Wien : M. Perles, 1878.

Gottingen : Dieterich, 1843.

Wien : W. Braumuller, 1867.

Stuttgart : Enke, 1896.

Hamburg : L. Voss, 1892.

Stuttgart : F. Enke, 1881.

Berlin : Rucker und Puchler, 1837-1838.

Leipzig : J. Naumann, 1862.

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[London?] : [publisher not identified], [1850]

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Polymyxins are increasingly used as the critical last-resort therapeutic options for multidrug-resistant gram-negative bacteria. Unfortunately, polymyxin resistance has increased gradually for the last few years. Although studies on mechanisms of polymyxin are expanding, system-wide analyses of the underlying mechanism for polymyxin resistance and stress response are still lacking. To understand how Klebsiella pneumoniae adapt to colistin (polymyxin E) pressure, we carried out proteomic analysis of Klebsiella pneumoniae strain cultured with different concentrations of colistin. Our results showed that the proteomic responses to colistin treatment in Klebsiella pneumoniae involving several pathways, including (i) gluconeogenesis and TCA cycle; (ii) arginine biosynthesis; (iii) porphyrin and chlorophyll metabolism; and (iv) enterobactin biosynthesis. Interestingly, decreased abundance of class A β-lactamases including TEM, SHV-11, SHV-4 were observed in cells treated with colistin. Moreover, we also present comprehensive proteome atlases of paired polymyxin-susceptible and -resistant Klebsiella pneumoniae strains. The polymyxin-resistant strain Ci, a mutant of Klebsiella pneumoniae ATCC BAA 2146, showed missense mutation in crrB. The crrB mutant Ci, which displayed lipid A modification with 4-amino-4-deoxy-L-arabinose (L-Ara4N) and palmitoylation, showed striking increases of CrrAB, PmrAB, PhoPQ, ArnBCADT and PagP. We hypothesize that crrB mutations induce elevated expression of the arnBCADTEF operon and pagP via PmrAB and PhoPQ. Moreover, multidrug efflux pump KexD, which was induced by crrB mutation, also contributed to colistin resistance. Overall, our results demonstrated proteomic responses to colistin treatment and the mechanism of CrrB-mediate colistin resistance, which may further offer valuable information to manage polymyxin resistance.

Klebsiella pneumoniae that produce extended spectrum beta lactamases (ESBLs) are a persistent public health threat. There are relatively few therapeutic options and there is undue reliance on carbapenems. Alternative therapeutic options are urgently required. A combination of cefepime and the novel beta lactamase inhibitor enmetazobactam is being developed for treatment of serious infections caused by ESBL-producing organisms. The pharmacokinetics-pharmacodynamics (PK-PD) of cefepime-enmetazobactam against ESBL-producing K. pneumoniae was studied in a neutropenic murine pneumonia model. Dose ranging studies were performed. Dose fractionation studies were performed to define the relevant PD index for the inhibitor. The partitioning of cefepime and enmetazobactam into the lung was determined by comparing area under the concentration time curve (AUC) in plasma and epithelial lining fluid. The magnitude of drug exposure for cefepime-enmetazobactam required for logarithmic killing in the lung was defined using 3 ESBL-producing strains. Cefepime 100 mg/kg q8h i.v. had minimal antimicrobial effect. When this background regimen of cefepime was combined with enmetazobactam half-maximal effect was induced with enmetazobactam 4.71 mg/kg q8h i.v. The dose fractionation study suggest both fT>threshold and fAUC:MIC are potentially relevant PD indices. The AUC_ELF:AUC_plasma for cefepime and enmetazobactam was 73.4% and 61.5%, respectively. A ≥2-log kill in the lung was achieved with a plasma and ELF cefepime fT>MIC of ≥20% and enmetazobactam fT>2 mg/L of ≥20% of the dosing interval. These data and analyses provide the underpinning evidence for the combined use of cefepime and enmetazobactam for nosocomial pneumonia.

Meropenem/vaborbactam resistance in Klebsiella pneumoniae is associated with loss of function mutations in the OmpK35 and OmpK36 porins. Here we identify two previously unknown loss of function mutations that confer cefuroxime resistance in K. pneumoniae. The proteins lost were NlpD and KvrA; the latter is a transcriptional repressor controlling capsule production. We demonstrate that KvrA loss reduces OmpK35 and OmpK36 porin production, which confers reduced susceptibility to meropenem/vaborbactam in a KPC-3 producing K. pneumoniae isolate.

The official UEFA EURO 2016 website has been nominated for two categories in the sixth Annual Lovie Awards which honour the best of the European internet.

Anyone with an organization, a small business, or just a passion needs a website to share it with the world. These are the best website builders we've tested for making it easy to create full-featured, mobile-compatible sites on a budget and with no coding required.

The Chinese government is getting local ISPs and cloud service providers to practice taking websites offline quickly when they are deemed harmful.

Governor Jack Markell, Delaware State Housing Authority, and their partners are pleased to announce the launch of a free housing locator website providing information about rental housing across the First State.

Governor Markell and the Delaware State Housing Authority announced the launch of a free housing locator website providing information about rental housing across the First State.

DOVER, DE – For anyone in Delaware looking to buy a home, Delaware State Housing Authority (DSHA) has launched a new website that provides convenient and detailed information about the authority’s homeownership programs and the home-buying process. The website, www.kissyourlandlordgoodbye.com, connects potential homebuyers in the state with resources on low interest mortgage loans, down payment […]

With the spread of COVID-19, Penn State’s Social Science Research Institute has launched a new website that provides resources for researchers, policy-makers and the general public to inform and to address impacts of the pandemic — with a focus on its broader implications for individuals, families, communities, and the commonwealth.

New tool to attract private investments in economically-distressed areas WILMINGTON, Del. – Governor John Carney announced on Thursday a new interactive website highlighting Delaware’s Opportunity Zones across the state. Opportunity Zones are an economic development tool designed to attract private investment and create economic opportunity in economically-distressed communities across Delaware. In April 2018, Governor Carney […]

Ashnoor Kaur is an Indian child actress associated with Hindi television and films. She is known for portraying Naira Singhania in Yeh Rishta Kya Kehlata Hai on Star Plus and Mini Khuranna on Patiala Babes that airs on Sony Entertainment Television

State employees, members of the public can submit ideas for cost savings, improvements across state government WILMINGTON, Del. – Governor Carney on Thursday announced the launch of a website for the Government Efficiency and Accountability Review Board, gear.delaware.gov, to identify opportunities for cost savings and system improvements across state government. In February, Governor Carney signed Executive […]

The Delaware Office of State Planning Coordination (OSPC) is proud to unveil our redesigned website Friday, August 31, 2018. This redesign improves the way information is delivered to citizens, developers and municipal stakeholders. A key objective of the redesigned site is to enable users to access our information from any device (PC, mobile phone, or […]

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