Leptospiras são bactérias espiroquetas altamente móveis dotadas de estratégias que possibilitam grande eficiência nos processos de invasão e disseminação no hospedeiro. Nosso grupo demonstrou previamente que leptospiras patogênicas secretam proteases capazes de clivar e inativar moléculas-chave do sistema complemento humano, o que confere a essas bactérias a capacidade de driblar os mecanismos de defesa do sistema imune inato. Dada a rápida disseminação das leptospiras durante o processo de infecção, aventou-se a hipótese de que essas proteases secretadas pudessem alvejar uma gama maior de moléculas do hospedeiro. No presente estudo, a atividade proteolítica de proteínas secretadas por leptospiras sobre um painel de moléculas da matriz extracelular e do plasma foi avaliada. O sobrenadante de cultura da estirpe virulenta L. interrogans sorovar Kennewicki Fromm degradou fibrinogênio humano, fibronectina plasmática, colágeno Tipo I, e as proteoglicanas decorina, biglicam e lumicam. A atividade proteolítica foi inibida por 1,10-fenantrolina, sugerindo o envolvimento de metaloproteases. Laminina, matrigel, plasminogênio e trombina não foram clivados por proteases presentes nos sobrenadantes. Ainda, os dados indicam que a produção de proteases deve ser um determinante de virulência importante, uma vez que os sobrenadantes de estirpes saprófitas ou patogênicas atenuadas em cultura não apresentaram atividade proteolítica sobre componentes da matriz ou do plasma. A análise dos genomas de leptospiras disponíveis nos levou à identificação de quatro termolisinas, metaloproteases presentes apenas nas espécies patogênicas. Uma delas, codificada pele LIC13322, foi produzida na forma recombinante e apresentou atividade proteolítica sobre fibrinogênio, biglicam e decorina. Em paralelo, foram também realizadas análises comparativas dos exoproteomas das estirpes Fromm e Patoc I. Algumas metaloproteases que podem estar envolvidas na degradação de moléculas do hospedeiro foram identificadas. A capacidade de clivar moléculas do tecido conjuntivo e proteínas da cascata de coagulação pode certamente contribuir para a invasão e a destruição tecidual observadas durante a infecção por Leptospira. / Leptospires are highly motile spirochetes equipped with strategies for efficient invasion and dissemination within the host. Our group previously demonstrated that pathogenic leptospires secrete proteases capable of cleaving and inactivating key molecules of the human complement system, allowing these bacteria to circumvent host´s innate immune defense mechanisms. Given the successful dissemination of leptospires during infection, we wondered if such proteases would target a broader range of host molecules. In the present study, the proteolytic activity of secreted leptospiral proteases against a panel of extracellular matrix and plasma proteins was assessed. The culture supernatant of the virulent L. interrogans serovar Kennewicki strain Fromm degraded human fibrinogen, plasma fibronectin, collagen Type 1, and the proteoglycans decorin, biglycan, and lumican. Proteolytic activity was inhibited by 1,10-phenanthroline, suggesting the participation of metalloproteases. Laminin, matrigel, plasminogen and thrombin were not cleaved by proteases present in the supernatants. Moreover, production of proteases might be an important virulence determinant since culture-attenuated or saprophytic Leptospira did not display proteolytic acticity against ECM or plasma components. A search against Leptospira genomes allowed identification of four thermolysins, which are metalloproteases found exclusively in pathogenic species. One of them, encoded by LIC13322, was produced in the recombinant form and displayed proteolytic activity against fibrinogen, biglycan and decorin. Comparative exoproteomic analyses using Fromm and Patoc I strains were also performed and allowed identification of a few metalloproteases that could be involved in the degradation of host components. The ability to cleave connective tissue molecules and coagulation cascade proteins may certainly contribute to invasion and tissue destruction observed upon infection with Leptospira.

