The SkyMapper Transient Survey

The SkyMapper 1.3 m telescope at Siding Spring Observatory has now begun regular operations. Alongside the Southern Sky Survey, a comprehensive digital survey of the entire southern sky, SkyMapper will carry out a search for supernovae and other transients. The search strategy, covering a total footprint area of ~2000 deg2 with a cadence of $\leq 5$ days, is optimised for discovery and follow-up of low-redshift type Ia supernovae to constrain cosmic expansion and peculiar velocities. We describe the search operations and infrastructure, including a parallelised software pipeline to discover variable objects in difference imaging; simulations of the performance of the survey over its lifetime; public access to discovered transients; and some first results from the Science Verification data.Comment: 13 pages, 11 figures; submitted to PAS

The Very Highly Ionized Broad Absorption Line System of the QSO SBS1542+541

We have analyzed the broad absorption line system of the bright (V=16.5) high-redshift (z=2.361) QSO SBS1542+541 using UV spectra from the HST FOS along with optical data from the MMT and the Steward Observatory 2.3m telescope. These spectra give continuous wavelength coverage from 1200 to 8000 Angstroms, corresponding to 340 to 2480 Angstroms in the QSO rest frame. This object therefore offers a rare opportunity to study broad absorption lines in the rest-frame extreme UV. We find that the absorption system is dominated by very high-ionization species, including O VI, NeVIII, and SiXII. We also identify apparently saturated broad Lyman-series lines of order Ly-gamma and higher. There is strong evidence for partial occultation of the QSO emission source, particularly from the higher-order Lyman lines which indicate a covered fraction less than 0.2. Overall, the data suggest a correlation between a larger covered fraction and a higher state of ionization. We suggest that the different covered fractions can be explained by either a special line of sight through a disk-like geometry or by the existence of density fluctuations of a factor >2 in the BAL gas. Our photoionization models of the system indicate a large column density and high ionization state similar to that found in X-ray ``warm absorbers''.Comment: 31 pages, 13 figures, to be published in Ap

Exosomes: key mediators of metastasis and pre-metastatic niche formation

While tumour cells are classically known to communicate via direct cell-to-cell contact and the secretion of soluble protein-based factors such as cytokines and growth factors, alternative novel mechanisms that promote tumour progression have recently emerged. Now, new critical components of the secretome thought to be involved in tumour progression are exosomes, small vesicles of endocytic origin that carry a variety of bioactive molecules, including proteins, lipids, RNA, as well as DNA molecules. Cancer cell-derived exosomes have been shown to participate in crucial steps of metastatic spread of a primary tumour, ranging from oncogenic reprogramming of malignant cells to formation of pre-metastatic niches. These effects are achieved through the mediation of intercellular cross-talk and subsequent modification of both local and distant microenvironments in an autocrine and paracrine fashion. Here, we summarise the recent findings that implicate this non-canonical signalling within the tumour as a critical driver of metastatic disease progression, and discuss how understanding the molecular mechanisms involved in exosome-mediated metastasis is of great value for the development of new therapeutic strategies to prevent cancer progression

Emerging pharmacotherapy of tinnitus

Tinnitus, the perception of sound in the absence of an auditory stimulus, is perceived by about 1 in 10 adults, and for at least 1 in 100, tinnitus severely affects their quality of life. Because tinnitus is frequently associated with irritability, agitation, stress, insomnia, anxiety and depression, the social and economic burdens of tinnitus can be enormous. No curative treatments are available. However, tinnitus symptoms can be alleviated to some extent. The most widespread management therapies consist of auditory stimulation and cognitive behavioral treatment, aiming at improving habituation and coping strategies. Available clinical trials vary in methodological rigor and have been performed for a considerable number of different drugs. None of the investigated drugs have demonstrated providing replicable long-term reduction of tinnitus impact in the majority of patients in excess of placebo effects. Accordingly, there are no FDA or European Medicines Agency approved drugs for the treatment of tinnitus. However, in spite of the lack of evidence, a large variety of different compounds are prescribed off-label. Therefore, more effective pharmacotherapies for this huge and still growing market are desperately needed and even a drug that produces only a small but significant effect would have an enormous therapeutic impact. This review describes current and emerging pharmacotherapies with current difficulties and limitations. In addition, it provides an estimate of the tinnitus market. Finally, it describes recent advances in the tinnitus field which may help overcome obstacles faced in the pharmacological treatment of tinnitus. These include incomplete knowledge of tinnitus pathophysiology, lack of well-established animal models, heterogeneity of different forms of tinnitus, difficulties in tinnitus assessment and outcome measurement and variability in clinical trial methodology. © 2009 Informa UK Ltd.Fil: Langguth, Berthold. Universitat Regensburg; AlemaniaFil: Salvi, Richard. State University of New York; Estados UnidosFil: Elgoyhen, Ana Belen. Consejo Nacional de Investigaciones Científicas y Técnicas. Instituto de Investigaciones en Ingeniería Genética y Biología Molecular "Dr. Héctor N. Torres"; Argentin

