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Dysfunctional stem and progenitor cells impair fracture healing with age

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World Journal of Stem Cells 2019年第6期11卷 281-296页

作者： Diane R wagner Sonali Karnik Zachary J Gunderson Jeffery J Nielsen Alanna Fennimore Hunter J Promer Jonathan W lowery M Terry loghmani Philip S low Todd O McKinley Melissa A Kacena Matthias Clauss Jiliang li Department of Mechanical and Energy Engineering Indiana University-Purdue University IndianapolisIndianapolisIN 46202United States Department of Orthopaedic Surgery Indiana University School of MedicineIndianapolisIN 46202United States Department of Medicinal Chemistry and Molecular Pharmacology Purdue UniversityWest LafayetteIN 47907United States Department of Physical Therapy Indiana University- Purdue University IndianapolisIndianapolisIN 46202United States Division of Biomedical Science Marian University College of Osteopathic MedicineIndianapolisIN 46222United States Department of Chemistry Purdue UniversityWest LafayetteIN 47907 United States Richard l. Roudebush VA Medical Center IndianapolisIN 46202United States Department of Medicine Indiana University School of MedicineIndianapolisIN 46202United States Department of Biology Indiana University-Purdue University IndianapolisIndianapolisIN 46202United States

Successful fracture healing requires the simultaneous regeneration of both the bone and vasculature;mesenchymal stem cells (MSCs) are directed to replace the bone tissue, while endothelial progenitor cells (EPCs) form the new vasculature that supplies blood to the fracture site. In the elderly, the healing process is slowed, partly due to decreased regenerative function of these stem and progenitor cells. MSCs from older individuals are impaired with regard to cell number, proliferative capacity, ability to migrate, and osteochondrogenic differentiation potential. The proliferation, migration and function of EPCs are also compromised with advanced age. Although the reasons for cellular dysfunction with age are complex and multidimensional, reduced expression of growth factors, accumulation of oxidative damage from reactive oxygen species, and altered signaling of the Sirtuin-1 pathway are contributing factors to aging at the cellular level of both MSCs and EPCs. Because of these geriatric-specific issues, effective treatment for fracture repair may require new therapeutic techniques to restore cellular function. Some suggested directions for potential treatments include cellular therapies, pharmacological agents, treatments targeting age-related molecular mechanisms, and physical therapeutics. Advanced age is the primary risk factor for a fracture, due to the low bone mass and inferior bone quality associated with aging;a better understanding of the dysfunctional behavior of the aging cell will provide a foundation for new treatments to decrease healing time and reduce the development of complications during the extended recovery from fracture healing in the elderly.

关键词： Fracture healing Aging Bone Angiogenesis Mesenchymal stem cells Endothelial progenitor cells

Unexpectedly low δ^(13)C in leaves,branches,stems and roots of three acacia species growing in hyper-arid environments

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Journal of Plant Ecology 2021年第1期14卷 117-131页

作者： Daphna Uni Elli Groner Elaine Soloway Amgad Hjazin Spencer Johnswick Gidon Winters Efrat Sheffer Ido Rog Yael wagner Tamir Klein Department of Plant and Environmental Sciences Weizmann Institute of ScienceRehovotIsrael The Dead Sea-Arava Science Center Tamar Regional CouncilNeve Zohar 86910Israel Institute of Plant Sciences and Genetic in Agriculture The Robert H.Smith Faculty of AgricultureFood and EnvironmentThe Hebrew University of JerusalemRehovotIsrael Arava Institute for Environmental Studies Kibbutz KeturaIsrael

Aims In plant eco-physiology,less negative(enriched)carbon 13(^(13)C)in the leaves indicates conditions of reducing leaf gas exchange through stomata,*** *** addition,^(13)C is expected to be less negative in non-photosynthetic tissues as compared with ***,these relationships inδ^(13)C from leaves(photosynthetic organs)to branches,stems and roots(non-photosynthetic organs)are rarely tested across multiple closely related tree species,multiple compartments,or in trees growing under extreme heat and *** We measured leaf-to-root^(13)C in three closely related desert acacia species(Acacia tortilis,*** and ***).We measuredδ^(13)C in leaf tissues from mature trees in southern *** parallel,a 7-year irrigation experiment with 0.5,1.0 or 4.0 l day1 was conducted in an experimental *** the end of the experiment,growth parameters andδ^(13)C were measured in leaves,branches,stems and *** Findings Theδ^(13)C in leaf tissues sampled from mature trees was ca.-27‰,far more depleted than expected from a desert tree growing in one of the Earth's driest and hottest *** acacia species and compartments,δ^(13)C was not enriched at all irrigation levels(-28‰to ca.-27‰),confirming our measurements in the mature *** compartments,leafδ^(13)C was unexpectedly similar to branch and rootδ^(13)C,and surprisingly,even less negative than stemδ^(13)*** highly depleted leafδ^(13)C suggests that these trees have high stomatai gas exchange,despite growing in extremely dry *** lack ofδ^(13)C enrichment in nonphotosynthetic tissues might be related to the seasonal coupling of growth of leaves and heterotrophic tissues.

