Lead(II)-induced formation and coordination of 3,4-dihydro-3-thioxo-1,2,4-triazin-5(2H)-one

Cyclization of (n)butyl glyoxylate thiosemicarbazone (HBuTSC) under reflux in the presence of Pb(OAc)(2) led to tile formation of the complex [Pb(HTz)(2)] (H(2)Tz = 3,4-dihydro-3-thioxo-1,2,4-triazin-5(2H)-one), which after recrystallization from DMSO afforded the polymer [Pb(Tz)](n), the first example of a Tz(2-) metal complex. (C) 2008 Elsevier B.V. All rights reserved.

Novel Zn(2+)-binding Sites in Human Transthyretin IMPLICATIONS FOR AMYLOIDOGENESIS AND RETINOL-BINDING PROTEIN RECOGNITION

Human transthyretin (TTR) is a homotetrameric protein involved in several amyloidoses. Zn(2+) enhances TTR aggregation in vitro, and is a component of ex vivo TTR amyloid fibrils. We report the first crystal structure of human TTR in complex with Zn(2+) at pH 4.6-7.5. All four structures reveal three tetra-coordinated Zn(2+)-binding sites (ZBS 1-3) per monomer, plus a fourth site (ZBS 4) involving amino acid residues from a symmetry-related tetramer that is not visible in solution by NMR.Zn(2+) binding perturbs loop E-alpha-helix-loop F, the region involved in holo-retinol-binding protein (holo-RBP) recognition, mainly at acidic pH; TTR affinity for holo-RBP decreases similar to 5-fold in the presence of Zn(2+). Interestingly, this same region is disrupted in the crystal structure of the amyloidogenic intermediate of TTR formed at acidic pH in the absence of Zn(2+). HNCO and HNCA experiments performed in solution at pH 7.5 revealed that upon Zn(2+) binding, although the alpha-helix persists, there are perturbations in the resonances of the residues that flank this region, suggesting an increase in structural flexibility. While stability of the monomer of TTR decreases in the presence of Zn(2+), which is consistent with the tertiary structural perturbation provoked by Zn(2+) binding, tetramer stability is only marginally affected by Zn(2+). These data highlight structural and functional roles of Zn(2+) in TTR-related amyloidoses, as well as in holo-RBP recognition and vitamin A homeostasis.

Coordination of nitro-thiosemicarbazones to ruthenium(II) as a strategy for anti-trypanosomal activity improvement

Complexes [RuCl(H4NO(2)Fo4M)(bipy)(dppb)]PF(6) (1), [RuCl(H4NO(2)Fo4M)(Mebipy)(dppb)]PF(6) (2), [RuCl(H4NO(2)Fo4M)(phen)(dppb)]PF(6) (3), [RuCl(H4NO(2)Ac4M)(bipy)(dppb)]PF(6) (4), [RuCl(H4NO(2)Ac4M)(Mebipy)(dppb)]PF(6) (5) and [RuCl(H4NO(2)Ac4M)(phen)(dppb)]PF(6) (6) with N(4)-methyl-4-nitrobenzalde hyde thiosemicarbazone (H4NO(2)Fo4M) and N(4)-methyl-4-nitroacetophenone thiosemicarbazone (H4NO(2) Ac4M) were obtained from [RuCl(2)(bipy)(dppb)], [RuCl(2)(Mebipy)(dppb)], and [RuCl(2)(phen)(dppb)], (dppb = 1,4-bis(diphenylphospine)butane; bipy = 2,2`-bipyridine: Mebipy = 4,4`-dimethyl-2,2`-bipyridine: phen = 1,10-phenanthroline). In all cases the thiosemicarbazone is attached to the metal center through the sulfur atom. Complexes (1-6), together with the corresponding ligands and the Ru precursors were evaluated for their ability to in vitro suppress the growth of Trypanosoma cruzi. All complexes were more active than their corresponding ligands and precursors. Complexes (1-3) and (5) revealed to be the most active among all studied compounds with ID(50) = 0.6-0.8 mu M. In all cases the association of the thiosemicarbazone with ruthenium, dppb and bipyridine or phenanthroline in one same complex proved to be an excellent strategy for activity improvement. (C) 2010 Elsevier Masson SAS. All rights reserved.

Formalization of an architectural model for exception handling coordination based on CA action concepts

Architectures based on Coordinated Atomic action (CA action) concepts have been used to build concurrent fault-tolerant systems. This conceptual model combines concurrent exception handling with action nesting to provide a general mechanism for both enclosing interactions among system components and coordinating forward error recovery measures. This article presents an architectural model to guide the formal specification of concurrent fault-tolerant systems. This architecture provides built-in Communicating Sequential Processes (CSPs) and predefined channels to coordinate exception handling of the user-defined components. Hence some safety properties concerning action scoping and concurrent exception handling can be proved by using the FDR (Failure Divergence Refinement) verification tool. As a result, a formal and general architecture supporting software fault tolerance is ready to be used and proved as users define components with normal and exceptional behaviors. (C) 2010 Elsevier B.V. All rights reserved.

