Association Study of 167 Candidate Genes for Schizophrenia Selected by a Multi-Domain Evidence-Based Prioritization Algorithm and Neurodevelopmental Hypothesis

Integrating evidence from multiple domains is useful in prioritizing disease candidate genes for subsequent testing. We ranked all known human genes (n = 3819) under linkage peaks in the Irish Study of High-Density Schizophrenia Families using three different evidence domains: 1) a meta-analysis of microarray gene expression results using the Stanley Brain collection, 2) a schizophrenia protein-protein interaction network, and 3) a systematic literature search. Each gene was assigned a domain-specific p-value and ranked after evaluating the evidence within each domain. For comparison to this
ranking process, a large-scale candidate gene hypothesis was also tested by including genes with Gene Ontology terms related to neurodevelopment. Subsequently, genotypes of 3725 SNPs in 167 genes from a custom Illumina iSelect array were used to evaluate the top ranked vs. hypothesis selected genes. Seventy-three genes were both highly ranked and involved in neurodevelopment (category 1) while 42 and 52 genes were exclusive to neurodevelopment (category 2) or highly ranked (category 3), respectively. The most significant associations were observed in genes PRKG1, PRKCE, and CNTN4 but no individual SNPs were significant after correction for multiple testing. Comparison of the approaches showed an excess of significant tests using the hypothesis-driven neurodevelopment category. Random selection of similar sized genes from two independent genome-wide association studies (GWAS) of schizophrenia showed the excess was unlikely by chance. In a further meta-analysis of three GWAS datasets, four candidate SNPs reached nominal significance. Although gene ranking using integrated sources of prior information did not enrich for significant results in the current experiment, gene selection using an a priori hypothesis (neurodevelopment) was superior to random selection. As such, further development of gene ranking strategies using more carefully selected sources of information is warranted.

Rigorous Specification and Low-Latency Implementation of Technical Market Indicators

Technical market indicators are tools used by technical an- alysts to understand trends in trading markets. Technical (market) indicators are often calculated in real-time, as trading progresses. This paper presents a mathematically- founded framework for calculating technical indicators. Our framework consists of a domain specific language for the un- ambiguous specification of technical indicators, and a run- time system based on Click, for computing the indicators. We argue that our solution enhances the ease of program- ming due to aligning our domain-specific language to the mathematical description of technical indicators, and that it enables executing programs in kernel space for decreased latency, without exposing the system to users’ programming errors.

Visual Literacy Standards in Higher Education: New Opportunities for Libraries and Student Learning

Visual literacy is essential for 21st century learners. Across the higher education curriculum, students are being asked to use and produce images and visual media in their academic work, and they must be prepared to do so. The Association of College and Research Libraries has published the Visual Literacy Competency Standards for Higher Education, which for the first time, outline specific visual literacy learning outcomes. These Standards present new opportunities for libraries to expand their role in student learning through standards-based teaching and assessment, and to contribute to campus-wide collaborative efforts to develop students’ skills and critical thinking with regard to visual materials.

A Bilingual Thesaurus of Everyday Life in Medieval England: Some Issues at the Interface of Semantics and Lexicography

This paper reports on issues at the interface between semantics and lexicography that arose out of the data collection and classification of vocabulary in Anglo-Norman and Middle English in order to create a bilingual thesaurus of everyday life in medieval England. The Bilingual Thesaurus project is based at Birmingham City University and the University of Westminster. Issues to be resolved included the definition of an occupational domain; the creation of a methodology of data collection; the delimitation of domain-specific vocabulary; making distinctions between sense and usage; and the categorisation of the lexical items. Some of these issues are general to thesaurus-making, some are specific to the making of historical thesauruses, while some are unique to the production of a thesaurus of two languages whose use overlapped for several centuries in the late medieval period in England.

