Finite Element Analysis of ECAP, TCAP, RUE and CGP Processes

A finite element method was applied to study the various severe plastic deformation processes like, Equal Channel Angular Pressing (ECAP), Tubular Channel Angular Pressing (TCAP), Repetitive Upsetting and Extrusion (RUE) and Constrained Groove Pressing (CGP), considering aluminum AA-390 alloy as specimen material for all these processes. FEA simulation was carried out using AFDEX simulation tool. Effect of the various ECAP process parameters like, die corner angle, channel angle, and the coefficient of friction were analyzed. The die corner angles were divided into 2 equal parts for increasing the effectiveness of ECAP process, thereby increasing the channel number from 2 to 3 and further, their influence on ECAP process was investigated. A 3D simulation of TCAP was carried out for die shapes like triangular and trapezoidal, and variation of the generated stress and strain was plotted. In CGP, four cycle operation was carried out; wherein each cycle is composed of corrugating the specimen and subsequent straightening to original dimension. During RUE process, a maximum effective stress of 683.1 MPa was induced in the specimen after processing it for four complete cycles of RUE process; whereas the maximum strain induced during the same condition was 3.715

A comparison of repetitive corrugation and straightening and high-pressure torsion using an Al-Mg-Sc alloy

A comparative study was conducted to evaluate the influence of two different severe plastic deformation (SPD) processes: repetitive corrugation and straightening (RCS) and high-pressure torsion (HPT). Samples of an Al-3Mg-0.25Sc alloy with an initial grain size of ∼150 μm were processed by RCS through 8 passes at room temperature either without any rotation during processing or with a rotation of 90° around the longitudinal axis between each pass. Thin discs of the alloy were also processed for up to 5 turns by HPT at room temperature. The results show that both procedures introduce significant grain refinement with average grain sizes of ∼0.6–0.7 μm after RCS and ∼95 nm after HPT. Measurements of the Vickers microhardness gave values of ∼128 after RCS and ∼156 after HPT. The results demonstrate that processing by HPT is the optimum processing technique in achieving both high strength and microstructural homogeneity

OptFlux: an open-source software platform for in silico metabolic engineering

<p>Abstract</p> <p>Background</p> <p>Over the last few years a number of methods have been proposed for the phenotype simulation of microorganisms under different environmental and genetic conditions. These have been used as the basis to support the discovery of successful genetic modifications of the microbial metabolism to address industrial goals. However, the use of these methods has been restricted to bioinformaticians or other expert researchers. The main aim of this work is, therefore, to provide a user-friendly computational tool for Metabolic Engineering applications.</p> <p>Results</p> <p><it>OptFlux </it>is an open-source and modular software aimed at being the reference computational application in the field. It is the first tool to incorporate strain optimization tasks, i.e., the identification of Metabolic Engineering targets, using Evolutionary Algorithms/Simulated Annealing metaheuristics or the previously proposed OptKnock algorithm. It also allows the use of stoichiometric metabolic models for (i) phenotype simulation of both wild-type and mutant organisms, using the methods of Flux Balance Analysis, Minimization of Metabolic Adjustment or Regulatory on/off Minimization of Metabolic flux changes, (ii) Metabolic Flux Analysis, computing the admissible flux space given a set of measured fluxes, and (iii) pathway analysis through the calculation of Elementary Flux Modes.</p> <p><it>OptFlux </it>also contemplates several methods for model simplification and other pre-processing operations aimed at reducing the search space for optimization algorithms.</p> <p>The software supports importing/exporting to several flat file formats and it is compatible with the SBML standard. <it>OptFlux </it>has a visualization module that allows the analysis of the model structure that is compatible with the layout information of <it>Cell Designer</it>, allowing the superimposition of simulation results with the model graph.</p> <p>Conclusions</p> <p>The <it>OptFlux </it>software is freely available, together with documentation and other resources, thus bridging the gap from research in strain optimization algorithms and the final users. It is a valuable platform for researchers in the field that have available a number of useful tools. Its open-source nature invites contributions by all those interested in making their methods available for the community.</p> <p>Given its plug-in based architecture it can be extended with new functionalities. Currently, several plug-ins are being developed, including network topology analysis tools and the integration with Boolean network based regulatory models.</p

Surfactant protein D inhibits HIV-1 infection of target cells via interference with gp120-CD4 interaction and modulates pro-inflammatory cytokine production

