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

Diffusion on a heptagonal lattice

We study the diffusion phenomena on the negatively curved surface made up of congruent heptagons. Unlike the usual two-dimensional plane, this structure makes the boundary increase exponentially with the distance from the center, and hence the displacement of a classical random walker increases linearly in time. The diffusion of a quantum particle put on the heptagonal lattice is also studied in the framework of the tight-binding model Hamiltonian, and we again find the linear diffusion like the classical random walk. A comparison with diffusion on complex networks is also made.Comment: 5 pages, 6 figure

Mid-mantle deformation inferred from seismic anisotropy

With time, convective processes in the Earth's mantle will tend to align crystals, grains and inclusions. This mantle fabric is detectable seismologically, as it produces an anisotropy in material properties—in particular, a directional dependence in seismic-wave velocity. This alignment is enhanced at the boundaries of the mantle where there are rapid changes in the direction and magnitude of mantle flow, and therefore most observations of anisotropy are confined to the uppermost mantle or lithosphere and the lowermost-mantle analogue of the lithosphere, the D" region. Here we present evidence from shear-wave splitting measurements for mid-mantle anisotropy in the vicinity of the 660-km discontinuity, the boundary between the upper and lower mantle. Deep-focus earthquakes in the Tonga–Kermadec and New Hebrides subduction zones recorded at Australian seismograph stations record some of the largest values of shear-wave splitting hitherto reported. The results suggest that, at least locally, there may exist a mid-mantle boundary layer, which could indicate the impediment of flow between the upper and lower mantle in this region

Emergent Semiclassical Time in Quantum Gravity. I. Mechanical Models

Strategies intended to resolve the problem of time in quantum gravity by means of emergent or hidden timefunctions are considered in the arena of relational particle toy models. In situations with `heavy' and `light' degrees of freedom, two notions of emergent semiclassical WKB time emerge; these are furthermore equivalent to two notions of emergent classical `Leibniz--Mach--Barbour' time. I futhermore study the semiclassical approach, in a geometric phase formalism, extended to include linear constraints, and with particular care to make explicit those approximations and assumptions used. I propose a new iterative scheme for this in the cosmologically-motivated case with one heavy degree of freedom. I find that the usual semiclassical quantum cosmology emergence of time comes hand in hand with the emergence of other qualitatively significant terms, including back-reactions on the heavy subsystem and second time derivatives. I illustrate my analysis by taking it further for relational particle models with linearly-coupled harmonic oscillator potentials. As these examples are exactly soluble by means outside the semiclassical approach, they are additionally useful for testing the justifiability of some of the approximations and assumptions habitually made in the semiclassical approach to quantum cosmology. Finally, I contrast the emergent semiclassical timefunction with its hidden dilational Euler time counterpart.Comment: References Update

RIPK3-Dependent Recruitment of Low-Inflammatory Myeloid Cells Does Not Protect from Systemic Salmonella Infection

ABSTRACT Regulated macrophage death has emerged as an important mechanism to defend against intracellular pathogens. However, the importance and consequences of macrophage death during bacterial infection are poorly resolved. This is especially true for the recently described RIPK3-dependent lytic cell death, termed necroptosis. Salmonella enterica serovar Typhimurium is an intracellular pathogen that precisely regulates virulence expression within macrophages to evade and manipulate immune responses, which is a key factor in its ability to cause severe systemic infections. We combined genetic and pharmacological approaches to examine the importance of RIPK3 for S. Typhimurium-induced macrophage death using conditions that recapitulate bacterial gene expression during systemic infection in vivo. Our findings indicate that noninvasive S. Typhimurium does not naturally induce macrophage necroptosis but does so in the presence of pan-caspase inhibition. Moreover, our data suggest that RIPK3 induction (following caspase inhibition) does not impact host survival following S. Typhimurium infection, which differs from previous findings based on inert lipopolysaccharide (LPS) injections. Finally, although necroptosis is typically characterized as highly inflammatory, our data suggest that RIPK3 skews the peritoneal myeloid population away from an inflammatory profile to that of a classically noninflammatory profile. Collectively, these data improve our understanding of S. Typhimurium-macrophage interactions, highlight the possibility that purified bacterial components may not accurately recapitulate the complexity of host-pathogen interactions, and reveal a potential and unexpected role for RIPK3 in resolving inflammation. IMPORTANCE Macrophages employ multiple strategies to limit pathogen infection. For example, macrophages may undergo regulated cell death, including RIPK3-dependent necroptosis, as a means of combatting intracellular bacterial pathogens. However, bacteria have evolved mechanisms to evade or exploit immune responses. Salmonella is an intracellular pathogen that avoids and manipulates immune detection within macrophages. We examined the contribution of RIPK3 to Salmonella-induced macrophage death. Our findings indicate that noninvasive Salmonella does not naturally induce necroptosis, but it does so when caspases are inhibited. Moreover, RIPK3 induction (following caspase inhibition) does not impact host survival following Salmonella systemic infection. Finally, our data show that RIPK3 induction results in recruitment of low-inflammatory myeloid cells, which was unexpected, as necroptosis is typically described as highly inflammatory. Collectively, these data improve our understanding of pathogen-macrophage interactions, including outcomes of regulated cell death during infection in vivo, and reveal a potential new role for RIPK3 in resolving inflammation