O capítulo 1 descreve o estudo da biorredução do grupo carbonílico de cetoazidas e β-ceto-1,2,3-triazois para a produção de β-hidroxi-1,2,3-triazois enantiomericamente puros ou enriquecidos. Cinco linhagens de fungos de origem marinha foram avaliadas para a redução da 2-azido-1-feniletanona 1 e duas linhagens, A. sydowii CBMAI 935 e M. racemosus CBMAI 847, foram selecionadas também para a biorredução das 2-azido-1-feniletanonas 2-4 para a produção dos (R)- e (S)-2-azido-1-feniletanois 2a-4a. Os azidoálcoois enantiomericamente enriquecidos obtidos 1a-4a das reações biocatalíticas foram empregados como material de partida para a síntese dos β-hidroxi-1,2,3-triazois 7a-10a enantiomericamente enriquecidos através da click reaction entre a azida terminal e o alcino, fenilacetileno. Uma segunda abordagem para a obtenção de β-hidroxi-1,2,3-triazois enantiomericamente enriquecidos foi o estudo da biorredução de β-ceto-1,2,3-triazois, que são cetonas contendo dois substituintes volumosos. Uma triagem inicial para a biorredução do β-ceto-1,2,3-triazol 7 foi realizada com seis linhagens de fungos de origem marinha, na qual a linhagem do fungo P. citrinum CBMAI 1186 foi selecionada para estudos de otimização da reação biocatalítica. Estudos com variação do meio reacional, utilização de co-solvente e efeito do pH mostraram que as condições ótimas de reação foram utilizando-se tampão fosfato (Na2HPO4/KH2PO4, 0,07 M) em pH 5 e metanol 5% (v/v) como co-solvente. O fungo P. citrinum CBMAI 1186 foi empregado na biorredução dos β-ceto-1,2,3-triazois 8-12 com excelentes resultados de rendimento e seletividade para a produção dos (S)-β-hidroxi-1,2,3-triazois 8a-12a. O Capítulo 2 apresenta a síntese multienzimática da diidropinidina, um alcaloide de origem natural. A nonano-2,6-diona utilizada como material de partida foi obtida através da descarboxilação do dicetoéster, 2-butiril-5-oxo-hexanoato de etila. Estudos para a otimização tanto da síntese do dicetoéster quanto da etapa de descarboxilação foram realizados. Condições ótimas de produção do 2-butiril-5-oxo-hexanoato de etila foram obtidas através da reação da but-3-em-2-ona com o 3-oxo-hexanoato de metila catalisada por CeCl3/NaI. A descarboxilação do dicetoéster foi avaliada através do método de Krapcho empregando-se sais de cloro e água em altas temperaturas, entretanto, a elevada formação de subprodutos estimulou a busca por uma diferente metodologia para a obtenção da nonano-2,6-diona. Foram avaliadas diferentes lipases e esterases para a hidrólise enzimática do dicetoéster seguida por descarboxilação por HCl, na qual a esterase de fígado de porco foi selecionada e promoveu a hidrólise de até 1,6 M de dicetoéster para a produção da nonano-2,6-diona. Diferentes transaminases (TAs) foram estudadas para a aminação redutiva assimétrica da nonano-2,6-diona e duas linhagens foram selecionadas para a produção da (R)- e (S)-2-metil-6-propil-2,3,4,5-tetra-hidropiridina, as TAs de Arthrobacter sp. e Arthrobacter citreus, respectivamente empregando-se isopropilamina como amino doador. As (R)- e (S)-2-metil-6-propil-2,3,4,5-tetra-hidropiridina foram avaliadas pela redução assimétrica para a síntese da diidropinidina por imina redutases (IREDs) e duas linhagens foram selecionadas, a IRED de Mesorhizobium sp. e Norcardiopsis alba, respectivamente. TAs e IREDs foram acopladas em um sistema one-pot multienzimático utilizando como material de partida a nonano2,6-diona (100 mM) para a obtenção dos isômeros cis da diidropinidina com excelentes excessos diastereoisoméricos. / The Chapter 1 describes the bioreduction of the carbonyl group of ketoazides and β-keto-1,2,3-triazoles to produce enantiomerically pure or enriched β-hydroxy-1,2,3-triazoles. Five marine-derived fungi strains were screened to perform the reduction of 2-azido-1-phenylethanone 1. The strains from A.sydowii CBMAI 935 and M. racemosus CBMAI 847 were selected for the bioreduction of the 2-azido-1-phenylethanones 2-4 to yield the (R)- and (S)-2-azido-1-phenylethanols 2a-4a. The enantiomerically enriched azidoalcohols 1a-4a obtained from biocatalytical reactions were used as starting materials for the synthesis of enantiomerically enriched β-hydroxy-1,2,3-triazoles 7a-10a through the click reaction between the terminal azide and phenylacetylene. A second approach for obtaining enantiomerically enriched β-hydroxy-1,2,3-triazoles was the bioreduction of β-keto-1,2,3-triazoles, which are ketones with two bulky substituents. The screening for the bioreduction of the β-keto-1,2,3-triazol 7 was performed with six marine-derived fungi strains and P. citrinum CBMAI 1186 was selected for the optimization studies for the biocatalytic reduction of β-keto-1,2,3-triazoles 8-12.Studies about the composition of reaction medium, use of cosolvent and pH effect showed that the optimal conditions was in phosphate buffer (Na2HPO4/KH2PO4, 0.07 M) at pH 5 and methanol 5% (v/v) as cosolvent. P. citrinum CBMAI 1186 was applied to the bioreduction of β-keto-1,2,3-triazoles 8-12 and good yields and selectivities were obtained for the (S)-β-hydroxy-1,2,3-triazoles 8a-12a. The Chapter 2 describes