A Wide-angle Multi-Octave Broadband Waveplate Based on Field Transformation Approach

J.Z. acknowledge the support from the National Nature Science Foundation of China (61571218, 61571216, 61301017, 61371034, 61101011), and the Ph.D. Programs Foundation of Ministry of Education of China (20120091110032, 20110091120052). Y. H. acknowledge the support from the UK EPSRC under the QUEST Programme Grant (EP/I034548/1)

RNAi Screening in Drosophila Cells Identifies New Modifiers of Mutant Huntingtin Aggregation

The fruitfly Drosophila melanogaster is well established as a model system in the study of human neurodegenerative diseases. Utilizing RNAi, we have carried out a high-throughput screen for modifiers of aggregate formation in Drosophila larval CNS-derived cells expressing mutant human Huntingtin exon 1 fused to EGFP with an expanded polyglutamine repeat (62Q). 7200 genes, encompassing around 50% of the Drosophila genome, were screened, resulting in the identification of 404 candidates that either suppress or enhance aggregation. These candidates were subjected to secondary screening in normal length (18Q)-expressing cells and pruned to remove dsRNAs with greater than 10 off-target effects (OTEs). De novo RNAi probes were designed and synthesized for the remaining 68 candidates. Following a tertiary round of screening, 21 high confidence candidates were analyzed in vivo for their ability to modify mutant Huntingtin-induced eye degeneration and brain aggregation. We have established useful models for the study of human HD using the fly, and through our RNAi screen, we have identified new modifiers of mutant human Huntingtin aggregation and aggregate formation in the brain. Newly identified modifiers including genes related to nuclear transport, nucleotide processes, and signaling, may be involved in polyglutamine aggregate formation and Huntington disease cascades

Suppression of MAPK11 or HIPK3 reduces mutant Huntingtin levels in Huntington's disease models.

Most neurodegenerative disorders are associated with accumulation of disease-relevant proteins. Among them, Huntington disease (HD) is of particular interest because of its monogenetic nature. HD is mainly caused by cytotoxicity of the defective protein encoded by the mutant Huntingtin gene (HTT). Thus, lowering mutant HTT protein (mHTT) levels would be a promising treatment strategy for HD. Here we report two kinases HIPK3 and MAPK11 as positive modulators of mHTT levels both in cells and in vivo. Both kinases regulate mHTT via their kinase activities, suggesting that inhibiting these kinases may have therapeutic values. Interestingly, their effects on HTT levels are mHTT-dependent, providing a feedback mechanism in which mHTT enhances its own level thus contributing to mHTT accumulation and disease progression. Importantly, knockout of MAPK11 significantly rescues disease-relevant behavioral phenotypes in a knockin HD mouse model. Collectively, our data reveal new therapeutic entry points for HD and target-discovery approaches for similar diseases

High-Content Chemical and RNAi Screens for Suppressors of Neurotoxicity in a Huntington's Disease Model

To identify Huntington's Disease therapeutics, we conducted high-content small molecule and RNAi suppressor screens using a Drosophila primary neural culture Huntingtin model. Drosophila primary neurons offer a sensitive readout for neurotoxicty, as their neurites develop dysmorphic features in the presence of mutant polyglutamine-expanded Huntingtin compared to nonpathogenic Huntingtin. By tracking the subcellular distribution of mRFP-tagged pathogenic Huntingtin and assaying neurite branch morphology via live-imaging, we identified suppressors that could reduce Huntingtin aggregation and/or prevent the formation of dystrophic neurites. The custom algorithms we used to quantify neurite morphologies in complex cultures provide a useful tool for future high-content screening approaches focused on neurodegenerative disease models. Compounds previously found to be effective aggregation inhibitors in mammalian systems were also effective in Drosophila primary cultures, suggesting translational capacity between these models. However, we did not observe a direct correlation between the ability of a compound or gene knockdown to suppress aggregate formation and its ability to rescue dysmorphic neurites. Only a subset of aggregation inhibitors could revert dysmorphic cellular profiles. We identified lkb1, an upstream kinase in the mTOR/Insulin pathway, and four novel drugs, Camptothecin, OH-Camptothecin, 18β-Glycyrrhetinic acid, and Carbenoxolone, that were strong suppressors of mutant Huntingtin-induced neurotoxicity. Huntingtin neurotoxicity suppressors identified through our screen also restored viability in an in vivo Drosophila Huntington's Disease model, making them attractive candidates for further therapeutic evaluation.National Institutes of Health (U.S.) (grant R01 EB007042)National Institutes of Health (U.S.

