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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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Risk of Tropical Cyclones and Floods to Power Grids in Southeast and East Asia

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INTERNATIONAL jOURNAL OF DISASTER RISK SCIENCE 2024年第4期15卷 494-507页

作者： Ye, Mengqi Ward, Philip j. Bloemendaal, Nadia Nirandjan, Sadhana Koks, Elco E. Vrije Univ Amsterdam Inst Environm Studies NL-1081 HV Amsterdam Netherlands Deltares NL-2629 HV Delft Netherlands Royal Netherlands Meteorol Inst KNMI NL-3731 GA De Bilt Netherlands

Power grids play a critical role in modern society, serving as the lifeline of a well-functioning economy. This article presents a first large-scale study on the risk estimation of tropical cyclone (TC)-induced winds and coastal floods, which can widely impact power grids in Southeast and East Asia. Our comprehensive risk model incorporates detailed infrastructure data from OpenStreetMap (OSM) and government power grid maps, along with global hazard maps and vulnerability curves. The results reveal that the estimated expected annual damages from TCs and coastal floods to OSM-mapped assets account for approximately 0.07% (0.00-0.38%) and 0.02% (0.00-0.02%) of the total GDP of the study area, respectively. We analyzed the main sources of uncertainty in the risk model and emphasized the importance of understanding asset vulnerability. These results highlight the urgent need to strengthen power infrastructure to withstand the impacts of natural hazards, and the significance of reliable risk information for improving power grid design and planning. Focusing on developing more region-specific infrastructure data and vulnerability curves will improve the accuracy of risk estimation and provide valuable insights not only for the electricity sector but also for customers of other infrastructure systems that heavily rely on a stable supply of electricity.

关键词： Asset level Coastal floods Power grids Risk analysis Tropical cyclones Vulnerability curves DAMAGE INFRASTRUCTURE ADAPTATION FRAMEWORK IMPACTS SYSTEMS COSTS

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Sustained adenosine release:Revealing its impact on osteogenic signalling pathways of human mesenchymal stromal cells

Engineered Regeneration

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Engineered Regeneration 2024年第2期5卷 255-268页

作者： Hadi Hajiali jane McLaren Cristina Gonzalez-García Salah Abdelrazig Dong-Hyun Kim Matthew j.Dalby Manuel Salmerón-Sánchez Felicity R.A.j.Rose School of Pharmacy Nottingham Biodiscovery InstituteUniversity of NottinghamNottinghamUK Healthcare Technologies Institute School of Chemical EngineeringUniversity of BirminghamBirminghamUK Centre for the Cellular Microenvironment University of GlasgowGlasgowUK Centre for Analytical Bioscience Advanced Materials&Healthcare Technologies DivisionSchool of PharmacyUniversity of NottinghamNottinghamUK Marine Microbiomics Program in BiologyDivision of Science and MathematicsNew York University Abu Dhabi(NYUAD)P.O.Box 129188Abu DhabiUnited Arab Emirates

Non-healing fractures,a global health concern arising from trauma,osteoporosis,and tumours,can lead to severe ***,integral to cellular energy metabolism,gains prominence in bone regeneration via adeno-sine A2 B receptor *** study introduces a controlled-release system for localized adenosine delivery,fostering human mesenchymal stromal cell(hMSC)differentiation into functional bone *** study investi-gates how the ratio of lactic acid to glycolic acid in microparticles can influence adenosine release and explores the downstream effects on gene expression and metabolic profiles of osteogenic differentiation in hMSCs cultured in growth and osteoinductive *** into adenosine-modulated signalling pathways during MSC differenti-ation,with osteogenic factors,provide a comprehensive understanding of the pathways *** gene expression and metabolic profiles unravels adenosine’s regulatory mechanisms in MSC *** adenosine release from microparticles induces mineralization,synergizing with osteogenic media supplements,showcasing the potential of adenosine for treating critical bone defects and metabolic *** study high-lights the efficacy of a polymeric microparticle-based delivery system,offering novel strategies for bone *** adenosine’s roles and associated signalling pathways advances our comprehension of molecular mech-anisms steering bone regeneration,propelling innovative biomaterial,combined with metabolites,approaches for clinical use.

