What can be patented? Technological innovation and the contemporary mess in patent law

The question of what types of inventions may be patented has becom

Realising the therapeutic potential of neuroactive steroid modulators of the GABA_A receptor

In the 1980s particular endogenous metabolites of progesterone and of deoxycorticosterone were revealed to be potent, efficacious, positive allosteric modulators (PAMs) of the GABAA receptor (GABAAR). These reports were followed by the discovery that such steroids may be synthesised not only in peripheral endocrine glands, but locally in the central nervous system (CNS), to potentially act as paracrine, or autocrine "neurosteroid" messengers, thereby fine tuning neuronal inhibition. These discoveries triggered enthusiasm to elucidate the physiological role of such neurosteroids and explore whether their levels may be perturbed in particular psychiatric and neurological disorders. In preclinical studies the GABAAR-active steroids were shown to exhibit anxiolytic, anticonvulsant, analgesic and sedative properties and at relatively high doses to induce a state of general anaesthesia. Collectively, these findings encouraged efforts to investigate the therapeutic potential of neurosteroids and related synthetic analogues. However, following over 30 years of investigation, realising their possible medical potential has proved challenging. The recent FDA approval for the natural neurosteroid allopregnanolone (brexanolone) to treat postpartum depression (PPD) should trigger renewed enthusiasm for neurosteroid research. Here we focus on the influence of neuroactive steroids on GABA-ergic signalling and on the challenges faced in developing such steroids as anaesthetics, sedatives, analgesics, anticonvulsants, antidepressants and as treatments for neurodegenerative disorders

On the dynamics of stochastic nonlinear dispersive partial differential equations

This thesis contributes towards the well-posedness theory of stochastic dispersive partial differential equations. Our investigation focuses on initial value problems as sociated with the stochastic nonlinear Schro¨dinger (SNLS) and stochastic Korteweg de Vries (SKdV) equations. We divide this thesis into four main topics, which are the contents of Chapters 2–5. Chapter 2 is concerned with the SNLS posed on the d-dimensional tori with either additive or multiplicative stochastic forcing. In particular, we prove local-in time well-posedness for initial data and noise at subcritical regularities. We are also able to extend this to global-in-time well-posedness at energy subcritical regularity for certain cases. In the next two chapters, we focus on SNLS posed on the d dimensional Euclidean space with additive noise. In Chapter 3, we prove local well posedness with the noise at supercritical regularity while the initial data stays at critical regularity. In Chapter 4, we restrict our attention to dimension 4 and study SNLS with non-vanishing boundary conditions. In particular, we use perturbative techniques to prove global well-posedness with data in H1(R4) + 1. In Chapter 5, we move on from SNLS to SKdV, where we prove L2(T)-global well-posedness of SKdV with multiplicative noise on the circle. We also verify that a result on the stabilisation of noise by Tsutsumi [84] continues to hold in our low regularity setting

Endogenous innovation, outward-bound international patenting and national economic development

In this paper we argue that countries whose residents exhibit a relativel

Perturbative behaviour of a vortex in a trapped Bose-Einstein condensate

We derive a set of equations that describe the shape and behaviour of a single perturbed vortex line in a Bose-Einstein condensate. Through the use of a matched asymptotic expansion and a unique coordinate transform a relation for a vortex's velocity, anywhere along the line, is found in terms of the trapping, rotation, and distortion of the line at that location. This relation is then used to find a set of differential equations that give the line's specific shape and motion. This work corrects a previous similar derivation by Anatoly A. Svidzinsky and Alexander L. Fetter [Phys. Rev. A \textbf{62}, 063617 (2000)], and enables a comparison with recent numerical results.Comment: 12 pages with 3 figure

Density functional theory study of the nematic-isotropic transition in an hybrid cell

We have employed the Density Functional Theory formalism to investigate the nematic-isotropic capillary transitions of a nematogen confined by walls that favor antagonist orientations to the liquid crystal molecules (hybrid cell). We analyse the behavior of the capillary transition as a function of the fluid-substrate interactions and the pore width. In addition to the usual capillary transition between isotropic-like to nematic-like states, we find that this transition can be suppressed when one substrate is wet by the isotropic phase and the other by the nematic phase. Under this condition the system presents interface-like states which allow to continuously transform the nematic-like phase to the isotropic-like phase without undergoing a phase transition. Two different mechanisms for the disappearance of the capillary transition are identified. When the director of the nematic-like state is homogeneously planar-anchored with respect to the substrates, the capillary transition ends up in a critical point. This scenario is analogous to the observed in Ising models when confined in slit pores with opposing surface fields which have critical wetting transitions. When the nematic-like state has a linearly distorted director field, the capillary transition continuously transforms in a transition between two nematic-like states.Comment: 31 pages, 10 figures, submitted to J. Chem. Phy

The value of hippocampal and temporal horn volumes and rates of change in predicting future conversion to AD.

Hippocampal pathology occurs early in Alzheimer disease (AD), and atrophy, measured by volumes and volume changes, may predict which subjects will develop AD. Measures of the temporal horn (TH), which is situated adjacent to the hippocampus, may also indicate early changes in AD. Previous studies suggest that these metrics can predict conversion from amnestic mild cognitive impairment (MCI) to AD with conversion and volume change measured concurrently. However, the ability of these metrics to predict future conversion has not been investigated. We compared the abilities of hippocampal, TH, and global measures to predict future conversion from MCI to AD. TH, hippocampi, whole brain, and ventricles were measured using baseline and 12-month scans. Boundary shift integral was used to measure the rate of change. We investigated the prediction of conversion between 12 and 24 months in subjects classified as MCI from baseline to 12 months. All measures were predictive of future conversion. Local and global rates of change were similarly predictive of conversion. There was evidence that the TH expansion rate is more predictive than the hippocampal atrophy rate (P=0.023) and that the TH expansion rate is more predictive than the TH volume (P=0.036). Prodromal atrophy rates may be useful predictors of future conversion to sporadic AD from amnestic MCI

Suppression of Kelvon-induced decay of quantized vortices in oblate Bose-Einstein Condensates

We study the Kelvin mode excitations on a vortex line in a three-dimensional trapped Bose-Einstein condensate at finite temperature. Our stochastic Gross-Pitaevskii simulations show that the activation of these modes can be suppressed by tightening the confinement along the direction of the vortex line, leading to a strong suppression in the vortex decay rate as the system enters a regime of two-dimensional vortex dynamics. As the system approaches the condensation transition temperature we find that the vortex decay rate is strongly sensitive to dimensionality and temperature, observing a large enhancement for quasi-two-dimensional traps. Three-dimensional simulations of the recent vortex dipole decay experiment of Neely et al. [Phys. Rev. Lett. 104, 160401 (2010)] confirm two-dimensional vortex dynamics, and predict a dipole lifetime consistent with experimental observations and suppression of Kelvon-induced vortex decay in highly oblate condensates.Comment: 8 pages, 8 figure

A new chiral electro-optic effect: Sum-frequency generation from optically active liquids in the presence of a dc electric field

We report the observation of sum-frequency signals that depend linearly on an applied electrostatic field and that change sign with the handedness of an optically active solution. This recently predicted chiral electro-optic effect exists in the electric-dipole approximation. The static electric field gives rise to an electric-field-induced sum-frequency signal (an achiral third-order process) that interferes with the chirality-specific sum-frequency at second-order. The cross-terms linear in the electrostatic field constitute the effect and may be used to determine the absolute sign of second- and third-order nonlinear optical susceptibilities in isotropic media.Comment: Submitted to Physical Revie