Delta opioid-receptor function in the dorsal striatum plays a role in high levels of ethanol consumption in rats

Binge-like patterns of excessive drinking during young adulthood increase the propensity for alcohol use disorders (AUDs) later in adult life; however, the mechanisms that drive this are not completely understood. Previous studies showed that the δ-opioid peptide receptor (DOP-R) is dynamically regulated by exposure to ethanol and that the DOP-R plays a role in ethanol-mediated behaviors. The aim of this study was to determine the role of the DOP-R in high ethanol consumption from young adulthood through to late adulthood by measuring DOP-R-mediated [(35)S]GTPγS binding in brain membranes and DOP-R-mediated analgesia using a rat model of high ethanol consumption in Long Evans rats. We show that DOP-R activity in the dorsal striatum and DOP-R-mediated analgesia changes during development, being highest during early adulthood and reduced in late adulthood. Intermittent access to ethanol but not continuous ethanol or water from young adulthood leads to an increase in DOP-R activity in the dorsal striatum and DOP-R-mediated analgesia into late adulthood. Multiple microinfusions of naltrindole into the dorsal striatum or multiple systemic administration of naltrindole reduces ethanol consumption, and following termination of treatment, DOP-R activity in the dorsal striatum is attenuated. These findings suggest that DOP-R activity in the dorsal striatum plays a role in high levels of ethanol consumption and suggest that targeting the DOP-R is an alternative strategy for the treatment of AUDs.

Exercise for health : a randomized, controlled trial evaluating impact of a pragmatic, translational exercise intervention on quality of life, function and treatment-related side effects following breast cancer

Purpose Exercise for Health was a randomized, controlled trial designed to evaluate two modes of delivering (face-to-face [FtF] and over-the-telephone [Tel]) an 8-month translational exercise intervention, commencing 6-weeks post-breast cancer surgery (PS). Methods Outcomes included quality of life (QoL), function (fitness and upper-body) and treatment-related side effects (fatigue, lymphoedema, body mass index, menopausal symptoms, anxiety, depression and pain). Generalised estimating equation modelling determined time (baseline [5-weeks PS], mid-intervention [6-months PS], post-intervention [12-months PS]), group (FtF, Tel, Usual Care [UC]) and time-by-group effects. 194 women representative of the breast cancer population were randomised to the FtF (n=67), Tel (n=67) and UC (n=60) groups. Results: There were significant (p<0.05) interaction effects on QoL, fitness and fatigue, with differences being observed between the treatment groups and the UC group. Trends observed for the treatment groups were similar. The treatment groups reported improved QoL, fitness and fatigue over time and changes observed between baseline and post-intervention were clinically relevant. In contrast, the UC group experienced no change, or worsening QoL, fitness and fatigue, mid-intervention. Although improvements in the UC group occurred by 12-months post-surgery, the change did not meet the clinically relevant threshold. There were no differences in other treatment-related side-effects between groups. Conclusion This translational intervention trial, delivered either face-to-face or over-the-telephone, supports exercise as a form of adjuvant breast cancer therapy that can prevent declines in fitness and function during treatment and optimise recovery post-treatment.

Evidence for a dual function of EphB4 as tumor promoter and suppressor regulated by the absence or presence of the ephrin-B2 ligand

Overexpression of the receptor tyrosine kinase EphB4 is common in epithelial cancers and linked to tumor progression by promoting angiogenesis, increasing survival and facilitating invasion and migration. However, other studies have reported loss of EphB4 suggesting a tumor suppressor function in some cancers. These opposing roles may be regulated by (i) the presence of the primary ligand ephrin-B2 that regulates pathways involved in tumor suppression or (ii) the absence of ephrin-B2 that allows EphB4 signaling via ligand-independent pathways that contribute to tumor promotion. To explore this theory, EphB4 was overexpressed in the prostate cancer cell line 22Rv1 and the mammary epithelial cell line MCF-10A. Overexpressed EphB4 localized to lipid-rich regions of the plasma membrane and confirmed to be ligand-responsive as demonstrated by increased phosphorylation of ERK1/2 and internalization. EphB4 overexpressing cells demonstrated enhanced anchorage-independent growth, migration and invasion, all characteristics associated with an aggressive phenotype, and therefore supporting the hypothesis that overexpressed EphB4 facilitates tumor promotion. Importantly, these effects were reversed in the presence of ephrin-B2 which led to a reduction in EphB4 protein levels, demonstrating that ligand-dependent signaling is tumor suppressive. Furthermore, extended ligand stimulation caused a significant decrease in proliferation that correlated with a rise in caspase-3/7 and -8 activities. Together, these results demonstrate that overexpression of EphB4 confers a transformed phenotype in the case of MCF-10A cells and an increased metastatic phenotype in the case of 22Rv1 cancer cells and that both phenotypes can be restrained by stimulation with ephrin-B2, in part by reducing EphB4 levels.

