Enhanced visuospatial memory following intracerebroventricular administration of nerve growth factor

The present work assessed the effects of intracerebroventricular injections of rh recombined human nerve growth factor (rh NGF) (5 micrograms/2.5 microl) at postnatal days 12 and 13 upon the development of spatial learning capacities. The treated rats were trained at the age of 22 days to escape onto an invisible platform at a fixed position in space in a Morris navigation task. For half of the subjects, the training position was also cued, a procedure aimed at facilitating escape and at reducing attention to the distant spatial cues. Later, at the age of 6 months, all the rats were trained in a radial-arm maze task. Treatment effects were found in both immature and adult rats. The injection of NGF improved the performance in the Morris navigation task in both training conditions. There was a significant reduction in the escape latency and an increased bias toward the training platform quadrant during probe trials. The most consistent effect was the precocious development of an adult-like spatial memory. In the radial-arm maze, the NGF-treated rats made significantly fewer reentries than vehicle rats and this effect was particularly marked in the treated female rats. Taken together, these experiments reveal that the development and the maintenance of an accurate spatial representation are tightly related to the development of brain structures facilitated by the action of NGF. Moreover, these experiments demonstrate that an acute pharmacological treatment that leads to a transient modification in the choline acetyltransferase activity can induce a behavioral change long after the treatment.

Trade, Extent of the Market, and Economic Growth 1960-1996

We find that trade and domestic market size are robust determinants of economic growth over the 1960-1996 period when trade openness is measured as the US dollar value of imports and exports relative to GDP in PPP US$ ('real openness'). When trade openness is measured as the US dollar value of imports and exports relative to GDP in exchange rate US$ ('nominal openness') however, trade and the size of domestic markets are often non-robust determinants of growth. We argue that real openness is the more appropriate measure of trade and that our empirical results should be seen as evidence in favor of the extent-of-the-market hypothesis.

NF-kappaB transmits Eda A1/EdaR signalling to activate Shh and cyclin D1 expression, and controls post-initiation hair placode down growth.

A novel function of NF-kappaB in the development of most ectodermal appendages, including two types of murine pelage hair follicles, was detected in a mouse model with suppressed NF-kappaB activity (c(IkappaBalphaDeltaN)). However, the developmental processes regulated by NF-kappaB in hair follicles has remained unknown. Furthermore, the similarity between the phenotypes of c(IkappaBADeltaN) mice and mice deficient in Eda A1 (tabby) or its receptor EdaR (downless) raised the issue of whether in vivo NF-kappaB regulates or is regulated by these novel TNF family members. We now demonstrate that epidermal NF-kappaB activity is first observed in placodes of primary guard hair follicles at day E14.5, and that in vivo NF-kappaB signalling is activated downstream of Eda A1 and EdaR. Importantly, ectopic signals which activate NF-kappaB can also stimulate guard hair placode formation, suggesting a crucial role for NF-kappaB in placode development. In downless and c(IkappaBalphaDeltaN) mice, placodes start to develop, but rapidly abort in the absence of EdaR/NF-kappaB signalling. We show that NF-kappaB activation is essential for induction of Shh and cyclin D1 expression and subsequent placode down growth. However, cyclin D1 induction appears to be indirectly regulated by NF-kappaB, probably via Shh and Wnt. The strongly decreased number of hair follicles observed in c(IkappaBalphaDeltaN) mice compared with tabby mice, indicates that additional signals, such as TROY, must regulate NF-kappaB activity in specific hair follicle subtypes.

Adjustment to Target Capital, Finance, and Growth

Does financial development result in capital being reallocated more rapidly to industries where it is most productive? We argue that if this was the case, financially developed countries should see faster growth in industries with investment opportunities due to global demand and productivity shifts. Testing this cross-industry cross-country growth implication requires proxies for (latent) global industry investment opportunities. We show that tests relying only on data from specific (benchmark) countries may yield spurious evidence for or against the hypothesis. We therefore develop an alternative approach that combines benchmark-country proxies with a proxy that does not reflect opportunities specific to a country or level of financial development. Our empirical results yield clear support for the capital reallocation hypothesis.

