73 research outputs found

    Universal spectrum of 2d conformal field theory in the large c limit

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    Two-dimensional conformal field theories exhibit a universal free energy in the high temperature limit T → ∞, and a universal spectrum in the Cardy regime, Δ → ∞. We show that a much stronger form of universality holds in theories with a large central charge c and a sparse light spectrum. In these theories, the free energy is universal at all values of the temperature, and the microscopic spectrum matches the Cardy entropy for all Δ≄c/6 . The same is true of three-dimensional quantum gravity; therefore our results provide simple necessary and sufficient criteria for 2d CFTs to behave holographically in terms of the leading spectrum and thermodynamics. We also discuss several applications to CFT and gravity, including operator dimension bounds derived from the modular bootstrap, universality in symmetric orbifolds, and the role of non-universal ‘enigma’ saddlepoints in the thermodynamics of 3d gravity

    Delayed expression of cell cycle proteins contributes to astroglial scar formation and chronic inflammation after rat spinal cord contusion

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    Background Traumatic spinal cord injury (SCI) induces secondary tissue damage that is associated with astrogliosis and inflammation. We previously reported that acute upregulation of a cluster of cell-cycle-related genes contributes to post-mitotic cell death and secondary damage after SCI. However, it remains unclear whether cell cycle activation continues more chronically and contributes to more delayed glial change. Here we examined expression of cell cycle-related proteins up to 4 months following SCI, as well as the effects of the selective cyclin-dependent kinase (CDKs) inhibitor CR8, on astrogliosis and microglial activation in a rat SCI contusion model. Methods Adult male rats were subjected to moderate spinal cord contusion injury at T8 using a well-characterized weight-drop model. Tissue from the lesion epicenter was obtained 4 weeks or 4 months post-injury, and processed for protein expression and lesion volume. Functional recovery was assessed over the 4 months after injury. Results Immunoblot analysis demonstrated a marked continued upregulation of cell cycle-related proteins − including cyclin D1 and E, CDK4, E2F5 and PCNA − for 4 months post-injury that were highly expressed by GFAP+ astrocytes and microglia, and co-localized with inflammatory-related proteins. CR8 administrated systemically 3 h post-injury and continued for 7 days limited the sustained elevation of cell cycle proteins and immunoreactivity of GFAP, Iba-1 and p22PHOX − a key component of NADPH oxidase − up to 4 months after SCI. CR8 treatment significantly reduced lesion volume, which typically progressed in untreated animals between 1 and 4 months after trauma. Functional recovery was also significantly improved by CR8 treatment after SCI from week 2 through week 16. Conclusions These data demonstrate that cell cycle-related proteins are chronically upregulated after SCI and may contribute to astroglial scar formation, chronic inflammation and further tissue loss

    Tensor networks, p-adic fields, and algebraic curves: arithmetic and the AdS_3/CFT_2 correspondence

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    One of the many remarkable properties of conformal field theory in two dimensions is its connection to algebraic geometry. Since every compact Riemann surface is a projective algebraic curve, many constructions of interest in physics (which a priori depend on the analytic structure of the spacetime) can be formulated in purely algebraic language. This opens the door to interesting generalizations, obtained by taking another choice of field: for instance, the p-adics. We generalize the AdS/CFT correspondence according to this principle; the result is a formulation of holography in which the bulk geometry is discrete—the Bruhat–Tits tree for PGL(2,Qp)—but the group of bulk isometries nonetheless agrees with that of boundary conformal transformations and is not broken by discretization. We suggest that this forms the natural geometric setting for tensor networks that have been proposed as models of bulk reconstruction via quantum error correcting codes; in certain cases, geodesics in the Bruhat–Tits tree reproduce those constructed using quantum error correction. Other aspects of holography also hold: Standard holographic results for massive free scalar fields in a fixed background carry over to the tree, whose vertical direction can be interpreted as a renormalization-group scale for modes in the boundary CFT. Higher-genus bulk geometries (the BTZ black hole and its generalizations) can be understood straightforwardly in our setting, and the Ryu–Takayanagi formula for the entanglement entropy appears naturally

