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

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Idea management revisited:A review of the literature and guide for implementation

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International journal of Innovation Studies 2017年第2期1卷 144-161页

作者： Sophia Gerlach Alexander brem Friedrich-Alexander-Universit€at Erlangen-Nürnberg Chair of Technology ManagementFürther Str.246c90429 NürnbergGermanyUniversity of Southern DenmarkMads Clausen InstituteAlsion 26400 SonderborgDenmark Detecon International GmbH Sternengasse 14-1650676 CologneGermany

Despite being an established topic in research and practice for many years,the literature on idea management lacks a general model for corporate idea management ***,the purpose of this study is to develop such a conceptual framework based on the findings of an extensive literature *** addition,this paper presents an idea management guide that addresses important aspects of an idea management *** simplify the guide's application for idea managers,it is summarized in a *** paper can serve researchers with a state-of-the-art review and idea managers with a tool for building new idea management programs or reviewing existing ones in companies of different sizes and industries.

关键词： Idea management Employee suggestion scheme Front end innovation

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An Energy Analysis on Gasification of Sewage Sludge by a Direct Injection in Supercritical Water

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American journal of Analytical Chemistry 2017年第12期8卷 753-773页

作者： Riza Yukananto Alexander C. Louwes Eddy A. Bramer Gerrit brem Thermal Engineering Group Faculty of Engineering Technology University of Twente Enschede The Netherlands

Supercritical Water Gasification is an efficient technology in converting wet biomass into H2 and CH4 in comparison to other conventional thermochemical processes. Coke deposition, however, remains as a major challenge in this technology. Coke formation is the result of polymerization reactions that take place at sub-critical conditions. Directly injecting the relatively unheated wet biomass feed into supercritical water increases the heating rate and reduces the residence time of the feed in the sub-critical condition. This leads to a minimized coke formation in the process. However, a non-isothermal mixing takes place during this direct injection that is less energy-efficient. In addition, the biomass feedstream experiences less pre-heating that means less heat recovery from the product gas. These two aspects might reduce the overall process performance. Parametric studies of key operating parameters, such as operating temperature, dry matter content, bypass water ratio and heat exchanger effectiveness, are carried out to investigate the influence of direct injection to the thermal efficiency of the system. Subsequently, optimization using pinch analysis is conducted to the system with direct injection. Finally, an operating window for optimum performance of the optimized direct injection gasification system is proposed.

关键词： Supercritical Water Gasification System Model Sewage Sludge Coke Formation Pinch Analysis

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Stemona species - a source of potent bioactive products

Stemona species - a source of potent bioactive products

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The 3～(rd) International Conference on Natural Products :Natural Products -a Must for Human Survival ABSTRACTS

作者： Harald Greger Brigitte brem Thomas Pacher Otmar Hofer Comparative Phytochemistry Department Institute of Botany University of Vienna Rennweg 14 A-1030 Vienna Austria Comparative Phytochemistry Department Institute of Botany University of Vienna Rennweg 14 A-1030 Vienna Austria Comparative Phytochemistry Department Institute of Botany University of Vienna Rennweg 14 A-1030 Vienna Austria Institute of Organic Chemistry University of Vienna Whringerstrasse 38 A-1090 Vienna Austria