Channeling radiation relation with the mean number of channeled particles

We considered planar positron channeling in 110 planes in Silicon. We used the appropriate Fokker-Planck type kinetic equation to calculate the values of the flux distribution function at several depths for the energies of 1 GeV, 5 GeV and 10 GeV and incidence angles 0, 0.5 Psi(L), and 0.8 Psi(L), where Psi(L) is the Lindhard angle. Using the values of the flux distribution function at the critical transverse energy, we calculated the mean number of particles with transverse energies equal to the critical one. The first maximum of the radiation intensity is proportional to this number. We conclude that the first maximum of the radiation intensity versus particle energy is expected to decrease dramatically with increasing depth

The REVERIE human representation addresses issues related to virtual presence, communication and interaction in collaborative virtual environments

Human embodiment/representation in virtual environments (VEs) similarly to the human body in real life is endowed with multimodal input/output capabilities that convey multiform messages enabling communication, interaction and collaboration in VEs. This paper demonstrates how the REal and Virtual Engagement In Realistic Immersive Environments (REVERIE) web platform’s virtual representation artefacts address human representation design guidelines (DGs) that have been generated based on extensive user centered research. The paper presents the human representation supported by REVERIE, a research project funded from the European Community's Seventh Framework Programme (FP7/2007-2013) and it demonstrates how they ultimately address virtual actor DGs generic to collaborative virtual environments (CVEs). The paper concludes with future directions for improving human representation in CVEs

Critical radius in axial channeling

When studying phenomena related to the channeling of charged particles it is of great importance to consider them as functions of the impact parameter. This point of view plays an important role to the interpretation of experimental results as well as to computer simulations. Thus the distance of minimum approach, for which channeling conditions still hold, either under axial or planar channeling is of importance. In the present work we use the Monte-Carlo method to investigate the correlation of the distance of minimum approach of axially channeled particles with the exit angle of those particles from the crystal. We calculated the distance of minimum approach for several incidence angles at different temperatures and for many crystal thickness. The results we obtained prove that the distance of minimum approach has two main properties. (a) It is independent of the crystal thickness and depends only slightly on the incidence angle (as long as the incidence angle does not exceed the Lindhard angle) and slightly decreases with increasing temperature. (b) It agrees with Lindhard’s theory predictions but at the same time it seems that some particles approach too close to the crystal axis without being dechanneled. (C) 2000 Elsevier Science B.V. All rights reserved

Edu-simulation: a serious games platform designed to engage and motivate students

This paper introduces a serious games web platform designed to simulate a teaching environment where lecturers are able to replicate their teaching environment by creating courses, modules, adding content and managing students effectively. Using a variety of tools available, lecturers are able to create a range of game simulations for students and observe student behavior in a controlled environment. The paper provides a description of the platform architecture and the main features, it presents a user testing session that aimed to review the usability, the cognitive accessibility (CoA) of the educational tasks completed and the quality of the user experience with the platform and it discusses the users testing results. The paper put emphasis on the gamified elements of the platform and their role in enhancing the pedagogic experience and concludes with directions of future work and development

A dynamic role-playing platform for simulations in legal and political education

One big challenge in deploying games-based learning, is the high cost and specialised skills associated with customised development. In this paper we present a serious games platform that offers tools that allow educators without special programming or artistic skills to dynamically create three dimensional (3D) scenes and verbal and non-verbal interaction with fully embodied conversational agents (ECAs) that can be used to simulate numerous educational scenarios. We present evaluation results based on the use of the platform to create two educational scenarios for politics and law in higher education. We conclude with a discussion of directions for the further work

Westminster Serious Games Platform (wmin-SGP) a tool for real-time authoring of roleplay simulations for learning

The use of serious games in education and their pedagogical benefit is being widely recognized. However, effective integration of serious games in education depends on addressing two big challenges: the successful incorporation of motivation and engagement that can lead to learning; and the highly specialised skills associated with customised development to meet the required pedagogical objectives. This paper presents the Westminster Serious Games Platform (wmin-SGP) an authoring tool that allows educators/domain experts without games design and development technical skills to create bespoke roleplay simulations in three dimensional scenes featuring fully embodied virtual humans capable of verbal and non-verbal interaction with users fit for specific educational objectives. The paper presents the wmin-SGP system architecture and it evaluates its effectiveness in fulfilling its purpose via the implementation of two roleplay simulations, one for Politics and one for Law. In addition, it presents the results of two types of evaluation that address how successfully the wmin-SGP combines usability principles and game core drives based on the Octalysis gamification framework that lead to motivating games experiences. The evaluation results shows that the wmin-SGP: provides an intuitive environment and tools that support users without advanced technical skills to create in real-time bespoke roleplay simulations in advanced graphical interfaces; satisfies most of the usability principles; and provides balanced simulations based on the Octalysis framework core drives. The paper concludes with a discussion of future extension of this real time authoring tool and directions for further development of the Octalysis framework to address learning