Polyglutamine monomer structure and its implications for molecular self-assembly

Polyglutamine is a naturally occurring peptide found within several proteins in neuronal cells of the brain, and its aggregation has been implicated in several neurodegenerative diseases, including Huntington's disease. The resulting aggregates have been demonstrated to possess ~-sheet structure, and aggregation has been shown to start with a single misfolded peptide. The current project sought to computationally examine the structural tendencies of three mutant poly glutamine peptides that were studied experimentally, and found to aggregate with varying efficiencies. Low-energy structures were generated for each peptide by simulated annealing, and were analyzed quantitatively by various geometry- and energy-based methods. According to the results, the experimentally-observed inhibition of aggregation appears to be due to localized conformational restraint placed on the peptide backbone by inserted prolines, which in tum confines the peptide to native coil structure, discouraging transition towards the ~sheet structure required for aggregation. Such knowledge could prove quite useful to the design of future treatments for Huntington's and other related diseases.

A Type-Preserving Compiler from System F to Typed Assembly Language

L'utilisation des méthodes formelles est de plus en plus courante dans le développement logiciel, et les systèmes de types sont la méthode formelle qui a le plus de succès. L'avancement des méthodes formelles présente de nouveaux défis, ainsi que de nouvelles opportunités. L'un des défis est d'assurer qu'un compilateur préserve la sémantique des programmes, de sorte que les propriétés que l'on garantit à propos de son code source s'appliquent également au code exécutable. Cette thèse présente un compilateur qui traduit un langage fonctionnel d'ordre supérieur avec polymorphisme vers un langage assembleur typé, dont la propriété principale est que la préservation des types est vérifiée de manière automatisée, à l'aide d'annotations de types sur le code du compilateur. Notre compilateur implante les transformations de code essentielles pour un langage fonctionnel d'ordre supérieur, nommément une conversion CPS, une conversion des fermetures et une génération de code. Nous présentons les détails des représentation fortement typées des langages intermédiaires, et les contraintes qu'elles imposent sur l'implantation des transformations de code. Notre objectif est de garantir la préservation des types avec un minimum d'annotations, et sans compromettre les qualités générales de modularité et de lisibilité du code du compilateur. Cet objectif est atteint en grande partie dans le traitement des fonctionnalités de base du langage (les «types simples»), contrairement au traitement du polymorphisme qui demande encore un travail substantiel pour satisfaire la vérification de type.

Design, synthèse et application en catalyse verte d’un ligand alkyl imidazolium β-cyclodextrine

Le 21e siècle est le berceau d’une conscientisation grandissante sur les impacts environnementaux des processus utilisés pour synthétiser des molécules cibles. Parmi les avancées qui ont marqué ces dernières décennies, il est également question de réduction de déchets, de conservation de l’énergie et de durabilité des innovations. Ces aspects constituent les lignes directrices de la chimie verte. De ce fait, il est impératif de développer des stratégies de synthèse dont les impacts environnementaux sont bénins. Dans ce mémoire nous présentons la synthèse, la caractérisation et l’étude des propriétés catalytiques en milieu aqueux d’un ligand composé d’une unité -cyclodextrine native, d’une unité imidazolium et d’une chaine alkyle à 12 carbones. Ce ligand hybride s’auto-assemble dans l’eau sous forme de micelles, permettant ainsi d’effectuer en sa présence des couplages de Suzuki-Miyaura dans l’eau, avec de bons rendements. La fonctionnalisation de la face primaire de la -cyclodextrine par un noyau alkyl-imidazolium, précurseur de ligand de type carbène N-hétérocyclique, a permis le développement d’un système catalytique vert et hautement recyclable. Dans un deuxième temps, nous présentons l’utilisation du même ligand hybride dans des couplages de Heck dans l’eau, démontrant ainsi la versatilité du ligand.

Design and Development of an Adaptable Frame -Based System for Dravidian Language Processing

This work is aimed at building an adaptable frame-based system for processing Dravidian languages. There are about 17 languages in this family and they are spoken by the people of South India.Karaka relations are one of the most important features of Indian languages. They are the semabtuco-syntactic relations between verbs and other related constituents in a sentence. The karaka relations and surface case endings are analyzed for meaning extraction. This approach is comparable with the borad class of case based grammars.The efficiency of this approach is put into test in two applications. One is machine translation and the other is a natural language interface (NLI) for information retrieval from databases. The system mainly consists of a morphological analyzer, local word grouper, a parser for the source language and a sentence generator for the target language. This work make contributios like, it gives an elegant account of the relation between vibhakthi and karaka roles in Dravidian languages. This mapping is elegant and compact. The same basic thing also explains simple and complex sentence in these languages. This suggests that the solution is not just ad hoc but has a deeper underlying unity. This methodology could be extended to other free word order languages. Since the frame designed for meaning representation is general, they are adaptable to other languages coming in this group and to other applications.

