranciscoCAUSA

The disability,mortality and costs caused by non-vertebral osteoporotic fractures are *** osteoporosis therapies are highly effective at reducing vertebral but not non-vertebral *** bone is a major determinant of non-vertebral bone *** identify novel osteoporosis drug targets,we phenotyped cortical bone of 3 366 viable mouse strains with global knockouts of druggable *** bone thickness was substantially elevated in Notum?/?*** is a secreted WNT lipase and we observed high NOTUM expression in cortical bone and osteoblasts but not *** orally active small molecules and a neutralizing antibody inhibiting NOTUM lipase activity were *** increased cortical bone thickness and strength at multiple skeletal sites in both gonadal intact and ovariectomized rodents by stimulating endocortical bone ***,inhibition of NOTUM activity is a potential novel anabolic therapy for strengthening cortical bone and preventing non-vertebral fractures.

关键词： disability osteoporosis fractures

Calcium channels caught in peripheral glia’s tug-of-war on axon regeneration in Drosophila

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Neural regeneration research 2025年第2期20卷 475-476页

作者： Jackson powell Tobias Steinschaden rose Horowitz Yuanquan Song raymond G.Perelman Center for Cellular and Molecular Therapeutics The Children’s Hospital of PhiladelphiaPhiladelphiaPAUSA The Neuroscience Graduate Group University of PennsylvaniaPhiladelphiaPAUSA Department of Pathology and Laboratory Medicine University of PennsylvaniaPhiladelphiaPAUSA Medical University of Vienna Center for Brain ResearchDepartment of NeuroimmunologyViennaAustria

Neural damage or degeneration is at the crux of many diseases,and treatment of these diseases will require the development of therapeutics to enhance and guide neural *** intrinsic and extrinsic factors dictate a neuron’s ability to regenerate,and the combination of these factors results in the great regenerative capacity of the peripheral nervous system(PNS)and the poor regenerative capacity of the central nervous system(CNS)following *** the core of a neuron’s function is its ability to relay electrochemical signals,and a neuron’s excitability is a key factor in its ability to *** works have focused on the changes in neuronal electrophysiological properties,firing patterns,and ion flux after injury,which differentially activate signaling pathways at the core of *** role of glia in neuron regeneration has long been studied.

关键词： degeneration firing system

Advanced casting technologies for lightweight automotive applications

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China Foundry 2010年第4期7卷 463-469页

作者： Alan A.Luo Anil K.Sachdev Bob r.powell General Motors Global research and Development Center

This paper provides an overview of alloy and process developments in aluminum and magnesium castings for lightweight automotive applications. Wear-resistant aluminum alloys, creep-resistant and high strength/ductility magnesium alloys have been developed for automotive applications. On the process front, vacuumassisted die casting and high vacuum die casting technologies have been developed for high-integrity body and chassis applications. Thin-wall and hollow casting components are being produced by low-pressure die casting processes for structural applications. Overcasting technology is gaining traction and has enabled mixed material designs for automotive sub-systems such as engine cradles and instrument panel beams. Simulation tools developed to predict the interfacial interactions of the dissimilar components and the structural integrity of the overcast systems are being validated in the casting trials.

关键词： lightweight aluminum alloy magnesium alloy die casting

Ultrahigh-pressure garnet peridotites from the devolatilization of sea-floor hydrated ultramafic rocks

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Ultrahigh-pressure garnet peridotites from the devolatilizat...

High-throughput screening of mouse gene knockouts identifies established and novel skeletal phenotypes

中国科学院地质与地球物理研究所2008学术年会

作者： r.powell School of Earth Sciences The University of MelbourneVictoria3010MelbourneAustralia

