Distinction between familial and sporadic forms of colorectal cancer showing DNA microsatellite instability

Attempts to classify colorectal cancer into subtypes based upon molecular characterisation are overshadowed by the classical stepwise model in which the adenoma-carcinoma sequence serves as the morphological counterpart. Clarity is achieved when cancers showing DNA microsatellite instability (MSI) are distinguished as sporadic MSI-low (MSI-L), sporadic MSI-high (MSI-H) and hereditary non-polyposis colorectal cancer (HNPCC). Divergence of the 'methylator' pathway into MSI-L and MSI-H is at least partly determined by the respective silencing of MGMT and hMLH1. Multiple differences can be demonstrated between sporadic and familial (HNPCC) MSI-H colorectal cancer with respect to early mechanisms, evolution, molecular characterisation, demographics and morphology. By acknowledging the existence of multiple pathways, rapid advances in the fields of basic and translational research will occur and this will lead to improved strategies for the prevention, early detection and treatment of colorectal cancer. (C) 2002 Elsevier Science Ltd. All rights reserved.

The effect of incentive reforms upon productivity: Evidence from the Vietnamese rice industry

In this study we use region-level panel data on rice production in Vietnam to investigate total factor productivity (TFP) growth in the period since reunification in 1975. Two significant reforms were introduced during this period, one in 1981 allowing farmers to keep part of their produce, and another in 1987 providing improved land tenure. We measure TFP growth using two modified forms of the standard Malmquist data envelopment analysis (DEA) method, which we have named the Three-year-window (TYW) and the Full Cumulative (FC) methods. We have developed these methods to deal with degrees of freedom limitations. Our empirical results indicate strong average TFP growth of between 3.3 and 3.5 per cent per annum, with the fastest growth observed in the period following the first reform. Our results support the assertion that incentive related issues have played a large role in the decline and subsequent resurgence of Vietnamese agriculture.

Microevolution in island forms: the roles of drift and directional selection in morphological divergence of a passerine bird

Theory predicts that in small isolated populations random genetic drift can lead to phenotypic divergence; however this prediction has rarely been tested quantitatively in natural populations. Here we utilize natural repeated island colonization events by members of the avian species complex, Zosterops lateralis, to assess whether or not genetic drift alone is an adequate explanation for the observed patterns of microevolutionary divergence in morphology. Morphological and molecular genetic characteristics of island and mainland populations are compared to test three predictions of drift theory: (1) that the pattern of morphological change is idiosyncratic to each island; (2) that there is concordance between morphological and neutral genetic shifts across island populations; and (3) for populations whose time of colonization is known, that the rate of morphological change is sufficiently slow to be accounted for solely by genetic drift. Our results are not consistent with these predictions. First, the direction of size shifts was consistently towards larger size, suggesting the action of a nonrandom process. Second, patterns of morphological divergence among recently colonized populations showed little concordance with divergence in neutral genetic characters. Third, rate tests of morphological change showed that effective population sizes were not small enough for random processes alone to account for the magnitude of microevolutionary change. Altogether, these three lines of evidence suggest that drift alone is not an adequate explanation of morphological differentiation in recently colonized island Zosterops and therefore we suggest that the observed microevolutionary changes are largely a result of directional natural selection.

Catalytically active Dengue virus NS3 protease forms aggregates that are separable by size exclusion chromatography

An active form of the Dengue virus protease NS3 (CF40.Gly.NS3pro) was expressed in Escherichia coli. This construct consists of a critical 40 amino acid cofactor domain from NS2B fused to the N-terminal 184 amino acid protease domain of NS3 via a flexible, covalent linker (Gly(4)SerGly(4)). The recombinantly produced protein is soluble and has a hexa-histidine tag engineered at the N-terminus for ease of purification using metal affinity chromatography. However, the presence of lower molecular weight impurities after affinity chromatography indicated the need for additional purification steps. The consistent appearance of these impurities suggested that they may be the products of proteolysis and/or auto-proteolysis. The latter possibility was subsequently excluded by the observation of the same impurities in a purified, catalytically inactive form of the recombinant protease (CF40.Gly.NS3pro.SA). Further analysis indicated that these impurities may represent premature translation termination products. Regardless of their origin, they were shown to form various sized aggregates with full-length CF40.Gly.NS3pro that can be separated by size exclusion chromatography, yielding fractions of active protease of sufficient purity for crystallisation trials. The ultimate goal of these studies is to obtain a crystal structure of a catalytically active form of the Dengue virus NS3 protease for structure-based drug design. (C) 2002 Elsevier Science (USA). All rights reserved.

