Equation of state and opacities for hydrogen atmospheres of magnetars

The equation of state and radiative opacities of partially ionized, strongly magnetized hydrogen plasmas, presented in a previous paper [ApJ 585, 955 (2003), astro-ph/0212062] for the magnetic field strengths 8.e11 G < B < 3.e13 G, are extended to the field strengths 3.e13 G < B < 1.e15 G, relevant for magnetars. The first- and second-order thermodynamic functions and radiative opacities are calculated and tabulated for 5.e5 < T < 4.e7 K in a wide range of densities. We show that bound-free transitions give an important contribution to the opacities in the considered range of B in the outer neutron-star atmosphere layers. Unlike the case of weaker fields, bound-bound transitions are unimportant.Comment: 7 pages, 6 figures, LaTeX using emulateapj.cls (included). Accepted by Ap

HOX GENES: Seductive Science, Mysterious Mechanisms

HOX genes are evolutionarily highly conserved. The HOX proteins which they encode are master regulators of embryonic development and continue to be expressed throughout postnatal life. The 39 human HOX genes are located in four clusters (A-D) on different chromosomes at 7p15, 17q21.2, 12q13, and 2q31 respectively and are assumed to have arisen by duplication and divergence from a primordial homeobox gene. Disorders of limb formation, such as hand-foot-genital syndrome, have been traced to mutations in HOXA13 and HOXD13. Evolutionary conservation provides unlimited scope for experimental investigation of the functional control of the Hox gene network which is providing important insights into human disease. Chromosomal translocations involving the MLL gene, the human homologue of the Drosophila gene trithorax, create fusion genes which exhibit gain of function and are associated with aggressive leukaemias in both adults and children. To date 39 partner genes for MLL have been cloned from patients with leukaemia. Models based on specific translocations of MLL and individual HOX genes are now the subject of intense research aimed at understanding the molecular programs involved, and ultimately the design of chemotherapeutic agents for leukaemia. Investigation of the role of HOX genes in cancer has led to the concept that oncology may recapitulate ontology, a challenging postulate for experimentalists in view of the functional redundancy implicit in the HOX gene network

Teraflop per second gravitational lensing ray-shooting using graphics processing units

Gravitational lensing calculation using a direct inverse ray-shooting approach is a computationally expensive way to determine magnification maps, caustic patterns, and light-curves (e.g. as a function of source profile and size). However, as an easily parallelisable calculation, gravitational ray-shooting can be accelerated using programmable graphics processing units (GPUs). We present our implementation of inverse ray-shooting for the NVIDIA G80 generation of graphics processors using the NVIDIA Compute Unified Device Architecture (CUDA) software development kit. We also extend our code to multiple-GPU systems, including a 4-GPU NVIDIA S1070 Tesla unit. We achieve sustained processing performance of 182 Gflop/s on a single GPU, and 1.28 Tflop/s using the Tesla unit. We demonstrate that billion-lens microlensing simulations can be run on a single computer with a Tesla unit in timescales of order a day without the use of a hierarchical tree code.Comment: 21 pages, 4 figures, submitted to New Astronom

An exploratory search for z ≳ 6 quasars in the UKIDSS early data release

We conducted an exploratory search for quasars at z ~ 6-8, using the Early Data Release (EDR) from the United Kingdom Infrared Deep Sky Survey (UKIDSS) cross-matched to panoramic optical imagery. High-redshift quasar candidates are chosen using multi-color selection in i, z, Y, J, H, and K bands. After removal of apparent instrumental artifacts, our candidate list consisted of 34 objects. We further refined this list with deeper imaging in the optical for ten of our candidates. Twenty-five candidates were followed up spectroscopically in the near-infrared and in the optical. We confirmed 25 of our spectra as very low-mass main-sequence stars or brown dwarfs, which were indeed expected as the main contaminants of this exploratory search. The lack of quasar detection is not surprising: the estimated probability of finding a single z > 6 quasar down to the limit of UKIDSS in 27.3 deg^2 of the EDR is <5%. We find that the most important limiting factor in this work is the depth of the available optical data. Experience gained in this pilot project can help refine high-redshift quasar selection criteria for subsequent UKIDSS data releases

