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Bone loss from Wnt inhibition mitigated by concurrent alendronate therapy

Bone Research 2018年第2期6卷 167-176页

作者： Babita madan mitchell J.mcDonald Gabrielle E.Foxa Cassandra R.Diegel Bart O.williams David m.Virshup Program in Cancer and Stem Cell Biology Duke-NUS Medical School Center for Cancer and Cell Biology and Program for Skeletal Disease and Tumor microenvironment Van Andel Research Institute Department of Pediatrics Duke University

Dysregulated Wnt signaling is associated with the pathogenesis of cancers, fibrosis, and vascular diseases. Inhibition of Wnt signaling has shown efficacy in various pre-clinical models of these disorders. One of the key challenges in developing targeted anti-cancer drugs is to balance efficacy with on-target toxicity. Given the crucial role Wnts play in the differentiation of osteoblasts and osteoclasts, acute inhibition of Wnt signaling is likely to affect bone homeostasis. In this study, we evaluated the skeletal effect of small molecule inhibitor of an o-acyl transferase porcupine（PORCN） that prevents Wnt signaling by blocking the secretion of all Wnts. micro-computed tomography and histomorphometric evaluation revealed that the bones of mice treated with two structurally distinct PORCN inhibitors LGK974 and ETC-1922159（ETC-159） had loss-of-bone volume and density within 4 weeks of exposure. This decreased bone mass was associated with a significant increase in adipocytes within the bone marrow. Notably,simultaneous administration of a clinically approved anti-resorptive, alendronate, a member of the bisphosphonate family,mitigated loss-of-bone mass seen upon ETC-159 treatment by regulating activity of osteoclasts and blocking accumulation of bone marrow adipocytes. Our results support the addition of bone protective agents when treating patients with PORCN *** of bone toxicity can extend the therapeutic utility of Wnt pathway inhibitors.

关键词： Wnt ETC Bone loss Wnt inhibition mitigated concurrent alendronate therapy

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Effect of molarity on sol-gel routed nano TiO_(2) thin films

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Journal of Advanced Dielectrics 2017年第6期7卷 57-63页

作者： Stephen Lourduraj Rayar Victor williams PG and Research Department of Physics St.Joseph’s College(Autonomous)Tiruchirapalli Tamil NaduIndia

The nanostructured titanium dioxide(TiO_(2))thin films have been prepared for the molar concentrations of titanium tetra isopropoxide(TTIP)0.05 m,0.1 m,0.15 m and 0.2 m by sol-gel routed spin coating technique with calcination at 450℃.The processing parameters such as,pH value(8),catalyst HCl(0.1 ml),spin speed(3000 rpm)and calcination temperature(450℃)are *** crystalline nature and surface morphology were analyzed by XRD,SEm and AFm *** XRD results confirm that the films are crystalline with anatase phase,and are *** SEm micrographs of the TiO_(2) film reveal the spherical nature of the *** analysis establishes that the uniformity of the TiO_(2) thin film was optimized at 0.2 *** optical measurements show that the transmittance depends on the molarity,and the optical band gap energy of TiO_(2) films is found to be inversely proportional to *** I-V characteristics exhibit that the molarity strongly influences the electrical conductivity of the *** results indicate that the significant effect of molarity on structural,optical and electrical properties of the nanostructured TiO_(2) thin films will be useful to photovoltaic application.

关键词： TiO_(2)thin film titanium tetra isopropoxide sol-gel precursor concentration calcination temperature

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Spatial sampling of terahertz fields with sub-wavelength accuracy via probe-beam encoding

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Light(Science & Applications) 2019年第1期8卷 680-687页

作者： Jiapeng Zhao Yiwen E Kaia williams Xi-Cheng Zhang Robert W.Boyd The Institute of Optics University of RochesterRochesterNY 14627USA Department of Physics University of OttawaOttawaON K1N 6N5Canada

Recently,computational sampling methods have been implemented to spatially characterize terahertz(THz)*** methods usually rely on either specialized THz devices such as THz spatial light modulators or complicated systems requiring assistance from photon-excited free carriers with high-speed synchronization among multiple optical ***,by spatially encoding an 800-nm near-infrared(NIR)probe beam through the use of an optical SLm,we demonstrate a simple sampling approach that can probe THz fields with a single-pixel *** design does not require any dedicated THz devices,semiconductors or nanofilms to modulate THz *** computational algorithms,we successfully measure 128×128 field distributions with a 62-μm transverse spatial resolution,which is 15 times smaller than the central wavelength of the THz signal(940μm).Benefitting from the noninvasive nature of THz radiation and sub-wavelength resolution of our system,this simple approach can be used in applications such as biomedical sensing,inspection of flaws in industrial products,and so on.

