On the stability of self-gravitating accreting flows

Analytic methods show stability of the stationary accretion of test fluids but they are inconclusive in the case of self-gravitating stationary flows. We investigate numerically stability of those stationary flows onto compact objects that are transonic and rich in gas. In all studied examples solutions appear stable. Numerical investigation suggests also that the analogy between sonic and event horizons holds for small perturbations of compact support but fails in the case of finite perturbations.Comment: 10 pages, accepted for publication in PR

General Relativistic versus Newtonian: a universality in radiation hydrodynamics

We compare Newtonian and general relativistic descriptions of the stationary accretion of self-gravitating fluids onto compact bodies. Spherical symmetry and thin gas approximation are assumed. Luminosity depends, amongst other factors, on the temperature and the contribution of gas to the total mass, in both -- general relativistic ($L_{GR}$) and Newtonian ($L_N$) -- models. We discover a remarkable universal behaviour for transonic flows: the ratio of respective luminosities $L_{GR}/L_N$ is independent of the fractional mass of the gas and depends on asymptotic temperature. It is close to 1 in the regime of low asymptotic temperatures and can grow by one order of magnitude for high temperatures. These conclusions are valid for a wide range of polytropic equations of state.Comment: 8 pages, 4 figure

Sox10 contributes to the balance of fate choice in dorsal root ganglion progenitors

The development of functional peripheral ganglia requires a balance of specification of both neuronal and glial components. In the developing dorsal root ganglia (DRGs), these compo- nents form from partially-restricted bipotent neuroglial precursors derived from the neural crest. Work in mouse and chick has identified several factors, including Delta/Notch signal- ing, required for specification of a balance of these components. We have previously shown in zebrafish that the Sry-related HMG domain transcription factor, Sox10, plays an unex- pected, but crucial, role in sensory neuron fate specification in vivo. In the same study we described a novel Sox10 mutant allele, sox10baz1, in which sensory neuron numbers are elevated above those of wild-types. Here we investigate the origin of this neurogenic pheno- type. We demonstrate that the supernumerary neurons are sensory neurons, and that enteric and sympathetic neurons are almost absent just as in classical sox10 null alleles; peripheral glial development is also severely abrogated in a manner similar to other sox10 mutant alleles. Examination of proliferation and apoptosis in the developing DRG reveals very low levels of both processes in wild-type and sox10baz1, excluding changes in the bal- ance of these as an explanation for the overproduction of sensory neurons. Using chemical inhibition of Delta-Notch-Notch signaling we demonstrate that in embryonic zebrafish, as in mouse and chick, lateral inhibition during the phase of trunk DRG development is required to achieve a balance between glial and neuronal numbers. Importantly, however, we show that this mechanism is insufficient to explain quantitative aspects of the baz1 phenotype. The Sox10(baz1) protein shows a single amino acid substitution in the DNA binding HMG domain; structural analysis indicates that this change is likely to result in reduced flexibility in the HMG domain, consistent with sequence-specific modification of Sox10 binding to DNA. Unlike other Sox10 mutant proteins, Sox10(baz1) retains an ability to drive neurogenin1 transcription. We show that overexpression of neurogenin1 is sufficient to produce supernu- merary DRG sensory neurons in a wild-type background, and can rescue the sensory neu- ron phenotype of sox10 morphants in a manner closely resembling the baz1 phenotype. We conclude that an imbalance of neuronal and glial fate specification results from the Sox10 (baz1) protein\u2019s unique ability to drive sensory neuron specification whilst failing to drive glial development. The sox10baz1 phenotype reveals for the first time that a Notch-dependent lat- eral inhibition mechanism is not sufficient to fully explain the balance of neurons and glia in the developing DRGs, and that a second Sox10-dependent mechanism is necessary. Sox10 is thus a key transcription factor in achieving the balance of sensory neuronal and glial fates

New interpretation of variational principles for gauge theories. I. Cyclic coordinate alternative to ADM split

I show how there is an ambiguity in how one treats auxiliary variables in gauge theories including general relativity cast as 3 + 1 geometrodynamics. Auxiliary variables may be treated pre-variationally as multiplier coordinates or as the velocities corresponding to cyclic coordinates. The latter treatment works through the physical meaninglessness of auxiliary variables' values applying also to the end points (or end spatial hypersurfaces) of the variation, so that these are free rather than fixed. [This is also known as variation with natural boundary conditions.] Further principles of dynamics workings such as Routhian reduction and the Dirac procedure are shown to have parallel counterparts for this new formalism. One advantage of the new scheme is that the corresponding actions are more manifestly relational. While the electric potential is usually regarded as a multiplier coordinate and Arnowitt, Deser and Misner have regarded the lapse and shift likewise, this paper's scheme considers new {\it flux}, {\it instant} and {\it grid} variables whose corresponding velocities are, respectively, the abovementioned previously used variables. This paper's way of thinking about gauge theory furthermore admits interesting generalizations, which shall be provided in a second paper.Comment: 11 page

