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Optical Detection of Distal Lung Enzyme Activity in Human Inflammatory Lung Disease

Biomedical Engineering Frontiers 2021年第1期2卷 44-54页

作者： Alicia Megia-Fernandez Adam Marshall Ahsan R.Akram Bethany Mills Sunay V.chankeshwara Emma Scholefield Amy Miele bruce c.mcgorum chesney Michaels Nathan Knighton Tom Vercauteren Francois Lacombe Veronique Dentan Annya M.bruce Joanne Mair Robert Hitchcock Nik Hirani chris Haslett Mark Bradley Kevin Dhaliwal EaStcHEM The University of Edinburgh School of ChemistryJoseph Black BuildingWest Mains RoadEdinburghUK EH93FJ Translational Healthcare Technologies Group Centre for Inflammation ResearchQueen’s Medical Research InstituteUniversity of Edinburgh47 Little France CrescentEdinburgh BioQuarterEdinburghUK EH164TJ The Roslin Institute and Royal(Dick)School of Veterinary Studies University of EdinburghEaster BushMidlothianUK EH259RG Department of Biomedical Engineering University of Utah36 S Wasatch DrSalt Lake CityUT 84112USA School of Biomedical Engineering&Imaging Sciences King’s College LondonLondonUK SE17EH Mauna Kea Technologies 9Rue d’EnghienParisFrance 75010

Objective and Impact *** is a need to develop platforms delineating inflammatory biology of the distal human *** describe a platform technology approach to detect in situ enzyme activity and observe drug inhibition in the distal human lung using a combination of matrix metalloproteinase(MMP)optical reporters,fibered confocal fluorescence microscopy(FcFM),and a bespoke delivery *** development of new therapeutic agents is hindered by the lack of in vivo in situ experimental methodologies that can rapidly evaluate the biological activity or drug-target engagement in *** optimised a novel highly quenched optical molecular reporter of enzyme activity(FIB One)and developed a translational pathway for in-human *** demonstrate the specificity for matrix metalloproteases(MMPs)2,9,and 13 and probe dequenching within physiological levels of MMPs and feasibility of imaging within whole lung models in preclinical ***,in a first-in-human exploratory experimental medicine study of patients with fibroproliferative lung disease,we demonstrate,through FcFM,the MMP activity in the alveolar space measured through FIB One fluorescence increase(with pharmacological inhibition).*** translational in situ approach enables a new methodology to demonstrate active drug target effects of the distal lung and consequently may inform therapeutic drug development pathways.

关键词： Lung lung specificity

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Your personal choices in transportation and food are important for lowering carbon emissions

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Frontiers of Environmental Science & Engineering 2024年第6期18卷 27-32页

作者： bruce Logan Fang Zhang Wulin Yang Le Shi Institute of Energy and the Environment The Pennsylvania State UniversityUniversity ParkPA 16802USA School of Environment Tsinghua UniversityBeijing 100084China college of Environmental Sciences and Engineering Peking UniversityBeijing 100871China college of Environmental and Resource Sciences Zhejiang UniversityHangzhou 310058China

There is a global need to reduce greenhouse gas emissions to limit the extent of climate change.A better understanding of how our own activities and lifestyle influence our energy use and carbon emissions can help us enable changes in activities that can lead to reductions in carbon *** we discuss an approach based on examining carbon emissions from the perspective of the unit c,where 1 c is the cO_(2)from food a person would on average eat every *** approach shows that total cO_(2)emissions in china,normalized by the population,is 22.5 c while carbon emissions for a person in the US is 43.9 c.A better appreciation of our own energy use can be obtained by calculating carbon emissions from our own activities in units of c,for example for driving a car gasoline or electric vehicle a certain number of kilometers,using electricity for our homes,and eating different *** this information,we can see how our carbon emissions compare to national averages in different countries and make decisions that could lower our personal cO_(2)emissions.

