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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

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Mathematical modeling for estimating influenza vaccine efficacy:A case study of the Valencian Community,Spain.

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Infectious Disease Modelling 2024年第3期9卷 744-762页

作者： Carlos Andreu-Vilarroig rafael J.Villanueva Gilberto González-Parra Instituto de Matemática Multidisciplinar Universitat Politècnica de ValènciaValenciaSpain Department of Mathematics New Mexico TechSocorroNMUSA

Vaccine efficacy and its quantification is a crucial concept for the proper design of public health vaccination *** this work we proposed a mathematical model to estimate the efficacy of the influenza vaccine in a real-word *** particular,our model is a SEIR-type epidemiological model,which distinguishes vaccinated and unvaccinated ***,its dynamics is governed by a nonlinear system of ordinary differential equations,where the non-linearity arises from the effective contacts between susceptible and infected *** key aspects of this study is that we use a vaccine distribution over time that is based on real data specific to the elderly people in the Valencian Community and the calibration process takes into account that over one influenza season a specific proportion of the population becomes infected with *** consider the effectiveness of the vaccine,the model incorporates a parameter,the vaccine attenuation factor,which is related with the vaccine efficacy against the influenza *** this framework,in order to calibrate the model parameters and to obtain an influenza vaccine efficacy estimation,we considered the 2016–2017 influenza season in the Valencian Community,Spain,using the influenza reported cases of vaccinated and *** order to ensure the model identifiability,we choose to deterministically calibrate the parameters for different scenarios and we find the one with the minimum error in order to determine the vaccine *** calibration results suggest that the influenza vaccine developed for 2016–2017 influenza season has an efficacy of approximately 76.7%,and that the risk of becoming infected is five times higher for an unvaccinated individual in comparison with a vaccinated *** estimation partially agrees with some previous studies related to the influenza *** study presents a new integrated mathematical approach to study the influenza vaccine efficacy and gives f

关键词： Mathematical modeling Epidemiology SEIR Vaccine efficacy Influenza Valencian community

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Structural foundation and Geometry of the Material Singularity (and Its Quantum Entanglement)

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Journal of High Energy Physics, Gravitation and Cosmology 2024年第3期10卷 1095-1137页

作者： rafael Cañete Mesa Independent Researcher Seville Spain

In this paper we develop and study, as the second part of one more general development, the energy transmutation equation for the material singularity, previously obtained through the symmetrisation of a wave packet, that is, we develop the correlation between the terms of this equation, which accounts for the formation of matter from a previous vibrational state, and the different possible energy species. These energetic species are ascribed, in a simplified form, to the equation E¯ω=E¯k+E¯f, which allows us, through its associated phase factor, to gain an insight into the wave character of the kinetic energy and thus to attain the basis of the matter-wave, and all sorts of related phenomenologies, including that concerning quantum entanglement. The formation of the matter was previously identified as an energetic process, analogous to the kinetic one, in which finally the inertial mass is consolidated as a mass in a different phase, now, in addition, the mass of the material singularity is identified as a volumetric density of waves of toroidal geometry created in the process of singularisation or energy transfer between species, which makes it possible to establish the real relation or correspondence between the corpuscular and photonic energy equation (E=mc2=hν), i.e. to explain through m the intimate sense of the first equivalence, which explains what νis in the second one.

关键词： Standard Model Wave-Packet Material Singularity Wave-Particle Dualism Wave Symmetrisation Matter-Wave Energetic Transmutation Quantum Entanglement

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促进慢性阻塞性肺疾病哮喘患者自我监控空气质量的护理干预措施: 整合性综述

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International Journal of Nursing Sciences 2024年第1期11卷 46-56页

作者： Bruna f.Sebastiao Raquel M.Hortelao Sara S.Granadas Jose M.faria Joana R.Pinto Helga rafael Henriques Nursing School of Lisbon LisbonPortugal Hospital Center of Central Lisbon Portugal CUf Tejo Hospital LisbonPortugal University Hospital Center of Northern Lisbon LisbonPortugal Nursing Research Innovation and Development Centre of Lisbon(CIDNUR)LisbonPortugal

