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Genetic interactions between polycystin-1 and Wwtr1 in osteoblasts define a novel mechanosensing mechanism regulating bone formation in mice

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Bone Research 2023年第4期11卷 772-783页

作者： Zhousheng Xiao Li Cao micholas dean smith Hanxuan Li Wei Li Jeremy C.smith Leigh Darryl Quarles Department of Medicine University of Tennessee Health Science CenterMemphisTN 38163USA UT/ORNL Center for Molecular Biophysics Oak Ridge National LaboratoryOak RidgeTN 37830USA Department of Biochemistry and Cellular and Molecular Biology The University of Tennessee-KnoxvilleKnoxvilleTN 37996-1939USA Department of Pharmaceutical Sciences University of Tennessee Health Science CenterMemphisTN 38163USA

Molecular mechanisms transducing physical forces in the bone microenvironment to regulate bone mass are poorly ***,we used mouse genetics,mechanical loading,and pharmacological approaches to test the possibility that polycystin-1 and Wwtr1 have interdependent mechanosensing functions in *** created and compared the skeletal phenotypes of control Pkd1^(flox/)+;Wwtr1^(flox/)+,Pkd1^(Oc-cKO),Wwtr1^(Oc-cKO),and Pkd1/Wwtr1^(Oc-cKO)mice to investigate genetic *** with an interaction between polycystins and Wwtr1 in bone in vivo,Pkd1/Wwtr1^(Oc-cKO)mice exhibited greater reductions of BMD and periosteal MAR than either Wwtr1Oc-cKOor Pkd1^(Oc-cKO)***-CT 3D image analysis indicated that the reduction in bone mass was due to greater loss in both trabecular bone volume and cortical bone thickness in Pkd1/Wwtr1Oc-cKO mice compared to either Pkd1Oc-cKOor Wwtr1^(Oc-cKO)***1/Wwtr1^(Oc-cKO)mice also displayed additive reductions in mechanosensing and osteogenic gene expression profiles in bone compared to Pkd1Oc-cKOor Wwtr1^(Oc-cKO)***,we found that Pkd1/Wwtr1^(Oc-cKO)mice exhibited impaired responses to tibia mechanical loading in vivo and attenuation of loadinduced mechanosensing gene expression compared to control ***,control mice treated with a small molecule mechanomimetic,MS2 that activates the polycystin complex resulted in marked increases in femoral BMD and periosteal MAR compared to vehicle *** contrast,Pkd1/Wwtr1^(Oc-cKO)mice were resistant to the anabolic effects of *** findings suggest that PC1 and Wwtr1 form an anabolic mechanotransduction signaling complex that mediates mechanical loading responses and serves as a potential novel therapeutic target for treating osteoporosis.

关键词： mec impaired additive

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Dapsone hypersensitivity syndrome

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Chinese Medical Journal 2023年第13期136卷 1560-1562页

作者： Qing Zhao Lele Sun Yonghu Sun dean Naisbitt Hong Liu Furen Zhang Shandong Provincial Hospital for Skin Diseases&Shandong Provincial Institute of Dermatology and Venereology Shandong First Medical University&Shandong Academy of Medical SciencesJinanShandong 250022China Department of Molecular and Clinical Pharmacology MRC Centre for Drug Safety ScienceUniversity of LiverpoolLiverpoolUK

Dapsone hypersensitivity syndrome(DHS)was first reported by Lowe and smith[1]in 1949 in Nigeria and was termed“dapsone syndrome”by Allday and Barnes[2]in *** is a drug-induced hypersensitivity syndrome(DIHS)caused by dapsone 404’-diaminodiphenylsulfone(DDS).DHS is characterized by fever,rash,lymphadenopathy,and hepatitis,which usually develop after patients receive DDS for 5 to 6 *** studies have estimated DHS prevalence and fatality rates of 1.4%and 9.9%,respectively.[3]Until recently,the“wait and see”approach was used for patients with suspected ***,we review recent developments in DHS research,focusing on its etiology,pathogenesis,diagnosis,and prevention,to make DDS a safer medication for most of the population through the prospective exclusion of susceptible patients before DDS administration.

关键词： DHS prevention diagnosis

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Accelerating material design with the generative toolkit for scientific discovery

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npj Computational Materials 2023年第1期9卷 1649-1654页

作者： Matteo Manica Jannis Born Joris Cadow Dimitrios Christofidellis Ashish Dave dean Clarke Yves Gaetan Nana Teukam Giorgio Giannone Samuel C.Hoffman Matthew Buchan Vijil Chenthamarakshan Timothy Donovan Hsiang Han Hsu Federico Zipoli Oliver Schilter Akihiro Kishimoto Lisa Hamada Inkit Padhi Karl Wehden Lauren McHugh Alexy Khrabrov Payel Das Seiji Takeda John R.smith IBM Research Europe-Zurich RüschlikonSwitzerland IBM Research-UK HursleyUK IBM Research-Yorktown Heights New YorkUSA IBM Research-Tokyo TokyoJapan IBM Research-Almaden San JoseUSA

With the growing availability of data within various scientific domains,generative models hold enormous potential to accelerate scientific *** harness powerful representations learned from datasets to speed up the formulation of novel hypotheses with the potential to impact material discovery *** present the Generative Toolkit for Scientific Discovery(GT4SD).This extensible open-source library enables scientists,developers,and researchers to train and use state-of-the-art generative models to accelerate scientific discovery focused on organic material design.