the multienzymatic synthesis of dihydropinidine, a natural alkaloid. The nonane-2,6-dione used as starting material was obtained through the reduction of the diketoester, methyl butyryl-5-oxohexanoate, and the optimization studies for both diketoester synthesis and decarboxylation reaction were performed. Optimal conditions for the synthesis of methyl butyryl-5-oxohexanoate were obtained by the reaction between but-3-en-2-one and 3-oxohexanoate catalyzed by CeCl3/NaI. The diketoester decarboxylation step was evaluated by the Krapcho method using chlorine and water at high temperatures. However, because of the production of side products by this method, a different procedure for the synthesis of nonane-2,6-dione was studied. Different enzymes (lipases and esterases) were evaluated for the diketoester hydrolysis followed by decarboxylation by HCl. The porcine liver esterase was selected to promote the diketoester hydrolysis up to 1.6 M, yielding nonane-2,6-dione. Different transaminases (TAs) were applied to the asymmetric reductive amination of the nonane-2,6-dione and TAs from Arthrobacter sp. e Arthrobacter citreus were selected for the production of (R)- and (S)-2-methyl-6-propyl-2,3,4,5-tetrahydropyridine, respectively, using isopropylamine as the amine donor. The asymmetric reduction of (R)- and (S)-2-methyl-6-propyl-2,3,4,5-tetrahydropyridine by imine reductases (IREDs) was evaluated and the IREDs from Mesorhizobium sp. and Norcardiopsis alba were selected. TAs and IREDs were coupled in multienzymatic one-pot system using nonane-2,6-dione (100 mM) as starting material for the syntheses of cis isomers of dihydropinidine in excellent diastereoisomeric excess.

O gerenciamento dos estoques pesqueiros, um dos instrumentos da biomanipulação, deve ter início com a classificação das espécies existentes e sua diversidade, a estrutura da rede alimentar e as relações reguladoras, como a relação predador-presa. O lago Paranoá (Brasília - DF) é um reservatório urbano que sofre pressões antrópicas devido a seus usos múltiplos. Após a construção enchimento, sucessivas introduções de espécies ictíicas exóticas causaram um desequilíbrio que, associado às pressões descritas acima, geraram uma aceleração no processo de eutrofização deste ambiente. Desta forma, os objetivos deste trabalho foram: avaliar os impactos ambientais da introdução das espécies predadoras sobre a cadeia trófica e a qualidade da água do reservatório; determinar a eficiência das diferentes espécies de predadores no controle das presas nas áreas marginais da represa, discutindo possíveis estratégias de manejo pesqueiro baseadas na estocagem de peixes predadores. Para tanto foram construídos 10 limnocurrais com lonas impermeáveis numa baía localizada no ETE-Norte (Estação de tratamento de esgotos - Norte). Em seu interior, após a retirada de todos os peixes, foram estocadas por um período de 28 dias, duas espécies de predadores (Cichla ocellaris e Pseudoplatytoma fasciatum) e uma comunidade simplificada de presas (Tilapia rendalli e Oreochromis niloticus), acima da capacidade do suporte do sistema, definida em 4 classes de tamanho. As biomassas de estocagem foram determinadas a partir da aplicação de retenona em uma área com dimensões conhecidas, e extrapoladas para as áreas dos limnocurrais. As variáveis físicas e químicos da água foram acompanhados semanalmente durante o experimento. Não houve diferenças significativas entre os tratamentos, em relação às variáveis limnológicas. Quanto ao controle das presas, o tucunaré mostrou-se um predador eficiente em relação às classes de tamanhos menores ) (2 - 6,9 cm e 7 - 12,9 cm), fato não observado para o tratamento com surubim. De acordo com os resultados obtidos, não foi comprovada a hipótese de cascata trófica devido à complexidade das interações entre os organismos em ambientes tropicais. / The managing of the fish stocks, one of the tools of the biomanipulation, must begin with the classification of the present species and their diversity, of the structure of the food web and of the regulation relations (as the relation predator-prey).The Paranoá Lake (Brasília, DF) is an urban reservoir that suffers human pressures as a result of its multiple uses. After its construction and filling, the successive introduction of many fish exotic species resulted in an unbalance that, associated with the pressures described above, generated an acceleration in the eutrophication process of the ambient. In this way, the objectives of this work were: evaluate the environmental impacts from the introduction of the species predators in food web and quality from the reservoir\'s water; decide the efficiency of the species of predators in the prey\'s control in the marginal areas from dam, discussing possible fishing strategies of management based in the Stocking of fish predators. Them, 10 limnocorrals were built with waterproof canvases in a bay located in ETE-NORTE (sewers handling Station - North). In its interior, after retreat of all fishes, by a period of 28 days, two species of predators were stocked (Cichla ocellaris and Pseudoplatystoma coruscans), and a community