293 research outputs found
BIOINFORMATICS TOOL AND MODEL DEVELOPMENT FOR STUDYING BIOLOGICAL NETWORKS AND PROTEIN-PROTEIN INTERACTIONS
Ph.DDOCTOR OF PHILOSOPH
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Belief-Space Planning for Resourceful Manipulation and Mobility
Robots are increasingly expected to work in partially observable and unstructured environments. They need to select actions that exploit perceptual and motor resourcefulness to manage uncertainty based on the demands of the task and environment. The research in this dissertation makes two primary contributions. First, it develops a new concept in resourceful robot platforms called the UMass uBot and introduces the sixth and seventh in the uBot series. uBot-6 introduces multiple postural configurations that enable different modes of mobility and manipulation to meet the needs of a wide variety of tasks and environmental constraints. uBot-7 extends this with the use of series elastic actuators (SEAs) to improve manipulation capabilities and support safer operation around humans. The resourcefulness of these robots is complemented with a belief-space planning framework that enables task-driven action selection in the context of the partially observable environment. The framework uses a compact but expressive state representation based on object models. We extend an existing affordance-based object model, called an aspect transition graph (ATG), with geometric information. This enables object-centric modeling of features and actions, making the model much more expressive without increasing the complexity. A novel task representation enables the belief-space planner to perform general object-centric tasks ranging from recognition to manipulation of objects. The approach supports the efficient handling of multi-object scenes. The combination of the physical platform and the planning framework are evaluated in two novel, challenging, partially observable planning domains. The ARcube domain provides a large population of objects that are highly ambiguous. Objects can only be differentiated using multi-modal sensor information and manual interactions. In the dexterous mobility domain, a robot can employ multiple mobility modes to complete navigation tasks under a variety of possible environment constraints. The performance of the proposed approach is evaluated using experiments in simulation and on a real robot
The role of branched muscle fibres and ACTN3 polymorphism as a genetic disease modifier in Duchenne nuscular dystrophy
Duchenne muscular dystrophy (DMD) is the second most common fatal genetic disease in humans, with an incidence of 1 in 3300 live male births. DMD is characterized by progressive cycles of skeletal muscle necrosis/regeneration triggered by the absence of the protein dystrophin from the inner surface of the sarcolemma. In DMD and dystrophin-negative mdx mice, regenerated skeletal muscle fibres are branched and deterioration of muscle contractile function with age is correlated with an increase in both the number and complexity of branched fibres. In this thesis, I present four papers in support of my hypothesis, that when the number and complexity of branched fibres in dystrophin-negative muscles reaches a critical threshold, termed ‘tipping point’, the branches in and of themselves, mechanically weaken the muscle and are susceptible to rupturing when subjected to high forces such as those experienced during eccentric/lengthening contractions. Methodologically, the papers utilise a combination of isolated muscle function contractile measurements coupled with single fibre imaging and confocal microscopy of cleared whole muscles. All experiments use intact muscles isolated from the dystrophic mdx mouse, double knockout (dk)Actn3KO/mdx (dKO) mouse and littermate controls. In conclusion, I propose a two-phase model to explain the aetiology of DMD. Phase-one involves the absence of dystrophin triggering a pathological increase in [Ca2+]in resulting in skeletal muscle fibre necrosis followed immediately by regeneration. The process proceeds cyclically, increasing the number of abnormally branched regenerated dystrophin-deficient muscle fibres. Once the number and complexity of branched fibres passes a level I term ‘tipping point’, phase-two occurs; now eccentric contractions cause force deficits as a consequence of branches rupturing. In the final stage, phase-two will tend to have a positive feedback component, as breaking branches will no longer support the eccentrically contracting muscle, placing additional stress on the remaining branches during the contraction. It is important to note that depending on the complexity of branching and forces experienced by the muscle, phase-one and phase-two are not mutually exclusive and will occur simultaneously
A semiotic evaluation of musical meaning in the works of Igor Stravinsky : decoding syntax and markedness and prototypicality theory.
SIGLEAvailable from British Library Document Supply Centre-DSC:DXN026379 / BLDSC - British Library Document Supply CentreGBUnited Kingdo
定量的構造物性相関/定量的構造活性相関モデルの逆解析を利用した化学構造創出に関する研究
学位の種別: 課程博士審査委員会委員 : (主査)東京大学教授 船津 公人, 東京大学教授 酒井 康行, 東京大学准教授 杉山 弘和, 東京大学准教授 伊藤 大知, 京都大学特任教授 奧野 恭史, スイス連邦工科大学教授 Gisbert SchneiderUniversity of Tokyo(東京大学
Development and use of databases for ligand-protein interaction studies
This project applies structure-activity relationship (SAR), structure-based and
database mining approaches to study ligand-protein interactions. To support these
studies, we have developed a relational database system called EDinburgh University
Ligand Selection System (EDULISS 2.0) which stores the structure-data files of +5.5
million commercially available small molecules (+4.0 million are recognised as
unique) and over 1,500 various calculated molecular properties (descriptors) for each
compound. A user-friendly web-based interface for EDULISS 2.0 has been
established and is available at http://eduliss.bch.ed.ac.uk/.
We have utilised PubChem bioassay data from an NMR based screen assay for a
human FKBP12 protein (PubChem AID: 608). A prediction model using a Logistic
Regression approach was constructed to relate the assay result with a series of
molecular descriptors. The model reveals 38 descriptors which are found to be good
predictors. These are mainly 3D-based descriptors, however, the presence of some
predictive functional groups is also found to give a positive contribution to the
binding interaction. The application of a neural network technique called Self
Organising Maps (SOMs) succeeded in visualising the similarity of the PubChem
compounds based on the 38 descriptors and clustering the 36 % of active compounds
(16 out of 44) in a cluster and discriminating them from 95 % of inactive compounds.
