The development of selective SmI2-H2O-mediated mono-reductions of cyclic-1,3-diesters to the corresponding 3-hydroxy acids is described. The reaction proceeds with complete selectivity for cyclic-1,3-diesters over acyclic esters. Sequential one-pot conjugate reduction-ester reduction of alkylidene cyclic-1,3-diesters is also reported. Furthermore, we describe the exploitation of the unusual ketyl radical intermediates formed via single electron reduction of the ester carbonyl in unprecedented 5-exo-trig cyclisations providing access to highly substituted, stereo-defined, cyclopentanols and cyclopentanones. Also described is the use of a silicon control element to direct the stereochemical outcome of the SmI2-MeOH-mediated conjugate reduction-intramolecular aldol cyclisations of α,β-unsaturated lactones. These cyclisations generate two contiguous quaternary centres with complete diastereocontrol; the utility of the silicon-directing group as a synthetic handle for derivatisation of the cyclisation products has also been demonstrated. These cyclisations have been applied in a model approach to the anti-mitotic natural product pseudolaric acid B.

This report, conducted at the School of Engineering in Jönköping within mechanical engineering: product development and design, focuses on the development of an exoskeleton for hedge trimmer operators. The project is aimed to create a mechanical solution to reduce the strain on hedge trimmer operator’s shoulders and upper bodies during long workdays. Tasks involving hedge trimmers cause significant stress on the shoulder area, which can lead to long-term injuries. Exoskeletons have the potential to support users by redistributing the load to stronger parts of the body. The goal of the project was to design an exoskeleton specifically for hedge trimmer operators to reduce the risk of work-related injuries and improve the work environment. The project began with a preliminary study that included market analysis, interviews with professional users, and testing of existing exoskeletons. A specification of requirements was formulated based on the collected data, and several concepts were generated through brainstorming. The final concept was selected using Pugh's matrix, where different options were compared against a reference product from Hilti. The chosen design for the exoskeleton includes a spring-loaded mechanism placed on the user's back. The springs provide support at the right angle and reduce shoulder strain by transferring the load to the back and hips. The prototype was based on Husqvarna's existing harness, which contributed to reduced production costs and adaptability. The prototype meets most of the requirements in the specification, such as providing mechanical support to the shoulders and the ability to adjust the force. However, further tests and adjustments are needed to optimize the design and ensure user-friendliness. Future research should include field tests with actual users and the implementation of adjustment options for the spring force. This study lays the foundation for the future development of exoskeletons for hedge trimmer operators and potentially other tools, aiming to improve the work environment and reduce the risk of work-related injuries in the gardening and forestry industries.

Este trabalho apresenta o desenvolvimento de algoritmos de adaptação do padrão de marcha com a utilização de redes neurais artificiais para uma órtese ativa para membros inferiores. Trajetórias estáveis são geradas durante o processo de otimização, considerando um gerador de trajetórias baseado no critério do ZMP (Zero Moment Point) e no modelo dinâmico do equipamento. Três redes neurais são usadas para diminuir o tempo de cálculo do modelo e da otimização do ZMP, e reproduzir o gerador de trajetórias analítico. A primeira rede aproxima a dinâmica do modelo fornecendo a variação de torque necessária para a realização do processo de otimização dos parâmetros de adaptação da marcha; a segunda rede trabalha no processo de otimização, fornecendo o parâmetro otimizado de acordo com a interação paciente-órtese; a terceira rede reproduz o gerador de trajetórias para um determinado intervalo de tempo do passo que pode ser repetido para qualquer quantidade de passos. Além disso, um controle do tipo torque calculado acrescido de um controle PD é usado para garantir que as trajetórias atuais estejam seguindo as trajetórias desejadas da órtese. O modelo dinâmico da órtese na sua configuração atual, com forças de interação incluídas, é usado para gerar resultados simulados. / This work deals with neural network-based gait-pattern adaptation algorithms for an active lower limbs orthosis. Stable trajectories are generated during the optimization process, considering a trajectory generator based on the Zero Moment Point criterion and on the dynamic model. Additionally, three neural network are used to decrease the time-consuming computation of the model and ZMP optimization and to reproduce the analitical trajectory generator. The first neural network approximates the dynamic model providing the necessary torque variation to gait adaptation parameters process; the second network works in the optimization procedure, giving the adapting parameter according to orthosis-patient interaction; and the third network replaces the trajectory generation for a stablished step time interval which can be reproduced any time during the walking. Also, a computed torque controller plus the PD controller is designed to guarantee the actual trajectories are following the orthosis desired trajectories. The dynamic model of the actual active orthosis, with interaction forces included, is used to generate simulation results.