The First Measurement of Spectral Lines in a Short-Period Star Bound to the Galaxy's Central Black Hole: A Paradox of Youth

We have obtained the first detection of spectral absorption lines in one of the high-velocity stars in the vicinity of the Galaxy's central supermassive black hole. Both Brgamma (2.1661 micron) and He I (2.1126 micron) are seen in absorption in S0-2 with equivalent widths (2.8+-0.3 Ang & 1.7+-0.4 Ang) and an inferred stellar rotational velocity (220+-40 km/s) that are consistent with that of an O8-B0 dwarf, which suggests that it is a massive (~15 Msun), young (<10 Myr) main sequence star. This presents a major challenge to star formation theories, given the strong tidal forces that prevail over all distances reached by S0-2 in its current orbit (130 - 1900 AU) and the difficulty in migrating this star inward during its lifetime from further out where tidal forces should no longer preclude star formation. The radial velocity measurements (-510+-40 km/s) and our reported proper motions for S0-2 strongly constrain its orbit, providing a direct measure of the black hole mass of 4.1(+-0.6)x10^6(Ro/8kpc)^3 Msun. The Keplerian orbit parameters have uncertainities that are reduced by a factor of 2-3 compared to previously reported values and include, for the first time, an independent solution for the dynamical center; this location, while consistent with the nominal infrared position of Sgr A*, is localized to a factor of 5 more precisely (+-2 milli-arcsec). Furthermore, the ambiguity in the inclination of the orbit is resolved with the addition of the radial velocity measurement, indicating that the star is behind the black hole at the time of closest approach and counter-revolving against the Galaxy. With further radial velocity measurements in the next few years, the orbit of S0-2 will provide the most robust estimate of the distance to the Galactic Center.Comment: 14 pages, Latex, Accepted for Publication in ApJ Letter

Improving bone properties and fracture susceptibility: experimental models of genetic manipulation, pharmacologic intervention, and cellular perturbation reveal new approaches for improving bone health

