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Inhibiting WNT secretion reduces high bone mass caused by Sost loss-of-function or gain-of-function mutations in Lrp5

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骨研究:英文版 2023年第3期11卷 595-606页

作者： Cassandra R.Diegel Ina Kramer charles Moes Gabrielle E.Foxa Mitchell j.McDonald Zachary B.Madaj Sabine Guth jun Liu jennifer L.Harris Michaela Kneissel Bart O.Williams Department of Cell Biology Van Andel Institute333 Bostwick Ave.NEGrand RapidsMI 49503USA Diseases of Aging and Regenerative Medicine Novartis Institutes for Biomedical ResearchCH-4002 BaselSwitzerland Bioinformatics and Biostatistics Core Van Andel Institute333 Bostwick Ave.NEGrand RapidsMI 49503USA Oncology Novartis Institutes for Biomedical ResearchSan DiegoCA 92121USA

Proper regulation of Wnt signaling is critical for normal bone development and *** in several Wnt signaling components,which increase the activity of the pathway in the skeleton,cause high bone mass in human subjects and mouse *** bone mass is often accompanied by severe headaches from increased intracranial pressure,which can lead to fatality and loss of vision or hearing due to the entrapment of cranial *** addition,progressive forehead bossing and mandibular overgrowth occur in almost all *** that would provide symptomatic relief in these subjects are ***-mediated palmitoylation is necessary for Wnt secretion and binding to the frizzled *** inhibition of porcupine is a highly selective method of Wnt signaling *** treated three different mouse models of high bone mass caused by aberrant Wnt signaling,including homozygosity for loss-of-function in Sost,which models sclerosteosis,and two strains of mice carrying different point mutations in Lrp5(equivalent to human G171V and A214V),at 3 months of age with porcupine inhibitors for 5–6 *** significantly reduced both trabecular and cortical bone mass in all three *** demonstrates that porcupine inhibition is potentially therapeutic for symptomatic relief in subjects who suffer from these disorders and further establishes that the continued production of Wnts is necessary for sustaining high bone mass in these models.

关键词： homeostasis function mass

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Effects of Health Record Computerization in the Context of the COVID-19 Pandemic in Burundi’ Hospitals: Propensity Score Matching

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Open journal of Epidemiology 2022年第3期12卷 245-260页

作者： Florence Munezero charles j. Sossa Glele Yolaine Ahanhanzo Leodegal Bazira National Institute of Public Health Department of Research Bujumbura Burundi University of Abomey-Calavi Regional Institute of Public Health Ouidah Benin Faculty of Medicine University of Burundi Bujumbura Burundi

Introduction: A great number of software are currently used to digitalize the patient records in order to optimize the quality of services offered to patients. The objective of this study was to evaluate the effects of Electronic Health Records use in Burundi’s hospitals, taking into account the COVID-19 pandemic context. Methods: This was a quasi-experimental study based on difference in difference method. Ten district hospitals were included in the study, five of them had the Electronic Health Records and five of which did not yet have the Electronic Health Records. The hospital’s control group were chosen using the propensity score matching method. The period before the project’s implementation was 2014 and the period after were 2019 and 2020. Results: After 5 years of the Electronic Health Record’s implementation, the results showed an increase in outpatient consultation (70%), deliveries (more than 100%), caesarean sections (56%) and major surgeries (43%) indicators. The overall quality score of hospitals’ care had a regressive effect of 37% and the income from performance-based funding had an increase by 31%. The indicators which were affected by the context of the COVID-19 pandemic were especially outpatient consultation, caesarian section, income from performance-based funding decreased by 3%, 5% and 20% respectively. Conclusion: The effects of Electronic Health Records use are effective. As the COVID-19 pandemic impacted the hospital’s indicators negatively, the resilient strategies alongside the potential shocks are recommended.

关键词： Effects Health Record Computerization COVID-19 Hospitals Propensity Score Matching

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Interference from HONO in the measurement of ambient air NO2 via photolytic conversion and quantification of NO

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journal of Environmental Sciences 2021年第9期33卷 184-193页

作者： Nicholas j.Gingerysty charles A.Odame-Ankrah Nick jordan Hans D.Osthoff Department of Chemistry University of CalgaryCalgary AB T2N 1N4Canada Global Analyzer Systems Ltd. Calgary AB T2E 7L6Canada