Derivation and consistency checking of models in early software product line engineering

Dissertação para obtenção do Grau de Doutor em Engenharia Informática

Sur l’utilisation du langage de programmation Scheme pour le développement de jeux vidéo

Ce mémoire vise à recenser les avantages et les inconvénients de l'utilisation du langage de programmation fonctionnel dynamique Scheme pour le développement de jeux vidéo. Pour ce faire, la méthode utilisée est d'abord basée sur une approche plus théorique. En effet, une étude des besoins au niveau de la programmation exprimés par ce type de développement, ainsi qu'une description détaillant les fonctionnalités du langage Scheme pertinentes au développement de jeux vidéo sont données afin de bien mettre en contexte le sujet. Par la suite, une approche pratique est utilisée en effectuant le développement de deux jeux vidéo de complexités croissantes: Space Invaders et Lode Runner. Le développement de ces jeux vidéo a mené à l'extension du langage Scheme par plusieurs langages spécifiques au domaine et bibliothèques, dont notamment un système de programmation orienté objets et un système de coroutines. L'expérience acquise par le développement de ces jeux est finalement comparée à celle d'autres développeurs de jeux vidéo de l'industrie qui ont utilisé Scheme pour la création de titres commerciaux. En résumé, l'utilisation de ce langage a permis d'atteindre un haut niveau d'abstraction favorisant la modularité des jeux développés sans affecter les performances de ces derniers.

Corrélats neuronaux sous-jacents aux expressions émotionnelles : une comparaison entre musique, voix et visage

Cette thèse a pour objectif de comparer les expressions émotionnelles évoquées par la musique, la voix (expressions non-linguistiques) et le visage sur les plans comportemental et neuronal. Plus précisément, le but est de bénéficier de l’indéniable pouvoir émotionnel de la musique afin de raffiner notre compréhension des théories et des modèles actuels associés au traitement émotionnel. Qui plus est, il est possible que cette disposition surprenante de la musique pour évoquer des émotions soit issue de sa capacité à s’immiscer dans les circuits neuronaux dédiés à la voix, bien que les évidences à cet effet demeurent éparses pour le moment. Une telle comparaison peut potentiellement permettre d’élucider, en partie, la nature des émotions musicales. Pour ce faire, différentes études ont été réalisées et sont ici présentées dans deux articles distincts. Les études présentées dans le premier article ont comparé, sur le plan comportemental, les effets d’expressions émotionnelles sur la mémoire entre les domaines musical et vocal (non-linguistique). Les résultats ont révélé un avantage systématique en mémoire pour la peur dans les deux domaines. Aussi, une corrélation dans la performance individuelle en mémoire a été trouvée entre les expressions de peur musicales et vocales. Ces résultats sont donc cohérents avec l’hypothèse d’un traitement perceptif similaire entre la musique et la voix. Dans le deuxième article, les corrélats neuronaux associés à la perception d’expressions émotionnelles évoquées par la musique, la voix et le visage ont été directement comparés en imagerie par résonnance magnétique fonctionnelle (IRMf). Une augmentation significative du signal « Blood Oxygen Level Dependent » (BOLD) a été trouvée dans l’amygdale (et à l’insula postérieure) en réponse à la peur, parmi l’ensemble des domaines et des modalités à l’étude. Une corrélation dans la réponse BOLD individuelle de l’amygdale, entre le traitement musical et vocal, a aussi été mise en évidence, suggérant à nouveau des similarités entre les deux domaines. En outre, des régions spécifiques à chaque domaine ont été relevées. Notamment, le gyrus fusiforme (FG/FFA) pour les expressions du visage, le sulcus temporal supérieur (STS) pour les expressions vocales ainsi qu’une portion antérieure du gyrus temporal supérieur (STG) particulièrement sensible aux expressions musicales (peur et joie), dont la réponse s’est avérée modulée par l’intensité des stimuli. Mis ensemble, ces résultats révèlent des similarités mais aussi des différences dans le traitement d’expressions émotionnelles véhiculées par les modalités visuelle et auditive, de même que différents domaines dans la modalité auditive (musique et voix). Plus particulièrement, il appert que les expressions musicales et vocales partagent d’étroites similarités surtout en ce qui a trait au traitement de la peur. Ces données s’ajoutent aux connaissances actuelles quant au pouvoir émotionnel de la musique et contribuent à élucider les mécanismes perceptuels sous-jacents au traitement des émotions musicales. Par conséquent, ces résultats donnent aussi un appui important à l’utilisation de la musique dans l’étude des émotions qui pourra éventuellement contribuer au développement de potentielles interventions auprès de populations psychiatriques.

