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Characterization of a novel murine Sost eRT2 Cre model targeting osteocytes

Bone Research 2019年第1期7卷 41-53页

作者： Delphine B.Maurel Tsutomu Matsumoto Julian A.Vallejo Mark L.Johnson Sarah L.Dallas Yukiko Kitase Marco Brotto Michael J.Wacker Marie A.harris stephen e.harris Lynda F.Bonewald Department of Oral and Craniofacial Sciences University of Missouri-Kansas City School of DentistryKansas CityMOUSA Department of Anatomy and Cell Biology Indiana University School of MedicineIndianapolisINUSA Bone.Muscle Collaborative Sciences College of Nursing and Health InnovationUniversity of Texas at ArlingtonArlingtonUSA Department of Biomedical Sciences University of Missouri-Kansas City School of MedicineKansas CityMOUSA University of Texas Health Science Center San AntonioTXUSA Department of Orthopaedic Surgery Indiana University School of MedicineIndianapolisINUSA Pharmaceutical Sciences Department Universite de BordeauxBio-TisINSERM Unité1026 BioTis146 Rue Léo Saignat33076 BordeauxFrance

Transgenic mice are widely used to delete or overexpress genes in a cell specific manner to advance knowledge of bone biology,function and *** numerous Cre models exist to target gene recombination in osteoblasts and osteoclasts,few target osteocytes specifically,particularly mature *** goal was to create a spatial and temporal conditional Cre model using tamoxifen to induce Cre activity in mature osteocytes using a Bac construct containing the 5’and 3’regions of the Sost gene(Sost eRT2 Cre).Four founder lines were crossed with the Ai9 Cre reporter *** founder line showed high and specific activity in mature *** and organs were imaged and fluorescent signal *** no activity was observed in 2 day old pups,by 2 months of age some osteocytes were positive as osteocyte Cre activity became spontaneous or‘leaky’with *** percentage of positive osteocytes increased following tamoxifen injection,especially in males,with 43%to 95%positive cells compared to 19%to 32%in *** signal was observed in any bone surface cell,bone marrow,nor in muscle with or without tamoxifen *** spontaneous signal was observed in any other ***,with tamoxifen injection,a few positive cells were observed in kidney,eye,lung,heart and *** other organs,28 in total,were negative with tamoxifen ***,with age,a muscle phenotype was apparent in the Sost-eRT2 Cre ***,although this mouse model may be useful for targeting gene deletion or expression to mature osteocytes,the muscle phenotype may restrict the use of this model to specific applications and should be considered when interpreting data.

关键词： cell knowledge model

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e11是骨陷窝细胞特异抗原和机械应力感应分子

E11是骨陷窝细胞特异抗原和机械应力感应分子

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中华医学会第三次全国骨质疏松和骨矿盐疾病学术会议

作者：张克勤叶林 Shiva Kotha Mark Dallas 陆永波 stephen e.harris 冯建全 Lynda.F.Bonewald 美国密苏里大学

成骨细胞合成骨基质和促进钙化,最终自身被骨基质包埋,细胞形态也从立方形转变成树枝状,此时称骨陷窝细胞(Osteocyte,简称ocy)。骨陷窝细胞在形态及功能方面均不同于其前体细胞——成骨细胞,因此我们推测骨陷窝细胞必然存在不同于成骨...

成骨细胞合成骨基质和促进钙化,最终自身被骨基质包埋,细胞形态也从立方形转变成树枝状,此时称骨陷窝细胞(Osteocyte,简称ocy)。骨陷窝细胞在形态及功能方面均不同于其前体细胞——成骨细胞,因此我们推测骨陷窝细胞必然存在不同于成骨细胞的特异蛋白。1996年WettenvaId等报告e11是大鼠骨陷窝细胞的特异蛋白,这种蛋白也特异地存在于肺泡Ⅰ

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Bone morphogenetic protein-2 gene controls tooth root development in coordination with formation of the periodontium