Finite, three-dimensional adsorbed phase growth in activated carbon mesopores

The role of PACs (primary adsorption centers) in the mesopore (i.e., transport) region of activated carbons during adsorption of polar species, such as water, is unclear. A classical model of three-dimensional adsorption on finite PACs is presented. The model is a preliminary, theoretical investigation into adsorption on mesopore PACs and is intended to give some insight into the energetic and physical processes at work. Work processes are developed to obtain isotherms and three-dimensional sorbate growth on PACs of varying size and energetic characteristics. The work processes allow two forms of adsorbed phase growth: densification at constant boundary and boundary growth at constant density. Relatively strong sorbate-sorbent interactions and strong surface tension favor adsorbed phase densification over boundary growth. Conversely, relatively weak sorbate-sorbent interactions and weak surface tension favor boundary growth over densification. If sorbate-sorbate interactions are strong compared to sorbate-sorbent interactions, condensation with hysteresis occurs. This can also give rise to delayed boundary growth, where all initial adsorption occurs in the monolayer only. The results indicate that adsorbed phase growth on PACs may be quite complex.

Surface diffusion of strong adsorbing vapours on porous carbon

Surface diffusion of strongly adsorbing hydrocarbon vapours on activated carbon was measured by using a constant molar flow method (D.D. Do, Dynamics of a semi-batch adsorber with constant molar supply rate: a method for studying adsorption rate of pure gas, Chem. Eng. Sci. 50 (1995) 549), where pure adsorbate is introduced into a semi-batch adsorber at a constant molar flow rate. The surface diffusivity was determined from the analysis of pressure response versus time, using a linear mathematical model developed earlier. To apply the linear theory over the non-linear range of the adsorption isotherm, we implement a differential increment method on the system which is initially equilibrated with some pre-determined loading. By conducting the experiments at different initial loadings, the surface diffusivity can be extracted as a function of loading. Propane, n-butane, n-hexane, benzene, and ethanol were used as diffusing adsorbate on a commercial activated carbon. It is found that the surface diffusivity of these strongly adsorbing vapours increases rapidly with loading, and the surface diffusion flux contributes significantly to the total flux and cannot be ignored. The surface diffusivity increases with temperature according to the Arrhenius law, and for the paraffins tested it decreases with the molecular weight of the adsorbate. (C) 2002 Elsevier Science Ltd. All rights reserved.

A comparative study of carbon gasification with O-2 and CO2 by density functional theory calculations

A comparative study of carbon gasification with O-2 and CO2 was conducted by using density functional theory calculations. It was found that the activation energy and the number of active sites in carbon gasification reactions are significantly affected by both the capacity and manner of gas chemisorption. O-2 has a strong adsorption capacity and the dissociative chemisorption of O-2 is thermodynamically favorable on either bare carbon surface or even isolated edge sites. As a result, a large number of semiquinone and o-quinone oxygen can be formed indicating a significant increase in the number of active sites. Moreover, the weaker o-quinone C-C bonds can also drive the reaction forward at (ca. 30%) lower activation energy. Epoxy oxygen forms under relatively high O-2 pressure, and it can only increase the number of active sites, not further reduce the activation energy. CO2 has a lower adsorption capacity. Dissociative chemisorption of CO2 can only occur on two consecutive edge sites and o-quinone oxygen formed from CO2 chemisorption is negligible, let alone epoxy oxygen. Therefore, CO2-carbon reaction needs (ca 30%) higher activation energy. Furthermore, the effective active sites are also reduced by the manner Of CO2 chemisorption. A combination of the higher activation energy and the fewer active sites leads to the much lower reaction rate Of CO2-carbon.

