464 research outputs found

    Finite type approximations of Gibbs measures on sofic subshifts

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    Consider a H\"older continuous potential ϕ\phi defined on the full shift A^\nn, where AA is a finite alphabet. Let X\subset A^\nn be a specified sofic subshift. It is well-known that there is a unique Gibbs measure μϕ\mu_\phi on XX associated to ϕ\phi. Besides, there is a natural nested sequence of subshifts of finite type (Xm)(X_m) converging to the sofic subshift XX. To this sequence we can associate a sequence of Gibbs measures (μϕm)(\mu_{\phi}^m). In this paper, we prove that these measures weakly converge at exponential speed to μϕ\mu_\phi (in the classical distance metrizing weak topology). We also establish a strong mixing property (ensuring weak Bernoullicity) of μϕ\mu_\phi. Finally, we prove that the measure-theoretic entropy of μϕm\mu_\phi^m converges to the one of μϕ\mu_\phi exponentially fast. We indicate how to extend our results to more general subshifts and potentials. We stress that we use basic algebraic tools (contractive properties of iterated matrices) and symbolic dynamics.Comment: 18 pages, no figure

    Spatial, Temporal, and Habitat-Related Variation in Abundance of Pelagic Fishes in the Gulf of Mexico: Potential Implications of the Deepwater Horizon Oil Spill

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    Time-series data collected over a four-year period were used to characterize patterns of abundance for pelagic fishes in the northern Gulf of Mexico (GoM) before (2007-2009) and after (2010) the Deepwater Horizon oil spill. Four numerically dominant pelagic species (blackfin tuna, blue marlin, dolphinfish, and sailfish) were included in our assessment, and larval density of each species was lower in 2010 than any of the three years prior to the oil spill, although larval abundance in 2010 was often statistically similar to other years surveyed. To assess potential overlap between suitable habitat of pelagic fish larvae and surface oil, generalized additive models (GAMs) were developed to evaluate the influence of ocean conditions on the abundance of larvae from 2007-2009. Explanatory variables from GAMs were then linked to environmental data from 2010 to predict the probability of occurrence for each species. The spatial extent of surface oil overlapped with early life habitat of each species, possibly indicating that the availability of high quality habitat was affected by the DH oil spill. Shifts in the distribution of spawning adults is another factor known to influence the abundance of larvae, and the spatial occurrence of a model pelagic predator (blue marlin) was characterized over the same four-year period using electronic tags. The spatial extent of oil coincided with areas used by adult blue marlin from 2007-2009, and the occurrence of blue marlin in areas impacted by the DH oil spill was lower in 2010 relative to pre-spill years

    Effective-Range Expansion of the Neutron-Deuteron Scattering Studied by a Quark-Model Nonlocal Gaussian Potential

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    The S-wave effective range parameters of the neutron-deuteron (nd) scattering are derived in the Faddeev formalism, using a nonlocal Gaussian potential based on the quark-model baryon-baryon interaction fss2. The spin-doublet low-energy eigenphase shift is sufficiently attractive to reproduce predictions by the AV18 plus Urbana three-nucleon force, yielding the observed value of the doublet scattering length and the correct differential cross sections below the deuteron breakup threshold. This conclusion is consistent with the previous result for the triton binding energy, which is nearly reproduced by fss2 without reinforcing it with the three-nucleon force.Comment: 21 pages, 6 figures and 6 tables, submitted to Prog. Theor. Phy

    Pathways of cellular internalisation of liposomes delivered siRNA and effects on siRNA engagement with target mRNA and silencing in cancer cells

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    Design of an efficient delivery system is a generally recognised bottleneck in translation of siRNA technology into clinic. Despite research efforts, cellular processes that determine efficiency of siRNA silencing achieved by different delivery formulations remain unclear. Here, we investigated the mechanism(s) of cellular internalisation of a model siRNA-loaded liposome system in a correlation to the engagement of delivered siRNA with its target and consequent silencing by adopting siRNA molecular beacon technology. Probing of cellular internalisation pathways by a panel of pharmacological inhibitors indicated that clathrin-mediated (dynamin-dependent) endocytosis, macropinocytosis (dynamine independent), and cell membrane cholesterol dependent process(es) (clathrin and caveolea-independent) all play a role in the siRNA-liposomes internalization. The inhibition of either of these entry routes was, in general, mirrored by a reduction in the level of siRNA engagement with its target mRNA, as well as in a reduction of the target gene silencing. A dramatic increase in siRNA engagement with its target RNA was observed on disruption of endosomal membrane (by chloroquine), accompanied with an increased silencing. The work thus illustrates that employing molecular beacon siRNA technology one can start to assess the target RNA engagement – a stage between initial cellular internalization and final gene silencing of siRNA delivery systems

    Endocytic uptake, transport and macromolecular interactions of anionic PAMAM dendrimers within lung tissue

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    Purpose: Polyamidoamine (PAMAM) dendrimers are a promising class of nanocarrier with applications in both small and large molecule drug delivery. Here we report a comprehensive evaluation of the uptake and transport pathways that contribute to the lung disposition of dendrimers. Methods: Anionic PAMAM dendrimers and control dextran probes were applied to an isolated perfused rat lung (IPRL) model and lung epithelial monolayers. Endocytosis pathways were examined in primary alveolar epithelial cultures by confocal microscopy. Molecular interactions of dendrimers with protein and lipid lung fluid components were studied using small angle neutron scattering (SANS). Results: Dendrimers were absorbed across the intact lung via a passive, size-dependent transport pathway at rates slower than dextrans of similar molecular sizes. SANS investigations of concentration-dependent PAMAM transport in the IPRL confirmed no aggregation of PAMAMs with either albumin or dipalmitoylphosphatidylcholine lung lining fluid components. Distinct endocytic compartments were identified within primary alveolar epithelial cells and their functionality in the rapid uptake of fluorescent dendrimers and model macromolecular probes was confirmed by co-localisation studies. Conclusions: PAMAM dendrimers display favourable lung biocompatibility but modest lung to blood absorption kinetics. These data support the investigation of dendrimer-based carriers for controlled-release drug delivery to the deep lung

