The chiral and flavour projection of Dirac-Kahler fermions in the geometric discretization

It is shown that an exact chiral symmetry can be described for Dirac-Kahler fermions using the two complexes of the geometric discretization. This principle is extended to describe exact flavour projection and it is shown that this necessitates the introduction of a new operator and two new structures of complex. To describe simultaneous chiral and flavour projection, eight complexes are needed in all and it is shown that projection leaves a single flavour of chiral field on each.Comment: v2: 17 pages, Latex. 5 images eps. Added references, reformatted and clarification of some point

Movement of Red Snapper, Lutjanus campechanus, in the North Central Gulf of Mexico: Potential Effects of Hurricanes

Site fidelity and movement of red snapper, Lutjanus campechanus, were estimated from a tagging study conducted off the coast of Alabama from March 1995 to January 1997. Red snapper were caught using rod and reel over nine artificial reef sites, with three reefs each located at 21-m, 27-m, and 32-m depths. During the study, 1,604 fish were tagged, and 174 recaptures were made of 167 individuals. On 4 October 1995, the eye of Hurricane Opal passed within 40 km of the artificial reef sites. When recaptures were stratified according to whether or not they were at liberty during Opal, storm effect was the most significant factor in predicting the likelihood of movement and magnitude of movement by tagged red snapper. Eighty percent of recaptured red snapper that were not at liberty during Opal were recaptured at their site of release. Fish that were at liberty during Opal, however, had a significantly higher likelihood of movement away from their site of release (P \u3c 0.001). These fish also moved significantly further than those that were not at liberty during Opal (P \u3c 0.001). Fish that were at liberty during Opal moved a mean distance (± SE) of 32.6 km (± 6.81), compared to a mean distance (± SE) of 2.5 km (± 1.10) for fish that were tagged and recaptured before Opal, and a mean distance (± SE) of 1.7 km (± 0.43) for fish that were tagged and recaptured after Opal. Heretofore, it has generally been accepted that adult red snapper demonstrate strong site fidelity and genetic homogeneity in the stock was hypothesized to result from larval drift or due to historic mixing on longer time scales. This study documents movement of adult red snapper on spatial scales that would facilitate stock mixing and implicates large-scale climatic events, such as hurricanes, as important factors in stock mixing dynamics

Differential transactivation of sphingosine-1-phosphate receptors modulates NGF-induced neurite extension

The process of neurite extension after activation of the TrkA tyrosine kinase receptor by nerve growth factor (NGF) involves complex signaling pathways. Stimulation of sphingosine kinase 1 (SphK1), the enzyme that phosphorylates sphingosine to form sphingosine-1-phosphate (S1P), is part of the functional TrkA signaling repertoire. In this paper, we report that in PC12 cells and dorsal root ganglion neurons, NGF translocates SphK1 to the plasma membrane and differentially activates the S1P receptors S1P1 and S1P2 in a SphK1-dependent manner, as determined with specific inhibitors and small interfering RNA targeted to SphK1. NGF-induced neurite extension was suppressed by down-regulation of S1P1 expression with antisense RNA. Conversely, when overexpressed in PC12 cells, transactivation of S1P1 by NGF markedly enhanced neurite extension and stimulation of the small GTPase Rac, important for the cytoskeletal changes required for neurite extension. Concomitantly, differentiation down-regulated expression of S1P2 whose activation would stimulate Rho and inhibit neurite extension. Thus, differential transactivation of S1P receptors by NGF regulates antagonistic signaling pathways that modulate neurite extension

Statistics of selectively neutral genetic variation

Random models of evolution are instrumental in extracting rates of microscopic evolutionary mechanisms from empirical observations on genetic variation in genome sequences. In this context it is necessary to know the statistical properties of empirical observables (such as the local homozygosity for instance). Previous work relies on numerical results or assumes Gaussian approximations for the corresponding distributions. In this paper we give an analytical derivation of the statistical properties of the local homozygosity and other empirical observables assuming selective neutrality. We find that such distributions can be very non-Gaussian.Comment: 4 pages, 4 figure

Genomic signatures of population decline in the malaria mosquito Anopheles gambiae