关键词： carbon dioxide climate change Daily energy Greenhouse gas

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Rationale and design of Tenecteplase Reperfusion Therapy in Acute Ischaemic cerebrovascular Events III (TRAcE III): a randomised, phase III, open- label, controlled trial

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Stroke & Vascular Neurology 2024年第1期9卷 82-89页

作者： Yunyun Xiong bruce c V campbell Marc Fisher Lee H Schwamm Mark Parsons Hao Li Yuesong Pan Xia Meng Xingquan Zhao Yongjun Wang Neurology Beijing Tiantan HospitalBeijingChina china National clinical Research center for Neurological Diseases BeijingChina Department of Medicine and Neurology The University of MelbourneMelbourneVictoriaAustralia Neurology Beth Israel Deaconess Medical CenterBostonMassachusettsUSA Department of Neurology and comprehensive Stroke center Massachusetts General HospitalBostonMassachusettsUSA Department of Neurology University of New South Wales South Western Sydney Clinical SchoolLiverpoolNew South WalesAustralia

Background and purpose Recombinant human TNK tissue-type plasminogen activator(rhTNK-tPA)was not inferior to alteplase for ischaemic stroke within *** study aimed to investigate the efficacy and safety of rhTNK-tPA in patients who had an ischaemic stroke due to large vessel occlusion(LVO)of anterior circulation beyond *** and design Tenecteplase Reperfusion Therapy in Acute Ischaemic cerebrovascular Events-III(TRAcE III)is a multicentre,prospective,randomised,open-label,blind endpoint,controlled clinical *** who had an ischaemic stroke due to anterior circulation LVO(internal carotid artery,middle cerebral artery M1 and M2 segments)within 4.5–24hours from last known well(including wake-up stroke and no witness stroke)and with salvageable tissue(ischaemic core volumech ratio≥1.8 and mismatch volume≥15mL)based on cT perfusion or MRI perfusion-weighted imaging(PWI)were included and randomised to rhTNK-tPA 0.25mg/kg(single bolus)to a maximum of 25mg or standard medical ***,we will exclude patients who are intended for direct *** will be followed up for 90 *** outcomes Primary efficacy outcome is modified Rankin Scale(mRS)score≤1 at 90 *** efficacy outcomes include ordinal distribution of mRS at 90 days,major neurological improvement defined by a decrease≥8 points compared with the initial deficit or a score≤1 on the National Institutes of Health Stroke Scale(NIHSS)at 72 hours,mRS score≤2 at 90 days,the rate of improvement on Tmax>6s at 24 hours and NIHSS score change from baseline at *** outcomes are symptomatic intracerebral haemorrhage within 36 hours and mortality at 90 *** TRAcE III will provide evidence for the efficacy and safety of rhTNK-tPA in patients who had an ischaemic strokes due to anterior circulation LVO beyond *** registration number NcT05141305.

关键词： Therapy random Rational

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Erratum to “Optical Detection of Distal Lung Enzyme Activity in Human Inflammatory Lung Disease”

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Biomedical Engineering Frontiers 2023年第1期4卷 30-30页

作者： Alicia Megia-Fernandez Adam Marshall Ahsan R.Akram Bethany Mills Sunay V.chankeshwara Emma Scholefield Amy Miele bruce c.mcgorum chesney Michaels Nathan Knighton Tom Vercauteren Francois Lacombe Veronique Dentan Annya M.bruce Joanne Mair Robert Hitchcock Nik Hirani chris Haslett Mark Bradley Kevin Dhaliwal EaStcHEM The University of Edinburgh School of ChemistryJoseph Black BuildingWest Mains RoadEdinburgh EH93FJUK Translational Healthcare Technologies Group Centre for Inflammation ResearchQueen’s Medical Research InstituteUniversity of Edinburgh47 Little France CrescentEdinburgh BioQuarterEdinburgh EH164TJUK The Roslin Institute and Royal(Dick)School of Veterinary Studies University of EdinburghEaster BushMidlothian EH259RGUK Department of Biomedical Engineering University of Utah36 S Wasatch DrSalt Lake CityUT 84112USA School of Biomedical Engineering&Imaging Sciences King’s College LondonLondon SE17EHUK Mauna Kea Technologies 9Rue d’EnghienParis 75010France

