Evolution of breast cancer therapeutics: Breast tumour kinase’s role in breast cancer and hope for breast tumour kinase targeted therapy

This is an open access article distributed under the terms of the Creative Commons Attribution (CC BY) license (http://creativecommons.org/licenses/by/4.0/). © 2014 Baishideng Publishing Group Inc.There have been significant improvements in the detection and treatment of breast cancer in recent decades. However, there is still a need to develop more effective therapeutic techniques that are patient specific with reduced toxicity leading to further increases in patients’ overall survival; the ongoing progress in understanding recurrence, resistant and spread also needs to be maintained. Better understanding of breast cancer pathology, molecular biology and progression as well as identification of some of the underlying factors involved in breast cancer tumourgenesis and metastasis has led to the identification of novel therapeutic targets. Over a number of years interest has risen in breast tumour kinase (Brk) also known as protein tyrosine kinase 6; the research field has grown and Brk has been described as a desirable therapeutic target in relation to tyrosine kinase inhibition as well as disruption of its kinase independent activity. This review will outline the current “state of play” with respect to targeted therapy for breast cancer, as well as discussing Brk’s role in the processes underlying tumour development and metastasis and its potential as a therapeutic target in breast cancer

Trade Liberalisation Policies, Intra-regional Trade and Opportunities for Sustainable Agricultural Development

Many of the Near East (NE) countries are currently opening their agricultural markets at three distinct but interacting levels: unilateral liberalisation, regional integration schemes and multilateral trade liberalisation. These changes hold important implications for intra- and extra-regional trade, use of agricultural resources and sustainability of agricultural development in the NE countries. Unilaterally, and since the late 1980s, most countries of the region have liberalised their agriculture sectors by eliminating or reducing input subsidies, removing or reducing guaranteed producer prices, reducing the number of subsidised commodities and liberalising the exchange rate and the trade regime. Most of the implicit and explicit subsidies for agricultural inputs and outputs were withdrawn. However, some of the NE countries were able to continue supporting agriculture mainly for food security reasons. Experiences showed that domestic reform is necessary but not sufficient condition for economic growth.

Frustrated Metastable Behavior of Magnetic and Transport Properties in Charge Ordered La1-xCaxMnO3+d Manganites

We have studied the effect of metastable, irreversibility induced by repeated thermal cycles on the electric transport and magnetization of polycrystalline samples of La1-xCaxMnO3 (0.48\leq x \leq 0.55) close to charge ordering. With time and thermal cycling (T<300 K) there is an irreversible transformation of the low-temperature phase from a partially ferromagnetic and metallic to one that is less ferromagnetic and highly resistive for the composition close to charge ordering (x=050 and 0.52). Irrespective of the actual ground state of the compound, the effect of thermal cycling is towards an increase of the amount of the insulating phase. We have observed the magnetic relaxation in the metastable state and also the revival of the metastable state (in a relaxed sample) due to high temperature thermal treatment. We observed changes in the resistivity and magnetization as the revived metastable state is cycled. The time changes in the magnetization are logarithmic in general and activation energies are consistent with those expected for electron transfer between Mn ions. Changes induced by thermal cycling can be inhibited by applying magnetic field. These results suggest that oxygen non-stoichiometry results in mechanical strains in this two-phase system, leading to the development of frustrated metastable states which relax towards the more stable charge-ordered and antiferromagnetic microdomains. Our results also suggest that the growth and coexistence of phases gives rise to microstructural tracks and strain accommodation, producing the observed irreversibility.Comment: 13 Pages, 10 Figure