目的哮喘-慢性阻塞性肺疾病肺重叠症(Asthma-chronie obst ructive pulmonary disease overlap,A-CO)患者的生活质量较低,肺功能较差,病情经常加重。由于暴露于污染环境会加重其症状,增加发病率和病死率,环境管理对其至关重要。旨在通... 详细信息

目的哮喘-慢性阻塞性肺疾病肺重叠症(Asthma-chronie obst ructive pulmonary disease overlap,A-CO)患者的生活质量较低,肺功能较差,病情经常加重。由于暴露于污染环境会加重其症状,增加发病率和病死率,环境管理对其至关重要。旨在通过系统性综述,寻找证据,以指导制订护理干预措施,促进ACO患者对空气质量的自我管理。方法2023年3月 ,系统检索CINAHL、Medline、Academie Search Complete .Scopus、WebofScience、Cochrane图书馆、乔安娜布里格斯研究所(JoannaBriggsInstitute,JBI)循证实践数据库,以及GoogleScholar。对纳人研究进行数据提取和综合,并对护理干预措施进行分类。采用JBI研究质量评估工具进行方法学质量评估。结果共纳入5篇来自不同国家的研究。促进ACO患者自我监控空气质量的干预措施包括:警觉性干预措施(医务人员定期巡诊、进行症状评估),监测干预措施(监测室内外诱发因素) ,教育干预措施(空气质量警报、避免接触过敏原),以及相关政策的影响,如无烟政策和改善空气质量的综合战略。尽管这些研究报告了不同的干预措施,方法质量也存在差异,但这些干预措施显示了预防患者病情恶化、尽量减少急诊就诊和住院治疗的潜力。这些关键点可作为护理干预措施的关键组成部分。结论有必要采取全面措施,让护士参与促进患者自我监控空气质量的多学科团队.提高认识、制订和实施护理干预,从而使ACO患者受益。同时,需要进--步开展研究,以扩大证据基础并完善这些干预措施。

关键词：空气质量哮喘哮喘-慢阻肺重叠慢性病慢性阻塞性肺疾病护理自我管理

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Predicting major adverse cardiovascular events after orthotopic liver transplantation using a supervised machine learning model:A cohort study

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World Journal of Hepatology 2024年第2期16卷 193-210页

作者： Jonathan Soldera Leandro Luis Corso Matheus Machado Rech Vinícius Remus Ballotin Lucas Goldmann Bigarella fernanda Tomé Nathalia Moraes rafael Sartori Balbinot Santiago Rodriguez Ajacio Bandeira de Mello Brandão Bruno Hochhegger Post Graduate Program at Acute Medicine and Gastroenterology University of South WalesCardiff CF371DLUnited Kingdom Postgraduate Program in Pathology Federal University of Health Sciences of Porto Alegre(UFCSPA)Porto Alegre 90050-170Brazil Department of Engineering Universidade de Caxias do SulCaxias do Sul 95070-560Brazil School of Medicine Universidade de Caxias do SulCaxias do Sul 95070-560Brazil Postgraduate Program in Hepatology Federal University of Health Sciences of Porto Alegre(UFCSPA)Porto Alegre 90050-170Brazil

