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Engineering 2024年第7期38卷 124-132页

作者： Zhuoren Ling Alistair james Macdonald Farley Aditya Lankapalli Yanfang Zhang Shonnette Premchand-Branker Kate Cook Andrei Baran charlotte Gray-Hammerton Claudia Orbegozo Rubio Edgars Suna jordan Mathias jürgen Brem Kirsty Sands Maria Nieto-Rosado Maria Mykolaivna Trush Nadira Naznin Rakhi Willames Martins Yuqing Zhou Christopher joseph Schofield Timothy Walsh Department of Biology&Ineos Oxford Institute for Antimicrobial Research University of OxfordOxford OX13REUK Chemistry Research Laboratory Department of Chemistry and the Ineos Oxford Institute for Antimicrobial ResearchUniversity of OxfordOxford OX13TAUK Latvian Institute of Organic Synthesis Riga LV-1006Latvia Department of Medical Microbiology Division of Infection and ImmunitySchool of MedicineCardiff UniversityCardiff CF144XNUK Enzymology and Applied Biocatalysis Research Center Faculty of Chemistry and Chemical EngineeringBabes-Bolyai UniversityCluj-Napoca 400028Romania

This work explores the potential of a triple combination of meropenem(MEM),a novel metallo-blactamase(MBL)inhibitor(indole-2-carboxylate 58(InC58)),and a serine-b-lactamase(SBL)inhibitor(avibactam(AVI))for broad-spectrum activity against carbapenemase-producing bacteria.A diverse panel comprising MBL-and SBL-producing strains was used for susceptibility testing of the triple combination using the agar dilution *** frequency of resistance(FoR)to MEM combined with InC58 was *** were sequenced and tested for cross resistance,fitness,and the stability of the resistance *** with the double combinations of MEM plus an SBL or MBL inhibitor,the triple combination extended the spectrum of activity to most of the isolates bearing SBLs(oxacillinase-48(OXA-48)and Klebsiella pneumoniae carbapenemase-2(KPC-2))and MBLs(New Delhi metallo-blactamases(NDMs)),although it was not effective against Verona integron-encoded metallo-blactamase(VIM)-carrying Pseudomonas aeruginosa(***)and OXA-23-carrying Acinetobacter baumannii(***).The FoR to MEM plus InC58 ranged from 2.22×10^(-7)to 1.13×10^(-6).The resistance correlated with mutations to ompC and comR,affecting porin C and copper permeability,*** mutants manifested a fitness cost,a decreased level of resistance during passage without antibiotic pressure,and cross resistance to another carbapenem(imipenem)and a b-lactamase inhibitor(taniborbactam).In conclusion,compared with the dual combinations,the triple combination of MEM with InC58 and AVI showed a much wider spectrum of activity against different carbapenemaseproducing bacteria,revealing a new strategy to combat b-lactamase-mediated antimicrobial resistance.

关键词： Carbapenemase Metallo/serine-b-lactamase inhibitor Avibactam Meropenem Antimicrobial resistance

CD4^(+)T cells produce IFN-I to license cDC1s for induction of cytotoxic T-cell activity in human tumors

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Cellular & Molecular Immunology 2024年第4期21卷 374-392页

作者： Xin Lei Daniël C.de Groot Marij j.P.Welters Tom de Wit Ellen Schrama Hans van Eenennaam Saskia j.Santegoets Timo Oosenbrug Annemarthe van der Veen joris L.Vos charlotte L.Zuur Noel F.C.C.de Miranda Heinz jacobs Sjoerd H.van der Burg jannie Borst Yanling Xiao Department of Immunology Leiden University Medical CenterLeidenThe Netherlands Oncode Institute Leiden University Medical CenterLeidenThe Netherlands Department of Tumor Biology and Immunology The Netherlands Cancer InstituteAmsterdamThe Netherlands Department of Medical Oncology Oncode InstituteLeiden University Medical CenterLeidenThe Netherlands IMMIOS B.V. OssThe Netherlands Division of Medical Oncology The Netherlands Cancer InstituteAmsterdamThe Netherlands Department of Otorhinolaryngology Leiden University Medical Center LeidenThe Netherlands Department of Pathology Leiden University Medical CenterLeidenThe Netherlands

