268 research outputs found

    Black Hole Emission in String Theory and the String Phase of Black Holes

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    String theory properly describes black-hole evaporation. The quantum string emission by Black Holes is computed. The black-hole temperature is the Hawking temperature in the semiclassical quantum field theory (QFT) regime and becomes the intrinsic string temperature, T_s, in the quantum (last stage) string regime. The QFT-Hawking temperature T_H is upper bounded by the string temperature T_S. The black hole emission spectrum is an incomplete gamma function of (T_H - T_S). For T_H << T_S, it yields the QFT-Hawking emission. For T_H \to T_S, it shows highly massive string states dominate the emission and undergo a typical string phase transition to a microscopic `minimal' black hole of mass M_{\min} or radius r_{\min} (inversely proportional to T_S) and string temperature T_S. The string back reaction effect (selfconsistent black hole solution of the semiclassical Einstein equations) is computed. Both, the QFT and string black hole regimes are well defined and bounded.The string `minimal' black hole has a life time tau_{min} simeq (k_B c)/(G hbar [T_S]^3). The semiclassical QFT black hole (of mass M and temperature T_H) and the string black hole (of mass M_{min} and temperature T_S) are mapped one into another by a `Dual' transform which links classical/QFT and quantum string regimes.Comment: LaTex, 22 pages, Lectures delivered at the Chalonge School, Nato ASI: Phase Transitions in the Early Universe: Theory and Observations. To appear in the Proceedings, Editors H. J. de Vega, I. Khalatnikov, N. Sanchez. (Kluwer Pub

    Thermodynamics of Superstring on Near-extremal NS5 and Effective Hagedorn Behavior

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    We study the thermodynamical torus partition function of superstring on the near-extremal black NS5-brane background. The exact partition function has been computed with the helps of our previous works:[arXiv:1012.5721 [hep-th]], [arXiv:1109.3365 [hep-th]], and naturally decomposed into two parts. The first part is contributed from strings freely propagating in the asymptotic region, which are identified as the superstring gas at the Hawking temperature on the linear-dilaton background. The second part includes the contribution localized around the `tip of cigar', which characterizes the non-extremality. Remarkably, the latter part includes massless excitations with non-vanishing thermal winding, which signifies that the Hagedorn-like behavior effectively appears, even though the Hawking temperature is much lower than the Hagedorn temperature. We also explore the high-temperature backgrounds defined by the orbifolding along the Euclidean time direction. In those cases, the thermal winding modes localized around the tip are found to be tachyonic, reflecting the singularities of Euclidean backgrounds caused by orbifolding.Comment: 1+29 pages, no figure; v2 the footnote 1 is enhanced, to appear in JHE

    The Human Fungal Pathogen Cryptococcus neoformans Escapes Macrophages by a Phagosome Emptying Mechanism That Is Inhibited by Arp2/3 Complex-Mediated Actin Polymerisation

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    The lysis of infected cells by disease-causing microorganisms is an efficient but risky strategy for disseminated infection, as it exposes the pathogen to the full repertoire of the host's immune system. Cryptococcus neoformans is a widespread fungal pathogen that causes a fatal meningitis in HIV and other immunocompromised patients. Following intracellular growth, cryptococci are able to escape their host cells by a non-lytic expulsive mechanism that may contribute to the invasion of the central nervous system. Non-lytic escape is also exhibited by some bacterial pathogens and is likely to facilitate long-term avoidance of the host immune system during latency. Here we show that phagosomes containing intracellular cryptococci undergo repeated cycles of actin polymerisation. These actin ‘flashes’ occur in both murine and human macrophages and are dependent on classical WASP-Arp2/3 complex mediated actin filament nucleation. Three dimensional confocal imaging time lapse revealed that such flashes are highly dynamic actin cages that form around the phagosome. Using fluorescent dextran as a phagosome membrane integrity probe, we find that the non-lytic expulsion of Cryptococcus occurs through fusion of the phagosome and plasma membranes and that, prior to expulsion, 95% of phagosomes become permeabilised, an event that is immediately followed by an actin flash. By using pharmacological agents to modulate both actin dynamics and upstream signalling events, we show that flash occurrence is inversely related to cryptococcal expulsion, suggesting that flashes may act to temporarily inhibit expulsion from infected phagocytes. In conclusion, our data reveal the existence of a novel actin-dependent process on phagosomes containing cryptococci that acts as a potential block to expulsion of Cryptococcus and may have significant implications for the dissemination of, and CNS invasion by, this organism.\ud \u

    QCD and the Hagedorn spectrum

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    It is shown that large Nc QCD must have a Hagedorn spectrum (i.e. a spectrum of hadron which grows exponentially with the hadrons mass) provided that certain technical assumptions concerning the applicability of perturbation theory to a certain class of correlation functions apply. The basic argument exploits the interplay of confinement and asymptotic freedom.Comment: 16 pages, 1 figure. This version is expanded from the original version. Additional discussion has been added to clarify the central issues. Typos have been fixed. The appendix has been updated and greatly expanded

