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Multiple sclerosis is at a checkpoint: advancing the program

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Neural Regeneration Research 2025年第3期20卷 811-812页

作者： Brandon C.Smith Jessica l.williams Department of Neurosciences Lerner Research InstituteCleveland ClinicClevelandOHUSA Department of Biological Geologicaland Environmental SciencesCleveland State UniversityClevelandOHUSA

Multiple sclerosis(MS) is a chronic inflammatory and demyelinating disease of the central nervous system(CNS). Patients with MS experience sensory and motor function loss due to myelin and/or axon damage perpetuated b... 详细信息

关键词： Hauser sclerosis damage

Modeling analytics in COVID-19: prediction, prevention, control, and evaluation

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Journal of Management Analytics 2021年第3期8卷 424-442页

作者： Yang lu Therese l.williams Department of Information Systems and Operations Management University of Central OklahomaEdmondOKUSA

The outbreak of COVID-19 has attracted attention from all around the *** and institutions have adopted ways to fight COVID-19, but itsprevalence is still strong. The SIR model has important reference value for thenovel coronavirus epidemic, offering both preventive measures and the ability topredict future trends. Based on an analysis of the classical epidemiological SIRmodel along with key parameters, this paper aims to analyze the patterns ofCOVID-19, to discuss potential anti-COVID-19 measures, and to explain whywe need to conduct appropriate measures against COVID-19. The use of theSIR model can play an important role in public health emergencies. Among theparameters of the SIR model, the contact ratio and the reproduction ratio arethe factors that have the potential to mitigate the consequences of ***-COVID-19 measures include wearing a mask, washing one’s hands,keeping social distance, and staying at home if possible.

关键词： COVID-19 epidemiological compartment model SIR model the contact ratio the reproduction ratio social distancing

Early Mesoproterozoic evolution of midcontinental laurentia: Defining the geon 14 Baraboo orogeny

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Geoscience Frontiers 2021年第5期12卷 37-53页

作者： l.Gordon Medaris Jr Brad S.Singer Brian R.Jicha David H.Malone Joshua J.Schwartz Esther K.Stewart Amanda Van lankvelt Michael l.williams Peter W.Reiners Department of Geoscience University of Wisconsin-MadisonMadisonWI 53706USA Department of Geography Geology&EnvironmentIllinois State UniversityNormalIL 61790USA Department of Geological Sciences California State University-NorthridgeNorthridgeCA 91330USA Wisconsin Geological&Natural History Survey MadisonWI 53705USA Cameca Instruments 5470 Nobel Dr.MadisonWI 54711USA Department of Geosciences University of Massachusetts-AmherstAmherstMA 01003USA Department of Geosciences University of ArizonaTucsonAZ 85721USA

New geochronologic data from midcontinental laurentia demonstrate that emplacement of the 1476-1470 Ma Wolf River granitic batholith was not an isolated igneous event,but was accompanied by regional metamorphism,deformation,and *** for such metamorphism and deformation is best seen in siliciclastic sedimentary rocks of the Baraboo Interval,which were deposited closely following the 1.65-1.63 Ga Mazatzal *** Baraboo Interval strata,muscovite parallel to slatey cleavage,in hydrothermal veins,in quartzite breccia,and in metamorphosed paleosol yielded ^(40)Ar/^(39)Ar plateau ages of 1493-1465 *** addition,U-Th-total Pb dating of neoblastic overgrowths on detrital monazite gave an age of 1488±20 Ma,and recrystallized hematite in folded metapelite gave a mean U/Th-He age of 1411±39 ***-Baraboo,arkosic polymictic conglomerate,which contains detrital zircon with a minimum peak age of 1493 Ma,was intruded by a 1470 Ma granite porphyry at the northeastern margin of the Wolf River *** episode of magmatism,regional deformation and metamorphism,and sedimentation,which is designated herein as the Baraboo orogeny,provides a midcontinental link between the Picuris orogeny to the southwest and the Pinware orogeny to the northeast,completing the extent of early Mesoproterozoic(Calymmian)orogenesis for 5000 km along the southern margin of *** transcontinental orogen is unique among Precambrian orogenies for its great width(-1600 km),the predominance of ferroan granites derived from partial melting of lower continental crust,and the prevalence of regional high T-P metamorphism related to advective heating by granitic magmas emplaced in the middle to upper crust.