Biologically relevant oxidants and terminology, classification and nomenclature of oxidatively generated damage to nucleobases and 2-deoxyribose in nucleic acids

A broad scientific community is involved in investigations aimed at delineating the mechanisms of formation and cellular processing of oxidatively generated damage to nucleic acids. Perhaps as a consequence of this breadth of research expertise, there are nomenclature problems for several of the oxidized bases including 8-oxo-7,8-dihydroguanine (8-oxoGua), a ubiquitous marker of almost every type of oxidative stress in cells. Efforts to standardize the nomenclature and abbreviations of the main DNA degradation products that arise from oxidative pathways are reported. Information is also provided on the main oxidative radicals, non-radical oxygen species, one-electron agents and enzymes involved in DNA degradation pathways as well in their targets and reactivity. A brief classification of oxidatively generated damage to DNA that may involve single modifications, tandem base modifications, intrastrand and interstrand cross-links together with DNA-protein cross-links and base adducts arising from the addition of lipid peroxides breakdown products is also included

Opipramol dihydro­chloride

The title compound (systematic name: 4-{3-[2-aza­tricyclo­[9.4.0.03,8]penta­deca-1(15),3,5,7,11,13-hexaen-2-yl]prop­yl}-1-(2-hy­droxy­eth­yl)piperazine-1,4-diium dichloride), C23H31N3O+·2Cl−, is the dihydro­chloride of a piperazine derivative bearing a bulky 3-(5H-dibenz[b,f]azepin-5-yl)propyl substituent. Protonation took place on both N atoms of the piperazine unit. The diaza­cyclo­hexane ring adopts a chair conformation. N—H⋯Cl, O—H⋯Cl and C—H⋯Cl hydrogen bonding as well as C—H⋯O contacts connect the components into a three-dimensional network in the crystal. Two C—H⋯π contacts are also observed

A Composite Extreme Ultraviolet QSO Spectrum from FUSE

The Far Ultraviolet Spectroscopic Explorer (FUSE) has surveyed a large sample (> 100) of active galactic nuclei in the low redshift universe (z < 1). Its response at short wavelengths makes it possible to measure directly the EUV spectral shape of QSOs and Seyfert 1 galaxies at z < 0.3. Using archival FUSE spectra, we form a composite extreme ultraviolet (EUV) spectrum of QSOs at z < 1 and compare it to UV/optical composite spectra of QSOs at higher redshift, particularly the composite spectrum from archival Hubble Space Telescope spectra.Comment: 4 pages, 3 figures, requires newpasp.sty, to appear in "AGN Physics with the Sloan Digital Sky Survey", ASP Conference Series, G.T. Richards and P.B. Hall, ed

Mycobacterial catalase–peroxidase is a tissue antigen and target of the adaptive immune response in systemic sarcoidosis

Sarcoidosis is a disease of unknown etiology characterized by noncaseating epithelioid granulomas, oligoclonal CD4+ T cell infiltrates, and immune complex formation. To identify pathogenic antigens relevant to immune-mediated granulomatous inflammation in sarcoidosis, we used a limited proteomics approach to detect tissue antigens that were poorly soluble in neutral detergent and resistant to protease digestion, consistent with the known biochemical properties of granuloma-inducing sarcoidosis tissue extracts. Tissue antigens with these characteristics were detected with immunoglobulin (Ig)G or F(ab′)2 fragments from the sera of sarcoidosis patients in 9 of 12 (75%) sarcoidosis tissues (150–160, 80, or 60–64 kD) but only 3 of 22 (14%) control tissues (all 62–64 kD; P = 0.0006). Matrix-assisted laser desorption/ionization time of flight mass spectrometry identified Mycobacterium tuberculosis catalase–peroxidase (mKatG) as one of these tissue antigens. Protein immunoblotting using anti-mKatG monoclonal antibodies independently confirmed the presence of mKatG in 5 of 9 (55%) sarcoidosis tissues but in none of 14 control tissues (P = 0.0037). IgG antibodies to recombinant mKatG were detected in the sera of 12 of 25 (48%) sarcoidosis patients compared with 0 of 11 (0%) purified protein derivative (PPD)− (P = 0.0059) and 4 of 10 (40%) PPD+ (P = 0.7233) control subjects, suggesting that remnant mycobacterial catalase–peroxidase is one target of the adaptive immune response driving granulomatous inflammation in sarcoidosis