β-Ketoiminato Iridium(III) Organometallic Complexes: Selective Cytotoxicity towards Colorectal Cancer Cells HCT116 p53-/-

This report presents a new library of organometallic iridium(III) compounds of the type [Cp*IrCl(L)] (Cp*=pentamethylcyclopentadienyl and L=a functionalized β-ketoiminato ligand) showing moderate to high cytotoxicity against a range of cancer cell lines. All compounds show increased activity towards colorectal cancer, with preferential activity observed against the immortalized p53-null colorectal cell line, HCT116 p53-/-, with sensitivity factors (SF) up to 26.7. Additionally, the compounds have excellent selectivity for cancerous cells when tested against normal cell types, with selectivity ratios (SR) up to 35.6, contrary to that of cisplatin, which is neither selective nor specific for cancerous cells (SF=0.43 and SR=0.7–2.3). This work provides a preliminary understanding of the cytotoxicity of iridium compounds in the absence of p53 and has potential applications in treatment of cancers for which the p53 gene is absent or mutant.     

Ruthenium‐Containing Linear Helicates and Mesocates with Tuneable p53‐Selective Cytotoxicity in Colorectal Cancer Cells

The ligands L¹ and L² both form separable dinuclear double‐stranded helicate and mesocate complexes with Ru^II. In contrast to clinically approved platinates, the helicate isomer of [Ru₂( L¹ )₂]⁴⁺ was preferentially cytotoxic to isogenic cells (HCT116 p53^?/?), which lack the critical tumour suppressor gene. The mesocate isomer shows the reverse selectivity, with the achiral isomer being preferentially cytotoxic towards HCT116 p53^+/+. Other structurally similar Ru^II‐containing dinuclear complexes showed very little cytotoxic activity. This study demonstrates that alterations in ligand or isomer can have profound effects on cytotoxicity towards cancer cells of different p53 status and suggests that selectivity can be “tuned” to either genotype. In the search for compounds that can target difficult‐to‐treat tumours that lack the p53 tumour suppressor gene, [Ru₂( L¹ )₂]⁴⁺ is a promising compound for further development.     

Plant elemental composition and portable X‐ray fluorescence (pXRF) spectroscopy: quantification under different analytical parameters

Emergence of portable X‐ray fluorescence (pXRF) systems presents new opportunities for rapid, low‐cost plant analysis, both as a lab system and in situ system. Numerous studies have extolled the virtues of using pXRF for a wide range of plant applications, however, for many such applications, there is need for further assessment with regards to analytical parameters for plant analysis. While pXRF is a potential powerful research tool for elemental composition analysis, its successful use in plant analysis is made more likely by having an understanding of X‐ray physics, calibration process, and ability to test a variety of homogenous and well‐characterized materials for developing a matrix‐specific calibration. Because potential pXRF users may often underestimate the complexity of proper analysis, this study aims at providing a technical background for plant analysis using pXRF. The focus is on elemental quantification under different analytical parameters and different methods of sample presentation: direct surface contact under vacuum, placement in a sample cup with prolene as a seal, and without the aid of a vacuum. Direct analysis on the surface of a pXRF provided highest sensitivity and accuracy (R² > 0.90) for light elements (Mg to P). Sulfur, K, and Ca can be reliably measured without the aid of a vacuum (R² > 0.99, 0.97, and 0.93 respectively), although lower detection limits may be compromised. pXRF instruments provide plant data of sufficient accuracy for many applications and will reduce the overall time and budget compared with the use of conventional techniques. Sensitivity and accuracy are dependent on the instrument's settings, make, and model. © 2015 The Authors. X‐Ray Spectrometry published by John Wiley & Sons, Ltd.     

Tensor splines for interpolation and approximation of DT-MRI with applications to segmentation of isolated rat hippocampi

In this paper, we present novel algorithms for statistically robust interpolation and approximation of diffusion tensors-which are symmetric positive definite (SPD) matrices-and use them in developing a significant extension to an existing probabilistic algorithm for scalar field segmentation, in order to segment diffusion tensor magnetic resonance imaging (DT-MRI) datasets. Using the Riemannian metric on the space of SPD matrices, we present a novel and robust higher order (cubic) continuous tensor product of B-splines algorithm to approximate the SPD diffusion tensor fields. The resulting approximations are appropriately dubbed tensor splines. Next, we segment the diffusion tensor field by jointly estimating the label (assigned to each voxel) field, which is modeled by a Gauss Markov measure field (GMMF) and the parameters of each smooth tensor spline model representing the labeled regions. Results of interpolation, approximation, and segmentation are presented for synthetic data and real diffusion tensor fields from an isolated rat hippocampus, along with validation. We also present comparisons of our algorithms with existing methods and show significantly improved results in the presence of noise as well as outliers.     

