411 research outputs found

    Fractional Hamiltonian type system on R\mathbb{R} with critical growth nonlinearity

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    This article investigates the existence and properties of ground state solutions to the following nonlocal Hamiltonian elliptic system: \begin{align*} \begin{cases} (-\Delta)^\frac12 u +V_0 u =g(v),~x\in \mathbb{R} (-\Delta)^\frac12 v +V_0 v =f(u),~x\in \mathbb{R}, \end{cases} \end{align*} where (Δ)12(-\Delta)^\frac12 is the square root Laplacian operator, V0>0V_0 >0 and f, gf,~g have critical exponential growth in R\mathbb{R}. Using minimization technique over some generalized Nehari manifold, we show that the set S\mathcal{S} of ground state solutions is non empty. Moreover for (u,v)S(u,v) \in \mathcal{S}, u, vu,~v are uniformly bounded in L(R)L^\infty(\mathbb{R}) and uniformly decaying at infinity. We also show that the set S\mathcal{S} is compact in H12(R)×H12(R)H^\frac12(\mathbb{R}) \times H^\frac12(\mathbb{R}) up to translations. Furthermore under locally lipschitz continuity of ff and gg we obtain a suitable Poho\v{z}aev type identity for any (u,v)S(u,v) \in \mathcal{S}. We deduce the existence of semi-classical ground state solutions to the singularly perturbed system \begin{align*} \begin{cases} \epsilon(-\Delta)^\frac12 \varphi +V(x) \varphi =g(\psi),~x\in \mathbb{R} \epsilon (-\Delta)^\frac12 \psi +V(x) \psi =f(\varphi),~x\in \mathbb{R}, \end{cases} \end{align*} where ϵ>0\epsilon>0 and VC(R)V \in C(\mathbb{R}) satisfy the assumption (V)(V) given below (see Section 1). Finally as ϵ0\epsilon \rightarrow 0, we prove the existence of minimal energy solutions which concentrate around the closest minima of the potential VV

    Abnormal Pain Sensation in Mice Lacking the Prokineticin Receptor PKR2: Interaction of PKR2 with Transient Receptor Potential TRPV1 and TRPA1

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    The amphibian Bv8 and the mammalian prokineticin 1 (PROK1) and 2 (PROK2) are new chemokine-like protein ligands acting on two G protein-coupled receptors, prokineticin receptor 1 (PKR1) and 2 (PKR2), participating to the mediation of diverse physiological and pathological processes. Prokineticins (PKs), specifically activating the prokineticin receptors (PKRs) located in several areas of the central and peripheral nervous system associated with pain, play a fundamental role in nociception. In this paper, to improve the understanding of the prokineticin system in the neurobiology of pain, we investigated the role of PKR2 in pain perception using pkr2 gene-deficient mice. We observed that, compared to wildtype, pkr2-null mice were more resistant to nociceptive sensitization to temperatures ranging from 46 to 48 \ub0C, to capsaicin and to protons, highlighting a positive interaction between PKR2 and the non-selective cation channels TRPV1. Moreover, PKR2 knock-out mice showed reduced nociceptive response to cold temperature (4 \ub0C) and to mustard oil-induced inflammatory hyperalgesia, suggesting a functional interaction between PKR2 and transient receptor potential ankyrin 1 ion (TRPA1) channels. This notion was supported by experiments in dorsal root ganglia (DRG) cultures from pkr1 and\u2013pkr2-null mice, demonstrating that the percentage of Bv8-responsive DRG neurons which were also responsive to mustard oil was much higher in PKR1 12/ 12 than in PKR2 12/ 12 mice. Taken together, these findings suggest a functional interaction between PKR2 and TRP channels in the development of hyperalgesia. Drugs able to directly or indirectly block these targets and/or their interactions may represent potential analgesics

    Effects of NSAIDs and paracetamol (acetaminophen) on protein kinase C epsilon translocation and on substance P synthesis and release in cultured sensory neurons.