Beating the One-half Limit of Ancilla-free Linear Optics Bell Measurements

We show that optically encoded two-qubit Bell states can be unambiguously discriminated with a success probability of more than 50% in both single-rail and dual-rail encodings by using active linear-optical resources that include Gaussian squeezing operations. These results are in contrast to the well-known upper bound of 50% for unambiguous discrimination of dual-rail Bell states using passive, static linear optics and arbitrarily many vacuum modes. We present experimentally feasible schemes that improve the success probability to 64.3% in dual-rail and to 62.5% in single-rail for a uniform random distribution of Bell states. Conceptually, this demonstrates that neither interactions that induce nonlinear mode transformations (such as Kerr interactions) nor auxiliary entangled photons are required to go beyond the one-half limit. We discuss the optimality of our single-rail scheme, and talk about an application of our dual-rail scheme in quantum communication.Comment: 4+5 pages, 4 figure

Length-scale cascade and spread rate of atomizing planar liquid jets

The primary breakup of a planar liquid jet is explored via direct numerical simulation (DNS) of the incompressible Navier-Stokes equation with level-set and volume-of-fluid interface capturing methods. PDFs of the local radius of curvature and the local cross-flow displacement of the liquid-gas interface are evaluated over wide ranges of the Reynolds number ($Re$), Weber number ($We$), density ratio and viscosity ratio. The temporal cascade of liquid-structure length scales and the spread rate of the liquid jet during primary atomization are analyzed. The formation rate of different surface structures, e.g. lobes, ligaments and droplets, are compared for different flow conditions and are explained in terms of the vortex dynamics in each atomization domain that we identified recently. With increasing $We$, the average radius of curvature of the surface decreases, the number of small droplets increases, and the cascade and the surface area growth occur at faster rates. The spray angle is mainly affected by $Re$ and density ratio, and is larger at higher $We$, at higher density ratios, and also at lower $Re$. The change in the spray spread rate versus $Re$ is attributed to the angle of ligaments stretching from the jet core, which increases as $Re$ decreases. Gas viscosity has negligible effect on both the droplet-size distribution and the spray angle. Increasing the wavelength-to-sheet-thickness ratio, however, increases the spray angle and the structure cascade rate, while decreasing the droplet size. The smallest length scale is determined more by surface tension and liquid inertia than by the liquid viscosity, while gas inertia and liquid surface tension are the key parameters in determining the spray angle.Comment: Submitted for publication to International Journal of Multiphase Flow. 37 pages; 33 figure

Understanding liquid-jet atomization cascades via vortex dynamics

Temporal instabilities of a planar liquid jet are studied using direct numerical simulation (DNS) of the incompressible Navier-Stokes equations with level-set (LS) and volume-of-fluid (VoF) surface tracking methods. $\lambda_2$ contours are used to relate the vortex dynamics to the surface dynamics at different stages of the jet breakup, namely, lobe formation, lobe perforation, ligament formation, stretching, and tearing. Three distinct breakup mechanisms are identified in the primary breakup, which are well categorized on the parameter space of gas Weber number ($We_g$) versus liquid Reynolds number ($Re_l$). These mechanisms are analyzed here from a vortex dynamics perspective. Vortex dynamics explains the hairpin formation, and the interaction between the hairpins and the Kelvin-Helmholtz (KH) roller explains the perforation of the lobes, which is attributed to the streamwise overlapping of two oppositely-oriented hairpin vortices on top and bottom of the lobe. The formation of corrugations on the lobe front edge at high $Re_l$ is also related to the location and structure of the hairpins with respect to the KH vortex. The lobe perforation and corrugation formation are inhibited at low $Re_l$ and low $We_g$ due to the high surface tension and viscous forces, which damp the small scale corrugations and resist hole formation. Streamwise vorticity generation - resulting in three-dimensional instabilities - is mainly caused by vortex stretching and baroclinic torque at high and low density ratios, respectively. Generation of streamwise vortices and their interaction with spanwise vortices produce the liquid structures seen at various flow conditions. Understanding the liquid sheet breakup and the related vortex dynamics are crucial for controlling the droplet size distribution in primary atomization.Comment: Submitted for publication in Journal of Fluid Mechanics. 56 pages; 52 figure