593 resultados para Ashley, Jessie
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Background—Increased production of reactive oxygen species (ROS) throughout the vascular wall is a feature of cardiovascular disease states, but therapeutic strategies remain limited by our incomplete understanding of the role and contribution of specific vascular cell ROS to disease pathogenesis. To investigate the specific role of endothelial cell (EC) ROS in the development of structural vascular disease, we generated a mouse model of endothelium-specific Nox2 overexpression and tested the susceptibility to aortic dissection after angiotensin II (Ang II) infusion. Methods and Results—A specific increase in endothelial ROS production in Nox2 transgenic mice was sufficient to cause Ang II–mediated aortic dissection, which was never observed in wild-type mice. Nox2 transgenic aortas had increased endothelial ROS production, endothelial vascular cell adhesion molecule-1 expression, matrix metalloproteinase activity, and CD45+ inflammatory cell infiltration. Conditioned media from Nox2 transgenic ECs induced greater Erk1/2 phosphorylation in vascular smooth muscle cells compared with wild-type controls through secreted cyclophilin A (CypA). Nox2 transgenic ECs (but not vascular smooth muscle cells) and aortas had greater secretion of CypA both at baseline and in response to Ang II stimulation. Knockdown of CypA in ECs abolished the increase in vascular smooth muscle cell Erk1/2 phosphorylation conferred by EC conditioned media, and preincubation with CypA augmented Ang II–induced vascular smooth muscle cell ROS production. Conclusions—These findings demonstrate a pivotal role for EC-derived ROS in the determination of the susceptibility of the aortic wall to Ang II–mediated aortic dissection. ROS-dependent CypA secretion by ECs is an important signaling mechanism through which EC ROS regulate susceptibility of structural components of the aortic wall to aortic dissection.
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Scope: The use of biomarkers in the objective assessment of dietary intake is a high priority in nutrition research. The aim of this study was to examine pentadecanoic acid (C15:0) and heptadecanoic acid (C17:0) as biomarkers of dairy foods intake. Methods and results: The data used in the present study were obtained as part of the Food4me Study. Estimates of C15:0 and C17:0 from dried blood spots and intakes of dairy from an FFQ were obtained from participants (n=1,180) across 7 countries. Regression analyses were used to explore associations of biomarkers with dairy intake levels and receiver operating characteristic (ROC) analyses were used to evaluate the fatty acids. Significant positive associations were found between C15:0 and total intakes of high-fat dairy products. C15:0 showed good ability to distinguish between low and high consumers of high-fat dairy products. Conclusion: C15:0 can be used as a biomarker of high-fat dairy intake and of specific high-fat dairy products. Both C15:0 and C17:0 performed poorly for total dairy intake highlighting the need for caution when using these in epidemiological studies.
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A quality assessment of the CFC-11 (CCl3F), CFC-12 (CCl2F2), HF, and SF6 products from limb-viewing satellite instruments is provided by means of a detailed intercomparison. The climatologies in the form of monthly zonal mean time series are obtained from HALOE, MIPAS, ACE-FTS, and HIRDLS within the time period 1991–2010. The intercomparisons focus on the mean biases of the monthly and annual zonal mean fields and aim to identify their vertical, latitudinal and temporal structure. The CFC evaluations (based on MIPAS, ACE-FTS and HIRDLS) reveal that the uncertainty in our knowledge of the atmospheric CFC-11 and CFC-12 mean state, as given by satellite data sets, is smallest in the tropics and mid-latitudes at altitudes below 50 and 20 hPa, respectively, with a 1σ multi-instrument spread of up to ±5 %. For HF, the situation is reversed. The two available data sets (HALOE and ACE-FTS) agree well above 100 hPa, with a spread in this region of ±5 to ±10 %, while at altitudes below 100 hPa the HF annual mean state is less well known, with a spread ±30 % and larger. The atmospheric SF6 annual mean states derived from two satellite data sets (MIPAS and ACE-FTS) show only very small differences with a spread of less than ±5 % and often below ±2.5 %. While the overall agreement among the climatological data sets is very good for large parts of the upper troposphere and lower stratosphere (CFCs, SF6) or middle stratosphere (HF), individual discrepancies have been identified. Pronounced deviations between the instrument climatologies exist for particular atmospheric regions which differ from gas to gas. Notable features are differently shaped isopleths in the subtropics, deviations in the vertical gradients in the lower stratosphere and in the meridional gradients in the upper troposphere, and inconsistencies in the seasonal cycle. Additionally, long-term drifts between the instruments have been identified for the CFC-11 and CFC-12 time series. The evaluations as a whole provide guidance on what data sets are the most reliable for applications such as studies of atmospheric transport and variability, model–measurement comparisons and detection of long-term trends. The data sets will be publicly available from the SPARC Data Centre and through PANGAEA (doi:10.1594/PANGAEA.849223).