The trans-membrane protein p25 forms highly specialized domains that regulate membrane composition and dynamics

Trans-membrane proteins of the p24 family are abundant, oligomeric proteins predominantly found in cis-Golgi membranes. They are not easily studied in vivo and their functions are controversial. We found that p25 can be targeted to the plasma membrane after inactivation of its canonical KKXX motif (KK to SS, p25SS), and that p25SS causes the co-transport of other p24 proteins beyond the Golgi complex, indicating that wild-type p25 plays a crucial role in retaining p24 proteins in cis-Golgi membranes. We then made use of these observations to study the intrinsic properties of these proteins, when present in a different membrane context. At the cell surface, the p25SS mutant segregates away from both the transferrin receptor and markers of lipid rafts, which are enriched in cholesterol and glycosphingolipids. This suggests that p25SS localizes to, or contributes to form, specialized membrane domains, presumably corresponding to oligomers of p25SS and other p24 proteins. Once at the cell surface, p25SS is endocytosed, together with other p24 proteins, and eventually accumulates in late endosomes, where it remains confined to well-defined membrane regions visible by electron microscopy. We find that this p25SS accumulation causes a concomitant accumulation of cholesterol in late endosomes, and an inhibition of their motility - two processes that are functionally linked. Yet, the p25SS-rich regions themselves seem to-exclude not only Lamp1 but also accumulated cholesterol. One may envision that p25SS accumulation, by excluding cholesterol from oligomers, eventually overloads neighboring late endosomal membranes with cholesterol beyond their capacity (see Discussion). In any case, our data show that p25 and presumably other p24 proteins are endowed with the intrinsic capacity to form highly specialized domains that control membrane composition and dynamics. We propose that p25 and other p24 proteins control the fidelity of membrane transport by maintaining cholesterol-poor membranes in the Golgi complex.

High rate of detection of primary aldosteronism, including surgically treatable forms, after 'non-selective' screening of hypertensive patients

Background Wide testing of the aldosterone: renin ratio among hypertensive individuals has revealed primary aldosteronism to be common, with most patients normokalaemic. Some investigators, however, have reported aldosterone-producing adenoma to be rare among patients so detected. Objective To test the hypothesis that differences among reported studies in the rate of detection of aldosterone-producing adenoma (as opposed to bilateral adrenal hyperplasia) reflect differences in the procedures used for diagnosis of primary aldosteronism, and the methods used to identify aldosterone-producing adenomas. Methods In the newly established Princess Alexandra Hospital Hypertension Unit (PAHHU), we used procedures developed by Greenslopes Hospital Hypertension Unit (which reports that more than 30% of patients with primary aldosteronism have aldosterone-producing adenomas) to diagnose primary aldosteronism and determine the subtype. All patients with an increased aldosterone: renin ratio (measured after correction for hypokalaemia and while the patient was not receiving interfering medications) underwent fludrocortisone suppression testing to confirm or exclude primary aldosteronism; if they were positive, they underwent genetic testing to exclude glucocorticoid-remediable aldosteronism before adrenal venous sampling was used to differentiate lateralizing from bilateral primary aldosteronism. Results This approach allowed PAHHU to diagnose, within 2 years, 54 patients [only seven (13%) hypokalaemic] with primary aldosteronism. All tested negative for glucocorticoid-remediable aldosteronism. Aldosterone production was lateralized to one adrenal in 15 patients (31%; only six hypokalaemic) and was bilateral in 34 (69%; all normokalaemic) of 49 patients who underwent adrenal venous sampling. Among patients with lateralizing adrenal hyperplasia, computed tomography revealed an ipsilateral mass in only six and a contralateral lesion in one. Fourteen patients underwent unilateral adrenalectomy, which cured the hypertension in seven and improved it in the remainder. In patients with bilateral primary aldlosteronism, hypertension responded to spironolactone (112.5-50 mg/ day) or amiloride (2.5-10 mg/day). Conclusion When performed with careful regard to confounding factors, measurement of the aldosterone: renin ratio in all hypertensive individuals, followed by fludrocortisone suppression testing to confirm or exclude primary aldosteronism and adrenal venous sampling to determine the subtype, can result in the detection of significant numbers of patients with specifically treatable or potentially curable hypertension. (C) 2003 Lippincott Williams Wilkins.

