Large-scale study of the NGC 1399 globular cluster system in Fornax

We present a Washington C and Kron-Cousins R photometric study of the globular cluster system of NGC 1399, the central galaxy of the Fornax cluster. A large areal coverage of 1 square degree around NGC 1399 is achieved with three adjoining fields of the MOSAIC II Imager at the CTIO 4-m telescope. Working on such a large field, we can perform the first indicative determination of the total size of the NGC 1399 globular cluster system. The estimated angular extent, measured from the NGC 1399 centre and up to a limiting radius where the areal density of blue globular clusters falls to 30 per cent of the background level, is 45 +/- 5 arcmin, which corresponds to 220 - 275 kpc at the Fornax distance. The bimodal colour distribution of this globular cluster system, as well as the different radial distribution of blue and red clusters, up to these large distances from the parent galaxy, are confirmed. The azimuthal globular cluster distribution exhibits asymmetries that might be understood in terms of tidal stripping of globulars from NGC 1387, a nearby galaxy. The good agreement between the areal density profile of blue clusters and a projected dark-matter NFW density profile is emphasized.Comment: 9 pages, 9 figures. Accepted for publication in A&

Drug hypersensitivity caused by alteration of the MHC-presented self-peptide repertoire

Idiosyncratic adverse drug reactions are unpredictable, dose independent and potentially life threatening; this makes them a major factor contributing to the cost and uncertainty of drug development. Clinical data suggest that many such reactions involve immune mechanisms, and genetic association studies have identified strong linkage between drug hypersensitivity reactions to several drugs and specific HLA alleles. One of the strongest such genetic associations found has been for the antiviral drug abacavir, which causes severe adverse reactions exclusively in patients expressing the HLA molecular variant B*57:01. Abacavir adverse reactions were recently shown to be driven by drug-specific activation of cytokine-producing, cytotoxic CD8+ T cells that required HLA-B*57:01 molecules for their function. However, the mechanism by which abacavir induces this pathologic T cell response remains unclear. Here we show that abacavir can bind within the F-pocket of the peptide-binding groove of HLA-B*57:01 thereby altering its specificity. This supports a novel explanation for HLA-linked idiosyncratic adverse drug reactions; namely that drugs can alter the repertoire of self-peptides presented to T cells thus causing the equivalent of an alloreactive T cell response. Indeed, we identified specific self-peptides that are presented only in the presence of abacavir, and that were recognized by T cells of hypersensitive patients. The assays we have established can be applied to test additional compounds with suspected HLA linked hypersensitivities in vitro. Where successful, these assays could speed up the discovery and mechanistic understanding of HLA linked hypersensitivities as well as guide the development of safer drugs

Variability of Luminous Stars in the Large Magellanic Cloud Using 10 Years of ASAS Data

Motivated by the detection of a recent outburst of the massive luminous blue variable LMC-R71, which reached an absolute magnitude M_V = -9.3 mag, we undertook a systematic study of the optical variability of 1268 massive stars in the Large Magellanic Cloud, using a recent catalog by Bonanos et al. (2009) as the input. The ASAS All Star Catalog (Pojmanski 2002) provided well-sampled light curves of these bright stars spanning 10 years. Combining the two catalogs resulted in 599 matches, on which we performed a variability search. We identified 117 variable stars, 38 of which were not known before, despite their brightness and large amplitude of variation. We found 13 periodic stars that we classify as eclipsing binary (EB) stars, eight of which are newly discovered bright, massive eclipsing binaries composed of OB type stars. The remaining 104 variables are either semi- or non-periodic, the majority (85) being red supergiants. Most (26) of the newly discovered variables in this category are also red supergiants with only three B and four O stars.Comment: 23 pages, 10 figures and 3 tables; published in A

Globular cluster candidates within the Fornax Cluster: intracluster globulars?