In spite of the wide use of Stemona species (Stemonaceae) as medicinal plants and naturally occurring pesticides improperly identified plant material has led to considerable confusions in chemical literature. Based on well documented plant material from natural habitats broad-based phytochemical comparisons linked with various bioassays inform now about the distribution of characteristic secondary metabolites as well as their biological activities. Different types of pyrrolo[l,2-a]azepine derived alkaloids (brem et al., 2002;Kaltenegger et al., 2003;Seger et al., 2004), stilbenoids (Pacher et al., 2002;Kostecki et al., 2004), and dehydrotocopherols (brem et al., 2004) contribute to a species grouping which is well in line with more recent data from DNA sequencing (Pfosser et al., in prep.)Whereas the pronounced insecticidal activities of some species could exclusively be attributed to the formation of alkaloids, the fungitoxic properties were caused by different stilbenoids. The antioxidant capacities of four new dehydrotocopherols (chromenols), e.g. (1), were comparable with that of a-tocopherol (vitamin E). Various bioassays with larvae of Spodoptera littoralis (Lepidoptera, Noctuidae) exhibited very high insect toxicity for the roots of S. collinsae, S. curtisii, and S. cochinchinensis, containing stemofoline-type alkaloids (2), whereas species from the S. tuberosa group, with dominating tuberostemonine (3)- or croomine-type derivatives (4), respectively, showed low toxicity but sometimes remarkable repellency. Four different types of stilbenoids, stilbenes, dihydrostilbenes, phenylbenzofurans (5), and dihydrophenanthrenes, displayed different antifungal activities from which some major compounds could only be detected as induced phytoalexins after fungal infection. Some stilbenoids from S. collinsae and S. cf. pierrei showed notably higher inhibitory effects on leucotriene metabolism than the commercial specific 5-lipoxygenase inhibitor zileuton (Adams et al., 2

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Local immunotherapy with interleuk in-2 delivered from biodegradable p olymer microspheres combined with interstitial chemotherapy:a novel treatme nt for experimental malignant glioma

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癌症 2003年第7期22卷 752-752页

作者： Rhines LD DiMeco F Lawson HC Tyler BM Hanes j Olivi A brem H

OBjECTIVE:Local delivery of carmustine(BCNU)from biodegradable polymers prolon gs survival against experimental brain ***,paracrine administration of inte rleukin-2(IL-2)has been shown to elicit a potent antitumor immune response and to improve survival in animal brain tumor *** r eport the use of a novel polymeric mic rosphere delivery vehicle to release *** demonstr ate both in vitro release of cytokine from the microspheres and histological evidence of the inflammatory response elicited by I L-2released from the microspheres i n the rat *** microspheres a re used to deliver IL-2,and biodegradable polymer wafers are used to deliver BCNU,directly at the site of an intracranially implanted glioma in the *** two agents administered locally show a s ynergistic ***:Fischer 344rats challenged intracranially with 9L gliosarcoma received an intracranial implant of either empty microspheres or microspheres containing IL-2(IL-2MS ).Five days later,animals in each group were randomized to receiv e polymer implants loaded with 0,3.8,or 10%BCNU at the tumor ***:Animals that received the combination of IL-2MS a nd 3.8%BCNU polymer(median survival,28.5d )or IL-2MS and 10%BCNU polymer(median survival,45.5d )showed significantly improved surv ival compared with animals that rece ived monotherapy with IL-2microsph eres(median survival,24d ),3.8%BCNU polymer(median survival,24d ),or 10%BCNU polymer(median survival,32.5d ).Control animals had a median survival of *** combination of either 3.8or 10%BCNU polymer with IL-2MS resulted in 7and 25%long-term survivors,***:By showing synergy of IL-2and BCNU in an animal glioma model and using a reproducible synthetic delivery sy stem for each agent (i.e.,one that did not rely on genetic ally engineered cells or viruses),we hope that the combination of local immunotherapy and chemotherapy can take an important step closer to clinical applic ation in patients with

关键词：实验性神经胶质瘤 IL-2 腔内化疗

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基因转移在动物育种中的研究与应用

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内蒙古畜牧科学 1992年第1期13卷 36-40,F003页

作者： Gottfried brem 李善如

目前,人工授精和胚胎移植已被成功地、广泛地应用于动物育种中,同时人们还在胚胎移植领域开展了胎胚显微手术、胚胎体外生产以及近几年发展极为迅速的基因转移技术。与其他育种方法和育种技术不同,基因转移首次通过单个基因的转移进行... 详细信息

