On the dependence of X-ray burst rate on accretion and spin rate

Nuclear burning and its dependence on the mass accretion rate are fundamental ingredients for describing the complicated observational phenomenology of neutron stars in binary systems. Motivated by high quality burst rate data emerging from large statistical studies, we report general calculations relating bursting rate to mass accretion rate and neutron star rotation frequency. In this first work we neglect general relativistic effects and accretion topology, though we discuss where their inclusion should play a role. The relations we derive are suitable for different burning regimes and provide a direct link between parameters predicted by theory and what is to be expected in observations. We illustrate this for analytical relations of different unstable burning regimes that operate on the surface of an accreting neutron star. We also use the observed behaviour of burst rate to suggest new constraints on burning parameters. We are able to provide an explanation for the long standing problem of the observed decrease of burst rate with increasing mass accretion that follows naturally from these calculations: when accretion rate crosses a certain threshold, ignition moves away from its initially preferential site and this can cause a net reduction of the burst rate due to the effects of local conditions that set local differences in both burst rate and stabilization criteria. We show under which conditions this can happen even if locally the burst rate keeps increasing with accretion.Comment: Accepted for publication on Ap

Can the UNAIDS modes of transmission model be improved? A comparison of the original and revised model projections using data from a setting in west Africa.

OBJECTIVE: The UNAIDS modes of transmission model (MoT) is a user-friendly model, developed to predict the distribution of new HIV infections among different subgroups. The model has been used in 29 countries to guide interventions. However, there is the risk that the simplifications inherent in the MoT produce misleading findings. Using input data from Nigeria, we compare projections from the MoT with those from a revised model that incorporates additional heterogeneity. METHODS: We revised the MoT to explicitly incorporate brothel and street-based sex-work, transactional sex, and HIV-discordant couples. Both models were parameterized using behavioural and epidemiological data from Cross River State, Nigeria. Model projections were compared, and the robustness of the revised model projections to different model assumptions, was investigated. RESULTS: The original MoT predicts 21% of new infections occur in most-at-risk-populations (MARPs), compared with 45% (40-75%, 95% Crl) once additional heterogeneity and updated parameterization is incorporated. Discordant couples, a subgroup previously not explicitly modelled, are predicted to contribute a third of new HIV infections. In addition, the new findings suggest that women engaging in transactional sex may be an important but previously less recognized risk group, with 16% of infections occurring in this subgroup. CONCLUSION: The MoT is an accessible model that can inform intervention priorities. However, the current model may be potentially misleading, with our comparisons in Nigeria suggesting that the model lacks resolution, making it challenging for the user to correctly interpret the nature of the epidemic. Our findings highlight the need for a formal review of the MoT

Measuring the neutron star equation of state using X-ray timing

One of the primary science goals of the next generation of hard X-ray timing instruments is to determine the equation of state of the matter at supranuclear densities inside neutron stars, by measuring the radius of neutron stars with different masses to accuracies of a few percent. Three main techniques can be used to achieve this goal. The first involves waveform modelling. The flux we observe from a hotspot on the neutron star surface offset from the rotational pole will be modulated by the star's rotation, giving rise to a pulsation. Information about mass and radius is encoded into the pulse profile via relativistic effects, and tight constraints on mass and radius can be obtained. The second technique involves characterising the spin distribution of accreting neutron stars. The most rapidly rotating stars provide a very clean constraint, since the mass-shedding limit is a function of mass and radius. However the overall spin distribution also provides a guide to the torque mechanisms in operation and the moment of inertia, both of which can depend sensitively on dense matter physics. The third technique is to search for quasi-periodic oscillations in X-ray flux associated with global seismic vibrations of magnetars (the most highly magnetized neutron stars), triggered by magnetic explosions. The vibrational frequencies depend on stellar parameters including the dense matter equation of state. We illustrate how these complementary X-ray timing techniques can be used to constrain the dense matter equation of state, and discuss the results that might be expected from a 10m$^2$ instrument. We also discuss how the results from such a facility would compare to other astronomical investigations of neutron star properties. [Modified for arXiv]Comment: To appear in Reviews of Modern Physics as a Colloquium, 23 pages, 9 figure

An adherent tissue-inspired hydrogel delivery vehicle utilised in primary human glioma models.

