886 resultados para Design structure matrix


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The aim of this work was to exemplify the specific contribution of both two- and three-dimensional (31)) X-ray computed tomography to characterise earthworm burrow systems. To achieve this purpose we used 3D mathematical morphology operators to characterise burrow systems resulting from the activity of an anecic (Aporrectodea noctunia), and an endogeic species (Allolobophora chlorotica), when both species were introduced either separately or together into artificial soil cores. Images of these soil cores were obtained using a medical X-ray tomography scanner. Three-dimensional reconstructions of burrow systems were obtained using a specifically developed segmentation algorithm. To study the differences between burrow systems, a set of classical tools of mathematical morphology (granulometries) were used. So-called granulometries based on different structuring elements clearly separated the different burrow systems. They enabled us to show that burrows made by the anecic species were fatter, longer, more vertical, more continuous but less sinuous than burrows of the endogeic species. The granulometry transform of the soil matrix showed that burrows made by A. nocturna were more evenly distributed than those of A. chlorotica. Although a good discrimination was possible when only one species was introduced into the soil cores, it was not possible to separate burrows of the two species from each other in cases where species were introduced into the same soil core. This limitation, partly due to the insufficient spatial resolution of the medical scanner, precluded the use of the morphological operators to study putative interactions between the two species.

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Purpose - Using Brandenburger and Nalebuff`s 1995 co-opetition model as a reference, the purpose of this paper is to seek to develop a tool that, based on the tenets of classical game theory, would enable scholars and managers to identify which games may be played in response to the different conflict of interest situations faced by companies in their business environments. Design/methodology/approach - The literature on game theory and business strategy are reviewed and a conceptual model, the strategic games matrix (SGM), is developed. Two novel games are described and modeled. Findings - The co-opetition model is not sufficient to realistically represent most of the conflict of interest situations faced by companies. It seeks to address this problem through development of the SGM, which expands upon Brandenburger and Nalebuff`s model by providing a broader perspective, through incorporation of an additional dimension (power ratio between players) and three novel, respectively, (rival, individualistic, and associative). Practical implications - This proposed model, based on the concepts of game theory, should be used to train decision- and policy-makers to better understand, interpret and formulate conflict management strategies. Originality/value - A practical and original tool to use game models in conflict of interest situations is generated. Basic classical games, such as Nash, Stackelberg, Pareto, and Minimax, are mapped on the SGM to suggest in which situations they Could be useful. Two innovative games are described to fit four different types of conflict situations that so far have no corresponding game in the literature. A test application of the SGM to a classic Intel Corporation strategic management case, in the complex personal computer industry, shows that the proposed method is able to describe, to interpret, to analyze, and to prescribe optimal competitive and/or cooperative strategies for each conflict of interest situation.

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Understanding the interfacial interactions and structure is important to better design and application of organic-inorganic nanohybrids. This paper presents our recent molecular dynamic studies on organoclays and polymer nanocomposites, including the layering behavior of organoclays, structural and dynamic properties of dioctadecyldimethyl ammoniums in organoclays, and interfacial interactions and structure of polyurethane nanocomposites. The results demonstrate that the layering behaviors of organoclays are closely related to the chain length of quaternary alkyl ammoniums and cation exchangeable capacity of clays. In addition to typical layered structures such as monolayer, bilayer and pseudo-trilayer, a pseudo-quadrilayer structure was also observed in organoclays modified with dioctadecyldimethyl ammoniums (DODDMA). In such a structure, alkyl chains do not lie flat within a single layer but interlace, and also jump to the next layer or even the next nearest layer. Moreover, the diffusion constants of nitrogen and methylene atoms increase with the temperature and methelene towards the tail groups. For polyurethane nanocomposite, the van der Waals interaction between apolar alkyl chains and soft segments of polyurethane predominates the interactions between organoclay and polyurethane. Different from most bulk polyurethane systems, there is no distinct phase-separated structure for the polyurethane.