We present the results of a search for globular clusters in the surroundings of 15 low surface brightness dwarf galaxies belonging to the Fornax Cluster, which was carried out on CCD images obtained with the C and T1 filters of the Washington photometric system. The globular cluster candidates show an extended and probably bimodal (C-T1) color distribution, which is inconsistent with the presence of a single population of metal-poor clusters detected in several dwarf galaxies. The surface number density of these candidates shows no concentration towards the respective dwarf galaxies, in whose outskirts they have been identified. On the contrary, if we split the candidates in two groups according to their projected distances to the center of the Fornax Cluster, those located closer to the center show a higher projected density than those located farther from it. These results suggest that the potential globular clusters might not be bound to the dwarf galaxies. Alternatively, these globulars could form part of the very peripheral regions of NGC 1399 (the central galaxy of the Fornax Cluster) or even belong to the intracluster medium.Comment: 8 pages, 6 figures. Accepted for publication in "Astronomy & Astrophysics

A theory of L1L^1-dissipative solvers for scalar conservation laws with discontinuous flux

We propose a general framework for the study of $L^1$ contractive semigroups of solutions to conservation laws with discontinuous flux. Developing the ideas of a number of preceding works we claim that the whole admissibility issue is reduced to the selection of a family of "elementary solutions", which are certain piecewise constant stationary weak solutions. We refer to such a family as a "germ". It is well known that (CL) admits many different $L^1$ contractive semigroups, some of which reflects different physical applications. We revisit a number of the existing admissibility (or entropy) conditions and identify the germs that underly these conditions. We devote specific attention to the anishing viscosity" germ, which is a way to express the "$\Gamma$-condition" of Diehl. For any given germ, we formulate "germ-based" admissibility conditions in the form of a trace condition on the flux discontinuity line $x=0$ (in the spirit of Vol'pert) and in the form of a family of global entropy inequalities (following Kruzhkov and Carrillo). We characterize those germs that lead to the $L^1$-contraction property for the associated admissible solutions. Our approach offers a streamlined and unifying perspective on many of the known entropy conditions, making it possible to recover earlier uniqueness results under weaker conditions than before, and to provide new results for other less studied problems. Several strategies for proving the existence of admissible solutions are discussed, and existence results are given for fluxes satisfying some additional conditions. These are based on convergence results either for the vanishing viscosity method (with standard viscosity or with specific viscosities "adapted" to the choice of a germ), or for specific germ-adapted finite volume schemes

Abacavir-Reactive memory T Cells are present in drug naïve individuals

Background Fifty-five percent of individuals with HLA-B*57:01 exposed to the antiretroviral drug abacavir develop a hypersensitivity reaction (HSR) that has been attributed to naïve T-cell responses to neo-antigen generated by the drug. Immunologically confirmed abacavir HSR can manifest clinically in less than 48 hours following first exposure suggesting that, at least in some cases, abacavir HSR is due to re-stimulation of a pre-existing memory T-cell population rather than priming of a high frequency naïve T-cell population. Methods To determine whether a pre-existing abacavir reactive memory T-cell population contributes to early abacavir HSR symptoms, we studied the abacavir specific naïve or memory T-cell response using HLA-B*57:01 positive HSR patients or healthy controls using ELISpot assay, intra-cellular cytokine staining and tetramer labelling. Results Abacavir reactive CD8+ T-cell responses were detected in vitro in one hundred percent of abacavir unexposed HLA-B*57:01 positive healthy donors. Abacavir-specific CD8+ T cells from such donors can be expanded from sorted memory, and sorted naïve, CD8+ T cells without need for autologous CD4+ T cells. Conclusions We propose that these pre-existing abacavir-reactive memory CD8+ T-cell responses must have been primed by earlier exposure to another foreign antigen and that these T cells cross-react with an abacavir-HLA-B*57:01-endogenous peptide ligand complex, in keeping with the model of heterologous immunity proposed in transplant rejection

