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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

Analysis of the combined effect of rs699 and rs5051 on angiotensinogen expression and hypertension

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Chronic Diseases and Translational Medicine 2024年第2期10卷 102-117页

作者： Nicholas r.powell Tyler Shugg Jacob Leighty Matthew Martin rolf P.Kreutz Michael T.Eadon Dongbing Lai Tao Lu Todd C.Skaar Division of Clinical Pharmacology Department of MedicineSchool of MedicineIndiana UniversityIndianapolisIndianaUSA Department of Pharmacology and Toxicology School of MedicineIndiana UniversityIndianapolisIndianaUSA Department of Cardiology School of MedicineKrannert Institute of CardiologyIndiana UniversityIndianapolisIndianaUSA Division of Nephrology Department of MedicineSchool of MedicineIndiana UniversityIndianapolisIndianaUSA Department of Medical and Molecular Genetics School of MedicineIndiana UniversityIndianapolisIndianaUSA

Background Hypertension(HTN)involves genetic variability in the renin-angiotensin system and influences antihypertensive *** previously reported that angiotensinogen(AGT)messenger rNA(mrNA)is endogenously bound by mir-122-5p and rs699 A>G decreases reporter mrNA in the microrNA functional-assay *** AGT promoter variant rs5051 C>T is in linkage disequilibrium(LD)with rs699 A>G and increases AGT *** independent effect of these variants is understudied due to their LD therefore we aimed to test the hypothesis that increased AGT by rs5051 C>T counterbalances AGT decreased by rs699 A>G,and when these variants occur independently,it translates to HTN-related *** We used in silico,in vitro,in vivo,and retrospective models to test this *** In silico,rs699 A>G is predicted to increase mir-122-5p binding affinity by 3%.Mir-eCLIP results show rs699 is 40–45 nucleotides from the strongest microrNA-binding site in the AGT ***,rs699 A>G increases AGT mrNA in an AGT-plasmid-cDNA HepG2 expression ***-Tissue Expression(GTEx)and UK Biobank analyses demonstrate liver AGT expression and HTN phenotypes are not different when rs699 A>G occurs independently from rs5051 C>***,GTEx and the in vitro experiments suggest rs699 A>G confers cell-type-specific effects on AGT mrNA abundance,and suggest paracrine renal renin-angiotensin-system perturbations could mediate the rs699 A>G associations with *** We found that rs5051 C>T and rs699 A>G significantly associate with systolic blood pressure in Black participants in the UK Biobank,demonstrating a fourfold larger effect than in White *** studies are warranted to determine if altered antihypertensive response in Black individuals might be due to rs5051 C>T or rs699 A>*** like this will help clinicians move beyond the use of race as a surrogate for genotype.

关键词： angiotensinogen genetic and genomic medicine hypertension rs699

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

A Global Imperative:Five Principles Of Peaceful Coexistence

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Beijing review 2024年第31期67卷 24-25页

作者： Warwick powell the Queensland University of Technology in Australia the Taihe Institute

Beijing hosted an event commemorating the 7Oth anniversary of the Five Principles of Peaceful Coexistence on June *** event served not only as a celebration of historical achievements,but also as a focal point for nat... 详细信息

关键词： Peace transformation. anniversary

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

China and the Changing Global Economic Order

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China Today 2024年第9期73卷 40-43页

作者： WArWICK powell Queensland University of Technology Taihe Institute China

A better understanding of China’s modernization presents an insight into a changing *** China has developed,so too has the global *** the past 200 years or so,the structure of the global economy was dominated first by the British empire,and more recently by the *** the global economic *** system of center-and-peripheries is now decentering,with a diversification of networks and connections creating a multinodal system of value growth and circulation.

关键词： Changing creating modernization

A radial Basis Function Method with Improved Accuracy for Fourth Order Boundary Value Problems

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Journal of Applied Mathematics and Physics 2024年第7期12卷 2559-2573页

作者： Scott A. Sarra Derek Musgrave Marcus Stone Joseph I. powell Department of Mathematics Marshall University Huntington WV USA

Accurately approximating higher order derivatives is an inherently difficult problem. It is shown that a random variable shape parameter strategy can improve the accuracy of approximating higher order derivatives with radial Basis Function methods. The method is used to solve fourth order boundary value problems. The use and location of ghost points are examined in order to enforce the extra boundary conditions that are necessary to make a fourth-order problem well posed. The use of ghost points versus solving an overdetermined linear system via least squares is studied. For a general fourth-order boundary value problem, the recommended approach is to either use one of two novel sets of ghost centers introduced here or else to use a least squares approach. When using either ghost centers or least squares, the random variable shape parameter strategy results in significantly better accuracy than when a constant shape parameter is used.

关键词： Numerical Partial Differential Equations Boundary Value Problems radial Basis Function Methods Ghost Points Variable Shape Parameter Least Squares

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：铸造技术汽车应用轻型镁合金铸件界面相互作用应用程序压铸技术结构完整性

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

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

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Ultrahigh-pressure garnet peridotites from the devolatilizat...