    Delayed mGluR5 activation limits neuroinflammation and neurodegeneration after traumatic brain injury

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    <p>Abstract</p> <p>Background</p> <p>Traumatic brain injury initiates biochemical processes that lead to secondary neurodegeneration. Imaging studies suggest that tissue loss may continue for months or years after traumatic brain injury in association with chronic microglial activation. Recently we found that metabotropic glutamate receptor 5 (mGluR5) activation by (<it>RS</it>)-2-chloro-5-hydroxyphenylglycine (CHPG) decreases microglial activation and release of associated pro-inflammatory factors <it>in vitro</it>, which is mediated in part through inhibition of reduced nicotinamide adenine dinucleotide phosphate (NADPH) oxidase. Here we examined whether delayed CHPG administration reduces chronic neuroinflammation and associated neurodegeneration after experimental traumatic brain injury in mice.</p> <p>Methods</p> <p>One month after controlled cortical impact traumatic brain injury, C57Bl/6 mice were randomly assigned to treatment with single dose intracerebroventricular CHPG, vehicle or CHPG plus a selective mGluR5 antagonist, 3-((2-Methyl-4-thiazolyl)ethynyl)pyridine. Lesion volume, white matter tract integrity and neurological recovery were assessed over the following three months.</p> <p>Results</p> <p>Traumatic brain injury resulted in mGluR5 expression in reactive microglia of the cortex and hippocampus at one month post-injury. Delayed CHPG treatment reduced expression of reactive microglia expressing NADPH oxidase subunits; decreased hippocampal neuronal loss; limited lesion progression, as measured by repeated T2-weighted magnetic resonance imaging (at one, two and three months) and white matter loss, as measured by high field <it>ex vivo </it>diffusion tensor imaging at four months; and significantly improved motor and cognitive recovery in comparison to the other treatment groups.</p> <p>Conclusion</p> <p>Markedly delayed, single dose treatment with CHPG significantly improves functional recovery and limits lesion progression after experimental traumatic brain injury, likely in part through actions at mGluR5 receptors that modulate neuroinflammation.</p

    Evaluation of appendicitis risk prediction models in adults with suspected appendicitis

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    Background Appendicitis is the most common general surgical emergency worldwide, but its diagnosis remains challenging. The aim of this study was to determine whether existing risk prediction models can reliably identify patients presenting to hospital in the UK with acute right iliac fossa (RIF) pain who are at low risk of appendicitis. Methods A systematic search was completed to identify all existing appendicitis risk prediction models. Models were validated using UK data from an international prospective cohort study that captured consecutive patients aged 16–45 years presenting to hospital with acute RIF in March to June 2017. The main outcome was best achievable model specificity (proportion of patients who did not have appendicitis correctly classified as low risk) whilst maintaining a failure rate below 5 per cent (proportion of patients identified as low risk who actually had appendicitis). Results Some 5345 patients across 154 UK hospitals were identified, of which two‐thirds (3613 of 5345, 67·6 per cent) were women. Women were more than twice as likely to undergo surgery with removal of a histologically normal appendix (272 of 964, 28·2 per cent) than men (120 of 993, 12·1 per cent) (relative risk 2·33, 95 per cent c.i. 1·92 to 2·84; P < 0·001). Of 15 validated risk prediction models, the Adult Appendicitis Score performed best (cut‐off score 8 or less, specificity 63·1 per cent, failure rate 3·7 per cent). The Appendicitis Inflammatory Response Score performed best for men (cut‐off score 2 or less, specificity 24·7 per cent, failure rate 2·4 per cent). Conclusion Women in the UK had a disproportionate risk of admission without surgical intervention and had high rates of normal appendicectomy. Risk prediction models to support shared decision‐making by identifying adults in the UK at low risk of appendicitis were identified

    Of yeast, mice and men: MAMs come in two flavors

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