This thesis summarizes the results of studies on two aspects of nucleic acids. Chemically modified antisense oligonucleotides (AONs) have been evaluated with regards to their suitability for mRNA targeting in an antisense approach (Paper I – III). The chemically modified nucleotidic units 2'-O-Me-T, 2'-O-MOE-T, oxetane-T, LNA-T, azetidine-T, aza-ENA-T, carbocyclic-ENA-T and carbocyclic-LNA-T were incorporated into 15-mer AONs and targeted against a 15-mer RNA chosen from the coding region of SV-40 large T antigen. The comparative study showed that a single modified nucleotide in the AON with North-East locked sugar (oxetane-T and azetidine-T) lowered the affinity for the complementary RNA whereas North locked sugars (LNA-T, aza-ENA-T, carbocyclic-ENA-T, and carbocyclic-LNA-T) significantly improved the affinity. A comparative RNase H digestion study showed that modifications of the same type (North-East type or North type) in different sequences gave rise to similar cleavage patterns. Determination of the Michaelis-Menten parameters by kinetic experiments showed that the modified AONs recruit RNase H resulting in enhanced turnover numbers (kcat) although with weaker enzyme-substrate binding (1/Km) compared to the unmodified AON. The modified AONs were also evaluated with regards to resistance towards snake venom phosphodiesterase and human serum to estimate their stability toward exonucleases. The aza-ENA-T and carbocyclic-ENA-T modified AONs showed improved stability compared to all other modified AONs. In general, the modified AONs with North type nucleotides (except LNA-T) were found to be superior to the North-East type as they showed improved target affinity, comparable RNase H recruitment capability and improved exonuclease stability. The second aspect studied in this thesis is based on physicochemical studies of short RNA molecules utilizing NMR based pH titration and alkaline hydrolysis reactions (Paper IV – V). The NMR based (1H and 31P) pH titration studies revealed the effect of guaninyl ion formation, propagated electrostatically through a single stranded chain in a sequence dependent manner. The non-identical electronic character of the internucleotidic phosphodiesters was further verified by alkaline hydrolysis experiments. The internucleotidic phosphodiesters, which were influenced by guaninyl ion formation, were hydrolyzed at a faster rate than those sequences where such guaninyl ion formation was prevented by replacing G with N1-Me-G.

