Targeting Endothelial Connexin37 Reduces Angiogenesis and Decreases Tumor Growth

Connexin37 (Cx37) and Cx40 form intercellular channels between endothelial cells (EC), which contribute to the regulation of the functions of vessels. We previously documented the participation of both Cx in developmental angiogenesis and have further shown that loss of Cx40 decreases the growth of different tumors. Here, we report that loss of Cx37 reduces (1) the in vitro proliferation of primary human EC; (2) the vascularization of subcutaneously implanted matrigel plugs in Cx37−/− mice or in WT using matrigel plugs supplemented with a peptide targeting Cx37 channels; (3) tumor angiogenesis; and (4) the growth of TC-1 and B16 tumors, resulting in a longer mice survival. We further document that Cx37 and Cx40 function in a collaborative manner to promote tumor growth, inasmuch as the injection of a peptide targeting Cx40 into Cx37−/− mice decreased the growth of TC-1 tumors to a larger extent than after loss of Cx37. This loss did not alter vessel perfusion, mural cells coverage and tumor hypoxia compared to tumors grown in WT mice. The data show that Cx37 is relevant for the control of EC proliferation and growth in different tumor models, suggesting that it may be a target, alone or in combination with Cx40, in the development of anti-tumoral treatments.     

A3M: an agent architecture for automated manufacturing

This paper proposes a software architecture based on mobile agents for distributed process control applications. A set of agents is employed to handle, in a single manufacturing cell, automatic assignment of control tasks to controllers, monitoring of cell functionalities and dynamic cell reconfiguration. The agents operate in a two‐layered structure: at the highest level, the planning agents analyse the inputs of the system designer and automatically create the field agents, which operate at the lowest level and embed the control tasks to be executed. Field agents, which are mobile, are able to reach autonomously the controllers of the cell, in order to perform the control activity there. Exploiting the mobility enables a field agent to change its running device when the variation of the design parameters or a system fault requires a new task distribution. A load‐balancing algorithm is introduced, with the objective of assigning each field agent to a controller of the manufacturing cell in order to fairly distribute the computation load. The algorithm uses a branch‐and‐bound technique to explore all possible solutions and applies two heuristics to throw away non‐feasible solutions and select the best branch to analyse. The algorithm is designed to run on‐line in order to allow a fast task redistribution when a fault condition occurs in the process control environment. Copyright © 2008 John Wiley & Sons, Ltd.     

Mapping the development of Open Access in Latin America and Caribbean countries. An analysis of Web of Science Core Collection and SciELO Citation Index (2005–2017)

Scientometrics - Open Access (OA) initiatives and knowledge infrastructure represent vital elements for both producing significant changes in scholarly communication and reducing limitations of...     

Membrane topology of the Rickettsia prowazekii ATP/ADP translocase revealed by novel dual pho-lac reporters

Here, we report the construction and characterization of dual reporters, consisting of both an Escherichia coli alkaline phosphatase (AP) gene and an alpha-fragment of the beta-galactosidase (BG) gene, for studying membrane protein topology by the gene fusion approach. Each of the reporters, when fused to periplasmic domains of polytopic proteins, produces fusions with high AP activity and, when fused to cytoplasmic domains, produces fusions with high BG activity in E. coli strains capable of alpha-complementation. The dual nature of these reporters simplifies interpretation of data obtained with poorly expressed fusions and allows one to evaluate the reliability of topological data. Deleterious effects resulting from the cell's attempt to export the full-length BG are eliminated in this approach. We describe dual indicator plates that allow for discrimination between colonies bearing cytoplasmic fusions, periplasmic fusions, and no fusions. We have generated a set of fusions to the topologically well-studied lactose permease of E. coli and demonstrated that topological information generated by these new reporters is in good agreement with the existing model. We used this new methodology for the determination of membrane topology of the Rickettsia prowazekii ATP/ADP translocase (Tlc). Our results were in agreement with the proposed in silico topological model in which Tlc traverses the cytoplasmic membrane of E. coli 12 times with its N and C termini facing the cytoplasm.     

Fuzzy clusterwise linear regression analysis with symmetrical fuzzy output variable

The traditional regression analysis is usually applied to homogeneous observations. However, there are several real situations where the observations are not homogeneous. In these cases, by utilizing the traditional regression, we have a loss of performance in fitting terms. Then, for improving the goodness of fit, it is more suitable to apply the so-called clusterwise regression analysis. The aim of clusterwise linear regression analysis is to embed the techniques of clustering into regression analysis. In this way, the clustering methods are utilized for overcoming the heterogeneity problem in regression analysis. Furthermore, by integrating cluster analysis into the regression framework, the regression parameters (regression analysis) and membership degrees (cluster analysis) can be estimated simultaneously by optimizing one single objective function. In this paper the clusterwise linear regression has been analyzed in a fuzzy framework. In particular, a fuzzy clusterwise linear regression model (FCWLR model) with symmetrical fuzzy output and crisp input variables for performing fuzzy cluster analysis within a fuzzy linear regression framework is suggested. For measuring the goodness of fit of the suggested FCWLR model with fuzzy output, a fitting index is proposed. In order to illustrate the usefulness of FCWLR model in practice, several applications to artificial and real datasets are shown.     

