Fatigue analysis-based numerical design of stamping tools made of cast iron

This work concerns stress and fatigue analysis of stamping tools made of cast iron with an essentially pearlitic matrix and containing foundry defects. Our approach consists at first, in coupling the stamping numerical processing simulations and structure analysis in order to improve the tool stiffness geometry for minimizing the stress state and optimizing their fatigue lifetime. The method consists in simulating the stamping process by considering the tool as a perfect rigid body. The estimated contact pressure is then used as boundary condition for FEM structure loading analysis of the tool. The result of this analysis is compared with the critical stress limit depending on the automotive model. The acceptance of this test allows calculating the fatigue lifetime of the critical zone by using the S–N curve of corresponding load ratio. If the prescribed tool life requirements are not satisfied, then the critical region of the tool is redesigned and the whole simulation procedures are reactivated. This method is applied for a cast iron EN-GJS-600-3. The stress-failure (S–N) curves for this material is determined at room temperature under push pull loading with different load ratios R0σmin/σmax0−2, R0−1 and R00.1. The effects of the foundry defects are determined by SEM observations of crack initiation sites. Their presence in tested specimens is associated with a reduction of fatigue lifetime by a factor of 2. However, the effect of the load ratio is more important

Pressure-sensitive paint measurements in a shock tube

Abstract Surface pressures were measured in the shortduration, transient flow environment of a small-scale, low pressure-ratio shock tube using thin-film pressure-sensitive paint (PSP). Issues regarding coating formulation, measurement uncertainty, optical system design, and temperature and illumination compensation are discussed. The pressure measurements were acquired during steady flow conditions following the passage of normal shocks and expansion regions along a flat sidewall and a wedge sidewall. The PSP characteristic response time was 3 to 6 ms. Overall pressure uncertainty for the shock tube measurements ranged up to 5% over one atmosphere and compared well with theoretical estimates of uncertainty

A novel approach to computer-aided diagnosis of mammographic images

This is a work-in-progress report of a research endeavor that deals with the design and development of a novel approach to computer-aided diagnosis (CAD) of mammographic images. With the initial emphasis being on the analysis of microcalcifications, the proposed approach defines a synergistic paradigm that utilizes new methodologies together with previously developed techniques. The new paradigm is intended to promote a higher degree of accuracy in CAD of mammograms with an increased overall throughput. The process of accomplishing these goals is initiated by the fractal encoding of the input image, which gives rise to the generation of focus-of-attention regions (FARs), that is, regions that contain anomalies. The primary thrust of this work is to demonstrate that by considering FARs, rather than the entire input image, the performances of the ensuing processes (i.e., segmentation, feature extraction, and classification) are enhanced in terms of accuracy and speed. After presenting the proposed approach to CAD of mammographic images, the paper describes the generation of FARs. Furthermore, an experimental study is included that demonstrates the impact of this front-end procedure on the process of microcalcification segmentation. Specifically, the experimentation reveals a dramatic decrease (increase) in the amount of input data (throughput), as well as a reduction in the number of false detections

Enhanced recovery after surgery: are we ready, and can we afford not to implement these pathways for patients undergoing radical cystectomy?

Enhanced recovery after surgery (ERAS) for radical cystectomy seems logical, but our study has shown a paucity in the level of clinical evidence. As part of the ERAS Society, we welcome global collaboration to collect evidence that will improve patient outcomes