关键词： Adenosine release Osteogenic signalling pathways Human mesenchymal stromal cells Bone regeneration

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Linkage Between European and East Asian Heatwaves on Synoptic Scales

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journal of Tropical Meteorology 2024年第2期30卷 97-105页

作者：蔡奋颖刘彩红杨崧邓开强 KURTHS jürgen School of Atmospheric Sciences Sun Yat-sen Universityand Southern Marine Science and Engineering Guangdong Laboratory(Zhuhai)ZhuhaiGuangdong 519082 China Department of Complexity Science Potsdam Institute for Climate Impact Research(PIK)Member of the Leibniz AssociationPotsdam 14473 Germany Department of Water and Climate Risk Institute for Environmental StudiesVrije Universiteit AmsterdamAmsterdam 1087HV Netherlands Guangdong Province Key Laboratory for Climate Change and Natural Disaster Studies Sun Yat-sen UniversityZhuhaiGuangdong 519082 China Department of Physics Humboldt-Universität zu BerlinBerlin 12489 Germany

Concurrent extreme weather events in geographically distant areas potentially cause high-end risks for *** using network analysis,the present study managed to identify significant nearly-simultaneous occurrences of heatwaves between the grid cells in East Asia and Eastern Europe,even though they are geographically far away from each *** further composite analysis,this study revealed that hot events first occurred in Eastern Europe,typically with a time lag of3-4 days before the East Asian heatwave *** eastward propagating atmospheric wave train,known as the circumglobal teleconnection(CGT)pattern,bridged the sequent occurrences of extreme events in these two remote *** blockings,amplified by surface warming over Eastern Europe,not only enhanced local heat extremes but also excited a CGT-like pattern characterized by alternative anomalies of high and low *** downstream anticyclones in the middle and upper troposphere reduced local cloud cover and increased downward solar radiation,thereby facilitating the formation of heatwaves over East *** half of East Asian heatwave events were preceded by Eastern European heatwave events in the 10-day time range before East Asian heatwave *** investigation of heatwave teleconnection in the two distant regions exhibits strong potential to improve the prediction accuracy of East Asian heatwaves.

关键词： concurrent heatwaves Eastern Europe East Asia circum-global teleconnection pattern

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Assessing the Impact of Catastrophic Electricity Loss on the Food Supply Chain

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INTERNATIONAL jOURNAL OF DISASTER RISK SCIENCE 2024年第4期15卷 481-493页

作者： Blouin, Simon Herwix, Alexander Rivers, Morgan Tieman, Ross j. Denkenberger, David C. Alliance Feed Earth Disasters ALLFED Lafayette CO 80026 USA Univ Canterbury Dept Mech Engn Christchurch 8041 New Zealand Univ Cologne Cologne Inst Informat Syst D-50969 Cologne Germany

The food supply chain's heavy reliance on electricity poses significant vulnerabilities in the event of prolonged and widespread power disruptions. This study introduces a system-dynamics model that integrates five critical infrastructures-electric grid, liquid fossil fuels, Internet, transportation, and human workforce-to evaluate the resilience of food supply chains to major power outages. We validated the model using the 2019 Venezuelan blackouts as a case study, demonstrating its predictive validity. We then explored how more extreme electricity losses would disrupt the supply chain. More specifically, we modeled the impact of a large-scale cyberattack on the US electric grid and a high-altitude electromagnetic pulse (HEMP) event. A cyberattack severely damaging the US electric grid and allowing for recovery within a few weeks or months would lead to substantial drops in food consumption. However, it would likely still be possible to provide adequate calories to everyone, assuming that food is equitably distributed. In contrast, a year-long recovery from a HEMP event affecting most of the continental United States could precipitate a state of famine. Our analysis represents a first attempt at quantifying how food availability progressively worsens as power outages extend over time. Our open-source model is made publicly available, and we encourage its application to other catastrophic scenarios beyond those specifically considered in this work (for example, extreme solar storms, high-lethality pandemics).