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    Celecoxib, diclofenac, ibuprofen, and nimesulide are nonsteroidal anti-inflammatory drugs (NSAIDs) very commonly used for the treatment of moderate to mild pain, together with paracetamol (acetaminophen), a very widely used analgesic with a lesser anti-inflammatory effect. In the study reported here, we tested the efficacy of celecoxib, diclofenac, and ibuprofen on preprotachykinin mRNA synthesis, substance P (SP) release, prostaglandin E(2) (PGE(2)) release, and protein kinase C epsilon (PKC\u25b) translocation in rat cultured sensory neurons from dorsal root ganglia (DRGs). The efficacy of these NSAIDs was compared with the efficacy of paracetamol and nimesulide in in vitro models of hyperalgesia (investigated previously). While nimesulide and paracetamol, as in previous experiments, decreased the percentage of cultured DRG neurons showing translocation of PKC\u25b caused by 100 nM thrombin or 1 \u3bcM bradykinin in a dose-dependent manner, the other NSAIDs tested did not have a significant effect. The amount of SP released by peptidergic neurons and the expression level of preprotachykinin mRNA were assessed in basal conditions and after 70 minutes or 36 hours of stimulation with an inflammatory soup (IS) containing potassium chloride, thrombin, bradykinin, and endothelin-1. The release of SP at 70 minutes was inhibited only by nimesulide, while celecoxib and diclofenac were effective at 36 hours. The mRNA basal level of the SP precursor preprotachykinin expressed in DRG neurons was reduced only by nimesulide, while the increased levels expressed during treatment with the IS were significantly reduced by all drugs tested, with the exception of ibuprofen. All drugs were able to decrease basal and IS-stimulated PGE(2) release. Our study demonstrates novel mechanisms of action of commonly used NSAIDS

    Global Optimization-Based Calibration Algorithm for a 2D Distributed Hydrologic-Hydrodynamic and Water Quality Model

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    Hydrodynamic models with rain-on-the-grid capabilities are usually computationally expensive. This makes the use of automatic calibration algorithms hard to apply due to the large number of model runs. However, with the recent advances in parallel processing, computational resources, and increasing high-resolution climatologic and GIS data, high-resolution hydrodynamic models can be used for optimization-based calibration. This paper presents a global optimization-based algorithm to calibrate a fully distributed hydrologic-hydrodynamic and water quality model (HydroPol2D) using observed data (i.e., discharge, or pollutant concentration) as input. The algorithm can find a near-optimal set of parameters to explain observed gauged data. The modeling framework presented here, although applied in a poorly-gauged catchment, can be adapted for catchments with more detailed observations. We applied the algorithm in different cases of the V-Tilted Catchment, the Wooden-Board catchment, and in an existing urban catchment with heterogeneous data. The results of automatic calibration indicate NSE=0.99\mathrm{NSE} = 0.99 for the V-Tilted catchment, RMSE=830 mgL1\mathrm{RMSE} = 830~\mathrm{mgL^{-1}} for salt concentration pollutographs (i.e., 8.3% of the event mean concentration), and NSE=0.89\mathrm{NSE} = 0.89 for the urban catchment case study. This paper also explores the issue of equifinality in modeling calibration (EqMC). Equifinality is defined as the set of different parameter combinations that can provide equally good or accepted results, within the physical parameter ranges. EqMC decreases with the number of events and increases with the choice of partially or nonproducing runoff ones. Furthermore, results indicate that providing more accurate parameter ranges based on a priori knowledge of the catchment is fundamental to reduce the chances of finding a set of parameters with equifinality.Comment: Preprint submitted to Journal of Hydrolog

    Mobilidade e a rastreabilidade da ferrugem asiática da soja no Brasil.

