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Intervertebral disc degeneration is rescued by TGFβ/BMP signaling modulation in an ex vivo flamin B mouse model

Bone Research 2022年第3期10卷 524-535页

作者： Jennifer Zieba Kimberly N.Forlenza kelly heard Jorge H.Martin Michaela Bosakova Daniel H.Cohn Stephen P.Robertson Pavel Krejci Deborah Krakow Department of Orthopedic Surgery Los AngelesCA 90095USA Department of Biology Faculty of MedicineMasaryk University62500 BrnoCzech Republic International Clinical Research Center St.Anne’s University Hospital65691 BrnoCzech Republic Institute of Animal Physiology and Genetics Czech Academy of Sciences60200 BrnoCzech Republic Department of Molecular Cell and Developmental Biology University of CaliforniaLos AngelesLos AngelesCA 90095USA Department of Women’s and Children’s Health Dunedin School of MedicineUniversity of OtagoDunedinNew Zealand Department of Human Genetics Los AngelesCA 90095USA Department of Obstetrics and Gynecology Los AngelesCA 90095USA Department of Pediatrics David Geffen School of Medicine at University of CaliforniaLos AngelesLos AngelesCA 90095USA

Spondylocarpotarsal syndrome(SCT) is a rare musculoskeletal disorder characterized by short stature and vertebral, carpal, and tarsal fusions resulting from biallelic nonsense mutations in the gene encoding filamin B(FLNB). Utilizing a FLNB knockout mouse,we showed that the vertebral fusions in SCT evolved from intervertebral disc(IVD) degeneration and ossification of the annulus fibrosus(AF), eventually leading to full trabecular bone formation. This resulted from alterations in the TGFβ/BMP signaling pathway that included increased canonical TGFβ and noncanonical BMP signaling. In this study, the role of FLNB in the TGFβ/BMP pathway was elucidated using in vitro, in vivo, and ex vivo treatment methodologies. The data demonstrated that FLNB interacts with inhibitory Smads 6 and 7(i-Smads) to regulate TGFβ/BMP signaling and that loss of FLNB produces increased TGFβ receptor activity and decreased Smad 1 ubiquitination. Through the use of small molecule inhibitors in an ex vivo spine model, TGFβ/BMP signaling was modulated to design a targeted treatment for SCT and disc degeneration. Inhibition of canonical and noncanonical TGFβ/BMP pathway activity restored Flnb-/-IVD morphology. These most effective improvements resulted from specific inhibition of TGFβand p38 signaling activation. FLNB acts as a bridge for TGFβ/BMP signaling crosstalk through i-Smads and is key for the critical balance in TGFβ/BMP signaling that maintains the IVD. These findings further our understanding of IVD biology and reveal new molecular targets for disc degeneration as well as congenital vertebral fusion disorders.

关键词： TGFβ vivo BMP treatment

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Clearing the air: discrepant policy and practice concerning neonatal cannabinoid exposure

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World Journal of Pediatrics 2017年第1期13卷 5-7页

作者： James Patrick Ronayne Anthony heard James William Antoon Division of General Pediatrics and Adolescent Medicine Children's HospitalUniversity of Illinois Hospital and Health Sciences SystemChicagoIL 60612USA Department of Health Social Work University of Illinois Hospital and Health Sciences SystemChicagoIL 60612USA

In the current medical environment,efforts to improve detection rates and *** for infants with neonatal abstinence syndrome (NAS),a condition typically associated with opiates,are being renewed and strengthened.[1] We laud recent legislation such as the Protecting Our Infants Act of 2015,as it is well established that alignment between research,policv and practice resuhs in better population health.