A evasão discente no contexto da reestruturação universitária : o caso dos cursos de Administração e Ciências Contábeis da Universidade Federal do Espírito Santo

O objetivo desta pesquisa foi levantar os motivos que influenciam a evasão discente em quatro cursos de graduação da Universidade Federal do Espírito Santo. A reestruturação universitária proposta pelo REUNI - Programa de Apoio a Planos de Expansão das Universidades Federais serviu como contexto ao estudo, pois instituiu diretrizes para o combate à evasão no ensino superior. O modelo de evasão de cunho sociológico proposto por Tinto (1997) baseou as análises realizadas nesta pesquisa porque toma a instituição como responsável por ações capazes de criar um ambiente de aprendizado necessário à permanência do estudante. A pesquisa de campo quali-quantitativa foi realizada com os alunos evadidos e com os coordenadores dos cursos de Administração Diurno e Ciências Contábeis Noturno e dos novos cursos Administração Noturno e Ciências Contábeis Vespertino. Foram alcançados 95 alunos evadidos e os quatro coordenadores, sendo aplicado questionário semiaberto aos alunos evadidos e feitas entrevistas semiestruturadas com os coordenadores. Dados do sistema acadêmico (SIE/UFES) foram utilizados para o levantamento das variáveis. Os números fornecem evidências de que o resultado da aprendizagem traduzido pelo desempenho acadêmico torna-se um forte causador da evasão por abandono. O baixo coeficiente de rendimento relacionou-se ao desligamento por abandono na maioria dos casos. Em relação às formas de evasão, a desistência e o desligamento por abandono totalizaram 87,4% dos casos, com maior incidência de evasão no segundo e terceiro ano do curso. O ponto crítico da evasão parece confirmar-se do 2º ao 5º semestre e 62% dos casos de evasão que se situaram nesse lapso temporal apresentaram coeficiente de rendimento de 0,00 a 3,00. Os resultados evidenciaram os motivos que mais influenciaram os alunos a deixar o curso: i) a necessidade de trabalhar enquanto frequentava o curso, ii) a descoberta de novos interesses; iii) a incompatibilidade entre os horários do trabalho e do curso; iv) a escolha da carreira profissional ainda muito jovem e v) a falta de orientação aos alunos sobre normas, penalidades, planejamento do curso, periodização, etc. e deficiências na comunicação institucional.

O mar não está para peixe : uma etnografia dos conflitos socioambientais em torno da Zona de Proteção Marinha e da comunidade pesqueira do Bugigão – RESEXMAR do Corumbau/Bahia.

A Reserva Extrativista Marinha (RESEXMAR) do Corumbau foi criada no ano de 2000, a partir de uma ação coletiva, iniciada em 1997 por meio das lideranças de pescadores locais, na busca de instrumento jurídico que garantisse o acesso exclusivo dos recursos pesqueiros contra a atividade da pesca comercial de camarão sete-barbas que se instalou na década de 1980. Durante o processo de criação da RESEXMAR do Corumbau, os pescadores obtiveram apoio de órgãos governamentais, como a Coordenação Nacional de Populações Tradicionais (CNPT) e de entidades ambientalistas do terceiro setor – Associação Pradense de Proteção Ambiental (APPA), e posteriormente a Conservation International do Brasil (CI-Brasil). Entretanto, após a criação da RESEXMAR do Corumbau – entre os anos 2000 e 2002 – foi elaborado o Plano de Manejo que orientaria a gestão da Unidade de Conservação (UC). O documento foi capitaneado pela equipe técnica e científica vinculada à CI-Brasil, tendo como ponto de destaque a criação de áreas de exclusão total da atividade da pesca, por meio da Zona de Proteção Marinha (ZPM). A ideia de uma ZPM, para a CI-Brasil, era que de forma indireta e em médio e longo prazo, os pescadores se beneficiariam com o possível aumento de produção de pescado, contanto que 30% de cobertura de recifes tivesse algum tipo de proteção dos processos ecológicos, tais como reprodução e crescimento de espécies. Durante as discussões do Plano de Manejo e atualmente uma parcela de pescadores locais contestaram os limites da ZPM, pois iria restringir o acesso aos recursos pesqueiros. No entanto, tal contestação foi suprimida pelas relações não formais que os membros da CI-Brasil possuíam com o núcleo familiar principal da Vila do Corumbau, forçando os demais em um acordo formal temporário. Tal questionamento evidenciou um conflito de conjunto de normas distintas entre pescadores artesanais em relação à CI-Brasil e IBAMA: a pesca artesanal ‒ um tipo de ação que segue normas específicas das quais elementos humanos e não humanos interagem conjuntamente, evidenciando um conhecimento prático e corporizado constituindo um modelo compreensivo de mundo e de natureza; conceitos modernos e globalizantes de uma natureza totalmente desvinculada das práticas locais artesanais, com forte articulação de uma entidade ambientalista de alcance internacional, guiada pela emergência das questões ambientais, imprimindo no local (o lugar da prática da pesca tradicional) a ideia de um espaço (Áreas Marinhas Protegidas), desencaixado de formas específicas de natureza/culturas.