poster abstractBone, a crucial support structure in the human body, is often taken for granted for its lightweight properties and unparalleled strength. Skeletal fracture is a major clinical condition affecting millions of Americans, which results from abnormal aging, hormonal imbalance, genetic conditions, and lifestyle choices (e.g., exercise). Because fractures are caused by a number of different factors, reducing fracture incidence requires a multifactorial approach to unraveling the underlying biology of bone metabolism, in order to discover new ways to improve bone properties and prevent fractures. We have taken such an approach by conducting (1) genetic manipulation experiments in mice, where genes predicted to be involved in bone mass regulation were mutated; (2) pharmacologic experiments to quantify the dose-response effect of an agent that inhibits bone loss, and (3) cell culture experiments, aimed at revealing molecular pathways activated by mechanical stimulation. METHODS: Mice with mutations in two genes, likely to regulate bone mass (SOST, DKK1) were generated and subjected to in vivo dual energy x-ray absorptiometry (DEXA) scans at 6-wk old. Whole body scans were analyzed for bone mineral density (BMD) using Lunar Piximus II v2.10 software. Mice (6-wk) were also dosed (0, 1, 10, 100, or 1000 mg/kg) with daily alendronate HCl, a bisphosphonate that inhibits osteoclast activity. Six wks later, the mice were sacrificed, and the femurs were dissected and sectioned for histological analysis of bone formation parameters, including mineralizing surface (MS/BS), mineral apposition rate (MAR), and bone formation rate (BFR/BS). To understand the cellular signaling events in response to mechanical loading, bone marrow mesenchymal stem cells (MSCs) were treated with 10, 20, 30, or 40μM PF7408671, an S6 kinase inhibitor. Cells then were subject to 100 cycles of biaxial mechanical strain (2%, 10 cycles/min). Protein lysates were separated by electrophoresis and probed for phosphorylation of Rictor and Akt by Western blot. RESULTS: Mice harboring mutations in either the SOST gene or the DKK1gene exhibited significantly increased BMD compared to wild-type control mice, though the SOST mutation had a stronger effect on BMD than DKK1. Mice with compound mutations (SOST and DKK1 mutations) had significantly greater BMD than mice with either single mutation, suggesting that inhibition of SOST and DKK1 might be an effective means to increase bone mass in patients susceptible to fracture. Mice treated with high-dose alendronate (100 or 1,000 mg/kg) exhibited significant decreases in bone formation parameters (MS/BS, MAR, and BFR/BS) compared to untreated (0 mg) mice, suggesting that while this compound might be beneficial for inhibiting bone loss, it also inhibits bone formation. The signaling hub, mTORC2, is a critical regulator of mechanical force in MSC progenitors. Our data demonstrate that S6 kinase is an upstream activator of mTORC2 in response to mechanical strain. CONCLUSION: Our experiments suggest that genetic manipulation of mice reveal viable protein targets (e.g., SOST, DKK1) that could ultimately be manipulated pharmacologically to improve bone mass. We also found that an FDA-approved class of drugs inhibits bone formation even at very low doses, suggesting that additional pro-anabolic compounds might benefit patients taking bisphosphonates. On a cell signaling level, we found that the mTORC2 pathway shows considerable promise for pharmacologic manipulation to simulate the effects of exercise. Taken together, these experiments highlight the utility of a broad approach to solving bone metabolism challenges that can affect fracture susceptibility

The effects of climatic fluctuations and extreme events on running water ecosystems

Most research on the effects of environmental change in freshwaters has focused on incremental changes in average conditions, rather than fluctuations or extreme events such as heatwaves, cold snaps, droughts, floods or wildfires, which may have even more profound consequences. Such events are commonly predicted to increase in frequency, intensity and duration with global climate change, with many systems being exposed to conditions with no recent historical precedent. We propose a mechanistic framework for predicting potential impacts of environmental fluctuations on running water ecosystems by scaling up effects of fluctuations from individuals to entire ecosystems. This framework requires integration of four key components: effects of the environment on individual metabolism, metabolic and biomechanical constraints on fluctuating species interactions, assembly dynamics of local food webs and mapping the dynamics of the meta-community onto ecosystem function. We illustrate the framework by developing a mathematical model of environmental fluctuations on dynamically assembling food webs. We highlight (currently limited) empirical evidence for emerging insights and theoretical predictions. For example, widely supported predictions about the effects of environmental fluctuations are: high vulnerability of species with high per capita metabolic demands such as large-bodied ones at the top of food webs; simplification of food web network structure and impaired energetic transfer efficiency; reduced resilience and top-down relative to bottom-up regulation of food web and ecosystem processes. We conclude by identifying key questions and challenges that need to be addressed to develop more accurate and predictive bio-assessments of the effects of fluctuations, and implications of fluctuations for management practices in an increasingly uncertain world

The X-ray Background and AGNs

Deep X-ray surveys have shown that the cosmic X-ray background (XRB) is largely due to the accretion onto supermassive black holes, integrated over the cosmic time. These surveys have resolved more than 80% of the 0.1-10 keV X-ray background into discrete sources. Optical spectroscopic identifications show that the sources producing the bulk of the X-ray background are a mixture of unobscured (type-1) and obscured (type-2) AGNs, as predicted by the XRB population synthesis models. A class of highly luminous type-2 AGN, so called QSO-2s, has been detected in the deepest Chandra and XMM-Newton surveys. The new Chandra AGN redshift distribution peaks at much lower redshifts (z~0.7) than that based on ROSAT data, and the new X-ray luminosity function indicates that the space density of Seyfert galaxies peaks at significantly lower redshifts than that of QSOs. It is shown here, that the low redshift peak applies both to absorbed and unabsorbed AGN and is also seen in the 0.5-2 keV band alone. Previous findings of a strong dependence of the fraction of type-2 AGN on luminosity are confirmed with better statistics here. Preliminary results from an 800 ksec XMM-Newton observation of the Lockman Hole are discussed.Comment: Proceedings of the conference: "The restless high energy universe", held in Amsterdam, May 2003. To be published in: Nucl. Physics B. Suppl. Ser., E.P.J. van den Heuvel, J.J.M. in 't Zand, and R.A.M.J. Wijers (eds.). 10 pages, 5 figure