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This study examines the corporate social responsibility (CSR) theme in Central Bank of Brazil (Bacen). The CSR movement is growing worldwide and it is related to values such as sustainability, ethics and transparency to the stakeholders. The study was performed in two parts. The first part consists of a bibliography research on the origins, the concept and the practice relating to CSR in the contemporary organizational environment. In the second part - field research - the Central Bank's Board of Directors and representatives of Ibase and Ethos Institute were interviewed and the content analysis method - a qualitative research method - was used in the interpretation of information obtained. The analysis of the interviews shows that the Board is receptive to the CSR development and that they consider the accomplishment of Central Bank's institutional mission fundamental in this process. The participation of the Bank's personnel and the incorporation of the CSR principles into the day-to-day practice are also considered necessary. Finally, one hundred indicators - based on the Ethos CSR Indicators - are proposed to evaluate the stage of development of social responsibility in Bacen on the following subjects: Values, Transparency and Governance; Internal Public; Natural Environment, Suppliers and Society. In summary, this study aims to contribute to the improvement of the knowledge of corporate social responsibility and the best practices in the public sector, particularly in Central Bank of Brazil.
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Even though the term corporate inversion has been heard globally for decades, it has only become more prevalent in the United States during the past two years. This case study examines two United States companies that recently had very high profile and public corporate inversion experiences. Complicated tax laws and high tax rales have long eroded the ability of United States companies to remain competitive on a global scale. During the past two years, tax reform has been elevated to the Presidential and Congressional levei. Because these reform efforts have stalled, however, and in the constant search for ways to become more competitive and profitable, United States dorniciled companies have begun to more aggressively explore corporate inversion. This case study of Walgreens Alliance Boots and Mylan N.V., is undertaken because while the reasons to pursue a corporate inversion for both companies were very similar and done during the same time period, the internai process and final outcome were dramatically different. The other dynamic studied is the role both internai and externai politics had on these two cornpanies and how they influenced the decisions made by the executives. Lastly, the Obama Administration continues to threaten so called "corporate America" to remain in the country through regulatory pressure, but this has not stopped companies frorn pursing corporate inversions. Legislatively, attempts at corporate tax reform, another way to encourage Untied States companies to remain, have also failed. I will not try to determine i f a corporate inversion is the right path for a company to take. I am examining how the rise o f the practice o f corporate inversions has been elevated in boardroorns, on Wall Street, in Congress and at the White House during the past two years.
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The theme Corporate Social Responsibility is relatively recent both in the academic field and in the business practice. Because of the lack of socialization of experiences and precision of concepts, there are gaps regarding the understanding of the subject and, also, how to conduct operations. This study just seeks to investigate such matter, focusing applications of social responsibility in business. It takes, as empirical field, winners of the PSQT - SESI Prize of Quality at Work in Rio Grande do Norte (2002-2007) in order to systematize the various approaches on the issue, aiming to reveal subjective visions and perspectives of the theme. It is characterized as a qualitative study, carried out by structured interview. The universe was composed by 15 companies. It was used analysis of content categorical as an axis for the interpretation of the information. Three approaches guided the analysis: Business Ethics, (normative); Business & Society (contractual); Social Issues Management (strategic). The findings are related in three ways: 1) reasons for the CSR practice; 2) the results obtained; 3) the means of CSR. It was found that the award participation occurs, mostly, linked to SESI invitations, so, as an articulated movement of industrial corporations in Brazil it occurs, also, because of the organizational commitment with the society and the possibility of internal and social growths and because of the importance attributed to the report as an instrument of consultancy. There are no indicators to check impacts of organizational interventions, in spite of the existence of planning for the actions. Social responsibility appears as a tool to reinforce the organizational image and to increase satisfaction of the employees. There is a tendency of large and medium firms to a contractual commitment while the small and the micros firms are on strategic or normative level. The analysis of the perspectives of social responsibility future revealed trends towards for strategic approach
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To understand the biology and evolution of ruminants, the cattle genome was sequenced to about sevenfold coverage. The cattle genome contains a minimum of 22,000 genes, with a core set of 14,345 orthologs shared among seven mammalian species of which 1217 are absent or undetected in noneutherian (marsupial or monotreme) genomes. Cattle-specific evolutionary breakpoint regions in chromosomes have a higher density of segmental duplications, enrichment of repetitive elements, and species-specific variations in genes associated with lactation and immune responsiveness. Genes involved in metabolism are generally highly conserved, although five metabolic genes are deleted or extensively diverged from their human orthologs. The cattle genome sequence thus provides a resource for understanding mammalian evolution and accelerating livestock genetic improvement for milk and meat production.
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Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP)
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Conselho Nacional de Desenvolvimento Científico e Tecnológico (CNPq)
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Conselho Nacional de Desenvolvimento Científico e Tecnológico (CNPq)
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Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP)
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Macrophage ingestion of the yeast Candida albicans requires its recognition by multiple receptors and the activation of diverse signaling programs. Synthesis of the lipid mediator prostaglandin E-2 (PGE(2)) and generation of cyclic adenosine monophosphate (cAMP) also accompany this process. Here, we characterized the mechanisms underlying PGE(2)-mediated inhibition of phagocytosis and filamentous actin (F-actin) polymerization in response to ingestion of C. albicans by alveolar macrophages. PGE(2) suppressed phagocytosis and F-actin formation through the PGE(2) receptors EP2 and EP4, cAMP, and activation of types I and II protein kinase A. Dephosphorylation and activation of the actin depolymerizing factor cofilin-1 were necessary for these inhibitory effects of PGE(2). PGE(2)-dependent activation of cofilin-1 was mediated by the protein phosphatase activity of PTEN (phosphatase and tensin homolog deleted on chromosome 10), with which it directly associated. Because enhanced production of PGE(2) accompanies many immunosuppressed states, the PTEN-dependent pathway described here may contribute to impaired antifungal defenses.