CD4^(+)T cells can"help"or"license" conventional type 1 dendritic cells(cDC1s)to induce CD8^(+)cytotoxic T lymphocyte(CTL)anticancer responses,as proven in mouse *** recently identified cDC1s with a transcriptomic imprint of CD4^(+)T-cell help,specifically in T-cell-infiltrated human cancers,and these cells were associated with a good prognosis and response to PD-1-targeting ***,we delineate the mechanism of cDC1 licensing by CD4^(+)T cells in *** CD4^(+)T cells produce IFNβvia the STING pathway,which promotes MHC-I antigen(cross-)presentation by cDC1s and thereby improves their ability to induce CTL anticancer *** cooperation with CD40 ligand(L),IFNβalso optimizes the costimulatory and other functions of cDC1s required for CTL response ***-I-producing CD4^(+)T cells are present in diverse T-cell-infiltrated cancers and likely deliver“help”signals to CTLs locally,according to their transcriptomic profile and colocalization with“helped/licensed”cDCs and tumor-reactive CD8^(+)T *** agreement with this scenario,the presence of IFN-I-producing CD4^(+)T cells in the TME is associated with overall survival and the response to PD-1 checkpoint blockade in cancer patients.

关键词： CD4^(+)T-cell help cDC1 licensing IFN-I signaling CD40 costimulation (cross-)presentation CTL priming Tumor control

Protein Precipitation to Remove Carbohydrates that Interfere in Protein-Bound Tryptophan Quantification in Soybean Seeds

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journal of Analysis and Testing 2020年第3期4卷 238-247页

作者： Zhentian Lei Santosh Kumar Saurav j.Sarma Ritesh Kumar Barbara W.sumner Minviluz G.Stacey Lloyd W.sumner University of Missouri Metabolomics Center ColumbiaMO 65211USA Division of Biochemistry University of MissouriColumbiaMO 65211USA Division of Plant Sciences University of MissouriColumbiaMO 65211USA

Tryptophan is one of the nine essential amino acids in humans that can only be obtained through diets and *** is a precursor to many biological processes,such as serotonin,melatonin,kynurenin,and niacin(nicotinamide)vitamin *** content of tryptophan in foods,such as soybean is an important indicator of nutritional ***,accurate quantification of tryptophan in soybean is crucial to soybean nutritional *** of soybean protein-bound amino acids first involves acid hydrolysis of total protein to liberate amino ***,tryptophan quantification following acid hydrolysis is difficult or impossible due to its reactions with soybean ***,removal of carbohydrates from soy proteins prior to acid hydrolysis is *** this study,we compared four common protein precipitation methods(i.e.,methanol,acetonitrile,acetone,and trichloroacetic acid(TCA)protein precipitation methods)to determine the best method to separate soy proteins from carbohydrates,and concluded that acetone provided the highest recovery of soy *** content in the precipitated proteins was determined after acid hydrolysis of the proteins using liquid chromatography-tandem mass spectrometry multiple reaction monitoring(LC-MS/MS-MRM).No significant difference in the tryptophan content was found among proteins precipitated with methanol,acetonitrile,and TCA,suggesting that these precipitated proteins have similar compositions.A slightly lower,but statistically significant tryptophan content was found in the acetonitrile-precipitated proteins,suggesting that these proteins contain slightly higher glycosylated proteins.

关键词： Tryptophan Acid hydrolysis LC-MS/MS MRM Soybean seeds Protein precipitation

Stress, hippocampal neurogenesis and cognition： functional correlations

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Frontiers in Biology 2016年第3期11卷 182-192页

作者： Paul j. Lucassen charlotte A. Oomen Centre for Neuroscienee Swammerdam Institute for Life Sciences University of Amsterdam Science Park 904 1098 XH Amsterdam The Netherlands Department of Molecular and Cellular Neurobiology Center for Neurogenomics and Cognitive ResearchNeuroscience Campus Amsterdam VU University Amsterdam De Boelelaan 1085 1081 HV Amsterdam The Netherlands