Population genomic features such as nucleotide diversity and linkage disequilibrium are expected to be strongly shaped by changes in population size, and might therefore be useful for monitoring the success of a control campaign. In the Kilifi district of Kenya, there has been a marked decline in the abundance of the malaria vector Anopheles gambiae subsequent to the rollout of insecticide-treated bed nets. To investigate whether this decline left a detectable population genomic signature, simulations were performed to compare the effect of population crashes on nucleotide diversity, Tajima's D, and linkage disequilibrium (as measured by the population recombination parameter ρ). Linkage disequilibrium and ρ were estimated for An. gambiae from Kilifi, and compared them to values for Anopheles arabiensis and Anopheles merus at the same location, and for An. gambiae in a location 200 km from Kilifi. In the first simulations ρ changed more rapidly after a population crash than the other statistics, and therefore is a more sensitive indicator of recent population decline. In the empirical data, linkage disequilibrium extends 100-1000 times further, and ρ is 100-1000 times smaller, for the Kilifi population of An. gambiae than for any of the other populations. There were also significant runs of homozygosity in many of the individual An. gambiae mosquitoes from Kilifi. These results support the hypothesis that the recent decline in An. gambiae was driven by the rollout of bed nets. Measuring population genomic parameters in a small sample of individuals before, during and after vector or pest control may be a valuable method of tracking the effectiveness of interventions

Fluoromycobacteriophages for rapid, specific, and sensitive antibiotic susceptibility testing of Mycobacterium tuberculosis

Rapid antibiotic susceptibility testing of Mycobacterium tuberculosis is of paramount importance as multiple- and extensively- drug resistant strains of M. tuberculosis emerge and spread. We describe here a virus-based assay in which fluoromycobacteriophages are used to deliver a GFP or ZsYellow fluorescent marker gene to M. tuberculosis, which can then be monitored by fluorescent detection approaches including fluorescent microscopy and flow cytometry. Pre-clinical evaluations show that addition of either Rifampicin or Streptomycin at the time of phage addition obliterates fluorescence in susceptible cells but not in isogenic resistant bacteria enabling drug sensitivity determination in less than 24 hours. Detection requires no substrate addition, fewer than 100 cells can be identified, and resistant bacteria can be detected within mixed populations. Fluorescence withstands fixation by paraformaldehyde providing enhanced biosafety for testing MDR-TB and XDR-TB infections. © 2009 Piuri et al

Early Stage Drug Treatment that Normalizes Proinflammatory Cytokine Production Attenuates Synaptic Dysfunction in a Mouse Model that Exhibits Age-Dependent Progression of Alzheimer\u27s Disease-Related Pathology

Overproduction of proinflammatory cytokines in the CNS has been implicated as a key contributor to pathophysiology progression in Alzheimer\u27s disease (AD), and extensive studies with animal models have shown that selective suppression of excessive glial proinflammatory cytokines can improve neurologic outcomes. The prior art, therefore, raises the logical postulation that intervention with drugs targeting dysregulated glial proinflammatory cytokine production might be effective disease-modifying therapeutics if used in the appropriate biological time window. To test the hypothesis that early stage intervention with such drugs might be therapeutically beneficial, we examined the impact of intervention with MW01-2-151SRM (MW-151), an experimental therapeutic that selectively attenuates proinflammatory cytokine production at low doses. MW-151 was tested in an APP/PS1 knock-in mouse model that exhibits increases in AD-relevant pathology progression with age, including increases in proinflammatory cytokine levels. Drug was administered during two distinct but overlapping therapeutic time windows of early stage pathology development. MW-151 treatment attenuated the increase in microglial and astrocyte activation and proinflammatory cytokine production in the cortex and yielded improvement in neurologic outcomes, such as protection against synaptic protein loss and synaptic plasticity impairment. The results also demonstrate that the therapeutic time window is an important consideration in efficacy studies of drugs that modulate glia biological responses involved in pathology progression and suggest that such paradigms should be considered in the development of new therapeutic regimens that seek to delay the onset or slow the progression of AD

