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Telomeric DNA breaks in human induced pluripotent stem cells trigger ATR-mediated arrest and telomerase-independent telomere damage repair

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Journal of Molecular Cell Biology 2024年第3期16卷 46-60页

作者： katrina N.Estep John W.Tobias Rafael J.Fernandez Brinley M.Beveridge F.Brad Johnson Department of Pathology and Laboratory Medicine University of PennsylvaniaPhiladelphiaPA 19104USA Quantiative Biosciences Merck&Co.Inc.West PointPA 19486USA Penn Genomic Analysis Core University of PennsylvaniaPhiladelphiaPA 19104USA

Although mechanisms of telomere protection are well-defined in differentiated cells,how stem cells sense and respond to telomere dysfunction,in particular telomeric double-strand breaks(DSBs),is poorly ***,we report the DNA damage signaling,cell cycle,and transcriptome changes in human induced pluripotent stem cells(iPscs)in response to telomere-internal *** engineer human iPscs with an inducible TRF1-FokI fusion protein to acutely induce DSBs at *** this model,we demonstrate that TRF1-FokI DSBs activate an ATR-dependent DNA damage response,which leads to p53-independent cell cycle arrest in *** CRISPR–Cas9 to cripple the catalytic domain of telomerase reverse transcriptase,we show that telomerase is largely dispensable for survival and lengthening of TRF1-FokI-cleaved telomeres,which instead are effectively repaired by robust homologous recombination(HR).In contrast to HR-based telomere maintenance in mouse embryonic stem cells,where HR causes ZscAN4-dependent extension of telomeres beyond their initial lengths,HR-based repair of telomeric breaks is sufficient to maintain iPsc telomeres at a normal length,which is compatible with sustained survival of the cells over several days of TRF1-FokI *** findings suggest a previously unappreciated role for HR in telomere maintenance in telomerase-positive iPscs and reveal distinct iPsc-specific responses to targeted telomeric DNA damage.

关键词： telomeres telomerase alternative lengthening of telomeres pluripotent stem cells DNA damage double-strand breaks

Voices From the Industry:How EdTech Leaders Responded to the COVID-19 Pandemic

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ECNU Review of Education 2024年第2期7卷 420-441页

作者： Deoksoon Kim katrina Borowiec Drina Kei Yatsu Stanton Wortham Boston College Lynch School of Education and Human DevelopmentI40 Commonwealth AvenueChestnut HillMA02467-3800USA

Purpose Educational technology(“EdTech”)served a pivotal role in keeping schools functioning during the beginning of the COVID-19 *** is known about EdTech leaders’roles in shaping this *** study explores EdTech leaders’perspectives and backgrounds,their response to the pandemic,how they envision their roles as educators,and their perspectives about how technology facilitates educational ***/Approach/Methods This study uses a qualitative,phenomenological approach to understand how 11 EdTech leaders experienced the *** were recruited for interviews in summer 2021 via purposive sampling to include diverse backgrounds and *** were analyzed *** The findings show that a four-category typology can be used to describe EdTech leaders’diverse backgrounds and *** emphasized equity and open collaboration in their pandemic responses,by expanding access to their tools and adapting their products as users’needs *** leaders anticipate streamlined user experiences,improvements in online learning,and increased adoption of artificial intelligence and simulated learning ***/Value This study addresses a gap in the research concerning EdTech leaders’perspectives on their efforts to support educators and their experiences during the *** hope this study sparks additional research on EdTech leaders’experiences and roles in education.

关键词： Collaboration COVID-19 pandemic educational technology innovation leadership technology access

A New Era in EdTech:Emerging Challenges and Opportunities

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ECNU Review of Education 2024年第2期7卷 252-257页

作者： Deoksoon Kim katrina Borowiec Stanton Wortham Lynch school of Education and Human Development Chestnut HillMassachusetts 02467-3800USA

The COVID-19 pandemic dramatically expanded the increasingly important role of educational technology(“EdTech”)in K-16 *** is“the introduction of information and technology tools in teaching and learning”(Ganimian et al.,2020,p.5).Examples of EdTech include audio-visual aids,computer-assisted learning,mobile devices,smart technologies,and virtual reality(Huang et al.,2019).One sign of the growing importance of technology in schools is the rapid increase in EdTech investments,which tripled between 2019(pre-COVID)and 2021(during COVID;HolonIQ,2022).Nonetheless,inequality in access to technology remains a barrier for students in underserved schools(Chapman et al.,2010;Dorn et al.,2020).

