Structural Investigation of Protonated Azidothymidine and Protonated Dimer

Infrared multiple photon dissociation (IRMPD) spectroscopy experiments and quantum chemical calculations have been used to explore the possible structures of protonated azidothymidine and the corresponding protonated dimer. Many interesting differences between the protonated and neutral forms of azidothymidine were found, particularly associated with keto-enol tautomerization. Comparison of computational vibrational and the experimental IMRPD spectra show good agreement and give confidence that the dominant protonated species has been identified. The protonated dimer of azidothymidine exhibits three intramolecular hydrogen bonds. The IRMPD spectrum of the protonated dimer is consistent with the spectrum of the most stable computational structure. This work brings to light interesting keto-enol tautomerization and exocyclic hydrogen bonding involving azidothymidine and its protonated dimer. The fact that one dominant protonated species is observed in the gas phase, despite both the keto and enol structures being similar in energy, is proposed to be the direct result of the electrospray ionization process in which the dominant protonated dimer structure dissociates in the most energetically favorable way.

E6 symmetry breaking in the superstring theory

We derive two methods for determining the symmetry breaking of E₆ in the low energy superstring theory, and classify all breaking patterns. A method for calculating the effective Higgs vacuum expectation values is presented. We show that there are theories with naturally light SU₂^w Higgs doublets, and classify all theories in which this occurs. The phenomenology of spontaneously broken E₆ theories is discussed, emphasizing the issues of nucleon decay and neutrino masses.     

On-demand controlled release of docetaxel from a battery-less MEMS drug delivery device

We report the development of a magnetically controlled MEMS device capable of on-demand release of defined quantities of an antiproliferative drug, docetaxel (DTX). Controlled release of DTX with a dosage suitable for the treatment of diabetic retinopathy has been achieved for 35 days. The device consists of a drug-loaded microreservoir (?6 mm ×～550 μm), sealed by an elastic magnetic PDMS (polydimethylsiloxane) membrane (?6 mm × 40 μm) with a laser-drilled aperture (～100 × 100 μm(2)). By applying a magnetic field, the magnetic PDMS membrane deforms, causing the discharge of the drug solution from the device. Controlled DTX release at a rate of 171 ± 16.7 ng per actuation interval has been achieved for 35 days using a 255 mT magnetic field. The background leakage of drug solution through the aperture was negligible at 0.053 ± 0.014 ng min(-1). The biological activity of the released drug was investigated using a cytotoxicity assay (cell apoptosis) for two cell lines, HUVEC (human umbilical vein endothelial cells) and PC3 (prostate cancer) cells. Reproducible release rates have been achieved and DTX within the PDMS MEMS reservoir maintains full pharmacological efficacy for more than two months. This device is a proof-of-concept development for targeted delivery of hydrophobic drugs such as DTX and other taxane-based agents that require accurate delivery in nanomolar concentrations.     

A magnetically controlled MEMS device for drug delivery: design, fabrication, and testing

We report the development of a magnetically controlled drug delivery device for on-demand drug release to treat chronic diseases. The devices consist of drug-loaded micro-reservoirs (6 mm in diameter and ～550 μm in depth), sealed by magnetic PDMS (polydimethylsiloxane) membranes (? 6 mm × 40 μm) with laser-drilled apertures and actuated by an external magnetic field. We present a detailed analysis of the magnetic actuation forces and provide an estimate of the resulting membrane deflections. The reservoirs are fabricated by PDMS molding and loaded with drugs using solvent evaporation methods. Post-processing procedures using bovine serum albumin (BSA) adsorption on magnetic PDMS surfaces are carried out to modify the surface wettability and to allow water filling and dissolution of the drugs in the reservoirs. Detailed surface modification processes are described and characterized. The device demonstrates on-demand delivery of methylene blue (MB) as a model drug. Intermittent magnetic actuations of the device in a ～200 mT magnetic field show 10-fold increase in MB release compared to background release when the device is not actuated.     

Towards the integration of system modelling with scenario planning to support strategy: the case of the UK energy industry

A key aspect of strategy is sense-making of the unfolding uncertainty in the business environment and responding appropriately to achieve organisational objectives. However, uncertainty means that there is more than one future open to an organisation. Sense-making is therefore problematic. Scenario planning is one approach to sense-making that helps to explore and understand uncertainty, aiming for the identification of potential predetermined elements in the business environment. In this paper we propose the integration of systems modelling with scenario planning to support the exploration of uncertainty, identify knowledge gaps that set a (subsequent) research agenda, understand the role and usefulness of historical data, and model research outcomes to help reveal potential predetermined elements. Specifically, scenario planning identifies potential predetermined elements in the business environment; system modelling in the form of behaviour-over-time graphs, causal mapping and feedback loops helps in structuring and linking variables and their interaction to provide an understanding of the systemic drivers of these predetermined elements. Methodological integration of this type enhances modellers’ ability to support strategy in organisations.     

Equipment selection with heterogeneous fleets for multiple-period schedules

In a simple surface mining scenario we consider a mine to have one mining location and dumpsite connected by a truck route. We determine a purchase and salvage policy for trucks and loaders, which minimises the cost of materials handling over a multiple period schedule. This problem becomes large scale when we consider large sets of equipment and long schedules. Pre-existing equipment can lead to heterogeneous fleets; non-uniformity in the operating cost function coupled with compatibility issues also adds to the complexity of the problem. We present an integer programme for this problem, where we introduce a specialised linear constraint set to ensure satisfaction of production requirements while accounting for equipment compatibility. Many aspects of the presented model, such as the consideration of multiple periods and pre-existing equipment, are novel for the mining industry and ensure that the model is both a new and advanced equipment selection tool.     

Extraction of lanthanides from aqueous solution by using room-temperature ionic liquid and supercritical carbon dioxide in conjunction

For the first time, the study of a three-step extraction system of water/ionic liquid/supercritical CO2 has been performed. Extraction of trivalent lanthanum and europium from an aqueous nitric acid solution to a supercritical CO2 phase via an imidazolium-based ionic liquid phase is demonstrated, and extraction efficiencies higher than 87 % were achieved. The quantitative extraction is obtained by using different fluorinated beta-diketones with and without the addition of tri(n-butyl)phosphate. The complexation phenomenon occurring in the room-temperature ionic-liquid (RTIL) phase was evidenced by using luminescence spectroscopy.