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Contemporary Approaches for Identifying rare Bone Disease Causing Genes

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Bone research 2013年第4期1卷 301-310页

作者： charles r.Farber Thomas L.Clemens Center for Public Health Genomics University of Virginia Departments of Public Health Sciences and Biochemistry and Molecular Genetics University of Virginia Department of Orthopaedic Surgery Johns Hopkins School of Medicine Baltimore Veterans Administration Medical Center

recent improvements in the speed and accuracy of DNA sequencing, together with increasingly sophisti- cated mathematical approaches for annotating gene networks, have revolutionized the field of human genetics and made these once time consuming approaches assessable to most investigators. In the field of bone research, a particularly active area of gene discovery has occurred in patients with rare bone disorders such as osteogenesis imperfecta （OI） that are caused by mutations in single genes. In this perspective, we highlight some of these technological advances and describe how they have been used to identify the genetic determinants underlying two previously unexplained cases of OI. The widespread availability of advanced methods for DNA sequencing and bioinformatics analysis can be expected to greatly facilitate identification of novel gene networks that normally function to control bone formation and maintenance.

关键词： exome sequencing genome sequencing bioinformatics osteogenesis imperfect pigment epithelium-derived factor (PEDF) bone restricted ifitm-like protein (Bril)

Scalable Methods for Device Patterning as an Outstanding Challenge in Translating Paper-Based Microfluidics from the Academic Benchtop to the Point-of-Care

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Journal of Analysis and Testing 2019年第1期3卷 50-60页

作者： Jessica C.Brooks charles r.Mace Department of Chemistry Tufts UniversityMedfordMA 02155USA

Paper-based microfluidic devices offer unparalleled adaptability for the development of low-cost,point-of-care analytical *** potential for these devices to drastically improve access to healthcare around the globe is obvious,but very few tests have found success in clinical ***,we identify manufacturing-specifically,methods to pattern paper devices at large scales-as a major barrier to translating prototype paper-based devices from the academic benchtop to the *** introduce current methods used to pattern papers and discuss their utility as means to prototype and manufacture paper-based devices.

关键词： Paper-based microfluidics μPAD Point-of-care Diagnostics Manufacturing

Fuzzy Logic Controller-based Synchronverter in Grid-connected Solar Power System with Adaptive Damping Factor

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Chinese Journal of Electrical Engineering 2021年第2期7卷 37-49页

作者： Kah Yung Yap Chee Ming Beh charles r.Sarimuthu Department of Electrical and Computer Systems Engineering(ECSE) School of EngineeringMonash University MalaysiaSubang Jaya 47500Malaysia

In recent years,renewable energy sources,specifically solar power systems,have developed rapidly owing to their technological maturity and cost ***,its grid integration deteriorates frequency stability because of insufficient rotating masses and inertial ***,a synchronverter,which is an inverter that mimics the operation of a synchronous generator,is crucial to interface solar power in a power *** stabilizes the power grid by emulating a virtual ***,a conventional proportional-integral(PI)-based synchronverter is not equipped with an adaptive damping factor(Dp)or a digitalized smart controller to manage fast-responding solar ***,a novel fuzzy logic controller(FLC)framework is proposed such that the synchronverter can operate in a grid-connected solar power *** this study,Dp is controlled in real time using an FLC to achieve balance between speed and stability for frequency error correction based on frequency *** of four case studies performed in Matlab/Simulink show that the proposed FLC-based synchronverter can stabilize the grid frequency by reducing the frequency deviation by at least 0.2 Hz(0.4%),as compared with the conventional PI-based synchronverter.

关键词： Fuzzy logic controller(FLC) synchronverter renewable energy system(rES) grid stability solar power system

review of 5-FU resistance mechanisms in colorectal cancer:clinical significance of attenuated on-target effects

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Cancer Drug resistance 2023年第2期6卷 257-272页

作者： William H.Gmeiner charles Chidi Okechukwu Department of Cancer Biology and Comprehensive Cancer Center Wake Forest University School of MedicineWinston-SalemNC 27157USA Integrative Physiology and Pharmacology Graduate Program InstitutionWake Forest University School of MedicineWinston-SalemNC 27157USA

The emergence of chemoresistant disease during chemotherapy with 5-Fluorouracil-based(5-FU-based)regimens is an important factor in the mortality of metastatic CrC(mCrC).The causes of 5-FU resistance are multifactorial,and besides DNA mismatch repair deficiency(MMr-D),there are no widely accepted criteria for determining which CrC patients are not likely to be responsive to 5-FU-based ***,there is a need to systematically understand the mechanistic basis for 5-FU treatment failure and an urgent need to develop new approaches for circumventing the major causes of 5-FU *** this manuscript,we review mechanisms of 5-FU resistance with an emphasis on:(1)altered anabolic metabolism limiting the formation of the primary active metabolite Fluorodeoxyuridylate(5-Fluoro-2'-deoxyuridine-5'-O-monophosphate;FdUMP);(2)elevated expression or activity of the primary enzymatic target thymidylate synthase(TS);and(3)dysregulated programmed cell death as important causes of 5-FU ***,these causes of 5-FU resistance can potentially be overcome through the use of next-generation fluoropyrimidine(FP)polymers(e.g.,CF10)that display reduced dependence on anabolic metabolism and more potent TS inhibitory activity.

关键词： Fluoropyrimidine 5-FU resistance colorectal cancer chemotherapy precision medicine thymidylate synthase

Cancer chemoprevention through dietary avonoids: what's limiting?