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The chi-conopeptides MrIA and MrIB are 13-residue peptides with two disulfide bonds that inhibit human and rat norepinephrine transporter systems and are of significant interest for the design of novel drugs involved in pain treatment. In the current study we have determined the solution structure of MrIA using NMR spectroscopy. The major element of secondary structure is a hairpin with the two strands connected by an inverse gamma-turn. The residues primarily involved in activity have previously been shown to be located in the turn region (Sharpe, I. A.; Palant, E.: Schroder, C. L; Kaye, D. M.; Adams, D. I.; Alewood, P. F.; Lewis, R. J. J Biol Client 2003, 278, 40317-40323), which appears to be more flexible than the beta-strands based on disorder in the ensemble of calculated structures. Analogues of MrIA with N-terminal truncations indicate that the N-terminal residues play a role in defining a stable conformation and the native disulfide connectivity. In particular, noncovalent interactions between Val3 and Hypl2 are likely to be involved in maintaining a stable conformation. The N-terminus also affects activity, as a single N-terminal deletion introduced additional pharmacology at rat vas deferens, while deleting the first two amino acids reduced chi-conopeptide potency. This article was originally published online as an accepted preprint. The Published Online date corresponds to the preprint version. You can request a copy of the preprint by entailing the Biopolymers editorial office at biopolymers@wiley.com (c) 2005 Wiley Periodicals, Inc.

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The efficient and correct folding of bacterial disulfide bonded proteins in vivo is dependent upon a class of periplasmic oxidoreductase proteins called DsbA, after the Escherichia coli enzyme. In the pathogenic bacterium Vibrio cholerae, the DsbA homolog (TcpG) is responsible for the folding, maturation and secretion of virulence factors. Mutants in which the tcpg gene has been inactivated are avirulent; they no longer produce functional colonisation pill and they no longer secrete cholera toxin. TcpG is thus a suitable target for inhibitors that could counteract the virulence of this organism, thereby preventing the symptoms of cholera. The crystal structure of oxidized TcpG (refined at a resolution of 2.1 Angstrom) serves as a starting point for the rational design of such inhibitors. As expected, TcpG has the same fold as E. coli DsbA, with which it shares similar to 40% sequence identity. Ln addition, the characteristic surface features of DsbA are present in TcpG, supporting the notion that these features play a functional role. While the overall architecture of TcpG and DsbA is similar and the surface features are retained in TcpG, there are significant differences. For example, the kinked active site helix results from a three-residue loop in DsbA, but is caused by a proline in TcpG (making TcpG more similar to thioredoxin in this respect). Furthermore, the proposed peptide binding groove of TcpG is substantially shortened compared with that of DsbA due to a six-residue deletion. Also, the hydrophobic pocket of TcpG is more shallow and the acidic patch is much less extensive than that of E. coli DsbA. The identification of the structural and surface features that are retained or are divergent in TcpG provides a useful assessment of their functional importance in these protein folding catalysts and is an important prerequisite for the design of TcpG inhibitors. (C) 1997 Academic Press Limited.

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Gangliosides are known to be important in many biological processes. However, details concerning the exact function of these glycosphingolipids in cell physiology are poorly understood. in this study, the role of gangliosides present on the surface of rodent mast cells in maintaining cell structure was examined using RBL-2H3 mast cells and two mutant cell lines (E5 and D1) deficient in the gangliosides, GM(1) and the alpha-galactosyl derivatives of the ganglioside GD(1b). The two deficient cell lines were morphologically different from each other as well as from the parental RBL-2H3 cells. Actin filaments in RBL-2H3 and E5 cells were under the plasma membrane following the spindle shape of the cells, whereas in D1 cells, they were concentrated in large membrane ruffles. Microtubules in RBL-2H3 and E5 cells radiated from the centrosome and were organized into long, straight bundles. The bundles in D1 cells were thicker and organized circumferentially under the plasma membrane. The endoplasmic reticulum, the Golgi complex, and the secretory granule matrix were also altered in the mutant cell lines. These results suggest that the mast cell-specific alpha-galactosyl derivatives of ganglioside GD(1b) and GM(1) are important in maintaining normal cell morphology. (J Histochern Cytochem 58:83-93, 2010)

