310 research outputs found

    Response of OH airglow emissions to the mesospheric gravity waves and its comparisons with full wave model simulation at a low latitude Indian station

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    Quasi-monochromatic gravity-wave-induced oscillations, monitored using the mesospheric OH airglow emission over Kolhapur (16.8° N, 74.2° E), India, during January to April 2010 and January to December 2011, have been characterized using the Krassovsky method. The nocturnal variability reveals prominent wave signatures with periods ranging from 5.2 to 10.8 h as the dominant nocturnal wave with embedded short-period waves having wave periods of 1.5–4.4 h. The results show that the magnitude of the Krassovsky parameter, viz. |η|, ranged from 2.1 to 10.2 h for principal or long nocturnal waves (5.2–10.8 h observed periods), and from 1.5 to 5.4 h for the short waves (1.5–4.4 h observed periods) during the years of 2010 and 2011, respectively. The phase (i.e., Φ) values of the Krassovsky parameters exhibited larger variability and varied from −8.1 to −167°. The deduced mean vertical wavelengths are found to be approximately −60.2 ± 20 and −42.8 ± 35 km for long- and short-period waves for the year 2010. Similarly, for 2011 the mean vertical wavelengths are found to be approximately −77.6 ± 30 and −59.2 ± 30 km for long and short wave periods, respectively, indicating that the observations over Kolhapur were dominated by upward-propagating waves. We use a full-wave model to simulate the response of OH emission to the wave motion and compare the results with observed values

    Salience-based selection: attentional capture by distractors less salient than the target

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    Current accounts of attentional capture predict the most salient stimulus to be invariably selected first. However, existing salience and visual search models assume noise in the map computation or selection process. Consequently, they predict the first selection to be stochastically dependent on salience, implying that attention could even be captured first by the second most salient (instead of the most salient) stimulus in the field. Yet, capture by less salient distractors has not been reported and salience-based selection accounts claim that the distractor has to be more salient in order to capture attention. We tested this prediction using an empirical and modeling approach of the visual search distractor paradigm. For the empirical part, we manipulated salience of target and distractor parametrically and measured reaction time interference when a distractor was present compared to absent. Reaction time interference was strongly correlated with distractor salience relative to the target. Moreover, even distractors less salient than the target captured attention, as measured by reaction time interference and oculomotor capture. In the modeling part, we simulated first selection in the distractor paradigm using behavioral measures of salience and considering the time course of selection including noise. We were able to replicate the result pattern we obtained in the empirical part. We conclude that each salience value follows a specific selection time distribution and attentional capture occurs when the selection time distributions of target and distractor overlap. Hence, selection is stochastic in nature and attentional capture occurs with a certain probability depending on relative salience

    Effective nebulization of interferon-γ using a novel vibrating mesh.

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    BACKGROUND: Interferon gamma (IFN-γ) is a clinically relevant immunomodulatory cytokine that has demonstrated significant potential in the treatment and management of respiratory diseases such as tuberculosis and pulmonary fibrosis. As with all large biomolecules, clinical translation is dependent on effective delivery to the disease site and delivery of IFN-γ as an aerosol offers a logical means of drug targeting. Effective localization is often hampered by instability and a lack of safe and efficient delivery systems. The present study sought to determine how effectively IFN-γ can be nebulized using two types of vibrating mesh nebulizer, each with differing mesh architectures, and to investigate the comparative efficiency of delivery of therapeutically active IFN-γ to the lungs. METHODS: Nebulization of IFN-γ was carried out using two different Aerogen vibrating mesh technologies with differing mesh architectures. These technologies represent both a standard commercially available mesh type (Aerogen Solo®) and a new iteration mesh (Photo-defined aperture plate (PDAP®). Extensive aerosol studies (aerosol output and droplet analysis, non-invasive and invasive aerosol therapy) were conducted in line with regulatory requirements and characterization of the stability and bioactivity of the IFN-γ post-nebulization was confirmed using SDS-PAGE and stimulation of Human C-X-C motif chemokine 10 (CXCL 10) also known as IFN-γ-induced protein 10KDa (IP 10) expression from THP-1 derived macrophages (THP-1 cells). RESULTS: Aerosol characterization studies indicated that a significant and reproducible dose of aerosolized IFN-γ can be delivered using both vibrating mesh technologies. Nebulization using both devices resulted in an emitted dose of at least 93% (100% dose minus residual volume) for IFN-γ. Characterization of aerosolized IFN-γ indicated that the PDAP was capable of generating droplets with a significantly lower mass median aerodynamic diameter (MMAD) with values of 2.79 ± 0.29 μm and 4.39 ± 0.25 μm for the PDAP and Solo respectively. The volume median diameters (VMD) of aerosolized IFN-γ corroborated this with VMDs of 2.33 ± 0.02 μm for the PDAP and 4.30 ± 0.02 μm for the Solo. SDS-PAGE gels indicated that IFN-γ remains stable after nebulization by both devices and this was confirmed by bioactivity studies using a THP-1 cell model in which an alveolar macrophage response to IFN-γ was determined. IFN-γ nebulized by the PDAP and Solo devices had no significant effect on the key inflammatory biomarker cytokine IP-10 release from this model in comparison to non-nebulized controls. Here we demonstrate that it is possible to combine IFN-γ with vibrating mesh nebulizer devices and facilitate effective aerosolisation with minimal impact on IFN-γ structure or bioactivity. CONCLUSIONS: It is possible to nebulize IFN-γ effectively with vibrating mesh nebulizer devices without compromising its stability. The PDAP allows for generation of IFN-γ aerosols with improved aerodynamic properties thereby increasing its potential efficiency for lower respiratory tract deposition over current technology, whilst maintaining the integrity and bioactivity of IFN-γ. This delivery modality therefore offers a rational means of facilitating the clinical translation of inhaled IFN-γ