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International Journal of Oral Science 2013年第2期5卷 75-84页

作者： Audrey Rakian Wu-Chen Yang Jelica Gluhak-Heinrich Yong Cui Marie A harris Demitri Villarreal Jerry Q Feng Mary MacDougall stephen e.harris Department of Periodontics University of Texas Health Science Center at San Antonio Baylor College of Dentistry Texas A&M System University of Alabama School of Dentistry

Formation of the periodontium begins following onset of tooth-root formation in a coordinated manner after birth. Dental follicle progenitor cells are thought to form the cementum, alveolar bone and Sharpey＇s fibers of the periodontal ligament （PDL）. However, little is known about the regulatory morphogens that control differentiation and function of these progenitor cells, as well as the progenitor cells involved in crown and root formation. We investigated the role of bone morphogenetic protein-2 （Bmp2） in these processes by the conditional removal of the Bmp2 gene using the Sp7-Cre-eGFP mouse model. Sp7-Cre-eGFP first becomes active at e18 in the first molar, with robust Cre activity at postnatal day 0 （PO）, followed by Cre activity in the second molar, which occurs after P0. There is robust Cre activity in the periodontium and third molars by 2 weeks of age. When the Bmp2gene is removed from Sp7＋（Osterix＋） cells, major defects are noted in root, cellular cementum and periodontium formation. First, there are major cell autonomous defects in root-odontoblast terminal differentiation. Second, there are major alterations in formation of the PDLs and cellular cementum, correlated with decreased nuclear factor IC （Nfic）, periostin and α-SMA＋ cells. Third, there is a failure to produce vascular endothelial growth factor A （VeGF-A） in the periodontium and the pulp leading to decreased formation of the microvascular and associated candidate stem cells in the Bmp2-cKOsp7-cre＇eGFe. Fourth, ameloblast function and enamel formation are indirectly altered in the Bmp2-cKOsp7-cre＇eGFe. These data demonstrate that the Bmp2 gene has complex roles in postnatal tooth development and periodontium formation.

关键词： Bmp2 gene cementum dentinogenesis periodontium development root formation

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Human dNK cell function is differentially regulated by extrinsic cellular engagement and intrinsic activating receptors in first and second trimester pregnancy

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Cellular & Molecular Immunology 2017年第2期14卷 203-213页

作者： Jianhong Zhang Caroline e Dunk Melissa Kwan Rebecca L Jones Lynda K harris Sarah Keating stephen J Lye Research Centre for Women's and Infants' Health Lunenfeld-Tanenbaum Research Institute Mount Sinai Hospital Toronto ON M5T 3H7 Canada Department of Obstetrics & Gynaecology University of Toronto Toronto ON M5G 1 L4 Canada Department of Physiology University of Toronto Toronto ON M5G 1L4 Canada Institute of Human Development University of Manchester Manchester M 13 9WL UK St. Mary's Hospital Central Manchester University Hospitals NHS Foundation Trust Manchester Academic Health Science Centre Manchester M13 9WL UK Department of Pathology University of Toronto Toronto ON M5G 1L4 Canada

Decidual natural killer （dNK） cells express an array of activation receptors to regulate placental immunity and development during early pregnancy. We investigated the functional character of human dNK cells during the first and second trimester of gestation and the interaction between dNK and trophoblast cells. Although the frequency of CD56＋CD16-dNK among the total CD45＋ leukocytes did not change over this period, the expression of the activating receptors, NKp80 and NKG2D, was greatly upregulated. We observed a significantly higher number of extravillous trophoblast cells in proximity to the dNK cells in the first trimester in comparison with the second trimester decidua. NKG2D expression by first trimester dNK cells was decreased when co-cultured with the HTR-8 trophoblast cell line. In the second trimester, functional markers of dNK activation, i.e., angiogenic factor production （e.g., vascular endothelial growth factor, interleukin-8, interferon-gamma）, remained stable despite an increase in NKp80 or NKG2D surface expression. Furthermore, the degranulation capacity of dNK cells, as assessed by CD107a, was decreased in the second trimester. We suggest that in the first trimester, trophoblast-dNK interactions generate a population of dNK cells with a suppressed activating phenotype. In the second trimester, the loss of trophoblast-dNK interactions led to the inhibition of dNK cell function, although their activating receptor expression was increased. We speculate that during pregnancy, two mechanisms operate to modulate the dNK cell activation：suppression of activating receptor levels in the first trimester by trophoblasts and disengagement of receptor-ligand coupling in the second trimester.