Orientador: Crispin Humberto Garcia Cruz / Banca: Eleni Gomes / Banca: Roberto Alves de Oliveira / Resumo: Os polímeros microbianos extracelulares (exo-biopolímeros) são moléculas que apresentam um grande potencial de aplicação nas indústrias de alimentos, farmacêuticas, petrolíferas, de cosméticos, têxteis, de papéis, tintas, produtos agrícolas entre outras. Como biorremediadores, podem ser utilizados na remoção de metais pesados em ambientes aquáticos poluídos, atuando como agentes de biossorção por meio da acumulação de nutrientes a partir do meio ambiente. O objetivo do trabalho foi a produção de exobiopolímeros a partir de três Ascomicetos endofíticos (Colletotrichum sp., Guignardia sp. e Phomopsis sp.). Foi selecionado o fungo que apresentou a maior produção desse material biológico. Tanto esse exo-biopolímero quanto a biomassa foram avaliados quanto aos seus potenciais de biossorção dos íons metálicos chumbo (Pb+2) e cádmio (Cd+2). Para a obtenção do meio de cultivo utilizado para a produção de exo-biopolímeros, foram testados o meio mínimo de sais de Vogel modificado com diferentes fontes de nitrogênio definidas e glicose como única fonte de carbono. Em seguida, foi realizado um planejamento fatorial 3(3-0) com 27 experimentos em duplicata, onde as variáveis independentes foram o tempo, temperatura de cultivo e a concentração inicial de glicose. O fungo Colletotrichum sp. apresentou a maior produção de exo-biopolímero (5,71 gL-1) utilizando a uréia como fonte de nitrogênio, em cultivo a 28 ºC, 150 rpm e glicose 6 % (p/v) em 192 horas de cultivo. A execução do planejamento fatorial demonstrou que a produção de biomassa seca foi favorecida por faixas de temperatura e concentração inicial de glicose entre 24 e 32 ºC e 35 e 75 gL-1, respectivamente. A produção de exo-biopolímero foi favorecida por faixas de temperatura e concentração... (Resumo completo, clicar acesso eletrônico abaixo) / Abstract: The microbial extracellular polymer (exo-biopolymers) are molecules that have a great potential for application in the industries of food, pharmaceutical, oil, cosmetics, textiles, paper, paints, agricultural products and others. As bioremediation, can be used in the removal of heavy metals in polluted aquatic environments, acting as agents of bioremediation through the accumulation of nutrients from the environment. Objective of this study was to produce exo-biopolymer from three endophytic Ascomycota (Colletotrichum sp., Guignardia sp. and Phomopsis sp.). Then, was selected the fungus that showed the highest production of exobiopolymer. Both the exo-biopolymer and biomass were assessed for their potential of biosorption of metallic ions lead (Pb+2) and cadmium (Cd+2). To obtain the culture medium used for the production of exo-biopolymers, was tested a minimal medium salts of Vogel modified with different nitrogen sources and glucose defined as the only carbon source. Next, was performed a factorial design 3(3-0) with 27 experiments in duplicate, where the independent variables were the time and temperature of cultivation and the initial concentration of glucose. Colletotrichum sp. had the highest production of exo-biopolymer (5.71 gL-1) using urea as the nitrogen source in cultivation at 28 ºC, 150 rpm, and glucose 6% (w/v) in 192 hours of culture. The implementation of the factorial design showed that the dry biomass production was enhanced by a range of temperatures and initial concentration of glucose between 24 and 32 ºC and 35 and 75 gL-1, respectively. The production of exobiopolymer was favored by a range of temperatures and initial concentration of glucose between 24 and 36 ºC and 35 and 70 gL-1, respectively. In the experiment, the fungus Colletotrichum sp. produced 6.11 gL-1 of... (Complete abstract click electronic access below) / Mestre

Este trabalho apresenta o desenvolvimento de algoritmos de adaptação do padrão de marcha com a utilização de redes neurais artificiais para uma órtese ativa para membros inferiores. Trajetórias estáveis são geradas durante o processo de otimização, considerando um gerador de trajetórias baseado no critério do ZMP (Zero Moment Point) e no modelo dinâmico do equipamento. Três redes neurais são usadas para diminuir o tempo de cálculo do modelo e da otimização do ZMP, e reproduzir o gerador de trajetórias analítico. A primeira rede aproxima a dinâmica do modelo fornecendo a variação de torque necessária para a realização do processo de otimização dos parâmetros de adaptação da marcha; a segunda rede trabalha no processo de otimização, fornecendo o parâmetro otimizado de acordo com a interação paciente-órtese; a terceira rede reproduz o gerador de trajetórias para um determinado intervalo de tempo do passo que pode ser repetido para qualquer quantidade de passos. Além disso, um controle do tipo torque calculado acrescido de um controle PD é usado para garantir que as trajetórias atuais estejam seguindo as trajetórias desejadas da órtese. O modelo dinâmico da órtese na sua configuração atual, com forças de interação incluídas, é usado para gerar resultados simulados. / This work deals with neural network-based gait-pattern adaptation algorithms for an active lower limbs orthosis. Stable trajectories are generated during the optimization process, considering a trajectory generator based on the Zero Moment Point criterion and on the dynamic model. Additionally, three neural network are used to decrease the time-consuming computation of the model and ZMP optimization and to reproduce the analitical trajectory generator. The first neural network approximates the dynamic model providing the necessary torque variation to gait adaptation parameters process; the second network works in the optimization procedure, giving the adapting parameter according to orthosis-patient interaction; and the third network replaces the trajectory generation for a stablished step time interval which can be reproduced any time during the walking. Also, a computed torque controller plus the PD controller is designed to guarantee the actual trajectories are following the orthosis desired trajectories. The dynamic model of the actual active orthosis, with interaction forces included, is used to generate simulation results.

