Neutrinos and Gamma Rays from Galaxy Clusters

The next generation of neutrino and gamma-ray detectors should provide new insights into the creation and propagation of high-energy protons within galaxy clusters, probing both the particle physics of cosmic rays interacting with the background medium and the mechanisms for high-energy particle production within the cluster. In this paper we examine the possible detection of gamma-rays (via the GLAST satellite) and neutrinos (via the ICECUBE and Auger experiments) from the Coma cluster of galaxies, as well as for the gamma-ray bright clusters Abell 85, 1758, and 1914. These three were selected from their possible association with unidentified EGRET sources, so it is not yet entirely certain that their gamma-rays are indeed produced diffusively within the intracluster medium, as opposed to AGNs. It is not obvious why these inconspicuous Abell-clusters should be the first to be seen in gamma-rays, but a possible reason is that all of them show direct evidence of recent or ongoing mergers. Their identification with the EGRET gamma-ray sources is also supported by the close correlation between their radio and (purported) gamma-ray fluxes. Under favorable conditions (including a proton spectral index of 2.5 in the case of Abell 85, and sim 2.3 for Coma, and Abell 1758 and 1914), we expect ICECUBE to make as many as 0.3 neutrino detections per year from the Coma cluster of galaxies, and as many as a few per year from the Abell clusters 85, 1758, and 1914. Also, Auger may detect as many as 2 events per decade at ~ EeV energies from these gamma-ray bright clusters.Comment: Accepted for publication in Ap

The inhibitory receptor LILRB4 (ILT3) modulates antigen presenting cell phenotype and, along with LILRB2 (ILT4), is upregulated in response to Salmonella infection.

BACKGROUND: Leukocyte Ig-like receptors (LILR) are a family of innate immune receptors with immunomodulatory functions. High-level expression of the receptors LILRB2 (ILT4) and LILRB4 (ILT3) is a feature of tolerogenic antigen presenting cells and has been observed in cancer and transplant situations. There are relatively few studies regarding these receptors in the context of infection and it is not yet clear how LILRB4 exerts its inhibitory effects. RESULTS: We studied the effects of LILRB4 ligation on antigen presenting cell phenotype, and the expression of LILRB2 and LILRB4 on Salmonella-infected antigen presenting cells. Ligation of LILRB4 throughout in vitro culture of dendritic cells led to an upregulation of the co-stimulatory protein CD86. Alterations in the production of IL-8 and IL-10 by LILRB4-ligated macrophages were also observed. Infection with Salmonella typhimurium or TLR stimulation with Salmonella components led to an upregulation of LILRB2 and LILRB4. CONCLUSION: Our results indicate that the inhibitory effects of LILRB4 do not result from a failure to upregulate co-stimulatory proteins. In addition to the high level expression that can render antigen presenting cells tolerogenic, there may be a role for lower level expression and activity of LILRB2 and LILRB4 in response to TLR signalling during an immune response to bacterial infection.RIGHTS : This article is licensed under the BioMed Central licence at http://www.biomedcentral.com/about/license which is similar to the 'Creative Commons Attribution Licence'. In brief you may : copy, distribute, and display the work; make derivative works; or make commercial use of the work - under the following conditions: the original author must be given credit; for any reuse or distribution, it must be made clear to others what the license terms of this work are

Impaired natural killer cell phenotype and function in idiopathic and heritable pulmonary arterial hypertension

BACKGROUND: Beyond their role as innate immune effectors, natural killer (NK) cells are emerging as important regulators of angiogenesis and vascular remodeling. Pulmonary arterial hypertension (PAH) is characterized by severe pulmonary vascular remodeling and has long been associated with immune dysfunction. Despite this association, a role for NK cells in disease pathology has not yet been described. METHODS AND RESULTS: Analysis of whole blood lymphocytes and isolated NK cells from PAH patients revealed an expansion of the functionally defective CD56(-)/CD16(+) NK subset that was not observed in patients with chronic thromboembolic pulmonary hypertension. NK cells from PAH patients also displayed decreased levels of the activating receptor NKp46 and the killer immunoglobulin-like receptors 2DL1/S1 and 3DL1, reduced secretion of the cytokine macrophage inflammatory protein-1β, and a significant impairment in cytolytic function associated with decreased killer immunoglobulin-like receptor 3DL1 expression. Genotyping patients (n=222) and controls (n=191) for killer immunoglobulin-like receptor gene polymorphisms did not explain these observations. Rather, we show that NK cells from PAH patients exhibit increased responsiveness to transforming growth factor-β, which specifically downregulates disease-associated killer immunoglobulin-like receptors. NK cell number and cytotoxicity were similarly decreased in the monocrotaline rat and chronic hypoxia mouse models of PAH, accompanied by reduced production of interferon-γ in NK cells from hypoxic mice. NK cells from PAH patients also produced elevated quantities of matrix metalloproteinase 9, consistent with a capacity to influence vascular remodeling. CONCLUSIONS: Our work is the first to identify an impairment of NK cells in PAH and suggests a novel and substantive role for innate immunity in the pathobiology of this disease