Insights into the role and function of L2, the minor capsid protein of papillomaviruses

Human papillomaviruses (HPV) are responsible for the most common human sexually transmitted viral infections, and high-risk types are responsible for causing cervical and other cancers. The minor capsid protein L2 of HPV plays important roles in virus entry into cells, localisation of viral components to the nucleus, in DNA binding, capsid formation and stability. It also elicits antibodies that are more cross-reactive between HPV types than does the major capsid protein L1, making it an attractive potential target for new-generation, more broadly protective subunit vaccines against HPV infections. However, its low abundance in natural capsids-12-72 molecules per 360 copies of L1-limits its immunogenicity. This review will explore the biological roles of the protein, and prospects for its use in new vaccines. © 2009 Springer-Verlag.

Post-match changes in neuromuscular function and the relationship to match demands in amateur rugby league matches

Objectives: The current study investigated the change in neuromuscular contractile properties following competitive rugby league matches and the relationship with physical match demands. Design: Eleven trained, male rugby league players participated in 2–3 amateur, competitive matches (n = 30). Methods: Prior to, immediately (within 15-min) and 2 h post-match, players performed repeated counter-movement jumps (CMJ) followed by isometric tests on the right knee extensors for maximal voluntary contraction (MVC), voluntary activation (VA) and evoked twitch contractile properties of peak twitch force (Pt), rate of torque development (RTD), contraction duration (CD) and relaxation rate (RR). During each match, players wore 1 Hz Global Positioning Satellite devices to record distance and speeds of matches. Further, matches were filmed and underwent notational analysis for number of total body collisions. Results: Total, high-intensity, very-high intensity distances covered and mean speed were 5585 ± 1078 m, 661 ± 265, 216 ± 121 m and 75 ± 14 m min−1, respectively. MVC was significantly reduced immediately and 2 h post-match by 8 ± 11 and 12 ± 13% from pre-match (p < 0.05). Moreover, twitch contractile properties indicated a suppression of Pt, RTD and RR immediately post-match (p < 0.05). However, VA was not significantly altered from pre-match (90 ± 9%), immediately-post (89 ± 9%) or 2 h post (89 ± 8%), (p > 0.05). Correlation analyses indicated that total playing time (r = −0.50) and mean speed (r = −0.40) were moderately associated to the change in post-match MVC, while mean speed (r = 0.35) was moderately associated to VA. Conclusions: The present study highlights the physical demands of competitive amateur rugby league result in interruption of peripheral contractile function, and post-match voluntary torque suppression may be associated with match playing time and mean speeds.

Network interactions and performance of a multi-function IEC 61850 process bus

New substation technology, such as non-conventional instrument transformers,and a need to reduce design and construction costs, are driving the adoption of Ethernet based digital process bus networks for high voltage substations. Protection and control applications can share a process bus, making more efficient use of the network infrastructure. This paper classifies and defines performance requirements for the protocols used in a process bus on the basis of application. These include GOOSE, SNMP and IEC 61850-9-2 sampled values. A method, based on the Multiple Spanning Tree Protocol (MSTP) and virtual local area networks, is presented that separates management and monitoring traffic from the rest of the process bus. A quantitative investigation of the interaction between various protocols used in a process bus is described. These tests also validate the effectiveness of the MSTP based traffic segregation method. While this paper focusses on a substation automation network, the results are applicable to other real-time industrial networks that implement multiple protocols. High volume sampled value data and time-critical circuit breaker tripping commands do not interact on a full duplex switched Ethernet network, even under very high network load conditions. This enables an efficient digital network to replace a large number of conventional analog connections between control rooms and high voltage switchyards.

