3,234 research outputs found

    Antimicrobial Peptides Designed against the Ί-Loop of Class A β-Lactamases to Potentiate the Efficacy of β-Lactam Antibiotics

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    Class A serine β-lactamases (SBLs) have a conserved non-active site structural domain called the omega loop (Ί-loop), in which a glutamic acid residue is believed to be directly involved in the hydrolysis of β-lactam antibiotics by providing a water molecule during catalysis. We aimed to design and characterise potential pentapeptides to mask the function of the Ί-loop of β-lactamases and reduce their efficacy, along with potentiating the β-lactam antibiotics and eventually decreasing β-lactam resistance. Considering the Ί-loop sequence as a template, a group of pentapeptide models were designed, validated through docking, and synthesised using solid-phase peptide synthesis (SPPS). To check whether the β-lactamases (BLAs) were inhibited, we expressed specific BLAs (TEM-1 and SHV-14) and evaluated the trans-expression through a broth dilution method and an agar dilution method (HT-SPOTi). To further support our claim, we conducted a kinetic analysis of BLAs with the peptides and employed molecular dynamics (MD) simulations of peptides. The individual presence of six histidine-based peptides (TSHLH, ETHIH, ESRLH, ESHIH, ESRIH, and TYHLH) reduced β-lactam resistance in the strains harbouring BLAs. Subsequently, we found that the combinational effect of these peptides and β-lactams sensitised the bacteria towards the β-lactam drugs. We hypothesize that the antimicrobial peptides obtained might be considered among the novel inhibitors that can be used specifically against the Ί-loop of the β-lactamases

    Azithromycin for treatment of bronchiolitis obliterans syndrome in adult lung transplant recipients

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    This is a protocol for a Cochrane Review (Intervention). The objectives are as follows: This review aims to look at the benefits and harms of azithromycin for the treatment of BOS in adult lung transplant recipients

    From early markers to neuro-developmental mechanisms of autism

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    A fast growing field, the study of infants at risk because of having an older sibling with autism (i.e. infant sibs) aims to identify the earliest signs of this disorder, which would allow for earlier diagnosis and intervention. More importantly, we argue, these studies offer the opportunity to validate existing neuro-developmental models of autism against experimental evidence. Although autism is mainly seen as a disorder of social interaction and communication, emerging early markers do not exclusively reflect impairments of the “social brain”. Evidence for atypical development of sensory and attentional systems highlight the need to move away from localized deficits to models suggesting brain-wide involvement in autism pathology. We discuss the implications infant sibs findings have for future work into the biology of autism and the development of interventions

    NGOs' strategies and the challenge of development and democracy in Bangladesh

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    Recent research Bangladesh has come to embody an interesting paradox. On the one hand, it has experienced rising rates of growth, a slow but steady decline in poverty and impressive progress in terms of social development, outperforming some of its richer neighbours on a number of Millennium Development Goals. On the other hand, it has an abysmal record on governance and was ranked as the world’s most corrupt country for five consecutive years by Transparency International. There is an emerging view that the country’s extremely active development NGO sector has contributed to some of the more positive achievements. The question that this paper sets out to address is why these organisations have not made an equivalent contribution on the governance front. The paper argues that while Bangladesh is reported to have more NGOs per capita than other developing countries, those organisations have gradually abandoned social mobilising and collective action strategies for a narrower focus on service delivery and microcredit provision. Our research with the members of six organisations that straddle the continuum between microfinance and social mobilisation suggests that the specific developmental strategies of these membership-based groups do indeed have consequences for both development and democracy in the country

    Information asymmetry, disclosure and foreign institutional investment: an empirical investigation of the impact of the Sarbanes-Oxley Act

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    Do foreign institutional investors (FII) regard the introduction of rigorous disclosure requirements as a major incentive to invest in U.S. equities? We investigate the role of information asymmetry and the impact of firm-level disclosure on FII decisions. We use a unique context for analysis -- the enactment of the Sarbanes-Oxley Act (SOX), and find that foreign institutional investors increase their equity holdings in U.S. listed firms following the passage of SOX. The increase in U.S. equity holdings is largely accounted by passive, non-monitoring FII, who have the most to gain from the SOX-led reduction in the value of private information

    Performance of CMS muon reconstruction in pp collision events at sqrt(s) = 7 TeV

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    The performance of muon reconstruction, identification, and triggering in CMS has been studied using 40 inverse picobarns of data collected in pp collisions at sqrt(s) = 7 TeV at the LHC in 2010. A few benchmark sets of selection criteria covering a wide range of physics analysis needs have been examined. For all considered selections, the efficiency to reconstruct and identify a muon with a transverse momentum pT larger than a few GeV is above 95% over the whole region of pseudorapidity covered by the CMS muon system, abs(eta) < 2.4, while the probability to misidentify a hadron as a muon is well below 1%. The efficiency to trigger on single muons with pT above a few GeV is higher than 90% over the full eta range, and typically substantially better. The overall momentum scale is measured to a precision of 0.2% with muons from Z decays. The transverse momentum resolution varies from 1% to 6% depending on pseudorapidity for muons with pT below 100 GeV and, using cosmic rays, it is shown to be better than 10% in the central region up to pT = 1 TeV. Observed distributions of all quantities are well reproduced by the Monte Carlo simulation.Comment: Replaced with published version. Added journal reference and DO

    Performance of CMS muon reconstruction in pp collision events at sqrt(s) = 7 TeV

    Get PDF
    The performance of muon reconstruction, identification, and triggering in CMS has been studied using 40 inverse picobarns of data collected in pp collisions at sqrt(s) = 7 TeV at the LHC in 2010. A few benchmark sets of selection criteria covering a wide range of physics analysis needs have been examined. For all considered selections, the efficiency to reconstruct and identify a muon with a transverse momentum pT larger than a few GeV is above 95% over the whole region of pseudorapidity covered by the CMS muon system, abs(eta) < 2.4, while the probability to misidentify a hadron as a muon is well below 1%. The efficiency to trigger on single muons with pT above a few GeV is higher than 90% over the full eta range, and typically substantially better. The overall momentum scale is measured to a precision of 0.2% with muons from Z decays. The transverse momentum resolution varies from 1% to 6% depending on pseudorapidity for muons with pT below 100 GeV and, using cosmic rays, it is shown to be better than 10% in the central region up to pT = 1 TeV. Observed distributions of all quantities are well reproduced by the Monte Carlo simulation.Comment: Replaced with published version. Added journal reference and DO
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