45 research outputs found

    Inhibition of TGF-β Signaling and Decreased Apoptosis in IUGR-Associated Lung Disease in Rats

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    Intrauterine growth restriction is associated with impaired lung function in adulthood. It is unknown whether such impairment of lung function is linked to the transforming growth factor (TGF)-β system in the lung. Therefore, we investigated the effects of IUGR on lung function, expression of extracellular matrix (ECM) components and TGF-β signaling in rats. IUGR was induced in rats by isocaloric protein restriction during gestation. Lung function was assessed with direct plethysmography at postnatal day (P) 70. Pulmonary activity of the TGF-β system was determined at P1 and P70. TGF-β signaling was blocked in vitro using adenovirus-delivered Smad7. At P70, respiratory airway compliance was significantly impaired after IUGR. These changes were accompanied by decreased expression of TGF-β1 at P1 and P70 and a consistently dampened phosphorylation of Smad2 and Smad3. Furthermore, the mRNA expression levels of inhibitors of TGF-β signaling (Smad7 and Smurf2) were reduced, and the expression of TGF-β-regulated ECM components (e.g. collagen I) was decreased in the lungs of IUGR animals at P1; whereas elastin and tenascin N expression was significantly upregulated. In vitro inhibition of TGF-β signaling in NIH/3T3, MLE 12 and endothelial cells by adenovirus-delivered Smad7 demonstrated a direct effect on the expression of ECM components. Taken together, these data demonstrate a significant impact of IUGR on lung development and function and suggest that attenuated TGF-β signaling may contribute to the pathological processes of IUGR-associated lung disease

    Evidence-based Kernels: Fundamental Units of Behavioral Influence

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    This paper describes evidence-based kernels, fundamental units of behavioral influence that appear to underlie effective prevention and treatment for children, adults, and families. A kernel is a behavior–influence procedure shown through experimental analysis to affect a specific behavior and that is indivisible in the sense that removing any of its components would render it inert. Existing evidence shows that a variety of kernels can influence behavior in context, and some evidence suggests that frequent use or sufficient use of some kernels may produce longer lasting behavioral shifts. The analysis of kernels could contribute to an empirically based theory of behavioral influence, augment existing prevention or treatment efforts, facilitate the dissemination of effective prevention and treatment practices, clarify the active ingredients in existing interventions, and contribute to efficiently developing interventions that are more effective. Kernels involve one or more of the following mechanisms of behavior influence: reinforcement, altering antecedents, changing verbal relational responding, or changing physiological states directly. The paper describes 52 of these kernels, and details practical, theoretical, and research implications, including calling for a national database of kernels that influence human behavior

    The Influence of Niobium and Niobium-Titanium Grain Size on the Drawing Instability of Niobium Diffusion Barriers in Niobium-Titanium Wire

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    A major source of extrinsic limitation to the critical current density in Nb--Ti superconductors has been sausaging initiated by the formation of hard Cu--Ti--Nb intermetallics during heat treatment. Traditionally, a Nb diffusion barrier is wrapped around each Nb--Ti filament as a means of protection. However, a Nb barrier is permeable to both Ti and Cu and local thinning, caused by non-uniform deformation during wire reduction, can decrease the amount of protection provided by a given barrier. We have examined the effect of varying the initial microstructural condition of both the Nb barrier and the Nb--Ti rod. Monofilaments were fabricated and their barrier deformation characteristics measured as a function of strain. Results show that an increasing initial Nb or Nb--Ti grain size escalates the rate at which the coefficient of barrier thickness variation increases as a function of strain. In addition, the two grain sizes appear to combine additively in promoting non-uniform deformat..
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