As práticas de responsabilidade social organizacional: uma análise nas empresas cabo-verdianas

A responsabilidade social organizacional (RSO) constitui um assunto cada vez mais discutido no seio dos diversos sectores e é considerado importante na gestão das organizações. As acções de responsabilidade social, gradualmente, têm vindo a tornar-se um diferencial em termos de estratégia e competitividade, contribuindo, no seu todo, para a sustentabilidade da sociedade e das pessoas que nela vivem. Assim, torna-se importante compreender a forma como as organizações e seus gestores entendem e assumem o seu compromisso para com todos os stakeholders, bem como despertar-lhes o interesse para os benefícios e vantagens que poderão obter com a prática e implementação de uma gestão da responsabilidade social nas organizações. Apesar de as práticas de RSO constituírem ainda um assunto muito recente em Cabo Verde, já é notável o crescimento das acções desencadeadas pelas organizações em prol de uma sociedade mais justa, responsável e transparente. Com o objectivo de identificar as práticas de responsabilidade social das organizações cabo-verdianas na sua vertente económica, social e ambiental, o presente trabalho inclui uma análise quantitativa e qualitativa, feita a partir da aplicação de um inquérito por questionário, com questões fechadas, complementado por questões abertas. Assim foi realizada uma pesquisa exploratória-descritiva nas organizações, escolhidas em função da sua notoriedade e da sua posição estratégica para o desenvolvimento do país. Entre os principais resultados obtidos pode-se destacar a preocupação com questões ambientais, o respeito pela Lei laboral e apoio regular às comunidades. Dos resultados obtidos e da análise efectuada, pode-se concluir que a cultura da RSO nas organizações cabo-verdianas, ainda se apresenta de forma incipiente. Espera-se, com este trabalho, explicitar o carácter estratégico da responsabilidade social organizacional, bem como fomentar reflexões posteriores de forma a efectivar uma mudança de cultura, levando gestores, colaboradores, e demais stakeholders a desenvolverem o interesse sobre esta matéria, uma vez que a RSO não é apenas um assunto das grandes empresas, mas sim, de todos nós. Social organizational responsibility (SOR) is an increasingly discussed subject amongst several sectors and it’s considered as extremely important on organization management. The social responsibility actions have gradually becoming a disparity regarding strategy and competitivety, contribution in its whole for the society’s and its inhabitant’s sustainability. Thus, it’s important to identify the way the organizations and its managers understand and assume their commitment with the stakeholders, as well as to bring up their interest for the benefits and advantages that they may obtain with the social responsibility management practice on the organizations. Although the SOR practices are still considered as a recent subject in Cape Verde, it’s already noticeable the organizations actions growth towards a fairer, responsible and transparent society. Aiming to identify the capeverdian social organizational responsibility practices on its economical, social and environmental string, this written presentation includes a quantitative and qualitative analysis, with closed questions, completed by open ones. It was therefore performed an explanatory-descriptive research for the organizations, each chosen regarding their notoriety and strategic position for the country’s development. Amongst the main results we may enhance the concern on environmental issues, the respect for the Labour law and the regular support for the communities. From the obtained results and the analysis done, we may conclude that the SOR culture on the Capeverdian organizations is still considered as quite insipient. With this written presentation, it’s expected to explain the social organizational responsibility strategic character, as well as to enhance the posterior reflections in order to implement a cultural change, influencing the managers, co-workers and remaining stakeholders to develop their interest on the subject, once the SOR should not only be some big companies issue, but instead, one regarding all of us.

A importância do sector microcrédito e o perfil do microempresário: Ilha de Santo Antão Cabo Verde

