To manufacture safe, effective and affordable medicines with greater efficiency, process analytical technology (PAT) has been introduced by the Food and Drug Agency to encourage the pharmaceutical industry to develop and design well-understood processes. PAT requires chemical imaging techniques to be used to collect process variables for real-time process analysis. Multivariate statistical analysis tools and process control tools are important for implementing PAT in the development and manufacture of pharmaceuticals as they enable information to be extracted from the PAT measurements. Multivariate statistical analysis methods such as principal component analysis (PCA) and independent component analysis (ICA) are applied in this thesis to extract information regarding a pharmaceutical tablet. ICA was found to outperform PCA and was able to identify the presence of five different materials and their spatial distribution around the tablet.Another important area for PAT is in improving the control of processes. In the pharmaceutical industry, many of the processes operate in a batch strategy, which introduces difficult control challenges. Near-infrared (NIR) spectroscopy is a non-destructive analytical technique that has been used extensively to extract chemical and physical information from a product sample based on the scattering effect of light. In this thesis, NIR measurements were incorporated as feedback information into several control strategies. Although these controllers performed reasonably well, they could only regulate the NIR spectrum at a number of wavenumbers, rather than over the full spectrum.In an attempt to regulate the entire NIR spectrum, a novel control algorithm was developed. This controller was found to be superior to the only comparable controller and able to regulate the NIR similarly. The benefits of the proposed controller were demonstrated using a benchmark simulation of a batch reactor.

Characterization of post-translational modifications (PTMs) of therapeutic proteins is very important during the bioprocess development to maintain desired product quality and during the submission process to regulatory authorities for product approval. Monitoring glycosylation in pharmacokinetic studies can be useful to evaluate the dependence of clearance rates on different glycoforms. The cost and efficiency of characterization affect the speed to market of biopharmaceutical proteins. A reduction in the number of manual processing steps, cost of reagents and consumption of sample, as well as the time required for chemical analysis, is therefore necessary. The research presented in this thesis is focused on the potential of using microfluidic discs for automated, miniaturized, parallel and rapid sample preparation for PTM characterization of therapeutic monoclonal antibodies. Paper I describes the method development for N-linked glycosylation profiling. Several sample preparation steps have been performed in an integrated process in the microfluidic compact disc (CD). Paper II demonstrates the use of the method presented in paper I in combination with multivariate statistics for discrimination of glycosylation profiles of different therapeutic antibodies and simulation of a real case of quality control. Paper III is focused on a method for monitoring changes in glycosylation profiles of therapeutic antibodies in serum over time by incubation with an exoglycosidase enzyme. Paper IV describes the method for peptide mapping of therapeutic antibodies. In addition, recent work (unpublished results) assesses the potential of this method for methionine oxidation detection. The developed methods were fast, robust with low sample/reagent consumption. Generation of glycosylation profile data for one sample was established in approximately 2 h. The amount of samples and antigens loaded into the CD platform for one replicate was less than 0.3 μg and approximately 0.06 μg, respectively. Furthermore, considering the parallel function of the CD, conducting the analysis for 54 samples can be completed within a day. / <p>At the time of the doctoral defense, the following paper was unpublished and had a status as follows: Paper 3: Manuscript.</p>

The overall objective of this dissertation research is to understand the spatiotemporal dynamics of water quality parameters in different water bodies of South Florida. Two major approaches (multivariate statistical techniques and remote sensing) were used in this study. Multivariate statistical techniques include cluster analysis (CA), principal component analysis (PCA), factor analysis (FA), discriminant analysis (DA), absolute principal component score-multiple linear regression (APCS-MLR) and PMF receptor modeling techniques were used to assess the water quality and identify and quantify the potential pollution sources affecting the water quality of three major rivers of South Florida. For this purpose, a 15-year (2000–2014) data set of 12 water quality variables, and about 35,000 observations were used. Agglomerative hierarchical CA grouped 16 monitoring sites into three groups (low pollution, moderate pollution, and high pollution) based on their similarity of water quality characteristics. DA, as an important data reduction method, was used to assess the water pollution status and analysis of its spatiotemporal variation. PCA/FA identified potential pollution sources in wet and dry seasons, respectively, and the effective mechanisms, rules, and causes were explained. The APCS-MLR and PMF models apportioned their contributions to each water quality variable. Also, the bio-physical parameters associated with the water quality of the two important water bodies of Lake Okeechobee and Florida Bay were investigated based on remotely sensed data. The principal objective of this part of the study is to monitor and assess the spatial and temporal changes of water quality using the application of integrated remote sensing, GIS data, and statistical techniques. The optical bands in the region from blue to near infrared and all the possible band ratios were used to explore the relation between the reflectance of a waterbody and observed data. The developed MLR models appeared to be promising for monitoring and predicting the spatiotemporal dynamics of optically active and inactive water quality characteristics in Lake Okeechobee and Florida Bay. It is believed that the results of this study could be very useful to local authorities for the control and management of pollution and better protection of water quality in the most important water bodies of South Florida.