Executive function development and stress effects on driving performance : preliminary findings from a young adult sample.

This chapter presents a pilot study examining the interactive contributions of executive function development/impairment and psychosocial stress to young adults’ (17-30 years old) driving behaviour in a simulator city scenario.

Natural convection flow in a strong cross magnetic field with radiation

The problem of MHD natural convection boundary layer flow of an electrically conducting and optically dense gray viscous fluid along a heated vertical plate is analyzed in the presence of strong cross magnetic field with radiative heat transfer. In the analysis radiative heat flux is considered by adopting optically thick radiation limit. Attempt is made to obtain the solutions valid for liquid metals by taking Pr≪1. Boundary layer equations are transformed in to a convenient dimensionless form by using stream function formulation (SFF) and primitive variable formulation (PVF). Non-similar equations obtained from SFF are then simulated by implicit finite difference (Keller-box) method whereas parabolic partial differential equations obtained from PVF are integrated numerically by hiring direct finite difference method over the entire range of local Hartmann parameter, $xi$ . Further, asymptotic solutions are also obtained for large and small values of local Hartmann parameter $xi$ . A favorable agreement is found between the results for small, large and all values of $xi$ . Numerical results are also demonstrated graphically by showing the effect of various physical parameters on shear stress, rate of heat transfer, velocity and temperature.

On the probability density function of the product of Rayleigh distributed random variables

In this paper we investigate the distribution of the product of Rayleigh distributed random variables. Considering the Mellin-Barnes inversion formula and using the saddle point approach we obtain an upper bound for the product distribution. The accuracy of this tail-approximation increases as the number of random variables in the product increase.

Effect of cold water immersion after exercise in the heat on muscle function, body temperatures, and vessel diameter

Cold water immersion (CWI) is a popular recovery modality, but actual physiological responses to CWI after exercise in the heat have not been well documented. The purpose of this study was to examine effects of 20-min CWI (14 degrees C) on neuromuscular function, rectal (T(re)) and skin temperature (T(sk)), and femoral venous diameter after exercise in the heat. Ten well-trained male cyclists completed two bouts of exercise consisting of 90-min cycling at a constant power output (216+/-12W) followed by a 16.1km time trial (TT) in the heat (32 degrees C). Twenty-five minutes post-TT, participants were assigned to either CWI or control (CON) recovery conditions in a counterbalanced order. T(re) and T(sk) were recorded continuously, and maximal voluntary isometric contraction torque of the knee extensors (MVIC), MVIC with superimposed electrical stimulation (SMVIC), and femoral venous diameters were measured prior to exercise, 0, 45, and 90min post-TT. T(re) was significantly lower in CWI beginning 50min post-TT compared with CON, and T(sk) was significantly lower in CWI beginning 25min post-TT compared with CON. Decreases in MVIC, and SMVIC torque after the TT were significantly greater for CWI compared with CON; differences persisted 90min post-TT. Femoral vein diameter was approximately 9% smaller for CWI compared with CON at 45min post-TT. These results suggest that CWI decreases T(re), but has a negative effect on neuromuscular function.

Detecting Symbian OS malware through static function call analysis

Smartphones become very critical part of our lives as they offer advanced capabilities with PC-like functionalities. They are getting widely deployed while not only being used for classical voice-centric communication. New smartphone malwares keep emerging where most of them still target Symbian OS. In the case of Symbian OS, application signing seemed to be an appropriate measure for slowing down malware appearance. Unfortunately, latest examples showed that signing can be bypassed resulting in new malware outbreak. In this paper, we present a novel approach to static malware detection in resource-limited mobile environments. This approach can be used to extend currently used third-party application signing mechanisms for increasing malware detection capabilities. In our work, we extract function calls from binaries in order to apply our clustering mechanism, called centroid. This method is capable of detecting unknown malwares. Our results are promising where the employed mechanism might find application at distribution channels, like online application stores. Additionally, it seems suitable for directly being used on smartphones for (pre-)checking installed applications.