Is the unfolding of the group discussion off-pattern? Improving coordination support in educational forums using mobile devices

A forum is a valuable tool to foster reflection in an in-depth discussion; however, it forces the course mediator to continually pay close attention in order to coordinate learners` activities. Moreover, monitoring a forum is time consuming given that it is impossible to know in advance when new messages are going to be posted. Additionally, a forum may be inactive for a long period and suddenly receive a burst of messages forcing forum mediators to frequently log on in order to know how the discussion is unfolding to intervene whenever it is necessary. Mediators also need to deal with a large amount of messages to identify off-pattern situations. This work presents a piece of action research that investigates how to improve coordination support in a forum using mobile devices for mitigating mediator`s difficulties in following the status of a forum. Based on summarized information extracted from message meta-data, mediators consult visual information summaries on PDAs and receive textual notifications in their mobile phone. This investigation revealed that mediators used the mobile-based coordination support to keep informed on what is taking place within the forum without the need to log on their desktop computer. (C) 2009 Elsevier Ltd. All rights reserved.

Group 11 (Cu, Ag, Au) promotion of 15%Co/Al(2)O(3) Fischer-Tropsch synthesis catalysts

Co/Al(2)O(3) Fischer-Tropsch synthesis catalysts promoted with different quantities of Group 11 metals (Cu, Ag, Au) were characterized and tested. The presence of relatively small quantities of such metals enhanced Co reducibility and, in the cases of Ag and Au, improved the surface Co metal active site densities. EXAFS experiments with the most loaded catalyst samples show that only Co-Co and Me-Me (Me = Cu, Ag and Au) coordination could be observed. This suggests that the greater fraction of the metals form different phases. However, the reduction promoting effect of the Group 11 metal is severely hampered once the catalyst receives a mild passivation treatment following primary reduction. An explanation in terms of promoter segregation during primary reduction is proposed. At lower promoter levels (0.83%Ag and 1.51%Au) and higher Ag levels (2.76%), significant gains in Co active site densities were achieved resulting in improved CO conversion levels relative to the unpromoted catalyst. Moreover, slight decreases in light product (e.g., CH(4)) selectivity and slight increases in C(5)+ selectivity were achieved. At high Au loading (5.05%), however, too much Au was loaded which, although significantly increasing the fraction of Co reduced, blocked Co surface sites and resulted in decreased Co conversion rates. While Cu facilitated Co reduction, the increased fraction of reduced Co did not translate to improved active site densities. It appears that a fraction of Cu tended to cover the rim of Co clusters, resulting in decreases in CO conversion rates and detrimental increases in light product selectivity. (C) 2009 Elsevier B.V. All rights reserved.

Automatic devices for monitoring environmentally induced auto-oxidative degradation of artistic materials in conservation sites

This paper describes an automatic device for in situ and continuous monitoring of the ageing process occurring in natural and synthetic resins widely used in art and in the conservation and restoration of cultural artefacts. The results of tests carried out under accelerated ageing conditions are also presented. This easy-to-assemble palm-top device, essentially consists of oscillators based on quartz crystal resonators coated with films of the organic materials whose response to environmental stress is to be addressed. The device contains a microcontroller which selects at pre-defined time intervals the oscillators and records and stores their oscillation frequency. The ageing of the coatings, caused by the environmental stress and resulting in a shift in the oscillation frequency of the modified crystals, can be straightforwardly monitored in this way. The kinetics of this process reflects the level of risk damage associated with a specific microenvironment. In this case, natural and artificial resins, broadly employed in art and restoration of artistic and archaeological artefacts (dammar and Paraloid B72), were applied onto the crystals. The environmental stress was represented by visible and UV radiation, since the chosen materials are known to be photochemically active, to different extents. In the case of dammar, the results obtained are consistent with previous data obtained using a bench-top equipment by impedance analysis through discrete measurements and confirm that the ageing of this material is reflected in the gravimetric response of the modified quartz crystals. As for Paraloid B72, the outcome of the assays indicates that the resin is resistant to visible light, but is very sensitive to UV irradiation. The use of a continuous monitoring system, apart from being obviously more practical, is essential to identify short-term (i.e. reversible) events, like water vapour adsorption/desorption processes, and to highlight ageing trends or sudden changes of such trends. (C) 2007 Elsevier B.V. All rights reserved.