Instant Storyboarding

This thesis aims at empowering software customers with a tool to build software tests them selves, based on a gradual refinement of natural language scenarios into executable visual test models. The process is divided in five steps: 1. First, a natural language parser is used to extract a graph of grammatical relations from the textual scenario descriptions. 2. The resulting graph is transformed into an informal story pattern by interpreting structurization rules based on Fujaba Story Diagrams. 3. While the informal story pattern can already be used by humans the diagram still lacks technical details, especially type information. To add them, a recommender based framework uses web sites and other resources to generate formalization rules. 4. As a preparation for the code generation the classes derived for formal story patterns are aligned across all story steps, substituting a class diagram. 5. Finally, a headless version of Fujaba is used to generate an executable JUnit test. The graph transformations used in the browser application are specified in a textual domain specific language and visualized as story pattern. Last but not least, only the heavyweight parsing (step 1) and code generation (step 5) are executed on the server side. All graph transformation steps (2, 3 and 4) are executed in the browser by an interpreter written in JavaScript/GWT. This result paves the way for online collaboration between global teams of software customers, IT business analysts and software developers.

The sight of silence : the conceptualisation of silence in the visual cultures of sign language communities

Deaf people are perceived by hearing people as living in a silent world. Yet, silence cannot exist without sound, so if sound is not heard, can there be silence? From a linguistic point of view silence is the absence of, or intermission in, communication. Silence can be communicative or noncommunicative. Thus, silence must exist in sign languages as well. Sign languages are based on visual perception and production through movement and sight. Silence must, therefore, be visually perceptible; and, if there is such a thing as visual silence, how does it look? The paper will analyse the topic of silence from a Deaf perspective. The main aspects to be explored are the perception and evaluation of acoustic noise and silence by Deaf people; the conceptualisation of silence in visual languages, such as sign languages; the qualities of visual silence; the meaning of silence as absence of communication (particularly between hearing and Deaf people); social rules for silence; and silencing strategies.

Neural mechanisms of visual object priming: evidence for perceptual and semantic distinctions in fusiform cortex

Previous functional imaging studies have shown that facilitated processing of a visual object on repeated, relative to initial, presentation (i.e., repetition priming) is associated with reductions in neural activity in multiple regions, including fusiforin/lateral occipital cortex. Moreover, activity reductions have been found, at diminished levels, when a different exemplar of an object is presented on repetition. In one previous study, the magnitude of diminished priming across exemplars was greater in the right relative to the left fusiform, suggesting greater exemplar specificity in the right. Another previous study, however, observed fusiform lateralization modulated by object viewpoint, but not object exemplar. The present fMRI study sought to determine whether the result of differential fusiform responses for perceptually different exemplars could be replicated. Furthermore, the role of the left fusiform cortex in object recognition was investigated via the inclusion of a lexical/semantic manipulation. Right fusiform cortex showed a significantly greater effect of exemplar change than left fusiform, replicating the previous result of exemplar-specific fusiform lateralization. Right fusiform and lateral occipital cortex were not differentially engaged by the lexical/semantic manipulation, suggesting that their role in visual object recognition is predominantly in the. C visual discrimination of specific objects. Activation in left fusiform cortex, but not left lateral occipital cortex, was modulated by both exemplar change and lexical/semantic manipulation, with further analysis suggesting a posterior-to-anterior progression between regions involved in processing visuoperceptual and lexical/semantic information about objects. The results are consistent with the view that the right fusiform plays a greater role in processing specific visual form information about objects, whereas the left fusiform is also involved in lexical/semantic processing. (C) 2003 Elsevier Science (USA). All rights reserved.

