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β-catenin mRNA encapsulated in SM-102 lipid nanoparticles enhances bone formation in a murine tibia fracture repair model

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Bioactive Materials 2024年第9期39卷 273-286页

作者： Anna Laura Nelson Chiara Mancino Xueqin Gao Joshua AChoe Laura Chubb Katherine Williams Molly Czachor ralph Marcucio Francesca Taraballi john P.Cooke johnny Huard Chelsea Bahney Nicole Ehrhart Steadman Philippon Research Institute(SPRI) Center for Regenerative and Personalized MedicineVailCOUSA Houston Methodist Research Institute Center for Musculoskeletal RegenerationHouston TXUSA University of Wisconsin-Madison Department of Orthopedics and RehabilitationDepartment of Biomedical EngineeringMedical Scientist Training ProgramMadisonWIUSA Colorado State University School of Biomedical EngineeringFort Collins COUSA Colorado State University Department of Clinical SciencesFort Collins COUSA Colorado State University Department of MicrobiologyImmunologyand PathologyFort CollinsCOUSA Houston Methodist Research Institute Center for RNA TherapeuticsDepartment of Cardiovascular SciencesHoustonTXUSA University of Californi1 San Francisco(UCSF)Orthopaedic Trauma InstituteSan FranciscoCAUSA

Fractures continue to be a global economic burden as there are currently no osteoanabolic drugs approved to accelerate fracture *** this study,we aimed to develop an osteoanabolic therapy which activates the Wnt/β-catenin pathway,a molecular driver of endochondral *** hypothesize that using an mRNAbased therapeutic encodingβ-catenin could promote cartilage to bone transformation formation by activating the canonical Wnt signaling pathway in *** optimize a delivery platform built on recent advancements in liposomal technologies,two FDA-approved ionizable phospholipids,DLin-MC3-DMA(MC3)and SM-102,were used to fabricate unique ionizable lipid nanoparticle(LNP)formulations and then tested for transfection efficacy both in vitro and in a murine tibia fracture *** firefly luciferase mRNA as a reporter gene to track and quantify transfection,SM-102 LNPs showed enhanced transfection efficacy in vitro and prolonged transfection,minimal fracture interference and no localized inflammatory response in vivo over MC3 *** generatedβ-cateninGOF mRNA encapsulated in SM-102 LNPs(SM-102-β-cateninGOF mRNA)showed bioactivity in vitro through upregulation of downstream canonical Wnt genes,axin2 and *** testing SM-102-β-cateninGOF mRNA therapeutic in a murine tibia fracture model,histomorphometric analysis showed increased bone and decreased cartilage composition with the 45μg concentration at 2 weeks post-fracture.μCT testing confirmed that SM-102-β-cateninGOF mRNA promoted bone formation in vivo,revealing significantly more bone volume over total volume in the 45μg ***,we generated a novel mRNA-based therapeutic encoding aβ-catenin mRNA and optimized an SM-102-based LNP to maximize transfection efficacy with a localized delivery.

关键词： Gene therapy Fracture healing Lipid nanoparticles mRNA Canonical Wnt

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QT-GWAS:A novel method for unveiling biosynthetic loci affecting qualitative metabolic traits

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Molecular Plant 2023年第7期16卷 1212-1227页

作者： Marlies Brouckaert Meng Peng RenéHofer lias El Houari Chiarina Darrah Veronique Storme Yvan Saeys Ruben Vanholme Geert Goeminne Vitaliy I.Timokhin john ralph Kris Morreel Wout Boerjan Ghent University Department of Plant Biotechnology and Bioinformatics9000 GhentBelgium VIB Center for Plant Systems Biology 9052 GhentBelgium Ghent University Department of Applied MathematicsComputer Science and Statistics9000 GhentBelgium VIB Center for Inflammation Research 9052 GhentBelgium vIB Metabolomics Core 9052 GhentBelgium Department of Biochemistry and US Department of Energy Great Lakes Bioenergy Research CenterWisconsin Energy InstituteUniversity of Wisconsin-MadisonMadisonWI53706USA Ghent University Department of Applied MathematicsComputer Science and StatisticsGhentBelgium ViB Center for Inflammation Research GhentBelgium BioNTech SE MainzRhineland-PalatinateGermany Eunomia Research&Consulting BristolUK VIB Agro-incubator NeveleBelgium Research Institute for Chromatography KortrijkBelgium

