Techniques for improving reliability of computers

Modular design techniques improve methods of error detection, diagnosis, and recovery. Theoretical computer (MARCS (Modular Architecture for Reliable Computer Systems)) study deals with postulated and modeled technology indigenous to 1975-1980. Study developments are discussed

Pathologic Prion Protein Infects Cells by Lipid-Raft Dependent Macropinocytosis

Transmissible spongiform encephalopathies, including variant-Creutzfeldt-Jakob disease (vCJD) in humans and bovine spongiform encephalopathies in cattle, are fatal neurodegenerative disorders characterized by protein misfolding of the host cellular prion protein (PrPC) to the infectious scrapie form (PrPSc). However, the mechanism that exogenous PrPSc infects cells and where pathologic conversion of PrPC to the PrPSc form occurs remains uncertain. Here we report that similar to the mechanism of HIV-1 TAT-mediated peptide transduction, processed mature, full length PrP contains a conserved N-terminal cationic domain that stimulates cellular uptake by lipid raft-dependent, macropinocytosis. Inhibition of macropinocytosis by three independent means prevented cellular uptake of recombinant PrP; however, it did not affect recombinant PrP cell surface association. In addition, fusion of the cationic N-terminal PrP domain to a Cre recombinase reporter protein was sufficient to promote both cellular uptake and escape from the macropinosomes into the cytoplasm. Inhibition of macropinocytosis was sufficient to prevent conversion of PrPC to the pathologic PrPSc form in N2a cells exposed to strain RML PrPSc infected brain homogenates, suggesting that a critical determinant of PrPC conversion occurs following macropinocytotic internalization and not through mere membrane association. Taken together, these observations provide a cellular mechanism that exogenous pathological PrPSc infects cells by lipid raft dependent, macropinocytosis

French feminism: national and international perspectives

During the 1980s, the French media proclaimed the death of feminism, but although the 1970s women’s movement had demobilised, feminists were still active in issue-specific groups, in academia and within the institutions of the state. Paying careful attention to the difficulties associated with defining feminisms and national feminisms in particular, this article situates an analysis of French feminism since the 1980s in a context of growing international feminist dialogue and activism and a renewed debate about the meaning of feminism. It focuses on the question of separatism and on changing relations between theory and practice, asking how feminists can act for change and form effective coalitions with men and with other movements. It argues that feminism is plural and often fragmented and diffuse. Feminism is shaped by local social, economic, political and cultural factors and by exchanges of people and ideas, and any analysis of feminist theory and activism needs to take these into account

Noncommutative probability, matrix models, and quantum orbifold geometry

Inspired by the intimate relationship between Voiculescu's noncommutative probability theory (of type A) and large-N matrix models in physics, we look for physical models related to noncommutative probability theory of type B. These turn out to be fermionic matrix-vector models at the double large-N limit. In the context of string theory, they describe different orbifolded string worldsheets with boundaries. Their critical exponents coincide with that of ordinary string worldsheets, but their renormalised tree-level one-boundary amplitudes differ.Comment: 22 pages, 8 eps figures, LaTeX2.09; title changed, mistakes correcte

Non-Douglas-Kazakov phase transition of two-dimensional generalized Yang-Mills theories

In two-dimensional Yang-Mills and generalized Yang-Mills theories for large gauge groups, there is a dominant representation determining the thermodynamic limit of the system. This representation is characterized by a density the value of which should everywhere be between zero and one. This density itself is determined through a saddle-point analysis. For some values of the parameter space, this density exceeds one in some places. So one should modify it to obtain an acceptable density. This leads to the well-known Douglas-Kazakov phase transition. In generalized Yang-Mills theories, there are also regions in the parameter space where somewhere this density becomes negative. Here too, one should modify the density so that it remains nonnegative. This leads to another phase transition, different from the Douglas-Kazakov one. Here the general structure of this phase transition is studied, and it is shown that the order of this transition is typically three. Using carefully-chosen parameters, however, it is possible to construct models with phase-transition orders not equal to three. A class of these non-typical models are also studied.Comment: 11 pages, accepted for publication in Eur. Phys. J.

Nonperturbative effects and nonperturbative definitions in matrix models and topological strings

We develop techniques to compute multi-instanton corrections to the 1/N expansion in matrix models described by orthogonal polynomials. These techniques are based on finding trans-series solutions, i.e. formal solutions with exponentially small corrections, to the recursion relations characterizing the free energy. We illustrate this method in the Hermitian, quartic matrix model, and we provide a detailed description of the instanton corrections in the Gross-Witten-Wadia (GWW) unitary matrix model. Moreover, we use Borel resummation techniques and results from the theory of resurgent functions to relate the formal multi-instanton series to the nonperturbative definition of the matrix model. We study this relation in the case of the GWW model and its double-scaling limit, providing in this way a nice illustration of various mechanisms connecting the resummation of perturbative series to nonperturbative results, like the cancellation of nonperturbative ambiguities. Finally, we argue that trans-series solutions are also relevant in the context of topological string theory. In particular, we point out that in topological string models with both a matrix model and a large N gauge theory description, the nonperturbative, holographic definition involves a sum over the multi-instanton sectors of the matrix modelComment: 50 pages, 12 figures, comments and references added, small correction

