eMelanoBase: An online locus-specific variant database for familial melanoma

A proportion of melanoma,prone individuals in both familial and non,familial contexts has been shown to carry inactivating mutations in either CDKN2A or, rarely, CDK4. CDKN2A is a complex locus that encodes two unrelated proteins from alternately spliced transcripts that are read in different frames. The alpha transcript (exons 1a, 2, and 3) produces the p16INK4A cyclin-dependent kinase inhibitor, while the beta transcript (exons 1beta and 2) is translated as p14ARF, a stabilizing factor of p53 levels through binding to MDM2. Mutations in exon 2 can impair both polypeptides and insertions and deletions in exons 1alpha, 1beta, and 2, which can theoretically generate p16INK4A,p14ARF fusion proteins. No online database currently takes into account all the consequences of these genotypes, a situation compounded by some problematic previous annotations of CDKN2A related sequences and descriptions of their mutations. As an initiative of the international Melanoma Genetics Consortium, we have therefore established a database of germline variants observed in all loci implicated in familial melanoma susceptibility. Such a comprehensive, publicly accessible database is an essential foundation for research on melanoma susceptibility and its clinical application. Our database serves two types of data as defined by HUGO. The core dataset includes the nucleotide variants on the genomic and transcript levels, amino acid variants, and citation. The ancillary dataset includes keyword description of events at the transcription and translation levels and epidemiological data. The application that handles users' queries was designed in the model,view. controller architecture and was implemented in Java. The object-relational database schema was deduced using functional dependency analysis. We hereby present our first functional prototype of eMelanoBase. The service is accessible via the URL www.wmi.usyd.e, du.au:8080/melanoma.html.

Ovary colonization by Claviceps africana is related to ergot resistance in male-sterile sorghum lines

Ergot, caused by Claviceps africana, has emerged as a serious threat to sorghum hybrid seed production worldwide. In the absence of gene-for-gene-based qualitative resistance in commercial cultivars, varieties with high pollen production that can escape ergot infection are preferred. Recent demonstration of differences in ergot susceptibility among male-sterile lines has indicated the presence of partial resistance. Using chitin-specific fluorescin-isothiocyanate-conjugated wheat germ agglutin and callose-specific aniline blue, this study investigated the process of sorghum ovary colonization by C. africana. Conidia germinated within 24 h after inoculation (a.i.); the pathogen was established in the ovary by 79 h a.i., and at least half of the ovary was converted into sphacelial tissue by 120 h a.i. Changes in fungal cell wall chitin content and strategic callose deposition in the host tissue were associated with penetration and invasion of the ovary. The rate of ovary colonization differed in three male-sterile lines that also differed in ergot susceptibility. This work demonstrates a possible histological basis for partial resistance in male-sterile sorghum lines that could lay the foundation for variety improvement through further breeding and selection.

Issues related to the wearing of fall-arrest harnesses in the construction industry

Work-related falls continues to be one of the leading causes of fatalities in the Australian construction industry, and the failure to use fall protection equipment, such as fall-arrest harnesses and arresting devices, has been found to be a contributing factor. In an attempt to gain an understanding of the issues surrounding the use of fallarrest harness systems by construction workers a study involving semi-structured interviews of 15 male construction workers was carried out at three construction sites. The majority of interviewees commented that there was discomfort in wearing a fall-arrest harness; that there were a number of problems when anchored via an arresting device; and that using a fall-arrest system reduced productivity. Most of the interviewees considered that they needed safety precautions against falls, and they expressed the view that workers’ attitudes towards safety depended critically upon their supervisors’ attitude towards safety. It was also found that workers were not trained in rescue procedures. Interviewees expressed concern that retrieval of a suspended worker may not be carried out in time to prevent the onset of suspension trauma. A number of issues were identified which require further research, such as, investigation into suspension trauma, harness and arresting device design, training provided to workers, and the provision for rescues.