Key aerodynamic technologies for aircraft engine nacelles

Customer requirements and vision in aerospace dictate that the next generation of civil transport aircraft should have a strong emphasis on increased safety, reduced environmental impact and reduced cost without sacrificing performance. In this context, the School of Mechanical and Aerospace Engineering at the Queen's University of Belfast and Bombardier have, in recent years, been conducting research into some of the key aerodynamic technologies for the next generation of aircraft engine nacelles. Investigations have been performed into anti-icing technology, efficient thrust reversal, engine fire zone safety, life cycle cost and integration of the foregoing with other considerations in engine and aircraft design. A unique correlation for heat transfer in an anti-icing system has been developed. The effect of normal vibration on heat transfer in such systems has been found to be negligible. It has been shown that carefully designed natural blockage thrust reversers without a cascade can reduce aircraft weight with only a small sacrifice in the reversed thrust. A good understanding of the pressure relief doors and techniques to improve the performance of such doors have been developed. Trade off studies between aerodynamics, manufacturing and assembly of engine nacelles have shown the potential for a significant reduction in life cycle cost

Regulation of cell survival by sphingosine-1-phosphate receptor S1P1 via reciprocal ERK-dependent suppression of bim and PI-3-kinase/protein kinase C-mediated upregulation of Mcl-1

Although the ability of bioactive lipid sphingosine-1-phosphate (S1P) to positively regulate anti-apoptotic/pro-survival responses by binding to S1P1 is well known, the molecular mechanisms remain unclear. Here we demonstrate that expression of S1P1 renders CCL39 lung fibroblasts resistant to apoptosis following growth factor withdrawal. Resistance to apoptosis was associated with attenuated accumulation of pro-apoptotic BH3-only protein Bim. However, although blockade of extracellular signal-regulated kinase (ERK) activation could reverse S1P1-mediated suppression of Bim accumulation, inhibition of caspase-3 cleavage was unaffected. Instead S1P1-mediated inhibition of caspase-3 cleavage was reversed by inhibition of phosphatidylinositol-3-kinase (PI3K) and protein kinase C (PKC), which had no effect on S1P1 regulation of Bim. However, S1P1 suppression of caspase-3 was associated with increased expression of anti-apoptotic protein Mcl-1, the expression of which was also reduced by inhibition of PI3K and PKC. A role for the induction of Mcl-1 in regulating endogenous S1P receptor-dependent pro-survival responses in human umbilical vein endothelial cells was confirmed using S1P receptor agonist FTY720-phosphate (FTY720P). FTY720P induced a transient accumulation of Mcl-1 that was associated with a delayed onset of caspase-3 cleavage following growth factor withdrawal, whereas Mcl-1 knockdown was sufficient to enhance caspase-3 cleavage even in the presence of FTY720P. Consistent with a pro-survival role of S1P1 in disease, analysis of tissue microarrays from ER+ breast cancer patients revealed a significant correlation between S1P1 expression and tumour cell survival. In these tumours, S1P1 expression and cancer cell survival were correlated with increased activation of ERK, but not the PI3K/PKB pathway. In summary, pro-survival/anti-apoptotic signalling from S1P1 is intimately linked to its ability to promote the accumulation of pro-survival protein Mcl-1 and downregulation of pro-apoptotic BH3-only protein Bim via distinct signalling pathways. However, the functional importance of each pathway is dependent on the specific cellular context

Phylogenetic Codivergence Supports Coevolution of Mimetic Heliconius Butterflies

The unpalatable and warning-patterned butterflies _Heliconius erato_ and _Heliconius melpomene_ provide the best studied example of mutualistic Müllerian mimicry, thought – but rarely demonstrated – to promote coevolution. Some of the strongest available evidence for coevolution comes from phylogenetic codivergence, the parallel divergence of ecologically associated lineages. Early evolutionary reconstructions suggested codivergence between mimetic populations of _H. erato_ and _H. melpomene_, and this was initially hailed as the most striking known case of coevolution. However, subsequent molecular phylogenetic analyses found discrepancies in phylogenetic branching patterns and timing (topological and temporal incongruence) that argued against codivergence. We present the first explicit cophylogenetic test of codivergence between mimetic populations of _H. erato_ and _H. melpomene_, and re-examine the timing of these radiations. We find statistically significant topological congruence between multilocus coalescent population phylogenies of _H. erato_ and _H. melpomene_, supporting repeated codivergence of mimetic populations. Divergence time estimates, based on a Bayesian coalescent model, suggest that the evolutionary radiations of _H. erato_ and _H. melpomene_ occurred over the same time period, and are compatible with a series of temporally congruent codivergence events. This evidence supports a history of reciprocal coevolution between Müllerian co-mimics characterised by phylogenetic codivergence and parallel phenotypic change