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AAV8 transduction capacity is reduced by prior exposure to endosome-like pH conditions

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Neural Regeneration Research 2021年第5期16卷 851-855页

作者： Jeffrey ALowell Kar Men Mah john LBixby Vance pLemmon Miami project to Cure paralysis University of MiamiMiamiFLUSA Department of Neurological Surgery University of MiamiMiamiFLUSA Department of Molecular and Cellular pharmacology University of MiamiMiamiFLUSA

Adeno-associated virus(AAV)is an essential instrument in the neuroscientist’s toolkit,which allows delivery of DNA to provide labeling with fluorescent proteins or genetic instructions to regulate gene *** the field of neural regeneration,the transduction of neurons enables the observation and regulation of axon growth and regeneration,and in the future will likely be a mechanism for delivering molecular therapies to promote sprouting and regeneration after central nervous system *** formulations of AAV preparations permit efficient viral transduction under physiologic conditions,but an improved understanding of the mechanistic limitations of AAV transduction may facilitate production of more resilient AAV strains for investigative and therapeutic *** studied AAV transduction in the context of prior exposure of AAV serotype 8(AAV8)to environmental pH within the range encountered during endosomal endocytosis(pH 7.4 to pH 4.4),during which low pH-triggered structural and autoproteolytic changes to the viral capsid are believed to be necessary for endosome escape and virus *** to the fundamental nature of these processes,we hypothesized that premature exposure of AAV8 particles to acidic pH would decrease viral transduction of HT1080 cells in vitro,as measured by fluorescent reporter gene expression using high-content imaging *** found that increasingly acidic incubation conditions were associated with concomitant reductions in transduction efficiency,and that quantitative levels of reporter gene expression in transduced cells were similarly *** biggest decrease in transduction occurred between pH 7.4 and pH 6.4,suggesting the possible co-occurrence of a pH-associated event and viral inactivation within that *** together,these findings indicate that exposure of AAV8 to acidic pH for as little as 1 hour is deleterious to transduction *** studies are necessary to understand the pH-associated

关键词： adeno-associated virus autolytic capsid low pH protease proteolytic temperature trafficking transduction viral inactivation

Sedimentary sources and processes in the eastern Arabian Sea:Insights from environmental magnetism,geochemistry and clay mineralogy

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Geoscience Frontiers 2016年第2期7卷 253-264页

作者： Kumar Avinash p.john Kurian Anish Kumar Warrier R.Shankar T.C.Vineesh Rasik Ravindra Earth System Science Organization National Centre for Antarctic and Ocean Research(ESSO-NCAOR)Ministry of Earth Sciences(MoES) Department of Marine Geology Mangalore University Earth System Science Organization Ministry of Earth Sciences(MoES)

The spatial distribution patterns of surficial sediment samples from different sedimentary domains （shallow to deep-sea regions） of the eastern Arabian Sea were studied using sediment proxies viz. environmental magnetism, geochemistry, particle size and clay mineralogy. Higher concentrations of magnetic minerals （high Xlf） were recorded in the deep-water sediments when compared with the shallow water sediments. The magnetic mineralogy of one of the shallow water samples is influenced by the presence of bacterial magnetite as evidenced from the XARM/Xlf VS. XARM/Xfd biplot. However, the other samples are catchment-derived. The high correlation documented for Xlf, anhysteretic remanent mag- netisation （XARM） and isothermal remanent magnetisation （IRM） with Al indicates that the deep-sea surflcial sediments are influenced by terrigenous fluxes which have been probably derived from the southern Indian rivers, the Sindhu （the Indus） and the Narmada-Tapti rivers. A lower Mn concentration is recorded in the upper slope sediments from the oxygen minimum zone （OMZ） but a higher Mn/AI ratio is documented in the lower slope and deep-sea sediments. Clay minerals such as illite （24-48.5%）, chlorite （14.1-34.9%）, smectite （10.6-28.7%） and kaolinite （11.9-27.5%） dominate the sediments of shallow and deep-sea regions and may have been derived from different sources and transported by fluvial and aeolian agents. Organic carbon （OC） data indicate a low concentration in the shallow/shelf region （well oxygenated water conditions） and deeper basins （increased bottom-water oxygen concentration and low sedimentation rate）. High OC concentrations were documented in the OMZ （very low bottom-water oxygen concentration with high sedimentation rate）. The calcium carbonate concentration of the surface sediments from the continental shelf and slope regions （〈 1800 m） up to the Chagos-Laccadive Ridge show higher concentrations （average - 58%） when compared to deep basin sediments （average - 44%）.

关键词： Magnetic minerals Major elements Organic carbon Calcium carbonate Terrigenous fluxes Eastern Arabian Sea

Current management of talar osteochondral lesions

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World Journal of Orthopedics 2017年第1期8卷 12-20页

作者： Arianna L Gianakos Youichi Yasui Charles p Hannon john G Kennedy Department of Orthopedic Surgery 2~(nd) Jersey City Medical Center Department of Foot and Ankle Hospital for Special Surgery Department of Orthopaedic Surgery 2~(nd) Teikyo University School of Medicine 2~(nd) Department of Orthopaedic Surgery Rush University Medical Center (C.P.H.)