One of the major factors in RF circuit design is the ability to predict the performance of these circuits in the presence of uncertainty in the key design parameters. This is referred to as uncertainty quantification in the mathematical literature. Uncertainty about the key design parameters arises mainly from the difficulty of controlling the physical or geometrical features of the underlying design, especially at the nanometer level. With the constant trend to scale down the process feature size, uncertainty quantification becomes crucial in shortening the design time. This thesis presents a new approach to statistically characterize the variability of the Harmonic Balance analysis and its application to Intermodulation distortion analysis in the presence of uncertainty in the design parameters. The new approach is based on the concept of Polynomial Chaos (PC) and Stochastic Galerkin (SG) methods. However, unlike the traditional PC, the proposed approach adopts a new mathematical formulation that decouples the Polynomial Chaos problem into several problems whose sizes are equal to the size of the original Harmonic Balance problem. The proposed algorithm produces significant CPU savings with equivalent accuracy to traditional Monte Carlo and standard PC approaches.

A traditional printed newspaper is being replaced by an online one. This is one of the reasons why I in this thesis focus just on internet journalism. The online journalism servers I present in a relation to other periodicals -- newspapers, broadcast and television. The thesis describes and analyses main development trends in the Czech media market. It puts an emphasis on economic sections of general news and it also compares these sections with specialized economic servers. An important part of the thesis is focused on an analysis of reader's attendance which results in a rank of the most popular news servers. The model of the time series analysis is set up for two websites and it predicts future development trend in the number of real users of online news. The aim of this thesis is to provide a general view on the contemporary situation and also to describe the developmental tendency of online reporting. The result of the dissertation is the prediction of future development trend of online reporting servers.

Approved for public release; distribution is unlimited. / This paper documents the development of a statistical analysis package for the TRS-80 microcoraputer. The package is comprised of six interactive programs which are generally divided into topical areas. The major emphasis is on exploratory data analysis and statistical inference, however, probability and inverse probability distributions are also included. The programming language is TRS-80 Level II BASIC enhanced by the input/output commands available through the ESF-80 (Exatron Stringy Floppy) mass storage subsystem. With the modification of these few commands, the package is compatible with most floppy disk operating systems designed for the TRS-80 Model I or Model III microcomputers. This statistical analysis capability implemented on a relatively inexpensive system provides a useful tool to the student or the trained analyst without ready access to a mainframe computer system. / Major, United States Marine Corps

This diploma thesis deals with the importance of municipal budgets for public budgets. The essential part of the public budgets is formed by municipal budgets therefore the condition and balance of state budget is largely influenced by balance of these budgets. From the general point of view, municipal budgets also influence the possibility of attaining the economic and political goals of state. The aim of this thesis is to show on the basis of financial indicators' analysis the changes in municipalities' budgets over time, to interpret the development of their financial situation and to create a projection of their future evolution. For these purposes, the municipalities will be divided according to their size category.