关键词： synchronization beam spatially

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LRP6 in mesenchymal stem cells is required for bone formation during bone growth and bone remodeling

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Bone Research 2014年第1期2卷 43-54页

作者： Changjun Li Bart O williams Xu Cao mei Wan Department of Orthopaedic Surgery Johns Hopkins University School of Medicine Center for Skeletal Disease and Tumor metastasis and Laboratory of Cell Signaling and Carcinogenesis Van Andel Research Institute

Lipoprotein receptor-related protein 6 （LRP6） plays a critical role in skeletal development and homeostasis in adults. However, the role of LRP6 in mesenchymal stem cells （mSCs）, skeletal stem cells that give rise to osteoblastic lineage, is unknown. In this study, we generated mice lacking LRP6 expression specifically in nestin＋ mSCs by crossing nestin-Cre mice with LRP6 flox mice and investigated the functional changes of bone marrow mSCs and skeletal alterations. mice with LRP6 deletion in nestin＋ cells demonstrated reductions in body weight and body length at I and 3 months of age. Bone architecture measured by microCT （uCT） showed a significant reduction in bone mass in both trabecular and cortical bone of homozygous and heterozygous LRP6 mutant mice. A dramatic reduction in the numbers of osteoblasts but much less significant reduction in the numbers of osteoclasts was observed in the mutant mice. Osterix＋ osteoprogenitors and osteocalcin＋ osteoblasts significantly reduced at the secondary spongiosa area, but only moderately decreased at the primary spongiosa area in mutant mice. Bone marrow mSCs from the mutant mice showed decreased colony forming, cell viability and cell proliferation. Thus, LRP6 in bone marrow mSCs is essential for their survival and proliferation, and therefore, is a key positive regulator for bone formation during skeletal growth and remodeling.

关键词： bone LRP6 in mesenchymal stem cells is required for bone formation during bone growth and bone remodeling stem

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Indoor environmental quality(IEQ)assessment of Nigerian university libraries:A pilot study

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Energy and Built Environment 2021年第3期2卷 302-314页

作者： williams P Akanmu Sunday S Nunayon Uche C Eboson Department of Building School of Environmental TechnologyFederal University of TechnologyMinnaP.M.B 65MinnaNiger StateNigeria Department of Architecture and Civil Engineering City University of Hong KongTat Chee AvenueKowloonHong Kong

An indoor environmental quality(IEQ)assessment of academic libraries in Nigeria was conducted through ob-jective *** selected university libraries were Abubakar Gimba Library;Awwal Ibrahim Library;and Ibrahim Badamosi Babangida Library *** libraries were evaluated under operating conditions and during their peak usage *** of the main descriptors of good IEQ,including the acoustical,visual,and thermal comfort conditions were performed using portable IEQ *** methodology employed for the assessment of these IEQ descriptors followed prescriptions of international standards ASHRAE standard 55 and ISO *** determine the time of the day in which the library buildings can achieve optimum IEQ,measurements were taken in the morning and *** results obtained were compared with reference values found in the international Standard CIBSE Guide A for adequate IEQ compliance of academic *** findings of this study are expected to help in improving the IEQ of academic libraries in Nigeria and other parts of the world.