Pediatric malignancies presenting as a possible infectious disease

<p>Abstract</p> <p>Background</p> <p>The clinical, laboratory, and radiological features of malignancy can overlap with those of infection. The purpose of this study was to determine the findings in children who were initially thought to have an infectious disease but ultimately proved to have a malignancy.</p> <p>Methods</p> <p>The database of patients diagnosed with a malignancy in the Northern Alberta Children's Cancer Program (NACCP) January 1, 1993 to December 31, 2003 was merged with the database of inpatients referred to the infectious diseases service at the Stollery Children's Hospital and charts were reviewed on all patients referred to the infectious diseases consult service prior to the diagnosis of malignancy.</p> <p>Results</p> <p>An infectious diseases consultation for diagnosis was requested in 21 of 561 patients prior to the confirmation of malignancy, and 3 of these 21 patients had both infection and malignancy (leukemia (N = 13), lymphoma (N = 3), rhabdomyosarcoma (N = 1), Langerhan's cell histiocytosis (N = 1), fibrous histicocytosis (N = 1), ependymoma (N = 1), and neuroblastoma (N = 1). The most common reason for infectious diseases consultation was suspected muskuloskeletal infection (N = 9). A palpable or radiographically enlarged spleen was noted in 11 patients (52%). All but 2 patients had abnormal hematologic parameters while an elevated lactate dehydrogenase (LDH) occurred in 10 patients (48%). Delay of diagnosis because of investigation or therapy for an infectious disease occurred in only 2 patients.</p> <p>Conclusion</p> <p>It is not common for treatment of pediatric malignancies to be delayed because infection is thought to be the primary diagnosis. However, pediatric infectious diseases physicians should consider malignancy in the differential diagnosis when they see patients with fever and bone pain, unexplained splenomegaly or abnormal complete blood cell counts. Other clues may include hepatomegaly or elevated LDH.</p

Functional Expression of Human Adenine Nucleotide Translocase 4 in Saccharomyces Cerevisiae

The adenine nucleotide translocase (ANT) mediates the exchange of ADP and ATP across the inner mitochondrial membrane. The human genome encodes multiple ANT isoforms that are expressed in a tissue-specific manner. Recently a novel germ cell-specific member of the ANT family, ANT4 (SLC25A31) was identified. Although it is known that targeted depletion of ANT4 in mice resulted in male infertility, the functional biochemical differences between ANT4 and other somatic ANT isoforms remain undetermined. To gain insight into ANT4, we expressed human ANT4 (hANT4) in yeast mitochondria. Unlike the somatic ANT proteins, expression of hANT4 failed to complement an AAC-deficient yeast strain for growth on media requiring mitochondrial respiration. Moreover, overexpression of hANT4 from a multi-copy plasmid interfered with optimal yeast growth. However, mutation of specific amino acids of hANT4 improved yeast mitochondrial expression and supported growth of the AAC-deficient yeast on non-fermentable carbon sources. The mutations affected amino acids predicted to interact with phospholipids, suggesting the importance of lipid interactions for function of this protein. Each mutant hANT4 and the somatic hANTs exhibited similar ADP/ATP exchange kinetics. These data define common and distinct biochemical characteristics of ANT4 in comparison to ANT1, 2 and 3 providing a basis for study of its unique adaptation to germ cells

A wide-field photometric study of the globular cluster system of NGC 4636

We investigate the unusually rich cluster system of NGC4636 with wide-field Washington photometry. The globular cluster luminosity function can be followed roughly 1 mag beyond the turn-over magnitude. This corresponds to a distance modulus of m-M=31.24+-0.17, 0.4 mag larger than the distance determined from surface brightness fluctuations. The high specific frequency is confirmed, yet the exact value remains uncertain because of the uncertain distance: it varies between 5.6+-1.2 and 8.9+-1.2. The globular cluster system has a clearly bimodal color distribution. The color peak positions show no radial dependence and are in good agreement with the values found for other galaxies studied in the same filter system. However, a luminosity dependence is found: brighter clusters with an ``intermediate'' color exist. The clusters exhibit a shallow radial distribution within 7'.Within the same radial interval, the galaxy light has a distinctly steeper profile. Because of the difference in the cluster and light distribution the specific frequency increases considerably with radius. At 7' and 9' the density profiles of the red and blue clusters, respectively, change strongly which indicates that we reach the outer rim of the cluster system at approximately 11'. This feature is seen for the first time in a globular cluster system. While the radial distribution of the cluster and field populations are rather different, this is not true for the ellipticity of the system: the elongation as well as the position angle of the cluster system agree well with the galaxy light. We compare the radial distribution of globular clusters with the light profiles for a sample of elliptical galaxies. The difference observed in NGC 4636 is typical of an elliptical galaxy of this luminosity.Comment: Accepted for publication in A&A, 16 pages, 15 figure