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The Triple Combination of Meropenem,Avibactam,and a Metallo-β-Lactamase Inhibitor Optimizes Antibacterial Coverage Against Different β-Lactamase Producers

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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 j.r.an Mathias j.r.en 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

Listening to People and Places teacher's tapescript V j cook.

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Listening to People and Places teacher's tapescript V J COOK...

粉末冶金Al-5.6Zn-2Mg合金在热压缩过程中加工硬化特性及本构模型的比较

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作者： V j cook.

来源：畅想之星图书光盘版（南... 评论

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journal of Central South University 2024年第2期31卷 346-368页

作者： KATIKA Harikrishna DAMODA r.K. DAVIDSON M.j. SEETHArAM r. KASAGANI Veera Venkata Nagaraju Department of Mechanical Engineering National Institute of TechnologyWarangal 506004India Department of Mechanical Engineering The Indian Institute of Information Technology Design and ManufacturingKurnool 518007India

在300~5000℃、应变速率为0.1~0.0001 s−1的条件下,在万能试验机上对Al-5.6Zn-2Mg铝合金进行热压缩试验,以确定动态再结晶开始时的加工硬化速率曲线σ_(c)(ε_(c))l以及关键特征σ_(c)(ε_(c))l、σ_(p)(ε_(p))和σ_(ss)与Z系数之间的... 详细信息

在300~5000℃、应变速率为0.1~0.0001 s−1的条件下,在万能试验机上对Al-5.6Zn-2Mg铝合金进行热压缩试验,以确定动态再结晶开始时的加工硬化速率曲线σ_(c)(ε_(c))l以及关键特征σ_(c)(ε_(c))l、σ_(p)(ε_(p))和σ_(ss)与Z系数之间的相关性。使用了四个本构模型,Arrhenius模型、改进的johnson-cook模型(MjC)、改进的Zerilli-Armstrong模型(MZA)和开发的人工神经网络(ANN)。结果表明,ANN型模型和Arrhenius模型的相对误差的绝对平均值最低,分别为0.486%和3.36%,MZA型模型和MjC型模型的相对误差的绝对平均值较高,分别为8.84%和3.93%。由于Arrhenius模型能够处理各种因素之间的非线性关系,因此它被认为是最合适的预测模型,但在材料性质未知或实验数据有限的情况下,MjC模型可能是一种更简单的替代方法。MZA模型不适合估计热压缩时的流变应力。此外,训练最好的神经网络模型的预测性能最好,相对误差的绝对平均值为0.486%,r值为0.99。

关键词：加工硬化速率曲线本构建模热压缩 EBSD分析流变曲线

t(14;18)(q32;q21)累及IGH和MALT1在皮肤MALT淋巴瘤和原发皮肤弥漫性大B细胞淋巴瘤中不常见

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世界核心医学期刊文摘（皮肤病学分册） 2006年第6期2卷 61-61页

作者： Wongchaowart N.T. Kim B. Hsi E.D. j.r. cook 冯义国 Department of Clinical Pathology Cleveland Clinic Foundation 9500 Euclid Avenue Cleveland OH 44195 United States Dr.

Background: t(14;18)(q32;q21) involving IGH and MALT1 has been demonstrated in cutaneous MALT lymphomas and in one case of primary cutaneous diffuse large B-cell lymphoma (DLBCL). However, the incidence of IGH/MALT1 translocations in these forms of cutaneous lymphoma remains unclear. Methods: We performed paraffin section interphase fluorescence in situ hybridization (FISH) analysis using MALT1 and IGH break-apart probes on 16 cutaneous MALT lymphomas and 16 primary cutaneous DLBCL in order to assess the frequency of IGH/MALT1 translocations and to screen for other potential translocations involving the IGH or MALT1 loci. results: Translocations involving MALT1 were not detected in any of 16 cutaneous MALT lymphomas or 16 primary cutaneous DLBCL. Of the 12 MALT lymphomas that could be analyzed for an IGH translocation, all were negative. In contrast, four of the 13 cases (31%) of primary cutaneous DLBCL that could be analyzed for translocations involving IGH were positive. Subsequent FISH analysis demonstrated one of these to be an IGH/BCL2 translocation and one to be a CMYC/IGH translocation, while the translocation partners in the remaining two cases are currently unidentified. Conclusions: This study demonstrates that translocations involving MALT1, including IGH/MALT1, are uncommon in cutaneous MALT lymphomas and primary cutaneous DLBCL. Other translocations involving IGH also are not involved in the pathogenesis of at least most cutaneous MALT lymphomas. In contrast, primary cutaneous DLBCL may contain one of several IGH translocations in a minority of cases.

