Conserved modularity and potential for alternate splicing in mouse and human Slit genes

The vertebrate Slit gene family currently consists of three members;Slit1,Slit2 and Slit3. Each gene encodes a protein containing multiple epidermal growth factor and leucine rich repeat motifs, which are likely to have importance in cell-cell interactions. In this study, we sought to fully define and characterise the vertebrate Slit gene family. Using long distance PCR coupled with in silico mapping, we determined the genomic structure of all three Slit genes in mouse and man. Analysis of EST and genomic databases revealed no evidence of further Slit family members in either organism. All three Slit genes were encoded by 36 (Slit3) or 37 (Slit1 and Slit2) exons covering at least 143 kb or 183 kb of mouse or human genomic DNA respectively. Two additional potential leucine-rich repeat encoding exons were identified within intron 12 of Slit2. These could be inserted in frame, suggesting that alternate splicing may occur in Slit2 A search for STS sequences within human Slit3 anchored this gene to D5S2075 at the 5' end (exon 4) and SGC32449 within the 3' UTR, suggesting that Slit3 may cover greater than 693 kb. The genomic structure of all Slit genes demonstrated considerable modularity in the placement of exon-intron boundaries such that individual leucine-rich repeat motifs were encoded by individual 72 by exons. This further implies the potential generation of multiple Slit protein isoforms varying in their number of repeat units. cDNA library screening and EST database searching verified that such alternate splicing does occur.

On lattices from combinatorial game theory modularity and a representation theorem: finite case

We show that a self-generated set of combinatorial games, S. may not be hereditarily closed but, strong self-generation and hereditary closure are equivalent in the universe of short games. In [13], the question "Is there a set which will give a non-distributive but modular lattice?" appears. A useful necessary condition for the existence of a finite non-distributive modular L(S) is proved. We show the existence of S such that L(S) is modular and not distributive, exhibiting the first known example. More, we prove a Representation Theorem with Games that allows the generation of all finite lattices in game context. Finally, a computational tool for drawing lattices of games is presented. (C) 2014 Elsevier B.V. All rights reserved.

Analysis of support for modularity in object teams based on design patterns

Dissertação de Mestrado em Engenharia Informática

A qualitative assessment of modularity in CaesarJ components based on implementations of design patterns

Tese de Mestrado em Engenharia Informática

Quantitative assessment of modularity of caesarJ components

Dissertação apresentada no âmbito do Mestrado em Engenharia Informática para obtenção do grau de Mestre em Engenharia Informática

Modularity of auditory spatial representations

Abstract : Auditory spatial functions are of crucial importance in everyday life. Determining the origin of sound sources in space plays a key role in a variety of tasks including orientation of attention, disentangling of complex acoustic patterns reaching our ears in noisy environments. Following brain damage, auditory spatial processing can be disrupted, resulting in severe handicaps. Complaints of patients with sound localization deficits include the inability to locate their crying child or being over-loaded by sounds in crowded public places. Yet, the brain bears a large capacity for reorganization following damage and/or learning. This phenomenon is referred as plasticity and is believed to underlie post-lesional functional recovery as well as learning-induced improvement. The aim of this thesis was to investigate the organization and plasticity of different aspects of auditory spatial functions. Overall, we report the outcomes of three studies: In the study entitled "Learning-induced plasticity in auditory spatial representations" (Spierer et al., 2007b), we focused on the neurophysiological and behavioral changes induced by auditory spatial training in healthy subjects. We found that relatively brief auditory spatial discrimination training improves performance and modifies the cortical representation of the trained sound locations, suggesting that cortical auditory representations of space are dynamic and subject to rapid reorganization. In the same study, we tested the generalization and persistence of training effects over time, as these are two determining factors in the development of neurorehabilitative intervention. In "The path to success in auditory spatial discrimination" (Spierer et al., 2007c), we investigated the neurophysiological correlates of successful spatial discrimination and contribute to the modeling of the anatomo-functional organization of auditory spatial processing in healthy subjects. We showed that discrimination accuracy depends on superior temporal plane (STP) activity in response to the first sound of a pair of stimuli. Our data support a model wherein refinement of spatial representations occurs within the STP and that interactions with parietal structures allow for transformations into coordinate frames that are required for higher-order computations including absolute localization of sound sources. In "Extinction of auditory stimuli in hemineglect: space versus ear" (Spierer et al., 2007a), we investigated auditory attentional deficits in brain-damaged patients. This work provides insight into the auditory neglect syndrome and its relation with neglect symptoms within the visual modality. Apart from contributing to a basic understanding of the cortical mechanisms underlying auditory spatial functions, the outcomes of the studies also contribute to develop neurorehabilitation strategies, which are currently being tested in clinical populations.

