A naturally selected dimorphism within the HLA-B44 supertype alters class I structure, peptide repertoire, and T cell recognition

HLA-B*4402 and B*4403 are naturally occurring MHC class I alleles that are both found at a hi,,h frequency in all human populations, and vet they only differ by one residue on the alpha2 helix (B*4402 Aspl56-->B*4403 Leu156) CTLs discriminate between HLA-B*4402 and B*4403, and these allotypes stimulate strong mutual allogeneic responses reflecting their known barrier to hemopoeitic stem cell transplantation. Although HLA-B*4402 and B*4403 share >95% of their peptide repertoire, B*4403 presents more unique peptides than B*4402, consistent with the stronger T cell alloreactivity observed toward B*4403 compared with B*4402. Crystal structures of B*4402 and B*4403 show how the polymorphisin at position 156 is completely buried and yet alters both the peptide and the heavy chain conformation, relaxing ligand selection by B*4403 compared with B*4402. Thus, the polymorphism between HLA-B*4402 and B 4403 modifies both peptide repertoire and T cell recognition, and is reflected lit the paradoxically powerful alloreactivity that occurs across this minimal mismatch. The findings suggest that these closely related class I genes are maintained lit diverse human populations through their differential impact on the selection of peptide ligands and the T cell repertoire.

Promiscuous CTL recognition of viral epitopes on multiple human leukocyte antigens: Biological validation of the proposed HLA A24 supertype

Multiple HLA class I alleles can bind peptides with common sequence motifs due to structural similarities in the peptide binding cleft, and these groups of alleles have been classified into supertypes. Nine major HLA supertypes have been proposed, including an A24 supertype that includes A*2301, A*2402, and A*3001. Evidence for this A24 supertype is limited to HLA sequence homology and/or similarity in peptide binding motifs for the alleles. To investigate the immunological relevance of this proposed supertype, we have examined two viral epitopes (from EBV and CMV) initially defined as HLA-A*2301-binding peptides. The data clearly demonstrate that each peptide could be recognized by CTL clones in the context of A*2301 or A*2402; thus validating the inclusion of these three alleles within an A24 supertype. Furthermore, CTL responses to the EBV epitope were detectable in both A*2301(+) and A*2402(+) individuals who had been previously exposed to this virus. These data substantiate the biological relevance of the A24 supertype, and the identification of viral epitopes with the capacity to bind promiscuously across this supertype could aid efforts to develop CTL-based vaccines or immunotherapy. The degeneracy in HLA restriction displayed by some T cells in this study also suggests that the dogma of self-MHC restriction needs some refinement to accommodate foreign peptide recognition in the context of multiple supertype alleles.

Mosquito host-feeding patterns and implications for Japanese encephalitis virus transmission in northern Australia and Papua New Guinea

Japanese encephalitis (JE) virus spread to northern Australia during the 1990s, transmitted by Culex annulirostris Skuse and other mosquitoes (Diptera: Culicidae). To determine the relative importance of various hosts for potential vectors of JE virus, we investigated the host-feeding patterns of mosquitoes in northern Australia and Western Province of Papua New Guinea, with particular attention to pigs, Sus scrofa L. - the main amplifying host of JE virus in South-east Asia. Mosquitoes were collected by CDC light traps baited with dry ice and 1-octen-3-ol, run 16.00-08.00 hours, mostly set away from human habitations, if possible in places frequented by feral pigs. Bloodmeals of 2569 mosquitoes, representing 15 species, were identified by gel diffusion assay. All species had fed mostly on mammals: only 30%) were trapped where domestic pigs were kept close to human habitation. From seven of eight locations on the Australian mainland, the majority of Cx. annulirostris had obtained their bloodmeals from marsupials, probably the Agile wallaby Macropus agilis (Gould). Overall proportions of mosquito bloodmeals identified as marsupial were 60% from the Gulf Plains region of Australia, 78% from the Cape York Peninsula and 64% from the Daru area of Papua New Guinea. Thus, despite the abundance of feral pigs in northern Australia, our findings suggest that marsupials divert host-seeking Cx. annulirostris away from pigs. As marsupials are poor JE virus hosts, the prevalence of marsupials may impede the establishment of JE virus in Australia.

