Synthesis and Evaluation of Functionalized Aryl and Biaryl Isothiocyanates against Human MCF-7 Cells

Organic isothiocyanates (ITCs) are a class of anticancer agents which naturally result from the enzymatic degradation of glucosinolates produced by Brassica vegetables. Previous studies have demonstrated that the structure of an ITC impacts its potency and mode(s) of anticancer properties, opening the way to preparation and evaluation of synthetic, non-natural ITC analogues. This study describes the preparation of a library of 79 non-natural ITC analogues intended to probe further structure-activity relationships for aryl ITCs and second-generation, functionalized biaryl ITC variants. ITC candidates were subjected to bifurcated evaluation of antiproliferative and antioxidant response element (ARE)-induction capacity against human MCF-7 cells. The results of this study led to the identification of (1) several key structure-activity relationships and (2) lead ITCs demonstrating potent antiproliferative properties.     

Novel Bayesian CUSUM and EWMA control charts via various loss functions for monitoring processes

In this work, both the cumulative sum (CUSUM) and exponentially weighted moving average (EWMA) control charts have been reconfigured to monitor processes using a Bayesian approach. Our construction of these charts are informed by posterior and posterior predictive distributions found using three loss functions: the squared error, precautionary, and linex. We use these control charts on count data, performing a simulation study to assess chart performance. Our simulations consist of sensitivity analysis of the out-of-control shift size and choice of hyper-parameters of the given distributions. Practical use of theses charts are evaluated on real data.     

Use of Profilometry-Based Indentation Plastometry to Study the Effects of Pipe Wall Flattening on Tensile Stress–Strain Curves of Steels

Herein, the flattening and subsequent tensile testing (in the hoop direction) of steel pipes used for transmission of oil and gas are concerned. A particular focus is on the use of a novel indentation plastometry test (PIP), applied to the outer free surface of an as-received pipe. This allows a stress–strain curve to be obtained from a relatively small volume (a disk of diameter about 1 mm and thickness around 100–200 μm). Whole section and reduced section tensile testing, of as-received and flattened samples are carried out. Four different pipes are studied. While there are some variations between them, there is a general trend for near-surface regions of the pipe to be a little harder than the interior, and for flattened pipes to be a little harder than unflattened ones, although these are not dramatic or well-defined effects. PIP testing also confirms that these pipes exhibit little or no anisotropy. It is in general concluded that PIP-derived stress–strain curves for testing of the outside of a pipe are likely to be quite close to those obtained by tensile testing of the whole section in the hoop direction, after flattening.     

Profilometry-Based Indentation Plastometry Testing for Characterization of Case-Hardened Steels

An attraction of the profilometry-based indentation plastometry (PIP) procedure is that, while it involves interrogation of volumes sufficiently large to ensure that bulk properties are obtained, it still allows stress–strain curves to be inferred for relatively small regions, such that local properties can be mapped where they are changing over short distances. It is employed here to obtain these characteristics as a function of depth in samples that have been case hardened by the diffusional penetration of carbon, to a depth of just over a mm. This has been done for a grade of steel that is commonly treated in this way. The thickness of the layer characterized by the PIP test is around 200 μm. In addition, curvature measurements on strip samples, after incremental removal of thin layers, have been used to evaluate the (compressive) residual stresses in near-surface regions. These range up to around 200 MPa. Such stresses have only a small effect on the PIP measurements. The carburization raises the peak yield stress from the base level of around 1000 MPa to about 1400 MPa, followed by considerable work hardening. The reliability of these PIP-derived stress–strain relationships has been confirmed by comparing experimental outcomes of Vickers hardness tests with FEM predictions based on their use.     