关键词： Mesoproterozoic orogeny Ferroan granite Detrital zircon ^(40)Ar/^(39)Ar geochronology U-Th-total Pb geochronology U/Th-He geochronology

High-throughput screening against thioredoxin glutathione reductase identifies novel inhibitors with potential therapeutic value for schistosomiasis

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Infectious Diseases of Poverty 2015年第1期4卷 300-315页

作者： Ting li Peter D.Ziniel Pan-qing He Valerie P.Kommer Gregory J.Crowther Min He Qing liu Wesley C.Van Voorhis David l.williams Ming-Wei Wang The National Center for Drug Screening Shanghai Institute of Materia MedicaChinese Academy of SciencesShanghai 201203China Department of Immunology and Microbiology Rush University Medical CenterChicagoIL 60612USA Division of Allergy and Infectious Diseases University of WashingtonSeattleWA 98195USA

Background:Schistosomiasis,a parasitic disease also known as bilharzia and snail fever,is caused by different species of flatworms,such as Schistosoma mansoni(***).Thioredoxin glutathione reductase(TGR)from ***(SmTGR)is a well-characterized drug target for schistosomiasis,yet no anti-SmTGR compounds have reached clinical trials,suggesting that therapeutic development against schistosomiasis might benefit from additional scaffolds targeting this ***:A high-throughput screening(HTS)assay in vitro against SmTGR was developed and applied to a diverse compound *** activity was quantified with ThioGlo®,a reagent that fluoresces upon binding to the free sulfhydryl groups of the reaction product GSH(reduced glutathione).Results:We implemented an HTS effort against 59,360 synthetic *** the primary screening,initial hits(928 or 1.56%)showing greater than 90%inhibition on SmTGR activity at a final concentration of 10μM for each compound were *** tests were carried out to confirm the effects of these hits and to explore the concentration-dependent response *** a result,74 of them(0.12%)representing 17 chemical scaffolds were confirmed and showed a great concentration-dependent inhibitory trend against SmTGR,including structures previously shown to be lethal to schistosomal *** these,two scaffolds displayed a limited structure-activity *** tested in cultured larvae,39 compounds had cidal activity in 48 h,and five of them killed larvae completely at 3.125μ*** these,three compounds also killed adult worms ex vivo at concentrations between 5μM and 10μ***:These confirmed hits may serve as starting points for the development of novel therapeutics to combat schistosomiasis.

关键词： High-throughput screening Schistosomiasis Inhibitor Thioredoxin glutathione reductase

loss of the Krüppel-like factor 4 tumor suppressor is associated with epithelial-mesenchymal transition in colorectal cancer

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Journal of Cancer Metastasis and Treatment 2019年第11期4卷 47-57页

作者： Kimberley C.Agbo Jessie Z.Huang Amr M.Ghaleb Jennie l.williams Kenneth R.Shroyer Agnieszka B.Bialkowska Vincent W.Yang Department of Medicine Stony Brook University School of MedicineStony BrookNY 11794USA Department of Pathology Stony Brook University School of MedicineStony BrookNY 11794USA Department of Family Population and Preventive MedicineStony BrookNY 11794USA Department of Physiology and Biophysics Stony Brook University School of MedicineStony BrookNY 11794USA

Aim: Colorectal cancer (CRC) is the third leading cancer-related cause of death due to its propensity to metastasize. Epithelial-mesenchymal transition (EMT) is a multistep process important for invasion and metastasis of CRC. Krüppel-like factor 4 (KlF4) is a zinc finger transcription factor highly expressed in differentiated cells of the intestinal epithelium. KlF4 has been shown to play a tumor suppressor role during CRC tumorigenesis - its loss accelerates development and progression of cancer. The present study examined the relationship between KlF4 and markers of EMT in CRC. Methods: Immunofluorescence staining for KlF4 and EMT markers was performed on archived patient samples after colorectal cancer resection and on colonic tissues of mice with colitis-associated cancer. Results: We found that KlF4 expression is lost in tumor sections obtained from CRC patients and in those of mouse colon following azoxymethane and dextran sodium sulfate (AOM/DSS) treatment when compared to their respective normal appearing mucosa. Importantly, in CRC patient tumor sections, we observed a negative correlation between KlF4 levels and mesenchymal markers including TWIST, β-catenin, claudin-1, N-cadherin, and ;vimentin. Similarly, in tumor tissues from AOM/DSS-treated mice, KlF4 levels were negatively correlated with mesenchymal markers including SNAI2, β-catenin, and vimentin and positively correlated with the epithelial marker E-cadherin. Conclusion: These findings suggest that the loss of KlF4 expression is a potentially significant indicator of EMT in CRC.

关键词： Krüppel-like factor 4 colorectal cancer epithelial-mesenchymal transition

Creation and judicious application of a wheat resistance gene atlas

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Molecular Plant 2021年第7期14卷 1053-1070页

作者： amber N.Hafeez Sanu Arora Sreya Ghosh David Gilbert Robert l.Bowden Brande B.H.Wulff John Innes Centre Norwich Research ParkNorwichUK USDA-ARS Hard Winter Wheat Genetics Research UnitManhattanKS 66506USA