Design And Development Of A Named Entity Based Question Answering System For Malayalam Language

This is a Named Entity Based Question Answering System for Malayalam Language. Although a vast amount of information is available today in digital form, no effective information access mechanism exists to provide humans with convenient information access. Information Retrieval and Question Answering systems are the two mechanisms available now for information access. Information systems typically return a long list of documents in response to a user’s query which are to be skimmed by the user to determine whether they contain an answer. But a Question Answering System allows the user to state his/her information need as a natural language question and receives most appropriate answer in a word or a sentence or a paragraph. This system is based on Named Entity Tagging and Question Classification. Document tagging extracts useful information from the documents which will be used in finding the answer to the question. Question Classification extracts useful information from the question to determine the type of the question and the way in which the question is to be answered. Various Machine Learning methods are used to tag the documents. Rule-Based Approach is used for Question Classification. Malayalam belongs to the Dravidian family of languages and is one of the four major languages of this family. It is one of the 22 Scheduled Languages of India with official language status in the state of Kerala. It is spoken by 40 million people. Malayalam is a morphologically rich agglutinative language and relatively of free word order. Also Malayalam has a productive morphology that allows the creation of complex words which are often highly ambiguous. Document tagging tools such as Parts-of-Speech Tagger, Phrase Chunker, Named Entity Tagger, and Compound Word Splitter are developed as a part of this research work. No such tools were available for Malayalam language. Finite State Transducer, High Order Conditional Random Field, Artificial Immunity System Principles, and Support Vector Machines are the techniques used for the design of these document preprocessing tools. This research work describes how the Named Entity is used to represent the documents. Single sentence questions are used to test the system. Overall Precision and Recall obtained are 88.5% and 85.9% respectively. This work can be extended in several directions. The coverage of non-factoid questions can be increased and also it can be extended to include open domain applications. Reference Resolution and Word Sense Disambiguation techniques are suggested as the future enhancements

Design and Development of a Frame Based MT System for English-to-ISL

This paper presents the design and development of a frame based approach for speech to sign language machine translation system in the domain of railways and banking. This work aims to utilize the capability of Artificial intelligence for the improvement of physically challenged, deaf-mute people. Our work concentrates on the sign language used by the deaf community of Indian subcontinent which is called Indian Sign Language (ISL). Input to the system is the clerk’s speech and the output of this system is a 3D virtual human character playing the signs for the uttered phrases. The system builds up 3D animation from pre-recorded motion capture data. Our work proposes to build a Malayalam to ISL

Design of a Knowledge-Based Geographic Information System

A GIS has been designed with limited Functionalities; but with a novel approach in Aits design. The spatial data model adopted in the design of KBGIS is the unlinked vector model. Each map entity is encoded separately in vector fonn, without referencing any of its neighbouring entities. Spatial relations, in other words, are not encoded. This approach is adequate for routine analysis of geographic data represented on a planar map, and their display (Pages 105-106). Even though spatial relations are not encoded explicitly, they can be extracted through the specially designed queries. This work was undertaken as an experiment to study the feasibility of developing a GIS using a knowledge base in place of a relational database. The source of input spatial data was accurate sheet maps that were manually digitised. Each identifiable geographic primitive was represented as a distinct object, with its spatial properties and attributes defined. Composite spatial objects, made up of primitive objects, were formulated, based on production rules defining such compositions. The facts and rules were then organised into a production system, using OPS5

FEM based Virtual Prototyping and Design of Third Harmonic Excitation System for Low Voltage Brushless Alternators