BACKGROUND Liver transplant(LT)patients have become older and *** rate of post-LT major adverse cardiovascular events(MACE)has increased,and this in turn raises 30-d post-LT *** cardiac stress testing loses accuracy when applied to pre-LT cirrhotic *** To assess the feasibility and accuracy of a machine learning model used to predict post-LT MACE in a regional *** This retrospective cohort study involved 575 LT patients from a Southern Brazilian academic *** developed a predictive model for post-LT MACE(defined as a composite outcome of stroke,new-onset heart failure,severe arrhythmia,and myocardial infarction)using the extreme gradient boosting(XGBoost)machine learning *** addressed missing data(below 20%)for relevant variables using the k-nearest neighbor imputation method,calculating the mean from the ten nearest neighbors for each *** modeling dataset included 83 features,encompassing patient and laboratory data,cirrhosis complications,and pre-LT cardiac *** performance was assessed using the area under the receiver operating characteristic curve(AUROC).We also employed Shapley additive explanations(SHAP)to interpret feature *** dataset was split into training(75%)and testing(25%)*** was evaluated using the Brier *** followed Transparent Reporting of a Multivariable Prediction Model for Individual Prognosis or Diagnosis guidelines for ***-learn and SHAP in Python 3 were used for all *** supplementary material includes code for model development and a user-friendly online MACE prediction *** Of the 537 included patients,23(4.46%)developed in-hospital MACE,with a mean age at transplantation of 52.9 *** majority,66.1%,were *** XGBoost model achieved an impressive AUROC of 0.89 during the training *** model exhibited accuracy,precision,recall,and f1-score values of 0.84,0.85,0.80,and 0.79,***

关键词： Liver transplantation Major adverse cardiac events Machine learning Myocardial perfusion imaging Stress test

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A RANS-Vof Numerical Model to Analyze the Output Power of An OWC-WEC Equipped with Wells and Impulse Turbines in A Hypothetical Sea-State

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China Ocean Engineering 2020年第6期34卷 760-771页

作者： Paulo R.f.Teixeira rafael A.A.C.Gonçalves Eric Didier Engineering School Universidade Federal do Rio Grande-FURGRio GrandeRS 96203-900Brazil Harbours and Maritime Structures Division Hydraulics and Environment DepartmentLaboratório Nacional de Engenharia Civil-LNECLisbon 1700-066Portugal

Wave energy is a renewable source with significant amount in relation to the global demand. A good concept of a device applied to extract this type of energy is the onshore oscillating water column wave energy converter(OWC-WEC). This study shows a numerical analysis of the diameter determination of two types of turbines, Wells and Impulse, installed in an onshore OWC device subjected to a hypothetical sea state. Commercial software fLUENT?,which is based on RANS-Vof(Reynolds-Averaged Navier-Stokes equations and Volume of fluid technique), is employed. A methodology that imposes air pressure on the chamber, considering the air compressibility effect, is used. The mathematical domain consists of a 10 m deep flume with a 10 m long and 10 m wide OWC chamber at its end(geometry is similar to that of the Pico's plant installed in Azores islands, Portugal). On the top of the chamber, a turbine works with air exhalation and inhalation induced by the water free surface which oscillates due to the incident wave. The hypothetical sea state, represented by a group of regular waves with periods from 6 to 12 s and heights from 1.00 to 2.00 m(each wave with an occurrence frequency), is considered to show the potential of the presented methodology. Maximum efficiency(relation between the average output and incident wave powers) of46% was obtained by using a Wells turbine with the diameter of 2.25 m, whereas the efficiency was 44% by an Impulse turbine with the diameter of 1.70 m.

关键词： wave energy oscillating water column Wells turbine Impulse turbine RANS-Vof compressible air

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促进慢性阻塞性肺疾病哮喘患者自我监控空气质量的护理干预措施:整合性综述（英文）

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International Journal of Nursing Sciences 2024年第1期 46-56页

作者： Bruna f.Sebasti?o Raquel M.Hortel?o Sara S.Granadas José M.faria Joana R.Pinto Helga rafael Henriques Nursing School of Lisbon Hospital Center of Central Lisbon CUf Tejo Hospital University Hospital Center of Northern Lisbon Nursing Research Innovation and Development Centre of Lisbon (CIDNUR)

