Binaries and Globular Cluster Dynamics

We summarize the results of recent theoretical work on the dynamical evolution of globular clusters containing primordial binaries. Even a very small initial binary fraction (e.g., 10%) can play a key role in supporting a cluster against gravothermal collapse for many relaxation times. Inelastic encounters between binaries and single stars or other binaries provide a very significant energy source for the cluster. These dynamical interactions also lead to the production of large numbers of exotic systems such as ultracompact X-ray binaries, recycled radio pulsars, double degenerate systems, and blue stragglers. Our work is based on a new parallel supercomputer code implementing Henon's Monte Carlo method for simulating the dynamical evolution of dense stellar systems in the Fokker-Planck approximation. This new code allows us to calculate very accurately the evolution of a cluster containing a realistic number of stars (N ~ 10^5 - 10^6) in typically a few hours to a few days of computing time. The discrete, star-by-star representation of the cluster in the simulation makes it possible to treat naturally a number of important processes, including single and binary star evolution, all dynamical interactions of single stars and binaries, and tidal interactions with the Galaxy.Comment: 15 pages, to appear in `The Influence of Binaries on Stellar Population Studies', ed. D. Vanbeveren (Kluwer

Flavour physics constraints in the BMSSM

We study the implications of the presence of the two leading-order, non-renormalizable operators in the Higgs sector of the MSSM to flavour physics observables. We identify the constraints of flavour physics on the parameters of the BMSSM when we: a) focus on a region of parameters for which electroweak baryogenesis is feasible, b) use a CMSSM-like parametrization, and c) consider the case of a generic NUHM-type model. We find significant differences as compared to the standard MSSM case.Comment: 22 pages, 7 figure

Regulation of the Cardiac Na+/K+ ATPase by Phospholemman

Hansraj Dhayan, Rajender Kumar, Andreas Kukol, ‘Regulation of the Cardiac Na+/K+ ATPase by Phospholemman’, in Sajal Chakraborti, Naranjan Dhalla, eds., Regulation of Membrane Na+-K+ ATPase, (Switzerland: Springer, 2016), ISBN 978-3-319-24748-9, eISBN 978-3-319-24750-2.Peer reviewe

Fine Tuning in General Gauge Mediation

We study the fine-tuning problem in the context of general gauge mediation. Numerical analyses toward for relaxing fine-tuning are presented. We analyse the problem in typical three cases of the messenger scale, that is, GUT ($2\times10^{16}$ GeV), intermediate ($10^{10}$ GeV), and relatively low energy ($10^6$ GeV) scales. In each messenger scale, the parameter space reducing the degree of tuning as around 10% is found. Certain ratios among gluino mass, wino mass and soft scalar masses are favorable. It is shown that the favorable region becomes narrow as the messenger scale becomes lower, and tachyonic initial conditions of stop masses at the messenger scale are favored to relax the fine-tuning problem for the relatively low energy messenger scale. Our spectra would also be important from the viewpoint of the $\mu-B$ problem.Comment: 22 pages, 16 figures, comment adde

Nuclear ING2 expression is reduced in human cutaneous melanomas

Cutaneous malignant melanoma is a severe and sometimes life-threatening cancer. The molecular mechanism of melanomagenesis is incompletely understood. Deregulation of apoptosis is probably one of the key factors contributing to the progression of melanoma. The inhibitor of growth (ING) family proteins are candidate tumour suppressors which play important roles in apoptosis. Downregulated expression of ING proteins have been reported in several tumour types, including the loss of nuclear expression of p33ING1b in melanoma. As ING2 exhibits 58.9% homology with p33ING1b, we hypothesized that the aberrant expression of ING2 may be involved in melanomagenesis. Here, we used tissue microarray technology and immunohistochemistry to examine ING2 expression in human nevi and melanoma biopsies. Our data showed that nuclear ING2 expression was significantly reduced in radial growth phase (RGP), vertical growth phase (VGP), and metastatic melanomas compared with dysplastic nevi (P<0.05). Our data also revealed that nuclear ING2 expression was not associated with patient's gender, age or tumour thickness, ulceration, American Joint Committee on Cancer (AJCC) stage, tumour subtype, location and 5-year survival (P>0.05). Taken together, our results suggest that nuclear ING2 expression is significantly reduced in human melanomas and that reduced ING2 may be an important molecular event in the initiation of melanoma development

