Duality and replicas for a unitary matrix model

In a generalized Airy matrix model, a power $p$ replaces the cubic term of the Airy model introduced by Kontsevich. The parameter $p$ corresponds to Witten's spin index in the theory of intersection numbers of moduli space of curves. A continuation in $p$ down to $p= -2$ yields a well studied unitary matrix model, which exhibits two different phases in the weak and strong coupling regions, with a third order critical point in-between. The application of duality and replica to the $p$-th Airy model allows one to recover both the weak and strong phases of the unitary model, and to establish some new results for these expansions. Therefore the unitary model is also indirectly a generating function for intersection numbers.Comment: 18 page, add referece

Poloxomer 188 Has a Deleterious Effect on Dystrophic Skeletal Muscle Function

Duchenne muscular dystrophy (DMD) is an X-linked, fatal muscle wasting disease for which there is currently no cure and limited palliative treatments. Poloxomer 188 (P188) is a tri-block copolymer that has been proposed as a potential treatment for cardiomyopathy in DMD patients. Despite the reported beneficial effects of P188 on dystrophic cardiac muscle function, the effects of P188 on dystrophic skeletal muscle function are relatively unknown. Mdx mice were injected intraperitoneally with 460 mg/kg or 30 mg/kg P188 dissolved in saline, or saline alone (control). The effect of single-dose and 2-week daily treatment was assessed using a muscle function test on the Tibialis Anterior (TA) muscle in situ in anaesthetised mice. The test comprises a warm up, measurement of the force-frequency relationship and a series of eccentric contractions with a 10% stretch that have previously been shown to cause a drop in maximum force in mdx mice. After 2 weeks of P188 treatment at either 30 or 460 mg/kg/day the drop in maximum force produced following eccentric contractions was significantly greater than that seen in saline treated control mice (P = 0.0001). Two week P188 treatment at either dose did not significantly change the force-frequency relationship or maximum isometric specific force produced by the TA muscle. In conclusion P188 treatment increases susceptibility to contraction-induced injury following eccentric contractions in dystrophic skeletal muscle and hence its suitability as a potential therapeutic for DMD should be reconsidered

Molecular Genetics of T Cell Development

T cell development is guided by a complex set of transcription factors that act recursively, in different combinations, at each of the developmental choice points from T-lineage specification to peripheral T cell specialization. This review describes the modes of action of the major T-lineage-defining transcription factors and the signal pathways that activate them during intrathymic differentiation from pluripotent precursors. Roles of Notch and its effector RBPSuh (CSL), GATA-3, E2A/HEB and Id proteins, c-Myb, TCF-1, and members of the Runx, Ets, and Ikaros families are critical. Less known transcription factors that are newly recognized as being required for T cell development at particular checkpoints are also described. The transcriptional regulation of T cell development is contrasted with that of B cell development, in terms of their different degrees of overlap with the stem-cell program and the different roles of key transcription factors in gene regulatory networks leading to lineage commitment

Mass extinctions and supernova explosions

A nearby supernova (SN) explosion could have negatively influenced life on Earth, maybe even been responsible for mass extinctions. Mass extinction poses a significant extinction of numerous species on Earth, as recorded in the paleontologic, paleoclimatic, and geological record of our planet. Depending on the distance between the Sun and the SN, different types of threats have to be considered, such as ozone depletion on Earth, causing increased exposure to the Sun's ultraviolet radiation, or the direct exposure of lethal x-rays. Another indirect effect is cloud formation, induced by cosmic rays in the atmosphere which result in a drop in the Earth's temperature, causing major glaciations of the Earth. The discovery of highly intensive gamma ray bursts (GRBs), which could be connected to SNe, initiated further discussions on possible life-threatening events in Earth's history. The probability that GRBs hit the Earth is very low. Nevertheless, a past interaction of Earth with GRBs and/or SNe cannot be excluded and might even have been responsible for past extinction events.Comment: Chapter for forthcoming book: Handbook of Supernovae, P. Murdin and A. Alsabeti (eds.), Springer International Publishing (in press

The a-theorem and conformal symmetry breaking in holographic RG flows

We study holographic models describing an RG flow between two fixed points driven by a relevant scalar operator. We show how to introduce a spurion field to restore Weyl invariance and compute the anomalous contribution to the generating functional in even dimensional theories. We find that the coefficient of the anomalous term is proportional to the difference of the conformal anomalies of the UV and IR fixed points, as expected from anomaly matching arguments in field theory. For any even dimensions the coefficient is positive as implied by the holographic a-theorem. For flows corresponding to spontaneous breaking of conformal invariance, we also compute the two-point functions of the energy-momentum tensor and the scalar operator and identify the dilaton mode. Surprisingly we find that in the simplest models with just one scalar field there is no dilaton pole in the two-point function of the scalar operator but a stronger singularity. We discuss the possible implications.Comment: 50 pages. v2: minor changes, added references, extended discussion. v3: we have clarified some of the calculations and assumptions, results unchanged. v4: published version 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