Identification of residues which regulate activity of the STE20-related kinase hMINK

Activity of the STE20-related kinase hMINK was investigated. hMINK was expressed widely, though not ubiquitously, in human tissues: highest levels being found in haematopoietic tissues but also in brain, placenta, and lung. Mutagenesis revealed that T-191. and Y-193 in the substrate recognition loop of the catalytic domain were critical for kinase activity against exogenous substrates and autophosphorylation. A mutation on T-187 showed reduced enzymatic activity against exogenous substrates but retained autophosphorylationactivity. Phosphorylation was confirmed by the use of a phospho-specific T-187 antibody. hMINK activated the JNK signal transduction pathway and optimal JNK activation occurred when the C-terminus was deleted. In addition, overexpression of the C-terminal domain devoid of kinase activity also resulted in significant activation of the JNK pathway. These data suggest that hMINK requires an activation step that dissociates the C terminal, thereby freeing the catalytic domain to interact with substrates. Models for receptor-mediated activation of hMINK are discussed. (C) 2002 Elsevier Science (USA). All rights reserved.

Differences in lung function, growth parameters and frequency of hospital admissions between adolescents with cystic fibrosis-related diabetes and controls

As survival of patients with CF increases,glucose intolerance and cystic fibrosisrelated diabetes (CFRD),ar e increasingly recognised common complications. CFRD may be preceded by a pre-diabetic state. Using markers identified as being associated with CFRD may improve targeted screening. Aim: To identify features consistently predicting CFRD in paediatric patients. Patients diagnosed with CFRD between January 1997–January 2002 were compared with age and sex matched controls. Clinical,micr obiological, and hospitalisation data was collected at time of CFRD diagnosis,and at six monthly intervals for 3 yr prior to diagnosis. Eight patients with CFRD were identified,mean age 13.7 yr (S.D. 3.49) at time of diagnosis. Control patients underwent OGTT to ensure normal glucose tolerance. Patients with CFRD had a lower FEV1 up to 12 months prior to diagnosis however, this was only significant at diagnosis. There was no difference in weight and height z scores between the 2 groups; however,the decrease in weight and height z scores in the CFRD group over 3 yr prior to diagnosis was significant. Mean number of days in hospital and admissions per patient significantly increased in the CFRD group,6 months prior to diagnosis. No other significant differences were observed between the 2 groups. Conclusions: This study has shown a difference in lung function,gr owth parameters and frequency of hospital admissions between patients with CFRD and controls. These differences may be utilised as tools for targeted screening in the paediatricyadolescent population. Further larger scale studies are required to improve guidelines for targeted screening in this population.

Isolation and characterization of a cone snail protease with homology to CRISP proteins of the pathogenesis-related protein superfamily

The pathogenesis-related (PR) protein superfamily is widely distributed in the animal, plant, and fungal kingdoms and is implicated in human brain tumor growth and plant pathogenesis. The precise biological activity of PR proteins, however, has remained elusive. Here we report the characterization, cloning and structural homology modeling of Tex31 from the venom duct of Conus textile. Tex31 was isolated to >95% purity by activity-guided fractionation using a para-nitroanilide substrate based on the putative cleavage site residues found in the propeptide precursor of conotoxin TxVIA. Tex31 requires four residues including a leucine N-terminal of the cleavage site for efficient substrate processing. The sequence of Tex31 was determined using two degenerate PCR primers designed from N-terminal and tryptic digest Edman sequences. A BLAST search revealed that Tex31 was a member of the PR protein superfamily and most closely related to the CRISP family of mammalian proteins that have a cysteine-rich C-terminal tail. A homology model constructed from two PR proteins revealed that the likely catalytic residues in Tex31 fall within a structurally conserved domain found in PR proteins. Thus, it is possible that other PR proteins may also be substrate-specific proteases.

Emergence of joint attention: Relationships between gaze following, social referencing, imitation, and naming in infancy

The authors investigated the extent to which the joint-attention behaviors of gaze following, social referencing, and object-directed imitation were related to each other and to infants vocabulary development in a sample of 60 infants between the ages of 8 and 14 months. Joint-attention skills and vocabulary development were assessed in a laboratory setting. Split-half reliability analyses on the joint-attention measures indicated that the tasks reliably assessed infants' capabilities. In the main analysis, no significant correlations were found among the joint-attention behaviors except for a significant relationship between gaze following and the number of names in infants' productive vocabularies. The overall pattern of results did not replicate results of previous studies (e.g., M. Carpenter, K. Nagell, & M. Tomasello, 1998) that found relationships between various emerging joint-attention behaviors.