A physical hydrogel cross-linked via the host-guest interactions of cucurbit[8]uril and utilised as an implantable drug-delivery vehicle for the brain is described herein. Constructed from hyaluronic acid, this hydrogel is biocompatible and has a high water content of 98%. The mechanical properties have been characterised by rheology and compared with the modulus of human brain tissue demonstrating the production of a soft material that can be moulded into the cavity it is implanted into following surgical resection. Furthermore, effective delivery of therapeutic compounds and antibodies to primary human glioblastoma cell lines is showcased by a variety of in vitro and ex vivo viability and immunocytochemistry based assays.This work was supported by The Brain Tumour Charity (RG89672), the National Institute for Health Research Cambridge Biomedical Research Centre; the Higher Education Funding Council for England. We acknowledge the Human Research Tissue Bank and Biomedical Research Centre for the tissue being accessed through the Human Research Tissue Bank. The Human Research Tissue Bank is supported by the NIHR Cambridge Biomedical Research Centre. MJR thanks the University of Cambridge Chemical Biology and Molecular Medicine PhD Training Programme for funding. CCP is thankful for the support of the EPSRC and the Brain Tumour Charity for funding. JHM acknowledges the support of the Gates Cambridge Scholarship programme. AKK was supported by a studentship from the John and Lucille van Geest Foundation

Synergistic effects between analogs of DNA and RNA improve the potency of siRNA-mediated gene silencing

We report that combining a DNA analog (2′F-ANA) with rigid RNA analogs [2′F-RNA and/or locked nucleic acid (LNA)] in siRNA duplexes can produce gene silencing agents with enhanced potency. The favored conformations of these two analogs are different, and combining them in a 1–1 pattern led to reduced affinity, whereas alternating short continuous regions of individual modifications increased affinity relative to an RNA:RNA duplex. Thus, the binding affinity at key regions of the siRNA duplex could be tuned by changing the pattern of incorporation of DNA-like and RNA-like nucleotides. These heavily or fully modified duplexes are active against a range of mRNA targets. Effective patterns of modification were chosen based on screens using two sequences targeting firefly luciferase. We then applied the most effective duplex designs to the knockdown of the eIF4E binding proteins 4E-BP1 and 4E-BP2. We identified modified duplexes with potency comparable to native siRNA. Modified duplexes showed dramatically enhanced stability to serum nucleases, and were characterized by circular dichroism and thermal denaturation studies. Chemical modification significantly reduced the immunostimulatory properties of these siRNAs in human peripheral blood mononuclear cells

The relationship between lipoprotein A and other lipids with prostate cancer risk:A multivariable Mendelian randomisation study

BACKGROUND: Numerous epidemiological studies have investigated the role of blood lipids in prostate cancer (PCa) risk, though findings remain inconclusive to date. The ongoing research has mainly involved observational studies, which are often prone to confounding. This study aimed to identify the relationship between genetically predicted blood lipid concentrations and PCa. METHODS AND FINDINGS: Data for low-density lipoprotein (LDL) cholesterol, high-density lipoprotein (HDL) cholesterol, triglycerides (TG), apolipoprotein A (apoA) and B (apoB), lipoprotein A (Lp(a)), and PCa were acquired from genome-wide association studies in UK Biobank and the PRACTICAL consortium, respectively. We used a two-sample summary-level Mendelian randomisation (MR) approach with both univariable and multivariable (MVMR) models and utilised a variety of robust methods and sensitivity analyses to assess the possibility of MR assumptions violation. No association was observed between genetically predicted concentrations of HDL, TG, apoA and apoB, and PCa risk. Genetically predicted LDL concentration was positively associated with total PCa in the univariable analysis, but adjustment for HDL, TG, and Lp(a) led to a null association. Genetically predicted concentration of Lp(a) was associated with higher total PCa risk in the univariable (OR(weighted median) per standard deviation (SD) = 1.091; 95% CI 1.028 to 1.157; P = 0.004) and MVMR analyses after adjustment for the other lipid traits (OR(IVW) per SD = 1.068; 95% CI 1.005 to 1.134; P = 0.034). Genetically predicted Lp(a) was also associated with advanced (MVMR OR(IVW) per SD = 1.078; 95% CI 0.999 to 1.163; P = 0.055) and early age onset PCa (MVMR OR(IVW) per SD = 1.150; 95% CI 1.015,1.303; P = 0.028). Although multiple estimation methods were utilised to minimise the effect of pleiotropy, the presence of any unmeasured pleiotropy cannot be excluded and may limit our findings. CONCLUSIONS: We observed that genetically predicted Lp(a) concentrations were associated with an increased PCa risk. Future studies are required to understand the underlying biological pathways of this finding, as it may inform PCa prevention through Lp(a)-lowering strategies

