Generation of replication-proficient influenza virus NS1 point mutants with interferon-hyperinducer phenotype

The NS1 protein of influenza A viruses is the dedicated viral interferon (IFN)-antagonist. Viruses lacking NS1 protein expression cannot multiply in normal cells but are viable in cells deficient in their ability to produce or respond to IFN. Here we report an unbiased mutagenesis approach to identify positions in the influenza A NS1 protein that modulate the IFN response upon infection. A random library of virus ribonucleoproteins containing circa 40 000 point mutants in NS1 were transferred to infectious virus and amplified in MDCK cells unable to respond to interferon. Viruses that activated the interferon (IFN) response were subsequently selected by their ability to induce expression of green-fluorescent protein (GFP) following infection of A549 cells bearing an IFN promoter-dependent GFP gene. Using this approach we isolated individual mutant viruses that replicate to high titers in IFN-compromised cells but, compared to wild type viruses, induced higher levels of IFN in IFN-competent cells and had a reduced capacity to counteract exogenous IFN. Most of these viruses contained not previously reported NS1 mutations within either the RNA-binding domain, the effector domain or the linker region between them. These results indicate that subtle alterations in NS1 can reduce its effectiveness as an IFN antagonist without affecting the intrinsic capacity of the virus to multiply. The general approach reported here may facilitate the generation of replication-proficient, IFN-inducing virus mutants, that potentially could be developed as attenuated vaccines against a variety of viruses.

The role of WNT singling activation and its blockage in the focal retinal lesion of Ccl2-/-/Cx3cr1-/- mice with and without rd8 background

Purpose: The canonical Wnt signaling is activated by retinal injury. Under disease conditions, the Wnt mediates inflammatory responses. Inflammation has been detected in age-related macular degeneration (AMD) retinas and Ccl2-/-/Cx3cr1-/- (DKO) mice with or without rd8 background, a model with progressive AMD-like lesions including focal photoreceptor/RPE degeneration and A2E accumulation. We evaluated the effects of Wnt-β-catenin activation and an antibody against LRP6, the co-receptor of Wnt on these two models.

Methods: anti-LRP6 antibody (2F1, 1 μl of 5 μg/μL) was intravitreally injected into the right eyes in 3 separate experiments (DKOrd8, N=35; DKO, N=10). The left eyes were injected with mouse IgG as controls. Fundoscopy was taken before injection and sequentially monthly after injection. Two months after injection, light-adapted ERG responses were recorded; then the eyes were harvested for histopathology, the determination of retinal A2E, and molecular analysis. The microarray of ocular mRNA of 92 Wnt genes was compared between the treated and the control eyes. The phosphorylated types of LRP6 and β-catenin and endogenous forms of the proteins were assayed by Western blotting.

Results: For DKOrd8 mice, the fundus showed a slower progression or alleviation of retinal lesions in the right eyes as compared to the left eyes. Among 35 pairs of eyes, 26 (74.3%) were improved, 7 (20%) stayed the same and 2 (5.7%) remained progressing. Histology confirmed the clinical observation. Light-adapted ERG of the treated eyes exhibited larger amplitudes compared to control eyes (n=6), with greater improvements under UV light stimulus. There was a significantly lower A2E in the treated eyes compared to controls. Microarray of 92 Wnt genes expression pattern was similar in both eyes. Western blotting indicated local administration of 2F1 antibody to suppress the activation of Wnt pathway in the retina. For DKO mice, the treatment improved ERG but less effect on RPE degeneration.

Conclusions: The canonical Wnt signaling plays a role in the focal retina lesion of both DKOrd8 and DKO mice; and intravitreal anti-LRP6 antibody might be neuroprotective via deactivation of canonical Wnt pathway.

Autism in the air: using Point of View Video Priming and Natural Environment Teaching to help children with autism travel by plane

This paper describes a study that used video materials and visits to an airport to prepare children on the autism spectrum for travel by plane. Twenty parents and carers took part in the study with children aged from 3 to 16 years. The authors explain that the methods they used were based on Applied Behaviour Analysis (ABA) research; a video modeling technique called Point-Of-View Video-priming and during visits to an airport they used procedures known as Natural Environment Teaching. The findings suggest that using video and preparing children by taking them through what is likely to happen in the real environment when they travel by plane is effective and the authors suggest these strategies could be used to support children with autism with other experiences they need or would like to engage in such as visits to the dentist or hairdressers and access to leisure centres and other public spaces.

