PDGFRA/NG2 glia generate new oligodendrocytes but few astrocytes in a murine EAE model of demyelinating disease

The adult mammalian brain and spinal cord contain glial precursors that express platelet-derived growth factor receptors (alpha subunit, PDGFRA) and the NG2 proteoglycan. These “NG2 cells” descend from oligodendrocyte precursors in the perinatal CNS and continue to generate myelinating oligodendrocytes in the grey and white matter of the postnatal brain. It has been proposed that NG2 cells can also generate reactive astrocytes at sites of CNS injury or demyelination. To test this we examined the fates of PDGFRA/ NG2 cells in the mouse spinal cord during experimental autoimmune encephalomyelitis (EAE) - a demyelinating condition that models some aspects of multiple sclerosis in humans. We administered tamoxifen to Pdgfra-CreERT2: Rosa26R-YFP mice in order to induce yellow fluorescent protein (YFP) expression in PDGFRA/ NG2 cells and their differentiated progeny. We subsequently induced EAE and observed a large (>4-fold) increase in the density of YFP+ cells, >90% of which were oligodendrocyte lineage cells. Many of these became CC1-positive, NG2-negative differentiated oligodendrocytes that expressed myelin markers CNP and Tmem10/ Opalin. PDGFRA/ NG2 cells generated very few GFAP+ reactive astrocytes (1-2% of all YFP+ cells) or NeuN+neurons (<0.02%). Thus, PDGFRA/ NG2 cells act predominantly as a reservoir of new oligodendrocytes in the demyelinated spinal cord

Generalized harmonic formulation in spherical symmetry

In this pedagogically structured article, we describe a generalized harmonic formulation of the Einstein equations in spherical symmetry which is regular at the origin. The generalized harmonic approach has attracted significant attention in numerical relativity over the past few years, especially as applied to the problem of binary inspiral and merger. A key issue when using the technique is the choice of the gauge source functions, and recent work has provided several prescriptions for gauge drivers designed to evolve these functions in a controlled way. We numerically investigate the parameter spaces of some of these drivers in the context of fully non-linear collapse of a real, massless scalar field, and determine nearly optimal parameter settings for specific situations. Surprisingly, we find that many of the drivers that perform well in 3+1 calculations that use Cartesian coordinates, are considerably less effective in spherical symmetry, where some of them are, in fact, unstable.Comment: 47 pages, 15 figures. v2: Minor corrections, including 2 added references; journal version

Origin of Life

The evolution of life has been a big enigma despite rapid advancements in the fields of biochemistry, astrobiology, and astrophysics in recent years. The answer to this puzzle has been as mind-boggling as the riddle relating to evolution of Universe itself. Despite the fact that panspermia has gained considerable support as a viable explanation for origin of life on the Earth and elsewhere in the Universe, the issue remains far from a tangible solution. This paper examines the various prevailing hypotheses regarding origin of life like abiogenesis, RNA World, Iron-sulphur World, and panspermia; and concludes that delivery of life-bearing organic molecules by the comets in the early epoch of the Earth alone possibly was not responsible for kick-starting the process of evolution of life on our planet.Comment: 32 pages, 8 figures,invited review article, minor additio

A critical reassessment of particle Dark Matter limits from dwarf satellites

Dwarf satellite galaxies are ideal laboratories for identifying particle Dark Matter signals. When setting limits on particle Dark Matter properties from null searches, it becomes however crucial the level at which the Dark Matter density profile within these systems is constrained by observations. In the limit in which the spherical Jeans equation is assumed to be valid for a given tracer stellar population, we study the solution of this equation having the Dark Matter mass profile as an output rather than as a trial parametric input. Within our new formulation, we address to what level dwarf spheroidal galaxies feature a reliable mass estimator. We assess then possible extrapolation of the density profiles in the inner regions and -- keeping explicit the dependence on the orbital anisotropy profile of the tracer population -- we derive general trends on the line-of-sight integral of the density profile squared, a quantity commonly dubbed J-factor and crucial to estimate fluxes from prompt Dark Matter pair annihilations. Taking Ursa Minor as a study case among Milky Way satellites, we perform Bayesian inference using the available kinematical data for this galaxy. Contrary to all previous studies, we avoid marginalization over quantities poorly constrained by observations or by theoretical arguments. We find minimal J-factors to be about 2 to 4 times smaller than commonly quoted estimates, approximately relaxing by the same amount the limit on Dark Matter pair annihilation cross section from gamma-ray surveys of Ursa Minor. At the same time, if one goes back to a fixed trial parametric form for the density, e.g. using a NFW or Burkert profile, we show that the minimal J can hardly be reduced by more than a factor of 1.5. \ua9 2016 IOP Publishing Ltd and Sissa Medialab srl