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Background: Enhanced cardiac matrix metalloproteinase activity (MMPs) has been associated with ventricular remodeling and cardiac dysfunction. It is unknown whether MMPs contribute to systolic/diastolic dysfunction and compensatory remodeling in 2-kidney, 1-clip (2K1C) hypertensive rats. To test this hypothesis, we used 2K1C rats after 2 weeks of surgery treated or not with a nonspecific inhibitor of MMPs (doxycycline). Methods and Results: We found that blood pressure and +/-dP/dt increased in 2K1C rats compared with sham groups, and these parameters were attenuated by doxycycline treatment (P < .05). Doxycycline also reversed cardiac hypertrophy observed in 2K1C rats (P < .05). Hypertensive rats showed increased MMP-2 levels in zymograms and in the tissue by immunofluorescence (P < .05) compared with sham groups. Increased total gelatinolytic activity was observed in untreated 2K1C rats when compared with sham groups (P < .05). Doxycycline decreased total gelatinolytic activity in 2K1C rats to control levels (P < .05). Conclusion: An imbalance in gelatinolytic activity, with increased MMP-2 levels and activity underlies the development of morphological and functional alterations found in the compensatory hypertrophy observed in 2K1C hearts. Because function and structure were restored by doxycycline, the inhibition of MMPs or their modulation may provide beneficial effects for therapeutic intervention in cardiac hypertrophy. (J Cardiac Fail 2010;16:599-608)

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Objectives: To compare the circulating levels of matrix metalloproteinase (MMP)-2, MMP-9, tissue inhibitors of metalloproteinase (TIMP)-1, TIMP-2, and the MMP-9/TIMP-1 and MMP-2/TIMP-2 ratios in preeclampsia and gestational hypertension with those found in normotensive pregnancies. Design and methods: We studied 83 pregnant women (30 healthy pregnant women with uncomplicated pregnancies, 26 with gestational hypertension, and 27 with preeclampsia) and 30 healthy nonpregnant women in a cross-sectional study. MMP and TIMP concentrations were measured in plasma samples by gelatin zymography and ELISA, respectively. Results: We found higher plasma pro-MMP-9 levels, and higher pro-MMP-9/TIMP-1 ratios in women with gestational hypertension (95%-CI: 1.031 to 2.357, and 0.012 to 0.031, respectively), but not with preeclampsia, compared with those found in normotensive pregnant women (95%-CI: 0.810 to 1.350, and 0.006 to 0.013, respectively; both P<0.05). We found no significant differences in pro-MMP-2 levels (P>0.05). Conclusions: The higher net MMP-9 (but not MMP-2) activity in gestational hypertension compared with normotensive pregnancy suggests that MMP-9 plays a role in the pathophysiology of gestational hypertension. Conversely, the lack of such alterations in preeclampsia is consistent with the notion that different pathophysiological mechanisms are involved in these hypertensive disorders. (C) 2008 The Canadian Society of Clinical Chemists. Published by Elsevier Inc. All rights reserved.

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The regulation of gene expression by environmental signals, such as temperature and osmolarity, has been correlated with virulence. In this study, we characterize the protein LipL53 from Leptospira interrogans, previously shown to react with serum sample of individual diagnosed with leptospirosis and to be up-regulated by shift to physiological osmolarity. The recombinant protein was expressed in Escherichia coli system, in insoluble form, recovered by urea solubilization and further refolded by decreasing the denaturing agent concentration during the purification procedure. The secondary structure content of the recombinant LipL53, as assessed by circular dichroism, showed a mixture of beta-strands and alpha-helix. The presence of LipL53 transcript at 28 degrees C was only detected within the virulent strains. However, upon shifted of attenuated cultures of pathogenic strains from 28 degrees C to 37 degrees C and to 39 degrees C, this transcript could also be observed. LipL53 binds laminin, collagen IV, cellular and plasma fibronectin in dose-dependent and saturable manner. Animal challenge studies showed that LipL53, although immunogenic, elicited only partial protection in hamsters. LipL53 is probably surface exposed as seen through immunofluorescence confocal microscopy. Our results suggest that LipL53 is a novel temperature regulated adhesin of L. interrogans that may be relevant in the leptospiral pathogenesis. (C) 2009 Elsevier Masson SAS. All rights reserved.

