Testing the Gaussian expansion method in exactly solvable matrix models

The Gaussian expansion has been developed since early 80s as a powerful analytical method, which enables nonperturbative studies of various systems using `perturbative' calculations. Recently the method has been used to suggest that 4d space-time is generated dynamically in a matrix model formulation of superstring theory. Here we clarify the nature of the method by applying it to exactly solvable one-matrix models with various kinds of potential including the ones unbounded from below and of the double-well type. We also formulate a prescription to include a linear term in the Gaussian action in a way consistent with the loop expansion, and test it in some concrete examples. We discuss a case where we obtain two distinct plateaus in the parameter space of the Gaussian action, corresponding to different large-N solutions. This clarifies the situation encountered in the dynamical determination of the space-time dimensionality in the previous works.Comment: 30 pages, 15 figures, LaTeX; added references for section

Topological String Amplitudes, Complete Intersection Calabi-Yau Spaces and Threshold Corrections

We present the most complete list of mirror pairs of Calabi-Yau complete intersections in toric ambient varieties and develop the methods to solve the topological string and to calculate higher genus amplitudes on these compact Calabi-Yau spaces. These symplectic invariants are used to remove redundancies in examples. The construction of the B-model propagators leads to compatibility conditions, which constrain multi-parameter mirror maps. For K3 fibered Calabi-Yau spaces without reducible fibers we find closed formulas for all genus contributions in the fiber direction from the geometry of the fibration. If the heterotic dual to this geometry is known, the higher genus invariants can be identified with the degeneracies of BPS states contributing to gravitational threshold corrections and all genus checks on string duality in the perturbative regime are accomplished. We find, however, that the BPS degeneracies do not uniquely fix the non-perturbative completion of the heterotic string. For these geometries we can write the topological partition function in terms of the Donaldson-Thomas invariants and we perform a non-trivial check of S-duality in topological strings. We further investigate transitions via collapsing D5 del Pezzo surfaces and the occurrence of free Z2 quotients that lead to a new class of heterotic duals.Comment: 117 pages, 1 Postscript figur

Vaccinia Virus Protein C6 Is a Virulence Factor that Binds TBK-1 Adaptor Proteins and Inhibits Activation of IRF3 and IRF7

Recognition of viruses by pattern recognition receptors (PRRs) causes interferon-β (IFN-β) induction, a key event in the anti-viral innate immune response, and also a target of viral immune evasion. Here the vaccinia virus (VACV) protein C6 is identified as an inhibitor of PRR-induced IFN-β expression by a functional screen of select VACV open reading frames expressed individually in mammalian cells. C6 is a member of a family of Bcl-2-like poxvirus proteins, many of which have been shown to inhibit innate immune signalling pathways. PRRs activate both NF-κB and IFN regulatory factors (IRFs) to activate the IFN-β promoter induction. Data presented here show that C6 inhibits IRF3 activation and translocation into the nucleus, but does not inhibit NF-κB activation. C6 inhibits IRF3 and IRF7 activation downstream of the kinases TANK binding kinase 1 (TBK1) and IκB kinase-ε (IKKε), which phosphorylate and activate these IRFs. However, C6 does not inhibit TBK1- and IKKε-independent IRF7 activation or the induction of promoters by constitutively active forms of IRF3 or IRF7, indicating that C6 acts at the level of the TBK1/IKKε complex. Consistent with this notion, C6 immunoprecipitated with the TBK1 complex scaffold proteins TANK, SINTBAD and NAP1. C6 is expressed early during infection and is present in both nucleus and cytoplasm. Mutant viruses in which the C6L gene is deleted, or mutated so that the C6 protein is not expressed, replicated normally in cell culture but were attenuated in two in vivo models of infection compared to wild type and revertant controls. Thus C6 contributes to VACV virulence and might do so via the inhibition of PRR-induced activation of IRF3 and IRF7

