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Adeno-associated virus as a delivery vector for gene therapy of human diseases

Signal Transduction and Targeted Therapy 2024年第5期9卷 1808-1840页

作者： jiang-Hui Wang Dominic j.Gessler Wei Zhan Thomas l.Gallagher Guangping Gao Horae Gene Therapy Center University of Massachusetts Chan Medical SchoolWorcesterMA01605USA Department of Microbiology and Physiological Systems University of Massachusetts Chan Medical SchoolWorcesterMA01605USA Centre for Eye Research Australia Royal Victorian Eye and Ear HospitalEast MelbourneVIC3002Australia Ophthalmology Department of SurgeryUniversity of MelbourneEast MelbourneVIC3002Australia Department of Neurological Surgery University of Massachusetts Chan Medical SchoolWorcesterMA01605USA Department of Neurosurgery University of MinnesotaMinneapolisMN55455USA Department of Medicine University of Massachusetts Chan Medical SchoolWorcesterMA01605USA li Weibo Institute for rare Diseases Research University of Massachusetts Chan Medical SchoolWorcesterMA01605USA

Adeno-associated virus(AAV)has emerged as a pivotal delivery tool in clinical gene therapy owing to its minimal pathogenicity and ability to establish long-term gene expression in different *** AAV(raAV)has been engineered for enhanced specificity and developed as a tool for treating various ***,as raAV is being more widely used as a therapy,the increased demand has created challenges for the existing manufacturing *** raAV-based gene therapy products have received regulatory approval,but there continue to be concerns about safely using high-dose viral therapies in humans,including immune responses and adverse effects such as genotoxicity,hepatotoxicity,thrombotic microangiopathy,and *** this review,we explore AAV biology with an emphasis on current vector engineering strategies and manufacturing *** discuss how raAVs are being employed in ongoing clinical trials for ocular,neurological,metabolic,hematological,neuromuscular,and cardiovascular diseases as well as *** outline immune responses triggered by raAV,address associated side effects,and discuss strategies to mitigate these *** hope that discussing recent advancements and current challenges in the field will be a helpful guide for researchers and clinicians navigating the ever-evolving landscape of raAV-based gene therapy.

关键词： diseases specificity approval

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Evaluation of the efficiency of urban solid waste management in Brazil by data envelopment analysis and possible variables of influence

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Waste Disposal and Sustainable Energy 2024年第2期6卷 283-295页

作者： Isabel das Merces Costa Marta ferreira Dias Margarita Robaina GOvCOPP-Research Unit on Governance Competitiveness and Public Policies and Analyst of UniversidadeEstadual de Feira de SantanaUniversidade de AveiroAveiroPortugal GOvCOPP-Research Unit on Governance Competitiveness and Public PoliciesDEGEIT-Department of EconomicsManagementIndustrial Engineering and TourismUniversidade de AveiroAveiroPortugal

This article has the general objective of estimating the efficiency of urban solid waste management in 940 Brazilian munici-palities through Data Envelopment Analysis(DEA)technique and has specific objectives:(i)to estimate efficiency scores;(ii)to compare the performance between different groups of municipalities;and(ii)to analyze the profile of efficient munici-palities from the perspective of the guidelines of law 12,305/2010 and socio-economic and environmental *** technique used was DEA with output-oriented and variable scale to return *** results showed higher efficiency scores in the municipalities with populations above 500,000 *** score variation ranged from 0.5(municipalities with populationslities with more than 500,000 inhabitants).Of the sample set,only 12.34%of the municipalities were considered efficient,and when analyzing the efficient group,it was found that adherence to legislation was not a major factor in achieving efficiency.

关键词： Urban solid waste management Data envelopment analysis Efficiency Brazil Municipalities

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Impact of Paenibacillus elgii supernatant on screening bacterial strains with potential for biotechnological applications

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Engineering Microbiology 2024年第3期4卷 1-15页

作者： I.C.Cunha-ferreira C.S.Vizzotto T.D.Frederico j.Peixoto l.S Carvalho M.R.Tótola R.H.Krüger laboratory of Enzymology Department of Cellular BiologyUniversity of Brasília(UNB)Brasília70910-900Brazil laboratory of Environmental Sanitation Department of Civil and Environmental EngineeringUniversity of Brasília(UNB)Brasília70910-900Brazil laboratório de Biotecnologia e Biodiversidade para o Meio Ambiente Universidade Federal de Viçosa(UFV)Viçosa36570-900Brazil

The biotechnological industry faces a crucial demand for novel bioactive compounds,particularly antimicrobial agents,to address the rising challenge of bacterial resistance to current available *** strate-gies for cultivating naturally occurring microorganisms often limit the discovery of novel antimicrobial *** study presents a protocol for targeted selection of bacterial strains using the supernatant of Paenibacillus el-gii,which produces abundant signal molecules and antimicrobial *** samples were inoculated in these enriched culture media to selectively cultivate bacteria resistant to the supernatant,indicating their potential to produce similar *** bacterial strains isolated through this method were assessed for their antibac-terial *** addition,the functional annotation of the genome of one of these strains revealed several gene clusters of biotechnological *** study highlights the effectiveness of using this approach for selective cultivation of microorganisms with potential for biotechnological applications.