Garnet peridotites occur in quartzofeldspathic gneisses in the Northern Qaidam Mountains,western *** are rich in Mg and Cr,with mineral compositions similar to those in mantle peridotites found in other orogenic belts and as xenoliths in ***-bearing lherzolites interlayered with dunite display oriented ilmenite and chromite lamellae in olivine and pyroxene lamellae in garnet that have been interpreted to indicate pressures in excess of 6 ***,some garnet porphyroblasts include hornblende,chlorite and spinel + orthopyroxene symplectite after garnet;some clinopyroxene porphyroblasts include abundant actinolite/edenite,calcite and lizardite in the lherzolite;some olivine porphyroblasts(Fo) include an earlier generation Mg-rich olivine(Fo),F-rich clinohumite, pyroxene,chromite,anthophyllite/cummingtonite,Cl-rich lizardite,carbonates and a new type of brittle mica,here termed ’Ca-phlogopite’,in the associated *** pyrope content of garnet increases from core to rim,reaching the pyrope content(72mol.%) of garnet typically found in the xenoliths in *** simplest interpretation of these observations is that the rock association was formerly mantle peridotite emplaced into the oceanic crust that was subjected to serpentinization by seawater-derived fluids near the sea *** during subduction to 3.0-3.5 GPa and 700℃transformed these serpentinites into garnet lherzolite and dunite,depending on their Al and Ca *** modelling using THErMOCALC shows that dehydration of the serpentinites is progressive,and involved three stages for Al-rich and two stages for Al-poor serpentinites, corresponding to the breakdown of the key hydrous *** burial and exhumation make olivine a pressure vessel for the pre-subduction mineral inclusions during ultrahigh-pressure(UHP) *** time span of the UHP event is constrained by the clear interface between the two generations of olivine to be very short,imp

关键词： garnet peridotites lizardite Northern Qaidam Mountains north-west China oceanic crust short-lived UHP metamorphism

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Bone research 2014年第3期2卷 152-181页

作者： robert Brommage Jeff Liu Gwenn M Hansen Laura L Kirkpatrick david G Potter Arthur T Ss Brian Zambrowicz david r.powell Peter Vogel Lexicon Pharmaceuticals The Woodlands TX USA

Screening gene function in vivo is a powerful approach to discover novel drug targets. We present high-throughput screening （HTS） data for 3 762 distinct global gene knockout （KO） mouse lines with viable adult homozygous mice generated using either gene-trap or homologous recombination technologies. Bone mass was determined from DEXA scans of male and female mice at 14 weeks of age and by microCT analyses of bones from male mice at 16 weeks of age. Wild-type （WT） cagemates/littermates were examined for each gene KO. Lethality was observed in an additional 850 KO lines. Since primary HTS are susceptible to false positive findings, additional cohorts of mice from KO lines with intriguing HTS bone data were examined. Aging, ovariectomy, histomorphometry and bone strength studies were performed and possible non-skeletal phenotypes were explored. Together, these screens identified multiple genes affecting bone mass： 23 previously reported genes （Calcr, Cebpb, Crtap, Dcstamp, Dkkl, Duoxa2, Enppl, Fgf23, Kissl/Kisslr, Kl （Klotho）, Lrp5, Mstn, Neol, Npr2, Ostml, Postn, Sfrp4, S1c30a5, Sic39a13, Sost, Sumf1, Src, Wnt10b）, five novel genes extensively characterized （Cldn18, Fam20c, Lrrkl, Sgpll, Wnt16）, five novel genes with preliminary characterization （Agpat2, rassfS, Slc10a7, Stc26a7, Slc30a10） and three novel undisclosed genes coding for potential osteoporosis drug targets.

关键词： KO High-throughput screening of mouse gene knockouts identifies established and novel skeletal phenotypes BMD HTS DEXA gene

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民兵导弹研制初期保障系统可靠性的途径

导弹与航天运载技术(中英文) 1981年第10期 1-11页

作者： Harry r.powell 葛法本

六十年代初期,民兵导弹系统就能满足其系统可靠性的要求,其原因在于民兵导弹的原始方案在管理方面和技术方面提出严格的要求。计划开始时就制定了各项管理政策,作出了一些必要的技术决策,为后来成功地实施可靠性计划奠定了良好的基础。... 详细信息

六十年代初期,民兵导弹系统就能满足其系统可靠性的要求,其原因在于民兵导弹的原始方案在管理方面和技术方面提出严格的要求。计划开始时就制定了各项管理政策,作出了一些必要的技术决策,为后来成功地实施可靠性计划奠定了良好的基础。实施可靠性计划需要有极高的技术水平,并要根据民兵导弹的特殊需要进行一些技术革新。本文将介绍民兵导弹各项管理政策和技术决策以及可靠性计划。