Although the plant kingdom provides an enormous diversity of metabolites with potentially beneficial applications for humankind,a large fraction of these metabolites and their biosynthetic pathways remain *** metabolite structures and their biosynthetic pathways is key to gaining biological understanding andto allow metabolic *** orderto retrieve novel biosynthetic genes involved in specialized metabolism,we developed a novel untargeted method designated as qualitative trait GWAs(QT-GWAS)that subjects qualitative metabolic traits to a genome-wide association study,while the conventional metabolite GWAS(mGWAS)mainly considers the quantitative variation of *** a proof of the validity of QT-GWAS,23 and 15of the retrieved associations identified in Arabidopsis thaliana by QTGWAS and mGWAS,respectively,were supported by previous ***,seven genemetabolite associations retrieved by QT-GWAS were confirmed in this study through reverse genetics combined with metabolomics and/or in vitro enzyme *** such,we established that CYTOCHROME P450706A5(CYP706A5)is involved in the biosynthesis of chroman derivatives,UDP-GLYCOSYLTRANSFERASE 76C3(UGT76C3)is able tohexosylate guanine in vitro and in planta,and SULFOTRANSFERASE 202B1(SULT202B1)catalyzes the sulfation of neolignans in ***,our study demonstrates that the untargeted QT-GWAS method can retrieve valid gene-metabolite associations at the level of enzyme-encoding genes,even new associations that cannot be found by the conventional mGwAs,providing a new approach for dissecting qualitative metabolic traits.

关键词： qualitative method proof

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Yohimbine in the treatment of orgasmic dysfunction

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Asian Journal of Andrology 2007年第3期9卷 403-407页

作者： Ade A. Adeniyi Giles S. Brindley john P. Pryor David J. ralph Institute of Urology and Nephrology London W1P 7EY UK I02 Ferdene Road London SE24 OAA UK

Aim： To study the effect of yohimbine in the treatment of men with orgasmic dysfunction. Methods： A 20-mg dose of yohimbine was first given to 29 men with orgasmic dysfunction of different aetiology in the clinic. Patients were then allowed to increase the dose at home （titration） under more favourable circumstances. The outcome and side effects were subsequently assessed. Results： The patients were classified into three groups of orgasmic dysfunction： primary complete （13）, primary incomplete （8） and secondary （8）. Nocturnal emissions were present in 75%, 40% and 50% of patients in the above groups, respectively （overall average 62%）. The men presented because of fertility problems （52%） or because they wanted to experience the pleasure of orgasm （48%）. Of the 29 patients who completed the treatment, 16 managed to reach orgasm and were able to ejaculate either during masturbation or sexual intercourse. A further three achieved orgasm, but only with the additional stimulation of a vibrator. A history of preceding nocturnal emissions was present in 69% of the men in whom orgasm was induced but only 50% who failed treatment. Of the patients, two have subsequently fathered children （one set of twins） and another 3 men were also cured. Side effects were not sufficient to cause the men to cease treatment. Conclusion： Yohimbine is a useful treatment option in orgasmic dysfunction.

关键词： Yohimbine anorgasmia orgasm orgasmic dysfunction impotence ejaculation

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On the Maximum of Wind Power Efficiency

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Journal of Power and Energy Engineering 2016年第1期4卷 1-39页

作者： Gerhard Kramm Gary Sellhorst Hannah K. Ross john Cooney ralph Dlugi Nicole Mölders Engineering Meteorology Consulting Fairbanks USA Geophysical Institute University of Alaska Fairbanks Fairbanks USA Department of Mechanical Engineering University of Washington Seattle USA Department of Atmospheric Sciences Texas A & M University College Station USA Arbeitsgruppe Atmosphärische Prozesse (AGAP) Munich Germany College of Natural Science and Mathematics and Geophysical Institute University of Alaska Fairbanks Fairbanks USA

In our paper we demonstrate that the filtration equation used by Gorban’ et al. for determining the maximum efficiency of plane propellers of about 30 percent for free fluids plays no role in describing the flows in the atmospheric boundary layer (ABL) because the ABL is mainly governed by turbulent motions. We also demonstrate that the stream tube model customarily applied to derive the Rankine-Froude theorem must be corrected in the sense of Glauert to provide an appropriate value for the axial velocity at the rotor area. Including this correction leads to the Betz-Joukowsky limit, the maximum efficiency of 59.3 percent. Thus, Gorban’ et al.’s 30% value may be valid in water, but it has to be discarded for the atmosphere. We also show that Joukowsky’s constant circulation model leads to values of the maximum efficiency which are higher than the Betz-Jow-kowsky limit if the tip speed ratio is very low. Some of these values, however, have to be rejected for physical reasons. Based on Glauert’s optimum actuator disk, and the results of the blade-element analysis by Okulov and Sørensen we also illustrate that the maximum efficiency of propeller-type wind turbines depends on tip-speed ratio and the number of blades.

