375 research outputs found

    Caveolin-3 differentially orchestrates cholinergic and serotonergic constriction of murine airways

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    The mechanisms of controlling airway smooth muscle (ASM) tone are of utmost clinical importance as inappropriate constriction is a hallmark in asthma and chronic obstructive pulmonary disease. Receptors for acetylcholine and serotonin, two relevant mediators in this context, appear to be incorporated in specialized, cholesterol-rich domains of the plasma membrane, termed caveolae due to their invaginated shape. The structural protein caveolin-1 partly accounts for anchoring of these receptors. We here determined the role of the other major caveolar protein, caveolin-3 (cav-3), in orchestrating cholinergic and serotonergic ASM responses, utilizing newly generated cav-3 deficient mice. Cav-3 deficiency fully abrogated serotonin-induced constriction of extrapulmonary airways in organ baths while leaving intrapulmonary airways unaffected, as assessed in precision cut lung slices. The selective expression of cav-3 in tracheal, but not intrapulmonary bronchial epithelial cells, revealed by immunohistochemistry, might explain the differential effects of cav-3 deficiency on serotonergic ASM constriction. The cholinergic response of extrapulmonary airways was not altered, whereas a considerable increase was observed in cav-3â -/- intrapulmonary bronchi. Thus, cav-3 differentially organizes serotonergic and cholinergic signaling in ASM through mechanisms that are specific for airways of certain caliber and anatomical position. This may allow for selective and site-specific intervention in hyperreactive states

    Dispersion Effects in Nucleon Polarisabilities

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    We present a formalism to extract the dynamical nucleon polarisabilities defined via a multipole expansion of the structure amplitudes in nucleon Compton scattering. In contradistinction to the static polarisabilities, dynamical polarisabilities gauge the response of the internal degrees of freedom of a composed object to an external, real photon field of arbitrary energy. Being energy dependent, they therefore contain additional information about dispersive effects induced by internal relaxation mechanisms, baryonic resonances and meson production thresholds of the nucleon. We give explicit formulae to extract the dynamical electric and magnetic dipole as well as quadrupole polarisabilities from low energy nucleon Compton scattering up to the one pion production threshold and discuss the connection to the definition of static nucleon polarisabilities. As a concrete example, we examine the results of leading order Heavy Baryon Chiral Perturbation Theory for the four leading spin independent iso-scalar polarisabilities of the nucleon. Finally, we consider the possible r{\^o}le of energy dependent effects in low energy extractions of the iso-scalar dipole polarisabilities from Compton scattering on the deuteron.Comment: 17 pages LaTeX2e with 2 figures, using includegraphicx (5 .eps files). Minor corrections, references updated. Contents identical to version to appear in Phys. Rev. C 65, spelling differen

    Overview of the Nordic Seas CARINA data and salinity measurements

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    Water column data of carbon and carbon relevant hydrographic and hydrochemical parameters from 188 previously non-publicly available cruises in the Arctic, Atlantic, and Southern Ocean have been retrieved and merged into a new database: CARINA (CARbon IN the Atlantic). The data have been subject to rigorous quality control (QC) in order to ensure highest possible quality and consistency. The data for most of the parameters included were examined in order to quantify systematic biases in the reported values, i.e. secondary quality control. Significant biases have been corrected for in the data products, i.e. the three merged files with measured, calculated and interpolated values for each of the three CARINA regions; the Arctic Mediterranean Seas (AMS), the Atlantic (ATL) and the Southern Ocean (SO). With the adjustments the CARINA database is consistent both internally as well as with GLODAP (Key et al., 2004) and is suitable for accurate assessments of, for example, oceanic carbon inventories and uptake rates and for model validation. The Arctic Mediterranean Seas include the Arctic Ocean and the Nordic Seas, and the quality control was carried out separately in these two areas. This contribution provides an overview of the CARINA data from the Nordic Seas and summarises the findings of the QC of the salinity data. One cruise had salinity data that were of questionable quality, and these have been removed from the data product. An evaluation of the consistency of the quality controlled salinity data suggests that they are consistent to at least ±0.005

    Low-Energy Compton Scattering of Polarized Photons on Polarized Nucleons

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    The general structure of the cross section of γN\gamma N scattering with polarized photon and/or nucleon in initial and/or final state is systematically described and exposed through invariant amplitudes. A low-energy expansion of the cross section up to and including terms of order ω4\omega^4 is given which involves ten structure parameters of the nucleon (dipole, quadrupole, dispersion, and spin polarizabilities). Their physical meaning is discussed in detail. Using fixed-t dispersion relations, predictions for these parameters are obtained and compared with results of chiral perturbation theory. It is emphasized that Compton scattering experiments at large angles can fix the most uncertain of these structure parameters. Predictions for the cross section and double-polarization asymmetries are given and the convergence of the expansion is investigated. The feasibility of the experimental determination of some of the struture parameters is discussed.Comment: 41 pages of text, 9 figures; minor revisions prior to publication in Phys. Rev.