O objetivo desta pesquisa é estudar a variabilidade e tendência dos elementos climáticos pluviosidade e temperatura, em quatro localidades do estado de São Paulo - Pirassununga, Rio Claro, São Carlos e São Simão -, que constituem parte da área de treinamento de voo da Academia da Força Aérea, para confirmar a hipótese de que essas alterações indicam indícios de mudanças climáticas de curto prazo, em escala local e que essas mudanças poderão afetar, no futuro, o planejamento das missões de treinamento de voo na AFA. Para isso foram utilizados, primeiramente, os dados mensais e anuais de temperatura e pluviosidade de uma série temporal de 34 anos (1976 a 2009) e, depois, de uma série mais curta, de 16 anos (1994 a 2009). Para a análise das condições climáticas de São Carlos, Rio Claro e São Simão foram utilizados os dados mensais e anuais de temperatura e pluviosidade de uma série temporal de 16 anos (1994 a 2009). Para efeito da análise estatística da variabilidade climática da temperatura e pluviosidade dentro da série temporal escolhida, foram aplicados os cálculos da média aritmética, do desvio padrão, do coeficiente de variação e da amplitude térmica. Para a análise da tendência, aplicou-se a técnica da regressão linear e os testes estatísticos não-paramétricos, conhecidos como testes de Mann-Kendall e Curvatura de Sen. Os resultados da pesquisa mostraram que a variabilidade mensal e anual da pluviosidade para as quatro localidade é semelhante e bem acentuada e que não existem tendências significativas para essa variável nas quatro localidades. Para as temperaturas em Pirassununga, a temperatura média apresentou grande variabilidade mensal. Para Rio Claro, São Carlos e São Simão a variabilidade anual das temperaturas foi baixa, próxima da estabilidade, com exceção da temperatura mínima, que apresentou grande variabilidade para as três localidades. Quanto à tendência para Pirassununga, apenas a temperatura média apresentou tendência decrescente e significativa. Os resultados obtidos para as temperaturas de Rio Claro, São Carlos e São Simão indicam tendências crescentes e/ou decrescentes, mas todas insignificantes. / The aim of this research is to study the variability and tendency in climatic elements, rainfall and temperature in four cities in the state of São Paulo: Pirassununga, Rio Claro, São Carlos and São Simão which are part of the flight training area of the Air Force Academy, in order to confirm the hypothesis that those alterations indicate signs of climatic variations in the short term, according to the local parameters and that those variations may change the schedule of the flight training missions at AFA. Monthly and annual data regarding to temperature and rainfall, recorded during a period of 34 years (1976-2009) were firstly considered during the study, followed by a shorter period of 16 years (1994-2009). In order to analyze the climatic conditions in São Carlos, Rio Claro and São Simão, monthly and annual data about temperature and rainfall collected during a period of 16 years (1994-2009) were considered. For purposes of statistical analysis of the climatic variability of temperature and rainfall within the chosen period of time, calculation of the arithmetic mean, standard deviation, coefficient of variation and temperature range were applied. In order to analyze such tendency, the linear regression model and non-parametric statistical tests, known as Mann-Kendall and Sen Curvature were applied. The results of the research showed that the monthly and annual variability of the rainfall in the four cities is similar and well marked and that there are not significant tendencies in that variable in the four cities. Relating to temperature in Pirassununga, the average temperature showed large monthly variability. In Rio Claro, São Carlos and São Simão, the annual temperature variability was low, tending to be stable, except for the minimum temperature which showed a large variability. Concerning to Pirassununga, just the average temperature tended to be decreasing and significant. The results obtained for the temperatures in Rio Claro, São Carlos and São Simão tended to be increasing and/or decreasing, but such tendencies were irrelevant.