As microempresas desempenham um papel fundamental na promoção do emprego, na inovação, na criação de rendimentos e no desenvolvimento económico e social. Para os países em vias de desenvolvimento, crê-se que a dinamização das microempresas pode ser um instrumento privilegiado de promoção e combate à pobreza, na medida em que esta poderá ser a via para incentivar as camadas mais pobres das populações rurais e urbanas a criarem os seus próprios negócios e a providenciarem os seus próprios rendimentos. A criação e o crescimento das microempresas estão, todavia, condicionados por vários constrangimentos. A inexistência de capital inicial (Start-Up Capital) é apontada na literatura financeira como uma das mais relevantes. O recurso ao capital externo, como fonte de financiamento, dependerá, por sua vez, de vários factores. O presente estudo foi realizado em Santo Antão, a ilha mais a norte e a mais montanhosa do Arquipélago de Cabo Verde. O sector micro crédito chama atenção pelo facto de ser um instrumento de importância primordial para Cabo Verde e, particularmente, para a ilha de Santo Antão que possui uma estrutura económica e social muito vulnerável o que nos leva a compreender melhor, o funcionamento das microempresas, instaladas nos três municípios da Ilha (Paul, Ribeira Grande e Porto Novo). Ao longo do estudo definimos o perfil sócio económico do micro empresário Santantonense, com o objectivo de compreender e quantificar o contributo do sector para o desenvolvimento empresarial da ilha, sem esquecer os constrangimentos e dificuldades que se colocam aos micros empresários na procura de financiamento. O processo de recolha de informação foi efectuado com recurso a pesquisas de campo, a partir da elaboração e aplicação de entrevistas de uma forma semi-estruturada, no sentido de identificar as principais características/perfil do empresário. Os dados recolhidos pelas entrevistas têm por base uma apreciação crítica da gestão para melhor compreender e comparar as fragilidades existentes e analisar a capacidade de sucesso dos micros empresários. A configuração da actividade económica foi feita com base na análise quantitativa e qualitativa, dos dados obtidos na aplicação dos questionários. De igual modo, analisamos e comparamos os casos de sucesso e insucesso nas microempresas em estudo, casos de sucesso no que diz respeito aos benefícios de micro créditos para a redução da pobreza e do desemprego, de criação do auto-emprego, e da formação/informação aos micros empresários santantonenses. Nos casos de insucesso analisamos as causas que estiveram na sua origem assim como as consequências daí advenientes. Uma das constatações do estudo, como se verá pela análise dos dados, é que o micro empresário Santantonense, possui um baixo nível de escolaridade e que na sua maioria são mulheres. Um outro resultado evidenciado pelo estudo, é que há uma necessidade da política pública de desenvolvimento no sentido de definição de incentivos à criação e à promoção de micro negócios, atendendo às características demográficas e às necessidades específicas dos beneficiários. Micro enterprises perform a fundamental component in promoting employment, innovation, and earnings-generation and in socio-economic development. For countries en route to development, the belief is that the dynamic engine of the micro enterprises could be a privileged instrument to promote in the battle against poverty, in the hope that this could be the venue to incentivize the poorest of the rural and urban populations to create their own businesses and forecast their own earnings. The creation and the growth of micro enterprises is, however, conditional upon various constraints. The inexistence of initial capital is cited in financial literature as one of the more important. To resort to external capital as a financing source, is itself dependent on various factors. The current study was conducted in Santo Antão, the most northern and mountainous island in the Archipelago of Cape Verde. The micro credit´s sector calls attention to the fact that it is an essential instrument in Cape Verde, particularly in the island of Santo Antão which has an economic and social structure extremely vulnerable, leading us to a better understanding of how micro enterprises operate in the three municipalities of the Island (Paul, Ribeira Grande and Porto Novo). During the course of the study we defined the socio-economic character of the micro entrepreneur Santantonense, with the goal of understanding and quantifying the sector´s contribution to the Island´s entrepreneurial development, keeping in mind the contraints and difficulties that confront the entrepreneurs when seeking financing. The process for gathering the information was performed through field research, beginning with elaboration and application of interviews, designed to identify the entrepreneur´s major characteristics and the importance of micro credit for the island of Santo Antão. The data gathered through the interviews have un underlying basic and critic appreciation of management for a better understanding and comparing the existing fragilities and for analyzing the micro entrepreneurs´ capacity to succeed. The configuration of economic activities was designed based on quantitative and qualitative analysis from data obtained from the questionnaires. Likewise, we analyzed and compared the success and non-success cases of the micro enterprises in the study, success cases with respect to the benefits of micro credit in reducing poverty and unemployment, creation of self-employment, and the education/information for the micro entrepreneurs of Santo Antão. In the non-success cases we analyzed the original causes as well as the impending consequences. One of the study´s contentions, as the data analysis shows, is that micro entrepreneur of Santo Antão has a low level of education with the majority of them being women. In addition the study shows that there is a need for a public discourse in terms of defining and developing incentives for creating and promoting micro businesses given the demographic characteristics and the specific necessities of the beneficiaries.