关键词： Cyberattack Electricity Food supply chains Global catastrophic risk High-altitude electromagnetic pulse System dynamics

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Sequential good lattice point sets for computer experiments

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Science China Mathematics 2024年第9期67卷 2153-2170页

作者： Xue-Ru Zhang Yong-Dao Zhou Min-Qian Liu Dennis K.j.Lin NITFID LPMC&KLMDASRSchool of Statistics and Data ScienceNankai UniversityTianjin 300071China Department of Statistics Purdue UniversityWest LafayetteIN 47907USA

Sequential Latin hypercube designs(SLHDs) have recently received great attention for computer experiments, with much of the research restricted to invariant spaces. The related systematic construction methods are inflexible, and algorithmic methods are ineffective for large designs. For designs in contracting spaces, systematic construction methods have not been investigated yet. This paper proposes a new method for constructing SLHDs via good lattice point sets in various experimental spaces. These designs are called sequential good lattice point(SGLP) sets. Moreover, we provide efficient approaches for identifying the(nearly)optimal SGLP sets under a given criterion. Combining the linear level permutation technique, we obtain a class of asymptotically optimal SLHDs in invariant spaces, where the L1-distance in each stage is either optimal or asymptotically optimal. Numerical results demonstrate that the SGLP set has a better space-filling property than the existing SLHDs in invariant spaces. It is also shown that SGLP sets have less computational complexity and more adaptability.

关键词： contracting space maximin distance nested Latin hypercube design sequential design space-fillingdesign

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Rodent management in Aotearoa New Zealand: approaches and challenges to landscape-scale control

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Integrative Zoology 2024年第1期19卷 8-26页

作者： john G.INNES Grant NORBURY Araceli SAMANIEGO Susan WALKER Deborah j.WILSON Manaaki Whenua-Landcare Research HamiltonNew Zealand Manaaki Whenua-Landcare Research AlexandraNew Zealand Manaaki Whenua-Landcare Research AucklandNew Zealand Manaaki Whenua-Landcare Research DunedinNew Zealand

Aotearoa—New Zealand has only four rodent species,all *** order of arrival,they are Pacific rat Rattus exulans,brown rat ***,house mouse Mus musculus,and black rat *** management in New Zealand aims mainly to conserve indigenous biodiversity rather than to protect crops or manage diseases,as is usual *** describe four major“regimes”and one major vision for rodent control in New Zealand to meet ecological restoration *** challenges for island eradications are for large islands that are remote or populated by *** 1080 is the only large-scale(tens of thousands of hectares)option for black rat control,but its application requires adjustment to counter subsequent rapid black rat ***“ecosanctuaries”(mean 720 ha)use ground-based traps and poisons to target mainly black rats and face constant *** with mammal-resistant fences(up to 3500 ha)limit reinvasion and target more pest species and have enabled the return of previously extirpated taxa to the main *** Free 2050 aims to eradicate the rat species(but not mice)plus some other introduced mammals from New Zealand by *** vision is not attainable with current tools,but research and experimental management is exploring techniques and *** large scale(to 100000 ha)at which black rats are now targeted for control to extremely low abundance seems to be unique to New Zealand.

关键词： black rat brown rat eradication house mouse rodent control

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Promoter engineering enables precise metabolic regulation towards efficientβ-elemene production in Ogataea polymorpha

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Synthetic and Systems Biotechnology 2024年第2期9卷 234-241页

作者： Min Ye jiaoqi Gao jingjing Li Wei Yu Fan Bai Yongjin j.Zhou Division of Biotechnology Dalian Institute of Chemical PhysicsChinese Academy of Sciences457 Zhongshan RoadDalian116023PR China CAS Key Laboratory of Separation Science for Analytical Chemistry Dalian Institute of Chemical PhysicsChinese Academy of SciencesDalian116023PR China Dalian Key Laboratory of Energy Biotechnology Dalian Institute of Chemical PhysicsChinese Academy of SciencesDalian116023PR China University of Chinese Academy of Sciences Beijing100049PR China