Structural refinement of systems specified in object-z and CSP

This paper is concerned with methods for refinement of specifications written using a combination of Object-Z and CSP. Such a combination has proved to be a suitable vehicle for specifying complex systems which involve state and behaviour, and several proposals exist for integrating these two languages. The basis of the integration in this paper is a semantics of Object-Z classes identical to CSP processes. This allows classes specified in Object-Z to be combined using CSP operators. It has been shown that this semantic model allows state-based refinement relations to be used on the Object-Z components in an integrated Object-Z/CSP specification. However, the current refinement methodology does not allow the structure of a specification to be changed in a refinement, whereas a full methodology would, for example, allow concurrency to be introduced during the development life-cycle. In this paper, we tackle these concerns and discuss refinements of specifications written using Object-Z and CSP where we change the structure of the specification when performing the refinement. In particular, we develop a set of structural simulation rules which allow single components to be refined to more complex specifications involving CSP operators. The soundness of these rules is verified against the common semantic model and they are illustrated via a number of examples.

Sex- and race-related differences in cross-sectional geometry and bone density of the femoral mid-shaft in older adults

Background : Femoral shaft fracture incidence increases in older adults and is associated with low-energy trauma. Apart from bone density, the distribution and size of bone contributes to its strength. Aim : To examine if bone geometry and density of the femoral mid-shaft in older adults differs by sex and race, we studied 197 White women, 225 Black women, 242 White men, and 148 Black men aged 70-79 years participating in the Health, Aging, and Body Composition study; a prospective cohort study in the USA. A secondary purpose of the study was to examine the association of site-specific muscle and fat to bone geometry and density. Subjects and methods : Subjects were community-dwelling and reported no difficulty walking one-quarter of a mile or climbing stairs. Mid-femoral volumetric bone mineral density (vBMD, mg cm -3 ), total area (TA), cortical area (CA), medullary area (MA), cross-sectional moments of inertia (CSMI: I x , I y , J ), and muscle and fat areas (cm 2 ) were determined by computed tomography (CT; GE CT-9800, 10 mm slice thickness). Results : vBMD was greater in men than women with no difference by race ( p < 0.001). Bone areas and area moments of inertia were also greater in men than women ( p < 0.001), with Black women having higher values than White women for TA and CA. Standardizing geometric parameters for body size differences by dividing by powers of femur length did not negate the sex difference for TA and MA. Significant differences ( p < 0.05) among the four groups also remained for I x and J . Mid-thigh muscle area was an independent contributor to TA in all groups (Std beta = 0.181-0.351, p < 0.05) as well as CA in women (Std beta = 0.246-0.254, p < 0.01) and CSMI in White women (Std beta = 0.175-0.185, p < 0.05). Further, muscle area was a significant contributor to vBMD in Black women. Conclusion : These results indicate that bone geometry and density of the femoral diaphysis differs primarily by sex, rather than race, in older well-functioning adults. In addition, site-specific muscle area appears to have a potential contributory role to bone geometry parameters, especially in women.

Injury related risk behavior - a study of Australian skydivers

Risk taking behaviour has been identified as an important host-related determinant of injury in young adults. The aim of this study is to clarify the relationship between the two key elements of risk taking behaviour - ie, risk assessment and risk acceptance - in participants of a high risk sporting activity. Skydivers registered with the Australian Parachute Federation were sampled at several jump meetings held at three 'drop-zones' in North Eastern Australia. A cross sectional survey of 215 skydivers ascertained each subject's risk assessment of each of nine hypothetical sky diving scenes and whether or not they would jump in the described conditions. Variables which independently predicted an individual's risk assessment were age group (p < 0.05), gender (p < 0.05) and scene details (p < 0.001). Risk assessment was found to be a statistically significant predictor of the decision to jump, with a 22% decrease in the odds of jumping with every unit increase in risk assessment (OR = 0.78: 95% Cl; 0.76, 0.80). Gender was also found to be a statistically significant predictor of the decision to jump, with males being 19% more likely to jump than females, after controlling for age, experience, currency and risk assessment (OR = 1.19: 95% CI; 1.04, 1.38). The importance of these results is that, by quantifying the relationship between two key elements of risk taking behaviour and several important host factor determinants, they facilitate more informed discussion about the possible role of risk taking behaviour in the causation of injury.

