Measurement and prediction of deformation in plane strain compression tests of AA5182

The present paper concerns the numerical prediction and experimental measurement of the distribution of strain in a plane strain compression test by means of a gridded insert. The insert was engraved with a 1 x 1 mm grid pitch and was embedded in an AA5182 sample. The tests were performed at 400°C with a reduction ratio of -20% and at a strain rate of 0·7 s-1. A thermocouple was used to record the temperature during the test. After the test, no detachment was observed between insert and sample, suggesting a close contact between them. The shape of the grid after deformation was analysed, and the in-plane component of the plastic strain calculated and compared with the numerical results obtained through finite element modelling of the test. In a comparison between experimental data and the results of a finite element (FE) model of the test that assumed perfect tool alignment, the fields of temperature agreed very well, while that for the in-plane component of strain was reasonable but inaccurate. However, significant misalignment of the tools was found in the experiments (a common occurrence in plane strain compression testing). When comparison was made with an FE model that included the geometry of the tool misalignment, the agreement was excellent. The paper discusses these effects and others such as the influence of 3D effects in the modelling

Measurement of deformation gradients in hot rolling of AA3004

In this paper we describe an experimental technique developed to measure the deformation gradients and temperature in a single hot rolling pass of an AA3004 sample that was fitted with an insert. The insert had been previously hand engraved with a 1 × 1 mm grid pitch, and the analysis of the data digitally captured from the image of the deformed grid enabled the calculation of the components of the deformation gradient tensor. Four steel pins prevented relative motion between the insert and the rest of the sample. No detachment was observed between insert and sample after rolling. The temperature was measured during rolling using two embedded thermocouples, one close to the surface and the other in the centerline. The commercial finite element code ABAQUS was used to create a three-dimensional model of the rolling process. The recorded temperature was compared to the numerical values evaluated after tuning the heat transfer coefficient. The shape of the grid after rolling was checked against the deformed mesh using different friction coefficients in order to obtain the optimum match. The unusually large length of the insert enabled the rolling process to be stopped halfway so that a picture of the roll-gap area could be obtained. This provided a partially deformed grid that represented the transient state during rolling. The experimentally determined deformation gradient in this area as well as in the steady-state area agreed well with the finite element predictions. © 2005 Society for Experimental Mechanics

The atypical retinoids ST1926 and CD437 are S-phase-specific agents causing DNA double strand breaks: significance for the cytotoxic and anti-proliferative activity

Retinoid-related molecules (RRM) are novel agents with tumor-selective cytotoxic/antiproliferative activity, a different mechanism of action from classic retinoids and no cross-resistance with other chemotherapeutics. ST1926 and CD437 are prototypic RRMs, with the former currently undergoing phase I clinical trials. We show here that ST1926, CD437, and active congeners cause DNA damage. Cellular and subcellular COMET assays, H2AX phosphorylation (;-H2AX), and scoring of chromosome aberrations indicate that active RRMs produce DNA double-strand breaks (DSB) and chromosomal lesions in NB4, an acute myeloid leukemia (AML) cell line characterized by high sensitivity to RRMs. There is a direct quantitative correlation between the levels of DSBs and the cytotoxic/antiproliferative effects induced by RRMs. NB4.437r blasts, which are selectively resistant to RRMs, do not show any sign of DNA damage after treatment with ST1926, CD437, and analogues. DNA damage is the major mechanism underlying the antileukemic activity of RRMs in NB4 and other AML cell lines. In accordance with the S-phase specificity of the cytotoxic and antiproliferative responses of AML cells to RRMs, increases in DSBs are maximal during the S phase of the cell cycle. Induction of DSBs precedes inhibition of DNA replication and is associated with rapid activation of ataxia telangectasia mutated, ataxia telangectasia RAD3-related, and DNAdependent protein kinases with subsequent stimulation of the p38 mitogen-activated protein kinase. Inhibition of ataxia telangectasia mutated and DNA-dependent protein kinases reduces phosphorylation of H2AX. Cells defective for homologous recombination are particularly sensitive to ST1926, indicating that this process is important for the protection of cells from the RRM-dependent DNA damage and cytotoxicity. [Mol Cancer Ther 2008;7(9):2941–54

Inhibition of the peptidyl-prolyl-isomerase Pin1 enhances the responses of acute myeloid leukemia cells to retinoic acid via stabilization of RARand PML-RAR

The peptidyl-prolyl-isomerase Pin1 interacts with phosphorylated proteins, altering their conformation. The retinoic acid receptor RARalpha and the acute-promyelocytic-leukemia-specific counterpart PML-RARalpha directly interact with Pin1. Overexpression of Pin1 inhibits ligand-dependent activation of RARalpha and PML-RARalpha. Inhibition is relieved by Pin1-targeted short interfering RNAs and by pharmacologic inhibition of the catalytic activity of the protein. Mutants of Pin1 catalytically inactive or defective for client-protein-binding activity are incapable of inhibiting ligand-dependent RARalpha transcriptional activity. Functional inhibition of RARalpha and PML-RARalpha by Pin1 correlates with degradation of the nuclear receptors via the proteasome-dependent pathway. In the acute myelogenous leukemia cell lines HL-60 and NB4, Pin1 interacts with RARalpha in a constitutive fashion. Suppression of Pin1 by a specific short hairpin RNA in HL-60 or NB4 cells stabilizes RARalpha and PML-RARalpha, resulting in increased sensitivity to the cytodifferentiating and antiproliferative activities of all-trans retinoic acid. Treatment of the two cell lines and freshly isolated acute myelogenous leukemia blasts (M1 to M4) with ATRA and a pharmacologic inhibitor of Pin1 causes similar effects. Our results add a further layer of complexity to the regulation of nuclear retinoic acid receptors and suggest that Pin1 represents an important target for strategies aimed at increasing the therapeutic index of retinoids

Analysis of the \u3c9\u3c0 12 system produced in the reaction \u3c0 12p\u2192\u3c0 12\u3c0 12\u3c0+\u3c00pat 11.2 GeV/c

The \u3c9\u3c0- mass spectrum, in the reaction \u3c0-p \u2192 \u3c9\u3c0-pat 11.2 GeV/c, shows the production of the B- meson with a cross section of 27 \ub1 5 \u3bcb as well as a clear enhancement around 1670 MeV. In the differential cross section for B- production, there is a strong forward peak and a change of slope at t' t 0.2 GeV2. From the spin-parity decomposition of the \u3c9\u3c0- system, performd using both a standard moments analysis and a partial-wave analysis, we have found that JP = 1+ is the most likely spin-parity assignment for the B-, thus confirming previous results. The spin-density matrix elements, evaluated in the GJ frame, suggest that natural parity exchange dominates the B- production. The \u3c9 helicity-zero contribution is |F01+|2 = 0.06 \ub1 0.04, implying a ratio |CD1+|/|CS1+| = 0.4 \ub1 0.1