目的哮喘-慢性阻塞性肺疾病肺重叠症(Asthma-chronic obstructive pulmonary disease overlap,ACO)患者的生活质量较低,肺功能较差,病情经常加重。由于暴露于污染环境会加重其症状,增加发病率和病死率,环境管理对其至关重要。旨在通过... 详细信息

目的哮喘-慢性阻塞性肺疾病肺重叠症(Asthma-chronic obstructive pulmonary disease overlap,ACO)患者的生活质量较低,肺功能较差,病情经常加重。由于暴露于污染环境会加重其症状,增加发病率和病死率,环境管理对其至关重要。旨在通过系统性综述,寻找证据,以指导制订护理干预措施,促进ACO患者对空气质量的自我管理。方法 2023年3月,系统检索CINAHL、Medline、Academic Search Complete、Scopus、Web of Science、Cochrane图书馆、乔安娜布里格斯研究所(Joanna Briggs Institute,JBI)循证实践数据库,以及Google Scholar。对纳入研究进行数据提取和综合,并对护理干预措施进行分类。采用JBI研究质量评估工具进行方法学质量评估。结果共纳入5篇来自不同国家的研究。促进ACO患者自我监控空气质量的干预措施包括:警觉性干预措施(医务人员定期巡诊、进行症状评估),监测干预措施(监测室内外诱发因素),教育干预措施(空气质量警报、避免接触过敏原),以及相关政策的影响,如无烟政策和改善空气质量的综合战略。尽管这些研究报告了不同的干预措施,方法质量也存在差异,但这些干预措施显示了预防患者病情恶化、尽量减少急诊就诊和住院治疗的潜力。这些关键点可作为护理干预措施的关键组成部分。结论有必要采取全面措施,让护士参与促进患者自我监控空气质量的多学科团队、提高认识、制订和实施护理干预,从而使ACO患者受益。同时,需要进一步开展研究,以扩大证据基础并完善这些干预措施。

关键词：空气质量哮喘哮喘-慢阻肺重叠慢性病慢性阻塞性肺疾病护理自我管理

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The Use of Secondary Grape Biomass in Beef Cattle Nutrition on Carcass Characteristics, Quality and Shelf Life of Meat

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food and Nutrition Sciences 2024年第6期15卷 447-469页

作者： Vitor L. Molosse Guilherme L. Deolindo rafael V. P. Lago Bruna Klein Claiton A. Zotti Marcelo Vedovato Marcylene V. da Silveira Priscila M. Copetti Maria R. C. Schetinger Juscivete f. favero Eliana L. fiorentin Aleksandro S. da Silva Universidade do Estado de Santa Catarina (UDESC) Chapec Brazil Department of Animal Science UDESC Chapec Brazil Department of Animal Science Universidade do Oeste de Santa Catarina Xanxere Brazil Dean Lee Research and Extension Center Louisiana State University Alexandria LA USA Department of Biochemistry Universidade Federal de Santa Maria Santa Maria Brazil Department of Medicina Veterinria UNOCHAPEC Chapec Brasil

We determined whether the inclusion of 100 g/kg dry matter of grape pomace silage (GPS) and grape pomace bran (GPB) as substitutes for other traditional fiber sources in the diet of steers (Charolais x Nellore) would improve carcass characteristics, meat quality and composition, and shelf life. Twenty-four animals (248 ± 19.32 kg of initial body weight) were fed a high concentrate diet for 121 days. Carcass characteristics were measured, and the longissimus dorsi muscle was analyzed for fatty acid (fA) profile and composition. The meat was sliced and stored in air-permeable packages for 10 days. On each sampling day (d 1, 3, 7, and 10), oxidative stability, bacterial load, lipid and protein oxidation, and staining were analyzed. The experimental diets influenced the pH of cold carcasses only. The GPS group had a higher pH than the control. The GPS and GPB groups showed improved oxidant status (i.e., lower lipid peroxidation and concentrations of reactive oxygen species were in the meat of both groups than in control). On the first day of storage, the antioxidant enzyme glutathione S-transferase activity was more significant in the meat of the GPS and GPB groups than in the control. The bacterial loads in the meat were attenuated by GPS inclusion;there were lower total coliform counts and a trend toward lower counts for enterobacteria in the control group. The diets altered the fA profile of the meat;i.e., the GPB diet allowed for a more significant amount of the n-6 omegas in the meat, while the GPS diet showed a tendency for a more significant amount of n-6 and 9 omegas. Both diets (GPS and GPB) increased the amounts of long-chain fAs. The GPS diet decreased saturated fA levels. We conclude that the dietary treatments GPS and GPB are a promising alternative to maintain meat quality standards throughout in real-world retail conditions. These treatments gave rise to an improvement in the nutritional value of the meat due to the more significant amounts of fAs that im

