Generation of testbenches for large DSP behavioral models is a complicated, labor intensive task. Also, tests generated manually satisfy no formal definition of completeness. To address these needs, high level approaches to test bench development are employed which relieve the modeler of the details of test bench development. Two basic approaches that are used currently for testbench development are behavioral and structural testbench development. This thesis concentrates on the development of a methodology for modeling a set of behavioral testbenches. Here, a CASE tool, I-Logix Express V-HDL, is used to model state-machine as well as data flow behavior of the testbench and then dump the corresponding VHDL code automatically. Two approaches are followed for the generation of data values for the inputs to the testbenches: 1) File I/O and 2) User interaction. This thesis also describes the development of an intelligent user interface (in C) which prompts the user for the input data values and combines this information with the testbench code. The intelligent interface also allows the user to specify and control file I/O as a data source. As an implementation of this methodology, testbenches for the following two DSP applications have been developed and are described here : 1) Infra-Red Search and Track algorithm and 2) Synthetic Aperture Radar. / Master of Science

Nature’s biodiversity is complex and filled with beauty and wonder which are all observable on the macroscopic scale. This exquisiteness of nature’s intricacies are mirrored on the molecular level such that substances, large or small, are assembled to serve as signaling molecules, protective agents, and fundamental composites of higher-order frameworks for the operation and survival of life. Over the years, chemists have isolated and synthesized these molecules, known as natural products, to understand and evaluate their functions in biology and potential for medicinal applications. Although bioactive natural products demonstrate medicinal promise, poor pharmacological effects require further derivatization because semisynthesis is not sufficient to refine adverse pharmacokinetics. For some active molecules, isolation results in poor yields. In addition to small quantity isolation, many natural products, reflecting the immense complexity of biology itself, pose difficult synthetic challenges to organic chemists because of skeletal heterogeneity, stereochemical complexity, and substitution divergence. As a result of these synthetic obstacles to natural product utilization, improvements are needed in current chemical approaches, and new innovative methodologies for synthesis and chemical space exploration are necessary. Pharmaceutically relevant frameworks, natural products, and synthetic biologically active molecules are comprised of polycarbocyclic and heterocyclic scaffolds. Traditionally, cycloadditions, transannular transformations, and annulation reactions serve as powerful methods for polycyclic formation. In order to assemble diverse polycycles, donor-acceptor cyclopropanes are useful, versatile synthetic equivalents for C-C bond formations. By taking advantage of the strain within these unique, polarized systems, differing molecular architectures can be accessed directly to perform contemporary organic synthesis. Moreover, the donor-acceptor cyclopropanes initially utilized in these studies provided a fundamental basis for new methods to synthesize other relevant scaffolds. Unique, efficient, Lewis acid-catalyzed intramolecular cyclization strategies for the construction of functionalized polycycles using Friedel-Crafts-type alkylation sequences are presented to expand the reaction repertoire of the molecular architect. Generally, products were formed from commercially-available starting materials in high yields with broad scope. The methodologies were demonstrated to be modular, operationally simple, and amenable to different substitution patterns and functional groups to afford tetrahydroindolizines, heteroaromatic cyclohexenones, hydropyrido[1,2-a]indoles, pyrrolo[1,2-a]indoles, pyrrolo[3,2,1-ij]quinolines, pyrrolizines, and tetrahydrobenzo[ij]quinolizines. To demonstrate the utility of the methodologies devised, progress toward, (±)-rhazinicine, a natural product, is discussed. This dissertation is organized into six chapters: (1) an introduction, paradoxical stress and molecular strain’s utility in synthesis; (2) annulation reactions for the formation of heteroaromatic cyclohexenones; (3) hydropyrido[1,2-a]indole formation via an In(III)-catalyzed cyclopropane ring-opening/Friedel-Crafts alkylation sequence; (4) tetrahydroindolizine formation and progress toward the total synthesis of (±)-rhazinicine (5) pyrrolo[1,2-a]indole synthesis using a Michael-type Friedel-Crafts cyclization approach; and (6) a versatile protocol for the intramolecular formation of functionalized pyrrolo[3,2,1-ij]quinolines.