关键词： Wind Power Power Efficiency General Momentum Theory Axial Momentum Theory Blade Element Analysis Betz-Joukowsky Limit Joukowsky’s Constant Circulation Model Glauert’s Optimum Actuator Disk Balance Equation for Momentum Equation of Continuity Balance Equation for Kinetic Energy Reynolds’ Average Hesselberg’s Average Favre’s Average Bernoulli’s Equation Integral Equations

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关于可控震源和记录系统的极性约定

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国外油气勘探 1995年第4X期7卷 29-36页

作者： ralph A.Landrum Rober A.Brook john J.Sallas 张宏乐 SEG技术标准小组委员会石油物探局装备研究所

本文是1975年SEG技术标准委员会关于可控震源/记录糸统极性问题建议的扩充。这些系统极性将涉及到以估算地面力(加权和)或反作用重锤(以下简称重锤)信号实现锁相的P(纵)波可控震源,还将涉及水平方向振动的S(横)波可控震源。在首次提出... 详细信息

本文是1975年SEG技术标准委员会关于可控震源/记录糸统极性问题建议的扩充。这些系统极性将涉及到以估算地面力(加权和)或反作用重锤(以下简称重锤)信号实现锁相的P(纵)波可控震源,还将涉及水平方向振动的S(横)波可控震源。在首次提出这份报告时,上面提到的这两类可控震源还没有广泛使用。本文概述了以前那篇文章的要点,还谈及了影响可控震源操作的一些约定。对这些极性约定,我们规定了一条推荐性的扩展定义,介绍了如何对纵波和横波可控震源/记录系统进行新的、完整的极性约定的简单过程。我们认为任何推荐的约定,只是一个简单的限定。这个限定可用于各类培训和实际操作间的系统联系。由于这些原因,我们希望能确定各系统间的差异,对极性约定的过程可作为比较这种差异的基础。

关键词：平板质量地面力压重独立监测信号导频信号反作用重锤可控震源锁相加权和信号

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We Didn＇t Mean to Go to Sea （I）

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考试与评价（英语高一专刊） 2017年第1期 45-47页

作者： ralph Mowat

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Wind Power Potential in Interior Alaska from a Micrometeorological Perspective

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Atmospheric and Climate Sciences 2014年第1期4卷 100-121页

作者： Hannah K.Ross john Cooney Megan Hinzman Samuel Smock Gary Sellhorst ralph Dlugi Nicole Molders Gerhard Kramm Department of Mechanical Engineering Tennessee Tech UniversityCookevilleUSA Department of Atmospheric Sciences College of GeosciencesTexas A&M UniversityCollege StationUSA College of Arts and Sciences University of WashingtonSeattleUSA Fu Foundation School of Engineering and Applied Science Columbia UniversityNew YorkUSA Geophysical Institute University of Alaska FairbanksFairbanksUSA Arbeitgruppe Atmospharische Prozesse(AGAP) MunichGermany Department of Atmospheric Sciences College of Natural Science and MathematicsUniversity of Alaska FairbanksFairbanksUSA

The wind power potential in Interior Alaska is evaluated from a micrometeorological perspective. Based on the local balance equation of momentum and the equation of continuity we derive the local balance equation of kinetic energy for macroscopic and turbulent systems, and in a further step, Bernoulli’s equation and integral equations that customarily serve as the key equations in momentum theory and blade-element analysis, where the Lanchester-Betz-Joukowsky limit, Glauert’s optimum actuator disk, and the results of the blade-element analysis by Okulov and Sorensen are exemplarily illustrated. The wind power potential at three different sites in Interior Alaska (Delta Junction, Eva Creek, and Poker Flat) is assessed by considering the results of wind field predictions for the winter period from October 1, 2008, to April 1, 2009 provided by the Weather Research and Forecasting (WRF) model to avoid time-consuming and expensive tall-tower observations in Interior Alaska which is characterized by a relatively low degree of infrastructure outside of the city of Fairbanks. To predict the average power output we use the Weibull distributions derived from the predicted wind fields for these three different sites and the power curves of five different propeller-type wind turbines with rated powers ranging from 2 MW to 2.5 MW. These power curves are represented by general logistic functions. The predicted power capacity for the Eva Creek site is compared with that of the Eva Creek wind farm established in 2012. The results of our predictions for the winter period 2008/2009 are nearly 20 percent lower than those of the Eva Creek wind farm for the period from January to September 2013.