The reference method to quantify mixing ratios of the criteria air pollutant nitrogen dioxide(NO_(2)) is NO-O_(3) chemiluminescence(CL), in which mixing ratios of nitric oxide(NO) are measured by sampling ambient air directly, and mixing ratios of NO_(x)(= sum of NO and NO_(2))are measured by converting NO_(2) to NO using, for example, heated molybdenum catalyst or,more selectively, photolytic conversion(P-CL).In this work, the nitrous acid(HONO) interference in the measurement of NO_(2) by P-CL was *** with two photolytic NO2 converters are *** first used radiation centered at 395 nm, a wavelength region commonly utilized in *** second used light at 415 nm, where the overlap with the HONO absorption spectrum and hence its photolysis rate are *** ratios of NO_(2),NO_(x) and HONO entering and exiting the converters were quantified by Thermal Dissociation Cavity Ring-down Spectroscopy(TD-CRDS).Both converters exhibited high NO_(2) conversion efficiency(CF_(NO2);> 90%) and partial conversion of *** of CF against flow rate were consistent with photolysis frequencies of 4.2 s^(-1) and 2.9 s^(-1) for NO_(2) and 0.25 s^(-1) and 0.10 s^(-1) for HONO at 395 nm and 415 nm, *** larger than predicted from the overlap of the emission and HONO absorption *** results imply that measurements of NO2 by P-CL marginally but systematically overestimate true NO_(2) concentrations,and that this interference should be considered in environments with high HONO:NO_(2) ratios such as the marine boundary layer or in biomass burning plumes.

关键词： Photolytic conversion of NO_(2) HONO interference

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Comparative study of the effect of solvents on the efficacy of neonicotinoid insecticides against malaria vector populations across Africa

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Infectious Diseases of Poverty 2022年第2期11卷 23-31页

作者： Magellan Tchouakui Tatiane Assatse Leon M.j.Mugenzi Benjamin D.Menze Daniel Nguifo-Nguete Williams Tchapga jonathan Kayondo Francis Watsenga Emile Zola Manzambi Michael Osae charles S.Wondji Centre for Research in Infectious Diseases(CRID) P.O.Box 13501YaoundeCameroon Parasitology and Ecology Laboratory Department of Animal Biology and PhysiologyFaculty of ScienceUniversity of Yaounde 1P.O.Box 812YaoundeCameroon Institut National de Recherche Biomedicale KinshasaDemocratic Republic of Congo Radiation Entomology and Pest Management Centre Biotechnology and Nuclear Agriculture Research InstituteGhana Atomic Energy CommissionP.O.Box LG80Legon-AccraGhana Department of Vector Biology Liverpool School of Tropical MedicinePembroke PlaceLiverpool L35QAUK International Institute of Tropical Agriculture(IITA) P.O.Box 2008YaoundeCameroon Entomology Department Uganda Virus Research Institute(UVRI)P.O.Box 49EntebbeUganda.

Background:New insecticides with a novel mode of action such as neonicotinoids have recently been recommended for public health by *** monitoring of such novel insecticides requires a robust protocol to monitor the development of resistance in natural *** this study,we comparatively used three different solvents to assess the susceptibility of malaria vectors to neonicotinoids across ***:Mosquitoes were collected from May to july 2021 from three agricultural settings in Cameroon(Njombe-Penja,Nkolondom,and Mangoum),the Democratic Republic of Congo(Ndjili-Brasserie),Ghana(Obuasi),and Uganda(Mayuge).Using the CDC bottle test,we compared the effect of three different solvents(ethanol,acetone,MERO)on the efficacy of neonicotinoids againstAnopheles gambiae *** addition,TaqMan assays were used to genotype key pyrethroid-resistant markers *** and odds ratio based on Fisher exact test were used to evaluate potential cross-resistance between pyrethroids and ***:Lower mortality was observed when using absolute ethanol or acetone alone as solvent for clothianidin(11.4-51.9% mortality in Nkolondom,31.7-48.2% in Mangoum,34.6-56.1% in Mayuge,39.4-45.6% in Obuasi,83.7-89.3% in Congo and 71.1-95.9% in Njombe pendja)compared to acetone+MERO for which 100% mortality were observed for all the *** observations were done for imidacloprid and *** assays(PBO,DEM and DEF)with clothianidin revealed a significant increase of mortality suggesting that metabolic resistance mechanisms are contributing to the reduced susceptibility.A negative association was observed between the L1014F-kdr mutation and clothianidin resistance with a greater frequency of homozygote resistant mosquitoes among the dead than among survivors(OR=0.5;P=0.02).However,the I114T-GSTe2 was in contrast significantly associated with a greater ability to survive clothianidin with a higher frequency of homozygote resistant among surv