Simultaneous determination of thiabendazole and mebendazole in tablets by high-performance liquid chromatography

Reversed-phase high performance liquid chromatography using an RP 18 column (4 × 125 mm), tetrahydrofuran-acetonitrile-0.5% formic acid (5:25:70, v/v/v) as mobile phase and UV detection at 254 nm enabled the simultaneous determination of thiabendazole (TZ) and mebendazole (MZ) in tablets. The method showed linearity over 4.0 to 40.0 μg TZ/ml and 6.0 to 60.0 μg MZ/ml. The correlation coefficient r was .9999 for both TZ and MZ. The coefficient of variation (CV) was 0.59-0.80% for TZ and 0.49-0.67% for MZ. The average recovery was 100.54-101.17% for TZ and 100.35-101.13% for MZ. The excipients of the tablets did not interfere in the proposed method. The developed method is precise, accurate, and selective for the determination of both benzimidazoles analyzed.     

A liposomal model that mimics the cutaneous production of vitamin D3. Studies of the mechanism of the membrane-enhanced thermal isomerization of previtamin D3 to vitamin D3

We reported previously that the rate of previtamin D3 (preD3) <==> vitamin D3 isomerization was enhanced by about 10 times in the skin compared with that in organic solvents. To elucidate the mechanism by which the rate of this reaction is enhanced in the skin, we developed a liposomal model that mimicked the enhanced isomerization of preD3 to vitamin D3 that was described in human skin. Using this model we studied the effect of changing the polarity of preD3 as well as changing the chain length and the degree of saturation of liposomal phospholipids on the kinetics of preD3 <==> vitamin D3 isomerization. We found that a decrease in the hydrophilic interaction of the preD3 with liposomal phospholipids by an esterification of the 3beta-hydroxy of preD3 (previtamin D3-3beta-acetate) reduced the rate of the isomerization by 67%. The addition of a hydroxyl on C-25 of the hydrophobic side chain (25-hydroxyprevitamin D3), which decreased the hydrophobic interaction of preD3 with the phospholipids, reduced the rate by 87%. In contrast, in an isotropic n-hexane solution, there was little difference among the rates of the conversion of preD3, its 3beta-acetate, and 25-hydroxy derivatives to their corresponding vitamin D3 compounds. We also determined rate constants (k) of preD3 <==> vitamin D3 isomerization in liposomes containing phosphatidylcholines with different carbon chain lengths. The rates of the reaction were found to be enhanced as the number of carbons (Cn) in the hydrocarbon chain of the phospholipids increased from 10 to 18. In conclusion, these results support our hypothesis that amphipathic interactions between preD3 and membrane phospholipids stabilize preD3 in its "cholesterol like" cZc-conformer, the only conformer of preD3 that can convert to vitamin D3. The stronger these interactions were, the more preD3 was likely in its cZc conformation at any moment and the faster was the rate of its conversion to vitamin D3.     

Marie-Fran?oise Collière--nurse and ethnohistorian: a conversation about nursing and the invisibility of care. Interview by Jocalyn Lawler

The purpose of this study was to describe an episode of increased mortality, whose cause was initially unknown. This retrospective cohort investigation was conducted on a dementia special care unit of a Department of Veterans Affairs facility, with more than 75% of residents clinically diagnosed with dementia of the Alzheimer type. One hundred five residents residing in the facility during February 1995 were included as subjects. A cluster of deaths occurred, triggering the investigation. Ultimately, 21 deaths (three times greater than any previous month in the past 5 years) occurred during the 1-month period. Measures included the presence of clinical influenza-like illness based on signs, serology, and autopsy results. Of the 105 residents, 45 (42.8%) met the clinical definition for influenza-like illness. Eight autopsies were performed, and the causes of death consisting of bronchopneumonia in seven and aspiration pneumonia in one were compatible with influenza. There were no differences among those who died from those who lived with regards to age, race, gender, clinical influenza-like illness, vaccination status, diagnosis of Alzheimer disease, or duration of dementia (all p > or = 0.2). However, those who died were at a higher risk of dying due to a greater number of coexisting conditions (p < 0.01). Also, overall the groups differed in Mini-Mental State Examination and Bedford Alzheimer Nursing Scale scores with those who died being more impaired (p < 0.01). Thus, the presentation of influenza-like illness can be subtle in onset, underappreciated in this population, and not recognized until excess mortality, which affects the most frail, is noted. Care providers need to be vigilant during the winter months for the presence of influenza.