Oncostatin M is a novel glucocorticoid-dependent neuroinflammatory factor that enhances oligodendrocyte precursor cell activity in demyelinated sites

The innate immune reaction to tissue injury is a natural process, which can have detrimental effects in the absence of negative feedbacks by glucocorticoids (GCs). Although acute lipopolysaccharide (LPS) challenge is relatively harmless to the brain parenchyma of adult animals, the endotoxin is highly neurotoxic in animals that are treated with the GC receptor antagonist RU486. This study investigated the role of cytokines of the gp130-related family in these effects, because they are essential components of the inflammatory process that provide survival signals to neurons. Intracerebral LPS injection stimulated expression of several members of this family of cytokines, but oncostatin M (Osm) was the unique ligand to be completely inhibited by the RU486 treatment. OSM receptor (Osmr) is expressed mainly in astrocytes and endothelial cells following LPS administration and GCs are directly responsible for its transcriptional activation in the presence of the endotoxin. In a mouse model of demyelination, exogenous OSM significantly modulated the expression of genes involved in the mobilization of oligodendrocyte precursor cells (OPCs), differentiation of oligodendrocyte, and production of myelin. In conclusion, the activation of OSM signaling is a mechanism activated by TLR4 in the presence of negative feedback by GCs on the innate immune system of the brain. OSM absence is associated with detrimental effects of LPS, whereas exogenous OSM favors repair response to demyelinated regions. (C) 2010 Elsevier Inc. All rights reserved.

Interaction of giant extracellular Glossoscolex paulistus hemoglobin (HbGp) with zwitterionic surfactant N-hexadecyl-N,N-dimethyl-3-ammonio-1-propanesulfonate (HPS): Effects of oligomeric dissociation

The present work focuses on the interaction between the zwitterionic surfactant N-hexadecyl-N,N-dimethyl-3-ammonio-1-propanesulfonate (HPS) and the giant extracellular hemoglobin of Glossoscolex paulistus (HbGp). Electronic optical absorption, fluorescence emission and circular dichroism spectroscopy techniques, together with Gel-filtration chromatography, were used in order to evaluate the oligomeric dissociation as well as the autoxidation of HbGp as a function of the interaction with HPS. A peculiar behavior was observed for the HPS-HbGp interaction: a complex ferric species formation equilibrium was promoted, as a consequence of the autoxidation and oligomeric dissociation processes. At pH 7.0, HPS is more effective up to 1 mM while at pH 9.0 the surfactant effect is more intense above 1 mM. Furthermore, the interaction of HPS with HbGp was clearly less intense than the interaction of this hemoglobin with cationic (CTAC) and anionic (SDS) surfactants. Probably, this lower interaction with HPS is due to two factors: (i) the lower electrostatic attraction between the HPS surfactant and the protein surface ionic sites when compared to the electrostatic interaction between HbGp and cationic and anionic surfactants, and (ii) the low cmc of HPS, which probably reduces the interaction of the surfactant in the monomeric form with the protein. The present work emphasizes the importance of the electrostatic contribution in the interaction between ionic surfactants and HbGp. Furthermore, in the whole HPS concentration range used in this study, no folding and autoxidation decrease induced by this surfactant were observed. This is quite different from the literature data on the interaction between surfactants and tetrameric hemoglobins, that supports the occurrence of this behavior for the intracellular hemoglobins at low surfactant concentration range. Spectroscopic data are discussed and compared with the literature in order to improve the understanding of hemoglobin-surfactant interaction as well as the acid isoelectric point (pI) influence of the giant extracellular hemoglobins on their structure-activity relationship. (c) 2007 Elsevier B.V. All rights reserved.

Languaging in virtual learning sites : studies of online encounters in the language-focused classroom

This thesis focuses upon a series of empirical studies which examine communication and learning in online glocal communities within higher education in Sweden. A recurring theme in the theoretical framework deals with issues of languaging in virtual multimodal environments as well as the making of identity and negotiation of meaning in these settings; analyzing the activity, what people do, in contraposition to the study of how people talk about their activity. The studies arise from netnographic work during two online Italian for Beginners courses offered by a Swedish university. Microanalyses of the interactions occurring through multimodal video-conferencing software are amplified by the study of the courses’ organisation of space and time and have allowed for the identification of communicative strategies and interactional patterns in virtual learning sites when participants communicate in a language variety with which they have a limited experience. The findings from the four studies included in the thesis indicate that students who are part of institutional virtual higher educational settings make use of several resources in order to perform their identity positions inside the group as a way to enrich and nurture the process of communication and learning in this online glocal community. The sociocultural dialogical analyses also shed light on the ways in which participants gathering in discursive technological spaces benefit from the opportunity to go to class without commuting to the physical building of the institution providing the course. This identity position is, thus, both experienced by participants in interaction, and also afforded by the ‘spaceless’ nature of the online environment.

Towards a Methodology for Coordination Mechanism Selection in Open Systems

Agent-oriented software engineering (AOSE) is a promising approach to developing applications for dynamic open systems. If well developed, these applications can be opportunistic, taking advantage of services implemented by other developers at appropriate times. However, methodologies are needed to aid the development of systems that are both flexible enough to be opportunistic and tightly defined by the application requirements. In this paper, we investigate how developers can choose the coordination mechanisms of agents so that the agents will best fulfil application requirements in an open system.