关键词： Environment Exposure Population health

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Assessment of toxicology knowledge in the fourth-year medical students:Three years of data

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World Journal of Emergency Medicine 2018年第3期9卷 191-194页

作者： Jennie Buchanan Daniel Windels Jeffrey Druck Kennon heard Department of Emergency Medicine University of Colorado School of Medicine AuroraDenverCO 80204USA Rocky Mountain Poison and Drug Center-Denver Health&Hospital Authority DenverDenverCO 80204USA Saint Anthony Hospital APEX Emergency GroupLakewoodColorado 80228USA

BACKGROUND:Pharmacology and toxicology are core content knowledge for *** students should demonstrate understanding of general pharmacology and basic treatment of *** objective of this study was to measure the knowledge of the 4th-year medical students(MS4)on these topics over 3 ***:A multiple-choice exam(15 questions)was administered to MS4 students in spring of 2010,2011,and *** were developed by medical toxicologists to evaluate basic knowledge in three areas:pharmacologic effects(PE),treatment of poisoning(TOP),and pharmacokinetics(PK).The students were grouped by intended specialtiesinto pharmacologic intense(anesthesia,emergency medicine,internal medicine,pediatrics,and psychiatry),less pharmacologic intense specialties(dermatology,OB/GYN,ophthalmology,pathology,physical medicine and rehabilitation,radiology,and surgery)and by completion of a pharmacology or toxicology *** group scores were compared using ***:Totally 332 of 401(83%)students completed the *** scores were stable over the three years,higher for students completing a toxicology rotation and for students entering a pharmacologically intense ***:The external validity is limited to a single medical school with incomplete participation and content was limited by the survey *** results over the three-year period and correlation of performance with completing a toxicology rotation and intent to enter a pharmacology intensive specialty suggest this survey may correlate with toxicology *** of required core courses focused on toxicology may improve core content knowledge in fourth year medical students.

关键词： Medical student Education Toxicology Knowledge

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A taste for honey

A taste for honey

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作者： H.F. heard

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The View from South Africa:Influence beyond Its Numbers

The View from South Africa:Influence beyond Its Numbers

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北京论坛（2011）文明的和谐与共同繁荣--传统与现代、变革与转型

作者： Anthony Hazlitt heard President Office South Africa

I speak as a born-and-bred white South African. By definition, I am part of the minority group in the now black-led democracy established in 1994 by that icon of our age, Nelson Mandela. I have had 40 years' experience in journalism, 32 of those on the oldest-established daily newspaper in South Africa, the Cape Times, Cape Town (16 as the Editor, 1971-1987). Then,

关键词： The View from South Africa:Influence beyond Its Numbers

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Microvascular response to transfusion in elective spine surgery

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世界骨科杂志：英文版 2017年第1期8卷 49-56页

作者： J Matthias Walz Ottokar Stundner Federico P Girardi Bruce A Barton Aimee R Koll-Desrosiers Stephen O heard Stavros G Memtsoudis Department of Anesthesi-ology and Perioperative Medicine UMass Memorial Healthcare Department of Anesthesiology Hospital for Special SurgeryWeill Cornell Medical Center Department of Anesthesiology PerioperativeMedicine and Intensive Care MedicineParacelsus Medical University Department of Orthopedic Surgery Hospital for Special SurgeryWeill Cornell Medical Center Department of Quantitative Health Sciences University of Massachusetts Medical School

