Pharmacological evaluation of selective α2c-adrenergic agonists in experimental animal models of nasal congestion

Nasal congestion is one of the most troublesome symptoms of many upper airways diseases. We characterized the effect of selective α2c-adrenergic agonists in animal models of nasal congestion. In porcine mucosa tissue, compound A and compound B contracted nasal veins with only modest effects on arteries. In in vivo experiments, we examined the nasal decongestant dose-response characteristics, pharmacokinetic/pharmacodynamic relationship, duration of action, potential development of tolerance, and topical efficacy of α2c-adrenergic agonists. Acoustic rhinometry was used to determine nasal cavity dimensions following intranasal compound 48/80 (1%, 75 µl). In feline experiments, compound 48/80 decreased nasal cavity volume and minimum cross-sectional areas by 77% and 40%, respectively. Oral administration of compound A (0.1-3.0 mg/kg), compound B (0.3-5.0 mg/kg), and d-pseudoephedrine (0.3 and 1.0 mg/kg) produced dose-dependent decongestion. Unlike d-pseudoephedrine, compounds A and B did not alter systolic blood pressure. The plasma exposure of compound A to produce a robust decongestion (EC(80)) was 500 nM, which related well to the duration of action of approximately 4.0 hours. No tolerance to the decongestant effect of compound A (1.0 mg/kg p.o.) was observed. To study the topical efficacies of compounds A and B, the drugs were given topically 30 minutes after compound 48/80 (a therapeutic paradigm) where both agents reversed nasal congestion. Finally, nasal-decongestive activity was confirmed in the dog. We demonstrate that α2c-adrenergic agonists behave as nasal decongestants without cardiovascular actions in animal models of upper airway congestion.

Forward and backward least angle regression for nonlinear system identification

A forward and backward least angle regression (LAR) algorithm is proposed to construct the nonlinear autoregressive model with exogenous inputs (NARX) that is widely used to describe a large class of nonlinear dynamic systems. The main objective of this paper is to improve model sparsity and generalization performance of the original forward LAR algorithm. This is achieved by introducing a replacement scheme using an additional backward LAR stage. The backward stage replaces insignificant model terms selected by forward LAR with more significant ones, leading to an improved model in terms of the model compactness and performance. A numerical example to construct four types of NARX models, namely polynomials, radial basis function (RBF) networks, neuro fuzzy and wavelet networks, is presented to illustrate the effectiveness of the proposed technique in comparison with some popular methods.

k-fold Subsampling based Sequential Backward Feature Elimination

We present a new wrapper feature selection algorithm for human detection. This algorithm is a hybrid featureselection approach combining the benefits of filter and wrapper methods. It allows the selection of an optimalfeature vector that well represents the shapes of the subjects in the images. In detail, the proposed featureselection algorithm adopts the k-fold subsampling and sequential backward elimination approach, while thestandard linear support vector machine (SVM) is used as the classifier for human detection. We apply theproposed algorithm to the publicly accessible INRIA and ETH pedestrian full image datasets with the PASCALVOC evaluation criteria. Compared to other state of the arts algorithms, our feature selection based approachcan improve the detection speed of the SVM classifier by over 50% with up to 2% better detection accuracy.Our algorithm also outperforms the equivalent systems introduced in the deformable part model approach witharound 9% improvement in the detection accuracy

Copyright and Parody:Taking Backward the Gowers Review

In 2006 the Gowers Review of Intellectual Property made a series of recommendations for reforming the intellectual property regime to better serve the interests of both consumers and industry. Among the proposed recommendations was that an exception for parody be introduced within the Copyright Designs and Patents Act 1988. In January 2008 the Intellectual Property Office (the IPO) launched the first part of a two-stage consultation process on exceptions to copyright. As part of that consultation process, the IPO proposed a ‘fair dealing style exception’ for parody, and sought views on whether a new exception should be introduced as well as what form it might take. In December 2009 the IPO launched the second stage of this consultation process. The second consultation document rejected the case for a new parody exception. This article considers the place of parody within the copyright regime and the objections levelled against the introduction of an exception set out within the IPO's second consultation document. It invites the IPO to reconsider its decision not to recommend the introduction of a specific exception for parody within the UK.