Este trabalho teve como principal objetivo o desenvolvimento da técnica de cromatografia líquida de alta eficiência para a análise SARA de amostras de petróleo. As amostras de petróleo foram separadas em frações contendo saturados, aromáticos, resinas e asfaltenos. Para se obter êxito no desenvolvimento da técnica de cromatografia líquida em escala preparativa, o primeiro passo foi o desenvolvimento da técnica em escala analítica. Os parâmetros encontrados foram então extrapolados para escala preparativa. Através da técnica de cromatografia líquida de alta eficiência desenvolvida, foi possível obter uma separação eficaz das frações SARA de amostras de petróleo, resultado que não se mostra tão eficiente quando se trabalha com cromatografia líquida clássica. As comparações entre as metodologias por cromatografia clássica de coluna aberta e cromatografia líquida de alta eficiência desenvolvida no trabalho mostram que a cromatografia líquida possui enorme vantagem em relação à metodologia clássica. Dentre elas podemos destacar a grande reprodutibilidade já que os parâmetros de análise são altamente controlados o que não ocorre em cromatografia de coluna aberta, além da capacidade de automação e menor risco ocupacional. As frações separadas foram caracterizadas por espectrometria de massas, espectroscopia de fluorescência e infravermelho. Através da espectrometria de massas foi possível observar uma distribuição de massas entre o intervalo de massa que vai do ion de m/z 100 Da até o íon de m/z 800 Da, com esta distribuição centrada em 350 Da. A espectrometria de massa aliada a software de identificação de componentes de frações de petróleo através de massas moleculares permitiu determinar a fórmula molecular dos compostos presentes nas frações de asfaltenos das amostras de petróleo analisadas. A análise realizada pelo programa gerou os seguintes resultados: o programa encontrou estrutura molecular para aproximadamente 60% dos picos contidos no espectro de massas, destes, 6,05% dos compostos encontrados possuíam enxofre, 45,2% dos compostos possuem N e 32,1% possuem oxigênio em sua composição. A análise dos espectros de emissão de fluorescência mostrou que petróleos mais leves apresentam emissão de fluorescência mais intensas isso se deve ao fato de que petróleos mais pesados, de menor API, possuem mais espécies propensas a desativar o estado excitado, justificando assim a diminuição da emissão de fluorescência com aumento do API. / This work had as main objective the development of the technique of high performance liquid chromatography for SARA analysis of oil samples. The oil samples were separated into fractions containing saturates, aromatics, resins and asphaltenes. To achieve successful development of the technique for preparative scale liquid chromatography, the first step was the development of the technique in analytical scale. The parameters obtained were then extrapolated to preparative scale. Through the technique of high performance liquid chromatography developed, it was possible to obtain an effective separation of SARA fractions of oil samples, a result that does not show as efficient when working with classical liquid chromatography. Comparisons between both methodologies, classical and HPLC has showed that HPLC has huge advantage over classical methods. The separated fractions were characterized by mass spectrometry, fluorescence spectroscopy and infrared. Through mass spectrometry was possible to observe a distribution of masses between the mass range that goes from the ion m / z 100 Da to the ion m / z 800 Da, with this distribution centered at 350 Da. The analysis of the fluorescence emission spectra showed that lighter oils exhibit more intense fluorescence emission that is due to the fact that heavier oils, smaller API, have more likely species to disable the excited state, thus justifying the reduction of emissions fluorescence with an increased API.