Direct evidence for attention-dependent influences of the frontal eye-fields on feature-responsive visual cortex

Voluntary selective attention can prioritize different features in a visual scene. The frontal eye-fields (FEF) are one potential source of such feature-specific top-down signals, but causal evidence for influences on visual cortex (as was shown for "spatial" attention) has remained elusive. Here, we show that transcranial magnetic stimulation (TMS) applied to right FEF increased the blood oxygen level-dependent (BOLD) signals in visual areas processing "target feature" but not in "distracter feature"-processing regions. TMS-induced BOLD signals increase in motion-responsive visual cortex (MT+) when motion was attended in a display with moving dots superimposed on face stimuli, but in face-responsive fusiform area (FFA) when faces were attended to. These TMS effects on BOLD signal in both regions were negatively related to performance (on the motion task), supporting the behavioral relevance of this pathway. Our findings provide new causal evidence for the human FEF in the control of nonspatial "feature"-based attention, mediated by dynamic influences on feature-specific visual cortex that vary with the currently attended property.

BDI4JADE: a BDI layer on top of JADE

Several agent platforms that implement the belief-desire-intention (BDI) architecture have been proposed. Even though most of them are implemented based on existing general purpose programming languages, e.g. Java, agents are either programmed in a new programming language or Domain-specific Language expressed in XML. As a consequence, this prevents the use of advanced features of the underlying programming language and the integration with existing libraries and frameworks, which are essential for the development of enterprise applications. Due to these limitations of BDI agent platforms, we have implemented the BDI4JADE, which is presented in this paper. It is implemented as a BDI layer on top of JADE, a well accepted agent platform.

LWiSSy: uma linguagem específica de domínio para modelagem de sistemas de redes de sensores e atuadores sem fio

The field of Wireless Sensor and Actuator Networks (WSAN) is fast increasing and has attracted the interest of both the research community and the industry because of several factors, such as the applicability of such networks in different application domains (aviation, civil engineering, medicine, and others). Moreover, advances in wireless communication and the reduction of hardware components size also contributed for a fast spread of these networks. However, there are still several challenges and open issues that need to be tackled in order to achieve the full potential of WSAN usage. The development of WSAN systems is one of the most relevant of these challenges considering the number of variables involved in this process. Currently, a broad range of WSAN platforms and low level programming languages are available to build WSAN systems. Thus, developers need to deal with details of different sensor platforms and low-level programming abstractions of sensor operational systems on one hand, and they also need to have specific (high level) knowledge about the distinct application domains, on the other hand. Therefore, in order to decouple the handling of these two different levels of knowledge, making easier the development process of WSAN systems, we propose LWiSSy (Domain Language for Wireless Sensor and Actuator Networks Systems), a domain specific language (DSL) for WSAN. The use of DSLs raises the abstraction level during the programming of systems and modularizes the system building in several steps. Thus, LWiSSy allows the domain experts to directly contribute in the development of WSANs without having knowledge on low level sensor platforms, and network experts to program sensor nodes to meet application requirements without having specific knowledge on the application domain. Additionally, LWiSSy enables the system decomposition in different levels of abstraction according to structural and behavioral features and granularities (network, node group and single node level programming)

Um método para desenvolvimento de abordagens generativas com composição de linguagens específicas de domínio

The software systems development with domain-specific languages has become increasingly common. Domain-specific languages (DSLs) provide increased of the domain expressiveness, raising the abstraction level by facilitating the generation of models or low-level source code, thus increasing the productivity of systems development. Consequently, methods for the development of software product lines and software system families have also proposed the adoption of domain-specific languages. Recent studies have investigated the limitations of feature model expressiveness and proposing the use of DSLs as a complement or substitute for feature model. However, in complex projects, a single DSL is often insufficient to represent the different views and perspectives of development, being necessary to work with multiple DSLs. In order to address new challenges in this context, such as the management of consistency between DSLs, and the need to methods and tools that support the development with multiple DSLs, over the past years, several approaches have been proposed for the development of generative approaches. However, none of them considers matters relating to the composition of DSLs. Thus, with the aim to address this problem, the main objectives of this dissertation are: (i) to investigate the adoption of the integrated use of feature models and DSLs during the domain and application engineering of the development of generative approaches; (ii) to propose a method for the development of generative approaches with composition DSLs; and (iii) to investigate and evaluate the usage of modern technology based on models driven engineering to implement strategies of integration between feature models and composition of DSLs