Sitting time and work patterns as indicators of overweight and obesity in Australian adults

BACKGROUND: Increasing levels of physical inactivity and sedentariness are contributing to the current overweight and obesity epidemic. In this paper, the findings of two recent studies are used to explore the relationships between sitting time ( in transport, work and leisure), physical activity and body mass index (BMI) in two contrasting samples of adult Australians. METHODS: Data on sitting time, physical activity, BMI and a number of demographic characteristics were compared for participants in two studies-529 women who were participants in a preschool health promotion project ('mothers'), and 185 men and women who were involved in a workplace pedometer study ('workers'). Relationships between age, number of children, physical activity, sitting time, BMI, gender and work patterns were explored. Logistic regression was used to predict the likelihood of being overweight or obese, among participants with different physical activity, sitting time and work patterns. RESULTS: The total reported time spent sitting per day ( across all domains) was almost 6 h less among the mothers than the workers (P

Life transitions and changing physical activity patterns in young women

Background: Physical activity (PA) patterns are likely to change in young adulthood in line with changes in lifestyle that occur in the transition from adolescence to adulthood. The aim of this study was to ascertain whether key life events experienced by young women in their early twenties are associated with increasing levels of inactivity. Methods: This was a 4-year follow-up of 7281 participants (aged 18 to 23 years at baseline) in the Australian Longitudinal Study of Women's Health, with self-reported measures of PA, life events, body mass index (BMI), and sociodemographic variables. Results: The cross-sectional data indicated no change in PA between baseline (57% active) and follow-up (56% active). However, for almost 40% of the sample, PA category changed between baseline and follow-up, with approximately 20% of the women changing from being active to inactive, and another 20% changing from being inactive to active. After adjustment for age, other sociodemographic variables, BMI, and PA at baseline, women who reported getting married, having a first or subsequent child, or beginning paid work were more likely to be inactive at follow-up than those who did not report these events. Conclusions: The results suggest that life events such as getting married, having children, and starting work are associated with decreased levels of PA in young adult women. Strategies are needed to promote maintenance of activity at the time when most women experience these key life-stage transitions.

Winding patterns for actively shielded shim coils with asymmetric target-fields

A method is presented for calculating the currents and winding patterns required to design independent zonal and tesseral shim coils for magnetic resonance imaging. Both actively shielded and unshielded configurations are considered, and the region of interest can be located asymmetrically with respect to the coil's length. Streamline, target-field and Fourier-series methods are utilized. The desired target-field is specified at two cylindrical radii, on and inside a circular conducting cylinder of length 2L and radius a. The specification is over some asymmetric portion pL < z < qL of the coil's length (-1 < p < q < 1). Arbitrary functions are used in the outer sections, -L < z < pL and qL < z < L, to ensure continuity of the magnetic field across the entire length of the coil. The entire field is then periodically extended as a half-range cosine Fourier series about either end of the coil. The resultant Fourier coefficients are then substituted into the Fourier-series expressions for the internal and external magnetic fields, and current densities and stream functions on both the primary coil and shield. A contour plot of the stream function directly gives the required coil winding patterns. Spherical harmonic analysis and shielding analysis on field calculations from a ZX shim coil indicate that example designs and theory are well matched.

Interaction of directional, neuromuscular and egocentric constraints on the stability of preferred bimanual coordination patterns

We investigated how the relative direction of limb movements in external space (iso- and non-isodirectionality), muscular constraints (the relative timing of homologous muscle activation) and the egocentric frame of reference (moving simultaneously toward/away the longitudinal axis of the body) contribute to the stability of coordinated movements. In the first experiment, we attempted to determine the respective stability of isodirectional and non-isodirectional movements in between-persons coordination. In a second experiment, we determined the effect of the relative direction in external space, and of muscular constraints, on pattern stability during a within-person bimanual coordination task. In the third experiment we dissociated the effects on pattern stability of the muscular constraints, relative direction and egocentric frame of reference. The results showed that (1) simultaneous activation of homologous muscles resulted in more stable performance than simultaneous activation of non-homologous muscles during within-subject coordination, and that (2) isodirectional movements were more stable than non-isodirectional movements during between-persons coordination, confirming the role of the relative direction of the moving limbs in the stability of bimanual coordination. Moreover, the egocentric constraint was to some extent found distinguishable from the effect of the relative direction of the moving limbs in external space, and from the effect of the relative timing of muscle activation. In summary, the present study showed that relative direction of the moving limbs in external space and muscular constraints may interact either to stabilize or destabilize coordination patterns. (C) 2003 Published by Elsevier B.V.