    Leptons in Holographic Composite Higgs Models with Non-Abelian Discrete Symmetries

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    We study leptons in holographic composite Higgs models, namely in models possibly admitting a weakly coupled description in terms of five-dimensional (5D) theories. We introduce two scenarios leading to Majorana or Dirac neutrinos, based on the non-abelian discrete group S4×Z3S_4\times \Z_3 which is responsible for nearly tri-bimaximal lepton mixing. The smallness of neutrino masses is naturally explained and normal/inverted mass ordering can be accommodated. We analyze two specific 5D gauge-Higgs unification models in warped space as concrete examples of our framework. Both models pass the current bounds on Lepton Flavour Violation (LFV) processes. We pay special attention to the effect of so called boundary kinetic terms that are the dominant source of LFV. The model with Majorana neutrinos is compatible with a Kaluza-Klein vector mass scale mKK≳3.5m_{KK}\gtrsim 3.5 TeV, which is roughly the lowest scale allowed by electroweak considerations. The model with Dirac neutrinos, although not considerably constrained by LFV processes and data on lepton mixing, suffers from a too large deviation of the neutrino coupling to the ZZ boson from its Standard Model value, pushing mKK≳10m_{KK}\gtrsim 10 TeV.Comment: 37 pages, 4 figures; v2: Note added in light of recent T2K and MINOS results, figures updated with new limit from MEG, references added, various minor improvements, matches JHEP published versio

    Mycobacterium tuberculosis Complex Mycobacteria as Amoeba-Resistant Organisms

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    International audienceBackground: Most environmental non-tuberculous mycobacteria have been demonstrated to invade amoebal trophozoites and cysts, but such relationships are largely unknown for members of the Mycobacterium tuberculosis complex. An environmental source has been proposed for the animal Mycobacterium bovis and the human Mycobacterium canettii.Methodology/Principal Findings: Using optic and electron microscopy and co-culture methods, we observed that 89±0.6% of M. canettii, 12.4±0.3% of M. tuberculosis, 11.7±2% of M. bovis and 11.2±0.5% of Mycobacterium avium control organisms were phagocytized by Acanthamoeba polyphaga, a ratio significantly higher for M. canettii (P = 0.03), correlating with the significantly larger size of M. canetti organisms (P = 0.035). The percentage of intraamoebal mycobacteria surviving into cytoplasmic vacuoles was 32±2% for M. canettii, 26±1% for M. tuberculosis, 28±2% for M. bovis and 36±2% for M. avium (P = 0.57). M. tuberculosis, M. bovis and M. avium mycobacteria were further entrapped within the double wall of <1% amoebal cysts, but no M. canettii organisms were observed in amoebal cysts. The number of intracystic mycobacteria was significantly (P = 10−6) higher for M. avium than for the M. tuberculosis complex, and sub-culturing intracystic mycobacteria yielded significantly more (P = 0.02) M. avium organisms (34×104 CFU/mL) than M. tuberculosis (42×101 CFU/mL) and M. bovis (35×101 CFU/mL) in the presence of a washing fluid free of mycobacteria. Mycobacteria survived in the cysts for up to 18 days and cysts protected M. tuberculosis organisms against mycobactericidal 5 mg/mL streptomycin and 2.5% glutaraldehyde.Conclusions/Significance: These data indicate that M. tuberculosis complex organisms are amoeba-resistant organisms, as previously demonstrated for non-tuberculous, environmental mycobacteria. Intercystic survival of tuberculous mycobacteria, except for M. canettii, protect them against biocides and could play a role in their life cycle

    Identification of the Biotransformation Products of 2-Ethylhexyl 4-(N,N-Dimethylamino)benzoate

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    Nowadays, 2-ethylhexyl 4-(N,N-dimethylamino)benzoate (EDP) is one of the most widely used UV filters in sunscreen cosmetics and other cosmetic products. However, undesirable processes such as percutaneous absorption and biological activity have been attributed to this compound. The in vitro metabolism of EDP was elucidated in the present work. First of all, the phase I biotransformation was studied in rat liver microsomes and two metabolites, N,N-dimethyl-p-aminobenzoic acid (DMP) and N-monomethyl-p-aminobenzoic acid (MMP), were identified by GC-MS analysis. Secondly, the phase II metabolism was investigated by means of LC-MS. The investigated reactions were acetylation and glucuronidation working with rat liver cytosol and with both human and rat liver microsomes, respectively. Analogue studies with p-aminobenzoic acid (PABA) were carried out in order to compare the well established metabolic pathway of PABA with the unknown biotransformation of EDP. In addition, a method for the determination of EDP and its two phase I metabolites in human urine was developed. The methodology requires a solid-phase extraction prior to LC-MS analysis. The method is based on standard addition quantification and has been fully validated. The repeatability of the method, expressed as relative standard deviation, was in the range 3.4–7.4% and the limit of detection for all quantified analytes was in the low ng mL−1 range

    Mycobacterium marinum antagonistically induces an autophagic response while repressing the autophagic flux in a TORC1- and ESX-1-dependent manner.