Variable expression and silencing of CRISPR-Cas9 targeted transgenes identifies the AAVS1 locus as not an entirely safe harbour

Background: Diseases such as hypertrophic cardiomyopathy (HCM) can lead to severe outcomes including sudden death. The generation of human induced pluripotent stem cell (hiPSC) reporter lines can be useful for disease modelling and drug screening by providing physiologically relevant in vitro models of disease. The AAVS1 locus is cited as a safe harbour that is permissive for stable transgene expression, and hence is favoured for creating gene targeted reporter lines. Methods: We generated hiPSC reporters using a plasmid-based CRISPR/Cas9 nickase strategy. The first intron of PPP1R12C, the AAVS1 locus, was targeted with constructs expressing a genetically encoded calcium indicator (R-GECO1.0) or HOXA9-T2A-mScarlet reporter under the control of a pCAG or inducible pTRE promoter, respectively. Transgene expression was compared between clones before, during and/or after directed differentiation to mesodermal lineages. Results: Successful targeting to AAVS1 was confirmed by PCR and sequencing. Of 24 hiPSC clones targeted with pCAG-R-GECO1.0, only 20 expressed the transgene and in these, the percentage of positive cells ranged from 0% to 99.5%. Differentiation of a subset of clones produced cardiomyocytes, wherein the percentage of cells positive for R-GECO1.0 ranged from 2.1% to 93.1%. In the highest expressing R-GECO1.0 clones, transgene silencing occurred during cardiomyocyte differentiation causing a decrease in expression from 98.93% to 1.3%. In HOXA9-T2A-mScarlet hiPSC reporter lines directed towards mesoderm lineages, doxycycline induced a peak in transgene expression after two days but this reduced by up to ten-thousand-fold over the next 8-10 days. Nevertheless, for R-GECO1.0 lines differentiated into cardiomyocytes, transgene expression was rescued by continuous puromycin drug selection, which allowed the Ca 2+ responses associated with HCM to be investigated in vitro using single cell analysis. Conclusions: Targeted knock-ins to AAVS1 can be used to create reporter lines but variability between clones and transgene silencing requires careful attention by researchers seeking robust reporter gene expression

The influence of collective neutrino oscillations on a supernova r-process

Recently, it has been demonstrated that neutrinos in a supernova oscillate collectively. This process occurs much deeper than the conventional matter-induced MSW effect and hence may have an impact on nucleosynthesis. In this paper we explore the effects of collective neutrino oscillations on the r-process, using representative late-time neutrino spectra and outflow models. We find that accurate modeling of the collective oscillations is essential for this analysis. As an illustration, the often-used "single-angle" approximation makes grossly inaccurate predictions for the yields in our setup. With the proper multiangle treatment, the effect of the oscillations is found to be less dramatic, but still significant. Since the oscillation patterns are sensitive to the details of the emitted fluxes and the sign of the neutrino mass hierarchy, so are the r-process yields. The magnitude of the effect also depends sensitively on the astrophysical conditions - in particular on the interplay between the time when nuclei begin to exist in significant numbers and the time when the collective oscillation begins. A more definitive understanding of the astrophysical conditions, and accurate modeling of the collective oscillations for those conditions, is necessary.Comment: 27 pages, 10 figure