High salt reduces the activation of IL-4- and IL-13-stimulated macrophages

A high intake of dietary salt (NaCl) has been implicated in the development of hypertension, chronic inflammation, and autoimmune diseases. We have recently shown that salt has a proinflammatory effect and boosts the activation of Th17 cells and the activation of classical, LPS-induced macrophages (M1). Here, we examined how the activation of alternative (M2) macrophages is affected by salt. In stark contrast to Th17 cells and M1 macrophages, high salt blunted the alternative activation of BM-derived mouse macrophages stimulated with IL-4 and IL-13, M(IL-4+IL-13) macrophages. Salt-induced reduction of M(IL-4+IL-13) activation was not associated with increased polarization toward a proinflammatory M1 phenotype. In vitro, high salt decreased the ability of M(IL-4+IL-13) macrophages to suppress effector T cell proliferation. Moreover, mice fed a high salt diet exhibited reduced M2 activation following chitin injection and delayed wound healing compared with control animals. We further identified a high salt-induced reduction in glycolysis and mitochondrial metabolic output, coupled with blunted AKT and mTOR signaling, which indicates a mechanism by which NaCl inhibits full M2 macrophage activation. Collectively, this study provides evidence that high salt reduces noninflammatory innate immune cell activation and may thus lead to an overall imbalance in immune homeostasis

Intra- and inter-individual genetic differences in gene expression

Genetic variation is known to influence the amount of mRNA produced by a gene. Given that the molecular machines control mRNA levels of multiple genes, we expect genetic variation in the components of these machines would influence multiple genes in a similar fashion. In this study we show that this assumption is correct by using correlation of mRNA levels measured independently in the brain, kidney or liver of multiple, genetically typed, mice strains to detect shared genetic influences. These correlating groups of genes (CGG) have collective properties that account for 40-90% of the variability of their constituent genes and in some cases, but not all, contain genes encoding functionally related proteins. Critically, we show that the genetic influences are essentially tissue specific and consequently the same genetic variations in the one animal may up-regulate a CGG in one tissue but down-regulate the same CGG in a second tissue. We further show similarly paradoxical behaviour of CGGs within the same tissues of different individuals. The implication of this study is that this class of genetic variation can result in complex inter- and intra-individual and tissue differences and that this will create substantial challenges to the investigation of phenotypic outcomes, particularly in humans where multiple tissues are not readily available.

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An effective all-atom potential for proteins

We describe and test an implicit solvent all-atom potential for simulations of protein folding and aggregation. The potential is developed through studies of structural and thermodynamic properties of 17 peptides with diverse secondary structure. Results obtained using the final form of the potential are presented for all these peptides. The same model, with unchanged parameters, is furthermore applied to a heterodimeric coiled-coil system, a mixed alpha/beta protein and a three-helix-bundle protein, with very good results. The computational efficiency of the potential makes it possible to investigate the free-energy landscape of these 49--67-residue systems with high statistical accuracy, using only modest computational resources by today's standards

ERK2 phosphorylation of serine 77 regulates Bmf pro-apoptotic activity

B-cell lymphoma 2 (Bcl-2) homology 3 (BH3)-only proteins represent a class of pro-apoptotic factors that neutralize pro-survival Bcl-2 proteins, and, in some cases, directly activate Bax. The mechanisms of control and the role of BH3-only proteins, such as Bcl-2 like protein 11 extra large and Bad are well studied. By contrast, relatively little is known about the regulation and role of Bcl-2 modifying factor (Bmf). The B-RAF oncogene is mutated in ∼8% of human tumors. We have previously shown that Bmf is upregulated at the transcript level and is required for apoptosis induced by targeting B-RAF signaling in tumor cells harboring mutant B-RAF. In this study, we show that Bmf is regulated at the post-translational level by mutant B-RAF-MEK-ERK2 signaling. Extracellular signal-regulated kinase (ERK2) directly phosphorylates Bmf on serine 74 and serine 77 residues with serine 77 being the predominant site. In addition, serine 77 phosphorylation reduces Bmf pro-apoptotic activity likely through a mechanism independent of altering Bmf localization to the mitochondria and/or interactions with dynein light chain 2 and the pro-survival proteins, B-cell lymphoma extra large, Bcl-2 and Mcl-1. These data identify a novel mode of regulation in Bmf that modulates its pro-apoptotic activity in mutant B-RAF tumor cells