Colorectal cancer (CRC) is one of the most deadly and commonly diagnosed tumors worldwide. Several genes are involved in its development and progression. The most frequent mutations concern APC, ...KRAS, SMAD4, and TP53 genes, suggesting that CRC relies on the concomitant alteration of the related pathways. However, with classic molecular approaches, it is not easy to simultaneously analyze the interconnections between these pathways. To overcome this limitation, recently these pathways have been included in a huge chemical reaction network (CRN) describing how information sensed from the environment by growth factors is processed by healthy colorectal cells. Starting from this CRN, we propose a computational model which simulates the effects induced by single or multiple concurrent mutations on the global signaling network. The model has been tested in three scenarios. First, we have quantified the changes induced on the concentration of the proteins of the network by a mutation in APC, KRAS, SMAD4, or TP53. Second, we have computed the changes in the concentration of p53 induced by up to two concurrent mutations affecting proteins upstreams in the network. Third, we have considered a mutated cell affected by a gain of function of KRAS, and we have simulated the action of Dabrafenib, showing that the proposed model can be used to determine the most effective amount of drug to be delivered to the cell. In general, the proposed approach displays several advantages, in that it allows to quantify the alteration in the concentration of the proteins resulting from a single or multiple given mutations. Moreover, simulations of the global signaling network of CRC may be used to identify new therapeutic targets, or to disclose unexpected interactions between the involved pathways.
Purpose - This study aims to analyse the gender composition of the 99 most liquid Brazilian companies listed in the Brazilian stock exchange (BM&FBovespa) in 2011. It proposes a discussion about ...gender inequality in Brazilian companies and provides data, made available for the first time to national and international literature, on gender composition in Brazilian boards.Design methodology approach - This is a quantitative study, whose data were collected from the Annual Report of Corporate Governance of Listed Companies 2011 prepared by the Capital Aberto magazine on the makeup of the boards of the 100 most liquid Brazilian publicly traded companies. Descriptive multivariate regression tests were carried out to refine these findings.Findings - The results show that only 5.4 per cent of the positions in the boards of these companies are occupied by women. Firms that have been listed for longer in the stock market and have more seats in their boards are more likely to have women directors in these boards, suggesting gender inequality in the 99 companies surveyed.Research limitations implications - This study has a limitation with regards to the type of female board members in the sample. In other words, the authors were unable to determine if they were external or internal to the companies.Practical implications - The study discusses gender inequality in Brazilian companies and contributes to the debate on a governmental proposal to adopt quota legislation to increase the number of women in boards of directors.Originality value - This study fulfils an identified need to know more about the gender composition of Brazilian boards.
As Ecoaquisições surgiram nas discussões referentes a preocupação com o clima, meio ambiente e questões sociais, e em primeira medida a intenção da ideia é a de utilizar os valores despendidos pelos ...governos para privilegiar, ou ainda, fomentar um mercado ecofriendly. O presente estudo visa avaliar, por meio dos documentos oficiais do município de Macapá, informações dos critérios e práticas de sustentabilidade adotadas pelo governo local. Os dados obtidos demonstram que houve aumento no incremento de exigências de cunho ambiental aos editais de licitação, seja de forma quantitativa ou qualitativa para a utilização de critérios no sentido de atender a promoção da sustentabilidade ambiental por intermédio das compras efetuadas pela administração municipal. No entanto, este dado está aquém do que necessariamente deveria sinalizar a administração pública, uma vez que, tal medida deixou de ser excepcional e passou a ser a regra geral.
The theory holds that in emerging economies, such as the Brazilian one, companies seek to strengthen ties with governmental and institutional actors in order to improve their performance. From the ...theoretical perspective of the Institutional Theory, this study intends to contribute to previous research, integrating the fields of strategy and finance, investigating the influence of political connections, through campaign donations, the cost of capital and the performance of listed companies on B3. We worked with panel data for data analysis on the period ranging from 1998 to 2016. Our findings do not corroborate the theoretical and intuitive prediction that “crony capitalism” reduces the cost of capital and improves the performance of companies, since we did not obtain empirical evidence that allows affirming that the effect of donations on the cost of capital and the performance of connected companies is different from zero.
Based on the need for organizational institutions to act, through public policies, in the establishment of programs focused on the inclusion of People with Disabilities (PwD) in the labor market in ...Brazil. The Supported Employment methodology (SE) was constituted by directing and providing support, in the workplace, to PwD.
The purpose of this article is to evaluate the intra-organizational management of the inclusion of people with disabilities in the labor market in the southern region of Santa Catarina and the alignment with the precepts of Supported Employment (SE).
Using a qualitative approach, the multi-case study was carried out through interviews, based on semi-structured questions, in five companies in the southern region of SC that are required to hire PwD.
The research points out the movement of companies in the development of policies and practices for the inclusion of PwD in the job market. However, there is still a significant gap between company practices and SE precepts. There are no formal programs and policies with wide internal dissemination, about the drivers for PwD.
This study helps to address eventual difficulties of companies regarding practices in the inclusion of PwD, contributes to the definition of guidelines aimed at improving existing policies or in the development of new practices aimed at the inclusion of PwD.