关键词： stable isotope δ^(13)C enrichment desert tree drought resistance Acacia raddiana Acacia tortilis

D-galactosamine based canine acute liver failure model

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Hepatobiliary & Pancreatic Diseases International 2002年第3期1卷 354-367页

作者： JohnF.PatzerⅡ GeoffreyD.Block AjaiKhannaErnestoMolmenti DavidGerber DavidJ.Kramer Victorl.Scott ShushmaAggarwal RobertA.wagner Melissal.Fulmer BruceP.Amiot GeorgeV.Mazariegos the Department of Surgery Thomas E Starzl Transplantation Institute Department of Chemical Engineering McGowan Center for Artificial Organ Development the Department of Surgery Thomas E Starzl Transplantation Institute the Department of Surgery Thomas E Starzl Transplantation Institute Department of Anesthesiology Department of Anesthesiology Department of laboratory Animal Resources Excorp Medical Inc. Oakdale MN USA the Department of Surgery Thomas E Starzl Tramsplantation Institute

Background: Appropriate preclinical evaluation of a bioartificial liver assist device (BAl) demands a large animal model, as presented here, that demon- strates many of the clinical features of acute liver failure and that is suitable for clinical qualitative and quantitative evaluation of the BAl. A lethal canine liver failure model of acute hepatic failure that re- moves many of the artifacts evidenced in prior canine models is presented. Methods: Six male hounds, 24-30 kg, under isoflu- rane anesthesia, were administered 1.5 g/kg D- galactosamine intravenously. Canine supportive care followed a well-defined management protocol that was guided by electrolyte and invasive monitoring consisting of arterial pressure, central venous pres- sure, extradural intracranial pressure (ICP), pul- monary artery pressure, and end-tidal CO_2. The animals were treated until death-equivalent, defined as inability to sustain systolic blood pressure>80 mmHg for 20 minutes despite maximal fluids and 20 μg·kg^(-1)·min^(-1) dopamine infusion. Results: The mean survival time was 43.7±4.6 hours (mean±SE). All animals showed evidence of progressive liver failure characterized by increasing liver enzymes (aspartate transaminase from 26 to 5977 IU/l; alanine transaminase from 32 to 9740 IU/l), bilirubin (0.25 to 1.30 mg/dl), ammonia (19. 8 to 85. 3 μmol/l), and coagulopathy (pro- thrombin time from 8.7 to 46 s). Increased lability and elevations in intracranial pressures were ob- served. All animals were refractory to maintenance of cerebral perfusion pressure even with only mode- rately elevated intracranial pressure. Severe neuro- logic obtundation, seen in 2 of 6 animals, was associ- ated with elevations of ICP above 50 mmHg. Post- mortem liver histology showed evidence of massive hepatic necrosis. Postmortem blood and ascites mi- crobial growth was consistent with possible transloca- tion of intestinal microbes. Conclusions: The improved lethal canine liver failure model presented here

关键词： bioartificial liver acute liver failure canine model

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微功率晶体管逻辑电路的静态性能和动态性能

计算机研究与发展 1965年第7期 26-30页

作者： J.D.Meindl l.F.wagner 石国华郑鹏洲

对微功率晶体管的基本要求是:1)结的反向电流小于最小的工作电流;2)在最小工作电流时,要求有适用的电流增益;3)为提高开关速度,要求结电容小。改进的直接耦合晶体管逻辑电路、二极管晶体管逻辑电路和晶体管晶体管逻辑电路的微功率性能... 详细信息

