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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

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

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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

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

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基于平面肖特基二极管的W波段检波器

太赫兹科学与电子信息学报 2016年第5期14卷 668-672页

作者：刘海瑞 powell jeff VIEGAS Colin ALDErMAN Byron 俞俊生北京邮电大学信息与通信工程学院北京100876 Teratech Components Limited OX110QXUK

肖特基二极管技术为常温下毫米波信号的检测提供了有效的解决方案。它具有极低的寄生电容和级联电阻,可用于该频段的倍频器、混频器和检波器当中。相比于Galey Cell和热辐射测定器(Bolometer),基于肖特基二极管的直接检波技术具有低噪... 详细信息

肖特基二极管技术为常温下毫米波信号的检测提供了有效的解决方案。它具有极低的寄生电容和级联电阻,可用于该频段的倍频器、混频器和检波器当中。相比于Galey Cell和热辐射测定器(Bolometer),基于肖特基二极管的直接检波技术具有低噪声、高反应率和常温使用的特点。本文介绍了一种基于波导结构的零偏置肖特基二极管检波器,采用E面探针传输波导基模电磁波,通过阻抗匹配实现微带线到二极管的耦合。测试结果表明,在-30 d Bm输入功率下:电压反应率的峰值可达8 900 V/W;在75 GHz^105 GHz的频率范围内,电压反应率在1 000 V/W以上。

关键词：毫米波平面肖特基二极管 W波段直接检波器电压反应率

A neuroligin-4 missense mutation associated with autism impairs neuroligin-4 folding and endoplasmic reticulum export

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A neuroligin-4 missense mutation associated with autism impa...