    Restriction of AID activity and somatic hypermutation by PARP-1

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    Affinity maturation of the humoral immune response depends on somatic hypermutation (SHM) of immunoglobulin (Ig) genes, which is initiated by targeted lesion introduction by activation-induced deaminase (AID), followed by error-prone DNA repair. Stringent regulation of this process is essential to prevent genetic instability, but no negative feedback control has been identified to date. Here we show that poly(ADP-ribose) polymerase-1 (PARP-1) is a key factor restricting AID activity during somatic hypermutation. Poly(ADP-ribose) (PAR) chains formed at DNA breaks trigger AID-PAR association, thus preventing excessive DNA damage induction at sites of AID action. Accordingly, AID activity and somatic hypermutation at the Ig variable region is decreased by PARP-1 activity. In addition, PARP-1 regulates DNA lesion processing by affecting strand biased A:T mutagenesis. Our study establishes a novel function of the ancestral genome maintenance factor PARP-1 as a critical local feedback regulator of both AID activity and DNA repair during Ig gene diversification

    The P_33(1232) resonance contribution into the amplitudes M_{1+}^{3/2},E_{1+}^{3/2},S_{1+}^{3/2} from an analysis of the p(e,e'p)\pi^0 data at Q^2 = 2.8, 3.2, and 4 (GeV/c)^2 within dispersion relation approach

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    Within the fixed-t dispersion relation approach we have analysed the TJNAF and DESY data on the exclusive p(e,e'p)\pi^0 reaction in order to find the P_{33}(1232) resonance contribution into the multipole amplitudes M_{1+}^{3/2},E_{1+}^{3/2},S_{1+}^{3/2}. As an input for the resonance and nonresonance contributions into these amplitudes the earlier obtained solutions of the integral equations which follow from dispersion relations are used. The obtained values of the ratio E2/M1 for the \gamma^* N \to P_{33}(1232) transition are: 0.039\pm 0.029, 0.121\pm 0.032, 0.04\pm 0.031 for Q^2= 2.8, 3.2, and 4 (GeV/c)^2, respectively. The comparison with the data at low Q^2 shows that there is no evidence for the presence of the visible pQCD contribution into the transition \gamma N \to P_{33}(1232) at Q^2=3-4 GeV^2. The ratio S_{1+}^{3/2}/M_{1+}^{3/2} for the resonance parts of multipoles is: -0.049\pm 0.029, -0.099\pm 0.041, -0.085\pm 0.021 for Q^2= 2.8, 3.2, and 4 (GeV/c)^2, respectively. Our results for the transverse form factor G_T(Q^2) of the \gamma^* N \to P_{33}(1232) transition are lower than the values obtained from the inclusive data. With increasing Q^2, Q^4G_T(Q^2) decreases, so there is no evidence for the presence of the pQCD contribution here too

    Compton scattering on the nucleon at intermediate energies and polarizabilities in a microscopic model

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    A microscopic calculation of Compton scattering on the nucleon is presented which encompasses the lowest energies -- yielding nucleon polarizabilities -- and extends to energies of the order of 600 MeV. We have used the covariant "Dressed K-Matrix Model" obeying the symmetry properties which are appropriate in the different energy regimes. In particular, crossing symmetry, gauge invariance and unitarity are satisfied. The extent of violation of analyticity (causality) is used as an expansion parameter.Comment: 35 pages, 15 figures, using REVTeX. Modified version to be published in Phys. Rev. C, more extensive comparison with data for Compton scattering, all results unchange

    Practices and values regarding milk consumption among pre-schoolers in Bangkok

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    Purpose: Thai government agencies and the business sector have been promoting milk consumption. Considering the robust and continual movements by those actors to promote milk consumption among children in Thailand at the national level, this study aims to investigate milk-consumption practices and values towards milk consumption at pre-school, family and individual levels. Methods: This cross-sectional qualitative study employs observation and interview methods, along with the Ecological System Theory as a framework. Data were collected from three kindergartens used by families of varying socio-economic status, and the homes of 18 pre-schoolers, aged 3-5 years old, attending these kindergartens, from October 2013-September 2014. Results: Findings reveal kindergartens implemented daily routines to make children drink milk. Practices at home include (i) overfeeding of milk, (ii) preference for fortified milk and (iii) using sweetness to make children drink milk. These practices were underpinned by values that milk is good for children and good parents feed their children milk. These values, in combination with other macro-level measures such as the government’s milk-promotion campaigns and the milk industry’s marketing, influence the milk-drinking practices of pre-schoolers. Conclusion: The promotion of the benefits of milk prompted children to exceed the recommended milk consumption of 400ml per day. Balanced information on moderation in milk drinking was absent

    The Self-Administered Witness Interview Tool (SAW-IT): Enhancing witness recall of workplace incidents

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    Given the often crucial role of witness evidence in Occupational Health and Safety investigation, statements should be obtained as soon as possible after an incident using best practice methods. The present research systematically tested the efficacy of a novel Self-Administered Witness Interview Tool (SAW-IT); an adapted version of the Self-Administered Interview (SAI©) designed to elicit comprehensive information from witnesses to industrial events. The present study also examined whether completing the SAW-IT mitigated the effect of schematic processing on witness recall. Results indicate that the SAW-IT elicited significantly more correct details, as well as more precise information than a traditional incident report form. Neither the traditional report from, nor the SAW-IT mitigated against biasing effects of contextual information about a worker’s safety history, confirming that witnesses should be shielded from extraneous post-event information prior to reporting. Importantly, these results demonstrate that the SAW-IT can enhance the quality of witness reports
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