The influence of anthropogenic nitrogen loading and meteorological conditions on the dynamics and toxicity of Alexandrium fundyense blooms in a New York (USA) estuary

Author Posting. © The Author(s), 2010. This is the author's version of the work. It is posted here by permission of Elsevier B.V. for personal use, not for redistribution. The definitive version was published in Harmful Algae 9 (2010): 402-412, doi:10.1016/j.hal.2010.02.003.The goal of this two-year study was to explore the role of nutrients and climatic conditions in promoting reoccurring Alexandrium fundyense blooms in the Northport-Huntington Bay complex, NY, USA. A bloom in 2007 was short and small (3 weeks, 103 cells L-1 maximal density) compared to 2008 when the A. fundyense bloom, which persisted for six weeks, achieved cell densities >106 cells L-1 and water column saxitoxin concentrations >2.4 x 104 pmol STX eq. L-1. During the 2008 bloom, both deployed mussels (used as indicator species) and wild soft shell clams became highly toxic (1,400 and 600μg STX eq./100g shellfish tissue, respectively) resulting in the closure of shellfish beds. The densities of benthic A. fundyense cysts at the onset of this bloom were four orders of magnitude lower than levels needed to account for observed cell densities, indicating in situ growth of vegetative cells was responsible for elevated bloom densities. Experimental enrichment of bloom water with nitrogenous compounds, particularly ammonium, significantly increased A. fundyense densities and particulate saxitoxin concentrations relative to unamended control treatments. The δ15N signatures (12 to 23‰) of particulate organic matter (POM) during blooms were similar to those of sewage (10 to 30‰) and both toxin and A. fundyense densities were significantly correlated with POM δ15N (p < 0.001). These findings suggest A. fundyense growth was supported by a source of wastewater such as the sewage treatment plant which discharges into Northport Harbor. Warmer than average atmospheric temperatures in the late winter and spring of 2008 and a cooler May contributed to an extended period of water column temperatures optimal for A. fundyense growth (12 – 20ºC), and thus may have also contributed toward the larger and longer bloom in 2008. Together this evidence suggests sewage-derived N loading and above average spring temperatures can promote intense and toxic A. fundyense blooms in estuaries.This work was supported by a grant from EPA’s Long Island Sound Study, New York Sea Grant, and the New York State Department of Environmental Conservation (to CJG) and from the NOAA Sea Grant Program (Grant No. NA06OAR4170021 (R/B-177)) to DMA

Congenital myasthenic syndrome in Golden Retrievers is associated with a novel COLQ mutation.

BackgroundCongenital myasthenic syndromes (CMSs) are a group of inherited disorders of neuromuscular transmission that may be presynaptic, synaptic, or postsynaptic. Causative mutations have been identified in 4 breeds including the Labrador Retriever, Jack Russell Terrier, Heideterrier, and Danish Pointing Dog.Hypothesis/objectiveClinical and genetic characterization of a neuromuscular disorder in Golden Retriever (GR) puppies.AnimalsFour GR puppies from California were evaluated for generalized muscle weakness beginning at weaning. Biological specimens were collected from the affected puppies, and familial information was obtained. Blood or buccal swabs were obtained from 63 unaffected GRs.MethodsComplete physical, neurological, electrodiagnostic, and histological evaluations and biochemical quantification of muscle acetylcholine receptors were performed. Polymerase chain reaction was used to amplify the 17 exons of COLQ, and sequences were obtained by Sanger sequencing. Variant frequency was assessed in unrelated GRs and a public database.ResultsClinical, neurological, and electrodiagnostic evaluations confirmed a disorder of neuromuscular transmission in a GR family. Sequencing of all exons and splice sites of a primary candidate gene, COLQ, identified a point mutation that predicts an amino acid substitution (G294R). The primary COLQ transcript was absent from affected muscle samples. All affected puppies were homozygous for the mutation, which was not detected outside this GR family or in other breeds.Conclusions and clinical importanceWe confirmed the diagnosis of a CMS in GR puppies and identified a novel COLQ mutation. The COLQ gene encodes the collagenous tail of acetylcholinesterase, the enzyme responsible for termination of skeletal muscle contraction by clearing acetylcholine at the neuromuscular junction. Clinicians and breeders should be aware of this CMS in GR puppies with an early onset of weakness

On Kaluza's sign criterion for reciprocal power series

T. Kaluza has given a criterion for the signs of the power series of a function that is the reciprocal of another power series. In this note the sharpness of this condition is explored and various examples in terms of the Gaussian hypergeometric series are given. A criterion for the monotonicity of the quotient of two power series due to M. Biernacki and J. Krzy\.z is applied.Comment: 13 page