Solution structure of a DNA duplex containing the exocyclic lesion 3,N4-etheno-2'-deoxycytidine opposite 2'-deoxyguanosine

Vinyl chloride reacts with cellular DNA producing 3,N4-etheno-2'-deoxycytidine (epsilonC) along with other exocyclic adducts. The solution structure of an oligodeoxynucleotide duplex containing an epsilonC.dG base pair was determined by high-resolution NMR spectroscopy and molecular dynamics simulations. NMR data indicated that the duplex adopts a right-handed helical structure having all residues in anti orientation around the glycosylic torsion angle. The epsilonC adduct has a sugar pucker in the C3'-endo/C4'-exo region while the rest of the residues are in the C2'-endo/C3'-exo range. NOE interactions established Watson-Crick alignments for canonical base pairs of the duplex. The imino proton of the lesion-containing base pair resonated as a sharp signal that was resistant to water exchange, suggesting hydrogen bonding. Restrained molecular dynamics simulations generated three-dimensional models in excellent agreement with the spectroscopic data. The refined structures are slightly bent at the lesion site without major perturbations of the sugar-phosphate backbone. The adduct is displaced and shifted toward the major groove of the helix while its partner on the complementary strand remains stacked. The epsilonC(anti).dG(anti) base pair alignment is sheared and stabilized by the formation of hydrogen bonds. The biological implications of structures of epsilonC-containing DNA duplexes are discussed.     

Differential expression of mammalian TRP homologues across tissues and cell lines

Mammalian homologues of the Drosophila trp gene have been invoked as the structural basis for the currents associated with capacitative Ca2+ entry (CCE) in many cell types. Trp homologues are members of a large protein family that may associate as channel subunits providing an explanation for the functional diversity of store-operated channels observed in these cells. However, there is little information as to which of these genes are co-expressed at the cellular level. We have examined the tissue specific expression of five mammalian trp genes and determined which are co-expressed in five different cell lines. The results show tissue- and cell-specific co-expression of multiple trp forms. This implies that the subunit composition of a particular CCE channel may vary depending on the cell type.     

Genetic mapping of a major susceptibility locus for juvenile myoclonic epilepsy on chromosome 15q

The epilepsies are a group of disorders characterised by recurrent seizures caused by episodes of abnormal neuronal hyperexcitability involving the brain. Up to 60 million people are affected worldwide and genetic factors may contribute to the aetiology in up to 40% of patients. The most common human genetic epilepsies display a complex pattern of inheritance. These are categorised as idiopathic in the absence of detectable structural or metabolic abnormalities. Juvenile myoclonic epilepsy (JME) is a distinctive and common variety of familial idiopathic generalised epilepsy (IGE) with a prevalence of 0.5-1.0 per 1000 and a ratio of sibling risk to population prevalence (lambda(s)) of 42. The molecular genetic basis of these familial idiopathic epilepsies is entirely unknown, but a mutation in the gene CHRNA4, encoding the alpha4 subunit of the neuronal nicotinic acetylcholine receptor (nAChR), was recently identified in a rare Mendelian variety of idiopathic epilepsy. Chromosomal regions harbouring genes for nAChR subunits were therefore tested for linkage to the JME trait in 34 pedigrees. Significant evidence for linkage with heterogeneity was found to polymorphic loci encompassing the region in which the gene encoding the alpha7 subunit of nAChR (CHRNA7) maps on chromosome 15q14 (HLOD = 4.4 at alpha = 0.65; Z(all) = 2.94, P = 0.0005). This major locus contributes to genetic susceptibility to JME in a majority of the families studied.     

Use of the polymerase chain reaction in the diagnosis of leprosy

A case is described in which a pericardial branch of a nongrafted left internal mammary artery communicated directly with the distal left anterior descending artery, following saphenous vein bypass grafting. This type of collateralization following coronary artery bypass surgery seems to be very rare, and perhaps could protect the myocardium from severe ischemia.     