关键词： Malaria Anopheles Insecticide resistance Neonicotinoids Clothianidin Cross-resistance

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SPECIAL ISSUE EDITORIAL ON MASS CUSTOMIZATION AND SUSTAINABLE VALUE SYSTEMS

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journal of Systems Science and Systems Engineering 2011年第3期20卷 257-259页

作者： Amy j.C.TRAPPEY P.M.WOGNUM charles V.TRAPPEY Department of Industrial Engineering and Engineering Management National Tsing Hua University Department of Social Sciences Wageningen UniversityThe Netherlands Department of Management Science National Chiao Tung University

Today, new products or services must be designed to satisfy ever changing consumer demand by companies to remain competitive. Mass customization, personalized services, and integration of information and decision processes are needed to produce an increasingly diverse range of products and services. At the same time efficiency as well as flexibility of design and production processes need to be improved.

关键词： SPECIAL ISSUE EDITORIAL ON MASS CUSTOMIZATION AND SUSTAINABLE VALUE SYSTEMS

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DATA DRIVEN MODELING FOR POWER TRANSFORMER LIFESPAN EVALUATION

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journal of Systems Science and Systems Engineering 2014年第1期23卷 80-93页

作者： charles V.TRAPPEY Amy j.C.TRAPPEY Lin MA Wan-Ting TSAO Department of Management Science National Chiao Tung University Department of Industrial Engineering and Engineering Management National Tsing Hua University School of Chemistry Physics and Mechanical EngineeringQueensland University of Technology

Large sized power transformers are important parts of the power supply chain. These very critical networks of engineering assets are an essential base of a nation＇s energy resource infrastructure. This research identifies the key factors influencing transformer normal operating conditions and predicts the asset management lifespan. Engineering asset research has developed few lifespan forecasting methods combining real-time monitoring solutions for transformer maintenance and replacement. Utilizing the rich data source from a remote terminal unit （RTU） system for sensor-data driven analysis, this research develops an innovative real-time lifespan forecasting approach applying logistic regression based on the Weibull distribution. The methodology and the implementation prototype are verified using a data series from 161 kV transformers to evaluate the efficiency and accuracy for energy sector applications. The asset stakeholders and suppliers significantly benefit from the real-time power transformer lifespan evaluation for maintenance and replacement decision support.

关键词： Condition based maintenance (CBM) prognostics and health management (PHM) logisticregression remaining life prediction sustainable engineering asset management

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Protein kinase small molecule inhibitors for rheumatoid arthritis: Medicinal chemistry/clinical perspectives

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World journal of Orthopedics 2014年第4期5卷 496-503页

作者： charles j Malemud David E Blumenthal The Arthritis Research Laboratory Department of Medicine Division of Rheumatic Diseases Case Western Reserve University Cleveland OH 44106-5076 United States Department of Anatomy Case Western Reserve University Cleveland OH 44106-5076 United States School of Medicine Division of Rheumatology Veteran’s Administration Medical Center Cleveland OH 44106 United States

Medicinal chemistry strategies have contributed to the development, experimental study of and clinical trials assessment of the first type of protein kinase small molecule inhibitor to target the janus kinase/Signal Transducers and Activators of Transcription(jAK/STAT) signaling pathway. The orally administered small molecule inhibitor, tofacitinib, is the first drug to target the jAK/STAT pathway for entry into the armamentarium of the medical therapy of rheumatoid arthritis. The introduction of tofacitinib into general rheumatologic practice coupled with increasing understanding that additional cellular signal transduction pathways including the mitogen-activated protein kinase and phosphatidylinositide-3-kinase/Akt/mammalian target of rapa-mycin pathways as well as spleen tyrosine kinase also contribute to immune-mediated inflammatory in rheumatoid arthritis makes it likely that further development of orally administered protein kinase small molecule inhibitors for rheumatoid arthritis will occur in the near future.