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

Hydrodynamics of a 5D Einstein-dilaton black hole solution and the corresponding BPS state

We apply the potential reconstruction approach to generate a series of asymptotically AdS (aAdS) black hole solutions, with a self-interacting bulk scalar field. Based on the method, we reproduce the pure AdS solution as a consistency check and we also generate a simple analytic 5D black hole solution. We then study various aspects of this solution, such as temperature, entropy density and conserved charges. Furthermore, we study the hydrodynamics of this black hole solution in the framework of fluid/gravity duality, e.g. the ratio of the shear viscosity to the entropy density. In a degenerate case of the 5D black hole solution, we find that the c function decreases monotonically from UV to IR as expected. Finally, we investigate the stability of the degenerate solution by studying the bosonic functional energy of the gravity and the Witten-Nester energy $E_{WN}$. We confirm that the degenerate solution is a BPS domain wall solution. The corresponding superpotential and the solution of the killing spinor equation are found explicitly.Comment: V2: 23 pages, no figure, minor changes, typos corrected, new references and comments added, version accepted by JHE

An 800-million-solar-mass black hole in a significantly neutral Universe at redshift 7.5

Quasars are the most luminous non-transient objects known and as a result they enable studies of the Universe at the earliest cosmic epochs. Despite extensive efforts, however, the quasar ULAS J1120+0641 at z=7.09 has remained the only one known at z>7 for more than half a decade. Here we report observations of the quasar ULAS J134208.10+092838.61 (hereafter J1342+0928) at redshift z=7.54. This quasar has a bolometric luminosity of 4e13 times the luminosity of the Sun and a black hole mass of 8e8 solar masses. The existence of this supermassive black hole when the Universe was only 690 million years old---just five percent of its current age---reinforces models of early black-hole growth that allow black holes with initial masses of more than about 1e4 solar masses or episodic hyper-Eddington accretion. We see strong evidence of absorption of the spectrum of the quasar redwards of the Lyman alpha emission line (the Gunn-Peterson damping wing), as would be expected if a significant amount (more than 10 per cent) of the hydrogen in the intergalactic medium surrounding J1342+0928 is neutral. We derive a significant fraction of neutral hydrogen, although the exact fraction depends on the modelling. However, even in our most conservative analysis we find a fraction of more than 0.33 (0.11) at 68 per cent (95 per cent) probability, indicating that we are probing well within the reionization epoch of the Universe.Comment: Updated to match the final journal versio

Holographic R-symmetric flows and the \u3c4_U conjecture

We discuss the holographic counterpart of a recent conjecture regarding R-symmetric RG flows in four-dimensional supersymmetric field theories. In such theories, a quantity \u3c4U can be defined at the fixed points which was conjectured in [1] to be larger in the UV than in the IR, \u3c4U UV>\u3c4U IR. We analyze this conjecture from a dual supergravity perspective: using some general properties of domain wall solutions dual to R-symmetric RG flows, we define a bulk quantity which interpolates between the correct \u3c4 U at the UV and IR fixed points, and study its monotonicity properties in a class of examples. We find a monotonic behavior for theories flowing to an interacting IR fixed point. For gapped theories, the monotonicity is still valid up to a finite value of the radial coordinate where the function vanishes, reflecting the gap scale of the field theory. \ua9 2013 SISSA, Trieste, Italy

Kinetic modelling of competition and depletion of shared miRNAs by competing endogenous RNAs

Non-conding RNAs play a key role in the post-transcriptional regulation of mRNA translation and turnover in eukaryotes. miRNAs, in particular, interact with their target RNAs through protein-mediated, sequence-specific binding, giving rise to extended and highly heterogeneous miRNA-RNA interaction networks. Within such networks, competition to bind miRNAs can generate an effective positive coupling between their targets. Competing endogenous RNAs (ceRNAs) can in turn regulate each other through miRNA-mediated crosstalk. Albeit potentially weak, ceRNA interactions can occur both dynamically, affecting e.g. the regulatory clock, and at stationarity, in which case ceRNA networks as a whole can be implicated in the composition of the cell's proteome. Many features of ceRNA interactions, including the conditions under which they become significant, can be unraveled by mathematical and in silico models. We review the understanding of the ceRNA effect obtained within such frameworks, focusing on the methods employed to quantify it, its role in the processing of gene expression noise, and how network topology can determine its reach.Comment: review article, 29 pages, 7 figure