关键词： Animal Nutrition Antioxidant Biomass Grape Meat Quality Microbiology Residue

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Microfibrillated Cellulose from Sugarcane Bagasse as a Biorefinery Product for Ethanol Production

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Journal of Renewable Materials 2018年第2期6卷 195-202页

作者： rafael Grande Eliane Trovatti Maria Tereza B.Pimenta Antonio J.f.Carvalho University of São Paulo Av.João Dagnone 1100CEP 13563-120São CarlosSão PauloBrazil University of Araraquara(UNIARA) R.Carlos Gomes1217CEP 14801-320AraraquaraSão PauloBrazil Suzano Papel e Celulose SA Av.Lirio Correa146506460-040LimeiraSão PauloBrazil

Research involving the preparation of microfibrillated cellulose(MfC)from sugarcane bagasse is a relevant topic to the production of new nanomaterials and more accessible cellulose substrates for the production of second generation *** the transformation of cellulose into glucose,the precursor of second generation ethanol,this nanosized cellulosic substrate represents a more appropriate material for the chemical hydrolysis *** high aspect ratio of MfC improves hydrolysis,requiring mild conditions and decreasing the generation of ***,MfC was prepared from sugarcane bagasse by ultrasound *** material was oxidized with 2,2,6,6-tetramethylpiperidine-N-oxyl(TEMPO)to produce negatively charged high defibrillated *** MfC was characterized by fourier transform infrared spectroscopy(fTIR),X-ray diffraction(XRD),scanning electron microscopy(SEM)and viscosity measurements.

关键词： Cellulose nanofibrils substrate second generation ethanol

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Genetic characteristics of H1N1 influenza virus outbreak in China in early 2023

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Virologica Sinica 2024年第3期39卷 520-523页

作者： Xuanxuan Li Zefeng Dong Jiaming Li Chuanran Dou Deyu Tian Zhenghai Ma Wenjun Liu George f.Gao Yuhai Bi College of Life Science and Technology Xinjiang UniversityUrumchi830046China cas Key Laboratory of Pathogen Microbiology and Immunology Institute of MicrobiologyCenter for Influenza Research and Early-warning(CASCIRE)CAS-TWAS Center of Excellence for Emerging Infectious Diseases(CEEID)Chinese Academy of SciencesBeijing100101China Suzhou Center for Disease Control and Prevention Suzhou215004China Lafayette College EastonPA 18042USA University of Chinese Academy of Sciences Beijing100049China D.H.Chen School of Universal Health Zhejiang UniversityHangzhou 310058China

Dear Editor,Influenza A virus(IAV)exhibits rapid mutability and antigenic *** the 20th century,IAV has caused at least four pandemics(Yang et al.,2022).Presently,seasonal H_(3)N_(2)and H1N1 are the prevailing human-adaptive IAV subvariants responsible for human *** implementation of public health interventions since the commencement of the COVID-19 pandemic has effectively curtailed global influenza circulation(Olsen et al.,2021).following the downregulation of the prevention and control strategies against COVID-19,global influenza activity is showing a recovery.

关键词： influenza prevention H1N1

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