Using Multimedia to Support Cooperative Editing

By Cooperative Editing we mean the coordinated manipulation of information by a group of authors. During the editing process the (co-)authors need to communicate their ideas, drafts and constraints (remotely or face-to-face) until a final version of the information is achieved. For the different phases of this process - discussion of ideas, editing, cross-checking - different media or media integration are adequate. Furthermore, analysing the transition from individual work to group work, within different human activities, two pitfalls are often detected if computer support is considered: a) technological communication difficulties, especially if the group is remotely located on heterogeneous hardware, associated with a fall in productivity and frequent social inadequacies of the group's computer support; b) the lack of integrated media processing tools available for group editing. In order to solve these problems, we suggest that Multimedia can be applied in two ways: to effectively support the necessary group communication links; and to enhance the expressiveness of the information edited. To test this statement we have been conceptualising and implementing a prototype system. Most of the techniques involved can be used in other tools that need multimedia capabilities or that support other specific types of group activities. The innovative aspects of the work are the use of multimedia techniques to support demanding applications, possibly on cross-platforms, and the integration of several concepts to support cooperation.     

Kinetic model for water/oil absorption of mesquite gum (Prosopis juliflora) and gum arabic (Acacia senegal)

The water and oil uptake of mesquite and arabic gums in powdered form was studied at temperatures of 23, 35 and 45°C. A previously proposed equation to predict osmotic equilibrium was tested using the experimental data with both gums and a good statistical fit was obtained. Mesquite gum showed the highest water and oil absorption at all temperatures studied. Temperature dependence of the reciprocal of the S₁ and WL_∞ were determined using an Arrhenius equation. The activation energy for water and oil absorption for gum arabic was 21.98 and 39.57 kJ mol⁻¹, compared to that of mesquite gum having values of 15.79 and 46.16 kJ mol⁻¹, respectively. A second order kinetic model was obtained for water and oil absorption for both gums.     

A systematic approach for product families formation in Reconfigurable Manufacturing Systems

The aim of this work is to establish a methodology for an effective working of Reconfigurable Manufacturing Systems (RMSs). These systems are the next step in manufacturing, allowing the production of any quantity of highly customised and complex products together with the benefits of mass production. In RMSs, products are grouped into families, each of which requires a system configuration. The system is configured to produce the first family of products. Once it is finished, the system is reconfigured in order to produce the second family, and so forth. Therefore, the effectiveness of a RMS depends on the formation of the best set of product families. Therefore, a methodology for grouping products into families, which takes into account the requirements of products in RMSs, is an issue of core importance. These requirements are modularity, commonality, compatibility, reusability, and product demand. The methodology starts by calculating, for each product requirement, a matrix that summarises the similarity between pairs of products. Then, through the use of the AHP methodology, a unique matrix that comprises the similarity values between products is obtained. The Average Linkage Clustering algorithm is applied to this matrix in order to obtain a dendogram that shows the diverse sets of product families that may be formed.     

Analytical model of displacement amplification and stiffness optimization for a class of flexure-based compliant mechanisms

The paper formulates an analytical method for displacement and stiffness calculations of planar compliant mechanisms with single-axis flexure hinges. The procedure is based on the strain energy and Castigliano’s displacement theorem and produces closed-form equations that incorporate the compliances characterizing any analytically-defined hinge, together with the other geometric and material properties of the compliant mechanism. Displacement amplification, input stiffness and output stiffness calculations can simply be performed for any serial compliant mechanism. The class of amplifying compliant mechanisms that contain symmetric corner-filleted or circular flexure hinges is specifically addressed here. A parametric study of the mechanism performance is performed, based on the mathematical model, and an optimization procedure is proposed, based on Lagrange’s multipliers and Kuhn-Tucker conditions, which identifies the design vector that maximizes the performance of these flexure-based compliant mechanisms. Independent finite element simulation confirms the analytical model predictions.