Modularity of the Consani-Scholten quintic

We prove that the Consani-Scholten quintic, a Calabi-Yau threefold over Q, is Hilbert modular. For this, we refine several techniques known from the context of modular forms. Most notably, we extend the Faltings-Serre-Livn´e method to induced four-dimensional Galois representations over Q. We also need a Sturm bound for Hilbert modular forms; this is developed in an appendix by José Burgos Gil and the second author.

Evolution of the ferric reductase domain (FRD) superfamily: modularity, functional diversification, and signature motifs.

A heme-containing transmembrane ferric reductase domain (FRD) is found in bacterial and eukaryotic protein families, including ferric reductases (FRE), and NADPH oxidases (NOX). The aim of this study was to understand the phylogeny of the FRD superfamily. Bacteria contain FRD proteins consisting only of the ferric reductase domain, such as YedZ and short bFRE proteins. Full length FRE and NOX enzymes are mostly found in eukaryotic cells and all possess a dehydrogenase domain, allowing them to catalyze electron transfer from cytosolic NADPH to extracellular metal ions (FRE) or oxygen (NOX). Metazoa possess YedZ-related STEAP proteins, possibly derived from bacteria through horizontal gene transfer. Phylogenetic analyses suggests that FRE enzymes appeared early in evolution, followed by a transition towards EF-hand containing NOX enzymes (NOX5- and DUOX-like). An ancestral gene of the NOX(1-4) family probably lost the EF-hands and new regulatory mechanisms of increasing complexity evolved in this clade. Two signature motifs were identified: NOX enzymes are distinguished from FRE enzymes through a four amino acid motif spanning from transmembrane domain 3 (TM3) to TM4, and YedZ/STEAP proteins are identified by the replacement of the first canonical heme-spanning histidine by a highly conserved arginine. The FRD superfamily most likely originated in bacteria.

Combining Customer Requirements and Modularity in Complete Tap Water Solution

This thesis studies forming a complete solution concept for tap water systems in project business environment. The aim of the study is to find tools and means for the target company to determine the scope of their tap water solution offering and to research what kind of organizational capabilities and resources are needed to supply such system solutions. With the help of literature, the characteristics of systems selling and project business and thematics of systems integration and integrated solutions are examined, and the significance of modularity and customer requirements in the given operational environment is discussed. After this, a checklist tool for customer requirements management is developed for the tap water system along with a module allocation method. The study proposes that with the checklist and module allocation the technical specifications can be extensively and innovatively defined for the system. The tools developed are a part of a complete tap water solution concept, which suggests that integrated solutions might constitute possibilities for the company to outperform its competitors when the traditional business methods of the industry are becoming obsolete.

Network Structures and Modularity among Biofuel Heating System Manufacturers

The aim of this thesis was to study network structures and modularity among biofuel heating system manufacturers in the Finnish bioenergy sector by utilizing the perspectives of numerous Finnish bioenergy specialists. The study is qualitative due to the fact that the research material was gathered with semi-structured theme interviews during May and June 2010. The research methodology used in the thesis combines conceptual and action-oriented approach. Networks, value nets, and modularity were studied from different perspectives. Three network and platform strategies were discovered and a general network structure was formed. Moreover, benefits and disadvantages of networks and modularity among biofuel heating system manufacturers were illustrated. The analysis provides a comprehensive perception of the industry. The results of the research were constructed by implementing existing theories into practice. Also future recommendations for the biofuel heating system manufacturers were given. The results can be considered to be beneficial because the number of previous studies about the subject is relatively small. The reliability of the study is eminent because the number of the interviews was inclusive.

Modularity in Health and Social Services: Perspectives on Organization and Management