Osteochondral lesions of the talus(OLT) occur in up to 70% of acute ankle sprains and fractures. OLT have become increasingly recognized with the advancements in cartilage-sensitive diagnostic imaging modalities. Although OLT may be treated nonoperatively, a number of surgical techniques have been described for patients whom surgery is indicated. Traditionally, treatment of symptomatic OLT have included either reparative procedures, such as bone marrow stimulation(BMS), or replacement procedures, such as autologous osteochondral transplantation(AOT). Reparative procedures are generally indicated for OLT placement strategies are used for large lesions or after failed primary repair procedures. Although shortand medium-term results have been reported, longterm studies on OLT treatment strategies are lacking. Biological augmentation including platelet-rich plasma and concentrated bone marrow aspirate is becoming increasingly popular for the treatment of OLT to enhance the biological environment during healing. In this review, we describe the most up-to-date clinical evidence of surgical outcomes, as well as both the mechanical and biological concerns associated with BMS and AOT. In addition, we will review the recent evidence for biological adjunct therapies that aim to improve outcomes and longevity of both BMS and AOT procedures.

关键词： Osteochondral lesions of talus Comprehensive review Diagnosis Bone marrow stimulation Autologous autograft transfer Biologics

ZONAL AND MERIDIONAL CIRCULATIONS IN THE EQUA-TORIALZONE AS DEDUCED FROM THE DIVERGENCE FIELD OF THE SURFACE WIND

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Advances in Atmospheric Sciences 1987年第4期4卷 432-446页

作者：王绍武,Todd p.Mitchell,john M.Wallace Department of Geophysics peking University Todd p. Mitchell and john M. Wallace Department of Atmospheric Sciences University of Washington U.S.A. Department of Atmospheric Sciences University of Washington U.S.A. Department of Atmospheric Sciences University of Washington U.S.A.

The zonal and meridional circulations and their variability arc examined on the basis of the surface wind data for 1950-1979. The climatological mean zonal wind and its divergence arc examined in reference to the Walker Circulation. The role played by the meridional circulation in contributing to convergence of the surface wind field within the equatorial zone is emphasized. Regression coefficients are used to infer seasonal mean anomalies of divergence of the surface wind in years when the sea level pressure is 1 hpa above normal at Darwin, a condition representative of El Nino events. It is shown that anomalies in the divergence associated with the meridional wind component are primarily responsible for the heavy precipitation in the Central pacific, while the anomalous divergence associated with the zonal wind component may cause the drought in the Western pacific near Indonesia. A similar pattern of divergence anomalies is evident during three consecutive seasons beginning in northern summer and end

关键词： Nino over ZONAL AND MERIDIONAL CIRCULATIONS IN THE EQUA-TORIALZONE AS DEDUCED FROM THE DIVERGENCE FIELD OF THE SURFACE WIND

Testing discrete symmetries at a super τ-charm factory

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Frontiers of physics 2016年第1期11卷 17-25页

作者： Adrian john Bevan particle physics Research Centre Queen Mary University of London Mile End Road London E1 4NS UK

Tests of discrete symmetry violation have played an important role in understanding the structure of weak interactions in the Standard Model of particle physics. Historically, these measurements have been extensively performed in experiments with large samples of K and B mesons. A high luminosity τ-charm facility presents physicists with the opportunity to comprehensively explore discrete symmetry violation and test the Standard Model using τ leptons, charm mesons, and charmed baryons. This paper discusses several possible measurements for a future T-charm factory.

关键词： discrete symmetries p C T Cp CpT violation

International perspectives on Natural Disasters: Occurrence, Mitigation, and Consequences 1

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The Transference Number

丛书名： Advances in Natural and Technological Hazards Research

2004年

作者： john Lidstone Lisa M. Dechano Joseph p. Stoltman

ISBN: (数字)9781402028519

ISBN: (纸本)9781402028502;9789401751315

Reports of natural disasters fill the media with regularity. places in the world are affected by natural disaster events every day. Such events include earthquakes, cyclones, tsunamis, wildfires – the list could go on for considerable length. In the 1990s there was a concentrated focus on natural disaster information and mitigation during the International Decade for Natural Disasters Reduction (IDNDR). The information was technical and provided the basis for major initiatives in building structures designed for seismic safety, slope stability, severe storm warning systems, and global monitoring and reporting. Mitigation, or planning in the event that natural hazards prevalent in a region would suddenly become natural disasters, was a major goal of the decade-long program. During the IDNDR, this book was conceptualized, and planning for its completion began. The editors saw the need for a book that would reach a broad range of readers who were not actively or directly engaged in natural disasters relief or mitigation planning, but who were in decision-making positions that provided an open window for addressing natural disaster issues. Those people were largely elected public officials, teachers, non-governmental organization staff, and staff of faith-based organizations. Those people, for the most part, come to know very well the human and physical characteristics of the place in which they are based. With that local outreach in mind, the editors intended the book to encourage readers to: 1.