Reforma do setor p??blico e participa????o sindical: o caso do sistema de pens??o italiano

O paper estuda o caso da recente reforma da Previd??ncia na It??lia, ilustrando a possibilidade de uma participa????o positiva dos sindicatos ??? tradicionalmente contr??rios ??s reformas ??? no processo de transforma????o do setor p??blico. Ap??s uma revis??o do sistema previdenci??rio italiano, altamente fragmentado e particularista na opini??o dos autores, e o apontamento de suas principais defici??ncias, o estudo concentra-se na an??lise de tr??s propostas de reforma ligadas aos governos de Amato (1992-93), Berlusconi (1994) e Dini (1995), respectivamente. O texto aborda tanto as propostas concretas de mudan??a, trazendo contribui????es sobre uma variedade consider??vel de medidas, seu impacto e aceita????o sociais e por categoria, como os objetivos visados e o processo pol??tico relacionado ?? sua discuss??o e tramita????o. Uma preocupa????o constante dos autores ?? a correla????o entre a postura e a participa????o dos sindicatos em mat??ria de reforma previdenci??ria, por um lado, e o avan??o das propostas governamentais, por outro. Segundo o estudo, a ampla participa????o da for??a sindical na negocia????o do projeto de reforma previdenci??ria do governo Dini representou um fator decisivo para sua aprova????o e implementa????o bem-sucedidas. Ao mesmo tempo, a delibera????o democr??tica para concilia????o de prefer??ncias e interesses (m??ltiplos no caso de assuntos norteados pela dicotomia bem comum/interesse particular) ??? objeto da ??ltima sess??o do estudo ??? ?? vista como uma forma de ampliar a participa????o sindical al??m das lideran??as, passando a incluir os rank-and-file trabalhadores, um procedimento que traz, igualmente, a for??a de uma decis??o majorit??ria. A an??lise da reforma da Previd??ncia italiana ?? ilustrada no paper com tabelas que trazem e comparam dados referentes ?? contribui????o previdenci??ria, ??s categorias de beneficiados e ??s diferentes propostas de reforma formuladas por sucessivos governos italianos.

O papel da cidade de Viçosa-MG na rede urbana : a especialização funcional de uma cidade média mineira

Rede é o nome dado para se referenciar qualquer forma que seja composta por linhas interligadas por pontos, sendo assim essa denominação é utilizada para participar de nomes e conceitos em diversas área do conhecimento. Na geografia isso não ocorre de forma diferente. As redes geográficas são a denominação dada as ligações feitas no espaço articuladas por pontos, notadamente são usadas para se fazer referência a redes materiais, mas podem ser mais imateriais ou abstratas a depender do objeto de pesquisa e do adjetivo adotado. A noção de redes urbanas nasceu vinculada aos objetos materiais, entretanto com a evolução da técnica passou a abranger objetos cada vez mais virtuais. As redes urbanas são compostas pelo conjunto de cidades, cada qual com sua centralidade representadas por pontos ou nós na rede, e pelas ligações entre elas, rodovias, hidrovias, infovias etc. As cidades que compõem a rede, por mais semelhanças que possam ter entre si, tem diferentes tipos e graus de centralidade, de poder de atração de pessoas, de recursos; sendo uma região de influência singular, que muda de tempos em tempos, face a evolução do território onde se insere. Tanto as centralidades quanto as redes de urbanas estão em constante mudança, necessitando sempre de atualização tornando o estudo das redes e das centralidades uma questão sempre nova; em especial quando considerado um território tão vasto e complexo como o brasileiro. Neste trabalho relatamos os resultados do estudo das especificidades da centralidade da cidade de Viçosa, que está localizada no interior do estado de Minas Gerais, Brasil. Este estudo fez uso de dados numéricos, fotográficos e cartográficos coletados em diversos momentos da evolução do município e da região onde este se insere, que revelaram as mudanças de qualidade e de intensidade na centralidade dessa cidade, hoje tipificada como média ou intermediária, inserida na rede urbana mineira. No período compreendido entre os anos de 1850 e 1930, Viçosa passou de uma inexpressiva localidade rural, a importante centro de produção de café, galgando ganhos políticos nesse período. Seguiu-se um período de menor pujança, por cerca de setenta anos, para depois, na virada do século XX para XXI, ressurgi como uma localidade especializada em oferecer serviços, notadamente vinculados ao ensino superior e à produção de ciência e tecnologia. Essa nova centralidade, ao contrário do que muitas vezes ocorre, não foi fruto nem de um recurso natural inerente ao território e nem, tão pouco, pela atuação de grandes grupos capitalistas. Foi galgado principalmente pela atuação do Estado que construiu ali as bases de uma especialização funcional, através da implantação de uma universidade pública.