A Mouse Model of Post-Arthroplasty Staphylococcus aureus Joint Infection to Evaluate In Vivo the Efficacy of Antimicrobial Implant Coatings

Post-arthroplasty infections represent a devastating complication of total joint replacement surgery, resulting in multiple reoperations, prolonged antibiotic use, extended disability and worse clinical outcomes. As the number of arthroplasties in the U.S. will exceed 3.8 million surgeries per year by 2030, the number of post-arthroplasty infections is projected to increase to over 266,000 infections annually. The treatment of these infections will exhaust healthcare resources and dramatically increase medical costs.To evaluate novel preventative therapeutic strategies against post-arthroplasty infections, a mouse model was developed in which a bioluminescent Staphylococcus aureus strain was inoculated into a knee joint containing an orthopaedic implant and advanced in vivo imaging was used to measure the bacterial burden in real-time. Mice inoculated with 5x10(3) and 5x10(4) CFUs developed increased bacterial counts with marked swelling of the affected leg, consistent with an acute joint infection. In contrast, mice inoculated with 5x10(2) CFUs developed a low-grade infection, resembling a more chronic infection. Ex vivo bacterial counts highly correlated with in vivo bioluminescence signals and EGFP-neutrophil fluorescence of LysEGFP mice was used to measure the infection-induced inflammation. Furthermore, biofilm formation on the implants was visualized at 7 and 14 postoperative days by variable-pressure scanning electron microscopy (VP-SEM). Using this model, a minocycline/rifampin-impregnated bioresorbable polymer implant coating was effective in reducing the infection, decreasing inflammation and preventing biofilm formation.Taken together, this mouse model may represent an alternative pre-clinical screening tool to evaluate novel in vivo therapeutic strategies before studies in larger animals and in human subjects. Furthermore, the antibiotic-polymer implant coating evaluated in this study was clinically effective, suggesting the potential for this strategy as a therapeutic intervention to combat post-arthroplasty infections

Impact of unstable housing on all-cause mortality among persons who inject drugs

BACKGROUND: Illicit drug injecting is a well-established risk factor for morbidity and mortality. However, a limited number of prospective studies have examined the independent effect of unstable housing on mortality among persons who inject drugs (PWIDs). In this study we sought to identify if a relationship exists between unstable housing and all-cause mortality among PWIDs living in Vancouver, Canada. METHODS: PWIDs participating in two prospective cohort studies in Vancouver, Canada were followed between May 1996 and December 2012. Cohort data were linked to the provincial vital statistics database to ascertain mortality rates and causes of death. We used multivariate Cox proportional hazards regression to determine factors associated with all-cause mortality and to investigate the independent relationship between unstable housing and time to all-cause mortality. RESULTS: During the study period, 2453 individuals were followed for a median of 69 months (Inter-quartile range [IQR]: 34 – 113). In total, there were 515 (21.0%) deaths for an incidence density of 3.1 (95% Confidence Interval [CI]: 2.8 – 3.4) deaths per 100 person years. In multivariate analyses, after adjusting for potential confounders including HIV infection and drug use patterns, unstable housing remained independently associated with all-cause mortality (adjusted hazard ratio [AHR] = 1.30, 95% CI: 1.08 – 1.56). CONCLUSIONS: These findings demonstrate that unstable housing is an important risk factor for mortality independent of known risk factors including HIV infection and patterns of drug use. This study highlights the urgent need to provide supportive housing interventions to address elevated levels of preventable mortality among this population

