Genomes of the Most Dangerous Epidemic Bacteria Have a Virulence Repertoire Characterized by Fewer Genes but More Toxin-Antitoxin Modules

We conducted a comparative genomic study based on a neutral approach to identify genome specificities associated with the virulence capacity of pathogenic bacteria. We also determined whether virulence is dictated by rules, or if it is the result of individual evolutionary histories. We systematically compared the genomes of the 12 most dangerous pandemic bacteria for humans ("bad bugs") to their closest non-epidemic related species ("controls").We found several significantly different features in the "bad bugs", one of which was a smaller genome that likely resulted from a degraded recombination and repair system. The 10 Cluster of Orthologous Group (COG) functional categories revealed a significantly smaller number of genes in the "bad bugs", which lacked mostly transcription, signal transduction mechanisms, cell motility, energy production and conversion, and metabolic and regulatory functions. A few genes were identified as virulence factors, including secretion system proteins. Five "bad bugs" showed a greater number of poly (A) tails compared to the controls, whereas an elevated number of poly (A) tails was found to be strongly correlated to a low GC% content. The "bad bugs" had fewer tandem repeat sequences compared to controls. Moreover, the results obtained from a principal component analysis (PCA) showed that the "bad bugs" had surprisingly more toxin-antitoxin modules than did the controls.We conclude that pathogenic capacity is not the result of "virulence factors" but is the outcome of a virulent gene repertoire resulting from reduced genome repertoires. Toxin-antitoxin systems could participate in the virulence repertoire, but they may have developed independently of selfish evolution

Formulating and Solving Sustainable Stochastic Dynamic Facility Layout Problem: A Key to Sustainable Operations

Facility layout design, a NP Hard problem, is associated with the arrangement of facilities in a manufacturing shop floor, which impacts the performance, and cost of system. Efficient design of facility layout is a key to the sustainable operations in a manufacturing shop floor. An efficient layout design not only optimizes the cost and energy due to proficient handling but also increase flexibility and easy accessibility. Traditionally, it is solved using meta-heuristic techniques. But these algorithmic or procedural methodologies do not generate effective and efficient layout design from sustainable point of view, where design should consider multiple criteria such as demand fluctuations, material handling cost, accessibility, maintenance, waste and more. In this paper, to capture the sustainability in the layout design these parameters are considered, and a new Sustainable Stochastic Dynamic Facility Layout Problem (SDFLP) is formulated and solved. SDFLP is optimized for material handling cost and rearrangement cost using various meta-heuristic techniques. The pool of layouts thus generated is then analyzed by Data Envelopment Analysis (DEA) to identify efficient layouts. A novel hierarchical methodology of consensus ranking of layouts is proposed which combines the multiple attributes/criteria. Multi Attribute decision-making (MADM) Techniques such as Technique for Order Preference by Similarity to Ideal Solution (TOPSIS), Interpretive Ranking Process (IRP) and Analytic hierarchy process (AHP), Borda-Kendall and Integer Linear Programming based rank aggregation techniques are applied. To validate the proposed methodology data sets for facility size N=12 for time period T=5 having Gaussian demand are considered

In Vivo Ectopic Implantation Model to Assess Human Mesenchymal Progenitor Cell Potential

Clinical interest on human mesenchymal progenitor cells (hMPC) relies on their potential applicability in cell-based therapies. An in vitro characterization is usually performed in order to define MPC potency. However, in vitro predictions not always correlate with in vivo results and thus there is no consensus in how to really assess cell potency. Our goal was to provide an in vivo testing method to define cell behavior before therapeutic usage, especially for bone tissue engineering applications. In this context, we wondered whether bone marrow stromal cells (hBMSC) would proceed in an osteogenic microenvironment. Based on previous approaches, we developed a fibrin/ceramic/BMP-2/hBMSCs compound. We implanted the compound during only 2 weeks in NOD-SCID mice, either orthotopically to assess its osteoinductive property or subcutaneously to analyze its adequacy as a cell potency testing method. Using fluorescent cell labeling and immunohistochemistry techniques, we could ascertain cell differentiation to bone, bone marrow, cartilage, adipocyte and fibrous tissue. We observed differences in cell potential among different batches of hBMSCs, which did not strictly correlate with in vitro analyses. Our data indicate that the method we have developed is reliable, rapid and reproducible to define cell potency, and may be useful for testing cells destined to bone tissue engineering purposes. Additionally, results obtained with hMPCs from other sources indicate that our method is suitable for testing any potentially implantable mesenchymal cell. Finally, we propose that this model could successfully be employed for bone marrow niche and bone tumor studies. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (doi:10.1007/s12015-013-9464-1) contains supplementary material, which is available to authorized users

On the inferences from the analyses of strain distributions in drawn sheet metal products