关键词： Clinical trials Protein kinase Signal transduction Small molecule inhibitor Rheumatoid arthritis

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An evaluation of the role played by remote sensing technology following the World Trade Center attack

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Earthquake Engineering and Engineering Vibration 2003年第1期2卷 159-168页

作者： charles K.Huyck Beverley j.Adams David I.Kehrlein ImageCat Inc.400 OceangateSuite 1050Long BeachCA90802USA Senior Vice President ImageCat Inc.400 OceangateSuite 1050Long BeachCA90802USA Project Scientist ImageCat Inc.6047 Woodhaven AvenueCarmichaelCA95608USA Vice PresidentGIS Operations

Remote sensing technology has been widely recognized for contributing to emergency response efforts after the World Trade Center attack on September 11th, 2001. The need to coordinate activities in the midst of a dense, yet relatively small area, made the combination of imagery and mapped data strategically useful. This paper reviews the role played by aerial photography, satellite imagery, and LIDAR data at Ground Zero. It examines how emergency managers utilized these datasets, and identifies significant problems that were encountered. It goes on to explore additional ways in which imagery could have been used, while presenting recommendations for more effective use in future disasters and Homeland Security applications. To plan adequately for future events, it was important to capture knowledge from individuals who responded to the World Trade Center attack. In recognition, interviews with key emergency management and geographic information system (GIS) personnel provide the basis of this paper. Successful techniques should not be forgotten, or serious problems dismissed. Although widely used after September 11th, it is important to recognize that with better planning, remote sensing and GIS could have played an even greater role. Together with a data acquisition timeline, an expanded discussion of these issues is available in the MCEER/NSF report “Emergency Response in the Wake of the World Trade Center Attack; The Remote Sensing Perspective” (Huyck and Adams, 2002) Keywords World Trade Center (WTC) - terrorism - emergency response - emergency management - ground zero - remote sensing - emergency operations - disasters - geographic information systems (GIS) - satellite imagery - synthetic aperture radar (SAR) - light detection and ranging imagery (LIDAR)

关键词： World Trade Center (WTC) terrorism emergency response emergency management ground zero remote sensing emergency operations disasters geographic information systems (GIS) satellite imagery synthetic aperture radar (SAR) light detection and ranging imagery (LIDAR)

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The Geology of the Everglades and Adjacent Areas Har/DVD

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2007年

作者： Petuch, Edward j. Roberts, charles

ISBN: (数字)9781420045598

ISBN: (纸本)9781420045581

Painting a complete picture of the history of the Everglades, The Geology of the Everglades and Adjacent Areas brings together theperspectives of various geoscientists to provides an overview of the geology, paleontology, and paleoceanography of the Everglades region. It emphasizes the upper 300 m of the geologic framework of the area and gi

关键词： Geology

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Rac1 regulates the release of Weibel-Palade Bodies in human aortic endothelial cells

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Chinese Medical journal 2004年第8期117卷 1143-1150页

作者：杨水祥闫娟 Shailesh S.Deshpande Kaikobad Irani charles j.Lowenstein Cardiovascular Center Tongren Hospital Capital University of Medical SciencesBeijing100730China Division of Cardiology Department of Medicine Department of PathologyJohns Hopkins UniversitySchool of MedicineBaltimoreMaryland 21205USA

Background The release of Weibel-Palade Bodies (WPB) is a form of endothelial cell activation But the signal transduction pathway leading to WPB release is not yet defined We hypothesized that small G-protein rac1 and reactive oxygen species (ROS) mediate the ligand induced release of Weibel-Palade Bodies Methods We tested this hypothesis by using wild-type and mutant adenoviral rac1 expression vectors, and by manipulating the production and destruction of superoxide and hydrogen peroxide in human aortic endothelial cells (HAEC) KH*2/5DResults Thrombin (1 0 Unit, 30 min) induced the increase of WPB release by 3 7-fold in HAEC, and that H 2O 2 (0 1 mmol/L, 30 min) induced by 4 5-fold These results correlated with thrombin-stimulated activation of rac-GTP binding activity by 3 5-fold, and increase of ROS production by 3 4-fold The dominant negative adenoviral rac-N17 gene transfer dramatically inhibited the release of WPB by 64 2% (control) and 77 3% (thrombin-stimulation), and decreased ROS production by 65 5% (control) and 83 6% (thrombin-stimulation) compared with non-infected cells, respectively Anti-oxidants, catalase and N-acetyl-cysteine significantly decreased the release of WPB by 34% and 79% in control cells, and further decreased by 63 6% and 46 7% in rac-N17 transferred cells compared with non-infected cells We also confirmed that rac1 was located upstream of ROS in the WPB release pathway KH*2/5DConclusions Small G-protein rac1 medicates ligand-induced release of Weibel-Palade Bodies in human aortic endothelial cells, and the signal pathway of WPB release is a rac1-dependent ROS regulating mechanism

关键词： Weibel-Palade Bodies von Willebrand factor P-selectin rac thrombin exocytosis reactive oxygen species

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