Indentation Plastometry for Study of Anisotropy and Inhomogeneity in Maraging Steel Produced by Laser Powder Bed Fusion

This work concerns the use of profilometry-based indentation plastometry (PIP) to obtain mechanical property information for maraging steel samples produced via an additive manufacturing route (laser powder bed fusion). Bars are produced in both “horizontal” (all material close to the build plate) and “vertical” (progressively increasing distance from the build plate) configurations. Samples are mechanically tested in both as-built and age-hardened conditions. Stress–strain curves from uniaxial testing (tensile and compressive) are compared with those from PIP testing. Tensile test data suggest significant anisotropy, with the horizontal direction harder than the vertical direction. However, systematic compressive tests, allowing curves to be obtained for both build and transverse directions in various locations, indicate that there is no anisotropy anywhere in these materials. This is consistent with electron backscattered diffraction results, indicating that there is no significant texture in these materials. It is also consistent with the outcomes of PIP testing, which can detect anisotropy with high sensitivity. Furthermore, both PIP testing and compression testing results indicate that the changing growth conditions at different distances from the build plate can lead to strength variations. It seems likely that what has previously been interpreted as anisotropy in the tensile response is in fact due to inhomogeneity of this type.     

Indentation Plastometry of Particulate Metal Matrix Composites,Highlighting Effects of Microstructural Scale

Herein, it is concerned with the use of profilometry-based indentation plastometry (PIP) to obtain mechanical property information for particulate metal matrix composites (MMCs). This type of test, together with conventional uniaxial testing, has been applied to four different MMCs (produced with various particulate contents and processing conditions). It is shown that reliable stress–strain curves can be obtained using PIP, although the possibility of premature (prenecking) fracture should be noted. Close attention is paid to scale effects. As a consequence of variations in local spatial distributions of particulate, the “representative volume” of these materials can be relatively large. This can lead to a certain amount of scatter in PIP profiles and it is advisable to carry out a number of repeat PIP tests in order to obtain macroscopic properties. Nevertheless, it is shown that PIP testing can reliably detect the relatively minor (macroscopic) anisotropy exhibited by forged materials of this type.     

The Role of Trp79 in β-Actin on Histidine Methyltransferase SETD3 Catalysis

N^τ-methylation of His73 in actin by histidine methyltransferase SETD3 plays an important role in stabilising actin filaments in eukaryotes. Mutations in actin and overexpression of SETD3 have been related to human diseases, including cancer. Here, we investigated the importance of Trp79 in β-actin on productive human SETD3 catalysis. Substitution of Trp79 in β-actin peptides by its chemically diverse analogues reveals that the hydrophobic Trp79 binding pocket modulates the catalytic activity of SETD3, and that retaining a bulky and hydrophobic amino acid at position 79 is important for efficient His73 methylation by SETD3. Molecular dynamics simulations show that the Trp79 binding pocket of SETD3 is ideally shaped to accommodate large and hydrophobic Trp79, contributing to the favourable release of water molecules upon binding. Our results demonstrate that the distant Trp79 binding site plays an important role in efficient SETD3 catalysis, contributing to the identification of new SETD3 substrates and the development of chemical probes targeting the biomedically important SETD3.     

Accelerating earthquake simulations on general‐purpose graphics processors

Parallelization strategies are presented for Virtual Quake, a numerical simulation code for earthquakes based on topologically realistic systems of interacting earthquake faults. One of the demands placed upon the simulation is the accurate reproduction of the observed earthquake statistics over three to four decades. This requires the use of a high‐resolution fault model in computations, which demands computational power that is well beyond the scope of off‐the‐shelf multi‐core CPU computers. However, the recent advances in general‐purpose graphic processing units have the potential to address this problem at moderate cost increments. A functional decomposition of Virtual Quake is performed, and opportunities for parallelization are discussed in this work. Computationally intensive modules are identified, and these are implemented on graphics processing units, significantly speeding up earthquake simulations. In the current best case scenario, a computer with six graphics processing units can simulate 500 years of fault activity in California at 1.5 km × 1.5 km element resolution in less than 1 hour, whereas a single CPU requires more than 2 days to perform the same simulation. Copyright © 2015 John Wiley & Sons, Ltd.