Trypanosoma cruzi prevalence and clinical forms in blood donor candidates in Brazil

The prevalence and clinical forms of Trypanosoma cruzi were evaluated among blood donor candidates attended at a general hospital in Rio de Janeiro, Brazil, from January 1997 to April 1999. The investigation was done by means of the indirect hemagglutination test and was confirmed via ELISA. Data were collected from clinical examinations, conventional electrocardiogram, chest radiography and echocar-diography. The results showed that despite Trypanosoma cruzi prevalence of 1.17% (128 patients), mainly in males aged 40 years or over, 70.8% of these patients, mainly males aged 19 to 39 years, demonstrated abnormalities that allowed the diagnosis of cardiopathy and/or esophagopathy. This once again corroborates the importance of Trypanosoma cruzi infection in urban centers.

When Corporate Governance crosses the firm borders: family firms in local productive systems

The family involvement in firms is observable is most economies around the world, although there are significant differences among these countries, not only regarding its predominance in these economies, but also in what refers to the levels of involvement of the family in business. This research aims at understanding the family-based firms’ management when compared to non family based, with particular regards to the forms of corporate governance. This analysis is based on case studies and on secondary data found in the literature to support the findings from the empirical research. The data was collected via face to face in-depth interviews with entrepreneurs from the furniture and the events organisation industries (where the family is predominantly present in the furniture but not on the events organisation industry) and with industry and regional business associations. The case studies used in this research allowed the comparison between the Portuguese firms when the family plays an important role in business and those in which the family is absent. It has been found that there are important differences in businesses in countries/industries/local productive systems in which the family is seen as a dominant institution in the society (where businesses are based on strong ties; there is a harmonious relationship between the family members; and the family is accepted locally and dominates the firm organization) and on situations in which the family plays a more marginal role in the society. In fact, the family brings special characteristics to the business, in terms of management, corporate governance, inter and intra firm relationships and succession. Our findings confirm other empirical studies’ results found in the literature. Thus, this article provides a discussion on the factors that play a role in the form of corporate governance structure in family firms highlighting the pros and cons of organising the firm around the family.

Strong and weak Allee effects and chaotic dynamics in Richards' growths

In this paper we define and investigate generalized Richards' growth models with strong and weak Allee effects and no Allee effect. We prove the transition from strong Allee effect to no Allee effect, passing through the weak Allee effect, depending on the implicit conditions, which involve the several parameters considered in the models. New classes of functions describing the existence or not of Allee effect are introduced, a new dynamical approach to Richards' populational growth equation is established. These families of generalized Richards' functions are proportional to the right hand side of the generalized Richards' growth models proposed. Subclasses of strong and weak Allee functions and functions with no Allee effect are characterized. The study of their bifurcation structure is presented in detail, this analysis is done based on the configurations of bifurcation curves and symbolic dynamics techniques. Generically, the dynamics of these functions are classified in the following types: extinction, semi-stability, stability, period doubling, chaos, chaotic semistability and essential extinction. We obtain conditions on the parameter plane for the existence of a weak Allee effect region related to the appearance of cusp points. To support our results, we present fold and flip bifurcations curves and numerical simulations of several bifurcation diagrams.