simplified of prey (Tilapia rendalli and Oreochromis niloticus), above from the capacity of the system, defined in 4 classes of size. The biomasses of stocking were determined from application of rotenona in an area with known dimensions, and overstepped for the areas of the limnocorrals. The physical-chemists parameters from the water were accompanied weekly during the experiment. It had no significant differences between the handlings, regarding the variables limnological. As regards the control of prey, C. ocellaris showed itself an efficient predator regarding the smallest classes of sizes (2 - 6,9 cm and 7 - 12,9 cm), fact do not observe for the handling with P. coruscans. Agreement with the results obtained, was not verified to hypothesis of trophic cascade due to the complexity of the interactions between the agencies in tropical environments.

Ce manuscrit présente le développement de nouvelles réactions énantiosélectives d’addition-carbocyclisation en cascade initiées par des acides boroniques pour la formation d’hétérocycles azotés chiraux. Les premiers travaux ont permis d’accéder à des pyrrolidines et des pipéridines énantioenrichies à partir d’énynes-1,6 et -1,7 possédant un alcyne en tant que point d’entrée et un ester α,β-insaturé comme seconde fonction électrophile. Une seconde réaction d’addition-carbocyclisation de céto-esters a également été mise au point pour conduire à des pipéridines chirales possédant trois centres stéréogènes contigus avec de très bonnes énantiosélectivités et diastéréosélectivités. Dans ces réactions asymétriques, les diènes chiraux ont été les ligands les plus adaptés permettant l’obtention d’énantiosélectivités élevées. Dans ce contexte, une nouvelle voie d’accès aux diènes chiraux monosubstitués de type Ar-MSBod utilisés pour la première réaction a été développée. / This manuscript presents the development of new asymmetric addition-carbocyclisation cascade reactions initiated by boronic acids for the formation of chiral N-heterocycles. Early works provided access to chiral pyrrolidines and piperidines from 1,6 and 1,7-enynes possessing an alkyne as the entry point and an α,β-unsaturated ester as a second electrophilic function. A second addition-carbocyclisation reaction of keto esters has also been developed to access polyfunctionnalised chiral piperidines with three contiguous stereogenic centers, with both high enantioselectivities and diastereoselectivities. In these enantioselective reactions, chiral dienes proved to be the most suitable class of ligands to achieve high enantioselectivities. In this context, a new route was developed to access chiral monosubstituted diene type Ar-MSBod, previously used in the first methodology.

Cette thèse étudie par trois modèles et une expérience les effets des interactions entre le réseau vert (basé sur la production primaire) et brun (basé sur la décomposition) sur le fonctionnement des écosystèmes. Trois interactions entre les deux réseaux sont étudiées: 1) les nutriments recyclés par tous les organismes couplent les réseaux verts et bruns par une relation de mutualisme/compétition entre les producteurs primaires et les décomposeurs; 2) les consommateurs généralistes se nourrissent de proies des deux réseaux trophiques et 3) les connexions spatiales par les consommateurs généralistes mobiles en haut des réseaux trophiques et les flux de nutriments et de détritus en bas. Les résultats montrent que ces interactions peuvent affecter le fonctionnement des écosystèmes y compris les cascades trophiques, la stabilité et l'importance relative de la chaîne verte et brune. Ces résultats conduisent à (1) de nouvelles perspectives sur la modélisation du fonctionnement des réseaux trophiques, (2) des prédictions originales, (3) des nouvelles interprétations de résultats empiriques, (4) des idées sur des différences fondamentales de fonctionnement entre types d’écosystèmes, (5) des prédictions sur la réponses des écosystèmes aux changements globaux. / This thesis studies through three models and an experiment the important effects of the interactions between the green (based on primary production) and brown (based on decomposition) food webs on ecosystem functioning. Three interactions between the two food webs are studied: 1) nutrients recycled from all organisms in the food web couple the green and brown food webs through mutualistic/competitive interaction between primary producers and decomposers; 2) generalist consumers feed on prey from both food webs; and 3) the spatial connections between the two food webs through mobile generalist consumers at the top and through nutrient and detritus fluxes at the bottom of the food webs. The results show that these interactions may affect the ecosystems functioning including trophic cascades, stability and the relative importance of green and brown food chains. These results lead to new (1) insights on the way to model food webs, (2) predictions on food web functioning, (3) interpretation of empirical results, (4) ideas to compare the functioning of different ecosystem types and (5) predictions on food web responses to global changes.