关键词： enable scientific formulation

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McLAREN 720S

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汽车与运动 2017年第6期 80-85,87-89页

作者： Stuart Gallagher dean smith 罗新雨

迈凯伦汽车已进入新篇章,全新一代Super Sports系列的首款车型已经亮相：720S720S将公司的设计语言向前推进至于这种进步是太快了还是不够快,就要看各位看官的口味了二年生症候。这就是迈凯轮用720S极力规避的问题。不仅仅是因为这款52... 详细信息

迈凯伦汽车已进入新篇章,全新一代Super Sports系列的首款车型已经亮相：720S720S将公司的设计语言向前推进至于这种进步是太快了还是不够快,就要看各位看官的口味了二年生症候。这就是迈凯轮用720S极力规避的问题。不仅仅是因为这款529kW的跑车是该公司第一款二代Super Series车款,650S的后继车型;它也是今后沃金工厂接下来5年内的15款新车的开发基础。而且是的,公司并没有引入任何SUV产品的计划。

关键词：迈凯轮凯伦开发基础首款 McLAREN 720S 设计语言

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675LT v P1

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汽车与运动 2018年第2期 60-67页

作者： DAN PROSSER ASTON PARROTT dean smith

几乎相同的性能,价格却差了十万八千里——675LT是否真的特别到足以让P1这样一款令人神经错乱的顶级跑车感到焦虑呢？那还是我们的＂2015年度车型＂评选的时候,已经是最后一天了,我们到了苏格兰,因为是英国的最北端,让人感觉是个无法的... 详细信息

几乎相同的性能,价格却差了十万八千里——675LT是否真的特别到足以让P1这样一款令人神经错乱的顶级跑车感到焦虑呢？那还是我们的＂2015年度车型＂评选的时候,已经是最后一天了,我们到了苏格兰,因为是英国的最北端,让人感觉是个无法的地方,再往北恐怕就要无天了。幸好老天还存在,在它的眷顾之下过去的三天一直是阳光明媚,但今天上午浓雾遮挡了周围的景物,拍摄的计划是告吹了。好在贴近地面的高度上能见度还不错,也就是说在路上驾车还是没问题的。

关键词：赛车车型品牌汽车运动

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HONDA CIVIC TYPE R

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汽车与运动 2017年第6期 90-93页

作者： Adam Towler dean smith 罗新雨

本田上一代思域Type R推出的十分滞后。这代反而来得十分同步,但它有怎样的变化呢？白色车漆,黑色饰条,红色logo,以及无可争议的钢炮市场最宽车体。你根本不需要我来告诉你这是全新本田思域Type R。通常我介绍到此就结束了,让你自由随... 详细信息

本田上一代思域Type R推出的十分滞后。这代反而来得十分同步,但它有怎样的变化呢？白色车漆,黑色饰条,红色logo,以及无可争议的钢炮市场最宽车体。你根本不需要我来告诉你这是全新本田思域Type R。通常我介绍到此就结束了,让你自由随心地理解它的外形。不过这次不行。老款上笨笨的、侧面线条有如整块石板相仿的比例外加那个极其生硬而且硕大的尾翼和其他空气动力套件实在相当有争议,有很多人都完全无法直视。

关键词：思域空气动力

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P1 GTR

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汽车与运动 2018年第2期 68-71页

作者： JETHRO BOVINGDON dean smith ASTON PARROTT

此前我们在Anglesey赛道测试过的最快的车是Radical RXC Turbo 500,圈速1分10秒5。P1 GTR还能再快些吗？但是要想表现英雄气概不是件容易的事不过不是因为这辆车令人恐惧,而是它的能力实在高强速度快到不合常理,技术极其先进,定位上超... 详细信息

此前我们在Anglesey赛道测试过的最快的车是Radical RXC Turbo 500,圈速1分10秒5。P1 GTR还能再快些吗？但是要想表现英雄气概不是件容易的事不过不是因为这辆车令人恐惧,而是它的能力实在高强速度快到不合常理,技术极其先进,定位上超出了一般的超级跑车——还有什么事能比接到这样一款车的试驾邀请更令人激动的吗？毕竟这样的经历能让你一窥比天价的单座赛车略＂低＂的顶级跑车这种神一般的存在。但是往往令人扫兴的是,邀请方只允许你在赛道上开三圈,而这条赛道你可能从来没跑过。他们让你能尝到那款车的味道,但你要想大快朵颐是绝无可能的。但今天的情况不同了。其实不单单是今天。

关键词：赛车车型品牌汽车运动

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M & M?