关键词： Wind Power Power Efficiency Wind Power Potential Wind Power Prediction WRF/Chem Micrometeorology Momentum Theory Blade Element Analysis Betz Limit Glauert’s Optimum Rotor Balance Equation for Momentum Equation of Continuity Balance Equation for Kinetic Energy Reynolds’Average Hesselberg’s Average Bernoulli’s Equation Integral Equations Weibull Distribution General Logistic Function Eva Creek Wind Farm

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Scalable, ultra-resistant structural colors based on network metamaterials

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Light(Science & Applications) 2016年第1期5卷 165-172页

作者： Henning Galinski Gael Favraud Hao Dong Juan S Totero Gongora Grégory Favaro Max Döbeli ralph Spolenak Andrea Fratalocchi Federico Capasso john A.Paulson School of Engineering and Applied Sciences Harvard UniversityCambridge 02138USA Laboratory for Nanometallurgy ETH ZurichVladimir-Prelog-Weg 1-5/10Zurich 8093Switzerland PRIMALIGHT King Abdullah University of Science and Technology(KAUST)Thuwal 23955-6900Saudi Arabia Anton Paar TriTec SA Peseux CH-2034Switzerland Ion Beam Physics ETH ZurichOtto-Stern-Weg 5Zurich 8093Switzerland

Structural colors have drawn wide attention for their potential as a future printing technology for various applications,ranging from biomimetic tissues to adaptive camouflage ***,an efficient approach to realize robust colors with a scalable fabrication technique is still lacking,hampering the realization of practical applications with this ***,we develop a new approach based on large-scale network metamaterials that combine dealloyed subwavelength structures at the nanoscale with lossless,ultra-thin dielectric *** using theory and experiments,we show how subwavelength dielectric coatings control a mechanism of resonant light coupling with epsilon-near-zero regions generated in the metallic network,generating the formation of saturated structural colors that cover a wide portion of the *** measurements support the efficient observation of these colors,even at angles of 70°.The network-like architecture of these nanomaterials allows for high mechanical resistance,which is quantified in a series of nano-scratch *** such remarkable properties,these metastructures represent a robust design technology for real-world,large-scale commercial applications.

关键词： nanophotonics plasmonics structural colors

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层迭电池的密封隔膜的组合系統

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电池 1977年第2期 37-38页

作者： ralph H.Feldhake john E.Oltman 上海电池二厂技术科

为高效率勒克朗谢电池发展了一个能封装所有元件的独特的密封隔膜单片。发展的非织丙烯酸酯,聚乙烯网状塑料是鉴于它的密封性,防短路,热稳定性,功率和在交复物质中出现腐蚀杂质。发展交叉折叠轧光的丙烯酸醋聚乙烯网状塑料是既符合高度... 详细信息

为高效率勒克朗谢电池发展了一个能封装所有元件的独特的密封隔膜单片。发展的非织丙烯酸酯,聚乙烯网状塑料是鉴于它的密封性,防短路,热稳定性,功率和在交复物质中出现腐蚀杂质。发展交叉折叠轧光的丙烯酸醋聚乙烯网状塑料是既符合高度自动化连续装配工艺的需要又符合勒克朗谢系统的电化学性能上的需要。它的物理性能要求具有抗张强度2000克/长时,弹性回复率在伸长1％时回复85％。这个物理性能是为了适用于两个工序的机器上

关键词：电池勒克聚乙烯轧光扁条儿聚烯烃光泽整理隔膜丙烯酸醋

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Bedrock aquifers and population growth in the Denver Basin, Colorado, USA

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Episodes 2007年第2期30卷 115-118页

作者： john E. Moore Robert G. Raynoldse Marieke Dechesne U.S. Geological Survey Denver Colorado USA. Denver Museum of Nature ＆ Science Denver Colorado USA.

The Denver Basin bedrock aquifer system consists of Tertiary and Cretaceous age sedimentary rocks known as the Dawson, Denver, Arapahoe and Laramie-Fox Hills aquifers. The number of bedrock wells has increased from 12,000 in 1985 to over 33,700 in 2001 and the withdrawal of groundwater has caused water level declines in excess of 75 meters. Water level declines now range from 3 to 12 meters per year in the critical Arapahoe Aquifer. The groundwater supplies were once thought to be sufficient for 100 years but there is concern that they may be depleted in 10 to 15 years in areas on the west side of the basin. Groundwater is being mined from the aquifer system because the withdrawal through wells exceeds the rate of recharge. Increased groundwater withdrawal will cause further water level declines, increased costs to pump groundwater, and reduced yield from existing wells. In the Denver Basin, hydrologists have some capability to monitor declines in water levels for the Arapaho Aquifer, but generally have a limited ability to monitor water use. More complete and accurate water use data are needed to predict groundwater longevity for the Arapahoe Aquifer. The life of the Arapahoe Aquifer can be extended with artificial recharge using imported surface water, water reuse, restrictions on lawn watering, well permit restrictions and other conservation measures. Availability of groundwater may limit growth in the Denver Basin over the next 20 years unless residents are willing to pay for additional new sources of supply.

关键词：基岩含水层丹佛盆地美国

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