Revisiting the relativistic ejection event in XTE J1550-564 during the 1998 outburst

We revisit the discovery outburst of the X-ray transient XTE J1550−564 during which relativistic jets were observed in 1998 September, and review the radio images obtained with the Australian Long Baseline Array, and light curves obtained with the Molonglo Observatory Synthesis Telescope and the Australia Telescope Compact Array. Based on Hi spectra, we constrain the source distance to between 3.3 and 4.9 kpc. The radio images, taken some 2 d apart, show the evolution of an ejection event. The apparent separation velocity of the two outermost ejecta is at least 1.3c and may be as large as 1.9c; when relativistic effects are taken into account, the inferred true velocity is ≥ 0.8c. The flux densities appear to peak simultaneously during the outburst, with a rather flat (although still optically thin) spectral index of −0.2

No excess of mitochondrial DNA deletions within muscle in progressive multiple sclerosis

BACKGROUND: Mitochondrial dysfunction is an established feature of multiple sclerosis (MS). We recently described high levels of mitochondrial DNA (mtDNA) deletions within respiratory enzyme-deficient (lacking mitochondrial respiratory chain complex IV with intact complex II) neurons and choroid plexus epithelial cells in progressive MS. OBJECTIVES: The objective of this paper is to determine whether respiratory enzyme deficiency and mtDNA deletions in MS were in excess of age-related changes within muscle, which, like neurons, are post-mitotic cells that frequently harbour mtDNA deletions with ageing and in disease. METHODS: In progressive MS cases (n=17), known to harbour an excess of mtDNA deletions in the central nervous system (CNS), and controls (n=15), we studied muscle (paraspinal) and explored mitochondria in single fibres. Histochemistry, immunohistochemistry, laser microdissection, real-time polymerase chain reaction (PCR), long-range PCR and sequencing were used to resolve the single muscle fibres. RESULTS: The percentage of respiratory enzyme-deficient muscle fibres, mtDNA deletion level and percentage of muscle fibres harbouring high levels of mtDNA deletions were not significantly different in MS compared with controls. CONCLUSION: Our findings do not provide support to the existence of a diffuse mitochondrial abnormality involving multiple systems in MS. Understanding the cause(s) of the CNS mitochondrial dysfunction in progressive MS remains a research priority

Stochastic Vehicle Routing with Recourse

We study the classic Vehicle Routing Problem in the setting of stochastic optimization with recourse. StochVRP is a two-stage optimization problem, where demand is satisfied using two routes: fixed and recourse. The fixed route is computed using only a demand distribution. Then after observing the demand instantiations, a recourse route is computed -- but costs here become more expensive by a factor lambda. We present an O(log^2 n log(n lambda))-approximation algorithm for this stochastic routing problem, under arbitrary distributions. The main idea in this result is relating StochVRP to a special case of submodular orienteering, called knapsack rank-function orienteering. We also give a better approximation ratio for knapsack rank-function orienteering than what follows from prior work. Finally, we provide a Unique Games Conjecture based omega(1) hardness of approximation for StochVRP, even on star-like metrics on which our algorithm achieves a logarithmic approximation.Comment: 20 Pages, 1 figure Revision corrects the statement and proof of Theorem 1.

Thermal effects on electron-phonon interaction in silicon nanostructures

Raman spectra from silicon nanostructures, recorded using excitation laser power density of 1.0 kW/cm^2, is employed here to reveal the dominance of thermal effects at temperatures higher than the room temperature. Room temperature Raman spectrum shows only phonon confinement and Fano effects. Raman spectra recorded at higher temperatures show increase in FWHM and decrease in asymmetry ratio with respect to its room temperature counterpart. Experimental Raman scattering data are analyzed successfully using theoretical Raman line-shape generated by incorporating the temperature dependence of phonon dispersion relation. Experimental and theoretical temperature dependent Raman spectra are in good agreement. Although quantum confinement and Fano effects persists, heating effects start dominating at higher temperatures than room tempaerature.Comment: 9 Pages, 3 Figures and 1 Tabl

Network model of immune responses reveals key effectors to single and co-infection dynamics by a respiratory bacterium and a gastrointestinal helminth