Role of beta-1 integrin in tumor growth and dissemination

SUMMARY Cancer is one of the leading causes of disease-related mortality. In most cases, death is due to the spread of cells from the primary tumor to distant sites causing formation of metastases. To become tumorigenic, cells should acquire ability, including self-sufficiency in growth signals, insensitivity to anti-growth signals, resistance to apoptosis, sustained angiogenesis, limitless replicative potential and tissue invasion and metastasis. Tumor progression depends, in part on the relationship between tumor cells and host tissue stroma, characterized by changes of tumor cell adhesion to their microenvironment and activation of a variety of extracellular proteases that play a role in ECM degradation. integrins are adhesion proteins implicated in tumorigenesis. Their main function is to mediate cell adhesion to the ECM or to other cells and to create a link between the ECM and the cytoskeleton. Tumor cells like normal cells use integrins to attach to ECM, migrate into surrounding tissues and derive survival and growth signals. Integrin-dependent adhesion and migration are thought to play an important role in tumor dissemination. A strategy was designed to address the role of β1 integrin tumor growth and dissemination. Murine mammary carcinoma (TA3) cells were stably transfected with a soluble β1 integrin construct, which is anticipated to play a dominant negative role, being able to associate with different α-subunits expressed on the cell surface but unable to transduce signals to the nucleus. Results from studies based on soluble β1 integrin TA3 transfectants showed that 1) the integrin expression pattern at the cell surface changed with an induction of α2β1 and α5β1 heterodimers; 2) adhesion to collagens, especially collagen I was increased; 3) tumor dissemination after intrape-ritoneal injection in syngeneic mice was abolished and 4) local growth after orthotopic injection was maintained but delayed. Taken together, the data presented here suggest that β1 integrin plays a potentially important role in the regulation of tumor behavior. RESUME Le cancer est une des principales causes de mortalité suite à une maladie. Dans la plupart des cas, la mort est la conséquence de la dissémination de cellules, provenant de la tumeur primaire, dans des endroits distants et causant la formation de métastases. Afin de devenir cancéreuse, une cellule doit acquérir certaines capacités, telles qu'une auto-suffisance en facteurs de croissance, une insensibilité aux facteurs empêchant la croissance cellulaire, une résistance à l'apoptose, une angiogénèse soutenue, un potentiel de réplication illimité et une capacité à pénétrer dans les tissus et à former des colonies métastatiques. La progression d'une tumeur dépend, en partie, de la relation entre les cellules tumorales et les cellules tissulaires de l'hôte. Cette relation est caractérisée par des modifications des cellules tumorales quant à leur adhésion au microenvironnement et à l'activation de protéases qui permettent de dégrader la matrice extracellulaire. Les intégrines sont des protéines impliquées dans le développement tumoral. Leur fonction principale est de réguler l'adhésion des cellules à la matrice extracellulaire, ou à d'autres cellules, et de créer un lien entre cette matrice extracellulaire et le cytosquelette. Les cellules tumorales utilisent également les intégrines pour se lier à la matrice extracellulaire, pour migrer dans les tissus adjacents et pour induire des signaux de croissance et de survie. Ces événements d'adhésion et de migration, qui dépendent des intégrines, jouent un rôle primordial dans la dissémination des cellules cancéreuses. Une stratégie a été élaborée afin de définir le rôle de l'intégrine β1 durant la croissance et la dissémination des cellules tumorales. Des cellules provenant d'un carcinome de la glande mammaire (TA3) ont été transfectées de manière stable avec un vecteur contenant la séquence codante de la partie extracellulaire de l'intégrine β1. L'intégrine tronquée doit être capable de se lier aux sous-unités α exprimées à la surface de la cellule, mais doit être incapable de transmettre un signal à l'intérieur de la cellule. Les résultats obtenus avec les cellules TA3 transfectées contenant l'intégrine β1 soluble montrent que I) le répertoire d'expression des intégrines à la surface de la cellule a changé en faveur des hétérodimères α2β1 et α5β1; 2) l'adhésion aux collagènes, particulièrement au collagène de type I a augmenté; 3) la dissémination des cellules tumorales après une injection intrapéritonéale est empêchée; 4) la croissance tumorale après une injection orthotopique est conservée mais retardée. Ces résultats montrent que l'intégrine β1 joue un rôle primordial dans la régulation du comportement tumoral.

Pharmacological inhibition of fibroblast growth factor (FGF) receptor signaling ameliorates FGF23-mediated hypophosphatemic rickets.

