988 resultados para 748
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(-)-CGP12177 is a non-conventional partial agonist that causes modest and transient increases of contractile force in human atrial trabeculae (Kaumann and Molenaar, 2008). These effects are markedly increased and maintained by inhibition of phosphodiesterase PDE3. As verified with recombinant receptors, the cardiostimulant effect of (-)-CGP12177 is mediated through a site at the beta1-adrenoceptor with lower affinity (beta1LAR) compared to the site through which (-)-CGP12177 antagonizes the effects of catecholamines (beta1HAR). However, in a recent report it was proposed that the positive inotropic effects of CGP12177 are mediated through beta3-adrenoceptors (Skeberdis et al 2008). We therefore investigated whether the effects of (-)-CGP12177 on human atrial trabeculae are antagonized by the beta3-adrenoceptor-selective antagonist L-748,337 (1 microM). (-)-CGP12177 (200 nM) caused a stable increase in force which was significantly reduced by the addition of (-)-bupranolol (1 microM), P = 0.002, (basal 4.45 ± 0.78 mN, IBMX (PDE inhibitor) 5.47 ± 1.01 mN, (-)-CGP12177 9.34 ± 1.33 mN, (-)-bupranolol 5.79 ± 1.08 mN, n = 6) but not affected by the addition of L-748,337 (1 microM), P = 0.12, (basal 4.48 ± 1.32 mN, IBMX 7.15 ± 2.28 mN, (-)-CGP12177 12.51 ± 3.71 mN, L-748,337 10.90 ± 3.49 mN, n = 6). Cumulative concentration-effect curves for (-)-CGP12177 were not shifted to the right by L-748,337 (1 microM). The –logEC50M values of (-)-CGP12177 in the absence and presence of L-748,337 were 7.21±0.09 and 7.41±0.13, respectively (data from 25 trabeculae from 8 patients, P=0.2) The positive inotropic effects of (-)-CGP12177 (IBMX present) were not antagonized by L-748,337 but were blunted by (-)-bupranolol (1 microM). The results rule out an involvement of beta3-adrenoceptors in the positive inotropic effects (-)-CGP12177 in human right atrial myocardium and are consistent with mediation through beta1LAR. Kaumann A and Molenaar P (2008) Pharmacol Ther 118, 303-336 Skeberdis VA et al (2008) J Clin Invest, 118, 3219-3227
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BACKGROUND AND PURPOSE It has been proposed that BRL37344, SR58611 and CGP12177 activate b3-adrenoceptors in human atrium to increase contractility and L-type Ca2+ current (ICa-L). b3-adrenoceptor agonists are potentially beneficial for the treatment of a variety of diseases but concomitant cardiostimulation would be potentially harmful. It has also been proposed that (-)-CGP12177 activates the low affinity binding site of the b1-adrenoceptor in human atrium. We therefore used BRL37344, SR58611 and (-)-CGP12177 with selective b-adrenoceptor subtype antagonists to clarify cardiostimulant b-adrenoceptor subtypes in human atrium. EXPERIMENTAL APPROACH Human right atrium was obtained from patients without heart failure undergoing coronary artery bypass or valve surgery. Cardiomyocytes were prepared to test BRL37344, SR58611 and CGP12177 effects on ICa-L. Contractile effects were determined on right atrial trabeculae. KEY RESULTS BRL37344 increased force which was antagonized by blockade of b1- and b2-adrenoceptors but not by blockade of b3-adrenoceptors with b3-adrenoceptor-selective L-748,337 (1 mM). The b3-adrenoceptor agonist SR58611 (1 nM–10 mM) did not affect atrial force. BRL37344 and SR58611 did not increase ICa-L at 37°C, but did at 24°C which was prevented by L-748,337. (-)-CGP12177 increased force and ICa-L at both 24°C and 37°C which was prevented by (-)-bupranolol (1–10 mM), but not L-748,337. CONCLUSIONS AND IMPLICATIONS We conclude that the inotropic responses to BRL37344 are mediated through b1- and b2-adrenoceptors. The inotropic and ICa-L responses to (-)-CGP12177 are mediated through the low affinity site b1L-adrenoceptor of the b1-adrenoceptor. b3-adrenoceptor-mediated increases in ICa-L are restricted to low temperatures. Human atrial b3-adrenoceptors do not change contractility and ICa-L at physiological temperature.
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The electron collection efficiency in dye-sensitized solar cells (DSCs) is usually related to the electron diffusion length, L = (Dτ)1/2, where D is the diffusion coefficient of mobile electrons and τ is their lifetime, which is determined by electron transfer to the redox electrolyte. Analysis of incident photon-to-current efficiency (IPCE) spectra for front and rear illumination consistently gives smaller values of L than those derived from small amplitude methods. We show that the IPCE analysis is incorrect if recombination is not first-order in free electron concentration, and we demonstrate that the intensity dependence of the apparent L derived by first-order analysis of IPCE measurements and the voltage dependence of L derived from perturbation experiments can be fitted using the same reaction order, γ ≈ 0.8. The new analysis presented in this letter resolves the controversy over why L values derived from small amplitude methods are larger than those obtained from IPCE data.
