Acidosis Is a Key Regulator of Osteoblast Ecto-Nucleotidase Pyrophosphatase/Phosphodiesterase 1 (NPP1) Expression and Activity

Previous work has shown that acidosis prevents bone nodule formation by osteoblasts in vitro by inhibiting mineralisation of the collagenous matrix. The ratio of phosphate (Pi) to pyrophosphate (PPi) in the bone microenvironment is a fundamental regulator of bone mineralisation. Both Pi and PPi, a potent inhibitor of mineralisation, are generated from extracellular nucleotides by the actions of ecto‐nucleotidases. This study investigated the expression and activity of ecto‐nucleotidases by osteoblasts under normal and acid conditions. We found that osteoblasts express mRNA for a number of ecto‐nucleotidases including NTPdase 1–6 (ecto‐nucleoside triphosphate diphosphohydrolase) and NPP1‐3 (ecto‐nucleotide pyrophosphatase/phosphodiesterase). The rank order of mRNA expression in differentiating rat osteoblasts (day 7) was Enpp1 > NTPdase 4 > NTPdase 6 > NTPdase 5 > alkaline phosphatase > ecto‐5‐nucleotidase > Enpp3 > NTPdase 1 > NTPdase 3 > Enpp2 > NTPdase 2. Acidosis (pH 6.9) upregulated NPP1 mRNA (2.8‐fold) and protein expression at all stages of osteoblast differentiation compared to physiological pH (pH 7.4); expression of other ecto‐nucleotidases was unaffected. Furthermore, total NPP activity was increased up to 53% in osteoblasts cultured in acid conditions (P < 0.001). Release of ATP, one of the key substrates for NPP1, from osteoblasts, was unaffected by acidosis. Further studies showed that mineralised bone formation by osteoblasts cultured from NPP1 knockout mice was increased compared with wildtypes (2.5‐fold, P < 0.001) and was partially resistant to the inhibitory effect of acidosis. These results indicate that increased NPP1 expression and activity might contribute to the decreased mineralisation observed when osteoblasts are exposed to acid conditions

Two-Dimensional Hydrodynamics of Pre-Core Collapse: Oxygen Shell Burning

By direct hydrodynamic simulation, using the Piecewise Parabolic Method (PPM) code PROMETHEUS, we study the properties of a convective oxygen burning shell in a SN 1987A progenitor star prior to collapse. The convection is too heterogeneous and dynamic to be well approximated by one-dimensional diffusion-like algorithms which have previously been used for this epoch. Qualitatively new phenomena are seen. The simulations are two-dimensional, with good resolution in radius and angle, and use a large (90-degree) slice centered at the equator. The microphysics and the initial model were carefully treated. Many of the qualitative features of previous multi-dimensional simulations of convection are seen, including large kinetic and acoustic energy fluxes, which are not accounted for by mixing length theory. Small but significant amounts of carbon-12 are mixed non-uniformly into the oxygen burning convection zone, resulting in hot spots of nuclear energy production which are more than an order of magnitude more energetic than the oxygen flame itself. Density perturbations (up to 8%) occur at the `edges' of the convective zone and are the result of gravity waves generated by interaction of penetrating flows into the stable region. Perturbations of temperature and electron fraction at the base of the convective zone are of sufficient magnitude to create angular inhomogeneities in explosive nucleosynthesis products, and need to be included in quantitative estimates of yields. Combined with the plume-like velocity structure arising from convection, the perturbations will contribute to the mixing of nickel-56 throughout supernovae envelopes. Runs of different resolution, and angular extent, were performed to test the robustness of theseComment: For mpeg movies of these simulations, see http://www.astrophysics.arizona.edu/movies.html Submitted to the Astrophysical Journa

Contestable adulthood: variability and disparity in markers for negotiating the transition to adulthood

Recent research has identified a discreet set of subjective markers that are seen as characterizing the transition to adulthood. The current study challenges this coherence by examining the disparity and variability in young people’s selection of such criteria. Four sentence-completion cues corresponding to four differentcontexts in which adult status might be contested were given to 156 British 16- to 17-year-olds. Their qualitative responses were analyzed to explore patterns whilst capturing some of their richness and diversity. An astonishing amount of variability emerged, both within and between cued contexts.The implications of this variability for how the transition to adulthood is experienced are explored. The argument is made that markers of the transition to adulthood are not merely reflective of the bio–psycho–social development of young people. Rather, adulthood here is seen as an essentially contested concept,located within the discursive interactional environment in which young people participate

Aseptic fluid transfer system

A method and means is provided, which permits the transfer of fluids between separate detached containers, in a manner which preserves the sterility of the fluids during and after their transfer

Modeling core collapse supernovae in 2 and 3 dimensions with spectral neutrino transport