Este trabalho teve como principal objetivo o desenvolvimento da técnica de cromatografia líquida de alta eficiência para a análise SARA de amostras de petróleo. As amostras de petróleo foram separadas em frações contendo saturados, aromáticos, resinas e asfaltenos. Para se obter êxito no desenvolvimento da técnica de cromatografia líquida em escala preparativa, o primeiro passo foi o desenvolvimento da técnica em escala analítica. Os parâmetros encontrados foram então extrapolados para escala preparativa. Através da técnica de cromatografia líquida de alta eficiência desenvolvida, foi possível obter uma separação eficaz das frações SARA de amostras de petróleo, resultado que não se mostra tão eficiente quando se trabalha com cromatografia líquida clássica. As comparações entre as metodologias por cromatografia clássica de coluna aberta e cromatografia líquida de alta eficiência desenvolvida no trabalho mostram que a cromatografia líquida possui enorme vantagem em relação à metodologia clássica. Dentre elas podemos destacar a grande reprodutibilidade já que os parâmetros de análise são altamente controlados o que não ocorre em cromatografia de coluna aberta, além da capacidade de automação e menor risco ocupacional. As frações separadas foram caracterizadas por espectrometria de massas, espectroscopia de fluorescência e infravermelho. Através da espectrometria de massas foi possível observar uma distribuição de massas entre o intervalo de massa que vai do ion de m/z 100 Da até o íon de m/z 800 Da, com esta distribuição centrada em 350 Da. A espectrometria de massa aliada a software de identificação de componentes de frações de petróleo através de massas moleculares permitiu determinar a fórmula molecular dos compostos presentes nas frações de asfaltenos das amostras de petróleo analisadas. A análise realizada pelo programa gerou os seguintes resultados: o programa encontrou estrutura molecular para aproximadamente 60% dos picos contidos no espectro de massas, destes, 6,05% dos compostos encontrados possuíam enxofre, 45,2% dos compostos possuem N e 32,1% possuem oxigênio em sua composição. A análise dos espectros de emissão de fluorescência mostrou que petróleos mais leves apresentam emissão de fluorescência mais intensas isso se deve ao fato de que petróleos mais pesados, de menor API, possuem mais espécies propensas a desativar o estado excitado, justificando assim a diminuição da emissão de fluorescência com aumento do API. / This work had as main objective the development of the technique of high performance liquid chromatography for SARA analysis of oil samples. The oil samples were separated into fractions containing saturates, aromatics, resins and asphaltenes. To achieve successful development of the technique for preparative scale liquid chromatography, the first step was the development of the technique in analytical scale. The parameters obtained were then extrapolated to preparative scale. Through the technique of high performance liquid chromatography developed, it was possible to obtain an effective separation of SARA fractions of oil samples, a result that does not show as efficient when working with classical liquid chromatography. Comparisons between both methodologies, classical and HPLC has showed that HPLC has huge advantage over classical methods. The separated fractions were characterized by mass spectrometry, fluorescence spectroscopy and infrared. Through mass spectrometry was possible to observe a distribution of masses between the mass range that goes from the ion m / z 100 Da to the ion m / z 800 Da, with this distribution centered at 350 Da. The analysis of the fluorescence emission spectra showed that lighter oils exhibit more intense fluorescence emission that is due to the fact that heavier oils, smaller API, have more likely species to disable the excited state, thus justifying the reduction of emissions fluorescence with an increased API.

Thesis advisor: Peter X. Zhang / Thesis advisor: James P. Morken / Radical reactions have attracted continuous research interest in recent year considering their diverse reactivities. Hydrogen-atom abstraction (HAA), as one type of the most well-explored radical reactions, has been identified as one of powerful tools for C–H functionalization. Reactions involving 1,4-HAA, which is typically a challenging process both entropically and enthalpically, are rather scarce, while 1,5-HAA have been well demonstrated for variety of synthetic applications. Guided by the concept of metalloradical catalysis (MRC), 1,4-HAA was for the first time utilized as the key step to achieve asymmetric construction of chiral ring structures: cyclobutanones, azetidines and tetrahydropyridines. The design of different D2-symmetric chiral amidoporphyrin as the supporting ligand is the key to all these transformations. The reactions can be conducted under mild conditions, affording corresponding ring structure in good yields with excellent selectivity. Furthermore, The combined computational and experimental studies have shed light on the mechanistic details of these new asymmetric radical intramolecular C–H alkylation processes, which are fundamentally different from existing catalytic systems involving metallocarbenes for concerted C–H insertion. We envision that these asymmetric radical processes via Co(II)-based MRC could become an alternative method for important chiral ring structures synthesis and potentially provide new opportunities for complex molecule construction. / Thesis (PhD) — Boston College, 2022. / Submitted to: Boston College. Graduate School of Arts and Sciences. / Discipline: Chemistry.