© 2014 Pandit et al. This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.Surfactant Protein SP-D, a member of the collectin family, is a pattern recognition protein, secreted by mucosal epithelial cells and has an important role in innate immunity against various pathogens. In this study, we confirm that native human SP-D and a recombinant fragment of human SP-D (rhSP-D) bind to gp120 of HIV-1 and significantly inhibit viral replication in vitro in a calcium and dose-dependent manner. We show, for the first time, that SP-D and rhSP-D act as potent inhibitors of HIV-1 entry in to target cells and block the interaction between CD4 and gp120 in a dose-dependent manner. The rhSP-D-mediated inhibition of viral replication was examined using three clinical isolates of HIV-1 and three target cells: Jurkat T cells, U937 monocytic cells and PBMCs. HIV-1 induced cytokine storm in the three target cells was significantly suppressed by rhSP-D. Phosphorylation of key kinases p38, Erk1/2 and AKT, which contribute to HIV-1 induced immune activation, was significantly reduced in vitro in the presence of rhSP-D. Notably, anti-HIV-1 activity of rhSP-D was retained in the presence of biological fluids such as cervico-vaginal lavage and seminal plasma. Our study illustrates the multi-faceted role of human SPD against HIV-1 and potential of rhSP-D for immunotherapy to inhibit viral entry and immune activation in acute HIV infection. © 2014 Pandit et al.The work (Project no. 2011-16850) was supported by Medical Innovation Fund of Indian Council of Medical Research, New Delhi, India (www.icmr.nic.in/)

Standardizing Clinical Trials Workflow Representation in UML for International Site Comparison

BACKGROUND: With the globalization of clinical trials, a growing emphasis has been placed on the standardization of the workflow in order to ensure the reproducibility and reliability of the overall trial. Despite the importance of workflow evaluation, to our knowledge no previous studies have attempted to adapt existing modeling languages to standardize the representation of clinical trials. Unified Modeling Language (UML) is a computational language that can be used to model operational workflow, and a UML profile can be developed to standardize UML models within a given domain. This paper's objective is to develop a UML profile to extend the UML Activity Diagram schema into the clinical trials domain, defining a standard representation for clinical trial workflow diagrams in UML. METHODS: Two Brazilian clinical trial sites in rheumatology and oncology were examined to model their workflow and collect time-motion data. UML modeling was conducted in Eclipse, and a UML profile was developed to incorporate information used in discrete event simulation software. RESULTS: Ethnographic observation revealed bottlenecks in workflow: these included tasks requiring full commitment of CRCs, transferring notes from paper to computers, deviations from standard operating procedures, and conflicts between different IT systems. Time-motion analysis revealed that nurses' activities took up the most time in the workflow and contained a high frequency of shorter duration activities. Administrative assistants performed more activities near the beginning and end of the workflow. Overall, clinical trial tasks had a greater frequency than clinic routines or other general activities. CONCLUSIONS: This paper describes a method for modeling clinical trial workflow in UML and standardizing these workflow diagrams through a UML profile. In the increasingly global environment of clinical trials, the standardization of workflow modeling is a necessary precursor to conducting a comparative analysis of international clinical trials workflows

Status of Intraductal Therapy for Ductal Carcinoma in Situ

The intraductal approach is particularly appealing in the setting of ductal carcinoma in situ (DCIS), a preinvasive breast neoplasm that is thought to be entirely intraductal in its extent. Based on an emerging understanding of the anatomy of the ductal system as well as novel techniques to leverage the access accorded by the intraductal approach, researchers are actively exploring how ductal lavage, ductoscopy, and intraductal infusion of therapeutic agents may enhance breast cancer treatment. Both cytologic and molecular diagnostics continue to improve, and work is ongoing to identify the most effective diagnostic biomarkers for DCIS and cancer, although optimal targeting of the diseased duct remains an important consideration. Ductoscopy holds potential in detection of occult intraductal lesions, and ductoscopically guided lumpectomy could increase the likelihood of a more comprehensive surgical excision. Exciting pilot studies are in progress to determine the safety and feasibility of intraductal chemotherapy infusion. These studies are an important starting point for future investigations of intraductal ablative therapy for DCIS, because as our knowledge and techniques evolve, it is likely that DCIS may be the target most amenable to treatment by intraductal therapy. If such studies are successful, these approaches will allow an important and meaningful transformation in treatment options for women diagnosed with DCIS