Flapping flexible fish

In order to analyze and model the body kinematics used by fish in a wide range of swimming behaviors, we developed a technique to separate the periodic whole-body motions that characterize steady swimming from the secular motions that characterize changes in whole-body shape. We applied this harmonic analysis technique to the study of the forward and backward swimming of lamprey. We found that in order to vary the unsteadiness of swimming, lamprey superimpose periodic and secular components of their body motion, modulate the patterns and magnitudes of those components, and change shape. These kinematic results suggest the following hydromechanical hypothesis: steady swimming is a maneuver that requires active suppression of secular body reconfigurations.     

A fluorescent probe for the detection of myeloperoxidase activity in atherosclerosis-associated macrophages

The myeloperoxidase (MPO)-derived oxidant hypochlorous acid (HOCl/OCl(-)) is implicated in the pathogenesis of atherosclerosis and other inflammatory states. We have synthesized an imaging probe, sulfonaphthoaminophenyl fluorescein (SNAPF), that selectively reacts with HOCl. SNAPF detects HOCl produced by stimulated MPO-expressing cells cultured from human whole blood, as well as HOCl from bone marrow (BM)-derived macrophages isolated from transgenic mice that express human MPO. Two lines of evidence indicate that SNAPF permits the in vivo imaging of HOCl production. First, we used this approach to demonstrate HOCl production by neutrophils in experimental murine peritonitis. Second, we detected HOCl production by MPO expressing cells in human atherosclerotic arteries. Thus, fluorescence reflectance imaging by SNAPF may provide a valuable noninvasive molecular imaging tool for implicating HOCl and MPO in the damage of inflamed tissues.     

Determination of phosphate using a highly sensitive paired emitter-detector diode photometric flow detector

The use of a novel inexpensive photometric device, a paired emitter-detector diode (PEDD) has been applied to the colorimetric determination of phosphate using the malachite green spectrophotometric method. The novel miniaturized flow detector applied within this manifold is a highly sensitive, low cost, miniaturized light emitting diode (LED) based detector. The optical flow cell was constructed from two LEDs, whereby one is the light source and the second is the light detector, with the LED light source forward biased and the LED detector reversed biased. The photocurrent generated by the LED light source discharges the junction capacitance of the detector diode from 5 V (logic 1) to 1.7 V (logic 0) and the time taken for this process to occur is measured using a simple timer circuit.The malachite green (MG) method employed for phosphate determination is based on the formation of a green molybdophosphoric acid complex, the intensity of which is directly related to phosphate concentration. Optimum analytical parameters such as reaction kinetics, reagent to sample concentration ratio and emitter wavelength intensity were investigated for the spectrophotometric method. Linear calibration plots that obeyed the Beer-Lambert law were obtained for phosphate in the range of 0.02-2 μM. The dynamic range, sensitivity and limits of detection are reported.     

Synthesis and Evaluation of Imidazo[1,2‐a]pyridine Analogues of the ZSTK474 Class of Phosphatidylinositol 3‐Kinase Inhibitors

Using a scaffold‐hopping approach, imidazo[1,2‐a]pyridine analogues of the ZSTK474 (benzimidazole) class of phosphatidylinositol 3‐kinase (PI3K) inhibitors have been synthesized for biological evaluation. Compounds were prepared using a heteroaryl Heck reaction procedure, involving the palladium‐catalysed coupling of 2‐(difluoromethyl)imidazo[1,2‐a]pyridines with chloro, iodo or trifluoromethanesulfonyloxy (trifloxy) substituted 1,3,5‐triazines or pyrimidines, with the iodo intermediates being preferred in terms of higher yields and milder reaction conditions. The new compounds maintain the PI3K isoform selectivity of their benzimidazole analogues, but in general show less potency.     

Bicoherence analysis of model-scale jet noise

Bicoherence analysis has been used to characterize nonlinear effects in the propagation of noise from a model-scale, Mach-2.0, unheated jet. Nonlinear propagation effects are predominantly limited to regions near the peak directivity angle for this jet source and propagation range. The analysis also examines the practice of identifying nonlinear propagation by comparing spectra measured at two different distances and assuming far-field, linear propagation between them. This spectral comparison method can lead to erroneous conclusions regarding the role of nonlinearity when the observations are made in the geometric near field of an extended, directional radiator, such as a jet.