关键词： Prospecting Supernatant Antibacterial activity

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Analysis of ancient mass extinction recoveries in marine environments: generating strategies for managing outcomes of the current mass extinction

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National Science Review 2024年第1期11卷 8-10页

作者： David j.Bottjer Department of Earth Sciences University of Southern California

The defining feature of a mass extinction and its associated recovery is the global amount of extinction that occurred[1]. However, there is finer-scale detail to the story, as seen in the ongoing modern mass extinction(the sixth mass extinction), which exhibits variable effects among marine ecosystems and environments, and hence geographic areas [1].

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Global weirding at mass extinction horizons

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National Science Review 2024年第1期11卷 10-12页

作者： Gregory j.Retallack Department of Earth Sciences University of Oregon

A strong motivation for studying mass extinctions is understanding how current climatic and biodiversity crises will affect creatures living on land such as ourselves. Perhaps the question is: how bad can it get? In that case, terrestrial Permian-Triassic mass extinctions are an irresistible worst-case scenario [1].

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Modelling dynamic pantograph loads with combined numerical analysis

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railway Engineering Science 2024年第1期32卷 81-94页

作者： F.F.jackson R.Mishra j.M.Rebelo j.Santos P.Antunes j.Pombo H.Magalhaes l.Wills M.Askill School of Computing and Engineering University of HuddersfieldHuddersfieldUK School of Computing and Engineering Institute of Railway ResearchUniversity of HuddersfieldHuddersfieldUK IDMEC Instituto Superior TecnicoUniversidade de LisboaLisbonPortugal ISEl Instituto Politecnico de LisboaLisbonPortugal Hitachi rail Newton AycliffeUK Wabtec/Brecknell Willis ChardUK

Appropriate interaction between pantograph and catenary is imperative for smooth operation of electric *** heights of overhead lines to accommodate level crossings,overbridges,and tunnels pose significant challenges in maintaining consistent current collection performance as the pantograph aerodynamic profile,and thus aerodynamic load changes significantly with operational *** research aims to analyse the global flow characteristics and aerodynamic forces acting on individual components of an HSX pantograph operating in different configurations and orientations,such that the results can be combined with multibody simulations to obtain accurate dynamic insight into contact ***,computational fluid dynamics simulations are used to investigate the pantograph component loads in a representative setting,such as that of the recessed cavity on a Class 800 *** an aerodynamic perspective,this study indicates that the total drag force acting on non-fixed components of the pantograph is larger for the knuckle-leading orientation rather than the knuckle-trailing,although the difference between the two is found to reduce with increasing pantograph *** the aerodynamic loads acting on individual components with multibody tools allows for realistic dynamic insight into the pantograph *** results obtained show how considering aerodynamic forces enhance the realism of the models,leading to behaviour of the pantograph-catenary contact forces closely matching that seen in experimental tests.

关键词： Pantograph-catenary interaction Pantograph aerodynamics Computational fluid dynamics Pantograph loads Current collection performance

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Decoding the genetic program of micronucleus formation: linking chromosomal instability to human disease

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Signal Transduction and Targeted Therapy 2024年第7期9卷 2840-2842页

作者： jörg Fahrer Division of Food Chemistry and Toxicology Department of ChemistryRPTU Kaiserslautern-Landau67663 KaiserslauternGermany

A recent study by Adams and colleagues published in Nature unveiled more than one hundred genes that are involved in micronucleus formation,1 which is a biomarker for genomic instability and associated with aging,cancer,and other disorders.2 As an outstanding achievement,the authors identified DSCC1(DNA Replication And Sister Chromatid Cohesion 1)as a critical gene protecting against early developmental defects,genomic instability,reduced proliferative capacity,cohesinopathy-related phenotypes,and tumor development in vivo.