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Chinese Journal of Cancer 2017年第10期36卷 455-467页

作者： Haneen Amawi charles r. Ashby Jr Amit K. Tiwari Department of Pharmacology and Systems Therapeutics College of Pharmacy and Pharmaceutical Sciences University of Toledo Toledo OH 43560USA Pharmaceutical Sciences College of Pharmacy St. John’s UniversityQueens NY 11432 USA Department of Pharmacology and Experimental Therapeutics College of Pharmacy and Pharmaceutical Sciences University of Toledo Toledo OH 43614 USA

Flavonoids are polyphenols that are found in numerous edible plant species. Data obtained from preclinical and clinical studies suggest that specific flavonoids are chemo-preventive and cytotoxic against various cancers via a multitude of mechanisms. However, the clinical use of flavonoids is limited due to challenges associated with their e ective use, including(1) the isolation and purification of flavonoids from their natural resources;(2) demonstration of the e ects of flavonoids in reducing the risk of certain cancer, in tandem with the cost and time needed for epidemiological studies, and(3) numerous pharmacokinetic challenges(e.g., bioavailability, drug–drug interactions, and metabolic instability). Currently, numerous approaches are being used to surmount some of these challenges, thereby increasing the likelihood of flavonoids being used as chemo-preventive drugs in the clinic. In this review, we summarize the most important challenges and e orts that are being made to surmount these challenges.

关键词： Flavonoids Chemoprevention Silybin Silymarin Natural product drug development Pharmacokinetic challenges

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

Does Tenure Security reduce Disaster risk? A Comparative Study of the Nairobi Settlements of Kibera and Kawangware

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International Journal of Disaster risk Science 2021年第4期12卷 445-457页

作者： rónán McDermott Pat Gibbons Dalmas Ochieng charles Owuor Olungah Desire Mpanje Centre for Humanitarian Action University College DublinDublinD04 V1W8Ireland Institute for Anthropology Gender and African StudiesUniversity of NairobiNairobi30197Kenya

While scholarship suggests that improving tenure security and housing significantly reduces disaster risk at the household level within urban settings,this assertion has not been adequately *** security can be conceived as being composed of three interrelated and overlapping forms:tenure security as determined by legal systems;de facto tenure security;and tenure security as perceived by *** article traces the relationship between tenure security,the quality of housing,and disaster risk on the basis of a mixed methods comparative case study of the settlements of Kawangware and Kibera in *** the findings suggest that owner-occupancy is associated with the structural integrity of dwellings to a greater extent than tenantship,no association was found between the length of occupancy by households and the structural integrity of the ***,tenantship is not found to be closely associated with fires and flooding affecting the dwelling as extant scholarship would *** ownership is linked with greater investment and upgrading of property with significant implications for disaster *** findings highlight the complex relationship between tenure security and disaster risk in urban informal settlements and provide impetus for further investigation.

关键词： Disaster risk Fire and flood risk Tenure security Urban hazards Urban informal settlements

Existence and Uniqueness of Almost Periodic Solution for a Mathematical Model of Tumor Growth

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Journal of Applied Mathematics and Physics 2022年第4期10卷 1013-1018页

作者： charles Bu Department of Mathematics Wellesley College Wellesley MA USA

This article is concerned with a mathematical model of tumor growth governed by 2nd order diffusion equation . The source of mitotic inhibitor is almost periodic and time-dependent within the tissue. The system is set up with the initial condition C(r, 0) = C0(r) and robin type inhomogeneous boundary condition . Under certain conditions we show that there exists a unique solution for this model which is almost periodic.

关键词： Mathematical Model of Tumor Growth Almost Periodic Solution robin Boundary Condition Pullback Attractor Non-Autonomous Dynamics

The El Niño-Southern Oscillation (ENSO) Effects on Cowpea and Winter Wheat Yields in the Semi-Arid region of the Southern US

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Agricultural Sciences 2023年第2期14卷 154-175页

作者： Prem Woli Gerald r. Smith charles r. Long Francis M. rouquette Jr. Texas A&M AgriLife research Center Overton TX USA

Information is limited on the effects of climate variability on cowpea (Vigna unguiculata L.) and winter wheat (Triticum aestivum L.) yields in the semiarid region of the southern US. Using the Decision Support System for Agrotechnology Transfer (DSSAT) crop model and weather data spanning 81 years, we assessed the impact of El Niño-Southern Oscillation (ENSO) on the grain yields of these crops in the Llano Estacado region of the southern US as affected by cowpea and wheat planting dates and N application rate. Simulated results showed that the El Niño phase of ENSO produced about 30% more yields of mono-cropped cowpea than those produced under the La Niña phase, especially with the cowpeas planted in July. The cowpea yields under El Niño were about 10% more than the 81-year average normal yield, whereas those under La Niña were about 20% less. At the N rates of 0, 50, and 100 kg·ha−1, regardless of wheat planting dates, the El Niño years produced, respectively, about 8%, 40%, and 60% higher wheat yields than those produced in the La Niña years, and about 5%, 20%, and 27% more than the 81-year average normal yield. In the La Niña years, the wheat yields at 0, 50, and 100 kg N ha−1 were, respectively, about 5%, 15%, and 20% less than the normal yield with similar N levels. The impact of ENSO on wheat yields under cowpea-wheat double-cropping systems was significant, especially for the wheat crops planted on October 15 (October 30) or later following the cowpea crops planted in June (July). At zero N, the mono-cropped wheat yields were not impacted by ENSO due to N limitation. However, the double-cropped wheat yields were impacted by ENSO even when no N fertilizer was applied due to high soil N status caused by N transfer from cowpea stover residues and roots. results indicated that management strategies need to be attentive to ENSO forecasts and adjust potential planting dates and N application rates with the ENSO phase to avert risks of crop fa

关键词： Climate Cowpea DSSAT Double-Crop El Niño ENSO Model Semi-Arid Wheat