On the Cognition of States of Affairs

The theory of speech acts put forward by Adolf Reinach in his "The A Priori Foundations of the Civil Law" of 1913 rests on a systematic account of the ontological structures associated with various different sorts of language use. One of the most original features of Reinach's account lies in hIs demonstration of how the ontological structure of, say, an action of promising or of commanding, may be modified in different ways, yielding different sorts of non-standard instances of the corresponding speech act varieties. The present paper is an attempt to apply this idea of standard and modified instances of ontological structures to the realm of judgement and cognition, and thereby to develop a Reinachian theory of how intentionality is mediated through language in acts of thinking and speaking

Charged Dilatonic AdS Black Branes in Arbitrary Dimensions

We study electromagnetically charged dilatonic black brane solutions in arbitrary dimensions with flat transverse spaces, that are asymptotically AdS. This class of solutions includes spacetimes which possess a bulk region where the metric is approximately invariant under Lifshitz scalings. Given fixed asymptotic boundary conditions, we analyze how the behavior of the bulk up to the horizon varies with the charges and derive the extremality conditions for these spacetimes.Comment: References update

Holography for Einstein-Maxwell-dilaton theories from generalized dimensional reduction

We show that a class of Einstein-Maxwell-Dilaton (EMD) theories are related to higher dimensional AdS-Maxwell gravity via a dimensional reduction over compact Einstein spaces combined with continuation in the dimension of the compact space to non-integral values (`generalized dimensional reduction'). This relates (fairly complicated) black hole solutions of EMD theories to simple black hole/brane solutions of AdS-Maxwell gravity and explains their properties. The generalized dimensional reduction is used to infer the holographic dictionary and the hydrodynamic behavior for this class of theories from those of AdS. As a specific example, we analyze the case of a black brane carrying a wave whose universal sector is described by gravity coupled to a Maxwell field and two neutral scalars. At thermal equilibrium and finite chemical potential the two operators dual to the bulk scalar fields acquire expectation values characterizing the breaking of conformal and generalized conformal invariance. We compute holographically the first order transport coefficients (conductivity, shear and bulk viscosity) for this system.Comment: v2, Important additions: (1) discussion of the entropy current, (2) postulated zeta/eta bound is generically violated. Some comments and references added, typos corrected. 50 page

Adaptive and Innate Immune Responses in Autism: Rationale for Therapeutic Use of Intravenous Immunoglobulin

Autism is a complex polygenic neurodevelopmental disorder characterized by deficits in communication and social interactions as well as specific stereotypical behaviors. Both genetic and environmental factors appear to contribute to the pathogenesis of autism. Accumulating data including changes in immune responses, linkage to major histocompatibility complex antigens, and the presence of autoantibodies to neural tissues/antigens suggest that the immune system plays an important role in its pathogenesis. In this brief review, we discuss the data regarding changes in both innate and adaptive immunity in autism and the evidence in favor of the role of the immune system, especially of maternal autoantibodies in the pathogenesis of a subset of patients with autism. The rationale for possible therapeutic use of intravenous immunoglobulin is also discussed

The Pioneer Anomaly

Radio-metric Doppler tracking data received from the Pioneer 10 and 11 spacecraft from heliocentric distances of 20-70 AU has consistently indicated the presence of a small, anomalous, blue-shifted frequency drift uniformly changing with a rate of ~6 x 10^{-9} Hz/s. Ultimately, the drift was interpreted as a constant sunward deceleration of each particular spacecraft at the level of a_P = (8.74 +/- 1.33) x 10^{-10} m/s^2. This apparent violation of the Newton's gravitational inverse-square law has become known as the Pioneer anomaly; the nature of this anomaly remains unexplained. In this review, we summarize the current knowledge of the physical properties of the anomaly and the conditions that led to its detection and characterization. We review various mechanisms proposed to explain the anomaly and discuss the current state of efforts to determine its nature. A comprehensive new investigation of the anomalous behavior of the two Pioneers has begun recently. The new efforts rely on the much-extended set of radio-metric Doppler data for both spacecraft in conjunction with the newly available complete record of their telemetry files and a large archive of original project documentation. As the new study is yet to report its findings, this review provides the necessary background for the new results to appear in the near future. In particular, we provide a significant amount of information on the design, operations and behavior of the two Pioneers during their entire missions, including descriptions of various data formats and techniques used for their navigation and radio-science data analysis. As most of this information was recovered relatively recently, it was not used in the previous studies of the Pioneer anomaly, but it is critical for the new investigation.Comment: 165 pages, 40 figures, 16 tables; accepted for publication in Living Reviews in Relativit

The Evolution of Compact Binary Star Systems

We review the formation and evolution of compact binary stars consisting of white dwarfs (WDs), neutron stars (NSs), and black holes (BHs). Binary NSs and BHs are thought to be the primary astrophysical sources of gravitational waves (GWs) within the frequency band of ground-based detectors, while compact binaries of WDs are important sources of GWs at lower frequencies to be covered by space interferometers (LISA). Major uncertainties in the current understanding of properties of NSs and BHs most relevant to the GW studies are discussed, including the treatment of the natal kicks which compact stellar remnants acquire during the core collapse of massive stars and the common envelope phase of binary evolution. We discuss the coalescence rates of binary NSs and BHs and prospects for their detections, the formation and evolution of binary WDs and their observational manifestations. Special attention is given to AM CVn-stars -- compact binaries in which the Roche lobe is filled by another WD or a low-mass partially degenerate helium-star, as these stars are thought to be the best LISA verification binary GW sources.Comment: 105 pages, 18 figure