    Unified treatment algorithm for the management of crotaline snakebite in the United States: results of an evidence-informed consensus workshop

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    <p>Abstract</p> <p>Background</p> <p>Envenomation by crotaline snakes (rattlesnake, cottonmouth, copperhead) is a complex, potentially lethal condition affecting thousands of people in the United States each year. Treatment of crotaline envenomation is not standardized, and significant variation in practice exists.</p> <p>Methods</p> <p>A geographically diverse panel of experts was convened for the purpose of deriving an evidence-informed unified treatment algorithm. Research staff analyzed the extant medical literature and performed targeted analyses of existing databases to inform specific clinical decisions. A trained external facilitator used modified Delphi and structured consensus methodology to achieve consensus on the final treatment algorithm.</p> <p>Results</p> <p>A unified treatment algorithm was produced and endorsed by all nine expert panel members. This algorithm provides guidance about clinical and laboratory observations, indications for and dosing of antivenom, adjunctive therapies, post-stabilization care, and management of complications from envenomation and therapy.</p> <p>Conclusions</p> <p>Clinical manifestations and ideal treatment of crotaline snakebite differ greatly, and can result in severe complications. Using a modified Delphi method, we provide evidence-informed treatment guidelines in an attempt to reduce variation in care and possibly improve clinical outcomes.</p

    STAT3 Regulates Monocyte TNF-Alpha Production in Systemic Inflammation Caused by Cardiac Surgery with Cardiopulmonary Bypass

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    BACKGROUND: Cardiopulmonary bypass (CPB) surgery initiates a controlled systemic inflammatory response characterized by a cytokine storm, monocytosis and transient monocyte activation. However, the responsiveness of monocytes to Toll-like receptor (TLR)-mediated activation decreases throughout the postoperative course. The purpose of this study was to identify the major signaling pathway involved in plasma-mediated inhibition of LPS-induced tumor necrosis factor (TNF)-α production by monocytes. METHODOLOGY/PRINCIPAL FINDINGS: Pediatric patients that underwent CPB-assisted surgical correction of simple congenital heart defects were enrolled (n = 38). Peripheral blood mononuclear cells (PBMC) and plasma samples were isolated at consecutive time points. Patient plasma samples were added back to monocytes obtained pre-operatively for ex vivo LPS stimulations and TNF-α and IL-6 production was measured by flow cytometry. LPS-induced p38 mitogen-activated protein kinase (MAPK) and nuclear factor (NF)-κB activation by patient plasma was assessed by Western blotting. A cell-permeable peptide inhibitor was used to block STAT3 signaling. We found that plasma samples obtained 4 h after surgery, regardless of pre-operative dexamethasone treatment, potently inhibited LPS-induced TNF-α but not IL-6 synthesis by monocytes. This was not associated with attenuation of p38 MAPK activation or IκB-α degradation. However, abrogation of the IL-10/STAT3 pathway restored LPS-induced TNF-α production in the presence of suppressive patient plasma. CONCLUSIONS/SIGNIFICANCE: Our findings suggest that STAT3 signaling plays a crucial role in the downregulation of TNF-α synthesis by human monocytes in the course of systemic inflammation in vivo. Thus, STAT3 might be a potential molecular target for pharmacological intervention in clinical syndromes characterized by systemic inflammation

    Dynamics of coupled cell networks: synchrony, heteroclinic cycles and inflation

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    Copyright © 2011 Springer. The final publication is available at www.springerlink.comWe consider the dynamics of small networks of coupled cells. We usually assume asymmetric inputs and no global or local symmetries in the network and consider equivalence of networks in this setting; that is, when two networks with different architectures give rise to the same set of possible dynamics. Focussing on transitive (strongly connected) networks that have only one type of cell (identical cell networks) we address three questions relating the network structure to dynamics. The first question is how the structure of the network may force the existence of invariant subspaces (synchrony subspaces). The second question is how these invariant subspaces can support robust heteroclinic attractors. Finally, we investigate how the dynamics of coupled cell networks with different structures and numbers of cells can be related; in particular we consider the sets of possible “inflations” of a coupled cell network that are obtained by replacing one cell by many of the same type, in such a way that the original network dynamics is still present within a synchrony subspace. We illustrate the results with a number of examples of networks of up to six cells

    The psychic costs of migration: evidence from Irish return migrants

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    Within the economics literature, the 'psychic costs' of migration have been incorporated into theoretical models since Sjaastad (J Polit Econ 70:80 93, 1962). However, the existence of such costs has rarely been investigated in empirical papers. In this paper, we look at the psychic costs of migration by using alcohol problems as an indicator. Rather than comparing immigrants and natives, we look at the native-born in a single country and compare those who have lived away for a period of their lives and those who have not. We use data from the first wave of the Irish Longitudinal Study on Ageing which is a large, nationally representative sample of older Irish adults. We find that men who lived away are more likely to have suffered from alcohol problems than men who stayed. For women, we again see a higher incidence of alcohol problems for short-term migrants. However, long-term female migrants are less likely to have suffered from alcohol problems. For these women, it seems that migration provided psychic benefits, and this is consistent with findings fro
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