Spitzer infrared spectrograph point source classification in the Small Magellanic Cloud

The Magellanic Clouds are uniquely placed to study the stellar contribution to dust emission. Individual stars can be resolved in these systems even in the mid-infrared, and they are close enough to allow detection of infrared excess caused by dust. We have searched the Spitzer Space Telescope data archive for all Infrared Spectrograph (IRS) staring-mode observations of the Small Magellanic Cloud (SMC) and found that 209 Infrared Array Camera (IRAC) point sources within the footprint of the Surveying the Agents of Galaxy Evolution in the Small Magellanic Cloud (SAGE-SMC) Spitzer Legacy programme were targeted, within a total of 311 staring-mode observations. We classify these point sources using a decision tree method of object classification, based on infrared spectral features, continuum and spectral energy distribution shape, bolometric luminosity, cluster membership and variability information. We find 58 asymptotic giant branch (AGB) stars, 51 young stellar objects, 4 post-AGB objects, 22 red supergiants, 27 stars (of which 23 are dusty OB stars), 24 planetary nebulae (PNe), 10 Wolf-Rayet stars, 3 H II regions, 3 R Coronae Borealis stars, 1 Blue Supergiant and 6 other objects, including 2 foreground AGB stars. We use these classifications to evaluate the success of photometric classification methods reported in the literature.

Using geotechnical and LIDAR spatial monitoring to determine key environmental slope instability thresholds of a Jurassic coastal landslide: Straidkilly Point, Northern Ireland, UK.

The Antrim Coast Road stretching from the seaport of Larne in the East of Northern Ireland to the famous Giant’s Causeway in the North has a well-deserved reputation for being one of the most spectacular roads in Europe (Day, 2006). At various locations along the route, fluid interactions between the problematic geology, Jurassic Lias Clay and Triassic Mudstone overlain by Cretaceous Limestone and Tertiary Basalt, and environmental variables result in frequent instances of slope instability within the vadose zone. During such instances of instability, debris flows and composite mudflows encroach on the carriageway posing a hazard to road users. This paper examines the site investigative, geotechnical and spatial analysis techniques currently being implemented to monitor slope stability for one site at Straidkilly Point, Glenarm, Northern Ireland. An in-depth understanding of the geology was obtained via boreholes, resistivity surveys and laboratory testing. Environmental variables recorded by an on-site weather station were correlated with measured pore water pressure and soil moisture infiltration dynamic data.
Terrestrial LiDAR (TLS) was applied to the slope for the monitoring of failures, with surveys carried out on a bi-monthly basis. TLS monitoring allowed for the generation of Digital Elevation Models (DEMs) of difference, highlighting areas of recent movement, erosion and deposition. Morphology parameters were generated from the DEMs and include slope, curvature and multiple measures of roughness. Changes in the structure of the slope coupled with morphological parameters are characterised and linked to progressive failures from the temporal monitoring. In addition to TLS monitoring, Aerial LiDARi datasets were used for the spatio-morphological characterisation of the slope on a macro scale. Results from the geotechnical and environmental monitoring were compared with spatial data obtained through Terrestrial and Airborne LiDAR, providing a multi-faceted approach to slope stability characterization, which facilitates more informed management of geotechnical risk by the Northern Ireland Roads Service.

A Computational Approach for Simulating P-type Silicon Piezoresistor Using Four Point Bending Setup

The piezoresistance effect is defined as change in resistance due to applied stress. Silicon has a relatively large piezoresistance effect which has been known since 1954. A four point bending setup is proposed and designed to analyze the piezoresistance effect in p-type silicon. This setup is used to apply uniform and uniaxial stress along the <110> crystal direction. The main aim of this work is to investigate the piezoresistive characteristic of p-type resistors as a function of doping concentrations using COMSOL Multiphysics. Simulation results are compared with experimental data.