关键词： chromosomal linking Replication

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Impact of device resistances in the performance of graphene‑based terahertz photodetectors

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Frontiers of Optoelectronics 2024年第2期17卷 87-97页

作者： O.Castelló Sofía M.lópez Baptista K.Watanabe T.Taniguchi E.Diez j.E.Velázquez-Pérez Y.M.Meziani j.M.Caridad j.A.Delgado-Notario Department of Applied Physics University of Salamanca37008 SalamancaSpain Unidad de Excelencia en luz y Materia Estructurada(lUMES) University of Salamanca37008 SalamancaSpain Research Center for Electronic and Optical Materials National Institute for Materials Science1-1 NamikiTsukuba 305-0044Japan Research Center for Materials Nanoarchitectonics National Institute for Materials Science1-1 NamikiTsukuba 305-0044Japan Nanotechnology Group USAL-NanolabUniversity of Salamanca37008 SalamancaSpain

In recent years,graphene field-effect-transistors(GFETs)have demonstrated an outstanding potential for terahertz(THz)photodetection due to their fast response and *** features are essential to enable emerging THz applications,including 6G wireless communications,quantum information,bioimaging and ***,the overall performance of these photodetectors may be utterly compromised by the impact of internal resistances presented in the device,so-called access or parasitic *** this work,we provide a detailed study of the influence of internal device resistances in the photoresponse of high-mobility dual-gate GFET *** dual-gate architectures allow us to fine tune(decrease)the internal resistance of the device by an order of magnitude and consequently demonstrate an improved responsivity and noise-equivalent-power values of the photodetector,*** results can be well understood by a series resistance model,as shown by the excellent agreement found between the experimental data and theoretical *** findings are therefore relevant to understand and improve the overall performance of existing high-mobility graphene photodetectors.

关键词： Graphene THz Photodetector Field-effect transistor Plasmonic

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Dental-derived stem cells in tissue engineering:the role of biomaterials and host response

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Regenerative Biomaterials 2024年第1期3卷 17-26页

作者： Weihao Yuan luiza de Almeida Queiroz ferreira Bo Yu Sahar Ansari Alireza Moshaverinia Weintraub Center for Reconstructive Biotechnology Section of ProsthodonticsSchool of DentistryUniversity of CaliforniaLos AngelesLos AngelesCA 90095USA Department of Restorative Dentistry School of DentistryUniversidade Federal de Minas GeraisBelo HorizonteMinas GeraisBrazil Section of Restorative Dentistry School of DentistryUniversity of CaliforniaLos AngelesLos AngelesCA 90095USA Department of Bioengineering Henry Samueli School of Engineering and Applied SciencesUniversity of CaliforniaLos AngelesLos AngelesCA 90095USA

Dental-derived stem cells(DSCs)are attractive cell sources due to their easy access,superior growth capacity and low *** can respond to multiple extracellular matrix signals,which provide biophysical and biochemical cues to regulate the fate of residing ***,the direct transplantation of DSCs suffers from poor proliferation and differentiation toward functional cells and low survival rates due to local ***,elegant advances in the design of novel biomaterials have been made to give promise to the use of biomimetic biomaterials to regulate various cell behaviors,including proliferation,differentiation and *** could be tailored with multiple functionalities,e.g.,*** is an emerging need to summarize recent advances in engineered biomaterials-mediated delivery and therapy of DSCs and their potential ***,we outlined the design of biomaterials for supporting DSCs and the host response to the transplantation.

关键词： dental-derived stem cells biomaterials host response tissue engineering

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Necrotic enteritis and antibiotic-free production of broiler chickens:Challenges in testing and using alternative products

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Animal Nutrition 2024年第1期16卷 288-298页

作者： Robert j.Moore School of Science RMIT University

The global trend towards raising broiler chickens without the use of in-feed antibiotics(IFAs) means that there is an ongoing need to develop alternative treatments capable of delivering the benefits that IFAs previously provided. IFAs supported the productivity performance of chickens and played a key role in maintaining their health. Necrotic enteritis(NE) is an important disease of broilers that affects health,productivity, and welfare, and was previously well controlled by IFAs. However, with the reduction in IFA use, NE is resurgent in some countries. Vaccines and various feed additives, including pre-, pro-, and postbiotics, phytobiotics, fatty acids, and phage therapies have been introduced as alternative methods of NE control. While some of these feed additives have specific activity against the NE pathogen, Clostridium perfringens, most have the more general goal of reinforcing gut health. Extensive reviews of the effects of many of these feed additives on gut health have been published recently. Hence, rather than cover previously well reviewed areas of research this review focuses on the challenges and pitfalls in undertaking experimental assessment of alternative NE treatments and translating laboratory research to real world commercial production settings. The review is based on the author's particular experience,reading, thoughts, and analysis of the available information and inevitably presents a particular understanding that is likely to be at odds with others thinking on these issues. It is put forward to stimulate thinking and discussion on the issues covered.

关键词： Necrotic enteritis Clostridium perfringens Vaccines Feed additive Farm management

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