Maximally-localized generalized Wannier functions for composite energy bands

We discuss a method for determining the optimally-localized set of generalized Wannier functions associated with a set of Bloch bands in a crystalline solid. By ``generalized Wannier functions'' we mean a set of localized orthonormal orbitals spanning the same space as the specified set of Bloch bands. Although we minimize a functional that represents the total spread sum_n [ _n - _n^2 ] of the Wannier functions in real space, our method proceeds directly from the Bloch functions as represented on a mesh of k-points, and carries out the minimization in a space of unitary matrices U_mn^k describing the rotation among the Bloch bands at each k-point. The method is thus suitable for use in connection with conventional electronic-structure codes. The procedure also returns the total electric polarization as well as the location of each Wannier center. Sample results for Si, GaAs, molecular C2H4, and LiCl will be presented.Comment: 22 pages, two-column style with 4 postscript figures embedded. Uses REVTEX and epsf macros. Also available at http://www.physics.rutgers.edu/~dhv/preprints/index.html#nm_wan

Influence of long-range correlated surface and near the surface disorder on the process of adsorption of long-flexible polymer chains

The influence of long-range correlated surface and decaying near surface disorder with quenched defects is studied. We consider a correlation function for the defects of the form $\frac{e^{-z/\xi}}{r^{a}}$, where $a<d-1$ and $z$ being the coordinate in the direction perpendicular to the surface and $r$ denotes the distance parallel to the surface. We investigate the process of adsorption of long-flexible polymer chains with excluded volume interactions on a "marginal" and attractive wall in the framework of renormalization group field theoretical approach up to first order of perturbation theory in a double ($\epsilon$,$\delta$)- expansion ($\epsilon=4-d$, $\delta=3-a$) for the semi-infinite $|\phi|^4$ $O(m,n)$ model with the above mentioned type of surface and near the surface disorder in the limit $m,n\to 0$. In particular we study two limiting cases. First, we investigate the scenario where the chain's extension it much larger then $\xi$. Second, we consider the case where the chain's extension is of the order of $\xi$. For both cases we obtained series for bulk and the whole set of surface critical exponents, characterizing the process of adsorption of long-flexible polymer chains at the surface. The polymer linear dimensions parallel and perpendicular to the surface and the corresponding partition functions as well as the behavior of monomer density profiles and the fraction of adsorbed monomers at the surface and in the volume are studied.Comment: 31 pages, 5 figures, 2 table

Comparative study of density functional theories of the exchange-correlation hole and energy in silicon

We present a detailed study of the exchange-correlation hole and exchange-correlation energy per particle in the Si crystal as calculated by the Variational Monte Carlo method and predicted by various density functional models. Nonlocal density averaging methods prove to be successful in correcting severe errors in the local density approximation (LDA) at low densities where the density changes dramatically over the correlation length of the LDA hole, but fail to provide systematic improvements at higher densities where the effects of density inhomogeneity are more subtle. Exchange and correlation considered separately show a sensitivity to the nonlocal semiconductor crystal environment, particularly within the Si bond, which is not predicted by the nonlocal approaches based on density averaging. The exchange hole is well described by a bonding orbital picture, while the correlation hole has a significant component due to the polarization of the nearby bonds, which partially screens out the anisotropy in the exchange hole.Comment: 16 pages, 5 figures, RevTeX, added conten

Spatial distribution of far-infrared rotationally excited CH⁺ and OH emission lines in the Orion Bar photodissociation region

Context. The methylidyne cation (CH+) and hydroxyl (OH) are key molecules in the warm interstellar chemistry, but their formation and excitation mechanisms are not well understood. Their abundance and excitation are predicted to be enhanced by the presence of vibrationally excited H2 or hot gas (~500−1000 K) in photodissociation regions (PDRs) with high incident far-ultraviolet (FUV) radiation field. The excitation may also originate in dense gas (>105 cm-3) followed by nonreactive collisions with H2, H, and electrons. Previous observations of the Orion Bar suggest that the rotationally excited CH+ and OH correlate with the excited CO, which is a tracer of dense and warm gas, and that formation pumping contributes to CH+ excitation.Aims. Our goal is to examine the spatial distribution of the rotationally excited CH+ and OH emission lines in the Orion Bar to establish their physical origin and main formation and excitation mechanisms.Methods. We present spatially sampled maps of the CH+ J = 3–2 transition at 119.8 μm and the OH Λ doublet at 84 μm in the Orion Bar over an area of 110″× 110″ with Herschel/PACS. We compare the spatial distribution of these molecules with those of their chemical precursors, C+ , O and H2, and tracers of warm and dense gas (high- J CO). We assess the spatial variation of the CH+ J = 2–1 velocity-resolved line profile at 1669 GHz with Herschel/HIFI spectrometer observations.Results. The OH and especially CH+ lines correlate well with the high-J CO emission and delineate the warm and dense molecular region at the edge of the Bar. While notably similar, the differences in the CH+ and OH morphologies indicate that CH+ formation and excitation are strongly related to the observed vibrationally excited H2. This, together with the observed broad CH+ line widths, indicates that formation pumping contributes to the excitation of this reactive molecular ion. Interestingly, the peak of the rotationally excited OH 84 μm emission coincides with a bright young object, proplyd 244–440, which shows that OH can be an excellent tracer of UV-irradiated dense gas.Conclusions. The spatial distribution of CH+ and OH revealed in our maps is consistent with previous modeling studies. Both formation pumping and nonreactive collisions in a UV-irradiated dense gas are important CH+ J = 3–2 excitation processes. The excitation of the OH Λ doublet at 84 μm is mainly sensitive to the temperature and density