The overwhelming evidence that the core collapse supernova mechanism is inherently multidimensional, the complexity of the physical processes involved, and the increasing evidence from simulations that the explosion is marginal presents great computational challenges for the realistic modeling of this event, particularly in 3 spatial dimensions. We have developed a code which is scalable to computations in 3 dimensions which couples PPM Lagrangian with remap hydrodynamics [1], multigroup, flux-limited diffusion neutrino transport [2], with many improvements), and a nuclear network [3]. The neutrino transport is performed in a ray-by-ray plus approximation wherein all the lateral effects of neutrinos are included (e.g., pressure, velocity corrections, advection) except the transport. A moving radial grid option permits the evolution to be carried out from initial core collapse with only modest demands on the number of radial zones. The inner part of the core is evolved after collapse along with the rest of the core and mantle by subcycling the lateral evolution near the center as demanded by the small Courant times. We present results of 2-D simulations of a symmetric and an asymmetric collapse of both a 15 and an 11 M progenitor. In each of these simulations we have discovered that once the oxygen rich material reaches the shock there is a synergistic interplay between the reduced ram pressure, the energy released by the burning of the shock heated oxygen rich material, and the neutrino energy deposition which leads to a revival of the shock and an explosion.Comment: 10 pages, 3 figure

Disparities in allele frequencies and population differentiation for 101 disease-associated single nucleotide polymorphisms between Puerto Ricans and Non-Hispanic Whites

BACKGROUND. Variations in gene allele frequencies can contribute to differences in the prevalence of some common complex diseases among populations. Natural selection modulates the balance in allele frequencies across populations. Population differentiation (FST) can evidence environmental selection pressures. Such genetic information is limited in Puerto Ricans, the second largest Hispanic ethnic group in the US, and a group with high prevalence of chronic disease. We determined allele frequencies and population differentiation for 101 single nucleotide polymorphisms (SNPs) in 30 genes involved in major metabolic and disease-relevant pathways in Puerto Ricans (n = 969, ages 45–75 years) and compared them to similarly aged non-Hispanic whites (NHW) (n = 597). RESULTS. Minor allele frequency (MAF) distributions for 45.5% of the SNPs assessed in Puerto Ricans were significantly different from those of NHW. Puerto Ricans carried risk alleles in higher frequency and protective alleles in lower frequency than NHW. Patterns of population differentiation showed that Puerto Ricans had SNPs with exceptional FST values in intronic, non-synonymous and promoter regions. NHW had exceptional FST values in intronic and promoter region SNPs only. CONCLUSION. These observations may serve to explain and broaden studies on the impact of gene polymorphisms on chronic diseases affecting Puerto Ricans.National Institutes of Health, National Institutes on Aging (P01AG02394, P01AG023394-SI); National Insitutes of Health (53-K06-5-10); US Department of Agriculture Research Service (58-1950-9-001, 58-1950-7-707); National Institutes of Health & Heart, Lung, and Blood Institute (U 01 HL72524, Genetic and Environmental Determinants of Triglycerides, HL54776

A Model For the Formation of High Density Clumps in Proto-Planetary Nebulae

The detection of NaCl at large radii in the Egg Nebula, CRL 2688, requires densities of 10^7 - 10^8 cm^-3 in a thick shell of r ~ a few X 10^17 cm. To explain these results, a mechanism is needed for producing high densities at a considerable distance from the central star. In two dimensional simulations of the interaction of the fast wind with an ambient medium, the material becomes thermally unstable. The resulting clumps can achieve the requisite conditions for NaCl excitation. We present 2D models with simple physics as proof-of-principle calculations to show that the clumping behavior is robust. Clumping is a natural outcome of cooling in the colliding wind model and comparable to that inferred from observations.Comment: 12 pages, 3 figures. Accepted for publication in the Astrophysical Journal Letter

Presupernova Structure of Massive Stars

Issues concerning the structure and evolution of core collapse progenitor stars are discussed with an emphasis on interior evolution. We describe a program designed to investigate the transport and mixing processes associated with stellar turbulence, arguably the greatest source of uncertainty in progenitor structure, besides mass loss, at the time of core collapse. An effort to use precision observations of stellar parameters to constrain theoretical modeling is also described.Comment: Proceedings for invited talk at High Energy Density Laboratory Astrophysics conference, Caltech, March 2010. Special issue of Astrophysics and Space Science, submitted for peer review: 7 pages, 3 figure

Computing and data processing

The applications of computers and data processing to astronomy are discussed. Among the topics covered are the emerging national information infrastructure, workstations and supercomputers, supertelescopes, digital astronomy, astrophysics in a numerical laboratory, community software, archiving of ground-based observations, dynamical simulations of complex systems, plasma astrophysics, and the remote control of fourth dimension supercomputers