The brain of many species including humans, harbors stem cells that continue to generate new neurons up into adulthood. This form of structural plasticity occurs in a limited number of brain regions, i.e. the subventricular zone and the hippocampal dentate gyrus and is regulated by environmental and hormonal factors. In this minireview, we provide an overview of the effects of stress and glucocorticoid hormones on adult hippocampal neurogenesis and discuss how these effects may be relevant for cognitive function and possibly, brain disease. While its exact functional role remains elusive, adult neurogenesis has been implicated in learning and memory, fear and mood regulation and recently, adult-born neurons were found to be involved in specific cognitive functions such as pattern separation （i.e. the ability to form unique memory representations） and cognitive flexibility. The process of adult neurogenesis is influenced by several factors; whereas e.g. exercise stimulates, exposure to stress and stress hormones generally inhibit neurogenesis. Effects of acute, mild stress are generally short-lasting and recover quickly, but chronic or severe forms of stress can induce lasting reductions in adult neurogenesis. Some of the inhibitory effects of stress can be rescued by exercise, by allowing a period of recovery from stress, by drugs that target the stress system, or by some, but not all, antidepressants. Stress may, partly through its effects on adult neurogenesis, alter structure and plasticity of the hippocampal circuit. This can lead to subsequent changes in stress responsivity and aspects of memory processing, which may be particularly relevant for stress related psychopathology or brain diseases that involve perturbed memory processing.

关键词： adult neurogenesis stem cells hippocampus stress memory pattern separation cognition

Nogo-A receptor internalization by cyclic adenosine monophosphate in overcoming axonal growth inhibitors after stroke

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Neural Regeneration Research 2022年第1期17卷 91-92页

作者： Rayudu Gopalakrishna charlotte Lin Mark S.Kindy William j.Mack Department of Integrative Anatomical Sciences Keck School of MedicineUniversity of Southern CaliforniaLos AngelesCAUSA Department of Neurological Surgery Keck School of MedicineUniversity of Southern CaliforniaLos AngelesCAUSA Department of Pharmaceutical Sciences College of PharmacyUniversity of South FloridaTampaFLUSA

Currently,there are no clinically proven drugs for recovery from stroke and other neuronal injuries such as traumatic brain injury and spinal cord *** therapy requires axonal regeneration,which is inhibited by diverse axonal growth inhibitors,such as Nogo-A,myelin-associated glycoprotein(MAG),oligodendrocyte myelin glycoprotein(OMgp),and chondroitin sulfate proteoglycans(CSPGs)(Chaudhry and Filbin,2007;Carmichael,2010;Schwab and Strittmatter,2014).

关键词： axonal injuries inhibited

Theoretical Analysis of the Fluctuation Theorem Applied to Electric Circuits

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Communications in Theoretical Physics 2014年第10期61卷 476-484页

作者： charlotte F.Petersen Elmars Krausz Denis j.Evans Stephen R.Williams Research School of Chemistry Australian National UniversityCanberraACT 0200Australia

We carry out a theoretical analysis of the fluctuations in the johnson–Nyquist noise in an RC electric circuit being driven by a non-ideal constant current source. Using the appropriate Langevin equation, we derive the fluctuation theorem for the system. This analysis exhibits some interesting features. Firstly, the average of the dissipation function is not necessarily just an instantaneous entropy production, i.e. the work being done on the circuit by the external power source divided by the ambient temperature. Secondly, by appropriate selection of the values for the circuit components,the transient response of the system can be made identical to the nonequilibrium steady state response. In the limit of an ideal current source, the average of the dissipation function reduces to the entropy production. Our analysis accurately reproduces published experimental results.

关键词： circuit analysis fluctuation theorems statistical machanics johnson noise

Control systems and data management for high-power laser facilities

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High Power Laser Science and Engineering 2023年第5期11卷 51-75页

作者： Scott Feister Kevin Cassou Stephen Dann Andreas Döpp Philippe Gauron Anthony j.Gonsalves Archis joglekar Victoria Marshall Olivier Neveu Hans-Peter Schlenvoigt Matthew j.V.Streeter charlotte A.j.Palmer California State University Channel Islands CamarilloCaliforniaUSA UniversitéParis-Saclay CNRS/IN2P3IJCLabOrsayFrance Central Laser Facility STFC Rutherford Appleton LaboratoryDidcotUK Ludwig–Maximilians–Universität München GarchingGermany BELLA Center Lawrence Berkeley National LaboratoryBerkeleyCaliforniaUSA Department of Nuclear Engineering and Radiological Sciences University of MichiganAnn ArborMichiganUSA Ergodic LLC San FranciscoCaliforniaUSA Helmholtz-Zentrum Dresden–Rossendorf DresdenGermany Queen’s University Belfast BelfastUK

The next generation of high-power lasers enables repetition of experiments at orders of magnitude higher frequency than what was possible using the prior *** requiring human intervention between laser repetitions need to adapt in order to keep pace with the new laser technology.A distributed networked control system can enable laboratory-wide automation and feedback control *** higher-repetition-rate experiments will create enormous quantities of data.A consistent approach to managing data can increase data accessibility,reduce repetitive data-software development and mitigate poorly organized *** opportunity arises to share knowledge of improvements to control and data infrastructure currently being *** compare platforms and approaches to state-of-the-art control systems and data management at high-power laser facilities,and we illustrate these topics with case studies from our community.