关键词：弥漫性大B细胞淋巴瘤 MALT淋巴瘤皮肤淋巴瘤 MALT1 IGH t(14 q21) 原发荧光原位杂交(FISH) DLBCL

CCS research Development and Deployment in a Clean Energy Future： Lessons from Australia over the Past Two Decades

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Engineering 2017年第4期3卷 477-484页

作者： Peter j. cook CO2CrC Ltd.& Peter cook Centre for Carbon Capture and Storage research The University of Melbourne Melbourne VIC 2010 Australia

There is widespread, though by no means universal, recognition of the importance of carbon capture and storage （CCS） as a carbon mitigation technology. However, the rate of deployment does not match what is required for global temperatures to stay well below 2℃. Although some consider the hurdles to achieving the widespread application of CCS to he almost insurmountable, a more optimistic view is that a great deal is now known about CCS through research, demonstration, and deployment. We know how to do it; we are confident it can be done safely and effectively; we know what it costs; and we know that costs are decreasing and will continue to do so. We also know that the world will need CCS as long as countries, companies, and communities continue to use fossil fuels for energy and industrial processes. What is lacking are the necessary policy drivers, along with a technology-neutral approach to decrease carbon emissions in a cost-effective and timely manner while retaining the undoubted benefits of ready access to reliable and secure electricity and energy-intensive industrial products. In this paper, Australia is used as an example of what has been undertaken in CCS over the past 20 years, particularly in research and demonstration, hut also in international collaboration. Progress in the large-scale deployment of CCS in Australia has been too slow. However, the world＇s largest storage project will soon be operational in Australia as part of the Gorgon liquefied natural gas （LNG） project, and investigations are underway into several large-scale CCS Flagship program opportunities. The organization and progress of the Cooperative research Centre for Greenhouse Gas Technologies （CO2CrC） Otway Project, which is currently Australia＇s only operational storage project, is discussed in some detail because of its relevance to the commercial deployment of CCS. The point is made that there is scope for building on this Otway activity to investigate more broadly （through the p

关键词： Carbon dioxide Carbon capture and storage Otway Australia

Estimates for Lyme borreliosis infections based on models using sentinel canine and human seroprevalence data

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Infectious Disease Modelling 2020年第1期5卷 871-888页

作者： Michael j.cook Basant K.Puri Vis a Vis Symposiums Bury St EdmundsUK CAr CambridgeUK

Two models were developed to estimate Lyme borreliosis(LB)*** was based on the seroprevalence of Borrelia infections in human *** model used corrections for false negative and false positive results from published test sensitivity and specificity measures.A second model based on Borrelia infections in sentinel dogs was used to quantify the prevalence of Lyme disease Borrelia infections in humans;the reference baseline for this model was human and canine infections in Germany.A comparison of the two models is shown and differences *** relationships between incidence,prevalence and total infection burden for LB were derived from published data and these were used in both models to calculate annual incidence,prevalence and total LB *** modelling was conservative and based on medical insurance records coded for erythema *** model growth rates were used in place of the commonly adopted exponential *** mean of the two models was used to create estimates for various countries and *** from the analyses for LB estimated for 2018 include:incidence e USA 473,000/year,Germany 471,000/year,France 434,000/year and UK 132,000/year;prevalence e USA 2.4 million,Germany 2.4 million,France 2.2 million and UK 667,000;total infections e USA 10.1 million,Germany 10.0 million,France 9.3 million and UK 2.8 *** for the world for 2018 are:incidence 12.3 million/year;prevalence 62.1 million;and total infection burden 262.0 *** figures are far higher than officially published data and reflect not only the underestimation of diagnosed cases,which is acknowledged by health agencies,but also undiagnosed and misdiagnosed cases.

关键词： Lyme disease Borreliosis Linear regression models Seropositive Companion animals Sentinel animals

Effect of oxygen and nitrogen functionalization on the physical and electronic structure of graphene

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Nano research 2015年第8期8卷 2620-2635页

作者： Alexander j. Marsden Peter Brommer james j. Mudd M. Adam Dyson robert cook Maria Asensio jose Avila Ana Levy j.r.my Sloan David Quigley Gavin r. Bell Neil r. Wilson Department of Physics University of Warwick Coventry UK Centre for Scientific Computing University of Warwick Coventry UK Synchrotron SOLEIL L'Orme des Merisiers Saint Aubin-BP 48 91192 Gifsur Yvette Cedex France

