Stability analysis of two-temperature radiative shocks; formulation, eigenfunctions, luminosity response and boundary conditions

We present a general formulation for stability analyses of radiative shocks with multiple cooling processes, longitudinal and transverse perturbations, and unequal electron and ion temperatures. Using the accretion shocks of magnetic cataclysmic variables as an illustrative application, we investigate the shock instabilities by examining the eigenfunctions of the perturbed hydrodynamic variables. We also investigate the effects of varying the condition at the lower boundary of the post-shock flow from a zero-velocity fixed wall to several alternative types of boundaries involving the perturbed hydrodynamic variables, and the variations of the emission from the post-shock flow under different modes of oscillations. We found that the stability properties for flow with a stationary-wall lower boundary are not significantly affected by perturbing the lower boundary condition, and they are determined mainly by the energy-transport processes. Moreover, there is no obvious correlation between the amplitude or phase of the luminosity response and the stability properties of the system. Stability of the system can, however, be modified in the presence of transverse perturbation. The luminosity responses are also altered by transverse perturbation

Gravitational and distributed heating effects of a cD galaxy on the hydrodynamical structure of its host cluster

We investigate the effects of a cD galaxy's gravity and AGN heating of the host galaxy cluster. We consider a standard prescription for the hydrodynamics, with the structures determined by mass continuity, momentum and energy conservation equations in spherical symmetry. The cluster comprises a dark matter halo (DM) and ionised X-ray emitting intracluster gas (ICM), which jointly determine the gravitational potential. The cD galaxy is an additive gravitational potential component. The DM assumes a polytropic equation of state (determined by its microphysics), which could be non-radiative self-interacting particles or more exotically interacting particles. The AGN provides distributed heating, counteracting radiative cooling. Stationary density and velocity dispersion profiles are obtained by numerically integrating the hydrodynamic equations with appropriate boundary conditions. The minimum gas temperature in the cluster core is higher when a cD galaxy is present than when it is absent. The solutions also yield a point-like mass concentration exceeding a minimum mass: presumably the AGN's supermassive black hole (SMBH). Consistency with observed SMBH masses constrains the possible DM equations of state. The constraints are looser when a cD galaxy is present. Distributed (AGN) heating alters cluster global properties, and also reduces the lower limits for the central point-mass, for the preferred DM models in which the dark particles have greater heat capacity than point particles. Eluding these constraints would require dominant non-spherical or anisotropic effects (e.g. bulk rotation, non-radial streaming, asymmetric lumps, or a strong magnetic field)

Oscillatory instability of radiative shocks with multiple cooling processes

The stand-off shock formed in the accretion flow on to a stationary wall, such as the surface of a white dwarf, may be thermally unstable, depending on the cooling processes which dominate the post-shock flow. Some processes lead to instability, while others tend to stabilize the shock. We consider competition between the destabilizing influence of thermal bremsstrahlung cooling, and a stabilizing process which is a power law in density and temperature. Cyclotron cooling and processes which are of order 1, 3/2 and 2 in density are considered. The relative efficiency and power-law indices of the second mechanism are varied, and particular effects on the stability properties and frequencies of oscillation modes are examined

Polarised radiative transfer, rotation measure fluctuations and large-scale magnetic fields

Faraday rotation measure at radio wavelengths is commonly used to diagnose large-scale magnetic fields. It is argued that the length-scales on which magnetic fields vary in large-scale diffuse astrophysical media can be inferred from correlations in the observed RM. RM is a variable which can be derived from the polarised radiative transfer equations in restrictive conditions. This paper assesses the usage of RMF (rotation measure fluctuation) analyses for magnetic field diagnostics in the framework of polarised radiative transfer. We use models of various magnetic field configurations and electron density distributions to show how density fluctuations could affect the correlation length of the magnetic fields inferred from the conventional RMF analyses. We caution against interpretations of RMF analyses when a characteristic density is ill-defined, e.g. in cases of log-normal distributed and fractal-like density structures. As the spatial correlations are generally not the same in the line-of-sight longitudinal direction and the sky plane direction, one also needs to clarify the context of RMF when inferring from observational data. In complex situations, a covariant polarised radiative transfer calculation is essential to capture all aspects of radiative and transport processes, which would otherwise ambiguate the interpretations of magnetism in galaxy clusters and larger-scale cosmological structures

Polarized radiative transfer, rotation measure fluctuations, and large-scale magnetic fields