Fibroblast growth factor 23 (FGF23) is a circulating factor secreted by osteocytes that is essential for phosphate homeostasis. In kidney proximal tubular cells FGF23 inhibits phosphate reabsorption and leads to decreased synthesis and enhanced catabolism of 1,25-dihydroxyvitamin D3 (1,25[OH]2 D3 ). Excess levels of FGF23 cause renal phosphate wasting and suppression of circulating 1,25(OH)2 D3 levels and are associated with several hereditary hypophosphatemic disorders with skeletal abnormalities, including X-linked hypophosphatemic rickets (XLH) and autosomal recessive hypophosphatemic rickets (ARHR). Currently, therapeutic approaches to these diseases are limited to treatment with activated vitamin D analogues and phosphate supplementation, often merely resulting in partial correction of the skeletal aberrations. In this study, we evaluate the use of FGFR inhibitors for the treatment of FGF23-mediated hypophosphatemic disorders using NVP-BGJ398, a novel selective, pan-specific FGFR inhibitor currently in Phase I clinical trials for cancer therapy. In two different hypophosphatemic mouse models, Hyp and Dmp1-null mice, resembling the human diseases XLH and ARHR, we find that pharmacological inhibition of FGFRs efficiently abrogates aberrant FGF23 signaling and normalizes the hypophosphatemic and hypocalcemic conditions of these mice. Correspondingly, long-term FGFR inhibition in Hyp mice leads to enhanced bone growth, increased mineralization, and reorganization of the disturbed growth plate structure. We therefore propose NVP-BGJ398 treatment as a novel approach for the therapy of FGF23-mediated hypophosphatemic diseases.

The effects of arterial flow on platelet activation, thrombus growth, and stabilization.

Injury of an arterial vessel wall acutely triggers a multifaceted process of thrombus formation, which is dictated by the high-shear flow conditions in the artery. In this overview, we describe how the classical concept of arterial thrombus formation and vascular occlusion, driven by platelet activation and fibrin formation, can be extended and fine-tuned. This has become possible because of recent insight into the mechanisms of: (i) platelet-vessel wall and platelet-platelet communication, (ii) autocrine platelet activation, and (iii) platelet-coagulation interactions, in relation to blood flow dynamics. We list over 40 studies with genetically modified mice showing a role of platelet and plasma proteins in the control of thrombus stability after vascular injury. These include multiple platelet adhesive receptors and other junctional molecules, components of the ADP receptor signalling cascade to integrin activation, proteins controlling platelet shape, and autocrine activation processes, as well as multiple plasma proteins binding to platelets and proteins of the intrinsic coagulation cascade. Regulatory roles herein of the endothelium and other blood cells are recapitulated as well. Patient studies support the contribution of platelet- and coagulation activation in the regulation of thrombus stability. Analysis of the factors determining flow-dependent thrombus stabilization and embolus formation in mice will help to understand the regulation of this process in human arterial disease.

Use and records of child health handbook focused on growth and development

Objective To evaluate the use and records of the Child Health Handbook (CHH), especially growth and development. Method Cross-sectional study with 358 mother-child pairs registered in 12 Primary Health Centers (PHCs) of a small municipality. Mothers were interviewed at the PHC from February to April 2013 using a questionnaire. Data analysis was done using WHO Anthro software, Epi InfoTM and Stata. Results Fifty-three percent of the mothers were carrying the CHH at the time of the interview, similar to the proportion of mothers who were instructed to bring the CHH to health appointments. Annotations in the CHH during the visits were reported by 49%. The vaccination schedule was completed in 97% of the CHH, but only 9% and 8% of the CHH, respectively, contained growth charts and properly completed developmental milestones. Conclusion Low rates of use and unsatisfactory record-keeping in the CHH reinforce the need for investment in professional training and community awareness for the CHH to become an effective instrument of promotion of child health.