对微功率晶体管的基本要求是:1)结的反向电流小于最小的工作电流;2)在最小工作电流时,要求有适用的电流增益;3)为提高开关速度,要求结电容小。改进的直接耦合晶体管逻辑电路、二极管晶体管逻辑电路和晶体管晶体管逻辑电路的微功率性能足以满足很多轻便型设备的现在和将来的要求。线路的正常工作温度范围、逻辑能力和容许抗扰度之间并不互相矛盾。有时需要稍微降低一些稳定界限,不过由于线路运用于微功率范围内,这种降低是容许的。对许多轻便型设备来说,在微功率晶体管电路中不可避免的会大大降低工作速度,但是,由于音频节拍频率已经够用,所以这样还是可以的。

关键词：微功率数字电路轻便型反向电流增益晶体管半导体三极管

CdS—CuGaS2异质二极管的绿色场致发光

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发光学报 1974年第1期 40-42页

作者： Sigurd wagner ,J.l.Shay ,B.Tell ,吕安德

用气相淀积方法,在P型CuGaS2上外延n型CdS,制成了异质二极管。典型的二极管在正向偏压下发绿光,外部量子效率在77°K时为0.1％,在室温时为0.001％。辐射复合是由于电子注入到CuGaS2中引起的。

关键词：二极管场致发光直流电流电致发光 CuGaS2 发光光谱 CdS 异质

时间、剂量和反转时间对基于MRI测定急性心肌梗死面积的影响:延迟造影增强

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世界核心医学期刊文摘（心脏病学分册） 2006年第7期2卷 55-56页

作者： wagner A. MahrholdtH. Thomson l. R.M. Judd 马超 Duke Cardiovascular MR Center Durham NC United States Dr.

Objectives: This study sought to investigate the influence of time, dose, and inversion time(TI) and their interactions on myocardial infarct size measurements to establish the foundation for a standardized protocol for multicenter trials. Background: There is growing interest in using magnetic resonance imaging(MRI) infarct size measurements as an end point in clinical trials. However, no standardized protocol exists, and there are limited data concerning the effects of time, contrast agent dose, and TI. Methods: First, we determined the influence of postcontrast imaging time(5 to 40 min), contrast agent dose(0.1 vs. 0.2 mmol/kg), TI, and their interactions in an animal model(n=14). Second, we tested whether the findings of the animal study apply to patients and are generalizable. Therefore, we retested the diagnostic window in a multicenter study. A total of 48 patients with first acute myocardial infarction(AMI) from three centers were imaged twice(5 and 30 min) after injection of 0.15 mmol/kg gadolinium diethylenetriamine-pentaacetate using an adjusted TI. Results: The animal study showed that the infarct size is independent of time and dose(p=0.9 and p=0.16, respectively) using an adjusted TI. Using a fixed TI, however, infarct size is a function of time and dose(p=0.0001 and p=0.01, respectively). The multicenter study showed that MRI 1(16.9±12%of left ventricle) was not statistically different from MRI 2(16.4±12%of left ventricle, p=NS)with no difference between sites(p=NS). Conclusions: The AMI size can be measured with MRI using a contrast dose between 0.1 and 0.2 mmol/kg and a time window of 5 to 30 min after contrast administration, provided that the TI is adjusted.

关键词：急性心肌梗死 MRI 反转时间磁共振成像乙酸钆左心室造影剂窗口期多中心试验动物模型

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Massive Pericardial Effusion as the First Manifestation of Hypothyroidism in a Male Patient

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Journal of Pharmacy and Pharmacology 2018年第4期6卷 420-424页

作者： livia Maria Carvalho Costa Flavia lunardelli Negreiros de Carvalho wagner leao leite Tostes General Medicine Hospital Geral de Roraima (HGR) Boa Vista 69305455 Brazil Residency Training Program in Anesthesiology Universidade Federal de Roraima (UFRR) Boa Vista 693100000 Brazil Department of Cardiology Hospital Geral de Roraima (HGR) Boa Vista 69305455 Brazil

This article intends to report a rare case of massive pericardial effusion as the first manifestation of hypothyroidism. A 45-year-old male patient, accompanied by a cardiology department, suddenly started to present signs of dyspnea and tiredness. He was submitted to an echocardiogram and diagnosed with dilated cardiomyopathy associated with a moderate pericardial effusion and low ejection of fraction. The laboratory tests showed elevated TSH levels （13.20 mIU/l）, what leads to the hypothyroidism diagnose and enable to start the treatment with levothyroxine. The patient has not followed correctly the treatment, reason why he has not showed any improves. He was admitted in the hospital to cardiology monitoring and the chest radiography confirmed an intense pericardial effusion. Then, the patient was submitted to the pericardiocentesis procedure, which was capable of remove the pericardial fluid for laboratory analysis and fragment of the pericardial sac for neoplastic cell research. After the hospital discharge, he was maintained in outpatient follow-up, when showed an important improvement in the clinical state.