Faraday rotation measure (RM) at radio wavelengths is commonly used to diagnose large-scale magnetic fields. It is argued that the length-scales on which magnetic fields vary in large-scale diffuse astrophysical media can be inferred from correlations in the observed RM. RM is a variable which can be derived from the polarized radiative transfer equations in restrictive conditions. This paper assesses the usage of rotation measure fluctuation (RMF) analyses for magnetic field diagnostics in the framework of polarized radiative transfer. We use models of various magnetic field configurations and electron density distributions to show how density fluctuations could affect the correlation length of the magnetic fields inferred from the conventional RMF analyses. We caution against interpretations of RMF analyses when a characteristic density is ill defined, e.g. in cases of lognormal-distributed and fractal-like density structures. As the spatial correlations are generally not the same in the line-of-sight longitudinal direction and the sky plane direction, one also needs to clarify the context of RMF when inferring from observational data. In complex situations, a covariant polarized radiative transfer calculation is essential to capture all aspects of radiative and transport processes, which would otherwise ambiguate the interpretations of magnetism in galaxy clusters and larger scale cosmological structures

Dark matter concentrations in galactic nuclei according to polytropic models

We calculate the radial profiles of galaxies where the nuclear region is self-gravitating, consisting of self-interacting dark matter (SIDM) with F degrees of freedom. For sufficiently high density this dark matter becomes collisional, regardless of its behaviour on galaxy scales. Our calculations show a spike in the central density profile, with properties determined by the dark matter microphysics, and the densities can reach the ‘mean density’ of a black hole (from dividing the black hole mass by the volume enclosed by the Schwarzschild radius). For a galaxy halo of given compactness (χ ≡ 2GM/Rc2), certain values for the dark matter entropy yield a dense central object lacking an event horizon. For some soft equations of state of the SIDM (e.g. F 6), there are multiple horizonless solutions at given compactness. Although light propagates around and through a sphere composed of dark matter, it is gravitationally lensed and redshifted. While some calculations give non-singular solutions, others yield solutions with a central singularity. In all cases, the density transitions smoothly from the central body to the dark matter envelope around it, and to the galaxy’s dark matter halo. We propose that pulsar timing observations will be able to distinguish between systems with a centrally dense dark matter sphere (for different equations of state) and conventional galactic nuclei that harbour a supermassive black hole

Study protocol to investigate the effects of testosterone therapy as an adjunct to exercise rehabilitation in hypogonadal males with chronic heart failure

BACKGROUND: Testosterone deficiency is a common occurrence in men with chronic heart failure (CHF) and may underpin features of advanced disease, including reduced skeletal muscle mass and fatigue. It is positively correlated with cardiac output and exercise capacity in patients with CHF, whereas a significant improvement in both these parameters has been observed following testosterone replacement therapy. Testosterone therapy has also been shown to reduce circulating levels of inflammatory markers, (TNF-α, sICAM-1 and sVCAM-1) in patients with established coronary artery disease and testosterone deficiency. This pilot study will assess the feasibility of a combined exercise rehabilitation and adjunctive testosterone therapy intervention for evoking improvements in exercise capacity, circulating inflammatory markers, cardiac and skeletal muscle function, indices of psychological health status and quality of life in hypogonadal males with chronic heart failure. METHODS/DESIGN: Following ethical approval, 36 patients will be randomly allocated to one of two groups: testosterone or placebo therapy during exercise rehabilitation. A combined programme of moderate intensity aerobic exercise and resistance (strength) training will be used. The primary outcome measure is exercise capacity, assessed using an incremental shuttle walk test. Secondary outcome measures include measures of peak oxygen uptake, cardiac function, lower-limb skeletal muscle contractile function and oxygenation during exercise, circulating inflammatory markers, psychological health status and quality of life. DISCUSSION: Exercise rehabilitation can safely increase exercise capacity in stable CHF patients but there is a need for studies which are aimed at evaluating the long-term effects of physical training on functional status, morbidity and mortality. This pilot study will provide valuable preliminary data on the efficacy of testosterone therapy as an adjunct to exercise rehabilitation on a range of functional, physiological and health-related outcomes in this patient population. Preliminary data will be used in the design of a large-scale randomised controlled trial, aimed at informing clinical practice with respect to optimisation of exercise rehabilitation in this patient group

Study protocol: a randomised controlled trial investigating the effect of exercise training on peripheral blood gene expression in patients with stable angina