Famine and land in Ireland and India 1845-1880: James Caird and the political economy of hunger

The perception of Ireland and India as ‘zones of famine’ led many nineteenth-century observers to draw analogies between these two troublesome parts of the British empire. This article investigates this parallel through the career of James Caird (1816–92), and specifically his interventions in the latter stages of both the Great Irish Famine of 1845–50, and the Indian famines of 1876–9. Caird is best remembered as the joint author of the controversial dissenting minute in the Indian famine commission report of 1880; this article locates the roots of his stance in his previous engagements with Irish policy. Caird's interventions are used to track the trajectory of an evolving ‘Peelite’ position on famine relief, agricultural reconstruction, and land reform between the 1840s and 1880s. Despite some divergences, strong continuities exist between the two interventions – not least concern for the promotion of agricultural entrepreneurship, for actively assisting economic development in ‘backward’ economies, and an acknowledgement of state responsibility for preserving life as an end in itself. Above all in both cases it involved a critique of a laissez-faire dogmatism – whether manifest in the ‘Trevelyanism’ of 1846–50 or the Lytton–Temple system of 1876–9.

Fully differential cross sections for transfer ionization - a sensitive probe of high level correlation effects in atoms

The transfer ionization process offers a unique opportunity to study radial and angular electron correlations in the helium atom. We report calculations for the multiple differential cross sections of the transfer ionization process p + He --> H + He++ + e(-). The results of these calculations demonstrate the strong sensitivity of the fully differential cross sections to fine details of electron correlation in the target atom. Specifically, angular electron correlation in the ground state of helium results in a broad peak in the electron emission spectra in the backward direction, relative to the incoming beam. Our model explains some of the key effects observed in measurements of multiple differential cross sections using the COLTRIMS technique.

Triply differential single ionization cross sections in coplanar and non-coplanar geometry for fast heavy ion-atom collisions

We have performed a kinematically complete experiment and calculations on single ionization in 100 MeV/amu C6+ + He collisions. For electrons ejected into the scattering plane (defined by the initial and final projectile momentum vectors) our first- and higher-order calculations are in good agreement with the data. In the plane perpendicular to the scattering plane and containing the initial projectile axis a strong forward-backward asymmetry is observed. In this plane both the first-order and the higher-order calculations do not provide good agreement neither with the data nor amongst each other.

Giant resonances in cold electron scattering by CS2

Experimental data are presented for the scattering of cold electrons by CS2, for both integral and backward scattering, between a few meV and a few hundred meV impact energy. Giant resonances with cross sections in excess of 50 Angstrom(2) are observed below 100 meV, associated with the transient formation of CS2- at 15 meV and with the bend and symmetric stretch of CS2 at thresholds of 49 and 82 meV, respectively. The resonance at 49 meV is 2 orders of magnitude greater in cross section than a dipole impulsive model predicts. These structures are superimposed on a sharp rise in the scattering cross section at low energy, which may be attributed to virtual state scattering.

Instability and dynamics of two nonlinearly coupled laser beams in a plasma

The nonlinear interaction between two laser beams in a plasma is investigated in the weakly nonlinear and relativistic regime. The evolution of the laser beams is governed by two nonlinear Schrodinger equations that are coupled with the slow plasma density response. A nonlinear dispersion relation is derived and used to study the growth rates of the Raman forward and backward scattering instabilities as well of the Brillouin and self-focusing/modulational instabilities. The nonlinear evolution of the instabilities is investigated by means of direct simulations of the time-dependent system of nonlinear equations. (c) 2006 American Institute of Physics.

Modelling the MAPK signalling pathway using a two-stage identification algorithm

Signal transduction pathways describe the dynamics of cellular response to input signalling molecules at receptors on the cell membrane. The Mitogen-Activated Protein Kinase (MAPK) cascade is one of such pathways that are involved in many important cellular processes including cell growth and proliferation. This paper describes a black-box model of this pathway created using an advanced two-stage identification algorithm. Identification allows us to capture the unique features and dynamics of the pathway and also opens up the possibility of regulatory control design. In the approach described, an optimal model is obtained by performing model subset selection in two stages, where the terms are first determined by a forward selection method and then modified using a backward selection model refinement. The simulation results demonstrate that the model selected using the two-stage algorithm performs better than with the forward selection method alone.