Neutral H density at the termination shock: a consolidation of recent results

We discuss a consolidation of determinations of the density of neutral interstellar H at the nose of the termination shock carried out with the use of various data sets, techniques, and modeling approaches. In particular, we focus on the determination of this density based on observations of H pickup ions on Ulysses during its aphelion passage through the ecliptic plane. We discuss in greater detail a novel method of determination of the density from these measurements and review the results from its application to actual data. The H density at TS derived from this analysis is equal to 0.087 \pm 0.022 cm-3, and when all relevant determinations are taken into account, the consolidated density is obtained at 0.09 \pm 0.022 cm-3. The density of H in CHISM based on literature values of filtration factor is then calculated at 0.16 \pm 0.04 cm-3.Comment: Submitted to Space Science Review

Towards Machine Wald

The past century has seen a steady increase in the need of estimating and predicting complex systems and making (possibly critical) decisions with limited information. Although computers have made possible the numerical evaluation of sophisticated statistical models, these models are still designed \emph{by humans} because there is currently no known recipe or algorithm for dividing the design of a statistical model into a sequence of arithmetic operations. Indeed enabling computers to \emph{think} as \emph{humans} have the ability to do when faced with uncertainty is challenging in several major ways: (1) Finding optimal statistical models remains to be formulated as a well posed problem when information on the system of interest is incomplete and comes in the form of a complex combination of sample data, partial knowledge of constitutive relations and a limited description of the distribution of input random variables. (2) The space of admissible scenarios along with the space of relevant information, assumptions, and/or beliefs, tend to be infinite dimensional, whereas calculus on a computer is necessarily discrete and finite. With this purpose, this paper explores the foundations of a rigorous framework for the scientific computation of optimal statistical estimators/models and reviews their connections with Decision Theory, Machine Learning, Bayesian Inference, Stochastic Optimization, Robust Optimization, Optimal Uncertainty Quantification and Information Based Complexity.Comment: 37 page

On the stability and uniqueness of the flow of a fluid through a porous medium

© 2016, The Author(s). In this short note, we study the stability of flows of a fluid through porous media that satisfies a generalization of Brinkman’s equation to include inertial effects. Such flows could have relevance to enhanced oil recovery and also to the flow of dense liquids through porous media. In any event, one cannot ignore the fact that flows through porous media are inherently unsteady, and thus, at least a part of the inertial term needs to be retained in many situations. We study the stability of the rest state and find it to be asymptotically stable. Next, we study the stability of a base flow and find that the flow is asymptotically stable, provided the base flow is sufficiently slow. Finally, we establish results concerning the uniqueness of the flow under appropriate conditions, and present some corresponding numerical results

MCMC implementation for Bayesian hidden semi-Markov models with illustrative applications

Copyright © Springer 2013. The final publication is available at Springer via http://dx.doi.org/10.1007/s11222-013-9399-zHidden Markov models (HMMs) are flexible, well established models useful in a diverse range of applications. However, one potential limitation of such models lies in their inability to explicitly structure the holding times of each hidden state. Hidden semi-Markov models (HSMMs) are more useful in the latter respect as they incorporate additional temporal structure by explicit modelling of the holding times. However, HSMMs have generally received less attention in the literature, mainly due to their intensive computational requirements. Here a Bayesian implementation of HSMMs is presented. Recursive algorithms are proposed in conjunction with Metropolis-Hastings in such a way as to avoid sampling from the distribution of the hidden state sequence in the MCMC sampler. This provides a computationally tractable estimation framework for HSMMs avoiding the limitations associated with the conventional EM algorithm regarding model flexibility. Performance of the proposed implementation is demonstrated through simulation experiments as well as an illustrative application relating to recurrent failures in a network of underground water pipes where random effects are also included into the HSMM to allow for pipe heterogeneity

Cytological changes related to Brucella canis variants uptake in vitro

In this study, evidence for in vitro uptake, invasion, and cytopathogonomic effects of normal and variant strains of B. canis on tissue culture, is presented. B. canis L-phase were penicillin-induced and these microorganisms produced revertants on penicillin-free media. Tissue culture (LLC-MK 2 ) cells were divided into different normal and variant-infected groups (I–IV), including controls. Bright-field and electron microscopic observations indicated uptake of all the strains and recognizable host cell damage (CPE) to varying degrees. At 72 h after infection, the extent of damage by L-phase was the least (55.5% CPE). The L-phase-derived revertants resulted in 80% damage; this approximates the adverse effect of normal B. canis (85%). In addition to these gross changes, various structural abnormalities, including pyknosis, nuclear disorganization, vacuolation, and karyorrhexis, were apparent. The implications of these findings and the indirect role of the L-phase in brucellosis due to B. canis are discussed.Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/47529/1/430_2005_Article_BF02123560.pd