A time frequency analysis of wave packet fractional revivals

We show that the time frequency analysis of the autocorrelation function is, in many ways, a more appropriate tool to resolve fractional revivals of a wave packet than the usual time domain analysis. This advantage is crucial in reconstructing the initial state of the wave packet when its coherent structure is short-lived and decays before it is fully revived. Our calculations are based on the model example of fractional revivals in a Rydberg wave packet of circular states. We end by providing an analytical investigation which fully agrees with our numerical observations on the utility of time-frequency analysis in the study of wave packet fractional revivals.Comment: 9 pages, 4 figure

Maximising the potential of AKT inhibitors as anti-cancer treatments.

PI3K/AKT signalling is commonly disrupted in human cancers, with AKT being a central component of the pathway, influencing multiple processes that are directly involved in tumourigenesis. Targeting AKT is therefore a highly attractive anti-cancer strategy with multiple AKT inhibitors now in various stages of clinical development. In this review, we summarise the role and regulation of AKT signalling in normal cellular physiology. We highlight the mechanisms by which AKT signalling can be hyperactivated in cancers and discuss the past, present and future clinical strategies for AKT inhibition in oncology

Critical parameters in targeted drug development: the pharmacological audit trail.

The Pharmacological Audit Trail (PhAT) comprises a set of critical questions that need to be asked during discovery and development of an anticancer drug. Key aspects include: (1) defining a patient population; (2) establishing pharmacokinetic characteristics; (3) providing evidence of target engagement, pathway modulation, and biological effect with proof of concept pharmacodynamic biomarkers; (4) determining intermediate biomarkers of response; (5) assessing tumor response; and (6) determining how to overcome resistance by combination or sequential therapy and new target/drug discovery. The questions asked in the PhAT should be viewed as a continuum and not used in isolation. Different drug development programmes derive different types of benefit from these questions. The PhAT is critical in making go-no-go decisions in the development of currently studied drugs and will continue to be relevant to discovery and development of future generations of anticancer agents

Entanglement by linear SU(2) transformations: generation and evolution of quantum vortex states

We consider the evolution of a two-mode system of bosons under the action of a Hamiltonian that generates linear SU(2) transformations. The Hamiltonian is generic in that it represents a host of entanglement mechanisms, which can thus be treated in a unified way. We start by solving the quantum dynamics analytically when the system is initially in a Fock state. We show how the two modes get entangled by evolution to produce a coherent superposition of vortex states in general, and a single vortex state under certain conditions. The degree of entanglement between the modes is measured by finding the explicit analytical dependence of the Von Neumann entropy on the system parameters. The reduced state of each mode is analyzed by means of its correlation function and spatial coherence function. Remarkably, our analysis is shown to be equally as valid for a variety of initial states that can be prepared from a two-mode Fock state via a unitary transformation and for which the results can be obtained by mere inspection of the corresponding results for an initial Fock state. As an example, we consider a quantum vortex as the initial state and also find conditions for its revival and charge conjugation. While studying the evolution of the initial vortex state, we have encountered and explained an interesting situation in which the entropy of the system does not evolve whereas its wave function does. Although the modal concept has been used throughout the paper, it is important to note that the theory is equally applicable for a two-particle system in which each particle is represented by its bosonic creation and annihilation operators.Comment: 6 figure

Off Resonant Pumping for Transition from Continuous to Discrete Spectrum and Quantum Revivals in Systems in Coherent States

We show that in parametrically driven systems and, more generally, in systems in coherent states, off-resonant pumping can cause a transition from a continuum energy spectrum of the system to a discrete one, and result in quantum revivals of the initial state. The mechanism responsible for quantum revivals in the present case is different from that in the non-linear wavepacket dynamics of systems such as Rydberg atoms. We interpret the reported phenomena as an optical analog of Bloch oscillations realized in Fock space and propose a feasible scheme for inducing Bloch oscillations in trapped ions.Comment: 5 pages, 4 figures, submitted to Jnl. of Optics

Titration of signalling output: insights into clinical combinations of MEK and AKT inhibitors.

Background We aimed to understand the relative contributions of inhibiting MEK and AKT on cell growth to guide combinations of these agents.Materials and methods A panel of 20 cell lines was exposed to either the MEK inhibitor, PD0325901, or AKT inhibitor, AKT 1/2 inhibitor. p-ERK and p-S6 ELISAs were used to define degrees of MEK and AKT inhibition, respectively. Growth inhibition to different degrees of MEK and AKT inhibition, either singly or in combination using 96-h sulphorhodamine assays was then studied.Results A significantly greater growth inhibition was seen in BRAF(M) and PIK3CA(M) cells upon maximal MEK (P = 0.004) and AKT inhibition (P = 0.038), respectively. KRAS(M) and BRAF/PIK3CA/KRAS(WT) cells were not significantly more likely to be sensitive to MEK or AKT inhibition. Significant incremental growth inhibition of the combination of MEK + AKT over either MEK or AKT inhibition alone was seen when MEK + AKT was inhibited maximally and not when sub-maximal inhibition of both MEK + AKT was used (11/20 cell lines versus 1/20 cell lines; P = 0.0012).Conclusions KRAS(M) cells are likely to benefit from combinations of MEK and AKT inhibitors. Sub-maximally inhibiting both MEK and AKT within a combination, in a majority of instances, does not significantly increase growth inhibition compared with maximally inhibiting MEK or AKT alone and alternative phase I trial designs are needed to clinically evaluate such combinations