A pesquisa de opinião tem um papel importante dentro da Engenharia de Produção, para o auxilio da confiabilidade da pesquisa é necessário ferramentas que sejam capazes de medir e trazer resultados de confiança. No presente estudo buscou-se apresentar a melhor forma da criação de um questionário com a utilização de uma escala confiável e conseqüentemente usar o pacote estatístico computacional SPSS para avaliar o caso. A Escala de Likert, utilizada para o questionário, é uma abordagem de resposta que mede a extensão de satisfação com um conjunto de instruções e perguntas realizadas através do questionário, este tipo de categoria de resposta faz com que seja fácil de quantificar, simplificando a análise de dados. Com a utilização do softwares o SPSS pode demonstrar que mesmo as pessoas pouco familiarizadas com softwares o SPSS pode auxiliar para tabulação e análise dos dados, pois sua plataforma é auto interativa e com resultados confiáveis. / The opinion survey has an important role within Production Engineeringor the help of the search reliability is necessary tools to be able to measure and bring reliable results. In the present study we sought to present the best way of creating a questionnaire using a reliable scale and therefore use the computer SPSS to evaluate the case. The Likert scale used for the questionnaire is a response approach to measuring the extent of satisfaction with a set of instructions and questions asked in the questionnaire, this type of response category makes it easy to quantify, simplifying the analysis data. Using the software SPSS can demonstrate that even people unfamiliar with SPSS software can help for tabulation and analysis of data because its platform is self interactive and reliable results.

<p>Шајкашка&nbsp; је географски&nbsp; субрегион у&nbsp;Србији. То је југоисточни део Бачке, лоциран&nbsp;у средишњем делу Аутономне Покрајине&nbsp;Војводине.&nbsp; Анализом природних и&nbsp;друштвених атрактивности, материјалне базе&nbsp;неопходне за развој туризма и садашњег&nbsp;стања развоја селективних облика туризма&nbsp;дошло се до закључка да Шајкашка, поред&nbsp;свих потенцијала, није афирмисана&nbsp;туристичка дестинација, чиме је потврђена&nbsp;основна хипотеза рада.</p><p>У раду су&nbsp;дефинисани кључни туристички ресурси&nbsp; и&nbsp;приоритетни облици&nbsp; туризма&nbsp; и&nbsp; са&nbsp;сигурношћу се може констатовати да&nbsp;Шајкашка&nbsp; може одмах или релативно&nbsp; брзо&nbsp;оформити конкурентно задовољавајући ниво&nbsp;у вези са&nbsp; следећим&nbsp; туристичким&nbsp;производима:&nbsp; наутички, излетнички, ловни и&nbsp;риболовни, сеоски, салашарски и спортско-рекреативни туризам, који би требало да&nbsp;представљају окосницу развоја туризма на&nbsp;овом простору.&nbsp; Услов је да се&nbsp; на новим, научно утемељеним и у&nbsp; пракси доказаним сазнањима, постави такав модел развоја, који ће да осигура&nbsp; да се&nbsp; Шајкашка&nbsp; позиционира као препознатљива и привлачна туристичка дестинација,&nbsp; са прецизно&nbsp; одређеном структуром&nbsp; туристичког производа&nbsp; и дефинисаним маркетинг планом развoja. У раду&nbsp; су дефинисани планови даљег развоја и предлози за унапређење туризма Шајкашке, базирани на резултатима анкетног истраживања туристичког тржишта. Испитивање туристичке тражње спроведено је на испитаницима из Новог Сада и Зрењанина, док је за потребе истраживања на страни туристичке понуде спроведено истраживање ставова локалног становништва Шајкашке о стању и перспективама развоја туризма у њиховим насељима. Резултати истраживања указују на чињеницу на Шајкашка није препознатљива туристичка дестинација, да нема изграђен имиџ, и да више од половине испитаника није посетило природне и друштвене атрактивности које се налазе на овом простору. Најбоље оцењени елементи Шајкашке, као туристичке дестинације су гастрономија, атрактивност вода и мултикултуралност, док је најслабије оцењен елеменат материјална основа.