Dendritic branching of pyramidal cells in the visual cortex of the nocturnal owl monkey: A fractal analysis

The branching structure of neurones is thought to influence patterns of connectivity and how inputs are integrated within the arbor. Recent studies have revealed a remarkable degree of variation in the branching structure of pyramidal cells in the cerebral cortex of diurnal primates, suggesting regional specialization in neuronal function. Such specialization in pyramidal cell structure may be important for various aspects of visual function, such as object recognition and color processing. To better understand the functional role of regional variation in the pyramidal cell phenotype in visual processing, we determined the complexity of the dendritic branching pattern of pyramidal cells in visual cortex of the nocturnal New World owl monkey. We used the fractal dilation method to quantify the branching structure of pyramidal cells in the primary visual area (V1), the second visual area (V2) and the caudal and rostral subdivisions of inferotemporal cortex (ITc and ITr, respectively), which are often associated with color processing. We found that, as in diurnal monkeys, there was a trend for cells of increasing fractal dimension with progression through these cortical areas. The increasing complexity paralleled a trend for increasing symmetry. That we found a similar trend in both diurnal and nocturnal monkeys suggests that it was a feature of a common anthropoid ancestor.

Morfologia e distribuição sedimentar em um sistema estuarino tropical : Baía de Vitória, ES

A Baía de Vitória é um sistema estuarino da costa leste do Brasil que apresenta grande importância econômica e características ímpares, já que se desenvolveu entre três unidades geomorfológicas distintas. Apesar disto, este ambiente apresenta poucos estudos relacionados às suas características geológicas e oceanográficas. O presente trabalho se focou no preenchimento desta lacuna através da descrição da morfologia, da distribuição sedimentar e dos padrões sonográficos da Baía de Vitória, buscando relações entre os mesmos e inferindo os processos sedimentares dominantes em cada trecho do estuário. A análise integrada mostrou boa correlação entre os métodos e revelou a grande complexidade deste sistema estuarino. Três diferentes regiões foram identificadas mostrando processos distintos: o estuário superior apresentou input sedimentar fluvial e processos estuarinos; um largo trecho da região central do sistema apresentou características erosivas, relacionadas a adaptações morfológicas e ao aumento das correntes provocadas pelos estreitamentos artificiais da baía, propiciando a formação de formas de fundo; e a boca do estuário se apresentou dominada por processos marinhos. Parte da região central do estuário mostrou características mascaradas pela atividade antrópica através da instalação de pontes, aterros e dragagens.

Using objects and patterns to implement domain ontologies

Ontologies are becoming an important mechanism to build information systems. Nevertheless, there is still no systematic approach to support the design of such systems using tools that are common to information systems developers. In this paper, we propose an approach for deriving object frameworks from domain ontologies and then we show the application of this approach in the software process domain.

On the discovery of business processes orchestration patterns

COORDINSPECTOR is a Software Tool aiming at extracting the coordination layer of a software system. Such a reverse engineering process provides a clear view of the actually invoked services as well as the logic behind such invocations. The analysis process is based on program slicing techniques and the generation of, System Dependence Graphs and Coordination Dependence Graphs. The tool analyzes Common Intermediate Language (CIL), the native language of the Microsoft .Net Framework, thus making suitable for processing systems developed in any .Net Framework compilable language. COORDINSPECTOR generates graphical representations of the coordination layer together with business process orchestrations specified in WSBPEL 2.0

Discovering coordination patterns

A large and growing amount of software systems rely on non-trivial coordination logic for making use of third party services or components. Therefore, it is of outmost importance to understand and capture rigorously this continuously growing layer of coordination as this will make easier not only the veri cation of such systems with respect to their original speci cations, but also maintenance, further development, testing, deployment and integration. This paper introduces a method based on several program analysis techniques (namely, dependence graphs, program slicing, and graph pattern analysis) to extract coordination logic from legacy systems source code. This process is driven by a series of pre-de ned coordination patterns and captured by a special purpose graph structure from which coordination speci cations can be generated in a number of di erent formalisms

Domain-Specific Language for Coordination patterns

The integration and composition of software systems requires a good architectural design phase to speed up communications between (remote) components. However, during implementation phase, the code to coordinate such components often ends up mixed in the main business code. This leads to maintenance problems, raising the need for, on the one hand, separating the coordination code from the business code, and on the other hand, providing mechanisms for analysis and comprehension of the architectural decisions once made. In this context our aim is at developing a domain-specific language, CoordL, to describe typical coordination patterns. From our point of view, coordination patterns are abstractions, in a graph form, over the composition of coordination statements from the system code. These patterns would allow us to identify, by means of pattern-based graph search strategies, the code responsible for the coordination of the several components in a system. The recovering and separation of the architectural decisions for a better comprehension of the software is the main purpose of this pattern language