关键词： Comfort conditions Illuminance Indoor environmental quality Nigerian university libraries Noise level Thermal comfort

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The insect-killing bacterium Photorhabdus luminescens has the lowest mutation rate among bacteria

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marine Life Science & Technology 2021年第1期3卷 20-27页

作者： Jiao Pan Emily williams Way Sung michael Lynch Hongan Long Institute of Evolution and marine Biodiversity KLMMEOcean University of ChinaQingdao 266003China Center for mechanisms of Evolution The Biodesign InstituteArizona State UniversityTempeAZ 85281USA Department of Bioinformatics and Genomics University of North CarolinaCharlotteNC 28223USA

mutation is a primary source of genetic variation that is used to power *** studies,however,have shown that most mutations are deleterious and,as a result,extremely low mutation rates might be benefcial for *** a mutation accumulation experiment,an unbiased method for mutation study,we found an extremely low base-substitution mutation rate of 5.94×10^(-11) per nucleotide site per cell division(95%Poisson confdence intervals:4.65×10^(-11),7.48×10^(-11))and indel mutation rate of 8.25×10^(-12) per site per cell division(95%confdence intervals:3.96×10^(-12),1.52×10^(-11))in the bacterium Photorhabdus luminescens *** mutations are strongly A/T-biased with a mutation bias of 10.28 in the A/T *** has been hypothesized that the ability for selection to lower mutation rates is inversely proportional to the efective population size(drift-barrier hypothesis)and we found that the efective population size of this bacterium is signifcantly greater than most other *** fnding further decreases the lower-bounds of bacterial mutation rates and provides evidence that extreme levels of replication fdelity can evolve within organisms that maintain large efective population sizes.

关键词： Neutral evolution mutation accumulation mutation spectrum Drift-barrier hypothesis Lower-limit of mutation rate

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Evolutionary Process from mockina bidentata to Parvigondolella andrusovi:Evidence from the Pizzo mondello Section,Sicily,Italy

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Journal of Earth Science 2021年第3期32卷 667-676页

作者： Yixing Du Tetsuji Onoue Viktor Karadi Ian S.williams manuel Rigo Department of Geosciences University of Padova35131 PadovaItaly Department of Earth and Planetary Sciences Kyushu UniversityFukuokaJapan Department of Palaeontology Eotvos Lorand UniversityBudapest 1117Hungary Research School of Earth Sciences The Australian National UniversityACT 2601 CanberraAustralia Institute of Geosciences and Earth Resources National Research Council of Italy35131 PadovaItaly

During their last phase of evolution,the pectiniform conodont elements manifested an evident trend of simplification and *** phase started from the late Norian(Sevatian)in the Late Triassic and the evolutionary process of genus mockina to Parvigondolella,in particular between mockina bidentata and Parvigondolella andrusovi,is one of the most significant *** has been reported worldwide since it was first described in the early ***,it has recently been suggested that genus Parvigondolella is an ecostratigraphic morphotype of genus mockina,and thus a phenotype controlled by the environmental conditions,and not an independent *** the Pizzo mondello Section(Sicily,Italy),transitional forms between *** and *** have been found at different evolutionary *** have investigated the oceanic conditions at the time by using redox-sensitive elements(mn,Fe,V,Cr,and Ni)and seawater temperatures from biogenetic δ^(18)Ophos to understand the possible environmental influences on the phylogenetic evolution between mockina and *** geochemical and isotope analyses indicate that the redox condition and temperature were stable during the evolution of genus Parvigondolella in Pizzo mondello,confirming that genus Parvigondolella is a real taxon and not a phenotype.A new conodont species named Parvigondolella ciarapicae *** described here for the first time.

关键词： conodont Late Triassic evolution oxygen isotope geochemistry

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Intracellular oxygen:Similar results from two methods of measurement using phosphorescent nanoparticles

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Journal of Innovative Optical Health Sciences 2014年第2期7卷 46-59页

作者： David Lloyd Catrin F.williams K.Vijayalakshmi m.Kombrabail Nick White Anthony J.Hayes miguel A.Aon G.Krishnamoorthy Biosciences and School of Optometry and Vision Sciences Cardif University Cathays Park and Maindy RoadCardifWalesUK Department of Chemical Sciences Tata Institute of Fundamental Research Homi Bhabha RoadMumbai 400005India The Johns Hopkins University Institute of Molecular Cardiobiology720 Rutland Au.1059 Ross BldgBatimore MDUSA

The ability to resolve the spatio-temporal complexity of intracelular O_(2) distribution is the“HolyGrail” of cellular *** an effort to obtain a minimally invasive approach to the mappingof intracllar O,tensions,two methods of phosphorescent lifetime imaging microscopy werecompared in the current study and gave similar *** were two-photon confocal laserscanning microscopy with pinhole shifting,and picosecond time-resolved epi-phosphorescencemicroscopy using a single 0.5μm focused *** methods utilized Ru coordination complexembedded nanopartidles(45 nm diameter)as the phosphorescent probe,excited using pulsedoutputs of a titanium sapphire Tsunami lasers(710-1050 nm).