Background: Exercise training has been shown to reduce angina and promote collateral vessel development in patients with coronary artery disease. However, the mechanism whereby exercise exerts these beneficial effects is unclear. There has been increasing interest in the use of whole genome peripheral blood gene expression in a wide range of conditions to attempt to identify both novel mechanisms of disease and transcriptional biomarkers. This protocol describes a study in which we will assess the effect of a structured exercise programme on peripheral blood gene expression in patients with stable angina, and correlate this with changes in angina level, anxiety, depression, and exercise capacity. Methods/Design: Sixty patients with stable angina will be recruited and randomised 1: 1 to exercise training or conventional care. Patients randomised to exercise training will attend an exercise physiology laboratory up to three times weekly for supervised aerobic interval training sessions of one hour in total duration. Patients will undergo assessments of angina, anxiety, depression, and peripheral blood gene expression at baseline, after six and twelve weeks of training, and twelve weeks after formal exercise training ceases. Discussion: This study will provide comprehensive data on the effect of exercise training on peripheral blood gene expression in patients with angina. By correlating this with improvement in angina status we will identify candidate peripheral blood transcriptional markers predictive of improvements in angina level in response to exercise training

Inhibition of the tyrosine phosphatase SHP-2 suppresses angiogenesis in vitro and in vivo

Endothelial cell survival is indispensable to maintain endothelial integrity and initiate new vessel formation. We investigated the role of SHP-2 in endothelial cell survival and angiogenesis in vitro as well as in vivo. SHP-2 function in cultured human umbilical vein and human dermal microvascular endothelial cells was inhibited by either silencing the protein expression with antisense-oligodesoxynucleotides or treatment with a pharmacological inhibitor (PtpI IV). SHP-2 inhibition impaired capillary-like structure formation (p < 0.01; n = 8) in vitro as well as new vessel growth ex vivo (p < 0.05; n = 10) and in vivo in the chicken chorioallantoic membrane (p < 0.01, n = 4). Additionally, SHP-2 knock-down abrogated fibroblast growth factor 2 (FGF-2)-dependent endothelial proliferation measured by MTT reduction ( p ! 0.01; n = 12). The inhibitory effect of SHP-2 knock-down on vessel growth was mediated by increased endothelial apoptosis ( annexin V staining, p ! 0.05, n = 9), which was associated with reduced FGF-2-induced phosphorylation of phosphatidylinositol 3-kinase (PI3-K), Akt and extracellular regulated kinase 1/2 (ERK1/2) and involved diminished ERK1/2 phosphorylation after PI3-K inhibition (n=3). These results suggest that SHP-2 regulates endothelial cell survival through PI3-K-Akt and mitogen-activated protein kinase pathways thereby strongly affecting new vessel formation. Thus, SHP-2 exhibits a pivotal role in angiogenesis and may represent an interesting target for therapeutic approaches controlling vessel growth. Copyright (C) 2007 S. Karger AG, Basel

Critical research gaps and translational priorities for the successful prevention and treatment of breast cancer

INTRODUCTION Breast cancer remains a significant scientific, clinical and societal challenge. This gap analysis has reviewed and critically assessed enduring issues and new challenges emerging from recent research, and proposes strategies for translating solutions into practice. METHODS More than 100 internationally recognised specialist breast cancer scientists, clinicians and healthcare professionals collaborated to address nine thematic areas: genetics, epigenetics and epidemiology; molecular pathology and cell biology; hormonal influences and endocrine therapy; imaging, detection and screening; current/novel therapies and biomarkers; drug resistance; metastasis, angiogenesis, circulating tumour cells, cancer 'stem' cells; risk and prevention; living with and managing breast cancer and its treatment. The groups developed summary papers through an iterative process which, following further appraisal from experts and patients, were melded into this summary account. RESULTS The 10 major gaps identified were: (1) understanding the functions and contextual interactions of genetic and epigenetic changes in normal breast development and during malignant transformation; (2) how to implement sustainable lifestyle changes (diet, exercise and weight) and chemopreventive strategies; (3) the need for tailored screening approaches including clinically actionable tests; (4) enhancing knowledge of molecular drivers behind breast cancer subtypes, progression and metastasis; (5) understanding the molecular mechanisms of tumour heterogeneity, dormancy, de novo or acquired resistance and how to target key nodes in these dynamic processes; (6) developing validated markers for chemosensitivity and radiosensitivity; (7) understanding the optimal duration, sequencing and rational combinations of treatment for improved personalised therapy; (8) validating multimodality imaging biomarkers for minimally invasive diagnosis and monitoring of responses in primary and metastatic disease; (9) developing interventions and support to improve the survivorship experience; (10) a continuing need for clinical material for translational research derived from normal breast, blood, primary, relapsed, metastatic and drug-resistant cancers with expert bioinformatics support to maximise its utility. The proposed infrastructural enablers include enhanced resources to support clinically relevant in vitro and in vivo tumour models; improved access to appropriate, fully annotated clinical samples; extended biomarker discovery, validation and standardisation; and facilitated cross-discipline working. CONCLUSIONS With resources to conduct further high-quality targeted research focusing on the gaps identified, increased knowledge translating into improved clinical care should be achievable within five years