关键词： big data community organization control systems data management feedback loops high-power lasers high repetition rate metadata stabilization standards

Introduction of laparoscopic gastrectomy for gastric cancer in a Western tertiary referral centre:A prospective cost analysis during the learning curve

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World journal of Gastrointestinal Oncology 2017年第5期9卷 228-234页

作者： juul j Tegels charlotte E Silvius Frederique E Spauwen Karel W Hulsewé Anton G Hoofwijk jan H Stoot Deptartment of Surgery Zuyderland Medical Centre6162BG SittardThe Netherlands

To evaluate the costs of the introduction of a laparoscopic surgery program for gastric cancer in a Western community training hospital and tertiary referral centre for gastric cancer surgery. METHODSAll patients who underwent surgery for gastric cancer with curative intent in 2013 and 2014 were prospectively included. Primary outcomes were costs regarding surgery and hospital stay. RESULTSLaparoscopic gastrectomy was used in 52 patients [mean age 68 years (± 9, range 50 to 87)] and open gastrectomy was used in 25 patients [mean age 70 years (± 10, range 46 to 85)]. Mean costs (in euro’s) of surgical instrumentation were significantly higher for laparoscopic surgery: 2270 ± 670 vs 1181 ± 680 in the open approach (P < 0.001). Costs of theatre use were higher in the laparoscopic group: mean 3819 ± 865 vs 2545 ± 1268 in the open surgery (P < 0.001). Total costs of hospitalization (i.e., costs of surgery and admission) were not different between laparoscopic and open surgery, 8187 ± 4864 and 7673 ± 8064 respectively (P = 0.729). Mean length of hospital stay was 9 ± 12 d in the laparoscopic group vs 14 ± 14 d in the open group (P = 0.044). CONCLUSIONThe introduction of laparoscopic gastrectomy for gastric cancer coincided with higher costs for theatre use and surgical instrumentation compared to the open technique. Total costs were not significantly different due to shorter length of stay and less intensive care unit (ICU) admissions and shorter ICU stay in the laparoscopic group.

关键词： Laparoscopic surgery Healthcare costs Gastric cancer

Groundwater arsenic biogeochemistry-Key questions and use of tracers to understand arsenic-prone groundwater systems

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Geoscience Frontiers 2019年第5期10卷 1635-1641页

作者： David A. Polya charlotte Sparrenbom Saugata Datta Huaming Guo School of Earth and Environmental Sciences and Williamson Research Centre for Molecular Environmental Science The University of ManchesterWilliamson BuildingOxford RoadManchesterM13 9PLUK Department of Geology Lund UniversityLundSweden Department of Geology Kansas State University108 Thompson HallManhattanKS66506-3201USA State Key Laboratory of Biogeology and Environmental Geology and School of Water Resources China University of GeosciencesBeijing 100083China

Over 100,000,000 people worldwide are exposed to high arsenic groundwater utilised for drinking or *** consequent global avoidable disease burden is estimated to be of the order of 100,000 avoidable deaths or more per annum from just direct exposures - *** indirect exposure (from rice and other foods) and excluding *** 1000s of papers published on arsenic (hydro)(bio)geochemistry,there remain a number of key outstanding questions to be addressed in relation to arsenic geoscience - these include questions related to:(i) the role of human activities - irrigation,agriculture and other land uses - on arsenic mobilisation in groundwaters;(ii) the specific sources,nature and role of organics,minerals and microbial communities involved in arsenic mobilisation;(iii) the relationship to microscopic to macroscopic scale geological (including tectonic) and evolution processes;(iv) unravelling the over-printing of multiple processes in complex highly heterogeneous aquifer systems and (v) using increasing understanding of the controls of arsenic mobility in groundwaters systems to informing improved locally-relevant remediation and mitigation *** article further summarises how the 9 further papers in this Special Issue address some of these questions through the use of chemical and/or isotopic tracers.

关键词： Arsenic Groundwater Biogeochemical cycles Tracers