关键词： decidual NK cells IFN-gamma NKG2D NKp80 pregnancy

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Geomechanical properties will constrain CO_(2)injection into the lower Ordovician Rose Run sandstone deep saline reservoir,Appalachian Basin,Kentucky,USA

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Journal of Rock Mechanics and Geotechnical engineering 2021年第5期13卷 947-960页

作者： John Richard Bowersox stephen F.Greb Junfeng Zhu David C.harris Kentucky Geological Survey University of KentuckyLexingtonKY40506-0107USA

The Kentucky Geological Survey(KGS)1 Hanson Aggregates stratigraphic research well,Carter County,Kentucky,USA,was drilled to a total depth of 1474 m as a field-scale test of potential CO2 storage reservoir properties in the Central Appalachian *** properties of the Rose Run sandstone(upper Ordovician Knox group)were tested for its suitability as a storage reservoir.A 9.8-m thick section of the Rose Run was penetrated at 1000 m drilled depth and a whole-diameter core and rotary sidewall cores were *** porosity and permeability measured in core plugs were 9.1%and 44.6 mD,*** vertical stress gradient calculated in the wellbore was 26 MPa/*** fractures in dolomites underlying and overlying the Rose Run follow the contemporary N53e Appalachian Basin stress *** Rose Run elastic geomechanical properties were calibrated to values measured in core plugs to evaluate its fracturing risk as a CO2 storage *** Young’s modulus and Poisson’s ratio values of the Rose Run were 45 GPa and 0.23,respectively,whereas Young’s modulus and Poisson’s ratio values were 77.1 GPa and 0.28,respectively,in the overlying Beekmantown dolomite,suggesting the Rose Run may fracture if overpressured during CO2 injection but be confined by the *** compressive strength measured in core plugs found the Rose Run and Beekmantown fractured at mean axial stresses of 156.5 MPa and 282.2 MPa,respectively,confirming the Beekmantown as suitable for confining CO2 injected into the Rose Run.A step-rate test was conducted in a mechanically-isolated 18.6-m interval bracketing the Rose *** Rose Run reservoir pressure was 9.3 MPa,and fracture gradient under injection was 13.6 MPa/km,suggesting step-rate testing before CO2 injection,and subsequent pressure monitoring to ensure *** the region around the KGS 1 Hanson Aggregates well is underpressured and adjacent to faulted Precambrian basement,further research is neede

关键词： Appalachian Basin Rose Run sandstone Geomechanics Carbon sequestration Step-rate testing

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The Fourier space restricted Hartree-Fock method for the electronic structure calculation of linear poly(tetrafluoroethylene)

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Science China Chemistry 2014年第10期57卷 1355-1362页

作者： FRIPIAT Joseph G. harris Frank e. Laboratoire de Chimie Théorique Unité de chimie physique théorique et structurale University of NamurRue de Bruxelles Department of Physics University of Utah Quantum Theory Project University of Florida

Building on the pioneering work of Jean-Marie Andre and working in the laboratory he founded, the authors have developed a code called FT-1D to make Hartree-Fock electronic structure computations for stereoregular polymers using ewald-type con- vergence acceleration methods. That code also takes full advantage of all line-group symmetries to calculate only the minimal set of two-electron integrals and to optimize the computation of the Fock matrix. The present communication reports a bench- mark study of the FT-1D code using polytetrafluoroethylene （PTFe） as a test case. Our results not only confirm the algorith- mic correctness of the code through agreement with other studies where they are applicable, but also show that the use of con- vergence acceleration enables accurate results to be obtained in situations where other widely-used codes （e.g., PLH and Crys- tal） fail. It is also found that full attention to the line-group symmetry of the PTFe polymer leads to an increase of between one and two orders of magnitude in the speed of computation. The new code can therefore be viewed as extending the range of electronic-structure computations for stereoregular polymers beyond the present scope of the successful and valuable code Crystal.