AIM To investigate the microvascular(skeletal muscle tissue oxygenation; SmO_2) response to transfusion in patients undergoing elective complex spine *** After IRB approval and written informed consent, 20 patients aged 18 to 85 years of age undergoing > 3level anterior and posterior spine fusion surgery were enrolled in the study. Patients were followed throughout the operative procedure, and for 12 h postoperatively. In addition to standard American Society of Anesthesiologists monitors, invasive measurements including central venous pressure, continual analysis of stroke volume(SV), cardiac output(CO), cardiac index(CI), and stroke volume variability(SVV) was performed. To measure skeletal muscle oxygen saturation(SmO_2) during the study period, a non-invasive adhesive skin sensor based on Near Infrared Spectroscopy was placed over the deltoid muscle for continuous recording of optical spectra. All administration of fluids and blood products followed standard procedures at the Hospital for Special Surgery, without deviation from usual standards of care at the discretion of the Attending Anesthesiologist based on individual patient comorbidities, hemodynamic status, and laboratory data. Time stamps were collected for administration of colloids and blood products, to allow for analysis of SmO_2 immediately before, during, and after administration of these fluids, and to allow for analysis of hemodynamic data around the same time points. Hemodynamic and oxygenation variables were collected continuously throughout the surgery, including heart rate, blood pressure, mean arterial pressure, SV, CO, CI, SVV, and SmO_2. Bivariate analyses were conducted to examine the potential associations between the outcome of interest, SmO_2, and each hemodynamic parameter measured using Pearson's correlation coeffi-cient, both for the overall cohort and within-patients individually. The association between receipt of packed red blood cells and SmO_2 was performed by runni

关键词： Transfusion Complex spine surgery Near infrared spectroscopy Microvascular blood flow Hemodynamic monitoring

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智能机器人需要机器视觉

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今日电子 2015年第8期 31-32页

作者： Carlton heard 美国国家仪器公司

机器人已经不再是科幻电影中的人物,而是成为我们日常生活中日益根深蒂固的一部分。除了工厂车间外,机器人在消费者领域的应用也在日益扩大。但是有许多因素正在阻碍机器人的普及,其中一个主要因素是：大多数机器人都是＂瞎子＂。它们... 详细信息

机器人已经不再是科幻电影中的人物,而是成为我们日常生活中日益根深蒂固的一部分。除了工厂车间外,机器人在消费者领域的应用也在日益扩大。但是有许多因素正在阻碍机器人的普及,其中一个主要因素是：大多数机器人都是＂瞎子＂。它们对周围环境完全没有感知能力或只有很低程度的感知能力,而这一能力却是我们大多数人每天习以为常的基本能力。

关键词：机器人系统机器视觉科幻电影智能机器人周围环境移动机器人深度信息图像处理算法立体视觉系统机器人应用

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SCE公司的水平连铸

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湘钢译丛 1993年第3期 6-18,23页

作者： heard,RA 唐勇

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数字扫描变换器

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电讯技术 1984年第2期 37-43页

作者： J.L.heard 陈世忠

本文介绍一种视频扫描变换器,这种变换器从某一信号源(如雷达接收机)在任一给定扫描方式(如PPI)下,以低的雷达扫描速率接收数字化的数据后,将该数据的格式转换成适于在CRT上显示的标准电视光栅或其它直角光栅体制,再以无闪烁的速率显示... 详细信息

本文介绍一种视频扫描变换器,这种变换器从某一信号源(如雷达接收机)在任一给定扫描方式(如PPI)下,以低的雷达扫描速率接收数字化的数据后,将该数据的格式转换成适于在CRT上显示的标准电视光栅或其它直角光栅体制,再以无闪烁的速率显示出来。由于采用了RAM(随机存取存贮器),因此它比迄今为止使用的其它数字扫描变换器都更加灵活与经济。视频数据格式的转换是通过数据向RAM中写入时产生适当的写入地址来完成的,而该写入地址则正好反映出数据本来的格式与显示的格式之间的函数关系。这样在读出时,只要用一个简单的计数器以需要的速率对RAM进行直角寻址就可以了。

关键词：数字扫描变换器平面位置显示器随机存取存贮器

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油矿营地又热又脏但有WiFi网络便足矣

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商业周刊（中文版） 2018年第21期 30-31页

作者： Rachel Adams-heard 永年(译)

在得克萨斯州戈德史密斯附近60多亩几乎没有一棵树的平地上，除了泥土、豆科灌木和山艾树之外，基本没什么可看的东西。Aries Residence Suites酒店在这里经营着一处居住营地，供流动中的石油工人们使用。

关键词：油矿网络得克萨斯州石油工人史密斯居住酒店

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