Salient pole brushless alternators coupled to IC engines are extensively used as stand-by power supply units for meeting in- dustrial power demands. Design of such generators demands high power to weight ratio, high e ciency and low cost per KVA out- put. Moreover, the performance characteristics of such machines like voltage regulation and short circuit ratio (SCR) are critical when these machines are put into parallel operation and alterna- tors for critical applications like defence and aerospace demand very low harmonic content in the output voltage. While designing such alternators, accurate prediction of machine characteristics, including total harmonic distortion (THD) is essential to mini- mize development cost and time. Total harmonic distortion in the output voltage of alternators should be as low as possible especially when powering very sophis- ticated and critical applications. The output voltage waveform of a practical AC generator is replica of the space distribution of the ux density in the air gap and several factors such as shape of the rotor pole face, core saturation, slotting and style of coil disposition make the realization of a sinusoidal air gap ux wave impossible. These ux harmonics introduce undesirable e ects on the alternator performance like high neutral current due to triplen harmonics, voltage distortion, noise, vibration, excessive heating and also extra losses resulting in poor e ciency, which in turn necessitate de-rating of the machine especially when connected to non-linear loads. As an important control unit of brushless alternator, the excitation system and its dynamic performance has a direct impact on alternator's stability and reliability. The thesis explores design and implementation of an excitation i system utilizing third harmonic ux in the air gap of brushless al- ternators, using an additional auxiliary winding, wound for 1=3rd pole pitch, embedded into the stator slots and electrically iso- lated from the main winding. In the third harmonic excitation system, the combined e ect of two auxiliary windings, one with 2=3rd pitch and another third harmonic winding with 1=3rd pitch, are used to ensure good voltage regulation without an electronic automatic voltage regulator (AVR) and also reduces the total harmonic content in the output voltage, cost e ectively. The design of the third harmonic winding by analytic methods demands accurate calculation of third harmonic ux density in the air gap of the machine. However, precise estimation of the amplitude of third harmonic ux in the air gap of a machine by conventional design procedures is di cult due to complex geome- try of the machine and non-linear characteristics of the magnetic materials. As such, prediction of the eld parameters by conven- tional design methods is unreliable and hence virtual prototyping of the machine is done to enable accurate design of the third har- monic excitation system. In the design and development cycle of electrical machines, it is recognized that the use of analytical and experimental methods followed by expensive and in exible prototyping is time consum- ing and no longer cost e ective. Due to advancements in com- putational capabilities over recent years, nite element method (FEM) based virtual prototyping has become an attractive al- ternative to well established semi-analytical and empirical design methods as well as to the still popular trial and error approach followed by the costly and time consuming prototyping. Hence, by virtually prototyping the alternator using FEM, the important performance characteristics of the machine are predicted. Design of third harmonic excitation system is done with the help of results obtained from virtual prototype of the machine. Third harmonic excitation (THE) system is implemented in a 45 KVA ii experimental machine and experiments are conducted to validate the simulation results. Simulation and experimental results show that by utilizing third harmonic ux in the air gap of the ma- chine for excitation purposes during loaded conditions, triplen harmonic content in the output phase voltage is signi cantly re- duced. The prototype machine with third harmonic excitation system designed and developed based on FEM analysis proved to be economical due to its simplicity and has the added advan- tage of reduced harmonics in the output phase voltage.

Assembly Guidance in Augmented Reality Environments Using a Virtual Interactive Tool

The application of augmented reality (AR) technology for assembly guidance is a novel approach in the traditional manufacturing domain. In this paper, we propose an AR approach for assembly guidance using a virtual interactive tool that is intuitive and easy to use. The virtual interactive tool, termed the Virtual Interaction Panel (VirIP), involves two tasks: the design of the VirIPs and the real-time tracking of an interaction pen using a Restricted Coulomb Energy (RCE) neural network. The VirIP includes virtual buttons, which have meaningful assembly information that can be activated by an interaction pen during the assembly process. A visual assembly tree structure (VATS) is used for information management and assembly instructions retrieval in this AR environment. VATS is a hierarchical tree structure that can be easily maintained via a visual interface. This paper describes a typical scenario for assembly guidance using VirIP and VATS. The main characteristic of the proposed AR system is the intuitive way in which an assembly operator can easily step through a pre-defined assembly plan/sequence without the need of any sensor schemes or markers attached on the assembly components.

Application of a support system to the design of wastewater treatment plants

This paper presents a case study that explores the advantages that can be derived from the use of a design support system during the design of wastewater treatment plants (WWTP). With this objective in mind a simplified but plausible WWTP design case study has been generated with KBDS, a computer-based support system that maintains a historical record of the design process. The study shows how, by employing such a historical record, it is possible to: (1) rank different design proposals responding to a design problem; (2) study the influence of changing the weight of the arguments used in the selection of the most adequate proposal; (3) take advantage of keywords to assist the designer in the search of specific items within the historical records; (4) evaluate automatically the compliance of alternative design proposals with respect to the design objectives; (5) verify the validity of previous decisions after the modification of the current constraints or specifications; (6) re-use the design records when upgrading an existing WWTP or when designing similar facilities; (7) generate documentation of the decision making process; and (8) associate a variety of documents as annotations to any component in the design history. The paper also shows one possible future role of design support systems as they outgrow their current reactive role as repositories of historical information and start to proactively support the generation of new knowledge during the design process