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A basic element in advertising strategy is the choice of an appeal. In business-to-business (B2B) marketing communication, a long-standing approach relies on literal and factual, benefit-laden messages. Given the highly complex, costly and involved processes of business purchases, such approaches are certainly understandable. This project challenges the traditional B2B approach and asks if an alternative approach—using symbolic messages that operate at a more intrinsic or emotional level—is effective in the B2B arena. As an alternative to literal (factual) messages, there is an emerging body of literature that asserts stronger, more enduring results can be achieved through symbolic messages (imagery or text) in an advertisement. The present study contributes to this stream of research. From a theoretical standpoint, the study explores differences in literal-symbolic message content in B2B advertisements. There has been much discussion—mainly in the consumer literature—on the ability of symbolic messages to motivate a prospect to process advertising information by necessitating more elaborate processing and comprehension. Business buyers are regarded as less receptive to indirect or implicit appeals because their purchase decisions are based on direct evidence of product superiority. It is argued here, that these same buyers may be equally influenced by advertising that stimulates internally-directed motivation, feelings and cognitions about the brand. Thus far, studies on the effect of literalism and symbolism are fragmented, and few focus on the B2B market. While there have been many studies about the effects of symbolism no adequate scale exists to measure the continuum of literalism-symbolism. Therefore, a first task for this study was to develop such a scale. Following scale development, content analysis of 748 B2B print advertisements was undertaken to investigate whether differences in literalism-symbolism led to higher advertising performance. Variations of time and industry were also measured. From a practical perspective, the results challenge the prevailing B2B practice of relying on literal messages. While definitive support was not established for the use of symbolic message content, literal messages also failed to predict advertising performance. If the ‘fact, benefit laden’ assumption within B2B advertising cannot be supported, then other approaches used in the business-to-consumer (B2C) sector, such as symbolic messages may be also appropriate in business markets. Further research will need to test the potential effects of such messages, thereby building a revised foundation that can help drive advances in B2B advertising. Finally, the study offers a contribution to the growing body of knowledge on symbolism in advertising. While the specific focus of the study relates to B2B advertising, the Literalism-Symbolism scale developed here provides a reliable measure to evaluate literal and symbolic message content in all print advertisements. The value of this scale to advance our understanding about message strategy may be significant in future consumer and business advertising research.
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The seawater neutralisation process is currently used in the Alumina industry to reduce the pH and dissolved metal concentrations in bauxite refinery residues, through the precipitation of Mg, Al, and Ca hydroxide and carbonate minerals. This neutralisation method is very similar to the co-precipitation method used to synthesise hydrotalcite (Mg6Al2(OH)16CO3•4H2O). This study looks at the effect of temperature on the type of precipitates that form from the seawater neutralisation process of Bayer liquor. The Bayer precipitates have been characterised by a variety of techniques, including X-ray diffraction, Raman spectroscopy and infrared spectroscopy. The mineralogical composition of Bayer precipitates largely includes hydrotalcite, hydromagnesite, and calcium carbonate species. XRD determined that Bayer hydrotalcites that are synthesised at 55 °C have a larger interlayer distance, indicating more anions are removed from Bayer liquor. Vibrational spectroscopic techniques have identified an increase in hydrogen bond strength for precipitates formed at 55 °C, suggesting the formation of a more stable Bayer hydrotalcite. Raman spectroscopy identified the intercalation of sulfate and carbonate anions into Bayer hydrotalcites using these synthesis conditions.
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Emotional processes modulate the size of the eyeblink startle reflex in a picture-viewing paradigm, but it is unclear whether emotional processes are responsible for blink modulation in human conditioning. Experiment 1 involved an aversive differential conditioning phase followed by an extinction phase in which acoustic startle probes were presented during CS+, CS-, and intertrial intervals. Valence ratings and affective priming showed the CS+ was unpleasant postacquisition. Blink startle magnitude was larger during CS+ than during CS-. Experiment 2 used the same design in two groups trained with pleasant or unpleasant pictorial USs. Ratings and affective priming indicated that the CS+ had become pleasant or unpleasant in the respective group. Regardless of CS valence, blink startle was larger during CS+ than CS- in both groups. Thus, startle was not modulated by CS valence.
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Objective To examine the risk factors for Mycobacterium tuberculosis infection (MTI) among Greenlandic children for the purpose of identifying those at highest risk of infection. Methods Between 2005 and 2007, 1797 Greenlandic schoolchildren in five different areas were tested for MTI with an interferon gamma release assay (IGRA) and a tuberculin skin test (TST). Parents or guardians were surveyed using a standardized self-administered questionnaire to obtain data on crowding in the household, parents’ educational level and the child’s health status. Demographic data for each child – i.e. parents’ place of birth, number of siblings, distance between siblings (next younger and next older), birth order and mother’s age when the child was born – were also extracted from a public registry. Logistic regression was used to check for associations between these variables and MTI, and all results were expressed as odds ratios (ORs) and 95% confidence intervals (CIs). Children were considered to have MTI if they tested positive on both the IGRA assay and the TST. Findings The overall prevalence of MTI was 8.5% (152/1797). MTI was diagnosed in 26.7% of the children with a known TB contact, as opposed to 6.4% of the children without such contact. Overall, the MTI rate was higher among Inuit children (OR: 4.22; 95% CI: 1.55–11.5) and among children born less than one year after the birth of the next older sibling (OR: 2.48; 95% CI: 1.33–4.63). Self-reported TB contact modified the profile to include household crowding and low mother’s education. Children who had an older MTI-positive sibling were much more likely to test positive for MTI themselves (OR: 14.2; 95% CI: 5.75–35.0) than children without an infected older sibling. Conclusion Ethnicity, sibling relations, number of household residents and maternal level of education are factors associated with the risk of TB infection among children in Greenland. The strong household clustering of MTI suggests that family sources of exposure are important.