Analysis of genotype effects for the immunosuppression via two-step method

This paper studies the main effects and interactive effects between genes on immunosuppression susceptibility caused by ultraviolet radiation in population of mice. We present a two-step strategy, i.e., we first establish one full linear model based on all main effects and interactive effects, and use the Dantzig selector method to screen the genotype effects preliminary; then via the idea of stepwise regression, under the other model we further detect the significant main effects and interactive effects for the UV-induced immunosuppression susceptibility. The most significant main effect site that we identified is D10Mit170, and the most significant interactive sites are D6Mit389 and D16Mit131

The pulsar force-free magnetosphere linked to its striped wind: time-dependent pseudo-spectral simulations

(abridged) Pulsar activity and its related radiation mechanism are usually explained by invoking some plasma processes occurring inside the magnetosphere. Despite many detailed local investigations, the global electrodynamics around those neutron stars remains poorly described. Better understanding of these compact objects requires a deep and accurate knowledge of their immediate electromagnetic surrounding within the magnetosphere and its link to the relativistic pulsar wind. The aim of this work is to present accurate solutions to the nearly stationary force-free pulsar magnetosphere and its link to the striped wind, for various spin periods and arbitrary inclination. To this end, the time-dependent Maxwell equations are solved in spherical geometry in the force-free approximation using a vector spherical harmonic expansion of the electromagnetic field. An exact analytical enforcement of the divergenceless of the magnetic part is obtained by a projection method. Special care has been given to design an algorithm able to look deeply into the magnetosphere with physically realistic ratios of stellar $R_*$ to light-cylinder \rlight radius. We checked our code against several analytical solutions, like the Deutsch vacuum rotator solution and the Michel monopole field. We also retrieve energy losses comparable to the magneto-dipole radiation formula and consistent with previous similar works. Finally, for arbitrary obliquity, we give an expression for the total electric charge of the system. It does not vanish except for the perpendicular rotator. This is due to the often ignored point charge located at the centre of the neutron star. It is questionable if such solutions with huge electric charges could exist in reality except for configurations close to an orthogonal rotator. The charge spread over the stellar crust is not a tunable parameter as is often hypothesized.Comment: 16 pages, 13 figures, accepted by MNRA

Introducing PHAEDRA: a new spectral code for simulations of relativistic magnetospheres

We describe a new scheme for evolving the equations of force-free electrodynamics, the vanishing-inertia limit of magnetohydrodynamics. This pseudospectral code uses global orthogonal basis function expansions to take accurate spatial derivatives, allowing the use of an unstaggered mesh and the complete force-free current density. The method has low numerical dissipation and diffusion outside of singular current sheets. We present a range of one- and two-dimensional tests, and demonstrate convergence to both smooth and discontinuous analytic solutions. As a first application, we revisit the aligned rotator problem, obtaining a steady solution with resistivity localised in the equatorial current sheet outside the light cylinder.Comment: 23 pages, 18 figures, accepted for publication in MNRA

Pharmacological depletion of RNA splicing factor RBM39 by indisulam synergizes with PARP inhibitors in high-grade serous ovarian carcinoma

Ovarian high-grade serous carcinoma (HGSC) is the most common subtype of ovarian cancer with limited therapeutic options and a poor prognosis. In recent years, poly-ADP ribose polymerase (PARP) inhibitors have demonstrated significant clinical benefits, especially in patients with BRCA1/2 mutations. However, acquired drug resistance and relapse is a major challenge. Indisulam (E7070) has been identified as a molecular glue that brings together splicing factor RBM39 and DCAF15 E3 ubiquitin ligase resulting in polyubiquitination, degradation, and subsequent RNA splicing defects. In this work, we demonstrate that the loss of RBM39 induces splicing defects in key DNA damage repair genes in ovarian cancer, leading to increased sensitivity to cisplatin and various PARP inhibitors. The addition of indisulam also improved olaparib response in mice bearing PARP inhibitor-resistant tumors. These findings demonstrate that combining RBM39 degraders and PARP inhibitors is a promising therapeutic approach to improve PARP inhibitor response in ovarian HGSC

Foundations of Black Hole Accretion Disk Theory

This review covers the main aspects of black hole accretion disk theory. We begin with the view that one of the main goals of the theory is to better understand the nature of black holes themselves. In this light we discuss how accretion disks might reveal some of the unique signatures of strong gravity: the event horizon, the innermost stable circular orbit, and the ergosphere. We then review, from a first-principles perspective, the physical processes at play in accretion disks. This leads us to the four primary accretion disk models that we review: Polish doughnuts (thick disks), Shakura-Sunyaev (thin) disks, slim disks, and advection-dominated accretion flows (ADAFs). After presenting the models we discuss issues of stability, oscillations, and jets. Following our review of the analytic work, we take a parallel approach in reviewing numerical studies of black hole accretion disks. We finish with a few select applications that highlight particular astrophysical applications: measurements of black hole mass and spin, black hole vs. neutron star accretion disks, black hole accretion disk spectral states, and quasi-periodic oscillations (QPOs).Comment: 91 pages, 23 figures, final published version available at http://www.livingreviews.org/lrr-2013-