Co-infections alter the host immune response but how the systemic and local processes at the site of infection interact is still unclear. The majority of studies on co-infections concentrate on one of the infecting species, an immune function or group of cells and often focus on the initial phase of the infection. Here, we used a combination of experiments and mathematical modelling to investigate the network of immune responses against single and co-infections with the respiratory bacterium Bordetella bronchiseptica and the gastrointestinal helminth Trichostrongylus retortaeformis. Our goal was to identify representative mediators and functions that could capture the essence of the host immune response as a whole, and to assess how their relative contribution dynamically changed over time and between single and co-infected individuals. Network-based discrete dynamic models of single infections were built using current knowledge of bacterial and helminth immunology; the two single infection models were combined into a co-infection model that was then verified by our empirical findings. Simulations showed that a T helper cell mediated antibody and neutrophil response led to phagocytosis and clearance of B. bronchiseptica from the lungs. This was consistent in single and co-infection with no significant delay induced by the helminth. In contrast, T. retortaeformis intensity decreased faster when co-infected with the bacterium. Simulations suggested that the robust recruitment of neutrophils in the co-infection, added to the activation of IgG and eosinophil driven reduction of larvae, which also played an important role in single infection, contributed to this fast clearance. Perturbation analysis of the models, through the knockout of individual nodes (immune cells), identified the cells critical to parasite persistence and clearance both in single and co-infections. Our integrated approach captured the within-host immuno-dynamics of bacteria-helminth infection and identified key components that can be crucial for explaining individual variability between single and co-infections in natural populations

Characterisation of the genomic landscape of CRLF2-rearranged acute lymphoblastic leukemia

Deregulated expression of the type I cytokine receptor, CRLF2, is observed in 5–15% of precursor B-cell acute lymphoblastic leukaemia (B-ALL). We aimed to determine the clinical and genetic landscape of those with IGH-CRLF2 or P2RY8-CRLF2 (CRLF2-r) using multiple genomic approaches. Clinical and demographic features of CRLF2-r patients were characteristic of B-ALL. Patients with IGH-CRLF2 were older (14 y vs. 4 y, P < .001), while the incidence of CRLF2-r among Down syndrome patients was high (50/161, 31%). CRLF2-r co-occurred with primary chromosomal rearrangements but the majority (111/161, 69%) had B-other ALL. Copy number alteration (CNA) profiles were similar to B-other ALL, although CRLF2-r patients harbored higher frequencies of IKZF1 (60/138, 43% vs. 77/1351, 24%) and BTG1 deletions (20/138, 15% vs. 3/1351, 1%). There were significant differences in CNA profiles between IGH-CRLF2 and P2RY8-CRLF2 patients: IKZF1 (25/35, 71% vs. 36/108, 33%, P < .001), BTG1 (11/35, 31% vs. 10/108, 9%, P =.004), and ADD3 deletions (9/19, 47% vs. 5/38, 13%, P =.008). A novel gene fusion, USP9X-DDX3X, was discovered in 10/54 (19%) of patients. Pathway analysis of the mutational profile revealed novel involvement for focal adhesion. Although the functional relevance of many of these abnormalities are unknown, they likely activate additional pathways, which may represent novel therapeutic targets

Differential regulation of NF-κB activation and function by topoisomerase II inhibitors

BACKGROUND: While many common chemotherapeutic drugs and other inducers of DNA-damage result in both NF-κB nuclear translocation and DNA-binding, we have previously observed that, depending on the precise stimulus, there is great diversity of the function of NF-κB. In particular, we found that treatment of U-2 OS osteosarcoma cells with the anthracycine daunorubicin or with ultraviolet (UV-C) light resulted in a form of NF-κB that repressed rather than induced NF-κB reporter plasmids and the expression of specific anti-apoptotic genes. Anthracyclines such as daunorubicin can induce DNA-damage though inhibiting topoisomerase II, intercalating with DNA and undergoing redox cycling to produce oxygen free radicals. In this study we have investigated other anthracyclines, doxorubicin and aclarubicin, as well as the anthracenedione mitoxantrone together with the topoisomerase II inhibitor ICRF-193, which all possess differing characteristics, to determine which of these features is specifically required to induce both NF-κB DNA-binding and transcriptional repression in U-2 OS cells. RESULTS: The use of mitoxantrone, which does not undergo redox cycling, and the reducing agent epigallocatechingallate (EGCG) demonstrated that oxygen free radical production is not required for induction of NF-κB DNA-binding and transcriptional repression by these agents and UV-C. In addition, the use of aclarubicin, which does not directly inhibit topoisomerase II and ICRF-193, which inhibits topoisomerase II but does not intercalate into DNA, demonstrated that topoisomerase II inhibition is not sufficient to induce the repressor form of NF-κB. CONCLUSION: Induction of NF-κB DNA-binding and transcriptional repression by topoisomerase II inhibitors was found to correlate with an ability to intercalate into DNA. Although data from our and other laboratories indicates that topoisomerase II inhibition and oxygen free radicals do regulate NF-κB, they are not required for the particular ability of NF-κB to repress rather than activate transcription. Together with our previous data, these results demonstrate that the nature of the NF-κB response is context dependent. In a clinical setting such effects could profoundly influence the response to chemotherapy and suggest that new methods of analyzing NF-κB function could have both diagnostic and prognostic value