Recently, several molecular genetic bases of polymorphic enzyme activities involved in drug activation and detoxification have been elucidated. Many molecular epidemiology studies based on these ...premises have sought to gather information on the association of genetically determined metabolic variants with different risks of environmentally induced cancer. While rare alterations of tumor suppressor genes dramatically raise cancer risk for the single affected subjects, far more common and less dramatic differences in genes encoding for drug metabolism enzymes can be responsible for a relatively small, but rather frequent increase of cancer risk at the population level. This increase could be especially important in specific cases of occupational, pharmacological or environmental exposure. Examination of the current literature reveals that the most extensively investigated metabolic polymorphisms are those of P450 1A1 and P450 2D6 cytochromes, glutathione
S-transferases (GSTs; M1 and, to a lesser extent, M3, P1 and T1) and
N-acetyltransferases (NATs; NAT1 and NAT2). Making reference to these enzymes, we have assayed the current knowledge on the relations among polymorphisms of human xenobiotic-metabolizing enzymes and cancer susceptibilities. We have found intriguing models of susceptibility toward different types of cancer. We have reviewed and commented these models on light of the complex balance among different enzyme activities that, in each individual, determines the degree of each cancer susceptibility. Moreover, we have found techniques of molecular genetic analysis, more suitable than previous ones on phenotypic expression, now allowing better means to detect individuals at risk of cancer. According to the models presently available, a systematic screening of individuals at risk seems to make sense only in situations of well defined carcinogenic exposures and when performed by the polymorphism analysis of coordinated enzyme activities concurring to the metabolism of the carcinogen(s) in question. Genetic polymorphism analysis can allow for the detection of patients more prone to some types of specific cancers, or to the adverse effects of specific pharmaceutical agents. Considering the increasingly confirmed double-edged sword nature of metabolism polymorphism (both wild-type and variant alleles can predispose to cancer, albeit in different situations of exposure), individual susceptibility to cancer should be monitored as a function of the nature, and mechanism of action, of the carcinogen(s) to which the individual under study is known to be exposed, and with reference to the main target organ of the considered type of exposure.
B-cell chronic lymphocytic leukemia (B-CLL) is the most common leukemia in human adults of the Western world and no definitive cure is yet available. The disease is characterized by accumulation of ...clonal malignant B lymphocytes resistant to apoptosis. Strategies to hit the anti-apoptotic drift of the Bcl-2 family in B-CLL cells are being explored. A novel peptidomimetic based on the BH3 domain of the pro-apoptotic protein Bim and recently shown to exert significant apoptotic activity on acute myeloid leukemia cells, both in vitro and in vivo, was assayed on ex-vivo derived leukemic cells from untreated B-CLL patients (n=7). We found that this peptide, named 072RB, induced apoptosis of B-CLL samples at a concentration that does not affect viability of peripheral and bone marrow derived lymphocytes from healthy donors. Apoptosis was demonstrated by activation of Bak and Bax, externalization of plasma membranes phosphadydilserines, appearance of hypodiploid events in DNA flow cytometry histograms and was accompanied by dissipation of the mitochondrial transmembrane potential. Before the onset of marked apoptotic signs a progressive decline of the relevant anti-apoptotic proteins Bcl-XL and Mcl-1 could be observed. The negative control peptide 072RBL94A was ineffective for B-CLL cells, supporting the sequence specificity of 072RB activity. No relationship was found between responsiveness to 072RB and Mcl-1/Bcl-XL basal levels or decrease magnitude, possibly because of the limited sample size of the study. Altogether, we demonstrate that 072RB induces significant apoptosis of B-CLL cells subsequent to Bcl-XL and Mcl-1 down-regulation.
This paper addresses the determinants of dominance by resource borrowers or savers in credit unions in the southern region of Brazil. The study is a prevalence of previous and convergent work that ...discuss the dominance and its effects. In order to evaluate the influence of the determining factors on credit unions about the type of domination, we adopted panel date the multivariate analysis technique. The results of the study pointed out that the objects investigated present dominance of members who are credit borrowers, and present determinant factors that are significant and that influence the rate of domination of the borrower. The proposition becomes relevant by contributing with empirical evidence already existing in other contexts. Given the growing participation of credit unions in the economy, and their impact on local development. Conflict of interests of the participants allied to the analysis of an environmental, balanced or turbulent context, can influence the movements, policies or group arrangements. Investigations that deal with decisions and power relations between quota holders, whether as board members or even managers, in a dual or trial function appearing to be important in future studies.
Contexto: A governança corporativa surgiu da necessidade de proteger os acionistas dos abusos da diretoria executiva das empresas, da inércia dos conselhos de administração e das falhas das ...auditorias. As cooperativas vêm aderindo às práticas de boa governança, buscando, com isso, melhorar o desempenho e a sustentabilidade. Objetivo: este estudo objetiva analisar como se apresenta a evolução da qualidade das práticas de governança e gestão das cooperativas do estado de Santa Catarina, e classificá-las segundo o nível de governança e gestão. Método: com o intuito de alcançar o objetivo da pesquisa, adotou-se uma pesquisa com abordagem quantitativa e de caráter descritiva. O procedimento adotado foi a pesquisa de levantamento, com dados obtidos na base de dados do SESCOOP-SC das cooperativas que participam do PDGC. Resultados: os resultados apontam para uma correlação na evolução entre a governança e a gestão. Também demonstram que a maioria das cooperativas 66,95% estão classificadas nos clusters avançado e em consolidação quanto à qualidade da governança e da gestão.
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