关键词：民兵导弹工作组承包商弹道导弹弹道式导弹系统可靠性

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汽车轻量化先进铸造技术

铸造 2011年第2期60卷 113-119页

作者：罗爱华 Anil K. Sachdev Bob r. powell 申泽骥(翻译) 通用汽车全球研究和发展中心 WarrenMI48090美国不详

全面评述了用于汽车轻量化的铸造铝和镁合金及铸造工艺的发展。已开发的汽车用新型合金有耐磨铝合金、抗蠕变镁合金及高强度/韧性镁合金。在工艺前沿方面,开发了真空辅助压铸和高真空压铸技术,用于生产高整体性的车体和底盘零件。用低... 详细信息

全面评述了用于汽车轻量化的铸造铝和镁合金及铸造工艺的发展。已开发的汽车用新型合金有耐磨铝合金、抗蠕变镁合金及高强度/韧性镁合金。在工艺前沿方面,开发了真空辅助压铸和高真空压铸技术,用于生产高整体性的车体和底盘零件。用低压金属型铸造工艺生产结构用薄壁空心铸件。包覆铸造技术不断得到发展,使用混合材料设计汽车的子系统,例如发动机支架、仪表板梁成为可能。开发的模拟工具用来预测不同组分之间的界面相互反应和包覆铸造系统的结构完整性,并且已被铸造实验证实。

关键词：汽车轻量化铝合金镁合金压铸

role of hospitalization for inflammatory bowel disease in the postbiologic era

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World Journal of Clinical Cases 2021年第26期9卷 7632-7642页

作者： Celine r Soriano Charleston r.powell Michael V Chiorean Vlad V Simianu Department of Surgery Virginia Mason Franciscan HealthSeattleWA 98101United States Department of Internal Medicine Madigan Army Medical CenterTacomaWA 98431United States Department of Gastroenterology Swedish Medical CenterSeattleWA 98109United States

Treatment for inflammatory bowel disease (IBD) often requires specialized *** much of IBD care has shifted to the outpatient setting, hospitalizationsremain a major site of healthcare utilization and a sizable proportion of patientswith inflammatory bowel disease require hospitalization or surgery during theirlifetime. In this review, we approach IBD care from the population-level with aspecific focus on hospitalization for IBD, including the shifts from inpatient tooutpatient care, the balance of emergency and elective hospitalizations, regionalizationof specialty IBD care, and contribution of surgery and endoscopy tohospitalized care.

关键词： Inflammatory bowel disease Hospitalization Elective Emergent surgery Endoscopy

Post-COVID recovery and renewal through whole-of-society resilience in cities

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Journal of Safety Science and resilience 2022年第3期3卷 222-228页

作者： Andrew G.McClelland roisin Jordan Szymon Parzniewski Duncan Shaw Nat O’Grady david powell Alliance Manchester Business School University of ManchesterManchester M139PLUK Alliance Manchester Business School Humanitarian&Conflict Response InstituteUniversity of ManchesterManchester M139PLUK Humanitarian&Conflict response Institute University of ManchesterManchester M139PLUK

This paper explores and extends understanding of the role and significance of whole-of-society resilience pro-grammes that support cities when dealing with complex crises,like the COVID-19 *** the complexity of whole-of-society resilience as different actors locally shape it,we ask the question:How can collab-oration between formal and informal resilience practices help to enhance resilience across the‘whole-of-society’?We answer this question by reviewing the importance of whole-of-society resilience and its complexity in a city’s governance of the COVID-19 *** argue that the necessity of renewing approaches to building lo-cal resilience capabilities across the whole-of-society requires synchronisation across and between formal and informal approaches-that is,“bottom-up”and governmental initiatives-to meet the diverse needs of ***,we detail two recent practice-orientated initiatives that have taken a renewal approach to building resilience through the involvement of whole-of-society in planning recovery from COVID-19 using in-ternational standard ISO/TS 22393;and a new initiative called the National Consortium for Societal resilience[UK+].Finally,we signpost a set of critical questions for whole-of-society resilience practice.

关键词： Whole-of-society resilience Crisis recovery renewal Cities,COVID-19