Nova V5116 Sgr and searching for superhumps in nova remnants

We present the period analysis of unfiltered photometric observations of V5116 Sgr (Nova Sgr 2005 #2) and we search for superhump candidates in novae remnants. The PDM method for period analysis is used. The masses of the novae componets are estimated from the secondary mass -- orbital period and primary mass -- decline time relations. We found that 13 nights of V5116 Sgr observations in the year 2006 are modulated with a period of $0.1238 \pm 0.0001$ d ($2.9712 \pm 0.0024$ h). Following the shape of the phased light curves and no apparent change in the value of the periodicity in different subsamples of the data, we interpret the period as orbital in nature. The binary system then falls within the period gap of the orbital period distribution of cataclysmic variables. From the maximum magnitude -- rate of decline relation, we estimate the maximum absolute visual magnitude of $M_{\rm Vmax} = -8.85 \pm 0.04$ mag using the measured value of decline $t_{\rm 2} = 6.5 \pm 1.0$ d. The mass-period relation for cataclysmic variables yields a secondary mass estimate of about $0.26 \pm 0.05 {\rm M}_{\rm \odot}$. We propose that V5116 Sgr is a high inclination system showing an irradiation effect of the secondary star. No fully developed accretion disc up to the tidal radius with the value lower than $3.5 10^{10}$ cm is probable. The mass ratio was estimated in a few novae and the presence or absence of superhumps in these systems was compared with the mass ratio limit for superhumps of about 0.35. We found that in the majority of novae with expected superhumps, this variability has not been found yet. Therefore, more observations of these systems is encouraged.Comment: 9 pages, 7 figures, accepted for publication in A&

Global and regional burden of hospital admissions for pneumonia in older adults::A systematic review and meta-analysis

Pneumonia constitutes a substantial disease burden among adults overall and those who are elderly. We aimed to identify all studies investigating the disease burden among older adults (age, ≥65 years) admitted to the hospital with pneumonia. We estimated the hospital admission rate and in-hospital case-fatality ratio (CFR) of pneumonia in older adults, stratified by age and economic status (industrialized vs developing), with data from a systematic review of studies published from 1996 through 2017 and from 8 unpublished population-based studies. We applied these rate estimates to population estimates for 2015 to calculate the global and regional burden in older adults who would have been admitted to the hospital with pneumonia that year. We estimated the number of in-hospital pneumonia deaths by combining in-hospital CFRs with hospital admission estimates from hospital-based studies. We identified 109 eligible studies; 73 used clinical pneumonia as the case definition, and 36 used radiologically confirmed pneumonia as the case definition. We estimated that, in 2015, 6.8 million episodes (uncertainty range [UR], 5.8-8.0 episodes) of clinical pneumonia resulted in hospital admissions of older adults worldwide. The hospital admission rate increased with advancing age and was higher in men. The total disease burden was likely underestimated when using the definition of radiologically confirmed pneumonia. Based on data from 52 hospital studies reporting data on pneumonia mortality, we estimated that about 1.1 million in-hospital deaths (UR, 0.9-1.4 in-hospital deaths) occurred among older adults. The burden of pneumonia requiring hospitalization among older adults is substantial. Appropriate prevention and management strategies should be developed to reduce its impact