Three essays in control, entrepreneurship and innovation

One of the key emphases of these three essays is to provide practical managerial insight. However, good practical insight, can only be created by grounding it firmly on theoretical and empirical research. Practical experience-based understanding without theoretical grounding remains tacit and cannot be easily disseminated. Theoretical understanding without links to real life remains sterile. My studies aim to increase the understanding of how radical innovation could be generated at large established firms and how it can have an impact on business performance as most businesses pursue innovation with one prime objective: value creation. My studies focus on large established firms with sales revenue exceeding USD $ 1 billion. Usually large established firms cannot rely on informal ways of management, as these firms tend to be multinational businesses operating with subsidiaries, offices, or production facilities in more than one country. I. Internal and External Determinants of Corporate Venture Capital Investment The goal of this chapter is to focus on CVC as one of the mechanisms available for established firms to source new ideas that can be exploited. We explore the internal and external determinants under which established firms engage in CVC to source new knowledge through investment in startups. We attempt to make scholars and managers aware of the forces that influence CVC activity by providing findings and insights to facilitate the strategic management of CVC. There are research opportunities to further understand the CVC phenomenon. Why do companies engage in CVC? What motivates them to continue "playing the game" and keep their active CVC investment status. The study examines CVC investment activity, and the importance of understanding the influential factors that make a firm decide to engage in CVC. The main question is: How do established firms' CVC programs adapt to changing internal conditions and external environments. Adaptation typically involves learning from exploratory endeavors, which enable companies to transform the ways they compete (Guth & Ginsberg, 1990). Our study extends the current stream of research on CVC. It aims to contribute to the literature by providing an extensive comparison of internal and external determinants leading to CVC investment activity. To our knowledge, this is the first study to examine the influence of internal and external determinants on CVC activity throughout specific expansion and contraction periods determined by structural breaks occurring between 1985 to 2008. Our econometric analysis indicates a strong and significant positive association between CVC activity and R&D, cash flow availability and environmental financial market conditions, as well as a significant negative association between sales growth and the decision to engage into CVC. The analysis of this study reveals that CVC investment is highly volatile, as demonstrated by dramatic fluctuations in CVC investment activity over the past decades. When analyzing the overall cyclical CVC period from 1985 to 2008 the results of our study suggest that CVC activity has a pattern influenced by financial factors such as the level of R&D, free cash flow, lack of sales growth, and external conditions of the economy, with the NASDAQ price index as the most significant variable influencing CVC during this period. II. Contribution of CVC and its Interaction with R&D to Value Creation The second essay takes into account the demands of corporate executives and shareholders regarding business performance and value creation justifications for investments in innovation. Billions of dollars are invested in CVC and R&D. However there is little evidence that CVC and its interaction with R&D create value. Firms operating in dynamic business sectors seek to innovate to create the value demanded by changing market conditions, consumer preferences, and competitive offerings. Consequently, firms operating in such business sectors put a premium on finding new, sustainable and competitive value propositions. CVC and R&D can help them in this challenge. Dushnitsky and Lenox (2006) presented evidence that CVC investment is associated with value creation. However, studies have shown that the most innovative firms do not necessarily benefit from innovation. For instance Oyon (2007) indicated that between 1995 and 2005 the most innovative automotive companies did not obtain adequate rewards for shareholders. The interaction between CVC and R&D has generated much debate in the CVC literature. Some researchers see them as substitutes suggesting that firms have to choose between CVC and R&D (Hellmann, 2002), while others expect them to be complementary (Chesbrough & Tucci, 2004). This study explores the interaction that CVC and R&D have on value creation. This essay examines the impact of CVC and R&D on value creation over sixteen years across six business sectors and different geographical regions. Our findings suggest that the effect of CVC and its interaction with R&D on value creation is positive and significant. In dynamic business sectors technologies rapidly relinquish obsolete, consequently firms operating in such business sectors need to continuously develop new sources of value creation (Eisenhardt & Martin, 2000; Qualls, Olshavsky, & Michaels, 1981). We conclude that in order to impact value creation, firms operating in business sectors such as Engineering & Business Services, and Information Communication & Technology ought to consider CVC as a vital element of their innovation strategy. Moreover, regarding the CVC and R&D interaction effect, our findings suggest that R&D and CVC are complementary to value creation hence firms in certain business sectors can be better off supporting both R&D and CVC simultaneously to increase the probability of generating value creation. III. MCS and Organizational Structures for Radical Innovation Incremental innovation is necessary for continuous improvement but it does not provide a sustainable permanent source of competitiveness (Cooper, 2003). On the other hand, radical innovation pursuing new technologies and new market frontiers can generate new platforms for growth providing firms with competitive advantages and high economic margin rents (Duchesneau et al., 1979; Markides & Geroski, 2005; O'Connor & DeMartino, 2006; Utterback, 1994). Interestingly, not all companies distinguish between incremental and radical innovation, and more importantly firms that manage innovation through a one-sizefits- all process can almost guarantee a sub-optimization of certain systems and resources (Davila et al., 2006). Moreover, we conducted research on the utilization of MCS along with radical innovation and flexible organizational structures as these have been associated with firm growth (Cooper, 2003; Davila & Foster, 2005, 2007; Markides & Geroski, 2005; O'Connor & DeMartino, 2006). Davila et al. (2009) identified research opportunities for innovation management and provided a list of pending issues: How do companies manage the process of radical and incremental innovation? What are the performance measures companies use to manage radical ideas and how do they select them? The fundamental objective of this paper is to address the following research question: What are the processes, MCS, and organizational structures for generating radical innovation? Moreover, in recent years, research on innovation management has been conducted mainly at either the firm level (Birkinshaw, Hamel, & Mol, 2008a) or at the project level examining appropriate management techniques associated with high levels of uncertainty (Burgelman & Sayles, 1988; Dougherty & Heller, 1994; Jelinek & Schoonhoven, 1993; Kanter, North, Bernstein, & Williamson, 1990; Leifer et al., 2000). Therefore, we embarked on a novel process-related research framework to observe the process stages, MCS, and organizational structures that can generate radical innovation. This article is based on a case study at Alcan Engineered Products, a division of a multinational company provider of lightweight material solutions. Our observations suggest that incremental and radical innovation should be managed through different processes, MCS and organizational structures that ought to be activated and adapted contingent to the type of innovation that is being pursued (i.e. incremental or radical innovation). More importantly, we conclude that radical can be generated in a systematic way through enablers such as processes, MCS, and organizational structures. This is in line with the findings of Jelinek and Schoonhoven (1993) and Davila et al. (2006; 2007) who show that innovative firms have institutionalized mechanisms, arguing that radical innovation cannot occur in an organic environment where flexibility and consensus are the main managerial mechanisms. They rather argue that radical innovation requires a clear organizational structure and formal MCS.