关键词： poly(tetrafluoroethylene) band structure Fourier-space Hartree-Fock lattice sum ewaid

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Region-specific microRNA signatures in the human epididymis

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Asian Journal of Andrology 2018年第6期20卷 539-544页

作者： James A Browne Shih-Hsing Leir Scott e eggener Ann harris Department of Genetics and Genome Sciences Case Western Reserve UniversityClevelandOH 44106USA Human Molecular Genetics Program Lurie Children＇s Research CenterChicagoIL 60614USA Department of Pediatrics Northwestern University Feinberg School of MedicineChicagoIL 60611USA Section of Urology University of Chicago Medical CenterChicagoIL 60611USA.

The epithelium of the human epididymis maintains an appropriate luminal environment for sperm maturation that is essential for male fertility. Regional expression of small noncoding RNAs such as microRNAs contributes to segment-specific gene expression and differentiated functions. MicroRNA profiles were reported in human epididymal tissues but not specifically in the epithelial cells derived from those regions. Here, we reveal miRNA signatures of primary cultures of caput, corpus, and cauda epididymis epithelial cells and of the tissues from which they were derived. We identify 324 epithelial cell-derived microRNAs and 259 tissue-derived microRNAs in the epididymis, some of which displayed regionalized expression patterns in cells and/or tissues. Caput cell-enriched miRNAs included miR-573 and miR-155. Cauda cell-enriched miRNAs included miR-1204 and miR-770. Next, we determined the gene ontology pathways associated with in silico predicted target genes of the differentially expressed miRNAs. The effect of androgen receptor stimulation on miRNA expression was also investigated. These data show novel epithelial cell-derived miRNAs that may regulate the expression of important gene networks that are responsible for the regionalized gene expression and function of the epididymis.

关键词： caput cauda corpus human epididymis microRNA

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Deep learning based classification of sheep behaviour from accelerometer data with imbalance

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Information Processing in Agriculture 2023年第3期10卷 377-390页

作者： Kirk e.Turner Andrew Thompson Ian harris Mark Ferguson Ferdous Sohel Discipline of Information Technology Murdoch UniversityMurdochWA 6150Australia Centre for Crop and Food Innovation Food Futures InstituteMurdoch UniversityMurdochWA 6150Australia College of Science HealthEngineering and EducationMurdoch UniversityMurdochWA 6150Australia neXtgen Agri Saint MartinsChristchurch 8022New Zealand

Classification of sheep behaviour from a sequence of tri-axial accelerometer data has the potential to enhance sheep *** behaviour is inherently imbalanced(e.g.,more ruminating than walking)resulting in underperforming classification for the minority activities which hold *** works have not addressed class imbalance and use traditional machine learning techniques,e.g.,Random Forest(RF).We investigated Deep Learning(DL)models,namely,Long Short Term Memory(LSTM)and Bidirectional LSTM(BLSTM),appropriate for sequential data,from imbalanced *** data sets were collected in normal grazing conditions using jaw-mounted and earmounted *** to this study,alongside typical single classes,e.g.,walking,depending on the behaviours,data samples were labelled with compound classes,e.g.,walking_-*** number of steps a sheep performed in the observed 10 s time window was also recorded and incorporated in the *** designed several multi-class classification studies with imbalance being addressed using synthetic *** models achieved superior performance to traditional ML models,especially with augmented data(e.g.,4-Class+Steps:LSTM 88.0%,RF 82.5%).DL methods showed superior generalisability on unseen sheep(i.e.,F1-score:BLSTM 0.84,LSTM 0.83,RF 0.65).LSTM,BLSTM and RF achieved sub-millisecond average inference time,making them suitable for real-time *** results demonstrate the effectiveness of DL models for sheep behaviour classification in grazing *** results also demonstrate the DL techniques can generalise across different *** study presents a strong foundation of the development of such models for real-time animal monitoring.