Triangleland. I. Classical dynamics with exchange of relative angular momentum

In Euclidean relational particle mechanics, only relative times, relative angles and relative separations are meaningful. Barbour--Bertotti (1982) theory is of this form and can be viewed as a recovery of (a portion of) Newtonian mechanics from relational premises. This is of interest in the absolute versus relative motion debate and also shares a number of features with the geometrodynamical formulation of general relativity, making it suitable for some modelling of the problem of time in quantum gravity. I also study similarity relational particle mechanics (`dynamics of pure shape'), in which only relative times, relative angles and {\sl ratios of} relative separations are meaningful. This I consider firstly as it is simpler, particularly in 1 and 2 d, for which the configuration space geometry turns out to be well-known, e.g. S^2 for the `triangleland' (3-particle) case that I consider in detail. Secondly, the similarity model occurs as a sub-model within the Euclidean model: that admits a shape--scale split. For harmonic oscillator like potentials, similarity triangleland model turns out to have the same mathematics as a family of rigid rotor problems, while the Euclidean case turns out to have parallels with the Kepler--Coulomb problem in spherical and parabolic coordinates. Previous work on relational mechanics covered cases where the constituent subsystems do not exchange relative angular momentum, which is a simplifying (but in some ways undesirable) feature paralleling centrality in ordinary mechanics. In this paper I lift this restriction. In each case I reduce the relational problem to a standard one, thus obtain various exact, asymptotic and numerical solutions, and then recast these into the original mechanical variables for physical interpretation.Comment: Journal Reference added, minor updates to References and Figure

Foundations of Relational Particle Dynamics

Relational particle dynamics include the dynamics of pure shape and cases in which absolute scale or absolute rotation are additionally meaningful. These are interesting as regards the absolute versus relative motion debate as well as discussion of conceptual issues connected with the problem of time in quantum gravity. In spatial dimension 1 and 2 the relative configuration spaces of shapes are n-spheres and complex projective spaces, from which knowledge I construct natural mechanics on these spaces. I also show that these coincide with Barbour's indirectly-constructed relational dynamics by performing a full reduction on the latter. Then the identification of the configuration spaces as n-spheres and complex projective spaces, for which spaces much mathematics is available, significantly advances the understanding of Barbour's relational theory in spatial dimensions 1 and 2. I also provide the parallel study of a new theory for which positon and scale are purely relative but orientation is absolute. The configuration space for this is an n-sphere regardless of the spatial dimension, which renders this theory a more tractable arena for investigation of implications of scale invariance than Barbour's theory itself.Comment: Minor typos corrected; references update

Triangleland. II. Quantum Mechanics of Pure Shape

Relational particle models are of value in the absolute versus relative motion debate. They are also analogous to the dynamical formulation of general relativity, and as such are useful for investigating conceptual strategies proposed for resolving the problem of time in quantum general relativity. Moreover, to date there are few explicit examples of these at the quantum level. In this paper I exploit recent geometrical and classical dynamics work to provide such a study based on reduced quantization in the case of pure shape (no scale) in 2-d for 3 particles (triangleland) with multiple harmonic oscillator type potentials. I explore solutions for these making use of exact, asymptotic, perturbative and numerical methods. An analogy to the mathematics of the linear rigid rotor in a background electric field is useful throughout. I argue that further relational models are accessible by the methods used in this paper, and for specific uses of the models covered by this paper in the investigation of the problem of time (and other conceptual and technical issues) in quantum general relativity.Comment: Journal Reference added, minor updates to References and Figure

The genetics of blood pressure regulation and its target organs from association studies in 342,415 individuals

To dissect the genetic architecture of blood pressure and assess effects on target-organ damage, we analyzed 128,272 SNPs from targeted and genome-wide arrays in 201,529 individuals of European ancestry and genotypes from an additional 140,886 individuals were used for validation. We identified 66 blood pressure loci, of which 17 were novel and 15 harbored multiple distinct association signals. The 66 index SNPs were enriched for cis-regulatory elements, particularly in vascular endothelial cells, consistent with a primary role in blood pressure control through modulation of vascular tone across multiple tissues. The 66 index SNPs combined in a risk score showed comparable effects in 64,421 individuals of non-European descent. The 66-SNP blood pressure risk score was significantly associated with target-organ damage in multiple tissues, with minor effects in the kidney. Our findings expand current knowledge of blood pressure pathways and highlight tissues beyond the classic renal system in blood pressure regulation

New genetic loci link adipose and insulin biology to body fat distribution.

Body fat distribution is a heritable trait and a well-established predictor of adverse metabolic outcomes, independent of overall adiposity. To increase our understanding of the genetic basis of body fat distribution and its molecular links to cardiometabolic traits, here we conduct genome-wide association meta-analyses of traits related to waist and hip circumferences in up to 224,459 individuals. We identify 49 loci (33 new) associated with waist-to-hip ratio adjusted for body mass index (BMI), and an additional 19 loci newly associated with related waist and hip circumference measures (P < 5 × 10(-8)). In total, 20 of the 49 waist-to-hip ratio adjusted for BMI loci show significant sexual dimorphism, 19 of which display a stronger effect in women. The identified loci were enriched for genes expressed in adipose tissue and for putative regulatory elements in adipocytes. Pathway analyses implicated adipogenesis, angiogenesis, transcriptional regulation and insulin resistance as processes affecting fat distribution, providing insight into potential pathophysiological mechanisms

Quantitative temporal viromics: an approach to investigate host-pathogen interaction

A systematic quantitative analysis of temporal changes in host and viral proteins throughout the course of a productive infection could provide dynamic insights into virus-host interaction. We developed a proteomic technique called “quantitative temporal viromics” (QTV), which employs multiplexed tandem-mass-tag-based mass spectrometry. Human cytomegalovirus (HCMV) is not only an important pathogen but a paradigm of viral immune evasion. QTV detailed how HCMV orchestrates the expression of >8,000 cellular proteins, including 1,200 cell-surface proteins to manipulate signaling pathways and counterintrinsic, innate, and adaptive immune defenses. QTV predicted natural killer and T cell ligands, as well as 29 viral proteins present at the cell surface, potential therapeutic targets. Temporal profiles of >80% of HCMV canonical genes and 14 noncanonical HCMV open reading frames were defined. QTV is a powerful method that can yield important insights into viral infection and is applicable to any virus with a robust in vitro model