Nanoparticles in cancer imaging and therapy

Nanoparticle contrast agents offer the potential to significantly improve existing methods of cancer diagnosis and treatment. Advantages include biocompatibility, selective accumulation in tumor cells, and reduced toxicity. Considerable research is underway into the use of nanoparticles as enhancement agents for radiation therapy and photodynamic therapy, where they may be used to deliver treatment agents, produce localized enhancements in radiation dose and selectively target tumor cells for localized damage. This paper reviews the current status of nanoparticles for cancer treatment and presents preliminary results of a pilot study investigating titanium dioxide nanoparticles for dual-mode enhancement of computed tomography (CT) imaging and kilovoltage radiation therapy. Although titanium dioxide produced noticeable image contrast enhancement in the CT scans, more sensitive detectors are needed to determine whether the nanoparticles can also produce localized dose enhancement for targeted radiation therapy.

Control of morphology and nucleation density of iron oxide nanostructures by electric conditions on iron surfaces exposed to reactive oxygen plasmas

The possibility to control the morphology and nucleation density of quasi-one-dimensional, single-crystalline α -Fe2 O3 nanostructures by varying the electric potential of iron surfaces exposed to reactive oxygen plasmas is demonstrated experimentally. A systematic increase in the oxygen ion flux through rf biasing of otherwise floating substrates and then an additional increase of the ion/neutral density resulted in remarkable structural transformations of straight nanoneedles into nanowires with controlled tapering/aspect ratio and also in larger nucleation densities. Multiscale numerical simulations relate the microscopic ion flux topographies to the nanostructure nucleation and morphological evolution. This approach is applicable to other metal-oxide nanostructures.

Development of reverse phase protein microarrays for clinical applications and patient-tailored therapy

While genomics provide important information about the somatic genetic changes, and RNA transcript profiling can reveal important expression changes that correlate with outcome and response to therapy, it is the proteins that do the work in the cell. At a functional level, derangements within the proteome, driven by post-translational and epigenetic modifications, such as phosphorylation, is the cause of a vast majority of human diseases. Cancer, for instance, is a manifestation of deranged cellular protein molecular networks and cell signaling pathways that are based on genetic changes at the DNA level. Importantly, the protein pathways contain the drug targets in signaling networks that govern overall cellular survival, proliferation, invasion and cell death. Consequently, the promise of proteomics resides in the ability to extend analysis beyond correlation to causality. A critical gap in the information knowledge base of molecular profiling is an understanding of the ongoing activity of protein signaling in human tissue: what is activated and “in use” within the human body at any given point in time. To address this gap, we have invented a new technology, called reverse phase protein microarrays, that can generate a functional read-out of cell signaling networks or pathways for an individual patient obtained directly from a biopsy specimen. This “wiring diagram” can serve as the basis for both, selection of a therapy and patient stratification.

Plasma-assembled carbon nanotubes : electric field–related effects

The paper presents results of comparative investigation of carbon nanotubes growth processes in dense low-temperature plasma and on substrate surface. Hybrid/Monte-Carlo numerical simulations were used to demonstrate the differences in the ion fluxes, growth rates and kinetics of adsorbed atoms re-distribution on substrate and nanotubes surfaces. We show that the plasma parameters significantly affect the nanotubes growth kinetics. We demonstrate that the growth rates of the nanotubes in plasma and on surface can differ by three orders, and the specific fluxes to the nanotube in the plasma can exceed the flux to surface-grown nanotube by six orders. We also show that the metal catalyst used for the nanotubes production on surface and in arc is a subject to very different conditions and this may be a key factor for the nanotube growth mode. The obtained dependencies for the ion fluxes to the nanotubes and nanotubes growth rates on the plasma parameters may be useful for selection of the production methods.

Excitation of surface plasma waves in crossed electric and magnetic fields

The efficiency of the excitation of surface plasma waves in the presence of external, steady crossed magnetic and electric fields is studied analytically and numerically for a geometry in which the waves propagate along the interface between a plasma-like medium and a metal in the direction transverse to both fields. The magnetic and electric fields are assumed to be parallel and transverse to the interface, respectively. The condition for which the drift instability of the surface wave arises is found.

A three-phase to single-phase matrix converter based bi-directional IPT system for charging electric vehicles

This paper presents a novel three-phase to single-phase matrix converter (TSMC) based bi-directional inductive power transfer (IPT) system for vehicle-to-grid (V2G) applications. In contrast to existing techniques, the proposed technique which employs a TSMC to drive an 8th order high frequency resonant network, requires only a single-stage power conversion process to facilitate bi-directional power transfer between electric vehicles (EVs) and a three-phase utility power supply. A mathematical model is presented to demonstrate that both magnitude and direction of power flow can be controlled by regulating either relative phase angles or magnitudes of voltages generated by converters. The viability of the proposed mathematical model is verified using simulated results of a 10 kW bi-directional IPT system and the results suggest that the proposed system is efficient, reliable and is suitable for high power applications which require contactless power transfer.

Network-targeted combination therapy : a new concept in cancer treatment

Toxicity is a major concern for anti-neoplastic drugs, with much of the existing pharmacopoeia being characterized by a very narrow therapeutic index. 'Network-targeted' combination therapy is a promising new concept in cancer therapy, whereby therapeutic index might be improved by targeting multiple nodes in a cell's signaling network, rather than a single node. Here, we examine the potential of this novel approach, illustrating how therapeutic benefit could be achieved with smaller doses of the necessary agents.