Garden and landscape-scale correlates of moths of differing conservation status: significant effects of urbanization and habitat diversity

Moths are abundant and ubiquitous in vegetated terrestrial environments and are pollinators, important herbivores of wild plants, and food for birds, bats and rodents. In recent years, many once abundant and widespread species have shown sharp declines that have been cited by some as indicative of a widespread insect biodiversity crisis. Likely causes of these declines include agricultural intensification, light pollution, climate change, and urbanization; however, the real underlying cause(s) is still open to conjecture. We used data collected from the citizen science Garden Moth Scheme (GMS) to explore the spatial association between the abundance of 195 widespread British species of moth, and garden habitat and landscape features, to see if spatial habitat and landscape associations varied for species of differing conservation status. We found that associations with habitat and landscape composition were species-specific, but that there were consistent trends in species richness and total moth abundance. Gardens with more diverse and extensive microhabitats were associated with higher species richness and moth abundance; gardens near to the coast were associated with higher richness and moth abundance; and gardens in more urbanized locations were associated with lower species richness and moth abundance. The same trends were also found for species classified as increasing, declining and vulnerable under IUCN (World Conservation Union) criteria

Remote in vivo stress assessment of aquatic animals with microencapsulated biomarkers for environmental monitoring

Remote in vivo scanning of physiological parameters is a major trend in the development of new tools for the fields of medicine and animal physiology. For this purpose, a variety of implantable optical micro- and nanosensors have been designed for potential medical applications. At the same time, the important area of environmental sciences has been neglected in the development of techniques for remote physiological measurements. In the field of environmental monitoring and related research, there is a constant demand for new effective and quick techniques for the stress assessment of aquatic animals, and the development of proper methods for remote physiological measurements in vivo may significantly increase the precision and throughput of analyses in this field. In the present study, we apply pH-sensitive microencapsulated biomarkers to remotely monitor the pH of haemolymph in vivo in endemic amphipods from Lake Baikal, and we compare the suitability of this technique for stress assessment with that of common biochemical methods. For the first time, we demonstrate the possibility of remotely detecting a change in a physiological parameter in an aquatic organism under ecologically relevant stressful conditions and show the applicability of techniques using microencapsulated biomarkers for remote physiological measurements in environmental monitoring

Cadmium hyperaccumulation protects Thlaspi caerulescens from leaf feeding damage by thrips (Frankliniella occidentalis)

Metal hyperaccumulation has been proposed as a plant defensive strategy. Here, we investigated whether cadmium (Cd) hyperaccumulation protected Thlaspi caerulescens from leaf feeding damage by thrips (Frankliniella occidentalis). Two ecotypes differing in Cd accumulation, Ganges (high) and Prayon (low), were grown in compost amended with 0-1000 mg Cd kg(-1) in two experiments under glasshouse conditions. F-2 and F-3 plants from the Prayon x Ganges crosses were grown with 5 mg Cd kg(-1). Plants were naturally colonized by thrips and the leaf feeding damage index (LFDI) was assessed. The LFDI decreased significantly with increasing Cd in both ecotypes, and correlated with shoot Cd concentration in a log-linear fashion. Prayon was more attractive to thrips than Ganges, but the ecotypic difference in the LFDI was largely accounted for by the shoot Cd concentration. In the F-2 and F-3 plants, the LFDI correlated significantly and negatively with shoot Cd, but not with shoot zinc (Zn) or sulphur (S) concentrations. We conclude that Cd hyperaccumulation deters thrips from feeding on T. caerulescens leaves, which may offer an adaptive benefit to the plant

Comb-Based Radio-Frequency Photonic Filters with Rapid Tunability and High Selectivity

Photonic technologies have received considerable attention for enhancement of radio-frequency (RF) electrical systems, including high-frequency analog signal transmission, control of phased arrays, analog-to-digital conversion, and signal processing. Although the potential of radio-frequency photonics for implementation of tunable electrical filters over broad RF bandwidths has been much discussed, realization of programmable filters with highly selective filter lineshapes and rapid reconfigurability has faced significant challenges. A new approach for RF photonic filters based on frequency combs offers a potential route to simultaneous high stopband attenuation, fast tunability, and bandwidth reconfiguration. In one configuration tuning of the RF passband frequency is demonstrated with unprecedented (~40 ns) speed by controlling the optical delay between combs. In a second, fixed filter configuration, cascaded four-wave mixing simultaneously broadens and smoothes comb spectra, resulting in Gaussian RF filter lineshapes exhibiting extremely high (>60 dB) main lobe to sidelobe suppression ratio and (>70 dB) stopband attenuation.Comment: Updated the submission with the most recent version of the pape