Periodontal diagnosis in the context of the 2017 classification system of periodontal diseases and conditions: Presentation of a middle-aged patient with localised periodontitis

The objective of this case report is to illustrate the diagnosis and classification of periodontitis according to the 2017 classification system as recommended in the British Society of Periodontology (BSP) implementation plan. We describe a case of a patient who was diagnosed with 'localised periodontitis; stage II, grade B; currently unstable'. The present case report presents an example for the application of the new classification system and illustrates how the new classification system captures disease severity, extent and disease susceptibility by staging and grading periodontitis

Search for π0→νμνˉμ\pi^0 \to \nu_{\mu}\bar\nu_{\mu} Decay in LSND

We observe a net beam-excess of $8.7 \pm 6.3$ (stat) $\pm 2.4$ (syst) events, above 160 MeV, resulting from the charged-current reaction of $\nu_{\mu}$ and/or $\bar\nu_{\mu}$ on C and H in the LSND detector. No beam related muon background is expected in this energy regime. Within an analysis framework of $\pi^0 \to \nu_{\mu}\bar\nu_{\mu}$, we set a direct upper limit for this branching ratio of $\Gamma(\pi^0 \to \nu_\mu \bar\nu_\mu) / \Gamma(\pi^0 \to all) < 1.6 \times 10^{-6}$ at 90% confidence level.Comment: 4 pages, 4 figure

Pralidoxime in Acute Organophosphorus Insecticide Poisoning-A Randomised Controlled Trial

Background: Poisoning with organophosphorus (OP) insecticides is a major global public health problem, causing an estimated 200,000 deaths each year. Although the World Health Organization recommends use of pralidoxime, this antidote's effectiveness remains unclear. We aimed to determine whether the addition of pralidoxime chloride to atropine and supportive care offers benefit. Methods and Findings: We performed a double-blind randomised placebo-controlled trial of pralidoxime chloride (2 g loading dose over 20 min, followed by a constant infusion of 0.5 g/h for up to 7 d) versus saline in patients with organophosphorus insecticide self-poisoning. Mortality was the primary outcome; secondary outcomes included intubation, duration of intubation, and time to death. We measured baseline markers of exposure and pharmacodynamic markers of response to aid interpretation of clinical outcomes. Two hundred thirty-five patients were randomised to receive pralidoxime (121) or saline placebo (114). Pralidoxime produced substantial and moderate red cell acetylcholinesterase reactivation in patients poisoned by diethyl and dimethyl compounds, respectively. Mortality was nonsignificantly higher in patients receiving pralidoxime: 30/121 (24.8%) receiving pralidoxime died, compared with 18/114 (15.8%) receiving placebo (adjusted hazard ratio HR] 1.69, 95% confidence interval CI] 0.88-3.26, p = 0.12). Incorporating the baseline amount of acetylcholinesterase already aged and plasma OP concentration into the analysis increased the HR for patients receiving pralidoxime compared to placebo, further decreasing the likelihood that pralidoxime is beneficial. The need for intubation was similar in both groups (pralidoxime 26/121 21.5%], placebo 24/114 21.1%], adjusted HR 1.27 95% CI 0.71-2.29]). To reduce confounding due to ingestion of different insecticides, we further analysed patients with confirmed chlorpyrifos or dimethoate poisoning alone, finding no evidence of benefit. Conclusions: Despite clear reactivation of red cell acetylcholinesterase in diethyl organophosphorus pesticide poisoned patients, we found no evidence that this regimen improves survival or reduces need for intubation in patients with organophosphorus insecticide poisoning. The reason for this failure to benefit patients was not apparent. Further studies of different dose regimens or different oximes are required

Potent Delivery of Functional Proteins into Mammalian Cells in Vitro and in Vivo Using a Supercharged Protein

The inability of proteins to potently penetrate mammalian cells limits their usefulness as tools and therapeutics. When fused to superpositively charged GFP, proteins rapidly (within minutes) entered five different types of mammalian cells with potency up to ∼100-fold greater than that of corresponding fusions with known protein transduction domains (PTDs) including Tat, oligoarginine, and penetratin. Ubiquitin-fused supercharged GFP when incubated with human cells was partially deubiquitinated, suggesting that proteins delivered with supercharged GFP can access the cytosol. Likewise, supercharged GFP delivered functional, nonendosomal recombinase enzyme with greater efficiencies than PTDs in vitro and also delivered functional recombinase enzyme to the retinae of mice when injected in vivo.Chemistry and Chemical Biolog