2,218 research outputs found

    Fission yeast SWI/SNF and RSC complexes show compositional and functional differences from budding yeast.

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    SWI/SNF chromatin-remodeling complexes have crucial roles in transcription and other chromatin-related processes. The analysis of the two members of this class in Saccharomyces cerevisiae, SWI/SNF and RSC, has heavily contributed to our understanding of these complexes. To understand the in vivo functions of SWI/SNF and RSC in an evolutionarily distant organism, we have characterized these complexes in Schizosaccharomyces pombe. Although core components are conserved between the two yeasts, the compositions of S. pombe SWI/SNF and RSC differ from their S. cerevisiae counterparts and in some ways are more similar to metazoan complexes. Furthermore, several of the conserved proteins, including actin-like proteins, are markedly different between the two yeasts with respect to their requirement for viability. Finally, phenotypic and microarray analyses identified widespread requirements for SWI/SNF and RSC on transcription including strong evidence that SWI/SNF directly represses iron-transport genes

    Elucidation of the RamA Regulon in Klebsiella pneumoniae Reveals a Role in LPS Regulation

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    Klebsiella pneumoniae is a significant human pathogen, in part due to high rates of multidrug resistance. RamA is an intrinsic regulator in K. pneumoniae established to be important for the bacterial response to antimicrobial challenge; however, little is known about its possible wider regulatory role in this organism during infection. In this work, we demonstrate that RamA is a global transcriptional regulator that significantly perturbs the transcriptional landscape of K. pneumoniae, resulting in altered microbe-drug or microbe-host response. This is largely due to the direct regulation of 68 genes associated with a myriad of cellular functions. Importantly, RamA directly binds and activates the lpxC, lpxL-2 and lpxO genes associated with lipid A biosynthesis, thus resulting in modifications within the lipid A moiety of the lipopolysaccharide. RamA-mediated alterations decrease susceptibility to colistin E, polymyxin B and human cationic antimicrobial peptide LL-37. Increased RamA levels reduce K. pneumoniae adhesion and uptake into macrophages, which is supported by in vivo infection studies, that demonstrate increased systemic dissemination of ramA overexpressing K. pneumoniae. These data establish that RamA-mediated regulation directly perturbs microbial surface properties, including lipid A biosynthesis, which facilitate evasion from the innate host response. This highlights RamA as a global regulator that confers pathoadaptive phenotypes with implications for our understanding of the pathogenesis of Enterobacter, Salmonella and Citrobacter spp. that express orthologous RamA proteins

    Evolution of Parton Distribution Functions in the Short-Distance Factorization Scheme

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    Lattice QCD offers the possibility of computing parton distributions from first principles, although not in the usual MS‾\overline{MS} factorization scheme. We study in this paper the evolution of non-singlet parton distribution functions (PDFs) in the short-distance factorization scheme which notably arises in lattice calculations in the pseudo-distribution approach. We provide an assessment of non-perturbative evolution of PDFs from already published lattice matrix elements, and show how this evolution can be used to reduce the fluctuation of the lattice data. We compare our result with expectations obtained thanks to a perturbative matching to MS‾\overline{MS}. By highlighting the limitations of the current computations, we advocate for a new strategy using lattice calculations in small volume.Comment: 57 pages, 28 figure

    The effect of additive noise on dynamical hysteresis

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    We investigate the properties of hysteresis cycles produced by a one-dimensional, periodically forced Langevin equation. We show that depending on amplitude and frequency of the forcing and on noise intensity, there are three qualitatively different types of hysteresis cycles. Below a critical noise intensity, the random area enclosed by hysteresis cycles is concentrated near the deterministic area, which is different for small and large driving amplitude. Above this threshold, the area of typical hysteresis cycles depends, to leading order, only on the noise intensity. In all three regimes, we derive mathematically rigorous estimates for expectation, variance, and the probability of deviations of the hysteresis area from its typical value.Comment: 30 pages, 5 figure

    The weak password problem: chaos, criticality, and encrypted p-CAPTCHAs

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    Vulnerabilities related to weak passwords are a pressing global economic and security issue. We report a novel, simple, and effective approach to address the weak password problem. Building upon chaotic dynamics, criticality at phase transitions, CAPTCHA recognition, and computational round-off errors we design an algorithm that strengthens security of passwords. The core idea of our method is to split a long and secure password into two components. The first component is memorized by the user. The second component is transformed into a CAPTCHA image and then protected using evolution of a two-dimensional dynamical system close to a phase transition, in such a way that standard brute-force attacks become ineffective. We expect our approach to have wide applications for authentication and encryption technologies.Comment: 5 pages, 6 figer

    Facing Up to Unpalatable Evidence for the Sake of Our Patients

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    Paul Mullen discusses Seena Fazel and colleagues' paper on the association between violent behavior and having been diagnosed with a schizophrenic disorder, and its implications for care of these individuals
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