&nbsp; У&nbsp; резултатима истраживања ставова локалног становништва дошло се до закључка да&nbsp;&nbsp;&nbsp; становништво има позитиван став према развоју туризма, али да није свесно локалних туристичких вредности, ни природних нити културних, те да је неопходно спровести програме туристичке едукације и подизања самосвести.&nbsp; Велики удео локалног становништва има магловите представе о туризму и не познаје кораке и поступке који могу од ове делатности направити сигуран &nbsp;извор допунске зараде.&nbsp; Из анализе резултата анкетног истраживања донети су важни и конкретни закључци који би могли бити од велике помоћи за даље планирање развоја туризма у Шајкашкој.&nbsp; У резултатима истраживања&nbsp; нагласак&nbsp; се ставља&nbsp; на&nbsp; циљне тржишне сегменте на &nbsp;које треба усмерити маркетинг активности, стратегије које би требало применити и предуслове&nbsp; које&nbsp; треба испунити&nbsp; да&nbsp; би&nbsp; туризам заиста&nbsp; постао&nbsp; један од&nbsp; водећих&nbsp; елемената&nbsp; свеукупног&nbsp; развоја овог простора,&nbsp; а&nbsp; Шајкашка постала препознатљива туристичка&nbsp; дестинација&nbsp; у Србији.</p> / <p>Šajkaška&nbsp; je geografski&nbsp; subregion u&nbsp;Srbiji. To je jugoistočni deo Bačke, lociran&nbsp;u središnjem delu Autonomne Pokrajine&nbsp;Vojvodine.&nbsp; Analizom prirodnih i&nbsp;društvenih atraktivnosti, materijalne baze&nbsp;neophodne za razvoj turizma i sadašnjeg&nbsp;stanja razvoja selektivnih oblika turizma&nbsp;došlo se do zaključka da Šajkaška, pored&nbsp;svih potencijala, nije afirmisana&nbsp;turistička destinacija, čime je potvrđena&nbsp;osnovna hipoteza rada.</p><p>U radu su&nbsp;definisani ključni turistički resursi&nbsp; i&nbsp;prioritetni oblici&nbsp; turizma&nbsp; i&nbsp; sa&nbsp;sigurnošću se može konstatovati da&nbsp;Šajkaška&nbsp; može odmah ili relativno&nbsp; brzo&nbsp;oformiti konkurentno zadovoljavajući nivo&nbsp;u vezi sa&nbsp; sledećim&nbsp; turističkim&nbsp;proizvodima:&nbsp; nautički, izletnički, lovni i&nbsp;ribolovni, seoski, salašarski i sportsko-rekreativni turizam, koji bi trebalo da&nbsp;predstavljaju okosnicu razvoja turizma na&nbsp;ovom prostoru.&nbsp; Uslov je da se&nbsp; na novim, naučno utemeljenim i u&nbsp; praksi dokazanim saznanjima, postavi takav model razvoja, koji će da osigura&nbsp; da se&nbsp; Šajkaška&nbsp; pozicionira kao prepoznatljiva i privlačna turistička destinacija,&nbsp; sa precizno&nbsp; određenom strukturom&nbsp; turističkog proizvoda&nbsp; i definisanim marketing planom razvoja. U radu&nbsp; su definisani planovi daljeg razvoja i predlozi za unapređenje turizma Šajkaške, bazirani na rezultatima anketnog istraživanja turističkog tržišta. Ispitivanje turističke tražnje sprovedeno je na ispitanicima iz Novog Sada i Zrenjanina, dok je za potrebe istraživanja na strani turističke ponude sprovedeno istraživanje stavova lokalnog stanovništva Šajkaške o stanju i perspektivama razvoja turizma u njihovim naseljima. Rezultati istraživanja ukazuju na činjenicu na Šajkaška nije prepoznatljiva turistička destinacija, da nema izgrađen imidž, i da više od polovine ispitanika nije posetilo prirodne i društvene atraktivnosti koje se nalaze na ovom prostoru. Najbolje ocenjeni elementi Šajkaške, kao turističke destinacije su gastronomija, atraktivnost voda i multikulturalnost, dok je najslabije ocenjen elemenat materijalna osnova.&nbsp; U&nbsp; rezultatima istraživanja stavova lokalnog stanovništva došlo se do zaključka da&nbsp;&nbsp;&nbsp; stanovništvo ima pozitivan stav prema razvoju turizma, ali da nije svesno lokalnih turističkih vrednosti, ni prirodnih niti kulturnih, te da je neophodno sprovesti programe turističke edukacije i podizanja samosvesti.&nbsp; Veliki udeo lokalnog stanovništva ima maglovite predstave o turizmu i ne poznaje korake i postupke koji mogu od ove delatnosti napraviti siguran &nbsp;izvor dopunske zarade.&nbsp; Iz analize rezultata anketnog istraživanja doneti su važni i konkretni zaključci koji bi mogli biti od velike pomoći za dalje planiranje razvoja turizma u Šajkaškoj.