In the research article“Optical Detection of Distal Lung Enzyme Activity in Human Inflammatory Lung Disease”[1],the data availability statement was inadvertently omitted by the *** has now been corrected in the PDF ... 详细信息

关键词： HTML Human Optical

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Treatment with intravenous alteplase in ischaemic stroke patients with onset time between 4.5 and 24 hours(HOPE):protocol for a randomised,controlled,multicentre study

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Stroke & Vascular Neurology 2024年第3期9卷 318-323,I0274-I0282页

作者： Zhongyu Luo Ying Zhou Yaode He Shenqiang Yan Zhicai chen Xuting Zhang Yi chen Lu-Sha Tong Wansi Zhong Haitao Hu Kemeng Zhang Jiansheng Yang bruce c V campbell Min Lou Department of Neurology Zhejiang University School of Medicine Second Affiliated HospitalHangzhouZhejiangChina Department of Medicine and Neurology Melbourne Brain Centre at Royal Melbourne HospitalParkvilleVictoriaAustralia

Background While intravenous thrombolysis is recommended for patients who had an acute ischaemic stroke(AIS)within 4.5hours of symptom onset,there are few randomised trials investigating the benefits of thrombolysis beyond this therapeutic *** To determine whether patients who had an AIS selected with the presence of potentially salvageable tissue on cT perfusion at 4.5–24hours after stroke onset(for stroke with unknown onset time,the midpoint of the time last known to be well and symptom recognition time;for wake-up stroke,the midpoint of the time last known to be well or sleep onset and wake up time)will benefit from intravenous *** HOPE is a prospective,multicentre,randomised,open-label blinded endpoint trial with the stage of phase *** treatment allocation employs 1:1 *** treatment arm under investigation is alteplase with standard therapy,the control arm is standard *** imaging criteria include ischaemic core volume≤70mL,penumbra≥10mL and mismatch≥20%.Study outcomes The primary outcome is non-disabled functional outcome(assessed as modified Rankin Scale score of 0–1 at 90 days).Discussion HOPE is the first trial to investigate whether intravenous thrombolysis with alteplase offers benefits in patients who had an AIS presenting within 4.5–24hours,which has the potential to extend time window and expand eligible population for thrombolysis therapy.

关键词： patients intravenous centre

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Multinuclear MR and MRI study of lithium-ion cells using a variable field magnet and a fixed frequency RF probe

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Magnetic Resonance Letters 2024年第1期4卷 10-20页

作者： Andrés Ramírez Aguilera Florin Marica Kevin J.Sanders Md Al Raihan c.Adam Dyker Gillian R.Goward bruce *** UNB MRI centre Department of PhysicsUniversity of New BrunswickFrederictonNew BrunswickE3B 5A3Canada Department of chemistry McMaster UniversityHamiltonOntarioL8S 4L8Canada Department of chemistry University of New BrunswickFrederictonNew BrunswickE3B 5A3Canada

An exploratory multinuclear magnetic resonance(MR)and magnetic resonance imaging(MRI)study was performed on lithium-ion battery cells with ^(7)Li,^(19)F,and ^(1)H measurements.A variable field superconducting magnet with a fixed frequency parallel-plate radiofrequency(RF)probe was employed in the *** magnetic field was changed to set the resonance frequency of each nucleus to the fixed RF probe frequency of 33.7 *** cartridge-like lithium-ion cells,with graphite anodes and LiNi_(0.5)Mn_(0.3)co_(0.2)O_(2)(NMc)cathodes,were *** cell was pristine,and one was charged to a cell voltage of 4.2 *** results presented demonstrate the great potential of the variable field magnet approach in multinuclear measurement of lithium-ion *** methods open the door for developing faster and simpler methods for detecting,quantifying,and interpreting MR and MRI data from lithium-ion and other batteries.