Financing essential HIV services: a new economic agenda.

Anna Vassall and colleagues discuss the need for, and challenges facing, innovative and sustainable financing of the HIV response. Please see later in the article for the Editors' Summary

High frequency oscillations during magnetar flares

The recent discovery of high frequency oscillations during giant flares from the Soft Gamma Repeaters SGR 1806-20 and SGR 1900+14 may be the first direct detection of vibrations in a neutron star crust. If this interpretation is correct it offers a novel means of testing the neutron star equation of state, crustal breaking strain, and magnetic field configuration. We review the observational data on the magnetar oscillations, including new timing analysis of the SGR 1806-20 giant flare using data from the Ramaty High Energy Solar Spectroscopic Imager (RHESSI) and the Rossi X-ray Timing Explorer (RXTE). We discuss the implications for the study of neutron star structure and crust thickness, and outline areas for future investigation.Comment: 5 pages, 1 figure, to appear in the proceedings of the conference "Isolated Neutron Stars: from the Interior to the Surface" (April 2006, London), eds. D. Page, R. Turolla, & S. Zane, Astrophysics & Space Science in pres

Colloquium: Measuring the neutron star equation of state using x-ray timing

One of the primary science goals of the next generation of hard x-ray timing instruments is to determine the equation of state of matter at supranuclear densities inside neutron stars by measuring the radius of neutron stars with different masses to accuracies of a few percent. Three main techniques can be used to achieve this goal. The first involves waveform modeling. The flux observed from a hotspot on the neutron star surface offset from the rotational pole will be modulated by the star's rotation, and this periodic modulation at the spin frequency is called a pulsation. As the photons propagate through the curved spacetime of the star, information about mass and radius is encoded into the shape of the waveform (pulse profile) via special and general-relativistic effects. Using pulsations from known sources (which have hotspots that develop either during thermonuclear bursts or due to channeled accretion) it is possible to obtain tight constraints on mass and radius. The second technique involves characterizing the spin distribution of accreting neutron stars. A large collecting area enables highly sensitive searches for weak or intermittent pulsations (which yield spin) from the many accreting neutron stars whose spin rates are not yet known. The most rapidly rotating stars provide a clean constraint, since the limiting spin rate where the equatorial surface velocity is comparable to the local orbital velocity, at which mass shedding occurs, is a function of mass and radius. However, the overall spin distribution also provides a guide to the torque mechanisms in operation and the moment of inertia, both of which can depend sensitively on dense matter physics. The third technique is to search for quasiperiodic oscillations in x-ray flux associated with global seismic vibrations of magnetars (the most highly magnetized neutron stars), triggered by magnetic explosions. The vibrational frequencies depend on stellar parameters including the dense matter equation of state, and large-area x-ray timing instruments would provide much improved detection capability. An illustration is given of how these complementary x-ray timing techniques can be used to constrain the dense matter equation of state and the results that might be expected from a 10 m2 instrument are discussed. Also discussed are how the results from such a facility would compare to other astronomical investigations of neutron star properties