Assessment of neuroretinal function in a group of functional amblyopes with documented LGN deficits

Purpose In this study we examine neuroretinal function in five amblyopes, who had been shown in previous functional MRI (fMRI) studies to have compromised function of the lateral geniculate nucleus (LGN), to determine if the fMRI deficit in amblyopia may have its origin at the retinal level. Methods We used slow flash multifocal ERG (mfERG) and compared averaged five ring responses of the amblyopic and fellow eyes across a 35 deg field. Central responses were also assessed over a field which was about 6.3 deg in diameter. We measured central retinal thickness using optical coherence tomography. Central fields were measured using the MP1-Microperimeter which also assesses ocular fixation during perimetry. MfERG data were compared with fMRI results from a previous study. Results Amblyopic eyes had reduced response density amplitudes (first major negative to first positive (N1-P1) responses) for the central and paracentral retina (up to 18 deg diameter) but not for the mid-periphery (from 18 to 35 deg). Retinal thickness was within normal limits for all eyes, and not different between amblyopic and fellow eyes. Fixation was maintained within the central 4° more than 80% of the time by four of the five participants; fixation assessed using bivariate contour ellipse areas (BCEA) gave rankings similar to those of the MP-1 system. There was no significant relationship between BCEA and mfERG response for either amblyopic or fellow eye. There was no significant relationship between the central mfERG eye response difference and the selective blood oxygen level dependent (BOLD) LGN eye response difference previously seen in these participants. Conclusions Retinal responses in amblyopes can be reduced within the central field without an obvious anatomical basis. Additionally, this retinal deficit may not be the reason why the LGN BOLD (blood oxygen level dependent) responses are reduced for amblyopic eye stimulation.

Exponential integrators and a dual-scale model for wood drying

For the timber industry, the ability to simulate the drying of wood is invaluable for manufacturing high quality wood products. Mathematically, however, modelling the drying of a wet porous material, such as wood, is a diffcult task due to its heterogeneous and anisotropic nature, and the complex geometry of the underlying pore structure. The well{ developed macroscopic modelling approach involves writing down classical conservation equations at a length scale where physical quantities (e.g., porosity) can be interpreted as averaged values over a small volume (typically containing hundreds or thousands of pores). This averaging procedure produces balance equations that resemble those of a continuum with the exception that effective coeffcients appear in their deffnitions. Exponential integrators are numerical schemes for initial value problems involving a system of ordinary differential equations. These methods differ from popular Newton{Krylov implicit methods (i.e., those based on the backward differentiation formulae (BDF)) in that they do not require the solution of a system of nonlinear equations at each time step but rather they require computation of matrix{vector products involving the exponential of the Jacobian matrix. Although originally appearing in the 1960s, exponential integrators have recently experienced a resurgence in interest due to a greater undertaking of research in Krylov subspace methods for matrix function approximation. One of the simplest examples of an exponential integrator is the exponential Euler method (EEM), which requires, at each time step, approximation of φ(A)b, where φ(z) = (ez - 1)/z, A E Rnxn and b E Rn. For drying in porous media, the most comprehensive macroscopic formulation is TransPore [Perre and Turner, Chem. Eng. J., 86: 117-131, 2002], which features three coupled, nonlinear partial differential equations. The focus of the first part of this thesis is the use of the exponential Euler method (EEM) for performing the time integration of the macroscopic set of equations featured in TransPore. In particular, a new variable{ stepsize algorithm for EEM is presented within a Krylov subspace framework, which allows control of the error during the integration process. The performance of the new algorithm highlights the great potential of exponential integrators not only for drying applications but across all disciplines of transport phenomena. For example, when applied to well{ known benchmark problems involving single{phase liquid ow in heterogeneous soils, the proposed algorithm requires half the number of function evaluations than that required for an equivalent (sophisticated) Newton{Krylov BDF implementation. Furthermore for all drying configurations tested, the new algorithm always produces, in less computational time, a solution of higher accuracy than the existing backward Euler module featured in TransPore. Some new results relating to Krylov subspace approximation of '(A)b are also developed in this thesis. Most notably, an alternative derivation of the approximation error estimate of Hochbruck, Lubich and Selhofer [SIAM J. Sci. Comput., 19(5): 1552{1574, 1998] is provided, which reveals why it performs well in the error control procedure. Two of the main drawbacks of the macroscopic approach outlined above include the effective coefficients must be supplied to the model, and it fails for some drying configurations, where typical dual{scale mechanisms occur. In the second part of this thesis, a new dual{scale approach for simulating wood drying is proposed that couples the porous medium (macroscale) with the underlying pore structure (microscale). The proposed model is applied to the convective drying of softwood at low temperatures and is valid in the so{called hygroscopic range, where hygroscopically held liquid water is present in the solid phase and water exits only as vapour in the pores. Coupling between scales is achieved by imposing the macroscopic gradient on the microscopic field using suitably defined periodic boundary conditions, which allows the macroscopic ux to be defined as an average of the microscopic ux over the unit cell. This formulation provides a first step for moving from the macroscopic formulation featured in TransPore to a comprehensive dual{scale formulation capable of addressing any drying configuration. Simulation results reported for a sample of spruce highlight the potential and flexibility of the new dual{scale approach. In particular, for a given unit cell configuration it is not necessary to supply the effective coefficients prior to each simulation.