Gauged Linear Sigma Models for toroidal orbifold resolutions

Toroidal orbifolds and their resolutions are described within the framework of (2,2) Gauged Linear Sigma Models (GLSMs). Our procedure describes two-tori as hypersurfaces in (weighted) projective spaces. The description is chosen such that the orbifold singularities correspond to the zeros of their homogeneous coordinates. The individual orbifold singularities are resolved using a GLSM guise of non-compact toric resolutions, i.e. replacing discrete orbifold actions by Abelian worldsheet gaugings. Given that we employ the same global coordinates for both the toroidal orbifold and its resolutions, our GLSM formalism confirms the gluing procedure on the level of divisors discussed by Lust et al. Using our global GLSM description we can study the moduli space of such toroidal orbifolds as a whole. In particular, changes in topology can be described as phase transitions of the underlying GLSM. Finally, we argue that certain partially resolvable GLSMs, in which a certain number of fixed points can never be resolved, might be useful for the study of mini-landscape orbifold MSSMs.Comment: 71 pages, 2 figure

Statistical Techniques Complement UML When Developing Domain Models of Complex Dynamical Biosystems

Computational modelling and simulation is increasingly being used to complement traditional wet-lab techniques when investigating the mechanistic behaviours of complex biological systems. In order to ensure computational models are fit for purpose, it is essential that the abstracted view of biology captured in the computational model, is clearly and unambiguously defined within a conceptual model of the biological domain (a domain model), that acts to accurately represent the biological system and to document the functional requirements for the resultant computational model. We present a domain model of the IL-1 stimulated NF-κB signalling pathway, which unambiguously defines the spatial, temporal and stochastic requirements for our future computational model. Through the development of this model, we observe that, in isolation, UML is not sufficient for the purpose of creating a domain model, and that a number of descriptive and multivariate statistical techniques provide complementary perspectives, in particular when modelling the heterogeneity of dynamics at the single-cell level. We believe this approach of using UML to define the structure and interactions within a complex system, along with statistics to define the stochastic and dynamic nature of complex systems, is crucial for ensuring that conceptual models of complex dynamical biosystems, which are developed using UML, are fit for purpose, and unambiguously define the functional requirements for the resultant computational model

Thermonuclear (type-I) X-ray bursts observed by the Rossi X-ray Timing Explorer

We have assembled a sample of 1187 thermonuclear (type-I) X-ray bursts from 48 accreting neutron stars by the Rossi X-ray Timing Explorer, spanning more than ten years. The sample contains examples of two of the three theoretical ignition regimes and likely examples of the third. We present a detailed analysis of the variation of the burst profiles, energetics, recurrence times, presence of photospheric radius expansion, and presence of burst oscillations, as a function of accretion rate. We estimated the distance for 35 sources exhibiting radius-expansion bursts, and found that the peak flux of such bursts varies typically by 13%. We classified sources into two main groups based on the burst properties: both long and short bursts (indicating mixed H/He accretion), and consistently short bursts (primarily He accretion). The decrease in burst rate observed for both groups at >0.06 Mdot_Edd (>~2E37 erg/s) is associated with a transition in the persistent spectral state and (as has been suggested previously) may be related to the increasing role of steady He-burning. We found examples of bursts separated by <30 min, including burst triplets and even quadruplets. We describe the oscillation amplitudes for 13 of the 16 burst oscillation sources, as well as the stages and properties of the bursts in which the oscillations are detected. The burst properties are correlated with the burst oscillation frequency; sources at <400 Hz generally have consistently short bursts, while the more rapidly-spinning systems have both long and short bursts. This correlation suggests either that shear-mediated mixing dominates the burst properties, or that the nature of the mass donor (and hence the evolutionary history) has an influence on the long-term spin evolution.Comment: 70 pages (emulateapj format), 22 figures, 11 tables, accepted by ApJS. The burst sample has been expanded with data made public since the previous submission; the discussion has been revised and substantially expanded following the referee team's report. Data tables will be available online in the usual places or from http://tinyurl.com/5rrg7