Online social media, such as Facebook, Twitter, and LinkedIn, provides users with services that enable them to interact both globally and instantly. The nature of social media interactions follows a constantly growing pattern that requires selection mechanisms to find and analyze interesting data. These interactions on social media can then be modeled into interaction networks, which enable network-based and graph-based methods to model and understand users’ behaviors on social media. These methods could also benefit the field of complex networks in terms of finding initial seeds in the information cascade model. This thesis aims to investigate how to efficiently collect user-generated content and interactions from online social media sites. A novel method for data collection that is using an exploratory research, which includes prototyping, is presented, as part of the research results in this thesis.   Analysis of social data requires data that covers all the interactions in a given domain, which has shown to be difficult to handle in previous work. An additional contribution from the research conducted is that a novel method of crawling that extracts all social interactions from Facebook is presented. Over the period of the last few years, we have collected 280 million posts from public pages on Facebook using this crawling method. The collected posts include 35 billion likes and 5 billion comments from 700 million users. The data collection is the largest research dataset of social interactions on Facebook, enabling further and more accurate research in the area of social network analysis.   With the extracted data, it is possible to illustrate interactions between different users that do not necessarily have to be connected. Methods using the same data to identify and cluster different opinions in online communities have also been developed and evaluated. Furthermore, a proposed method is used and validated for finding appropriate seeds for information cascade analyses, and identification of influential users. Based upon the conducted research, it appears that the data mining approach, association rule learning, can be used successfully in identifying influential users with high accuracy. In addition, the same method can also be used for identifying seeds in an information cascade setting, with no significant difference than other network-based methods. Finally, privacy-related consequences of posting online is an important area for users to consider. Therefore, mitigating privacy risks contributes to a secure environment and methods to protect user privacy are presented.

Amine transaminases are enzymes that catalyze the mild and selective formation of primary amines, which are useful building blocks for biologically active compounds and natural products. In order to make the production of these kinds of compounds more efficient from both a practical and an environmental point of view, amine transaminases were incorporated into multi-step one-pot reactions. With this kind of methodology there is no need for isolation of intermediates, and thus unnecessary work-up steps can be omitted and formation of waste is prevented. Amine transaminases were successfully combined with other enzymes for multi-step synthesis of valuable products: With ketoreductases all four diastereomers of a 1,3-amino alcohol could be obtained, and the use of a lipase allowed for the synthesis of natural products in the form of capsaicinoids. Amine transaminases were also successfully combined with metal catalysts based on palladium or copper. This methodology allowed for the amination of alcohols and the synthesis of chiral amines such as the pharmaceutical compound Rivastigmine. These examples show that the use of amine transaminases in multi-step one-pot reactions is possible, and hopefully this concept can be further developed and applied to make industrial processes more sustainable and efficient in the future. / <p>QC 20170113</p>

Orientador: Orlando Luís Goulart Peres / Dissertação (mestrado) - Universidade Estadual de Campinas, Instituto de Física Gleb Wataghin / Made available in DSpace on 2018-08-28T09:46:02Z (GMT). No. of bitstreams: 1 Stenico_GabrielaVitti_M.pdf: 1514550 bytes, checksum: b70ae6f3e134ec870b16bf48feb2f637 (MD5) Previous issue date: 2015 / Resumo: Neutrinos atmosféricos são produzidos a partir de interações de raios cósmicos com a atmosfera terrestre que geram partículas secundárias instáveis as quais decaem fracamente em neutrinos. Por possuirem um amplo espectro de energia, que engloba algumas centenas de MeV a energias na ordem de TeV, esses neutrinos são bons objetos no teste de novas teorias, bem como no estudo do fenômeno de oscilação de neutrinos, onde há mudança do estado de sabor do neutrino para outro. Além disso, neutrinos atmosféricos constituem o ruído de fundo na calibração de telescópios de neutrinos astrofísicos e na