This study examines the extent of the impact of proficiency and language use on sociophonetic variation in Indian English (IE). It is based on an oral corpus using the methods and tools of the PAC project and derived from a pool of South Delhi-based highly proficient speakers. The investigation was conducted using quantitative and qualitative methods and focused on two understudied variables: (1) the fricative realisation of th, and (2) the realisations of the vowels in words of the NORTH and FORCE lexical sets. First, the results demonstrate that a significant amount of variation which cannot be accounted for by the traditional age, gender and social class factors can be explained by the language use parameter. A degree of correlation was found between the volume of use of English in a range of domains, and how speakers take advantage of the sociolinguistic potential of prestigious forms. This offers indications on the location of the leaders of the linguistic change. The second central feature of this study is derived from the investigation of the NORTH versus FORCE distinction. It is argued that the general maintenance of this distinction in IE provides evidence for the endo-normative nature of this variety. In the light of these findings, issues ultimately relating to the debate over nativeness are discussed.

No description available.

This thesis deals with development of guidance laws for advanced applications. Two class of guidance problems, namely, impact angle constrained guidance and pulsed guidance for exo-atmospheric engagements, are considered here. Three impact angle constrained guidance schemes are developed using (i) Proportional navigation guidance (PNG), (ii) State Dependent Riccati Equation (SDRE) technique and (iii) geometric concepts, respectively. A collision course based pulsed guidance law is presented for exo-atmospheric interceptors. Proportional Navigation Guidance (PNG) law is the most widely used guidance law because of its ease of implementation and efficiency. However, in its original form, it achieves only a limited set of impact angles. A two stage PNG law is presented for achieving all impact angles against a stationary target. In the first phase of guidance, an orientation PNG command is used. The orientation navigation constant (N ) is a function of the initial engagement geometry and has a lower value (N less than 2). It is proved that following the orientation trajectory, the interceptor can switch to N = 2 and achieve the desired impact angle. Simulations, with a constant speed and with a realistic interceptor model, show successful interception of the target with all desired impact angles. Feedback implementation of the guidance law results in negligible errors in impact angle with uncompensated autopilot delays. The idea of a two-stage PNG law with impact angle constraint is further used to develop a guidance law for intercepting moving targets. Following the orientation trajectory, the interceptor can switch to N = 3 and achieve the desired impact angle. It is proved that the guidance achieves all impact angles in a surface-to-surface engagement scenario with receding and approaching targets, respectively. In a air-to-surface engagement scenario, it is proved that the guidance law achieves all impact angles in a deterministic set. Constant speed and realistic interceptor models are used for simulations. Results show negligible error in impact angle and miss distance for moving targets. The guidance law, in its feedback implementation form, achieves the desired impact angle for interceptors with delay and with a maneuvering target. The impact angle errors are low with negligible errors in miss distance. Next, the impact angle constrained guidance problem against a stationary target is solved as a non-linear regulator problem using the SDRE technique. The interceptor guidance problems are of finite time nature. As the main contribution of this part of the work, we solve a finite time interceptor guidance problem with infinite horizon SDRE formulation by choosing the state weighting matrix as a function of time-to-go. Numerical simulations are carried out both for a constant speed interceptor model and a realistic interceptor model. Simulations for both the models are carried out for various impact angles and firing angles. Robustness of the proposed guidance law with respect to autopilot lag is also verified by simulations. Results obtained show the efficiency of the SDRE approach for impact angle constrained missile guidance. A geometric guidance scheme is proposed for lateral interception of targets in a planar engagement scenario in the absence of line-of-sight rate information. A kill-band is defined for target initial positions capturable by an arc maneuver, followed by a straight line path by the interceptor. Guidance law for capturing targets inside the kill-band is presented and is further modified for targets outside the kill-band. Based on analytical studies on the kill-band, a guidance law is proposed for lateral interception of maneuvering targets. Simulations are carried with for typical low speed engagements. The concept of kill-band provides an inherent robustness to the proposed guidance law with respect to uncompensated system delays and target maneuver. As the final part of the work, an interceptor endgame pulsed guidance law for exoatmospheric engagements is derived by using the notion of collision heading. The proposed guidance law is derived in steps by (i) Obtaining the collision heading based on the collision triangle engagement geometry and then (ii) Computing the width of the pulse fired by the divert thruster to attain the collision heading. It is shown that this strategy is more effective than the existing zero effort miss (ZEM) based guidance laws for intercepting targets with higher heading angles off the nominal head-on collision course. A result on pulse firing sequence is also presented showing that firing pulses in quick succession results in minimum pulse widths and hence minimum control effort for a desired miss distance. Simulations are carried out for various engagement scenarios. Results show better miss-distance and divert thrust performance as compared to the existing ZEM based law.