BRAF inhibitor therapy for melanoma, thyroid and colorectal cancers : development of resistance and future prospects

BRAF is a major oncoprotein and oncogenic mutations in BRAF are found in a significant number of cancers, including melanoma, thyroid cancer, colorectal cancer and others. Consequently, BRAF inhibitors have been developed as treatment options for cancers with BRAF mutations which have shown some success in improving patient outcomes in clinical trials. Development of resistance to BRAF kinase inhibitors is common, however, and overcoming this resistance is an area of significant concern for clinicians, patients and researchers alike. In this review, we identify the mechanisms of BRAF kinase inhibitor resistance and discuss the implications for strategies to overcome this resistance in the context of new approaches such as multi-kinase targeted therapies and emerging RNA interference based technologies.

Electric breakdown in liquids : faster ignition using less energy

The formation of vapor layers around an electrode immersed in a conducting liquid prior to generation of a plasma discharge is studied using numerical simulations. This study quantifies and explains the effects of the electrode geometry and applied voltage pulses, as well as the electrical and thermal properties of the liquids on the temporal dynamics of the pre-breakdown conditions in the vapor layer. This model agrees well with experimental data, in particular, the time needed to reach the electrical breakdown threshold. Because the time needed for discharge ignition can be accurately predicted from the model, the parameters such as the pulse shape, voltage, and electrode configuration can be optimized under different liquid conditions, which facilitates a faster and more energy-efficient plasma generation.

Contactless and replaceable modularized battery energy storage system for electric vehicles

A novel replaceable, modularized energy storage system with wireless interface is proposed for a battery operated electric vehicle (EV). The operation of the proposed system is explained and analyzed with an equivalent circuit and an averaged state-space model. A non-linear feedback linearization based controller is developed and implemented to regulate the DC link voltage by modulating the phase shift ratio. The working and control of the proposed system is verified through simulation and some preliminary results are presented.

Controller synthesis of a bidirectional inductive power interface for electric vehicles

Bidirectional Inductive Power Transfer (IPT) systems are preferred for Vehicle-to-Grid (V2G) applications. Typically, bidirectional IPT systems consist of high order resonant networks, and therefore, the control of bidirectional IPT systems has always been a difficulty. To date several different controllers have been reported, but these have been designed using steady-state models, which invariably, are incapable of providing an accurate insight into the dynamic behaviour of the system A dynamic state-space model of a bidirectional IPT system has been reported. However, currently this model has not been used to optimise the design of controllers. Therefore, this paper proposes an optimised controller based on the dynamic model. To verify the operation of the proposed controller simulated results of the optimised controller and simulated results of another controller are compared. Results indicate that the proposed controller is capable of accurately and stably controlling the power flow in a bidirectional IPT system.

Control of solar powered micro-grids using electric vehicles

Large scale solar plants are gaining recognition as potential energy sources for future. In this paper, the feasibility of using electric vehicles (EVs) to control a solar powered micro-grid is investigated in detail. The paper presents a PSCAD/EMTDC based model for the solar powered micro-grid with EVs. EVs are expected to have both the vehicle-to-grid (V2G) and grid-to-vehicle (G2V) capability, through which energy can either be injected into or extracted from the solar powered micro-grid to control its energy imbalance. Using the model, the behaviour of the micro-grid is investigated under a given load profile, and the results indicate that a minimum number of EVs are required to meet the energy imbalance and it is time dependent and influenced by various factors such as depth of charge, commuting profiles, reliability etc...

A unique battery/supercapacitor direct integration scheme for hybrid electric vehicles

Battery/supercapacitor hybrid energy storage systems have been gaining popularity in electric vehicles due to their excellent power and energy performances. Conventional designs of such systems require interfacing dc-dc converters. These additional dc-dc converters increase power loss, complexity, weight and cost. Therefore, this paper proposes a new direct integration scheme for battery/supercapacitor hybrid energy storage systems using a double ended inverter system. This unique approach eliminates the need for interfacing converters and thus it is free from aforementioned drawbacks. Furthermore, the proposed system offers seven operating modes to improve the effective use of available energy in a typical drive cycle of a hybrid electric vehicle. Simulation results are presented to verify the efficacy of the proposed system and control techniques.

Assessment of cone beam CT registration for prostate radiation therapy : fiducial marker and soft tissue methods

Introduction This investigation aimed to assess the consistency and accuracy of radiation therapists (RTs) performing cone beam computed tomography (CBCT) alignment to fiducial markers (FMs) (CBCTFM) and the soft tissue prostate (CBCTST). Methods Six patients receiving prostate radiation therapy underwent daily CBCTs. Manual alignment of CBCTFM and CBCTST was performed by three RTs. Inter-observer agreement was assessed using a modified Bland–Altman analysis for each alignment method. Clinically acceptable 95% limits of agreement with the mean (LoAmean) were defined as ±2.0 mm for CBCTFM and ±3.0 mm for CBCTST. Differences between CBCTST alignment and the observer-averaged CBCTFM (AvCBCTFM) alignment were analysed. Clinically acceptable 95% LoA were defined as ±3.0 mm for the comparison of CBCTST and AvCBCTFM. Results CBCTFM and CBCTST alignments were performed for 185 images. The CBCTFM 95% LoAmean were within ±2.0 mm in all planes. CBCTST 95% LoAmean were within ±3.0 mm in all planes. Comparison of CBCTST with AvCBCTFM resulted in 95% LoA of −4.9 to 2.6, −1.6 to 2.5 and −4.7 to 1.9 mm in the superior–inferior, left–right and anterior–posterior planes, respectively. Conclusions Significant differences were found between soft tissue alignment and the predicted FM position. FMs are useful in reducing inter-observer variability compared with soft tissue alignment. Consideration needs to be given to margin design when using soft tissue matching due to increased inter-observer variability. This study highlights some of the complexities of soft tissue guidance for prostate radiation therapy.