Cidade-paisagem : novas perspectivas sobre a preservação da paisagem urbana no Brasil

The edification of the landscape in the scientific and social field, in speech as in the method, is taken in this study as a complex process, from which were developed relationships of dominance on the perception of space, which persist strongly consolidated, since the genesis of the conceptual practice till its actual praxis. Historically, the landscape studies took place slowly, immersed in many questions, in face of the multiplicity of meanings that the concept offers. In the psyche, the notion of landscape is present since a long time ago, as an unconscious human being practice, even before any ideological hypothesis formulation. However its materialization in the social conscious will come only from painting, and specially with the perspective, through the technicity of the view, at first wandering the infinity, now ordained in a frame‟. Since then, the landscape is perceived according to the order of the view, as the equivalent of nature and beauty, assuming at the same time, an important symbolic value, since it is linked to mnemonic and subjective processes that the being build with the territory. The domain on this space-cognitive experience, characteristic of the contemporary, consolidates in the social imaginary, building consensus on the landscape, whose aesthetic references make a cultural appeal, very pertinent to the actual capitalist dynamics of production the space worldwide, mainly of the spectacle and commodification of cities promoted by the city marketing. In Brazil, this consensual ideology of the landscape surpass the social imaginary and also dominates the political imaginary, whereas the main instrument for preserving the landscape, Decree-law 25, from November 30, 1937, and its limit to those of exceptional value or remarkable feature. The analysis of the processes for putting under governmental trust for inscription of goods by the landscape value, reveals the dominant, if not exclusive, adoption of selection criteria related to aesthetic aspects. Abstain, therefore, from what the nation considers patrimony , other landscapes that, besides not having, at first, remarkable aesthetic value, play a crucial role as an inheritance from ancestor relations between man and space and pre- existing condition for the same present and future relations. From this historical background, the research seeks to transfer into contemporaneity, the ideological analysis of the concept and its relation with the building of the landscape in the collective imaginary, in order to recognize, in current practices to landscape preservation, as much this genesis, rooted in aesthetics, remains strongly consolidated, feeding the current dynamics of consumption and commodification of the city. Therefore, as preliminary conclusion, one can state that the identification of landscapes of different value, especially aesthetic, maintains and intensify the treatment of the city as an object, a standard‟ commodity to be sold / traded on the world market, in detriment of its recognition as a dynamic process that, even though inserted in the global context, develops specificifities and peculiarities, inherent to the production of space, as Lefebvre preconizes, that is, to the production of life, social product , as characteristic, dissent generator

Tradutor das galáxias : questões de competência tradutória da cultura pop em webcomics

Dissertação (mestrado)—Universidade de Brasília, Instituto de Letras, Departamento de Línguas Estrangeiras e Tradução, Programa de Pós-Graduação em Estudos da Tradução, 2016.