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汽车与运动 2014年第6期 100-104页

作者： Dan Prosser dean smith 王兴宇

M235i这辆车带有"M"标识,但BMW却没有按照M家族命名体系给它"正名"。这辆双门轿跑车是否还具备纯正的"M"血统?为此,我们特地找到一辆跟他售价相近的二手E92 M3,通过对比来验证一下它的成色如何费劲干辛万苦,我们赶在日出之前到达了布雷... 详细信息

M235i这辆车带有"M"标识,但BMW却没有按照M家族命名体系给它"正名"。这辆双门轿跑车是否还具备纯正的"M"血统?为此,我们特地找到一辆跟他售价相近的二手E92 M3,通过对比来验证一下它的成色如何费劲干辛万苦,我们赶在日出之前到达了布雷肯山顶,但是事情往往不会一帆风顺——大雨在我们之前来到了这里。东方一大片乌云将我们希冀的一轮红日遮了个严实,更别提那夹杂着冰陵的刺骨寒风了。在这样的天气下,我们惟一能做的,就是躲在车内以免被冻伤。在M235i车内暖风的照料下,我凝视着车窗外的那辆E92 M3,开始从久远的记忆中梳理出关于它的点点线索。隆起的引擎盖。

关键词：一轮红日日出之前购车计划做事方式给你限滑差速器手动变速器从车抓地力冰棱

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Shear stress effect on endothelial nitric oxide synthase in cultured human umbilical vein endothelial cells

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Journal of Biomedical Science and Engineering 2013年第10期6卷 982-986页

作者： Qiuying Gu dean O. smith Karlene A. Hoo Departments of Biological Sciences Texas Tech University Lubbock USA Departments of Chemical Engineering Texas Tech University Lubbock USA

Background: Low shear stress caused by disturbed or turbulent flow at arterial branch points is known to associate with atherosclerosis. However, shear stress at the venous valve location and its association with deep vein thrombosis are less understood due to the complex and poorly understood bi-directional flow in the valve pocket region. We investigated how venous endothelial cells respond to flow shear stress around the venous valve region using a novel in vitro system that mimics venous flow. Results: Human umbilical vein EAhy. 926 cells were cultured on a flexible silastic membrane that mimicked venous tissue. Confluent cells were exposed to sinusoidal uni-and bi-directional pulsatile shear stress (0.1 to 1 dyne/cm2) for up to 6 h. Western-blot analyses indicated that endothelial nitric oxide (eNOS) expression levels decreased regardless of all tested flow patterns, stress magnitude, and shearing time. In contrast, the expression levels of inhibitor of κB (kappa B) and α (alpha)-tubulin were unaffected by the shear stress. Conclusions: Our results indicate that shear stress causes a decrease specifically in eNOS expression, suggesting that it may play a significant role in regulating inflammation related protein expression in endothelial cells.

关键词： Shear Stress Endothelial Cells Endothelial Nitric Oxide Synthase Inflammation Thrombosis

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ASSISTING THE AUSTRALIAN FURNITURE MANUFACTURING INDUSTRY USING QFD: VOICE OF THE CUSTOMER COLLECTION AND PREPARATION

ASSISTING THE AUSTRALIAN FURNITURE MANUFACTURING INDUSTRY US...

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The 11th Annual Conference of Asia Pacific Decision Sciences Institute

作者： dean W.K.smith Robert A.Hunt CRC Wood Innovations The University of Melbourne ParkvilleAustralia Graduate School of Management Macquarie University SydneyAustralia Centre for Management Innovation and Technology Graduate School of Management Macquarie University Sydney Australia

＜正＞The Australian furniture manufacturing industry has experienced a substantial loss of local market share due to globalisation. A typical response for domestic firms encountering intense global competition is to seek export markets that yield competitive advantages. However, with a lack of export experience and small average firm size, the challenges faced by Australian furniture producers to enter foreign markets are great. Being successful in foreign markets requires a strategic approach to advanced understanding of the needs of the target market and how to meet those needs. As a process specifically designed to accomplish this, quality function deployment （QFD） has the potential to provide a formalised framework for the Australian furniture manufacturing industry. The input to QFD is the Voice of the Customer （VOC）. This paper uses a case study to demonstrate the VOC phase of QFD to Australian furniture producers. A structured list of customer needs is developed and then a quantitative customer survey is conducted on German furniture producers to ascertain and importance rank needs when purchasing wooden furniture components. These needs are structured using an affinity and tree diagram. The resulting structured and prioritised needs are analysed for input to the house of quality （HOQ） for conversion into quantified product specifications.

关键词： Quality Function Deployment (QFD) Voice of the Customer(VOC) Wood Industry

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