Advanced energy efficient coordinated multi-point transmission for OFDMA

The ever-growing energy consumption in mobile networks stimulated by the expected growth in data tra ffic has provided the impetus for mobile operators to refocus network design, planning and deployment towards reducing the cost per bit, whilst at the same time providing a signifi cant step towards reducing their operational expenditure. As a step towards incorporating cost-eff ective mobile system, 3GPP LTE-Advanced has adopted the coordinated multi-point (CoMP) transmission technique due to its ability to mitigate and manage inter-cell interference (ICI). Using CoMP the cell average and cell edge throughput are boosted. However, there is room for reducing energy consumption further by exploiting the inherent exibility of dynamic resource allocation protocols. To this end packet scheduler plays the central role in determining the overall performance of the 3GPP longterm evolution (LTE) based on packet-switching operation and provide a potential research playground for optimizing energy consumption in future networks. In this thesis we investigate the baseline performance for down link CoMP using traditional scheduling approaches, and subsequently go beyond and propose novel energy e fficient scheduling (EES) strategies that can achieve power-e fficient transmission to the UEs whilst enabling both system energy effi ciency gain and fairness improvement. However, ICI can still be prominent when multiple nodes use common resources with di fferent power levels inside the cell, as in the so called heterogeneous networks (Het- Net) environment. HetNets are comprised of two or more tiers of cells. The rst, or higher tier, is a traditional deployment of cell sites, often referred to in this context as macrocells. The lower tiers are termed small cells, and can appear as microcell, picocells or femtocells. The HetNet has attracted signiffi cant interest by key manufacturers as one of the enablers for high speed data at low cost. Research until now has revealed several key hurdles that must be overcome before HetNets can achieve their full potential: bottlenecks in the backhaul must be alleviated, as well as their seamless interworking with CoMP. In this thesis we explore exactly the latter hurdle, and present innovative ideas on advancing CoMP to work in synergy with HetNet deployment, complemented by a novel resource allocation policy for HetNet tighter interference management. As system level simulator has been used to analyze the proposed algorithm/protocols, and results have concluded that up to 20% energy gain can be observed.

Les meilleures pratiques en prévention de la toxicomanie point de vue des adolcescents(es)

Au cours des dix dernières années, la proportion d'adolescents consommateurs de psychotropes a diminué (Institut National de Santé Publique du Québec (INSPQ), 2009). Bien que cette proportion ait diminué, il demeure évident que le nombre de jeunes consommateurs demeure préoccupant (INSPQ, 2009), et ce, malgré tous les efforts des gouvernements pour prévenir l'usage et l'abus de psychotropes. Or, tous les programmes de prévention ne se valent pas. Ce projet de recherche de type exploratoire permettra d'identifier les critères des activités de prévention en toxicomanie qui (1) ont influencé leur perception de la toxicomanie et (2) ont influencé leur propre consommation de psychotropes (soit à la hausse ou à la baisse), et ce, par la consultation d'adolescents. Les données résultent d'entrevues semi-structurées réalisées à partir d'un échantillon composé de 12 adolescents(es). Plusieurs critères ont été abordés lors des discussions soient les approches utilisées, les médiums utilisés, la nature du message, le niveau d'exposition, la nature de l'intervention, la nature des animateurs, les stratégies pédagogiques, les jeunes ciblés et enfin, le niveau d'implication des jeunes. Ce présent projet de mémoire présente donc la prise de position que les jeunes ont émise quant à ces critères.

Last End Point / Pinckney Island PSG - R036/R037

The South Carolina Department of Natural Resources provides maps to recreational and state shellfish grounds, available to the public for recreational harvesting or to commercial harvest. This map shows the location of Last End Point / Pinckney Island PSG - R036/R0378 Recreational Shellfish Ground in Beaufort County.

Chechessee Point PSG - R061

The South Carolina Department of Natural Resources provides maps to recreational and state shellfish grounds, available to the public for recreational harvesting or to commercial harvest. This map shows the location of Chechessee Point PSG - R061 Recreational Shellfish Ground in Beaufort County.

Haig Point S005

The South Carolina Department of Natural Resources provides maps to recreational and state shellfish grounds, available to the public for recreational harvesting or to commercial harvest. This map shows the location of Haig Point S005 Recreational Shellfish Ground in Beaufort County.