Restorative Justice as a Response to Sexual Offending – Addressing the Failings of Current Punitive Approaches

This article explores the use of restorative justice as a response to sexual crime. The management of high risk sex offenders, particularly in the community post-release, has been a key focus of contemporary popular and political debates on sexual offending. Many offenders fail to come to the attention of the criminal justice system. For those that do, there is the almost blanket application of recent control in the community measures such as sex offender registries and community notification which have failed to prevent reoffending. The response by the media and the public to the presence of sex offenders in the community may also impede offender rehabilitation. The use of punishment alone via formal criminal justice is, therefore, an inadequate deterrent for sexual crimes. Although controversial, this article advocates the use of restorative practices with sexual crime as a proactive, holistic response to the problem and ultimately as a more effective means of reducing the incidence of sexual offences and sex offender recidivism.

Query cost estimation through remote system contention states analysis over the Internet

Query processing over the Internet involving autonomous data sources is a major task in data integration. It requires the estimated costs of possible queries in order to select the best one that has the minimum cost. In this context, the cost of a query is affected by three factors: network congestion, server contention state, and complexity of the query. In this paper, we study the effects of both the network congestion and server contention state on the cost of a query. We refer to these two factors together as system contention states. We present a new approach to determining the system contention states by clustering the costs of a sample query. For each system contention state, we construct two cost formulas for unary and join queries respectively using the multiple regression process. When a new query is submitted, its system contention state is estimated first using either the time slides method or the statistical method. The cost of the query is then calculated using the corresponding cost formulas. The estimated cost of the query is further adjusted to improve its accuracy. Our experiments show that our methods can produce quite accurate cost estimates of the submitted queries to remote data sources over the Internet.

Metamaterial made of paired planar conductors: Particle resonances, phenomena and properties

The properties and characteristics of a recently proposed anisotropic metamaterial based upon layered arrays of tightly coupled pairs of "dogbone" shaped stripe conductors have been explored in detail. It has been found that a metamaterial composed of such stacked layers exhibits artificial magnetism and may support backward wave propagation. The equivalent network models of the constitutive conductor pairs arranged in the periodic array have been devised and applied to the identification of the specific types of resonances, and to the analysis of their contribution into the effective dielectric and magnetic properties of the artificial medium. The proposed "dogbone" configuration of conductor pairs has the advantage of being entirely realizable and assemblable in planar technology. It also appears more prospective than simple cut-wire or metal-plate pairs because the additional geometrical parameters provide an efficient control of separation between the electric and magnetic resonances that, in turn, makes it possible to obtain a fairly broadband left-handed behaviour of the structure at low frequencies.

Cue Competition Effects and Young Children's Causal and Counterfactual Inferences

The authors examined cue competition effects in young children using the blicket detector paradigm, in which objects are placed either singly or in pairs on a novel machine and children must judge which objects have the causal power to make the machine work. Cue competition effects were found in a 5- to 6-year-old group but not in a 4-year-old group. Equivalent levels of forward and backward blocking were found in the former group. Children's counterfactual judgments were subsequently examined by asking whether or not the machine would have gone off in the absence of I of 2 objects that had been placed on it as a pair. Cue competition effects were demonstrated only in 5- to 6-year-olds using this mode of assessing causal reasoning.

A programmable architecture for layered multimedia streams in IPv6 networks

A new configurable architecture is presented that offers multiple levels of video playback by accommodating variable levels of network utilization and bandwidth. By utilizing scalable MPEG-4 encoding at the network edge and using specific video delivery protocols, media streaming components are merged to fully optimize video playback for IPv6 networks, thus improving QoS. This is achieved by introducing “programmable network functionality” (PNF) which splits layered video transmission and distributes it evenly over available bandwidth, reducing packet loss and delay caused by out-of-profile DiffServ classes. An FPGA design is given which gives improved performance, e.g. link utilization, end-to-end delay, and that during congestion, improves on-time delivery of video frames by up to 80% when compared to current “static” DiffServ.