Small-molecule libraries with enhanced structural diversity are of value in drug discovery campaigns where novel biologically active hits are desired. As such, multicomponent reactions (MCRs) have proven fruitful to enhance the molecular diversity of chemical collections and expedite forward progression of the drug discovery chain. Bicalutamide (Casodex), an anticancer drug, and Telaprevir (Incivek), an antiviral, are two examples of marketed drugs that can be synthesized using an MCR. The research topic of this dissertation involves the design, discovery, and development of novel MCRs and new combinations of MCRs with post-condensation modifications to generate over twenty-five new drug-like scaffolds in an operationally friendly, atom-economical, time- and cost-effective fashion. The developed chemical methodologies possess inherent 'iterative efficiency','high exploratory power', and 'bond forming efficiency' that allow them to quickly explore chemical space and navigate the 'hypothesis-synthesis-screening' loop that is key for a medicinal chemistry project. The prepared molecules were submitted to the Community for Open Antimicrobial Drug Discovery (CO-ADD) for antimicrobial screening against pathogens that are known to cause drug-resistance infections.

is thesis explores the overarching topic of the capacity of strategic urban development decisions and initiatives (including planning initiatives) to positively and powerfully influence the ability of a city to promote sustainable patterns of development. The work is presented in six scientific papers, the first four of which focus on the development of an inter-disciplinary conceptual framework and research methodology. The concept of Situations of Opportunity and its related Field of Options is proposed as a means to identify and analyse periods in the growth of cities when urbanisation can be more easily managed so as to promote sustainable development goals. Historical studies in the cities of Stockholm, Dar es Salaam and Curitiba are used to develop the methodology. Another paper looks ahead and refines the methodology in combination with future studies, presenting a research strategy that employs Situations of Opportunity as a means to identify and explore periods in the future urban growth with significant potential for change. Building on the method developed, the remaining two papers consider the social dimension of sustainable development and how it can be promoted in the urban context, during ongoing Situations of Opportunity. The concept of social sustainability is reviewed and discussed from two different disciplinary perspectives (urban development; companies and products), exploring commonalities and differences in approaches, and identifying core themes that cross disciplinary boundaries. A case study of Eastside, a brownfield redevelopment site in Birmingham (UK), reveals how the retention of established small food outlets can provide opportunities for promoting social sustainability goals in an urban regeneration area. Overall, this thesis provides a better understanding of how transformative change can happen in cities. The Situations of Opportunity concept developed here can be a helpful way to study strategic initiatives that promote sustainability in cities. / <p>QC 20101216</p>

Made available in DSpace on 2014-07-29T16:11:45Z (GMT). No. of bitstreams: 1 Dissertacao Julliana Rodrigues Moura.pdf: 204207 bytes, checksum: 56a1561a44aeb00b316511d72cd22e73 (MD5) Previous issue date: 2009-12-14 / Olanzapine is an antipsychotic active ingredient and its marketing in Brazil, in the form of terminated product, is protected by patent up to 2011. As it is recent in the pharmaceutical market and there is not a methodology described in officials forms that is capable of assuring the quality of new formulations, the objective of this paper was to characterize Olanzapine physical-chemical parameters, to develop and validate, in accordance with RE N°899, from May 29 th 2003, the analytical methodology for assay and dissolution and to apply the developed and validated methodologies in the pharmacotechnical development of tablets. It was characterized some physicalchemical parameters of solubility and of light absorption (from 200 to 400nm) in several solvents and it was developed and validated