Análise Económica e Financeira como Instrumento de Apoio ao Processo Decisório

O foco central deste relatório consiste em mostrar a total importância da Análise Económica e Financeira como instrumento de apoio ao processo decisório. No contexto actual onde a concorrência é cada vez mais forte e a busca pela competitividade é uma necessidade constante, as empresas necessitam de informações precisas e oportunas para apoiar o processo decisório. A escassez de recursos financeiros e o elevado custo, aliado com a falta de planeamento e controle, têm contribuído para que muitas empresas encerrem suas actividades. A tomada de boas decisões torna-se, então, um factor crucial para assegurar a sobrevivência, crescimento e permanência da empresa no mercado. Neste sentido, buscamos trazer para todos os interessados alguns conceitos e técnicas fundamentais de análise e medição da performance económica e financeira das empresas que será igualmente útil, quer a nível académica, como também a nível profissional. Procuramos evidenciar a importância de se conhecer os indicadores que podem ser vistos como alertas de possíveis falências de empresas e com base nisso, tomar decisões que determinam que estratégias utilizar para enfrentar a concorrência. A finalizar este relatório procedemos a uma pesquisa Estudo de Caso que engloba uma análise económica e financeira, baseada na análise das Demonstrações Financeiras e demais informações complementares da TRANSCOR-SV, S.A. Foram explorados alguns conceitos relacionados com o tema, mostrando de forma simples e objectiva a situação de como a empresa vem actuando no mercado. Constámos algumas deficiências, pois, foram verificados alguns pontos fracos. Diante dos problemas, sugerimos formas de mudanças e de viabilidade dos mesmos. Esperamos, então, que este relatório contribua para a empresa analisar melhor a forma de administrar a parte económica e financeira e demais sectores.The central focus of this report consists of showing to total importance of the Analysis Economic and Financial as support instrument to the ruling process. In the context actual where the competition is more and more strong and the search for the competitiveness is a constant need, the companies need necessary and opportune information to support the ruling process. The shortage of financial resources and the high cost, ally with the planning lack and control, they have been contributing so that a lot of companies contain their activities. The socket of good decisions becomes, then, a crucial factor to assure the survival, growth and permanence of the company in the market. In this sense, we looked for to bring for all the interested parties, some concepts and fundamental techniques of analysis and measurement of the performance economic and financial of the companies, which will be equally useful, he/she wants to academic level, as well as at professional level. We tried to evidence, the importance of knowing the indicators that you/they can be seen as alerts of possible bankruptcies of companies and with base in that, to make decisions that determine which strategies to use to face the competition. To conclude this report we proceeded to a research Study of Case that includes an analysis economic and financial, based on the analysis of the Financial Demonstrations and other complementary information of TRANSCOR-S.V., S.A. Some concepts related with the theme were explored, showing the situation of simple form and objective of as the company is acting in the market. It was verified some deficiencies, because, some weak points were verified. Before the problems, we suggested forms of changes and of viability of the same ones.We waited, then, which this report contributes to company to analyze the form better of administering the part economic and financial and other sectors.