When a flat sheet is deformed into desired shape, a distribution of strain is created. It is the resultant outcome of a number of factors and their interactions, including the shape of the product, design of the tool, forming conditions and the material properties. While one would desire a very uniform strain all over the formed product, this is never achieved. Effects of material properties on the strain distribution for axisymmetric shapes have been documented. Quantification of strain distribution has been attempted by many but few applications of these are available in the literature. In the present work, methods of analysing the simulated strain distribution profiles obtained using the PAMSTAMP-2G software have been demonstrated to (a) perform process design for a drawn product and (b) explore the possibility of predicting the strain distribution of a full scale product based on a geometrically scaled down model

Minimizing wastage of sheet metal for economical manufacturing

Large quantities of sheet metal are consumed every month in various sectors of industry, the automotive, furniture, white and brown goods, electrical and body building (including coaches and containers) being the chief consumers. A large number of "critical" automotive sheet metal parts lead to rejections leading to wastage of sheet metal during manufacturing. Here, a product that permits a smaller window of variation in material properties compared to that permitted by the standards is said to be "critical". The wastage due to layout (utilization) of blanks on the sheet and that on account of rejections constitutes total wastage. While a number of algorithms are available to maximize sheet utilization and curtail the wastage, there appears to be none to minimize rejections. Thus, it will always be helpful to an industry to use a system capable of predicting and minimizing these rejections at the sheet layout stage. This paper views wastage in totality and attempts to minimize the total wastage arising from layout as well as rejections. Highly strained regions in a sheet metal blank are identified. Based on the permissible window of variation in the material properties, a 'defect map' is generated on the sheet. The blanks are laid out and the possible number of rejections is predicted probabilistically, leading to the prediction of the actual utilization of the material. (c) 2006 Elsevier B.V. All rights reserved

Analytical and finite element modeling of strain generated in equal channel angular extrusion

Various analytical models have been developed to predict the strain in ECAP. Comparisons of the predictions are difficult in view of the differing assumptions. A detailed study of strain prediction models, their predictions, applicability, and inherent assumptions has not been carried out. In the current work an alternate approach for the derivation of strain has been adopted. The generation of strain is viewed to be the result of the path difference between two metal particles, in the channel, as they travel from the inlet to the outlet. The previous models have been examined in the same frame work so as to compare and understand better the assumptions therein. This approach has been used to derive the expression for strain in dies with external arc of curvature and in round corner dies. In addition, FE simulations have been carried out, for different channel geometries and frictional conditions, using the commercially available code ABAQUS and the results compared with analytical models. It was found that the models derived, better predict the strains obtained through FE simulations. (C) 2012 Elsevier Ltd. All rights reserved

Evaluation of the mean plastic strain ratio r(m) of metallic sheets prestrained along different biaxial strain paths

ASTM standards are widely used to determine the plastic strain ratio r to characterize the normal anisotropy and the planar anisotropy of sheet metal. The values determined by mechanical testing are quoted at a strain of 15%. These are used for comparing two techniques of measuring the plastic strain ratio or the anisotropy of two materials. The present work reports the variation in the plastic strain ratio of prestrained material. The r values of biaxially prestrained steel sheet have been investigated using the ASTM as well as the magnetostrictive methods of measurement. An error analysis on the mechanical measurements has been performed to examine the agreement between the different definitions of the plastic strain ratio (r(r), r(int), r(t), and r(mxi)) and the accuracy (based on coefficient of variation), in view of the need to measure the plastic strain ratio at low strain levels. Various means to ensure accuracy in measurement are described. Plastic strain ratio of sheet deformed to different biaxial prestrains has also been characterized using the magnetostrictive method (Modul r test). It is found that the difference between the r values determined using the ASTM and the Modul r methods changes with strain and strain path. The nominal difference between the two methods was found to be comparatively consistent over strain paths ranging from plane strain to equibiaxial tension. The Modul r values for prestrains along these strain paths investigated were found to be relatively consistent and hence usable. For prestrain along the strain path beta = -0.45 (negative minor strain regime), the nominal difference was considerable. In view of the above, it is not appropriate to measure rapidly the r value of the material in the negative minor strain regime, in particular using magnetostrictive means, and to correct it using the "systematic error" between the two techniques. This restricts the usability of the Modul r test in measuring the plastic strain ratio of deformed sheet metal, particularly after a prestrain in the negative minor strain region

Simulation based control of weld line movement in tailor welded blanks

A Tailor welded blank (TWB) consists of sheet materials of different thicknesses or different alloy compositions that are welded together prior to forming. The weaker of the two sheets deforms more causing weld line movement.. This paper proposes methods to predict optimum position of the weld line in a flat tailor welded blank so as to reduce weld line movement in formed tailor welded blanks. Two simulation based methods - back propagation and contour of minimum strain are studied to reduce weld line movement. These methods are based on blank shape modification