assay and dissolution methodologies by spectrophotometry with ultraviolet detection (UV) and the assay by high efficiency liquid chromatography with ultraviolet detection (HPLC-UV) for the quantification of olanzapine present in film coated tablets of 2.5, 5.0 and 10.0mg. The active ingredient presented a low solubility in water and the wave lengths of maximum light absorption were within the range of 254 and 273nm. For the dissolution methodology by UV spectrophotometry, the parameters were chloride acid 0.1 mol/L as the dissolution media, volume of 1,000mL (5 and 10mg of Olanzapine) and 500mL (2.5mg of Olanzapine), apparatus II (paddles) and a rotation of 50 rpm. The spectrophotometric parameters were chloride acid 0.1 mol/L as blank and 259nm of wave length. For the assay methodology by UV spectrophotometry, it was used as a solvent and as a blank solution chloride acid 0.1 mol/L and a wave length of 259nm. It was used a ProStar 210 UV/VIS VARIAN high efficient liquid chromatographer, a C18 (150x4,6)mm 5&#956;m column in room temperature (25ºC), a flux of 0,8mL/min, a wave length of 254nm and a mobile phase constituted of a mixture of monobasic potassium phosphate buffer 0,01 mol/L pH 2,5 and acetonitrile (70:30) for the assay methodology by HPLC-UV. The results found from the parameters of specificity, linearity, accuracy, precision, quantification and detection limits and stability in the methodologies validations confirm that they were adequate for the purpose proposed. The methodologies developed and validated were applied in Olanzapine determination in several formulation propositions which have been developed and they assisted the pharmacotechnical development team in the definition of the best olanzapine formulation in the 2.5mg strength. / A olanzapina é um fármaco antipsicótico e sua comercialização no Brasil, na forma de produto acabado, está protegida por patente até 2011. Como é recente no mercado farmacêutico e não há descrição da metodologia em formulários oficiais capazes de assegurar a qualidade das novas formulações, o objetivo deste trabalho foi caracterizar os parâmetros físico-químicos da olanzapina, desenvolver e validar, segundo RE N°899, de 29 de maio de 2003, método analítico para doseamento e dissolução e aplicar os métodos desenvolvidos e validados no desenvolvimento farmacotécnico dos comprimidos. Foram caracterizados alguns parâmetros físico-químicos, de solubilidade e de absorção da luz (200 a 400 nm) em diversos solventes e foram desenvolvidos e validados métodos de doseamento e dissolução por espectrofotometria com detecção ultravioleta (UV) e de doseamento por cromatografia líquida de alta eficiência com detecção ultravioleta (HPLC-UV) para quantificação de olanzapina presente em comprimidos revestidos de 2,5, 5,0 e 10,0 mg. O fármaco apresentou baixa solubilidade em água e os comprimentos de onda de máxima absorção da luz ficaram entre 254 e 273 nm. Para o método de dissolução por espectrofotometria UV, os melhores parâmetros foram ácido clorídrico 0,1 mol/L como meio de dissolução, volume de 1.000 mL (5 e 10 mg de Olanzapina) e 500mL (2,5mg de Olanzapina), aparato II (pás) e rotação de 50rpm. Os parâmetros espectrofotométricos foram ácido clorídrico 0,1 mol/L como branco e 259nm de comprimento de onda. Para o método de doseamento por espectrofotometria UV foi utilizado como solvente e solução branco ácido clorídrico 0,1 mol/L e comprimento de onda de 259 nm. Foi utilizado cromatógrafo líquido de alta eficiência ProStar 210 UV/VIS VARIAN, coluna C18 (150x4,6) mm 5&#956;m a temperatura ambiente (25ºC), fluxo de 0,8mL/min, comprimento de onda de 254 nm e fase móvel constituída por uma mistura de tampão fosfato de potássio monobásico 0,01 mol/L pH 2,5 e acetonitrila (70:30) para o método de doseamento por HPLC-UV. Os resultados encontrados dos parâmetros de especificidade, linearidade, exatidão, precisão, limites de quantificação e detecção e estabilidade nas validações dos métodos confirmam que os mesmos foram adequados para a finalidade proposta. Os métodos desenvolvidos e validados foram aplicados na determinação de olanzapina em várias propostas de formulações que foram desenvolvidas e auxiliou a equipe de desenvolvimento farmacotécnico na definição da melhor formulação da olanzapina na concentração de 2,5mg.