Potential mechanisms underlying the acute lung dysfunction and bacterial extrapulmonary dissemination during Burkholderia cenocepacia respiratory infection

<p>Abstract</p> <p>Background</p> <p><it>Burkholderia cenocepacia</it>, an opportunistic pathogen that causes lung infections in cystic fibrosis (CF) patients, is associated with rapid and usually fatal lung deterioration due to necrotizing pneumonia and sepsis, a condition known as cepacia syndrome. The key bacterial determinants associated with this poor clinical outcome in CF patients are not clear. In this study, the cytotoxicity and procoagulant activity of <it>B. cenocepacia </it>from the ET-12 lineage, that has been linked to the cepacia syndrome, and four clinical isolates recovered from CF patients with mild clinical courses were analysed in both <it>in vitro </it>and <it>in vivo </it>assays.</p> <p>Methods</p> <p><it>B. cenocepacia-</it>infected BEAS-2B epithelial respiratory cells were used to investigate the bacterial cytotoxicity assessed by the flow cytometric detection of cell staining with propidium iodide. Bacteria-induced procoagulant activity in cell cultures was assessed by a colorimetric assay and by the flow cytometric detection of tissue factor (TF)-bearing microparticles in cell culture supernatants. Bronchoalveolar lavage fluids (BALF) from intratracheally infected mice were assessed for bacterial proinflammatory and procoagulant activities as well as for bacterial cytotoxicity, by the detection of released lactate dehydrogenase.</p> <p>Results</p> <p>ET-12 was significantly more cytotoxic to cell cultures but clinical isolates Cl-2, Cl-3 and Cl-4 exhibited also a cytotoxic profile. ET-12 and CI-2 were similarly able to generate a TF-dependent procoagulant environment in cell culture supernatant and to enhance the release of TF-bearing microparticles from infected cells. In the <it>in vivo </it>assay, all bacterial isolates disseminated from the mice lungs, but Cl-2 and Cl-4 exhibited the highest rates of recovery from mice livers. Interestingly, Cl-2 and Cl-4, together with ET-12, exhibited the highest cytotoxicity. All bacteria were similarly capable of generating a procoagulant and inflammatory environment in animal lungs.</p> <p>Conclusion</p> <p><it>B. cenocepacia </it>were shown to exhibit cytotoxic and procoagulant activities potentially implicated in bacterial dissemination into the circulation and acute pulmonary decline detected in susceptible CF patients. Improved understanding of the mechanisms accounting for <it>B. cenocepacia</it>-induced clinical decline has the potential to indicate novel therapeutic strategies to be included in the care <it>B. cenocepacia</it>-infected patients.</p

Proteomics approaches to fibrotic disorders

This review provides an introduction to mass spectrometry based proteomics and discusses several proteomics approaches that are relevant in understanding the pathophysiology of fibrotic disorders and the approaches that are frequently used in biomarker discovery

A Multilevel Measurement Model of Social Cohesion

In spite of its currency both in academic research and political rhetoric, there are numerous attempts to define and conceptualize the social cohesion concept but there has been paid little attention to provide a rigorous and empirically tested definition. There are even fewer studies that address social cohesion in a framework of cross-cultural validation of the indicators testing the equivalence of the factorial structure across countries. Finally, as far as we know there is no study that attempt to provide an empirically tested multilevel definition of social cohesion specifying a Multilevel Structural Equation Model. This study aims to cover this gap. First, we provide a theoretical construct of social cohesion taking into account not only its multidimensionality but also its multilevel structure. In the second step, to test the validity of this theoretical construct, we perform a multilevel confirmatory factor analysis in order to verify if the conceptual structure suggested in first step holds. In addition, we test the cross-level structural equivalence and the measurement invariance of the model in order to verify if the same multilevel model of social cohesion holds across the 29 countries analysed. In the final step, we specify a second-order multilevel CFA model in order to identify the existence of a general factor that can be called “social cohesion” operating in society that accounts for the surface phenomena that we observe