Effects of the TLR2 Agonists MALP-2 and Pam3Cys in Isolated Mouse Lungs

Background: Gram-positive and Gram-negative bacteria are main causes of pneumonia or acute lung injury. They are recognized by the innate immune system via toll-like receptor-2 (TLR2) or TLR4, respectively. Among all organs, the lungs have the highest expression of TLR2 receptors, but little is known about the pulmonary consequences of their activation. Here we studied the effects of the TLR2/6 agonist MALP-2, the TLR2/1 agonist Pam 3Cys and the TLR4 agonist lipopolysaccharide (LPS) on pro-inflammatory responses in isolated lungs. Methodology/Principal Findings: Isolated perfused mouse lungs were perfused for 60 min or 180 min with MALP-2 (25 ng/ mL), Pam3Cys (160 ng/mL) or LPS (1 mg/mL). We studied mediator release by enzyme linked immunosorbent assay (ELISA), the activation of mitogen activated protein kinase (MAPK) and AKT/protein kinase B by immunoblotting, and gene induction by quantitative polymerase chain reaction. All agonists activated the MAPK ERK1/2 and p38, but neither JNK or AKT kinase. The TLR ligands upregulated the inflammation related genes Tnf, Il1b, Il6, Il10, Il12, Ifng, Cxcl2 (MIP-2a) and Ptgs2. MALP-2 was more potent than Pam 3Cys in inducing Slpi, Cxcl10 (IP10) and Parg. Remarkable was the strong induction of Tnc by MALP2, which was not seen with Pam 3Cys or LPS. The growth factor related genes Areg and Hbegf were not affected. In addition, all three TLR agonists stimulated the release of IL-6, TNF, CXCL2 and CXCL10 protein from the lungs

Joint analysis of the energy spectrum of ultra-high-energy cosmic rays measured at the Pierre Auger Observatory and the Telescope Array

The measurement of the energy spectrum of ultra-high-energy cosmic rays (UHECRs) is of crucial importance to clarify their origin and acceleration mechanisms. The Pierre Auger Observatory in Argentina and the Telescope Array (TA) in the US have reported their measurements of UHECR energy spectra observed in the southern and northern hemisphere, respectively. The region of the sky accessible to both Observatories ([−15,+24] degrees in declination) can be used to cross-calibrate the two spectra. The Auger-TA energy spectrum working group was organized in 2012 and has been working to understand the uncertainties in energy scale in both experiments, their systematic differences, and differences in the shape of the spectra. In previous works, we reported that there was an overall agreement of the energy spectra measured by the two observatories below 10 EeV while at higher energies, a remaining significant difference was observed in the common declination band. We revisit this issue to understand its origin by examining the systematic uncertainties, statistical effects, and other possibilities. We will also discuss the differences in the spectra in different declination bands and a new feature in the spectrum recently reported by the Auger Collaboration

UHECR arrival directions in the latest data from the original Auger and TA surface detectors and nearby galaxies

The distribution of ultra-high-energy cosmic-ray arrival directions appears to be nearly isotropic except for a dipole moment of order $6 \times (E/10~\mathrm{EeV})$ per cent. Nonetheless, at the highest energies, as the number of possible candidate sources within the propagation horizon and the magnetic deflections both shrink, smaller-scale anisotropies might be expected to emerge. On the other hand, the flux suppression reduces the statistics available for searching for such anisotropies. In this work, we consider two different lists of candidate sources: a sample of nearby starburst galaxies and the 2MRS catalog tracing stellar mass within 250 Mpc. We combine surface-detector data collected at the Pierre Auger Observatory until 2020 and the Telescope Array until 2019, and use them to test models in which UHECRs comprise an isotropic background and a foreground originating from the candidate sources and randomly deflected by magnetic fields. The free parameters of these models are the energy threshold, the signal fraction, and the search angular scale. We find a correlation between the arrival directions of $11.8\%_{-3.1\%}^{+5.0\%}$ of cosmic rays detected with $E \ge 38~\mathrm{EeV}$ by Auger or with $E \gtrsim 49~\mathrm{EeV}$ by TA and the position of nearby starburst galaxies on a ${15.5^\circ}_{-3.2^\circ}^{+5.3^\circ}$ angular scale, with a 4.2σ post-trial significance, as well as a weaker correlation with the overall galaxy distribution