busca por processos raros, o que nos motiva a estudar como se dá sua produção e evolução na atmosfera. Desse modo, buscamos determinar o fluxo de neutrinos atmosféricos através das reações básicas de criação dos mesmos por interações fracas e dos processos de absorção e espalhamento das partículas-mães carregadas, como píons e múons, gerados pela interação de prótons, principal constituinte dos raios cósmicos, com a atmosfera. Para isso, procederemos a resolver sistemas de equações de cascatas que relacionam termos sumidouros e fonte das partículas do fluxo para obtermos sua evolução até a superfície terrestre, de modo a incluir as características da atmosfera e geometria de incidência do feixe de partículas primárias, avaliando a consistência dos cálculos e comparando-os com resultados presentes na literatura. Feito isso, estenderemos o resultado incluindo um decaimento exótico, que não existe no Modelo Padrão, para ver se podemos testá-lo em experimentos de neutrinos atmosféricos / Abstract: Atmospheric neutrinos are produced by interactions of cosmic rays with the Earth¿s atmosphere that create unstable secondary particles which weakly decay into neutrinos. Because of its wide energy spectrum, that covers energies of few hundred of MeV until energies on the order of TeV, these neutrinos are good objects on the test of new theories as well as the study of neutrino oscillation phenomenon where there is a change in the state of neutrino flavour to another. In addition, atmospheric neutrinos constitute background and calibration beam for astrophysical neutrino telescopes and the search for rare processes, which motivates us to study how is its production and evolution in the atmosphere. In this way, we want to determine the flux of atmospheric neutrinos through the basic reactions of its creation by weak interactions and the processes of absorption and scattering of charged parent particles, as pions and muons, generated by the interaction of protons, main constituent of cosmic rays with the atmosphere. For this, we will solve cascade equations that relate source and sink terms of the particle flux to obtain its evolution until the earth surface, including the atmosphere characteristics and geometry of primary particle incidence beam, evaluating the consistency of the calculations and comparing them with the results found in the literature. Done that, we will extend the results including an exotic decay, which does not exist in the Standard Model, to see if we can test it on atmospheric neutrino experiments / Mestrado / Física / Mestra em Física / 156339/2013 / 2014/00347-3 / CNPQ / FAPESP

Recent reductions in healthcare funding in the United States has pressured clinical laboratories to provide the same quality of diagnostic testing with fewer resources. Testing cascades have been developed to assist in the diagnosis of various illnesses, which use fewer tests and subsequently reduce costs. However, the cost effectiveness of a celiac disease (CD) testing cascade compared to a panel is currently unknown. Therefore, the purpose of this study was to determine if a CD testing cascade was equivalent to a panel in identifying patients deemed likely for CD, and to compare their cost effectiveness in a sample of symptomatic patients from Northeast Tennessee. A retrospective analysis using a CD testing cascade was performed on 933 outpatient samples referred to our laboratory from 2012 to 2017 with a request for a celiac disease serology panel. The seroprevalence of CD for the panel and the cascade were the same in this population (1.82%, 95% binomial confidence interval: 1.06% to 2.90%). The total cost of the CD cascade was 268% less than the cost of the panel resulting in a savings of $44,705, which translates to a savings of $47.92/patient. Based on these findings, we recommend utilization of the cascade to identify patients with likely CD. In the future, creative use of novel testing strategies can have significant contributions to healthcare reform and afford patients more cost-effective clinical diagnostic testing.

The aim of this thesis is to quantify the impact of atmospheric turbulence on optical signal used in free space optic communication systems. The first part is associated with atmosphere as transmission medium. Following part deals with interferometry and components of interferometers. Various methods of analysis of trasmission environment for optical beam are introduced theoretically and experimentally. Mathematical apparatus based on Kolmogorov’s cascade theory, Rytov’s variance was used to find value of structural parameter of refraction as a main measure of turbulence intensity. Experimentally obtained data were subjected to statistical analysis. The visualization of interference pattern fluctuations under turbulent conditions is shown in the last section. Interferometric method was realized with Michelson interferometer.