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Objective: Although the general mechanisms of dentinogenesis are understood, several aspects regarding tertiary dentine formation still deserve investigation, especially regarding the presence and distribution of some noncollagenous matrix proteins. As dentine matrix protein 1 (DMP 1) is present in primary dentine, it is possible that this protein may also be present in the dentine matrix secreted after injury, but there are no immunocytochemical studies attempting its detection in tertiary dentine. The aim of this study was to examine the ultrastructural immunolocalization of DMP 1 in the tertiary dentine after extrusion of the rat incisor. Study design: Upper incisors were extruded 3 mm and then repositioned into their sockets. After several periods, the incisors were fixed and processed for transmission electron microscopy and for immunocytochemistry for DMP 1. Results: Extrusion yielded both types of tertiary dentine, which varied in aspect and related cells. DMP 1 was found in the mineralized matrix of all types of dentine, presenting high affinity for collagen, but rare colloidal gold particles over predentine. DMP 1 was evident in the supranuclear region and inside the nucleus of some odontoblast-like cells. Conclusion: The observed association between DMP 1 and collagen seem to be essential for reactionary and reparative dentine formation. (C) 2010 Elsevier Ltd. All rights reserved.

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Objective. The objective of this study was to determine the expression of matrix metalloproteinase-9 (MMP-9) in apical periodontitis lesions. Study design. Nineteen epithelialized and 18 nonepithelialized apical periodontitis lesions were collected after periapical surgery. After histological processing, serial sectioning, H&E staining, and microscopic analysis, 10 epithelialized and 10 nonepithelialized lesions were selected for immunohistochemical analysis for MMP-9 and CD 68. At least one third of each specimen collected was frozen at -70 degrees C for further mRNA isolation and reverse transcription into cDNA for real-time-PCR procedures. Geometric averaging of multiple housekeeping genes normalized MMP-9 mRNA expression level. Results. Polymorphonuclear neutrophils, macrophages and lymphocytes presented MMP-9 positive immunostaining in both types of lesions. When present, epithelial cells were also stained. The number and the ratio of MMP-9(+)/total cells were greater in nonepithelialized than epithelialized lesions (P = .0001) presenting a positive correlation to CD68(+)/total cells (P = .045). Both types of lesions presented increased MMP-9 expression (P < .0001) when compared to healthy periapical ligaments. However, no significant differences were observed for MMP-9 mRNA expression between ephithelized and nonephithelized lesions. Conclusion. The present data suggest the participation of several inflammatory cells, mainly CD68(+) cells, in the MMP-9 expression in apical periodontitis lesions. MMP-9 could be actively enrolled in the extracellular matrix degradation in apical periodontitis lesions. (Oral Surg Oral Med Oral Pathol Oral Radiol Endod 2009; 107: 127-132)

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Objective: The objective of this study was to determine the expression of matrix metalloproteinase-2 (MMP-2) and -9 (MMP-9) during apical periodontitis development. Methods: Using an experimental design of induced periapical lesions in rats and immunohistochemistry assay as investigative tool, the MMP-2 and MMP-9 expression and distribution were evaluated at 3, 7,14, 21, 30,60 and 90 days after coronary access and pulp exposure of the first left mandibular molar to the oral environment. Two blind observers scored the immunoreactivity. A semi-quantitative analysis was performed. Results: Except at day 3, MMP-2 and MMP-9 immunostaining was observed in all experimental periods. The MMP-2 (p = 0.004) and MMP-9 (p = 0.005) immunostaining was higher in the period between 7 and 21 days. They were mainly observed in cells surrounding the apical foramen and adjacent periapical areas. Cells into the hypercementosis areas were strongly stained while both osteoblasts and osteoclasts; presented discrete staining along of this study. No staining was observed on epithelial walls. At 30, 60 and 90 days, the subjacent connective tissue presented intense MMP-2 and MMP-9 immunostaining in mononuclear cells (suggestive of fibroblasts, macrophages, infiltrating neutrophils and lymphocytes). Conclusion: The results observed in this study suggest that MMP-2 and MMP-9 play a critical role in the development of inflammatory periapical lesions, probably involved in the extracellular matrix (ECM) degradation during the initial phase of the lesion development. (C) 2009 Elsevier Ltd. All rights reserved.