Covalent functionalization of graphene offers opportunities for tailoring its properties and is an unavoidable consequence of some graphene synthesis techniques. However, the changes induced by the functionalization are not well understood. By using atomic sources to control the extent of the oxygen and nitrogen functionalization, we studied the evolution in the structure and properties at the atomic scale. Atomic oxygen reversibly introduces epoxide groups whilst, under similar conditions, atomic nitrogen irreversibly creates diverse functionalities including substitutional, pyridinic, and pyrrolic nitrogen. Atomic oxygen leaves the Fermi energy at the Dirac point （i.e., undoped）, whilst atomic nitrogen results in a net n-doping; however, the experimental results are consistent with the dominant electronic effect for both being a transition from delocalized to localized states, and hence the loss of the signature electronic structure of graphene.

关键词： graphene functionalization chemical vapor deposition density functional theory

resistance to ErK1/2 pathway inhibitors;sweet spots,fitness deficits and drug addiction

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Cancer Drug resistance 2019年第2期2卷 365-380页

作者： Matthew j.Sale Kathryn Balmanno Simon j.cook Signalling Programme The Babraham InstituteBabraham Research CampusCambridge CB223ATUK

MEK1/2 inhibitors are clinically approved for the treatment of BrAF-mutant melanoma,where they are used in combination with BrAF inhibitors,and are undergoing evaluation in other *** resistance to MEK1/2 inhibitors,including selumetinib(AZD6244/ArrY-142866),can arise through amplification of BrAF^(V600E) or KrAS^(G13D) to reinstate ErK1/2 *** have found that BrAF^(V600E) amplification and selumetinib resistance are fully reversible following drug *** is because resistant cells with BrAF^(V600E) amplification become addicted to selumetinib to maintain a precise level of ErK1/2 signalling(2%-3%of total ErK1/2 active),that is optimal for cell proliferation and *** withdrawal drives ErK1/2 activation outside of this critical“sweet spot”(~20%-30%of ErK1/2 active)resulting in a p57^(KIP2)-dependent G1 cell cycle arrest and senescence or expression of NOXA and cell death with features of autophagy;these terminal responses select against cells with amplified BrAF^(V600E).ErK1/2-dependent p57^(KIP2) expression is required for loss of BrAF^(V600E) amplification and determines the rate of reversal of selumetinib *** of selumetinib-resistant cells with BrAF^(V600E) amplification as tumour xenografts also requires the presence of selumetinib to“clamp”ErK1/2 activity within the sweet ***,BrAF^(V600E) amplification confers a selective disadvantage or“fitness deficit”during drug withdrawal,providing a rationale for intermittent dosing to forestall ***,selumetinib resistance driven by KrAS^(G13D) amplification/upregulation is not *** these cells ErK1/2 reactivation does not inhibit proliferation but drives a ZEB1-dependent epithelial-to-mesenchymal transition that increases cell motility and promotes resistance to traditional chemotherapy *** results reveal that the emergence of drug-addicted,MEKi-resistant cells,and the opportunity this may afford for intermittent dosing

关键词： BrAF CDKN1C/p57^(KIP2) EMT ErK KrAS MEK MEK inhibitor resistance selumetinib

Evaluation of an automated spike-and-wave complex detection algorithm in the EEG from a rat model of absence epilepsy

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Neuroscience Bulletin 2015年第5期31卷 601-610页

作者： Sebastien H.Bauquier Alan Lai jonathan L.jiang Yi Sui Mark j.cook Faculty of Veterinary and Agricultural Sciences The University of Melbourne Department of Electrical and Electronic Engineering The University of Melbourne Department of Clinical Neurosciences St Vincent's Hospital Faculty of Medicine The University of Melbourne Department of Neurology Shenyang First People's Hospital

The aim of this prospective blinded study was to evaluate an automated algorithm for spike-andwave discharge（SWD） detection applied to EEGs from genetic absence epilepsy rats from Strasbourg（GAErS）.Five GAErS underwent four sessions of 20-min EEG *** EEG was manually analyzed for SWDs longer than one second by two investigators and automatically using an algorithm developed in MATLAB（？）.The sensitivity,specificity,positive predictive value（PPV）,and negative predictive value（NPV） were calculated for the manual（reference） versus the automatic（test） *** results showed that the algorithm had specificity,sensitivity,PPV and NPV 〉94%,comparable to published methods that are based on analyzing EEG changes in the frequency *** provides a good alternative as a method designed to mimic human manual marking in the time domain.

关键词： GAErS seizure detection epilepsy