This thesis focuses on methodology development using N-sulfinyl metallodienamines and metalloenamines derived from Davis-Ellman N-sulfinyl imines. The application of these methodologies toward the total syntheses of (+)-epiibogamine and (+)-chimonanthine is described. The vinylogous aldol reaction of N-sulfinyl metallodienamines was first reported in 2017 in the total synthesis of (−)-albocycline. However, the diastereoselectivity of this reaction was found to be incorrectly reported. Mosher ester analysis and HPLC analysis with a chiral column were employed to determine the dr. The vinylogous aldol reaction was optimized. Studies on the mechanisms affecting stereoselectivity revealed that stereochemical erosion occurred using SnCl4 combined with LiHMDS, but not with NaHMDS or KHMDS. A (Z)-metallodienamine with metal chelated transition state was proposed and supported by DFT calculations to rationalize the stereochemical course of the reaction. Iboga alkaloids have been historically used for anti-addictive properties and recently brought more attention as potential drug candidates for neurological disorders. However, the complex isoquinuclidine fused azapine scaffold of Iboga alkaloids are challenging to synthesize. To construct the key chiral 2-aminocyclohexene intermediate and isoquinuclidine ring more efficiently, three new methods were explored. These included the domino-Michael/Mannich annulation of N-sulfinyl metallodienamines, the Diels-Alder reaction of N-sulfinyl imines, and the three-component domino-Michael/Michael/Mannich (DM3) annulation of N-sulfinyl metalloenamines. The DM3 reaction provided the 1-amino-2,4-diester scaffold to access isoquinuclidine in high yield (84−94%) and excellent diastereoselectivity (up to >95:5 dr). Chiral N-sulfinyl silylenamines, were introduced to serve as a surrogate for poorly reacting N-sulfinyl aldimines in the DM3 reaction. This silyl-modified DM3 reaction enabled the shortest asymmetric total synthesis of (+)-epiibogamine in 7 steps. This isoquinuclidine intermediate would also provide access to (+)-dihydrocatharanthine and other Iboga alkaloids in future studies. Oxidative enolate coupling, via radical intermediates, was used to construct 1,4-dicarbonyl scaffold from the reaction between two enolate nucleophiles. An oxidative coupling of N-sulfinyl metalloenamines was discovered having the ability to construct vicinal quaternary stereocenters in high diastereoselectivity (16:1 dr). To showcase this new methodology, the synthesis of dimeric indole alkaloids, (+)-chimonanthine, was investigated. A new class of compounds, bis N-sulfinyl amidines, were prepared as the potential oxidative coupling monomers for the synthesis of (+)-chimonanthine in future studies. / Chemistry

Nosso objetivo foi desenvolver um método para atestar a presença ou ausência de seis espécies de aves (Basileuterus leucoblepharus, Batara cinerea, Carpornis cucullatus, Chiroxiphia caudata, Pyriglena leucoptera e Trogon surrucura) em fragmentos florestais. Foi determinado o horário do dia e época do ano em que o play-back é mais eficiente em atestar a presença dessas aves. Os testes ocorreram na Reserva Florestal do Morro Grande (Cotia, SP). Três horários foram testados (manhã, meio do dia e tarde) ao longo de um ano. O teste G verificou a variação de eficiência entre os diferentes horários, e o teste de Rayleigh a variação anual. A manhã e o meio do dia apresentaram-se mais eficientes que a tarde para B. leucoblepharus, C. caudata e T. surrucura. A única ave a apresentar uma época do ano mais eficiente foi B. cinerea. Para avaliar sua eficiência, a capacidade do método em atestar a presença das aves em 13 fragmentos foi correlacionada com sua abundância nos mesmos. Os testes ocorreram quatro vezes em cada área nos momentos de maior eficiência. Os resultados indicam que C. caudata seja recenseada pelo menos duas vezes por fragmento. Três visitas é o mínimo para B. cinerea, B. leucoblepharus, P. leucoptera e T. surrucura. Para C. cucullatus deve-se ser repetir quatro vezes. O método foi criado para gerar rapidamente dados de presença e ausência em grande quantidade de fragmentos. Essa informação pode auxiliar estudos sobre dinâmica de metapopulações destas espécies. / In order to provide rapid access to presence/absence data of six species of birds (Basileuterus leucoblepharus, Batara cinerea, Carpornis cucullatus, Chiroxiphia caudata, Pyriglena leucoptera and Trogon surrucura) inside forest fragments, an efficient playback method was developed. The broadcast of these birds’ vocalizations was carried out at the Morro Grande Forrest Reserve (Cotia, SP). Playback tests were executed three times a day (sunrise, noon and before sunset) during one year. Daily and seasonal variations in the efficiency of the play-back were tested with G-statistics and the Rayleigh test. Sunrise and noon were more efficient than the period before sunrise to B. leucoblepharus, C. caudata and T. surrucura. The only species to show an annual period of higher rate of response was B. cinerea. To evaluate the real efficiency of the method, 13 forest fragments were surveyed for presence of these birds. The data was compared to the abundance of the birds in these areas. Each fragment was surveyed four times. At least two surveys are needed for C. caudata. Three surveys are the minimum effort to access the distributional pattern of B. leucoblepharus, B. cinerea, P. leucoptera and T. surrucura. Due to its rarity, C. cucullatus must be censused not less than four times. The method developed in the current study was created to provide a rapid access to the patch occupancy patterns of these six species in a large number of fragments. That kind of data may be very useful in studies about metapopulation dynamics and conservation ecology.