关键词： Multinuclear MR/MRI Variable field magnet Lithium-ion battery Parallel-plate rf probe

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Generation of Eco-Friendly and Disease-Resistant channel catfish(Ictalurus punctatus)Harboring the Alligator cathelicidin Gene via cRISPR/cas9 Engineering

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Engineering 2024年第8期39卷 273-286页

作者： Jinhai Wang Baofeng Su De Xing Timothy J.bruce Shangjia Li Logan Bern Mei Shang Andrew Johnson Rhoda Mae c.Simora Michael coogan Darshika U.Hettiarachchi Wenwen Wang Tasnuba Hasin Jacob Al-Armanazi cuiyu Lu Rex A.Dunham School of Fisheries Aquacultureand Aquatic SciencesAuburn UniversityAuburnAL 36849USA

As a precise and versatile tool for genome manipulation,the clustered regularly interspaced short palindromic repeats(cRISPR)/cRISPR-associated protein 9(cas9)platform holds promise for modifying fish traits of *** the aim of reducing transgene introgression and controlling reproduction,upscaled disease resistance and reproductive intervention in catfish species have been studied to lower the potential environmental risks of the introgression of escapees as transgenic *** advantage of the cRISPR/cas9-mediated system,we succeeded in integrating the cathelicidin gene(As-cath)from an alligator(Alligator sinensis)into the target luteinizing hormone(lh)locus of channel catfish(Ictalurus punctatus)using two delivery systems assisted by double-stranded DNA(dsDNA)and single-stranded oligodeoxynucleotides(ssODNs),*** this study,high knock in(KI)efficiency(22.38%,64/286)but low ontarget events was achieved using the ssODN strategy,whereas adopting a dsDNA as the donor template led to an efficient on-target KI(10.80%,23/213).The on-target KI of As-cath was instrumental in establishing the lh knockout(LH^(–)_As-cath^(+))catfish line,which displayed heightened disease resistance and reduced fecundity compared with the wild-type(WT)sibling ***,administration of human chorionic gonadotropin(HcG)and luteinizing hormone-releasing hormone analogue(LHRHa)can restore the reproduction of the transgenic fish ***,we replaced the lh gene with an alligator cathelicidin transgene and then administered hormone therapy to move towards complete reproductive control of diseaseresistant transgenic catfish in an environmentally responsible *** strategy not only effectively improves consumer-valued traits but also guards against unwanted introgression,providing a breakthrough in aquaculture genetics to confine fish reproduction and prevent the establishment of transgenic or domestic genotypes in the natural environment.

关键词： Genome editing ssODN dsDNA Antimicrobial peptide Reproductive confinement Aquaculture

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Assessment of groundwater quantity, quality, and associated health risk of the Tano river basin, Ghana

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Acta Geochimica 2024年第2期43卷 325-353页

作者： Adwoba Kua-Manza Edjah bruce Banoeng-Yakubo Anthony Ewusi Enoch Sakyi-Yeboah David Saka clara Turetta Giulio cozzi David Atta-Peters Larry Pax chegbeleh Water Resources Research centre Ghana Atomic Energy CommissionAccraGhana Earth Science Department University of GhanaLegonAccraGhana Geological Engineering Department University of Mines and TechnologyTarkwaGhana Department of Statistics University of GhanaAccraLegonGhana Institute of Polar Sciences National Research Council of ItalyVeniceItaly

In the Tano River Basin,groundwater serves as a crucial resource;however,its quantity and quality with regard to trace elements and microbiological loadings remain poorly understood due to the lack of groundwater logs and limited water *** study presents a comprehensive analysis of the Tano River Basin,focusing on three key ***,it investigated the aquifer hydraulic parameters and the results showed signiﬁcant spatial variations in borehole depths,yields,transmissivity,hydraulic conductivity,and speciﬁc *** boreholes were concentrated in the northeastern and southeastern zones,while geological formations,particu-larly the Apollonian Formation,exhibit a strong inﬂuence on borehole *** study identiﬁed areas with high transmissivity and hydraulic conductivity in the southern and eastern regions,suggesting good groundwater avail-ability and suitability for sustainable water ***-ondly,the research investigated the groundwater quality and observed that the majority of borehole samples fall within WHO(Guidelines for Drinking-water Quality,Environmental Health criteria,Geneva,2011,***://***)***,some samples have pH levels below the standards,although the groundwater generally qualiﬁes as *** study further explores hydrochemical facies and health risk assessment,highlighting the dominance of ca–HcO3 water *** element analysis reveals minimal health risks from most elements,with chromium(cr)as the primary contributor to chronic health ***,this study has provided a key insights into the Tano River Basin’s hydrogeology and associated health *** outcome of this research has contributed to the broader understanding of hydrogeologi-cal dynamics and the importance of managing groundwater resources sustainably in complex geological environments.