The Pseudomonas aeruginosa toxin L-2-amino-4-methoxy-trans-3-butenoic acid inhibits growth and induces encystment in Acanthamoeba castellanii.

L-2-Amino-4-methoxy-trans-3-butenoic acid (AMB) is a toxic antimetabolite produced by the opportunistic pathogen Pseudomonas aeruginosa. To evaluate its importance as a potential virulence factor, we tested the host response towards AMB using an Acanthamoeba castellanii cell model. We found that AMB (at concentrations ≥ 0.5 mM) caused amoebal encystment in salt buffer, while inhibiting amoebal growth in rich medium in a dose-dependent manner. However, no difference in amoebal plaque formation was observed on bacterial lawns of wild type and AMB-negative P. aeruginosa strains. We thereby conclude that AMB may eventually act as a virulence factor, but only at relatively high concentrations.

Controlled nerve growth factor release from multi-ply alginate/chitosan-based nerve conduits.

The delivery kinetics of growth factors has been suggested to play an important role in the regeneration of peripheral nerves following axotomy. In this context, we designed a nerve conduit (NC) with adjustable release kinetics of nerve growth factor (NGF). A multi-ply system was designed where NC consisting of a polyelectrolyte alginate/chitosan complex was coated with layers of poly(lactide-co-glycolide) (PLGA) to control the release of embedded NGF. Prior to assessing the in vitro NGF release from NC, various release test media, with and without stabilizers for NGF, were evaluated to ensure adequate quantification of NGF by ELISA. Citrate (pH 5.0) and acetate (pH 5.5) buffered saline solutions containing 0.05% Tween 20 yielded the most reliable results for ELISA active NGF. The in vitro release experiments revealed that the best results in terms of reproducibility and release control were achieved when the NGF was embedded between two PLGA layers and the ends of the NC tightly sealed by the PLGA coatings. The release kinetics could be efficiently adjusted by accommodating NGF at different radial locations within the NC. A sustained release of bioactive NGF in the low nanogram per day range was obtained for at least 15days. In conclusion, the developed multi-ply NGF loaded NC is considered a suitable candidate for future implantation studies to gain insight into the relationship between local growth factor availability and nerve regeneration.

Phenotypic variability of retinocytomas: preregression and postregression growth patterns.

AIM: To describe the incidence of retinocytomas, their variability at presentation and their growth patterns both before and after regression.¦METHODS: Medical notes of the 525 patients of the Jules-Gonin Eye Hospital Retinoblastoma Clinic between 1964 and 2008 were reviewed and the charts of 36 patients with retinocytomas and/or phthisis bulbi were selected.¦RESULTS: The proportion of patients with retinocytomas and/or phthisis bulbi was 3.2%. The mean age at diagnosis was 28.7±17 years. Five tumours presented a cystic pattern (5.8%). Evidence of aggressive exophytic disease prior to spontaneous regression was documented in two eyes, and of invasive endophytic disease (regressed vitreous seeding or internal limiting membrane disruption) in three eyes. Twenty patients were followed with a mean follow-up of 44±60 months. Tumour growth was observed in 16% cases, benign cystic enlargement in 4% and malignant transformation in 12%.¦CONCLUSION: This large study of retinocytomas substantially expands the published features of retinocytoma by describing the cystic nature of some retinocytomas as well as clinical characteristics of the endophytic and exophytic preregression growth patterns. The authors report two different patterns of reactivation: benign cystic enlargement and malignant transformation with or without cystic growth. Higher than previously reported frequency of growth and possible life-threatening complications impose close lifetime follow-up of retinocytoma patients.