Astrobiological Complexity with Probabilistic Cellular Automata

Search for extraterrestrial life and intelligence constitutes one of the major endeavors in science, but has yet been quantitatively modeled only rarely and in a cursory and superficial fashion. We argue that probabilistic cellular automata (PCA) represent the best quantitative framework for modeling astrobiological history of the Milky Way and its Galactic Habitable Zone. The relevant astrobiological parameters are to be modeled as the elements of the input probability matrix for the PCA kernel. With the underlying simplicity of the cellular automata constructs, this approach enables a quick analysis of large and ambiguous input parameters' space. We perform a simple clustering analysis of typical astrobiological histories and discuss the relevant boundary conditions of practical importance for planning and guiding actual empirical astrobiological and SETI projects. In addition to showing how the present framework is adaptable to more complex situations and updated observational databases from current and near-future space missions, we demonstrate how numerical results could offer a cautious rationale for continuation of practical SETI searches.Comment: 37 pages, 11 figures, 2 tables; added journal reference belo

LILRB3 (ILT5) is a myeloid cell checkpoint that elicits profound immunomodulation.

Despite advances in identifying the key immunoregulatory roles of many of the human leukocyte immunoglobulin-like receptor (LILR) family members, the function of the inhibitory molecule LILRB3 (ILT5, CD85a, LIR3) remains unclear. Studies indicate a predominant myeloid expression; however, high homology within the LILR family and a relative paucity of reagents have hindered progress toward identifying the function of this receptor. To investigate its function and potential immunomodulatory capacity, a panel of LILRB3-specific monoclonal antibodies (mAbs) was generated. LILRB3-specific mAbs bound to discrete epitopes in Ig-like domain 2 or 4. LILRB3 ligation on primary human monocytes by an agonistic mAb resulted in phenotypic and functional changes, leading to potent inhibition of immune responses in vitro, including significant reduction in T cell proliferation. Importantly, agonizing LILRB3 in humanized mice induced tolerance and permitted efficient engraftment of allogeneic cells. Our findings reveal powerful immunosuppressive functions of LILRB3 and identify it as an important myeloid checkpoint receptor

Allele-specific recognition by LILRB3 and LILRA6 of a cytokeratin 8-associated ligand on necrotic glandular epithelial cells.

The LILRs are a family of receptors that regulate the activities of myelomonocytic cells. We found that specific allelic variants of two related members of the LILR family, LILRB3 and LILRA6, interact with a ligand exposed on necrotic glandular epithelial cells. The extracellular domains of LILRB3 and LILRA6 are very similar and their genes are highly polymorphic. A commonly occurring allele, LILRB3*12, displayed particularly strong binding of these necrotic cells and further screening of the products of LILRB3 alleles identified motifs that correlated with binding. Immunoprecipitation of the ligand from epithelial cell lysates using recombinant LILRB3*12, identified cytokeratins 8, 18 and 19. Purified proteins obtained from epithelial cell lysates, using anti-cytokeratin 8 antibodies, were able to activate LILRB3*12 reporter cells. Knock-down of cytokeratin 8 in epithelial cells abrogated expression of the LILRB3 ligand, while staining with recombinant LILRB3*12 showed co-localisation with cytokeratin 8 and 18 in permeabilised breast cancer cells. Necrosis is a common feature of tumours. The finding of a necrosis-associated ligand for these two receptors raises the possibility of a novel interaction that alters immune responses within the tumour microenvironment. Since LILRB3 and LILRA6 genes are highly polymorphic the interaction may influence an individual's immune response to tumours.DCJ and JT are funded by Worldwide Cancer Research (formerly the AICR), project grant number 13-0074. Additional funding was provided by grants from the MRC (G0901682) and Wellcome Trust (094207 and 089821). MRL-A was funded by Ministerio de Educación of Spain, under the program “Programa Nacional de Movilidad de Recursos Humanos del Plan Nacional de I-D+i 2008-2011” and Fundación Séneca 04087/GERM/06 Project