关键词： Groundwater Unsupervised machine learning technique Hydrochemistry Aquifer hydraulic parameter Health risk

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Lactate-mediated medium-chain fatty acid production from expired dairy and beverage waste

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Environmental Science and Ecotechnology 2024年第5期21卷 278-286页

作者： Bin Bian Wenxiang Zhang Najiaowa Yu Wei Yang Jiajie Xu bruce E.Logan Pascal E.Saikaly Water Desalination and Reuse center(WDRc) King Abdullah University of Science and Technology(KAUST)Thuwal 23955-6900Kingdom of Saudi Arabia Environmental Science and Engineering Program Biological and Environmental Science and Engineering(BESE)DivisionKing Abdullah University of Science and Technology(KAUST)Thuwal 23955-6900Kingdom of Saudi Arabia Department of civil and Environmental Engineering The Pennsylvania State UniversityUniversity ParkPA16802USA Research centre of Ecology&Environment for coastal Area and Deep Sea Southern Marine Science and Engineering Guangdong Laboratory(Guangzhou)Guangzhou511458China School of Marine Science Ningbo UniversityNingbo315211China

Fruits,vegetables,and dairy products are typically the primary sources of household food ***,anaerobic digestion is the most used bioprocess for the treatment of food waste with concomitant generation of ***,to achieve a circular carbon economy,the organics in food waste should be converted to new chemicals with higher value than *** we demonstrate the feasibility of medium-chain carboxylic acid(MccA)production from expired dairy and beverage waste via a chain elongation platform mediated by *** a two-stage fermentation process,the first stage with optimized operational conditions,including varying temperatures and organic loading rates,transformed expired dairy and beverage waste into lactate at a concentration higher than 900 mM c at 43℃.This lactate was then used to produce>500 mM c caproate and>300 mM c butyrate via microbial chain ***,lactate-producing microbes such as Lactobacillus and Lacticaseibacillus were regulated by temperature and could be highly enriched under mesophilic conditions in the firststage *** the second-stage chain elongation reactor,the dominating microbes were primarily from the genera Megasphaera and caproiciproducens,shaped by varying feed and inoculum *** network analysis revealed positive correlations among species from the genera caproiciproducens,Ruminococcus,and cAG-352,as well as Megasphaera,Bacteroides,and Solobacterium,indicating strong microbial interactions that enhance caproate *** findings suggest that producing MccAs from expired dairy and beverage waste via lactate-mediated chain elongation is a viable method for sustainable waste management and could serve as a chemical production platform in the context of building a circular bioeconomy.

关键词： Microbial chain elongation Medium chain carboxylic acids Food waste Fermentation

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Amarts on Riesz Spaces

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Acta Mathematica Sinica,English Series 2008年第2期24卷 329-342页

作者： coenraad c.A. LABUScHAGNE bruce A.WATSON School of Mathematics University of the Witwatersrand Private Bag 3 P O WITS 2050 South Africa

The concepts of conditional expectations, martingales and stopping times were extended to the Riesz space context by Kuo, Labuschagne and Watson （Discrete time stochastic processes on Riesz spaces, Indag. Math.,15（2004）, 435-451）. Here we extend the definition of an asymptotic martingale （amart） to the Riesz spaces context, and prove that Riesz space amarts can be decomposed into the sum of a martingale and an adapted sequence convergent to zero. consequently an amart convergence theorem is deduced.

关键词： amart martingale Riesz space Banach lattice

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