968 resultados para advanced glycosylation end-product receptor
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This study will collaborate by bringing some detailed analysis and findings on a special case study of a discontinuous product development process, trying to answer how the discontinuous product development process takes place and the main factors that influence this process. Additionally, it tried to explore some explanations for the difficulties generally faced by the companies to sustain innovation. The case is about the Motorola cell phone RAZR V3, launched in 2004. RAZR V3 was noted by industry experts as game-changing feat of design and engineering, selling more than 110 million units by end of 2008 and recognized as one of the fastest selling products in the industry. The study uses a single case methodology, which is appropriate given the access to a phenomenon that happened inside corporate dominium and it is not easily accessed for academic studies, besides being a rare case of success in the cellular phone industry. In order to magnify the understanding of the phenomenon, the exploration was extended to contrast the RAZR development process and the standard product development process in Motorola. Additionally, it was integrated a longitudinal reflection of the company product development evolution until the next breakthrough product hitting the cellular phone industry. The result of the analysis shows that discontinuous products do not fit well traditional product development process (in this case, stage-gate). This result reinforces the results obtained on previous studies of discontinuous product development conducted by other authors. Therefore, it is clear that the dynamics of discontinuous product development are different from the continuous product development, requiring different treatment to succeed. Moreover, this study highlighted the importance of the management influence in all the phases of the process as one of the most important factors, suggesting a key component to be carefully observed in future researches. Some other findings of the study that were considered very important for a discontinuous product development process: have champions (who believe and protect the project) and not only one champion; create a right atmosphere to make flow the creative process; question paradigms to create discontinuous products; simple guiding light to focus the team; company culture that accepts and knows how to deal with risks; and undoubtedly, have a company strategy that understands the different dynamics of continuous and discontinuous product development processes and treat them accordingly.
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This thesis develops and evaluates a business model for connected full electric vehicles (FEV) for the European market. Despite a promoting political environment, various barriers have thus far prevented the FEV from becoming a mass-market vehicle. Besides cost, the most noteworthy of these barriers is represented by range anxiety, a product of FEVs’ limited range, lacking availability of charging infrastructure, and long recharging times. Connected FEVs, which maintain a constant connection to the surrounding infrastructure, appear to be a promising element to overcome drivers’ range anxiety. Yet their successful application requires a well functioning FEV ecosystem which can only be created through the collaboration of various stakeholders such as original equipment manufacturers (OEM), first tier suppliers (FTS), charging infrastructure and service providers (CISP), utilities, communication enablers, and governments. This thesis explores and evaluates how a business model, jointly created by these stakeholders, could look like, i.e. how stakeholders could collaborate in the design of products, services, infrastructure, and advanced mobility management, to meet drivers with a sensible value proposition that is at least equivalent to that of internal combustion engine (ICE) cars. It suggests that this value proposition will be an end-2-end package provided by CISPs or OEMs that comprises mobility packages (incl. pay per mile plans, battery leasing, charging and battery swapping (BS) infrastructure) and FEVs equipped with an on-board unit (OBU) combined with additional services targeted at range anxiety reduction. From a theoretical point of view the thesis answers the question which business model framework is suitable for the development of a holistic, i.e. all stakeholder-comprising business model for connected FEVs and defines such a business model. In doing so the thesis provides the first comprehensive business model related research findings on connected FEVs, as prior works focused on the much less complex scenario featuring only “offline” FEVs.
