Ageing and the immune system: focus on macrophages

A fully functioning immune system is essential in order to maintain good health. However, the immune system deteriorates with advancing age, and this contributes to increased susceptibility to infection, autoimmunity, and cancer in the older population. Progress has been made in identifying age-related defects in the adaptive immune system. In contrast, relatively little research has been carried out on the impact of ageing on the innate immune response. This area requires further research as the innate immune system plays a crucial role in protection against infection and represents a first line of defence. Macrophages are central effector cells of the innate immune system and have many diverse functions. As a result, age-related impairments in macrophage function are likely to have important consequences for the health of the older population. It has been reported that ageing in macrophages impacts on many processes including toll-like receptor signalling, polarisation, phagocytosis, and wound repair. A detailed understanding of the impact of ageing on macrophages is required in order to develop therapeutics that will boost immune responses in the older population.

VLT DETECTION OF A RED SUPERGIANT PROGENITOR OF THE TYPE II-P SUPERNOVA 2008bk

We report the identification of a source coincident with the position of the nearby Type II-P supernova (SN) 2008bk in high-quality optical and near-infrared preexplosion images from the ESO Very Large Telescope (VLT). The SN position in the optical and near-infrared preexplosion images is identified to within about +/- 70 and +/- 40 mas, respectively, using postexplosion-band images obtained with the NAOS CONICA adaptive optics system K-s on the VLT. The preexplosion source detected in four different bands is precisely coincident with SN 2008bk and is consistent with being dominated by a single point source. We determine the nature of the point source using the STARS stellar evolutionary models and find that its colors and luminosity are consistent with the source being a red supergiant progenitor of SN 2008bk with an initial mass of 8.5 +/- 1.0 M-circle dot.

Expression of toll-like receptors by human muscle cells in vitro and in vivo:TLR3 is highly expressed in inflammatory and HIV myopathies, mediates IL-8 release and up-regulation of NKG2D-ligands

The particular microenvironment of the skeletal muscle can be the site of complex immune reactions. Toll-like receptors (TLRs) mediate inflammatory stimuli from pathogens and endogenous danger signals and link the innate and adaptive immune system. We investigated innate immune responses in human muscle. Analyzing TLR1-9 mRNA in cultured myoblasts and rhabdomyosarcoma cells, we found constitutive expression of TLR3. The TLR3 ligand Poly (I:C), a synthetic analog of dsRNA, and IFN-gamma increased TLR3 levels. TLR3 was mainly localized intracellularly and regulated at the protein level. Poly (I:C) challenge 1) activated nuclear factor-kappaB (NF-kappaB), 2) increased IL-8 release, and 3) up-regulated NKG2D ligands and NK-cell-mediated lysis of muscle cells. We examined muscle biopsy specimens of 6 HIV patients with inclusion body myositis/polymyositis (IBM/PM), 7 cases of sporadic IBM and 9 nonmyopathic controls for TLR3 expression. TLR3 mRNA levels were elevated in biopsy specimens from patients with IBM and HIV-myopathies. Muscle fibers in inflammatory myopathies expressed TLR3 in close proximity of infiltrating mononuclear cells. Taken together, our study suggests an important role of TLR3 in the immunobiology of muscle, and has substantial implications for the understanding of the pathogenesis of inflammatory myopathies or therapeutic interventions like vaccinations or gene transfer.

A Syntactic Approach to Revising Epistemic States with Uncertain Inputs

Revising its beliefs when receiving new information is an important ability of any intelligent system. However, in realistic settings the new input is not always certain. A compelling way of dealing with uncertain input in an agent-based setting is to treat it as unreliable input, which may strengthen or weaken the beliefs of the agent. Recent work focused on the postulates associated with this form of belief change and on finding semantical operators that satisfy these postulates. In this paper we propose a new syntactic approach for this form of belief change and show that it agrees with the semantical definition. This makes it feasible to develop complex agent systems capable of efficiently dealing with unreliable input in a semantically meaningful way. Additionally, we show that imposing restrictions on the input and the beliefs that are entailed allows us to devise a tractable approach suitable for resource-bounded agents or agents where reactiveness is of paramount importance.

Molecular and physiological roles of Pellino E3 ubiquitin ligases in immunity

The sensing of foreign agents by the innate and adaptive immune system triggers complex signal transduction cascades that culminate in expression of gene patterns that facilitate host protection from the invading agent. Post-translational modification of intracellular signaling proteins in these pathways is a key regulatory mechanism with ubiquitination being one of the important processes that controls levels and activities of signaling molecules. E3 ubiquitin ligases are the determining enzymes in dictating the ubiquitination status of individual proteins. Among these hundred E3 ubiquitin ligases are a family of Pellino proteins that are emerging to be important players in immunity and beyond. Herein, we review the roles of the Pellino E3 ubiquitin ligases in innate and adaptive immunity. We discuss their early discovery and characterization and how this has been aided by the highly conserved nature of innate immune signaling across evolution. We describe the molecular roles of Pellino proteins in immune signaling with particular emphasis on their involvement in pathogen recognition receptor (PRR) signaling. The growing appreciation of the importance of Pellino proteins in a wide range of immune-mediated diseases are also evaluated.

Towards an intelligent score following system: Handling of mistakes and jumps encountered during piano practicing

Score following has been an important area of research in AI and music since the mid 80's. Various systems were developed, but they were predominantly for providing automated accompaniment to live concert performances, dealing mostly with issues relating to pitch detection and identification of embellished melodies. They have a big potential in the area of education where student performers benefit in practice situations. Current accompaniment systems are not designed to deal with errors that may occur during practising. In this paper we present a system developed to provide accompaniment for students practising at home. First a survey of score following will be given. Then the capabilities of the system will be explained, and the results from the first experiments of the monophonic score following system will be presented.

Moving window kernel PCA for adaptive monitoring of nonlinear processes

This paper discusses the monitoring of complex nonlinear and time-varying processes. Kernel principal component analysis (KPCA) has gained significant attention as a monitoring tool for nonlinear systems in recent years but relies on a fixed model that cannot be employed for time-varying systems. The contribution of this article is the development of a numerically efficient and memory saving moving window KPCA (MWKPCA) monitoring approach. The proposed technique incorporates an up- and downdating procedure to adapt (i) the data mean and covariance matrix in the feature space and (ii) approximates the eigenvalues and eigenvectors of the Gram matrix. The article shows that the proposed MWKPCA algorithm has a computation complexity of O(N2), whilst batch techniques, e.g. the Lanczos method, are of O(N3). Including the adaptation of the number of retained components and an l-step ahead application of the MWKPCA monitoring model, the paper finally demonstrates the utility of the proposed technique using a simulated nonlinear time-varying system and recorded data from an industrial distillation column.