关键词： Pericardial effusion dilated cardiomyopathy hypothyroidism thyroxine pericardiocentesis.

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磁敏感加权成像对椎体骨折的评估

国际医学放射学杂志 2018年第4期 492-493页

作者： S.M.Bker l.C.Adams Y.Y.Bender M.wagner T.Diekhoff E.Fallenberg 陈圣妮 Department of Radiology Charité

目的以CT为参考标准,检测MR磁敏感加权成像（s MRI）和常规序列评估椎体骨折的诊断性能。方法这项前瞻性研究共纳入39例病人行MRI T1/T2/快速反转恢复（TIRM）和s MRI扫描,共发现88个椎体骨折（45个已愈合,43个未愈合）。所有骨折均以C... 详细信息

目的以CT为参考标准,检测MR磁敏感加权成像（s MRI）和常规序列评估椎体骨折的诊断性能。方法这项前瞻性研究共纳入39例病人行MRI T1/T2/快速反转恢复（TIRM）和s MRI扫描,共发现88个椎体骨折（45个已愈合,43个未愈合）。所有骨折均以CT作为参考标准。评估所有序列中椎体后部皮质移位程度和高度,有无骨折线及皮质断裂。计算MRI和CT之间的敏感度、特异度和一致性。结果相比T1/T2/TIRM序列,sMRI显示椎体后部皮质受累（敏感度98%,特异度100%）、骨折线（86%/99%）和皮质断裂（93%/100%）的诊断准确度最高。对椎体后部皮质移位和高度的评价,sMRI与CT结果的一致性最接近（R2=0.96;95%CI:-0.92～0.89/R2=0.97;95%CI:-1.67～1.23）,观察者间一致性也最接近（R2=0.97;95%CI:-0.71～1.01）。结论 sMRI能够可靠地评估椎体骨折时椎体后部皮质移位和高度改变、皮质断裂以及骨折线,较常规MRI准确性更高,尤其是对未愈合的骨折椎体。

关键词：磁敏感加权成像 CT 椎体骨折 MRI

Components Qualification for the Safe Operation of Nuclear Power Plants

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Journal of Energy and Power Engineering 2016年第10期10卷 581-590页

作者： Holger Schmidt Martin Beetz Ingo Ganzmann Achim Beisiegel Thomas wagner Christian Bonneau Darryl Gordon Sun Jing AREVA GmbH-Thermal Hydraulics and Components Testing Paul-Gossenstr 100 Erlangen 91052 Germany ARE VA GmbH-Thermal Hydraulics and Components Testing Seligenstadter Strasse 100 Karlstein 63791 Germany AREVA SAS-Thermal Hydraulics and Components Testing 30 boulevard de l'Industrie Le Creusot 71205 France ARE VA Inc.-Thermal Hydraulics and Components Testing 3315 Old Forest Road Lynchburg VA 24501 USA Keysur International F11 Tower A Millennium Plaza No. 72 Beijing 100037 China

AREVA operates a world-wide unique thermal hydraulic platform to ensure high safety standards in the nuclear industries. This platform is operated as an accredited test and inspection body according to ISO 17025 and 17020 to grant a high and independently confmned quality standard. The accreditation also ensures the independency of the organization and confidentiality to the individual stakeholders, for example research centers, utilities, components suppliers, engineering companies and vendors. Especially for nuclear power plants, it is very relevant to consider that reliability depends on the integrity of its components during its life time-from design through construction, operation and maintenance. For example, a typical NPP （nuclear power plant） has 1,000 to 2,000 large valves and 7,500 to 12,500 small valves, of which about 200 to 400 are designated Safety Class 1. The qualification of these Safety Class 1 components is relevant for reactor new builds but also for installed plants. This paper explains newly established qualification tasks, the corresponding testing infrastructure, and the state of the art of testing technology. By way of example, the paper describes the program and possible sequence of qualifying NPP safety-related components.

关键词： Components testing nuclear qualification thermal hydraulics testing nuclear safety