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Objectives: To compare the circulating levels of matrix metalloproteinase (MMP)-8, pro-MMP-2, pro-MMP-9, and total MMP-9, their endogenous inhibitors, the tissue inhibitors of metalloproteinases (TIMP)-1 and TIMP-2, and the MMP-8/TIMP-1, MMP-9/TIMP-1, and MMP-2/TIMP-2 ratios in normotensive obese children and adolescents with those found in non obese children and adolescents. Design and methods: We studied 40 obese and 40 non obese (controls) children and adolescents in this cross-sectional study. MMP and TIMP concentrations were measured in plasma samples by gelatin zymography and ELISA. Results: Obese children and adolescents had higher circulating MMP-8 concentrations, lower plasma TIMP-1 concentrations, and higher MMP-8/TIMP-1 ratios than non obese controls (P < 0.05). We found no differences in pro-MMP-9 or total MMP-9 levels, or in MMP-9/TIMP-1 ratios between groups (P > 0.05). While we found no significant differences in pro-MMP-2 levels (P > 0.05) obese Subjects had higher TIMP-2 concentrations and lower pro-MMP-2/TIMP-2 ratios (P < 0.05) than non obese controls. Conclusions: In conclusion, we found evidence indicating higher net MMP-8 (but not MMP-9 and MMP-2) activity in childhood obesity. The increased MMP-8 levels found in obese children suggest a possibly relevant pathophysiological mechanism that may be involved in the increase of cardiovascular risk associated with childhood obesity. (c) 2009 The Canadian Society of Clinical Chemists. Published by Elsevier Inc. All rights reserved.

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Objective: This study aimed at investigating the influence of the porous titanium (Ti) structure on the osteogenic cell behaviour. Materials and methods: Porous Ti discs were fabricated by the powder metallurgy process with the pore size typically between 50 and 400 mm and a porosity of 60%. Osteogenic cells obtained from human alveolar bone were cultured until subconfluence and subcultured on dense Ti (control) and porous Ti for periods of up to 17 days. Results: Cultures grown on porous Ti exhibited increased cell proliferation and total protein content, and lower levels of alkaline phosphatase (ALP) activity than on dense Ti. In general, gene expression of osteoblastic markers-runt-related transcription factor 2, collagen type I, alkaline phosphatase, bone morphogenetic protein-7, and osteocalcin was lower at day 7 and higher at day 17 in cultures grown on porous Ti compared with dense Ti, a finding consistent with the enhanced growth rate for such cultures. The amount of mineralized matrix was greater on porous Ti compared with the dense one. Conclusion: These results indicate that the porous Ti is an appropriate substrate for osteogenic cell adhesion, proliferation, and production of a mineralized matrix. Because of the three-dimensional environment it provides, porous Ti should be considered an advantageous substrate for promoting desirable implant surface-bone interactions.

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We have isolated a novel family of insect-selective neurotoxins that appear to be the most potent blockers of insect voltage-gated calcium channels reported to date. These toxins display exceptional phylogenetic specificity, with at least a 10,000-fold preference for insect versus vertebrate calcium channels. The structure of one of the toxins reveals a highly structured, disulfide-rich core and a structurally disordered C-terminal extension that is essential for channel blocking activity. Weak structural/functional homology with omega -agatoxin-IVA/B, the prototypic inhibitor of vertebrate P-type calcium channels, suggests that these two toxin families might share a similar mechanism of action despite their vastly different phylogenetic specificities.