Made available in DSpace on 2014-06-11T19:27:20Z (GMT). No. of bitstreams: 0 Previous issue date: 2010-04-23Bitstream added on 2014-06-13T20:35:42Z : No. of bitstreams: 1 silva_lj_me_sjrp.pdf: 1135399 bytes, checksum: 5c78b7f4373a9244db399ef5e02efdad (MD5) / Conselho Nacional de Desenvolvimento Científico e Tecnológico (CNPq) / Os polímeros microbianos extracelulares (exo-biopolímeros) são moléculas que apresentam um grande potencial de aplicação nas indústrias de alimentos, farmacêuticas, petrolíferas, de cosméticos, têxteis, de papéis, tintas, produtos agrícolas entre outras. Como biorremediadores, podem ser utilizados na remoção de metais pesados em ambientes aquáticos poluídos, atuando como agentes de biossorção por meio da acumulação de nutrientes a partir do meio ambiente. O objetivo do trabalho foi a produção de exobiopolímeros a partir de três Ascomicetos endofíticos (Colletotrichum sp., Guignardia sp. e Phomopsis sp.). Foi selecionado o fungo que apresentou a maior produção desse material biológico. Tanto esse exo-biopolímero quanto a biomassa foram avaliados quanto aos seus potenciais de biossorção dos íons metálicos chumbo (Pb+2) e cádmio (Cd+2). Para a obtenção do meio de cultivo utilizado para a produção de exo-biopolímeros, foram testados o meio mínimo de sais de Vogel modificado com diferentes fontes de nitrogênio definidas e glicose como única fonte de carbono. Em seguida, foi realizado um planejamento fatorial 3(3-0) com 27 experimentos em duplicata, onde as variáveis independentes foram o tempo, temperatura de cultivo e a concentração inicial de glicose. O fungo Colletotrichum sp. apresentou a maior produção de exo-biopolímero (5,71 gL-1) utilizando a uréia como fonte de nitrogênio, em cultivo a 28 ºC, 150 rpm e glicose 6 % (p/v) em 192 horas de cultivo. A execução do planejamento fatorial demonstrou que a produção de biomassa seca foi favorecida por faixas de temperatura e concentração inicial de glicose entre 24 e 32 ºC e 35 e 75 gL-1, respectivamente. A produção de exo-biopolímero foi favorecida por faixas de temperatura e concentração... / The microbial extracellular polymer (exo-biopolymers) are molecules that have a great potential for application in the industries of food, pharmaceutical, oil, cosmetics, textiles, paper, paints, agricultural products and others. As bioremediation, can be used in the removal of heavy metals in polluted aquatic environments, acting as agents of bioremediation through the accumulation of nutrients from the environment. Objective of this study was to produce exo-biopolymer from three endophytic Ascomycota (Colletotrichum sp., Guignardia sp. and Phomopsis sp.). Then, was selected the fungus that showed the highest production of exobiopolymer. Both the exo-biopolymer and biomass were assessed for their potential of biosorption of metallic ions lead (Pb+2) and cadmium (Cd+2). To obtain the culture medium used for the production of exo-biopolymers, was tested a minimal medium salts of Vogel modified with different nitrogen sources and glucose defined as the only carbon source. Next, was performed a factorial design 3(3-0) with 27 experiments in duplicate, where the independent variables were the time and temperature of cultivation and the initial concentration of glucose. Colletotrichum sp. had the highest production of exo-biopolymer (5.71 gL-1) using urea as the nitrogen source in cultivation at 28 ºC, 150 rpm, and glucose 6% (w/v) in 192 hours of culture. The implementation of the factorial design showed that the dry biomass production was enhanced by a range of temperatures and initial concentration of glucose between 24 and 32 ºC and 35 and 75 gL-1, respectively. The production of exobiopolymer was favored by a range of temperatures and initial concentration of glucose between 24 and 36 ºC and 35 and 70 gL-1, respectively. In the experiment, the fungus Colletotrichum sp. produced 6.11 gL-1 of... (Complete abstract click electronic access below)