关键词： physical Geography Geophysics Human Geography Education Environmental Sciences Regional Cultural Studies

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Energy & Environmental Materials 2022年第2期5卷 366-369页

作者： Kevin W.Gao Chao Fang David M.Halat Aashutosh Mistry john Newman Nitash p.Balsara Materials Sciences Division Lawrence Berkeley National LaboratoryBerkeleyCA 94720USA Department of Chemical and Biomolecular Engineering University of CaliforniaBerkeleyCA 94720USA Joint Center for Energy Storage Research Argonne National LaboratoryLemontIL 60439USA Chemical Sciences and Engineering Division Argonne National LaboratoryLemontIL 60439USA

The performance of rechargeable batteries and other electrochemical systems depends on the rate at which the working ion(often a cation)is transported from one electrode to the *** cation transference number is an important transport parameter that affects this *** purpose of this perspective is to distinguish between approximate and rigorous methods used in the literature to measure the transference *** emphasize the fact that this parameter is dependent on the reference frame used in the analysis;care must be taken when comparing values obtained from different sources to account for differences in reference *** present data obtained from a well-characterized *** compare rigorously determined transference numbers in two reference frames with values obtained by an approximate *** conclude with a qualitative discussion of the relationship between the transference number and salt concentration gradients that are obtained when current is drawn through a battery。

关键词： battery electrolytes concentrated solution theory ion transport reference frames transference number

Digital imaging approaches for phenotyping whole plant nitrogen and phosphorus response in Brachypodium distachyon

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Journal of Integrative plant Biology 2014年第8期56卷 781-796页

作者： Richard poiré Vincent Chochois Xavier R.R.Sirault john p.Vogel Michelle Watt Robert T.Furbank CSIRO plant Industry High Resolution plant phenomics Centre CSIRO Plant Industry USDA-ARS Western Regional Research Center

This work evaluates the phenotypic response of the model grass （Brachypodium distacbyon （L.） p. Beauv.） to nitrogen and phosphorus nutrition using a combination of imaging techniques and destructive harvest of shoots and roots. Reference line Bd21-3 was grown in pots using 11 phosphorus and 11 nitrogen concentrations to establish a dose-response curve. Shoot biovolume and biomass, root length and biomass, and tissue phosphorus and nitrogen concentrations increased with nutrient concentration. Shoot biovolume, estimated by imaging, was highly correlated with dry weight （R2 〉 0.92） and both biovolume and growth rate responded strongly to nutrient availability. Higher nutrient supply increased nodal root length more than other root types. photochemical efficiency was strongly reduced by low phosphorus concentrations as early as 1 week after germination, suggesting that this measurement may be suitable for high throughput screening of phosphorus response. In contrast, nitrogen concentration had little effect on photochemical efficiency. Changes in biovolume over time were used to compare growth rates of four accessions in response tonitrogen and phosphorus supply. We demonstrate that a time series image-based approach coupled with mathematical modeling provides higher resolution of genotypic response to nutrient supply than traditional destructive techniques and shows promise for high throughput screening and determina- tion of genomic regions associated with superior nutrient use efficiency.

关键词： Nutrients uptake phenomics photosynthesis root shootCitation: poire R, Chochois V, Sirault XRR, Vogel Jp, Watt M, Furbank RT(2o14) Digital imaging approaches for phenotyping whole plantnitrogen and phosphorus response in Brachypodium distachyon.

Adjuvant therapy in pancreatic cancer

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World Journal of Gastroenterology 2001年第4期7卷 482-489页

作者： paula Ghaneh john Slavin Robert Sutton Mark Hartley john p Neoptolemos Department of Surgery.University of Liverpool 5~(th)Floor UCD Building.Daulby StreetLiverpool.L69 3GA.UK

The outlook for patients with pancreatic cancer has been grim. There have been major advances in the surgical treatment of pancreatic cancer, leading to a dramatic reduction in post-operative mortality from the development of high volume specialized centres. This stimulated the study of adjuvant and neoadjuvant treatments in pancreatic cancer including chemoradiotherapy and chemotherapy. Initial protocols have been based on the original but rather small GITSG study first reported in 1985. There have been two large European trials totalling over 600 patients (EORTC and ESpAC-1) that do not support the use of chemoradiation as adjuvant therapy. A second major finding from the ESpAC-1 trial (541 patients randomized) was some but not conclusive evidence for a survival benefit associated with chemotherapy. A third major finding from the ESpAC-1 trial was that the quality of life was not affected by the use of adjuvant treatments compared to surgery alone. The ESpAC-3 trial aims to assess the definitive use of adjuvant chemotherapy in a randomized controlled trial of 990 patients.

关键词： pancreatic Neoplasms Antineoplastic Agents Combined Modality Therapy Humans Research Support, Non-U.S. Gov't