关键词： smart teaching expanded

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黑客利用“社交工程”入侵IT部门

商业周刊（中文版） 2024年第2期 18-19页

作者： Margi Murphy katrina Manson 融汐(译) 不详

从许多方面来说,这是一次平淡无奇的交谈。一名IT技术支持部门的员工接了一个电话,自我介绍后问道:“您想问的是关于新机票还是已买机票的?”来电者听起来像是一个20岁出头的美国人,他解释说,他在登录自己的账户时遇到了麻烦:“我不知... 详细信息

从许多方面来说,这是一次平淡无奇的交谈。一名IT技术支持部门的员工接了一个电话,自我介绍后问道:“您想问的是关于新机票还是已买机票的?”来电者听起来像是一个20岁出头的美国人,他解释说,他在登录自己的账户时遇到了麻烦:“我不知道如何重置密码,所以我今天打电话来是要重置密码的。”来电者提供了他的名字,而这个名字与一名员工的名字相符。

关键词： IT技术自我介绍黑客 IT部门密码机票入侵重置

Estimating geographic variation of infection fatality ratios during epidemics

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Infectious Disease Modelling 2024年第2期9卷 634-643页

作者： Joshua Ladau Eoin L.Brodie Nicola Falco Ishan Bansal Elijah B.Hoffman Marcin P.Joachimiak Ana M.Mora Angelica M.Walker Haruko M.Wainwright Yulun Wu Mirko Pavicic Daniel Jacobson Matthias Hess James B.Brown katrina Abuabara Departments of Computational Precision Health and Dermatology University of CaliforniaSan FranciscoCA94115USA Arva Intelligence Inc.Salt Lake CityUT84101USA Computational Biosciences Group Lawrence Berkeley National LaboratoryBerkeleyCA94720USA Earth and Environmental sciences Area Lawrence Berkeley National LaboratoryBerkeleyCA94720USA Graduate Group in Biostatistics University of CaliforniaBerkeleyCA94720USA Biosystems Data science Environmental Genomics and Systems BiologyLawrence Berkeley National LaboratoryBerkeleyCA94720USA Center for Environmental Research and Community Health(CERCH) School of Public HealthUniversity of CaliforniaBerkeleyCA94720USA Bredesen Center for Interdisciplinary Research and Graduate Education University of TennesseeKnoxvilleTN37996USA Department of Nuclear science and Engineering Massachusetts Institute of TechnologyBostonMA02139USA Biosciences Oak Ridge National LaboratoryOak RidgeTN37830USA University of California DavisCA95616USA Statistics Department University of CaliforniaBerkeleyCA94720USA Division of Epidemiology and Biostatistics University of California Berkeley School of Public Health2121 Berkeley WayBerkeleyCA94720USA

Objectives We aim to estimate geographic variability in total numbers of infections and infection fatality ratios(IFR;the number of deaths caused by an infection per 1,000 infected people)when the availability and quality of data on disease burden are limited during an *** We develop a noncentral hypergeometric framework that accounts for differential probabilities of positive tests and reflects the fact that symptomatic people are more likely to seek *** demonstrate the robustness,accuracy,and precision of this framework,and apply it to the United States(U.S.)COVID-19 pandemic to estimate county-level SARS-CoV-2 *** The estimators for the numbers of infections and IFRs showed high accuracy and precision;for instance,when applied to simulated validation data sets,across counties,Pearson correlation coefficients between estimator means and true values were 0.996 and 0.928,respectively,and they showed strong robustness to model *** the county-level estimators to the real,unsimulated COVID-19 data spanning April 1,2020 to September 30,2020 from across the U.S.,we found that IFRs varied from 0 to 44.69,with a standard deviation of 3.55 and a median of *** The proposed estimation framework can be used to identify geographic variation in IFRs across settings.

关键词： Infection fatality ratio Infection fatality rate Noncentral hypergeometric distribution COVID-19 SARS-CoV-2

Measurement and quantification of caking in excipients and food products with emphasis on the non-homogeneous interaction with ambient moisture

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Particuology 2021年第3期19卷 75-83页

作者： katrina Brockbank Brian Armstrong Jamie Clayton Freeman Technology Ltd 1 Miller CourtSevern DriveTewkesburyGloucestershireGL208DNUK

Whilst caking occurs via several different mechanisms,absorption and migration of moisture is frequently the most dominant mechanism within the food and pharmaceutical *** understanding the propensity to cake is important for minimising down-stream process issues,however most characterisation techniques assume that moisture induced caking occurs homogenously through the sample resulting in a uniformly caked powder *** this study,the effect of moisture induced caking on powder flowability was investigated using powder *** materials,including skimmed milk powder(SMP)and sulphated methyl ester(SME)were stored for several days under controlled humidity *** flow energies,a measure of the resistance to flow,were measured at 24 h intervals using an FT4 Powder *** the energy is measured as a function of the bed height,variations in the powder bed are also *** results demonstrated that caking does not always occur uniformly,instead a caked region(or crust)forms at the air-powder interface and then progresses through the powder ***,the strength of this caked region was shown to increase over several days before stabilising.