关键词： Time-resolved phosphorescence intracellular O2 two-photon excitation pinholeshifting.

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Evaluation of fall armyworm resistance in maize germplasm lines using visual leaf injury rating and predator survey

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Insect Science 2014年第5期21卷 541-555页

作者： Xinzhi Ni Wenwei Xu michael H. Blanco W. Paul williams USDA-ARS Crop Genetics and Breeding Research Unit University of Georgia-Tifton Tifton GA 31793 Agricultural Research &Extension Center Texas A&M University Lubbock TX 79403 USDA-ARS Plant Introduction Research Unit Iowa State UniversityAmes IA 50011 Corn Host Plant Resistance Research Unit USDA-ARS Mississippi State MS 39762 USA

After examining ear-colonizing pest resistance, 20 maize lines from the USDA- ARS Germplasm Enhancement of maize （GEm） Program were evaluated for whorl-feeding fall armyworm （FAW）（Spodopterafrugiperda） resistance using 4 maize inbred lines as the resistant and susceptible controls. Both FAW injury ratings at 7- and 14-d after infestation, and predator abundance and diversity at whorl stage （V6-V8） were recorded in 2009 and 2010. The survey of the diversity and abundance of predators in each experimental plot were conducted 7 d after the FAW infestation. Of the 20 germplasm lines examined, 3 of them （i.e., entries 9, 15, and 19 that were derived from tropical maize germplasm lines were originated from Uruguay, Cuba, and Thailand, respectively） were identified as the best FAW-resistant germplasm lines using the leaf injury ratings and predator survey data. In addition, the abundance and diversity of the predators were greater in 2010 than in 2009, which might have caused the low level of the FAW injury ratings on all lines examined in 2010. The 2-year data showed that the FAW injury ratings were negatively correlated to the predator abundance and diversity, which is also influence by genotype × environment interactions. The findings suggested that tropical germplasm is an important source of native resistance to the FAW and the corn earworm. At the same time, the maize genotype x environment interaction （e.g., predator attractiveness, and varying weather conditions） should be included in the multiple-year evaluations of insect and disease resistance of maize germplasm lines under field conditions.

关键词： field screening genotype × environment interactions multiple insect resistance predator abundance and diversity whorl-feeding

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mapping tree canopies in urban environments using airborne laser scanning (ALS):a Vancouver case study

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Forest Ecosystems 2018年第4期5卷 429-437页

作者： Giona matasci Nicholas C.Coops David A.R.williams Nick Page Department of Forest Resource management Unlversity of British Columbia2424Main MallVancouverBC V6T IZ4Canada Vancouver Board of Parks and Recreation 2099Beach AvenueVancouverBC V6G IZ4Canada

Background: The distribution of forest vegetation within urban environments is critically important as it influences urban environmental conditions and the energy exchange through the absorption of solar radiation and modulation of evapotranspiration. It also plays an important role filtering urban water systems and reducing storm water ***: We investigate the capacity of ALS data to individually detect, map and characterize large(taller than15 m) trees within the City of Vancouver. Large trees are critical for the function and character of Vancouver’s urban forest. We used an object-based approach for individual tree detection and segmentation to determine tree locations(position of the stem), to delineate the shape of the crowns and to categorize the latter either as coniferous or ***: Results indicate a detection rate of 76.6% for trees > 15 m with a positioning error of 2.11 m(stem location). Extracted tree heights possessed a RmSE of 2.60 m and a bias of-1.87 m, whereas crown diameter was derived with a RmSE of 3.85 m and a bias of-2.06 m. missed trees are principally a result of undetected treetops occurring in dense, overlapping canopies with more accurate detection and delineation of trees in open ***: By identifying key structural trees across Vancouver’s urban forests, we can better understand their role in providing ecosystem goods and services for city residents.

关键词： Urban forest Large trees Light detection and ranging Airborne laser scanning

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