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    A ferrugem asiática da soja, causada pelo fungo Phakopsora pachyrhizi possui fácil disseminação e pode causar perdas de 30% à 75% na produção. O monitoramento da ferrugem e sua identificação nos estádios iniciais são essenciais para um controle eficiente (YORINORI, 2005). Afim de permitir uma rápida visualização sobre a dispersão desta doença no Brasil, foi desenvolvida uma versão móvel para a plataforma iOS do sistema Web do Consórcio Antiferrugem. O usuário, com o uso do aplicativo em um iPhone, iPod Touch ou iPad, pode ter acesso às informações sobre a dispersão da doença diretamente no seu dispositivo, a qualquer hora e lugar, podendo perceber a aproximação dos focos da doença na sua região e adiantar-se na procura por sinais de infecção na sua lavoura, evitando grandes perdas na produção. O aplicativo traz como diferencial, além da sua mobilidade, a possibilidade de apresentação de informações completas sobre as ocorrências da doença, registradas por laboratórios conveniados ao consórcio. Permite, também, a rastreabilidade sobre a evolução da doença no decorrer das safras, apresentando pontos geolocalizados para os focos da doença. O aplicativo foi desenvolvido sob uma arquitetura de serviços disponíveis na plataforma Web do Consórcio Antiferrugem. Desde que foi disponibilizado, o aplicativo já foi baixado centenas de vezes por usuários do mundo todo, deixando claro o interesse pelas informações não só por produtores e técnicos brasileiros, mas também pelo mercado comprador de soja. Objetivando proporcionar maior agilidade na disseminação das informações, suporte a tecnologia push, para notificações automáticas, está sendo implementado e disponibilizado na loja de aplicativos da Apple (APPLE, 2011).SBIAGRO

    Protease activated receptors 1 and 4 sensitize TRPV1 in nociceptive neurones.

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    Protease-activated receptors (PAR1-4) are activated by proteases released by cell damage or blood clotting, and are known to be involved in promoting pain and hyperalgesia. Previous studies have shown that PAR2 receptors enhance activation of TRPV1 but the role of other PARs is less clear. In this paper we investigate the expression and function of the PAR1, 3 and 4 thrombin-activated receptors in sensory neurones. Immunocytochemistry and in situ hybridization show that PAR1 and PAR4 are expressed in 10 - 15% of neurons, distributed across all size classes. Thrombin or a specific PAR1 or PAR4 activating peptide (PAR1/4-AP) caused functional effects characteristic of activation of the PLCβ/PKC pathway: intracellular calcium release, sensitisation of TRPV1, and translocation of the epsilon isoform of PKC (PKCε) to the neuronal cell membrane. Sensitisation of TRPV1 was significantly reduced by PKC inhibitors. Neurons responding to thrombin or PAR1-AP were either small nociceptive neurones of the peptidergic subclass, or larger neurones which expressed markers for myelinated fibres. Sequential application of PAR1-AP and PAR4-AP showed that PAR4 is expressed in a subset of the PAR1-expressing neurons. Calcium responses to PAR2-AP were by contrast seen in a distinct population of small IB4+ nociceptive neurones. PAR3 appears to be non-functional in sensory neurones. In a skin-nerve preparation the release of the neuropeptide CGRP by heat was potentiated by PAR1-AP. Culture with nerve growth factor (NGF) increased the proportion of thrombin-responsive neurons in the IB4- population, while glial-derived neurotropic factor (GDNF) and neurturin upregulated the proportion of thrombin-responsive neurons in the IB4+ population. We conclude that PAR1 and PAR4 are functionally expressed in large myelinated fibre neurons, and are also expressed in small nociceptors of the peptidergic subclass, where they are able to potentiate TRPV1 activity.RIGHTS : This article is licensed under the BioMed Central licence at http://www.biomedcentral.com/about/license which is similar to the 'Creative Commons Attribution Licence'. In brief you may : copy, distribute, and display the work; make derivative works; or make commercial use of the work - under the following conditions: the original author must be given credit; for any reuse or distribution, it must be made clear to others what the license terms of this work are
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