Precisely controlling gene expression is beneficial for optimizing biosynthetic pathways for improving the ***,promoters in nonconventional yeasts such as Ogataea polymorpha are always limited,which results in incompatible gene ***,we expanded the promoter library in *** based on transcriptional data,among which 13 constitutive promoters had the strengths ranging from 0–55%of PGAP,the commonly used strong constitutive promoter,and 2 were growth phase-dependent ***,2 hybrid growth phase-dependent promoters were constructed and characterized,which had 2-fold higher ***,promoter engineering was applied to precisely regulate cellular metabolism for efficient production ofβ-*** glyceraldehyde-3-phosphate dehydrogenase gene GAP was downregulated to drive more flux into pentose phosphate pathway(PPP)and then to enhance the supply of acetyl-CoA by using phosphoketolase-phosphotransacetylase(PK-PTA)*** with the phase-dependent expression of synthase module(ERG20∼LsLTC2 fusion),the highest titer of 5.24 g/L with a yield of 0.037 g/(g glucose)was achieved in strain YY150U under fed-batch fermentation in shake *** work characterized and engineered a series of promoters,that can be used to fine-tune genes for constructing efficient yeast cell factories.

关键词： Promoter library Growth phase-dependent promoters Promoter engineering Precise metabolic regulation Ogataea polymorpha

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Dominance of transposable element‑related satDNAs results in great complexity of“satDNA library”and invokes the extension towards“repetitive DNA library”

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Marine Life Science & Technology 2024年第2期6卷 236-251页

作者： Monika Tunjić‑Cvitanić Daniel García‑Souto juan j.Pasantes EvaŠatović‑Vukšić Division of Molecular Biology Ruđer BoškovićInstitute10000 ZagrebCroatia Genomes and Disease Centre for Research in Molecular Medicine and Chronic Diseases(CIMUS)Universidade de Santiago de Compostela15706 Santiago de CompostelaSpain Department of Zoology Genetics and Physical AnthropologyUniversidade de Santiago de Compostela15706 Santiago de CompostelaSpain Centro de Investigación Mariña Dpto de BioquímicaXenética e InmunoloxíaUniversidade de Vigo36310 VigoSpain

Research on bivalves is fast-growing,including genome-wide analyses and genome *** characteristics qualify oysters as a valuable model to explore repetitive DNA sequences and their genome *** we char-acterize the satellitomes of five species in the family Ostreidae(Crassostrea angulata,***,***,***,Ostrea edulis),revealing a substantial number of satellite DNAs(satDNAs)per genome(ranging between 33 and 61)and peculiarities in the composition of their *** satDNAs were either associated to or derived from transposable elements,displaying a scarcity of transposable element-unrelated satDNAs in these *** to the non-conventional satellitome constitution and dominance of Helitron-associated satDNAs,comparative satellitomics demanded more in-depth analyses than standardly *** analyses(including ***,the first bivalve species with a defined satellitome)revealed that 13 satDNAs occur in all six oyster genomes,with Cg170/HindIII satDNA being the most abundant in all of *** the“satDNA library model”highlighted the necessity to adjust this term when studying tandem repeat evolution in organisms with such *** repetitive sequences with potential variation in the organizational form and repeat-type affiliation are examined across related species,the introduction of the terms“TE library”and“repetitive DNA library”becomes essential.

关键词： Satellitome Comparative satellitomics Helitron Bivalves “Dark matter of the genome”

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Automating selective area electron diffraction phase identification using machine learning

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journal of Materiomics 2024年第4期10卷 896-905页

作者： M.Mika N.Tomczak C.Finney j.Carter A.Aitkaliyeva Nuclear Engineering Program in Department of Materials Science University of Florida100 Rhines HallGainesville32611FLUSA Department of Materials Science&Engineering Case Western Reserve University2111 Martin Luther King Jr DrCleveland44106OHUSA

Selective area electron diffraction(SAED)patterns can provide valuable insight into the structure of a ***,the manual identification of collected patterns can be a significant bottleneck in the overall phase classification *** this work,we utilize the recent advances in computer vision and machine learning(ML)to automate the indexing of SAED *** performance of six different ML algorithms is demonstrated using metallic plutonium-zirconium *** most successful approach trained a neural network(NN)to make a classification of the phase and zone axis,and then utilized a second NN to synthesize multiple independent predictions of different tilts in a single sample to make an overall phase *** results demonstrate that automated SAED phase identification using ML is a viable route to accelerate materials characterization.

关键词： Selective area electron diffraction Machine learning Phase identification Metallic fuels Pu alloys

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