Disease-resistance(R)gene cloning in wheat(Triticum aestivum)has been accelerated by the recent surge of genomic resources,facilitated by advances in sequencing technologies and ***,with the challenges of population growth and climate change,it is vital not only to clone and functionally characterize a few handfuls of R genes,but also to do so at a scale that would facilitate the breeding and deployment of crops that can recognize the wide range of pathogen effectors that threaten *** populations are continually changing,and breeders must have tools and resources available to rapidly respond to those changes if we are to safeguard our daily *** meet this challenge,we propose the creation of a wheat R-gene atlas by an international community of researchers and *** atlas would consist of an online directory from which sources of resistance could be identified and deployed to achieve more durable resistance to the major wheat pathogens,such as wheat rusts,blotch diseases,powdery mildew,and wheat *** present a costed proposal detailing how the inter-acting molecular components governing disease resistance could be captured from both the host and the pathogen through biparental mapping,mutational genomics,and whole-genome association *** explore options for the configuration and genotyping of diversity panels of hexaploid and tetraploid wheat,as well as their wild relatives and major pathogens,and discuss how the atlas could inform a dynamic,durable approach to R-gene *** against the current magnitude of wheat yield losses worldwide,recently estimated at 21%,this endeavor presents one route for bringing R genes from the lab to the field at a considerable speed and quantity.

关键词： wheat Triticum aestivum disease resistance R genes association genetics gene stewardship durable resistance

Advancing How We learn from Biodesign to Mitigate Risks with Next-Generation Genome Engineering

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BioDesign Research 2020年第1期2020卷 138-140页

作者： Paul E.Abraham Jessy l.labbé amber A.McBride Chemical Sciences Division Oak Ridge National LaboratoryOak RidgeTennessee 37831USA Biosciences Division Oak Ridge National LaboratoryOak RidgeTennessee 37831USA

In the last decade,the unprecedented simplicity and flexibility of the CRISPR-Cas system has made it the dominant transformative tool in gene and genome ***,this democratized technology is both a boon and a bane,for which we have yet to understand the full potential to investigate and rewrite genomes(also named“genome biodesign”).Rapid CRISPR advances in a range of applications in basic research,agriculture,and clinical applications pose new risks and raise several biosecurity *** such a fast-moving field of research,we emphasize the importance of properly communicating the quality and accuracy of results and recommend new reporting requirements for results derived from next-generation genome engineering.

关键词： Genome properly simplicity

U and Th Contents and Th/U Ratios of Zircon in Felsic and Mafic Magmatic Rocks:Improved Zircon-Melt Distribution Coefficients

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Acta Geologica Sinica(English Edition) 2011年第1期85卷 164-174页

作者： WANG Xiang williams l. GRIFFIN CHEN Jie HUANG Pinyun lI Xiang State Key laboratory for Mineral Deposit Research Department of Earth Sciences Nanjing University Nanjing 210093 China GEMOC ARC National Key Center Department of Earth and Planetary Sciences Macquarie University Sydney New South Wales Australia

High-precision data on U and Th contents and Th/U ratios of zircon obtained using secondary ion mass spectrometry analysis have been collected from the literature. Zircon in the granitic rocks has median values of 350 ppm U, 140 ppm Th, and Th/U=0.52; the recommended zircon-melt partition coefficients are 81 for Du and 8.2 for DTh. In zircon from mafic and intermediate rocks, the median values are 270 ppm U, 170 ppm Th, and Th/U=0.81, and the recommended zirconmelt partition coefficients are 169 for Du and 59 for DTh. The U and Th contents and Th/U ratios of magmatic zircon are low when zircon crystallizes in equilibrium with the melt. Increasing magma temperature should promote higher Th contents relative to U contents, resulting in higher Th/U ratios for zircon in mafic to intermediate rocks than in granitic rocks. However, when zircon crystallizes in disequilibrium with the melt, U and Th are more easily able to enter the zircon lattice, and their contents and Th/U ratios depend mainly on the degree of disequilibrium. The behavior of U and Th in magmatic zircon can be used as a geochemical indicator to determine the origins and crystallization environments of magmatic zircon.

关键词： zircon Th/U ratio granitic rock mafic to intermediate rock zircon-melt distributioncoefficient

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阿育吠陀医学--被遗忘的历史

亚太传统医药 2017年第7期13卷 1-2页

作者： Yogini s.Jaiswal leonard l.williams 北卡罗来纳州农业技术州立大学美国坎纳波利斯

阿育吠陀被认为是世界上最古老的医学体系之一,在这个神奇又神秘的医学体系中,还有许多智慧未被挖掘出来。世界上存在着许多种传统医学体系,不同传统医学体系的交融可为草药医学的发展带来新的契机。而目前,人们缺乏对传统医学体系间相... 详细信息

阿育吠陀被认为是世界上最古老的医学体系之一,在这个神奇又神秘的医学体系中,还有许多智慧未被挖掘出来。世界上存在着许多种传统医学体系,不同传统医学体系的交融可为草药医学的发展带来新的契机。而目前,人们缺乏对传统医学体系间相似性和差异性的理解,导致融合出现障碍。拟阐述阿育吠陀医学的古老历史和基本准则,以期帮助学者、研究人员和行医者更加深刻地了解传统医学体系,进而使阿育吠陀医学与其他传统医学体系之间求同存异,克服障碍,获得全球的认可和相互和谐共存。

关键词：阿育吠陀自然疗法顺势疗法