目前,人工授精和胚胎移植已被成功地、广泛地应用于动物育种中,同时人们还在胚胎移植领域开展了胎胚显微手术、胚胎体外生产以及近几年发展极为迅速的基因转移技术。与其他育种方法和育种技术不同,基因转移首次通过单个基因的转移进行育种。基因转移就是把在体外重组的基因导入到动物基因组型内。所转移的基因是在体外由结构基因和调节物(操纵子)重组而成的转录单位。已被整合到动物基因组型内的基因被称为转基因,获得这种转基因的动物被称为转基因动物。如果这种转基因被后代所继承,那么就可发展成为转基因系。

关键词：基因转移动物育种

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日本需要一种新的经济模式

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商业周刊（中文版） 1999年第3期 41-44页

作者： brem.,B 文学朴

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牛半胚的低温冷冻和不同时出生的同卵双生

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畜牧兽医杂志 1988年第2期 46-48页

作者： G.brem 张锐

非手术方法回收七日龄的牛胚,进行显微分割,将半胚低温冷冻并贮存于液氮中。半胚解冻后,按形态分类并非手术移植给同期发情的受体牛。移植的23例中有7例怀孕(30%),其中包括一对由两个半胚发育生出的同卵双生。鲜胚分割移植(n=19)受胎率... 详细信息

非手术方法回收七日龄的牛胚,进行显微分割,将半胚低温冷冻并贮存于液氮中。半胚解冻后,按形态分类并非手术移植给同期发情的受体牛。移植的23例中有7例怀孕(30%),其中包括一对由两个半胚发育生出的同卵双生。鲜胚分割移植(n=19)受胎率达47%。然而解冻后再进行分割的胚胎(8个半胚)移植后无一例怀孕。此外本文还讨论了有关胚胎分割和低温冷冻相结合应用于畜牧业的一些问题。

关键词：半胚冷冻贮存液氮受体牛分割胚流体低温冷冻胚胎分割单卵双生同卵双生

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转基因家畜

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郑州牧业工程高等专科学校学报 1993年第1期16卷 1-5页

作者： G.brem 杨龙骐

1980年,首次报道了应用DNA显微注射法成功地获得转基因鼠的实验(Gordon等,1980),从此建立了单一离体基因的转移方法。利用70年代发展起来的分子生物学技术,对有利育种的基因已能分离、测序和同调控结构重组,并在体内和体外检测其表达能... 详细信息

1980年,首次报道了应用DNA显微注射法成功地获得转基因鼠的实验(Gordon等,1980),从此建立了单一离体基因的转移方法。利用70年代发展起来的分子生物学技术,对有利育种的基因已能分离、测序和同调控结构重组,并在体内和体外检测其表达能力。虽然这种基础研究的方法在家畜育种上的应用才刚刚开始,但未来前景广阔。本文综述了近年来对一些家畜进行人工基因转移的技术。

关键词：转基因动物家畜育种显微注射法基因转移技术人工基因细胞基因组插入突变基础研究结构重组整合位点

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家兔和猪的基因转移

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国外畜牧科技 1987年第3期 8-9页

作者： G.brem 朱裕鼎蒙文柱

从超数排卵处理的供体母兔和母猪获取单细胞胚胎.由人生长激素结构基因和小鼠金属巯因基因的启动子部分组成的 DNA 片段用于微注射.将注射基因的胚胎移植后,生出37只(9.6%)仔兔,15只(3.4%)仔猪.5只小兔和1头小猪用点杂交和 Southern 印... 详细信息

从超数排卵处理的供体母兔和母猪获取单细胞胚胎.由人生长激素结构基因和小鼠金属巯因基因的启动子部分组成的 DNA 片段用于微注射.将注射基因的胚胎移植后,生出37只(9.6%)仔兔,15只(3.4%)仔猪.5只小兔和1头小猪用点杂交和 Southern 印渍技术确定为基因转移后代.

关键词：基因转移小鼠供体点杂交生长激素转基因小家鼠微注射卵细胞生殖细胞卵子 DNA 受精卵合子母兔超排处理小猪

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