Neutrophil elastase reduces secretion of secretory leukoproteinase inhibitor (SLPI) by lung epithelial cells: role of charge of the proteinase-inhibitor complex

<p>Abstract</p> <p>Background</p> <p>Secretory leukoproteinase inhibitor (SLPI) is an important inhibitor of neutrophil elastase (NE), a proteinase implicated in the pathogenesis of lung diseases such as COPD. SLPI also has antimicrobial and anti-inflammatory properties, but the concentration of SLPI in lung secretions in COPD varies inversely with infection and the concentration of NE. A fall in SLPI concentration is also seen in culture supernatants of respiratory cells exposed to NE, for unknown reasons. We investigated the hypothesis that SLPI complexed with NE associates with cell membranes <it>in vitro</it>.</p> <p>Methods</p> <p>Respiratory epithelial cells were cultured in the presence of SLPI, varying doses of proteinases over time, and in different experimental conditions. The likely predicted charge of the complex between SLPI and proteinases was assessed by theoretical molecular modelling.</p> <p>Results</p> <p>We observed a rapid, linear decrease in SLPI concentration in culture supernatants with increasing concentration of NE and cathepsin G, but not with other serine proteinases. The effect of NE was inhibited fully by a synthetic NE inhibitor only when added at the same time as NE. Direct contact between NE and SLPI was required for a fall in SLPI concentration. Passive binding to cell culture plate materials was able to remove a substantial amount of SLPI both with and without NE. Theoretical molecular modelling of the structure of SLPI in complex with various proteinases showed a greater positive charge for the complex with NE and cathepsin G than for other proteinases, such as trypsin and mast cell tryptase, that also bind SLPI but without reducing its concentration.</p> <p>Conclusion</p> <p>These data suggest that NE-mediated decrease in SLPI is a passive, charge-dependent phenomenon <it>in vitro</it>, which may correlate with changes observed <it>in vivo</it>.</p

The unfolded protein response and its relevance to connective tissue diseases

The unfolded protein response (UPR) has evolved to counter the stresses that occur in the endoplasmic reticulum (ER) as a result of misfolded proteins. This sophisticated quality control system attempts to restore homeostasis through the action of a number of different pathways that are coordinated in the first instance by the ER stress-senor proteins IRE1, ATF6 and PERK. However, prolonged ER-stress-related UPR can have detrimental effects on cell function and, in the longer term, may induce apoptosis. Connective tissue cells such as fibroblasts, osteoblasts and chondrocytes synthesise and secrete large quantities of proteins and mutations in many of these gene products give rise to heritable disorders of connective tissues. Until recently, these mutant gene products were thought to exert their effect through the assembly of a defective extracellular matrix that ultimately disrupted tissue structure and function. However, it is now becoming clear that ER stress and UPR, because of the expression of a mutant gene product, is not only a feature of, but may be a key mediator in the initiation and progression of a whole range of different connective tissue diseases. This review focuses on ER stress and the UPR that characterises an increasing number of connective tissue diseases and highlights novel therapeutic opportunities that may arise

On shape dependence of holographic entanglement entropy in AdS4/CFT3

We study the finite term of the holographic entanglement entropy of finite domains with smooth shapes and for four dimensional gravitational backgrounds. Analytic expressions depending on the unit vectors normal to the minimal area surface are obtained for both stationary and time dependent spacetimes. The special cases of AdS4, asymptotically AdS4 black holes, domain wall geometries and Vaidya-AdS backgrounds have been analysed explicitly. When the bulk spacetime is AdS4, the finite term is the Willmore energy of the minimal area surface viewed as a submanifold of the three dimensional flat Euclidean space. For the static spacetimes, some numerical checks involving spatial regions delimited by ellipses and non convex domains have been performed. In the case of AdS4, the infinite wedge has been also considered, recovering the known analytic formula for the coefficient of the logarithmic divergence

Liverpool telescope 2: a new robotic facility for rapid transient follow-up

The Liverpool Telescope is one of the world's premier facilities for time domain astronomy. The time domain landscape is set to radically change in the coming decade, with surveys such as LSST providing huge numbers of transient detections on a nightly basis; transient detections across the electromagnetic spectrum from other facilities such as SVOM, SKA and CTA; and the era of `multi-messenger astronomy', wherein events are detected via non-electromagnetic means, such as gravitational wave emission. We describe here our plans for Liverpool Telescope 2: a new robotic telescope designed to capitalise on this new era of time domain astronomy. LT2 will be a 4-metre class facility co-located with the LT at the Observatorio del Roque de Los Muchachos on the Canary island of La Palma. The telescope will be designed for extremely rapid response: the aim is that the telescope will take data within 30 seconds of the receipt of a trigger from another facility. The motivation for this is twofold: firstly it will make it a world-leading facility for the study of fast fading transients and explosive phenomena discovered at early times. Secondly, it will enable large-scale programmes of low-to-intermediate resolution spectral classification of transients to be performed with great efficiency. In the target-rich environment of the LSST era, minimising acquisition overheads will be key to maximising the science gains from any follow-up programme. The telescope will have a diverse instrument suite which is simultaneously mounted for automatic changes, but it is envisaged that the primary instrument will be an intermediate resolution, optical/infrared spectrograph for scientific exploitation of transients discovered with the next generation of synoptic survey facilities. In this paper we outline the core science drivers for the telescope, and the requirements for the optical and mechanical design