In situ SANS study of the surface and pore filling adsorption of subcritical and supercritical CO2 in porous silica as a function of pore size

We applied small-angle neutron scattering (SANS) and ultra small-angle neutron scattering (USANS) to monitor evolution of the CO2 adsorption in porous silica as a function of CO2 pressure and temperature in pores of different sizes. The range of pressures (0 < P < 345 bar) and temperatures (T=18 OC, 35 OC and 60 OC) corresponded to subcritical, near critical and supercritical conditions of bulk fluid. We observed that the adsorption behavior of CO2 is fundamentally different in large and small pores with the sizes D > 100 Å and D < 30 Å, respectively. Scattering data from large pores indicate formation of a dense adsorbed film of CO2 on pore walls with the liquid-like density (ρCO2)ads≈0.8 g/cm3. The adsorbed film coexists with unadsorbed fluid in the inner pore volume. The density of unadsorbed fluid in large pores is temperature and pressure dependent: it is initially lower than (ρCO2)ads and gradually approaches it with pressure. In small pores compressed CO2 gas completely fills the pore volume. At the lowest pressures of the order of 10 bar and T=18 OC, the fluid density in smallest pores available in the matrix with D ~ 10 Å exceeds bulk fluid density by a factor of ~ 8. As pressure increases, progressively larger pores become filled with the condensed CO2. Fluid densification is only observed in pores with sizes less than ~ 25 – 30 Å. As the density of the invading fluid reaches (ρCO2)bulk~ 0.8 g/cm3, pores of all sizes become uniformly filled with CO2 and the confinement effects disappear. At higher densities the fluid in small pores appears to follow the equation of state of bulk CO2 although there is an indication that the fluid density in the inner volume of large pores may exceed the density of the adsorbed layer. The equivalent internal pressure (Pint) in the smallest pores exceeds the external pressure (Pext) by a factor of ~ 5 for both sub- and supercritical CO2. Pint gradually approaches Pext as D → 25 – 30 Å and is independent of temperature in the studied range of 18 OC ≤ T ≤ 60 OC. The obtained results demonstrate certain similarity as well as differences between adsorption of subcritical and supercritical CO2 in disordered porous silica. High pressure small angle scattering experiments open new opportunities for in situ studies of the fluid adsorption in porous media of interest to CO2 sequestration, energy storage, and heterogeneous catalysis.

The impact of legislation on divorce : a hazard function approach

The paper examines the impact of the introduction of no-fault divorce legislation in Australia. The approach used is rather novel, a hazard model of the divorce rate is estimated with the role of legislation captured via a time-varying covariate. The paper concludes that contrary to US empirical evidence, no-fault divorce legislation appears to have had a positive impact upon the divorce rate in Australia.