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    Autophagy is a eukaryotic catabolic process also participating in cell-autonomous defence. Infected host cells generate double-membrane autophagosomes that mature in autolysosomes to engulf, kill and digest cytoplasmic pathogens. However, several bacteria subvert autophagy and benefit from its machinery and functions. Monitoring infection stages by genetics, pharmacology and microscopy, we demonstrate that the ESX-1 secretion system of Mycobacterium marinum, a close relative to M. tuberculosis, upregulates the transcription of autophagy genes, and stimulates autophagosome formation and recruitment to the mycobacteria-containing vacuole (MCV) in the host model organism Dictyostelium. Antagonistically, ESX-1 is also essential to block the autophagic flux and deplete the MCV of proteolytic activity. Activators of the TORC1 complex localize to the MCV in an ESX-1-dependent manner, suggesting an important role in the manipulation of autophagy by mycobacteria. Our findings suggest that the infection by M. marinum activates an autophagic response that is simultaneously repressed and exploited by the bacterium to support its survival inside the MCV

    Role of "external facilitation" in implementation of research findings: a qualitative evaluation of facilitation experiences in the Veterans Health Administration

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    BACKGROUND: Facilitation has been identified in the literature as a potentially key component of successful implementation. It has not, however, either been well-defined or well-studied. Significant questions remain about the operational definition of facilitation and about the relationship of facilitation to other interventions, especially to other change agent roles when used in multi-faceted implementation projects. Researchers who are part of the Quality Enhancement Research Initiative (QUERI) are actively exploring various approaches and processes, including facilitation, to enable implementation of best practices in the Veterans Health Administration health care system – the largest integrated healthcare system in the United States. This paper describes a systematic, retrospective evaluation of implementation-related facilitation experiences within QUERI, a quality improvement program developed by the US Department of Veterans Affairs. METHODS: A post-hoc evaluation was conducted through a series of semi-structured interviews to examine the concept of facilitation across several multi-site QUERI implementation studies. The interview process is based on a technique developed in the field of education, which systematically enhances learning through experience by stimulating recall and reflection regarding past complex activities. An iterative content analysis approach relative to a set of conceptually-based interview questions was used for data analysis. FINDINGS: Findings suggest that facilitation, within an implementation study initiated by a central change agency, is a deliberate and valued process of interactive problem solving and support that occurs in the context of a recognized need for improvement and a supportive interpersonal relationship. Facilitation was described primarily as a distinct role with a number of potentially crucial behaviors and activities. Data further suggest that external facilitators were likely to use or integrate other implementation interventions, while performing this problem-solving and supportive role. PRELIMINARY CONCLUSIONS: This evaluation provides evidence to suggest that facilitation could be considered a distinct implementation intervention, just as audit and feedback, educational outreach, or similar methods are considered to be discrete interventions. As such, facilitation should be well-defined and explicitly evaluated for its perceived usefulness within multi-intervention implementation projects. Additionally, researchers should better define the specific contribution of facilitation to the success of implementation in different types of projects, different types of sites, and with evidence and innovations of varying levels of strength and complexity

    Data for improvement and clinical excellence: protocol for an audit with feedback intervention in long-term care

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    <p>Abstract</p> <p>Background</p> <p>There is considerable evidence about the effectiveness of audit coupled with feedback, although few audit with feedback interventions have been conducted in long-term care (LTC) settings to date. In general, the effects have been found to be modest at best, although in settings where there has been little history of audit and feedback, the effects may be greater, at least initially. The primary purpose of the Data for Improvement and Clinical Excellence (DICE) Long-Term Care project is to assess the effects of an audit with feedback intervention delivered monthly over 13 months in four LTC facilities. The research questions we addressed are:</p> <p indent="1">1. What effects do feedback reports have on processes and outcomes over time?</p> <p indent="1">2. How do different provider groups in LTC and home care respond to feedback reports based on data targeted at improving quality of care?</p> <p>Methods/design</p> <p>The research team conducting this study comprises researchers and decision makers in continuing care in the province of Alberta, Canada. The intervention consists of monthly feedback reports in nine LTC units in four facilities in Edmonton, Alberta. Data for the feedback reports comes from the Resident Assessment Instrument Minimum Data Set (RAI) version 2.0, a standardized instrument mandated for use in LTC facilities throughout Alberta. Feedback reports consist of one page, front and back, presenting both graphic and textual information. Reports are delivered to all staff working in the four LTC facilities. The primary evaluation uses a controlled interrupted time series design both adjusted and unadjusted for covariates. The concurrent process evaluation uses observation and self-report to assess uptake of the feedback reports. Following the project phase described in this protocol, a similar intervention will be conducted in home care settings in Alberta. Depending on project findings, if they are judged useful by decision makers participating in this research team, we plan dissemination and spread of the feedback report approach throughout Alberta.</p
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