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Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP)
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Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP)
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Little evidence-based guidance is available to aid clinicians in determining short-term prognoses in very severe COPD patients. Therefore, the present study was designed to provide a prospective assessment (1) of the mortality rates and (2) whether the baseline measurements may be determinants of 1-year mortality in hypoxemic COPD patients receiving long-term oxygen therapy (LTOT).Seventy-eight clinically stable patients with advanced COPD treated using LTOT were enrolled in a prospective cohort study. Outcome variable: first-year mortality. Baseline measurements: categorical variables: age (<60 or >= 60 years); gender; body mass index (<20 or >= 20 kg/m(2)); fat-free mass (FFM) index (<16 [men] and <15kg/m(2) [women]; baseline dyspnea index (BDI) (<= 3 or >3); and corticosteroid use. Continuous variables: smoking history; lung function; FFM; fat mass; hemoglobin; hematocrit; arterial blood gases; forearm muscle strength; St. George's Respiratory Questionnaire (SGRQ); and comorbidity score. By the end of 1-year of follow-up, 12 patients (15.4%) had died. Kaplan-Meier curves showed that BDI <= 3 was the only variable associated with higher mortality. Cox proportional hazards analysis revealed that tower PaO2 and SPO2, higher PaCO2 and SGRQ scores were associated with reduced survival. In the multivariate analysis, BDI remained predictive of mortality (hazard ratio [HR], 0.50; 95% confidence interval [CI], 0.31-0.81), as did PaO2 (HR, 0.49; 95% CI, 0.26-0.95). These data suggest that readily available parameters as dyspnea intensity and hypoxemia severity may be useful in predicting first-year survival rates in advanced COPD patients receiving LTOT (C) 2007 Elsevier Ltd. All rights reserved.
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Infertility represents one of the main long-term consequences of the chemotherapy used for the adjuvant treatment of breast cancer. Approximately 60-65% of breast cancers express the nuclear hormone receptor in premenopausal women. Adjuvant endocrine therapy is an integral component of care for patients with hormone receptor-positive (HR+) tumours. The GnRH agonist (GnRHa) alone or in combination with tamoxifen produces results at least similar to those obtained with the different chemotherapy protocols in patients with HR+ breast cancer with respect to recurrence-free survival and overall survival. It is time to indicate adjuvant therapy with GnRHa associated with tamoxifen for patients with breast cancer (HR+ tumours) if they want to preserve their reproductive function. The evaluation of ovarian reserve tests: follicle stimulating hormone (FSH), anti-Mullerian hormone (AMH), inhibin B, antral follicle count (AFC) and ovarian volume 6 months, and 1 year after the end of therapy with GnRHa/tamoxifen must be realised. The recurrence-free survival and overall survival should be analysed. The major implication of this hypothesis will be to avoid adjuvant chemotherapy for patients with breast cancer (HR+ tumours) that request fertility preservation. It is expected that ovarian function should not be altered in almost all cases and subsequent pregnancy a real possibility. (C) 2012 Elsevier Ltd. All rights reserved.
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The nucleus of the solitary tract (NTS) receives primary afferents involved in cardiovascular regulation. We investigated the role of NK1-receptor bearing neurons in the NTS on cardiovascular reflexes in awake rats fitted with chronic venous and arterial cannulae. These neurons were lesioned selectively with saporin conjugated with substance P (SP-SAP, 2 mu M, bilateral injections of 20 nL in the subpostremal NTS, or 200 nL in both the subpostremal and the commissural NTS). Before, and 7 and 14 days after injection of SP-SAP, we measured changes in blood pressure and heart rate induced by i.v. injection of phenylephrine and nitroprusside (baroreceptor reflex), cyanide (arterial chemoreceptor reflex), and phenylbiguanide (Bezold-Jarisch reflex). The smaller injections with SP-SAP completely abolished NK1 receptor staining in the subpostremal NTS. The larger injections abolished NK1 receptor immunoreactivity in an area that extended from the commissural NTS to the rostral end of the subpostremal NTS. The lesions seemed to affect only a limited number of neurons, since neutral red stained sections did not show any obvious reduction in cell number. The smaller lesions reduced the gain of baroreflex bradycardia and the hypotension induced by phenylbiguanide. The larger lesions completely abolished the response to phenylbiguanide, blocked the baroreflex bradycardia induced by phenylephrine, severely blunted the baroreflex tachycardia, and blocked the bradycardia and reduced the hypertension induced by cyanide. Thus, these responses depend critically on NK1-receptor bearing neurons in the NTS. (c) 2006 Elsevier B.V. All rights reserved.