Organizations that provide health and social services operate in a complex and constantly changing environment. Changes occur, for example, in ageing, technology and biotechnology, and customers’ expectations, as well as the global economic situation. Organizations typically aim to adapt the changes by introducing new organizational structures and managerial practices, such as process and lean management. Only recently has there been an interest in evaluating whether organizations providing health and social services could apply modularity in order to respond to some of the changes. The concept of modularity originates from manufacturing, but is applied in many other disciplines, such as information technology and logistics. However, thus far, the literature concerning modularity in health and social services is scarce. Therefore the purpose of this thesis is to increase understanding concerning modularity and the possibilities to apply modularity in the health and social services context. In addition, the purpose is to shed light on the viewpoints that are worth taking into account when considering the application of modularity in the health and social services context. The aim of the thesis is to analyze the way in which the modular structures are applied in the health and social services context and to analyze what advantages and possible barriers, as well as managerial concerns, might occur if modularity is applied in the health and social services context. The thesis is conducted by using multiple methods in order to provide a broad aspect to the topic. A systematic literature review provided solid ground for pre-understanding the topic and supported the formulation of the research questions. Theoretical reasoning provided a general overview of the special characteristics of the health and social services context and their effect on application of modularity. Empirical studies concentrated on managerial concerns of modularity particularly from the perspective of health and social services for the elderly. Results of the thesis reveal that structures in products, services, processes, and organizations are rather modular in health and social services. They can be decomposed in small independent units, while the challenges seem to occur especially in the compatibility of the services. It seems that health and social services managers have recognized this problem and they are increasingly paying attention to this challenge in order to enhance the flexible compatibility of services. Advantages and possible barriers of modularity are explored in this thesis, and from the theoretical perspective it could be argued that modularity seems to be beneficial in the context of health and social services. In fact, it has the potential to alleviate several of the challenges that the health and social services context is confronting. For example, modular structures could support organizations in their challenging task to respond to customers’ increasing demand for heterogeneous services. However, special characteristics of the health and social services context create barriers and provide significant challenges in application of modularity. For example, asymmetry of information, negative externalities, uncertainty of demand, and rigid regulation prevent managers from extensively drawing benefits from modularity. Results also reveal that modularity has managerial implications in health and social service. Modularity has the potential to promote and support new service development and outsourcing. Results also provide insights into network management and increases managerial understanding of different network management strategies. Standardization in health and social services is extensive due to legislation and recommendations. Modularity provides alternative paths to take an advantage of standardization while still ensuring the quality of the services. Based on this thesis, it can be concluded, both from a theoretical perspective and from empirical results concerning modularity in health and social services, that modularity might fit well and be beneficial. However, the special characteristics of the health and social services context prevent some of the benefits of modularity and complicate its application. This thesis contributes to the academic literature on the organization and management of health and social services by describing modularity as an alternative way for organizing and managing health and social services. In addition, it contributes to the literature of modularity by exploring the applicability of modularity in the context of health and social services. It also provides practical contribution to health and social services managers by evaluating the pros and cons of modularity when applied to health and social services.

Intelligence by Design: Principles of Modularity and Coordination for Engineerin

All intelligence relies on search --- for example, the search for an intelligent agent's next action. Search is only likely to succeed in resource-bounded agents if they have already been biased towards finding the right answer. In artificial agents, the primary source of bias is engineering. This dissertation describes an approach, Behavior-Oriented Design (BOD) for engineering complex agents. A complex agent is one that must arbitrate between potentially conflicting goals or behaviors. Behavior-oriented design builds on work in behavior-based and hybrid architectures for agents, and the object oriented approach to software engineering. The primary contributions of this dissertation are: 1.The BOD architecture: a modular architecture with each module providing specialized representations to facilitate learning. This includes one pre-specified module and representation for action selection or behavior arbitration. The specialized representation underlying BOD action selection is Parallel-rooted, Ordered, Slip-stack Hierarchical (POSH) reactive plans. 2.The BOD development process: an iterative process that alternately scales the agent's capabilities then optimizes the agent for simplicity, exploiting tradeoffs between the component representations. This ongoing process for controlling complexity not only provides bias for the behaving agent, but also facilitates its maintenance and extendibility. The secondary contributions of this dissertation include two implementations of POSH action selection, a procedure for identifying useful idioms in agent architectures and using them to distribute knowledge across agent paradigms, several examples of applying BOD idioms to established architectures, an analysis and comparison of the attributes and design trends of a large number of agent architectures, a comparison of biological (particularly mammalian) intelligence to artificial agent architectures, a novel model of primate transitive inference, and many other examples of BOD agents and BOD development.

Dethroning the myth: cognitive dissociations and innate modularity in Williams syndrome

Despite increasing empirical data to the contrary, it continues to be claimed that morphosyntax and face processing skills of people with Williams syndrome are intact, This purported intactness, which coexists with mental retardation, is used to bolster claims about innately specified, independently functioning modules, as if the atypically developing brain were simply a normal brain with parts intact and parts impaired. Yet this is highly unlikely, given the dynamics of brain development and the fact that in a genetic microdeletion syndrome the brain is developing differently from the moment of conception, throughout embryogenesis, and during postnatal brain growth. In this article, we challenge the intactness assumptions, using evidence from a wide variety of studies of toddlers, children, and adults with Williams syndrome.