Human mitochondrial glutathione transferases: Kinetic parameters and accommodation of a mitochondria-targeting group in substrates

Glutathione-S-transferases are key to the cellular detoxification of xenobiotics and products of oxidative damage. GSTs catalyse the reaction of glutathione (GSH) with electrophiles to form stable thioether adducts. GSTK1-1 is the main GST isoform in the mitochondrial matrix, but the GSTA1-1 and GSTA4-4 isoforms are also thought to be in the mitochondria with their distribution altering in transformed cells, thus potentially providing a cancer specific target. A mitochondria-targeted version of the GST substrate 1-chloro-2,4-dinitrobenzene (CDNB), MitoCDNB, has been used to manipulate the mitochondrial GSH pool. To finesse this approach to target particular GST isoforms in the context of cancer, here we have determined the kcat/Km for the human isoforms of GSTK1-1, GSTA1-1 and GSTA4-4 with respect to GSH and CDNB. We show how the rate of the GST-catalysed reaction between GSH and CDNB analogues can be modified by both the electron withdrawing substituents, and by the position of the mitochondria-targeting triphenylphosphonium on the chlorobenzene ring to tune the activity of mitochondria-targeted substrates. These findings can now be exploited to selectively disrupt the mitochondrial GSH pools of cancer cells expressing particular GST isoforms

Protomers of Benzocaine: Solvent and Permittivity Dependence

The immediate environment of a molecule can have a profound influence on its properties. Benzocaine, the ethyl ester of para-aminobenzoic acid, which finds an application as a local anesthetic (LA), is found to adopt in its protonated form at least two populations of distinct structures in the gas phase and their relative intensities strongly depend on the properties of the solvent used in the electrospray ionization (ESI) process. Here we combine IR-vibrational spectroscopy with ion mobility-mass spectrometry (IM-MS) to yield gas-phase IR spectra of simultaneously m/z and drift-time resolved species of benzocaine. The results allow for an unambiguous identification of two protomeric species - the N- and O-protonated form. Density functional theory (DFT) calculations link these structures to the most stable solution and gas-phase structures, respectively, with the electric properties of the surrounding medium being the main determinant for the preferred protonation site. The fact that the N-protonated form of benzocaine can be found in the gas phase is owed to kinetic trapping of the solution phase structure during transfer into the experimental setup. These observations confirm earlier studies on similar molecules where N- and O-protonation has been suggested

An AC Loss Model for Bi2223 Superconductors in Partial Core Transformers

This paper presents a modelling technique for calculating the ac losses for a high temperature superconducting partial core transformer using Bi2223 superconducting tape. The model is a function of the current in the tape and the magnetic field of the transformer. A time harmonic, two dimensional, finite element analysis of the transformer was used to determine the magnetic field in the winding area. This analysis showed that there was significant radial flux in the end winding regions, resulting in an elliptical nature of the magnetic field. The major and minor axes of the ellipse were used in the ac loss model. The AC losses modelled were compared with measured data from a sample HTS partial core transformer

A Comparison Between the Circuit Theory Model and Finite Element Model Reactive Components

This paper presents two different modelling techniques for the reactive components of a partial-core transformer; a circuit theory model and a finite element model. Each model was used to simulate a hypothetical partial-core transformer with a varying winding aspect ratio and the results compared. Analysis of the simulation results suggested modification of two parameters of the circuit theory model, the leakage function and the magnetising function. The models were then compared to test results from three different partial-core transformers that were built

Equivalent Circuit Model of Cascade Connected Partial Core Resonant Transformers

“© 2013 IEEE. Personal use of this material is permitted. Permission from IEEE must be obtained for all other uses, in any current or future media, including reprinting/republishing this material for advertising or promotional purposes, creating new collective works, for resale or redistribution to servers or lists, or reuse of any copyrighted component of this work in other works.”This paper presents a proof of concept and equivalent circuit analysis of a cascade arrangement of tunable HV testing transformers intended for field use. The transformers use a partial core with air completing the flux path and are tuned to resonate with insulation capacitance. This minimises the power drawn from the supply and the size and weight of the transformer. A prototype set of transformers were built to validate the model. Each transformer was modelled as a set of coupled inductors to determine the input impedance frequency response. Good agreement is shown between the modelled and measured input impedance. The inclusion of core loss resistance was shown to significantly increase the accuracy of the cascade model

A Comparison of VLF and 50 Hz Field Testing of Medium Voltage Cables

A series of PD and tan δ tests were conducted on 11 kV cables with both a VLF and a 50 Hz HV source. This research was aimed at illustrating the difference between the two methods and assessing the feasibility of the partial core resonant transformer as a portable 50 Hz test kit. The cables had hybrid PILCA/XLPE insulation systems and were up to 2 km in length. Tan δ values measured at VLF were an order of magnitude higher than those at 50 Hz. The VLF test displayed a negative DDF whilst the 50 Hz test showed a positive tip up tan δ characteristic. The 50 Hz test showed more PD than the VLF test which was expected but no consistent difference was observed between the PDIVs. The PCRTX proved to be suitable for field testing cables. All the equipment was light enough to be carried in and small enough to be set up in a confined space. With a trained technician, the tuning procedure was accomplished relatively quickly. With coarse tuning, a 2km, 0.76 μF, 11 kV cable was energised to 2U0 at 50 Hz and drew only 13 A from the supply. The VA supplied to the load exceeded the VA drawn from the supply by a factor of 20 to 30

An Experimental High Temperature Superconducting Transformer: Design, Construction and Testing

In 2005, the development of a 50Hz, 15kVA, 30V:115V partial core high temperature superconductor (HTS) transformer was completed. The transformer was designed purely as a proof of concept, rather than as a unit that would be put into service. The transformer windings were layer wound using Bi2223 HTS tape from American Superconductors. The transformer failed while endurance testing under full load with the internal primary winding failing to open circuit. This prompted an investigation into the cause of failure. Results from the investigation suggested the cause of failure to be insufficient cooling of the windings. This paper presents a new experimental full core HTS transformer with an alternative winding design to enable greater cooling for the HTS wire. The design involves the use of cooling channels allowing direct contact of the HTS wire to the liquid nitrogen coolant. A mock up transformer was constructed first using copper wire of similar dimensions to the HTS wire. The idea was to construct two similar windings, while using the same core, but using two different winding material types so that a direct performance comparison could be made between the two. Open circuit, short circuit and loaded tests were performed on the copper mock up transformer submerged in liquid nitrogen. Test results gave an efficiency of 88% in liquid nitrogen, and a 17% voltage regulation at 11kVA load. In terms of mechanical integrity, the copper mock-up transformer withstood all stresses subjected to it when submerged in liquid nitrogen. Following successful testing of the copper mock up transformer, a set of HTS windings were constructed using Bi2223 superconductors. The transformer was a full core, 50Hz, 15kVA, 230V:230V two winding transformer. Open circuit, short circuit and loaded tests were performed on the HTS transformer while submerged in liquid nitrogen. Test results gave an efficiency of 97%, and a 13% voltage regulation at 14kVA load