&nbsp; U rezultatima istraživanja&nbsp; naglasak&nbsp; se stavlja&nbsp; na&nbsp; ciljne tržišne segmente na &nbsp;koje treba usmeriti marketing aktivnosti, strategije koje bi trebalo primeniti i preduslove&nbsp; koje&nbsp; treba ispuniti&nbsp; da&nbsp; bi&nbsp; turizam zaista&nbsp; postao&nbsp; jedan od&nbsp; vodećih&nbsp; elemenata&nbsp; sveukupnog&nbsp; razvoja ovog prostora,&nbsp; a&nbsp; Šajkaška postala prepoznatljiva turistička&nbsp; destinacija&nbsp; u Srbiji.</p> / <p>&Scaron;ajka&scaron;ka is geographical subregion in Serbia. It is located in southeastern part of Bačka, in middle part of Autonomous Province of Vojvodina. Through&nbsp;analyzes of natural and social attractiveness, material base essential for development of tourism and present condition of development of selective forms of&nbsp;tourism, it is concluded that &Scaron;ajka&scaron;ka, regardless of all its potential, is not an affirmed tourist destination, which&nbsp; confirms the basic hypothesis&nbsp; of the&nbsp;dissertation.</p><p>Dissertation defines key tourist resources and priority forms of tourism, and it can be ascertain that &Scaron;ajka&scaron;ka may now, or relatively soon form competitive satisfying level in relation with following tourist products:&nbsp; nautical tourism,&nbsp; excursion and&nbsp;sightseeing,&nbsp; hunting and fishing, rural and&nbsp; farm tourism,&nbsp; and&nbsp; sports-recreational &nbsp;tourism, which supposed to be framework for future development of tourism in this area. It is required&nbsp; that, on the grounds of&nbsp; new,&nbsp; scientifically&nbsp; based&nbsp; and in practice&nbsp; proven facts, a&nbsp; model&nbsp; of development should be created, which will&nbsp; ensure&nbsp; &Scaron;ajka&scaron;ka&nbsp; position&nbsp; as a recognizable and&nbsp; attractive&nbsp; tourist destination,&nbsp; with&nbsp; a precise structure of tourism product and the defined marketing plan development.</p><p>Dissertation defines plans for further development and suggestions on improving tourism of &Scaron;ajka&scaron;ka, based on results of survey of tourist market. Survey was conducted on respondents from Novi Sad and Zrenjanin,&nbsp; and&nbsp; for the purpose of research&nbsp; on&nbsp; the tourist&nbsp; offer,&nbsp; a survey&nbsp; of attitudes&nbsp; of local people from &Scaron;ajka&scaron;ka,&nbsp; on the status and&nbsp; perspectives&nbsp; of tourism development in their neighborhoods was conducted.</p><p>Results of survey indicates that &Scaron;ajka&scaron;ka is not recognizable tourist destination, it is without defined image, and more than half of respondents didn&#39;t visit natural and social attractiveness that are found in this area. Best graded elements of &Scaron;ajka&scaron;ka, as &nbsp;tourist destination is gastronomy, attractiveness of&nbsp; water and multiculturalism, and lowest grade was given to the material base.</p><p>Based on survey results of attitudes of local people it is concluded that they have positive attitude towards development of tourism, but unaware of local tourist&nbsp;<br />values, neither&nbsp; natural nor cultural, and that is necessary to implement a program of tourism education and raising&nbsp; awareness. Majority of population has wage idea of tourism and it is not familiar with procedures and steps which can make this activity secure source of additional earnings.</p><p>Based on survey findings analyze important and concrete conclusions were drawn, &nbsp;which could be of great assistance for further planning of development tourism in &Scaron;ajka&scaron;ka. Dissertation emphasizes survey findings, target&nbsp; market segments on which &nbsp;marketing activities should be focused, strategies that should be applied and preconditions that should be required in order to make tourism as one of the leading elements of entire development of this area, and &Scaron;ajka&scaron;ka to become recognizable tourist destination in Serbia.</p>