关键词： Sheep behaviour classification Data synthesis Class imbalance Grazing sheep

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铅盐探测器

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红外技术 1985年第1期 1-5页

作者： Richard e.harris ,杨川梅

一、前言四十年来,造价低、应用广泛的硫化铅(PbS)和硒化铅(PbSe)探测器在1～3μm和3～5μm光谱范围的许多应用中,仍占优先地位。在二次世界大战期间,铅盐光导探测器被广泛地应用于各种红外装置。大战一结束,美国政府立即在通讯、火控... 详细信息

一、前言四十年来,造价低、应用广泛的硫化铅(PbS)和硒化铅(PbSe)探测器在1～3μm和3～5μm光谱范围的许多应用中,仍占优先地位。在二次世界大战期间,铅盐光导探测器被广泛地应用于各种红外装置。大战一结束,美国政府立即在通讯、火控和搜索系统的红外应用方面开始了强有力的发展,直延续至今。五十年代末,热寻的红外制导导弹“响尾蛇”引起了人们的极大关注。后来这一技术在行星温度测量、无损检测和早期癌症检查方面得到广泛的应用。就在这些年里,许多红外科学家预言,铅盐探测器不久将被新的传感器材料所代替。二十五年后,多数军用系统以及工业、商业和医疗应用上对铅盐探测器的需求量仍

关键词：探测器有效面积负载电阻制造厂商探测率铅盐

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Cyclooxygenase-2 and the inflammogenesis of breast cancer

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World Journal of Clinical Oncology 2014年第4期5卷 677-692页

作者： Randall e.harris Bruce C Casto Zachary M harris The Ohio State University Comprehensive Cancer Center The Ohio State University College of Medicine Columbus OH 43210-1351 United States College of Medicine and College of Public Health Center of Molecular Epidemiology and Environmental Health The Ohio State University Medical Center Columbus OH 43210-1351 United States

Cohesive scientific evidence from molecular, animal, and human investigations supports the hypothesis that constitutive overexpression of cyclooxygenase-2(COX-2) is a ubiquitous driver of mammary carcinogenesis, and reciprocally, that COX-2 blockade has strong potential for breast cancer prevention and therapy. Key findings include the following:(1) COX-2 is constitutively expressed throughout breast cancer development and expression intensifies with stage at detection, cancer progression and metastasis;(2) essential features of mammary carcinogenesis(mutagenesis, mitogenesis, angiogenesis, reduced apoptosis, metastasis and immunosuppression) are linked to COX-2-driven prostaglandin e2(PGe-2) biosynthesis;(3) upregulation of COX-2 and PGe-2 expression induces transcription of CYP-19 and aromatase-catalyzed estrogen biosynthesis which stimulates unbridled mitogenesis;(4) extrahe-patic CYP-1B1 in mammary adipose tissue converts paracrine estrogen to carcinogenic quinones with mutagenic impact; and(5) agents that inhibit COX-2 reduce the risk of breast cancer in women without disease and reduce recurrence risk and mortality in women with breast cancer. Recent sharp increases in global breast cancer incidence and mortality are likely driven by chronic inflammation of mammary adipose and upregulation of COX-2 associated with the obesity pandemic. The totality of evidence clearly supports the supposition that mammary carcinogenesis often evolves as a progressive series of highly specific cellular and molecular changes in response to induction of constitutive overexpression of COX-2 and the prostaglandin cascade in the "inflammogenesis of breast cancer".

关键词： Breast Cancer Cyclooxygenase-2 Nonsteroidal anti-inflammatory drugs Inflammogenesis estrogen Aromatase

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