    Corruption and bicameral reforms

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    During the last decade unicameral proposals have been put forward in fourteen US states. In this paper we analyze the effects of the proposed constitutional reforms, in a setting where decision making is subject to ‘hard time constraints’, and lawmakers face the opposing interests of a lobby and the electorate. We show that bicameralism might lead to a decline in the lawmakers’ bargaining power vis-a-vis the lobby, thus compromising their accountability to voters. Hence, bicameralism is not a panacea against the abuse of power by elected legislators and the proposed unicameral reforms could be effective in reducing corruption among elected representatives

    Molecular and Cellular Basis of Microvascular Perfusion Deficits Induced by Clostridium perfringens and Clostridium septicum

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    Reduced tissue perfusion leading to tissue ischemia is a central component of the pathogenesis of myonecrosis caused by Clostridium perfringens. The C. perfringens α-toxin has been shown capable of inducing these changes, but its potential synergy with perfringolysin O (θ-toxin) is less well understood. Similarly, Clostridium septicum is a highly virulent causative agent of spontaneous gas gangrene, but its effect on the microcirculation has not been examined. Therefore, the aim of this study was to use intravital microscopy to examine the effects of C. perfringens and C. septicum on the functional microcirculation, coupled with the use of isogenic toxin mutants to elucidate the role of particular toxins in the resultant microvascular perfusion deficits. This study represents the first time this integrated approach has been used in the analysis of the pathological response to clostridial toxins. Culture supernatants from wild-type C. perfringens induced extensive cell death within 30 min, as assessed by in vivo uptake of propidium iodide. Furthermore, significant reductions in capillary perfusion were observed within 60 min. Depletion of either platelets or neutrophils reduced the alteration in perfusion, consistent with a role for these blood-borne cells in obstructing perfusion. In addition, mutation of either the α-toxin or perfringolysin O structural genes attenuated the reduction in perfusion, a process that was reversed by genetic complementation. C. septicum also induced a marked reduction in perfusion, with the degree of microvascular compromise correlating with the level of the C. septicum α-toxin. Together, these data indicate that as a result of its ability to produce α-toxin and perfringolysin O, C. perfringens rapidly induces irreversible cellular injury and a marked reduction in microvascular perfusion. Since C. septicum induces a similar reduction in microvascular perfusion, it is postulated that this function is central to the pathogenesis of clostridial myonecrosis, irrespective of the causative bacterium

    Cross-sectional validation of the Aging Perceptions Questionnaire: a multidimensional instrument for assessing self-perceptions of aging

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    <p>Abstract</p> <p>Background</p> <p>Self-perceptions of aging have been implicated as independent predictors of functional disability and mortality in older adults. In spite of this, research on self-perceptions of aging is limited. One reason for this is the absence of adequate measures. Specifically, there is a need to develop a measure that is theoretically-derived, has good psychometric properties, and is multidimensional in nature. The present research seeks to address this need by adopting the Self-Regulation Model as a framework and using it to develop a comprehensive, multi-dimensional instrument for assessing self-perceptions of aging. This study describes the validation of this newly-developed instrument, the Aging Perceptions Questionnaire (APQ).</p> <p>Methods</p> <p>Participants were 2,033 randomly selected community-dwelling older (+65 yrs) Irish adults who completed the APQ alongside measures of physical and psychological health. The APQ assesses self-perceptions of aging along eight distinct domains or subscales; seven of these examine views about own aging, these are: timeline chronic, timeline cyclical, consequences positive, consequences negative, control positive, control negative, and emotional representations; the eighth domain is the identity domain and this examines the experience of health-related changes.</p> <p>Results</p> <p>Mokken scale analysis showed that the majority of items within the views about aging subscales were strongly scalable. Confirmatory factor analysis also indicated that the model provided a good fit for the data. Overall, subscales had good internal reliabilities. Hierarchical linear regression was conducted to investigate the independent contribution of APQ subscales to physical and psychological health and in doing so determine the construct validity of the APQ. Results showed that self-perceptions of aging were independently related to physical and psychological health. Mediation testing also supported a role for self-perceptions of aging as partial mediators in the relationship between indices of physical functioning and physical and psychological health outcomes.</p> <p>Conclusion</p> <p>Findings support the complex and multifaceted nature of the aging experience. The good internal reliability and construct validity of the subscales suggests that the APQ is a promising instrument that can enable a theoretically informed, multidimensional assessment of self-perceptions of aging. The potential role of self-perceptions of aging in facilitating physical and psychological health in later life is also highlighted.</p

    Cervico-vaginal immunoglobulin g levels increase post-ovulation independently of neutrophils

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    The prevalence of sexually transmitted infections (STIs) is often higher in females than in males. Although the reproductive cycle profoundly modulates local immunity in the female reproductive tract (FRT) system, significant gaps in our knowledge of the immunobiology of the FRT still exist. An intriguing and frequently observed characteristic of the FRT is the predominant presence of immunoglobulin (Ig) G in cervico-vaginal secretions. We show here that in the mouse, IgG accumulation was enhanced approximately 5-fold post-ovulation, and was accompanied by an influx of neutrophils into the FRT. To determine whether these two events were causally related, we performed short-term neutrophil depletion experiments at individual stages throughout the estrous cycle. Our results demonstrate that neutrophils were not necessary for cycle-dependent tissue remodeling and cycle progression and that cycle-dependent IgG accumulation occurred independent of neutrophils. We thus conclude that neutrophil influx and IgG accumulation are independent events that occur in the FRT during the reproductive cycle
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