Design, implementation and characterisation of a contactless power transfer system for rotating applications

This paper describes the design, implementation and characterisation of a contactless power transfer system for rotating applications. The power transfer system is based upon a zero-voltage-switched, full-bridge, DC-DC converter, but utilises a non-standard transformer. This transformer allows power transfer between its primary and secondary windings while also allowing free rotation between these windings. The aim of this research is to develop a solution that could replace mechanical slip-rings in certain applications where a non-contacting system would be advantageous. Based upon the design method presented in this paper, a 2 kW prototype system is constructed. Results obtained from testing the 2 kW prototype are presented and discussed. This discussion considers how the performance of the transformer varies with rotation and also the overall efficiency of the system

Design of a new foldamer turn-linker-turn in acyclic hexapeptides and formation of channels through self-assembly

Single crystal X-ray diffraction studies and solvent dependent NMR titration reveal that the designed pepticles I and 11, Boc-Xx(1)-Aib(2)-Yy(3)-NH(CH2)(2)NH-Yy(3)-Aib(2)-Xx(1)-Boc, where Xx and Yy are lie and Leu in peptide I and Leu and Val in peptide 11, respectively, fold into a turn-linker-turn (T-L-T) conformation both in the solid state and in solution. In the crystalline state the T-L-T foldamers; of peptide I and II self-assemble to form a three-dimensional framework of channels. The insides of the channels are hydrophilic and found to contain solvent CHCl3 hydrogen bonded to exposed C=O of Aib located at the turn regions. (c) 2008 Elsevier B.V. All rights reserved.

Low-molecular-weight gelators: Elucidating the principles of gelation based on gelator solubility and a cooperative self-assembly model

This paper highlights the key role played by solubility in influencing gelation and demonstrates that many facets of the gelation process depend on this vital parameter. In particular, we relate thermal stability (T-gel) and minimum gelation concentration (MGC) values of small-molecule gelation in terms of the solubility and cooperative self-assembly of gelator building blocks. By employing a van't Hoff analysis of solubility data, determined from simple NMR measurements, we are able to generate T-calc values that reflect the calculated temperature for complete solubilization of the networked gelator. The concentration dependence of T-calc allows the previously difficult to rationalize "plateau-region" thermal stability values to be elucidated in terms of gelator molecular design. This is demonstrated for a family of four gelators with lysine units attached to each end of an aliphatic diamine, with different peripheral groups (Z or Bee) in different locations on the periphery of the molecule. By tuning the peripheral protecting groups of the gelators, the solubility of the system is modified, which in turn controls the saturation point of the system and hence controls the concentration at which network formation takes place. We report that the critical concentration (C-crit) of gelator incorporated into the solid-phase sample-spanning network within the gel is invariant of gelator structural design. However, because some systems have higher solubilities, they are less effective gelators and require the application of higher total concentrations to achieve gelation, hence shedding light on the role of the MGC parameter in gelation. Furthermore, gelator structural design also modulates the level of cooperative self-assembly through solubility effects, as determined by applying a cooperative binding model to NMR data. Finally, the effect of gelator chemical design on the spatial organization of the networked gelator was probed by small-angle neutron and X-ray scattering (SANS/SAXS) on the native gel, and a tentative self-assembly model was proposed.

Design of supramolecular beta-sheet forming beta-turns containing aromatic rings and non-coded alpha-aminoisobutyric acid and the formation of flat fibrillar structures through self-assembly

Single crystal X-ray diffraction studies show that the three designed tripeptides Boc-Leu-Aib-m-NA-NO2 (I), Boc-Phe-Aib-m-NA-NO2 (II) and Boc-Pro-Aib-m-ABA-OMe (III) (Aib, -aminoisobutyric acid; m-NA, m-nitroaniline; m-ABA, m-aminobenzoic acid; Boc, t-butyloxycarbonyl) containing aromatic rings in the backbones adopt -turn structures that are self-assembled through intermolecular hydrogen bonds and van der Waals interactions to create layers of -sheets. Solvent-dependent NMR titration and CD studies show that the -turn structures of the peptides also exist in the solution phase. The field emission scanning electron microscopic and transmission electron microscopic images of the peptides in the solid state reveal fibrillar structures of flat morphology that are formed through -sheet mediated self-assembly of the preorganised -turn building blocks.