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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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Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP)
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Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP)
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This study was aimed at testing the hypothesis that serotoninergic receptors in the locus coeruleus (LC) play a role in bacterial lipopolysaccharide-induced fever. To this end, 5-HT1A (WAY-100635; 3 mu g/100 nL) and 5-HT2A (ketanserin; 2 mu g/100 nL) antagonists were microinjected into the LC and body temperature was monitored by biotelemetry. Intra-LC microinjections of ketanserin or WAY-100635 caused no change in body temperature of euthermic animals. 5-HT2A antagonism abolished the first phase of the lipopolysaccharide-induced fever. Taken together, these results indicate that serotonin acting on 5-HT2A receptors in the LC mediates the first phase of the febrile response, whereas 5-HT1A receptors are not involved in the lipopolysaccharide-induced fever.
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The N-linked glycosylation of secretory and membrane proteins is the most complex posttranslational modification known to occur in eukaryotic cells. It has been shown to play critical roles in modulating protein function. Although this important biological process has been extensively studied in mammals, much less is known about this biosynthetic pathway in plants. The enzymes involved in plant N-glycan biosynthesis and processing are still not well defined and the mechanism of their genetic regulation is almost completely unknown. In this paper we describe our first attempt to understand the N-linked glycosylation mechanism in a plant species by using the data generated by the Sugarcane Expressed Sequence Tag (SUCEST) project. The SUCEST database was mined for sugarcane gene products potentially involved in the N-glycosylation pathway. This approach has led to the identification and functional assignment of 90 expressed sequence tag (EST) clusters sharing significant sequence similarity with the enzymes involved in N-glycan biosynthesis and processing. The ESTs identified were also analyzed to establish their relative abundance.
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Infertility represents one of the main long-term consequences of combination chemotherapy used for the treatment of breast cancer. Approximately 60%-65% of breast cancers express the nuclear hormone receptor in premenopausal women. Adjuvant endocrine therapy is an integral component of care for patients with hormone receptor-positive (HR+) tumours. The GnRH agonist (GnRHa) alone or in combination with tamoxifen produces results at least similar to those obtained with the different chemotherapy protocols in patients with HR+ tumors with respect to recurrence-free survival and overall survival, Presentation of the hypothesis: It is time to indicate adjuvant therapy with GnRHa associated with tamoxifen for patients with breast cancer (HR+ tumours) if they want to preserve their reproductive function. Testing the hypothesis: Assessment of ovarian reserve tests: follicle stimulating hormone (FSH), anti-Mullerian hormone (AMH), inhibin B, antral follicle count (AFC) and ovarian volume 6 months, and 1 year after the end of therapy with GnRHa/tamoxifen. The recurrence-free survival and overall survival should be analysed. Implications of the hypothesis: The major implication will be to avoid adjuvant chemotherapy for patients with breast cancer (HR+ tumours) that request fertility preservation. It is expected that ovarian function should not be altered in almost all cases. © Todos os direitos reservados a SBRA - Sociedade Brasileira de Reprodução Assistida.
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This paper introduces a methodology for predicting the surface roughness of advanced ceramics using Adaptive Neuro-Fuzzy Inference System (ANFIS). To this end, a grinding machine was used, equipped with an acoustic emission sensor and a power transducer connected to the electric motor rotating the diamond grinding wheel. The alumina workpieces used in this work were pressed and sintered into rectangular bars. Acoustic emission and cutting power signals were collected during the tests and digitally processed to calculate the mean, standard deviation, and two other statistical data. These statistics, as well the root mean square of the acoustic emission and cutting power signals were used as input data for ANFIS. The output values of surface roughness (measured during the tests) were implemented for training and validation of the model. The results indicated that an ANFIS network is an excellent tool when applied to predict the surface roughness of ceramic workpieces in the grinding process.