关键词： Powder Caking Crust formation Powder rheometry Relative humidity

Alcoholic pancreatitis:Lessons from the liver

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World Journal of Gastroenterology 2010年第11期16卷 1314-1320页

作者： Dahn L Clemens katrina J Mahan Department of Internal Medicine University of Nebraska Medical Center Research Service Veterans Administration Medical Center

The association between alcohol consumption and pancreatitis has been recognized for over 100 years. Despite the fact that this association is well recognized, the mechanisms by which alcohol abuse leads to pancreatic tissue damage are not entirely clear. Alcohol abuse is the major factor associated with pancreatitis in the Western world. Interestingly, although most cases of chronic pancreatitis and many cases of acute pancreatitis are associated with alcohol abuse, only a small percentage of individuals who abuse alcohol develop this disease. This situation is reminiscent of the association between alcohol abuse and the incidence of alcoholic liver disease. The liver and the pancreas are developmentally very closely related. Even though these two organs are quite different, they exhibit a number of general structural and functional similarities. Furthermore, the diseases mediated by alcohol abuse in these organs exhibit some striking similarities. The diseases in both organs are characterized by parenchymal cell damage, activation of stellate cells, aberrant wound healing, and fibrosis. Because of the similarities between the liver and the pancreas, and the alcohol-associated diseases of these organs, we may be able to apply much of the knowledge that we have gained regarding the effects of alcohol on the liver to the pancreas.

关键词： Alcoholic pancreatitis Alcohol metabolism Stellate cells Fibrosis

Behavioral and physiological flexibility are used by birds to manage energy and support investment in the early stages of reproduction

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Current Zoology 2010年第6期56卷 767-792页

作者： Franois VZINA katrina G. SALVANTE Département de Biologie chimie et géographieGroupe de recherche sur les environnements nordiques BORASUniversité du Québec à Rimouski Department of Biological sciences Simon Fraser University

Interest in phenotypic flexibility has increased dramatically over the last decade, but flexibility during reproduction has received relatively little attention from avian scientists, despite its possible impact on fitness. Because most avian species maintain atrophied reproductive organs when not active, reproduction in birds requires major tissue remodeling in preparation for breeding. Females undergo rapid （days） recrudescence and regression of their reproductive organs at each breeding attempt, while males grow their organs ahead of time at a much slower rate （weeks） and may maintain them at maximal size throughout the breeding season. Reproduction is associated with significant metabolic costs. Egg production leads to a 22%-27% increase in resting metabolic rate （RMR） over non-reproductive values. This is partly due to the activity of the oviduct, an organ that may allow females to adjust reproductive investment by modulating egg size and quality. In males, gonadal recrudescence may lead to a 30% increase in RMR, but the data are inconsistent and general conclusions regarding energetic costs of reproduction in males will require more research. Recent studies on captive female zebra finches describe the impacts of these costs on daily energy budgets and highlight the strategies used by birds to maintain their investment in reproduction when energy is limited. Whenever possible, birds use behavioral flexibility as a first means of saving energy. Decreasing locomotor activity saves energy during challenges such as egg production or exposure to cold temperatures and is an efficient way to buffer variation in individual daily energy budgets. However, when behavioral flexibility is not possible, birds must rely on flexibility at the physiological level to meet energy demands. In zebra finches breeding in the cold, this results in a reduced pace of laying, likely due to down-regulation of both reproductive and non-reproductive function, allowing females to defend mini

关键词： Phenotypic plasticity Phenotypic flexibility BMR Energy budget Organ Egg size Physiological tradeoff Fitness

Photocatalytic degradation of Chicago Sky Blue 6B and Benzopurpurin 4B using titanium dioxide thin film

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Journal of Environmental sciences 2005年第5期17卷 869-872页

作者： Abdul K. Mohammed katrina T. McKenzie Department of Chemistry Winston-Salem State UniversityDepartment of Chemistry North Carolina Agricultural and Technical State University 601 S. Martin Luther King Jr. Drive Winston-Salem North Carolina 27110 USA1601 E. Market Street Greensboro North Carolina 27411 USA

Aqueous solutions of azo dyes undergo degradation to form harmless intermediates and colorless products following irradiation by visible light in the presence of titanium dioxide thin films. The dyes that were studied in this work are： Chicago Sky Blue 6B and Benzopurpurin 4B. Results obtained indicated that complete mineralization of the dyes took place under the experimental conditions. There was an increase in conductivity after the complete mineralization experiments possibly indicating the formation of ions such as NO3^- and SO4^2-. Chemical oxygen demand（COD） measurements show a decrease in organic matter for both dyes following complete degradation. The effect of how changing experimental conditions such as pH, temperature and starting concentrations of dyes affected the rate of dye degradation was measured. There was an increase in the rate of disappearance of the dye color at lower pH. High concentrations of dye solutions reauired Iona dearadation time.

关键词： titanium dioxide photocatalysis photocatalytic degradation azo dyes