We have developed a molecular descriptor called the Atomic Characteristic Distance
(ACD) to profile the distribution of specified atom types in a compound. ACD has
been implemented as a pharmacophore searching tool within EDULISS 2.0. A
structure-based screen succeeded in finding inhibitors for pyruvate kinase and the
ligand-protein complexes have been successfully crystallised.
This study also discusses the interaction of metal-binding sites in metalloproteins.
We developed a database system and web-based interface to store and apply
geometrical information of these metal sites. The programme is called MEtal Sites
in Proteins at Edinburgh UniverSity (MESPEUS;
http://eduliss.bch.ed.ac.uk/MESPEUS/). MESPEUS is an exceptionally versatile
tool for the collation and abstraction of data on a wide range of structural questions.
As an example we carried out a survey using this database indicating that the most
common protein types which contain Mg-OATP-phosphate site are transferases and the
most common pattern is linkage through the β- and γ-phosphate groups
Binarism and indeterminacy in the novels of Thomas Pynchor
Bibliography: pages 397-401.I attempt in this thesis, to graft together a close critical, and predominantly thematic, reading of Thomas Pynchon's novels with selected issues treated in the work of Jacques Derrida on philosophy and textuality, illustrating how this work demands the revision and interrogation of several major critical issues, concepts, dualisms and presuppositions. The thesis consists of an Introduction which sets forth a brief rationale for the graft described above, followed by a short and unavoidably inadequate synopsis of Derrida's work with a brief review and explication of those of his 'concepts' which play an important role in my reading of Pynchon's texts. The Introduction is succeeded by three lengthy chapters in which I discuss, more or less separately, each of Pynchon's three novels to date. These are V. (1963), The Crying of Lot 49, (1966) and Gravity's Rainbow (1973), and I discuss them in the order of their appearance, devoting a chapter to each. I attempt to treat different but related issues, preoccupations, themes and tropes in each of the novels to avoid repeating myself, engaging the apparatuses derived from Derrida's writing where deemed strategic and instructive. I suggest moreover, that several of the issues examined apropos the novel under consideration in any one chapter apply mutandis rnutandi to the other novels. Each chapter therefore to some extent conducts a reading of the novels which it does not treat directly. Finally, supervising these separate chapters is a sustained focus on the epistemology of binarism and digitalism, and the conceptual dualisms which structure and inform major portions of the thematic and rhetorical dimensions The thesis concludes with a Bibliography and a summary Epilogue which seeks to assess briefly the 'achievement' of Pynchon's writing
Hypertext Semiotics in the Commercialized Internet
Die Hypertext Theorie verwendet die selbe Terminologie, welche seit Jahrzehnten in der semiotischen Forschung untersucht wird, wie z.B. Zeichen, Text, Kommunikation, Code, Metapher, Paradigma, Syntax, usw. Aufbauend auf jenen Ergebnissen, welche in der Anwendung semiotischer Prinzipien und Methoden auf die Informatik erfolgreich waren, wie etwa Computer Semiotics, Computational Semiotics und Semiotic Interface Engineering, legt diese Dissertation einen systematischen Ansatz für all jene Forscher dar, die bereit sind, Hypertext aus einer semiotischen Perspektive zu betrachten. Durch die Verknüpfung existierender Hypertext-Modelle mit den Resultaten aus der Semiotik auf allen Sinnesebenen der textuellen, auditiven, visuellen, taktilen und geruchlichen Wahrnehmung skizziert der Autor Prolegomena einer Hypertext-Semiotik-Theorie, anstatt ein völlig neues Hypertext-Modell zu präsentieren. Eine Einführung in die Geschichte der Hypertexte, von ihrer Vorgeschichte bis zum heutigen Entwicklungsstand und den gegenwärtigen Entwicklungen im kommerzialisierten World Wide Web bilden den Rahmen für diesen Ansatz, welcher als Fundierung des Brückenschlages zwischen Mediensemiotik und Computer-Semiotik angesehen werden darf. Während Computer-Semiotiker wissen, dass der Computer eine semiotische Maschine ist und Experten der künstlichen Intelligenz-Forschung die Rolle der Semiotik in der Entwicklung der nächsten Hypertext-Generation betonen, bedient sich diese Arbeit einer breiteren methodologischen Basis. Dementsprechend reichen die Teilgebiete von Hypertextanwendungen, -paradigmen, und -strukturen, über Navigation, Web Design und Web Augmentation zu einem interdisziplinären Spektrum detaillierter Analysen, z.B. des Zeigeinstrumentes der Web Browser, des Klammeraffen-Zeichens und der sogenannten Emoticons. Die Bezeichnung ''Icon'' wird als unpassender Name für jene Bildchen, welche von der graphischen Benutzeroberfläche her bekannt sind und in Hypertexten eingesetzt werden, zurückgewiesen und diese Bildchen durch eine neue Generation mächtiger Graphic Link Markers ersetzt. Diese Ergebnisse werden im Kontext der Kommerzialisierung des Internet betrachtet. Neben der Identifizierung der Hauptprobleme des eCommerce aus der Perspektive der Hypertext Semiotik, widmet sich der Autor den Informationsgütern und den derzeitigen Hindernissen für die New Economy, wie etwa der restriktiven Gesetzeslage in Sachen Copyright und Intellectual Property. Diese anachronistischen Beschränkungen basieren auf der problematischen Annahme, dass auch der Informationswert durch die Knappheit bestimmt wird. Eine semiotische Analyse der iMarketing Techniken, wie z.B. Banner Werbung, Keywords und Link Injektion, sowie Exkurse über den Browser Krieg und den Toywar runden die Dissertation ab
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