In der vorliegenden Arbeit haben wir unter Nutzung bioinformatischer Methoden eine innovative Strategie zur Eindämmung der Malaria entwickelt. Die genetische Modifikationsstrategie beinhaltet sowohl Manipulationen aufseiten des gefährlichsten Erregers, Plasmodium falciparum, als auch des Hauptvektors, Anopheles gambiae. In den Genomen beider Spezies wurden eine Reihe neuer konkreter targets identifiziert. Auch bereits beschriebene targets und Ansätze wurden in die Strategie einbezogen bzw. weiter ausgestaltet. Bezüglich der Vektormoskitos wird die Verbreitung eines gegenüber Plasmodien resistenten Genotyps angestrebt. Es werden einerseits effiziente natürliche und künstliche Resistenzgene diskutiert und andererseits eine bekannte Strategie zur Fixierung natürlicher Resistenzallele in natürlichen Populationen verbessert. Auf der Seite der Plasmodien erweiterten wir einen bereits von A. Burt (2003) beschriebenen Eradikationsansatz um weitere targets. Aus ethischen und evolutionsbiologischen Erwägungen bevorzugen wir jedoch eine alternative Strategie, welche die Etablierung von in ihrer Virulenz gemilderten Parasiten zum Ziel hat. Der attenuierte Genotyp wird unter anderem durch komplexe Pathway-Remodellierungen beschrieben (Löwe, Sauerborn, Schirmer, Dandekar, A refined genome engineering strategy against parasites and vectors, Manuskript beim Journal „Genome Biology“ eingereicht). Da sich Mutanten in der Natur gegen Wildtyp-Organismen kaum durchsetzen können, werden zwei drive-Systeme beschrieben, welche für die Implementierung der genetischen Manipulationsstrategie entwickelt wurden. Beide Konstrukte wurden zur Patentierung angemeldet (Patentanmeldung U30010 DPMA bzw. Aktenzeichen 102006029354.1). Zusätzlich zur deutschen wurde für eines der beiden Konstrukte eine PCT-Anmeldung eingereicht, welche in Zukunft einen internationalen Patentschutz ermöglichen soll. Es werden Kalkulationen vorgelegt, welche die Verbreitungstendenzen der Konstrukte in natürlichen Populationen vorhersagen. Die Beschreibung der entwickelten Konstrukte beschränkt sich nicht auf das primäre Anwendungsgebiet der Arbeit (Malaria), sondern beinhaltet auch andere Anwendungsgebiete, vor allem im Bereich der Medizin und Molekularbiologie. / Background: Gene drive strategies are an important alternative to control tropical diseases such as malaria. Results: Here we introduce a new gene drive strategy based on gene conversion constructs. We identify a gene drive strategy both for plasmodia and for anopheles including design of an inducible modification vector. Our constructs are based on group II introns or homing endonuclease genes. They include besides the intron to modify vector or parasite genome sites inducible promoters for gene activation. We thus separate gene modification from activation of the modified gene. Moreover, we provide a detailed list of suitable targets in vector and plasmodia for the modification strategy. Finally, we discuss the control effect of an eradication strategy versus a mild strategy of the gene construct for vector and parasite populations. Conclusions: A new eukaryotic vector and parasite control strategy using gene drive systems is presented and discussed.

O objetivo desta tese é estudar os romances The Coup e Brazil, de John Updike, para mostrar que muito mais que apresentar contradições dos países onde estão ambientados, esses romances lidam com os Estados Unidos - tema constante do autor. Ambos romances mostram, por meio de uma organização formal diversa ao restante da obra de Updike, uma visão que países centrais têm dos países periféricos e, ao apresentar sua percepção do Outro, o Norte fala de si mesmo. Assim, por meio de uma leitura política - como proposto por Fredric Jameson - desses romances pode-se verificar como elementos como a Guerra Fria, o expansionismo, irreversibilidade histórica, igualdade racial, por exemplo, demonstram o movimento do modo de produção capitalista na qual os Estados Unidos são protagonistas. É essa revelação, escondida pelas estratégias de contenção e contida na forma dos romances, que proponho mapear na (re)leitura desses textos literários. / The objective of this thesis is to study the novels The Coup and Brazil, by John Updike, in order to show that much more than presenting contradictions from the countries where they are settled, these novels deal with the United States - the author's constant theme. Both novels show, through a formal organization which is different from the rest of the author's literary work, a vision the central countries have of the peripheral countries and, by showing its perception of the Other, North speaks about itself. Thus, through a political reading - as proposed by Fredric Jameson -of these novels, it is possible to verify how elementssuch as the Cold War, expansionism, historical irreversibility, racial equality, for instance, demonstrate the moviment of the caitalist mode of production in which the United States are protagonist. It is this revelation, hidden by the strategies of containment and in the form of the novels, which I propose to map in the (re)reading of these literary texts.

Este trabalho visa verificar a integridade da contenção do reator de Angra 2, com uma abordagem mais realista, da possibilidade de conter todos os radionuclídeos gerados durante Acidentes de Perda de Refrigerante Primário por Grande Ruptura (Large Break Loss of Coolant Accident - LBLOCA). Além disso, essas informações são utilizadas para o cálculo mais realista do Pico de Temperatura do Encamisamento (PTE) da vareta mais realista do núcleo deste reator durante esse acidente. Os resultados desse estudo possibilitarão verificar a integridade da Planta após a ocorrência de acidentes considerados base de projeto. Alguns dos programas utilizados para analisar a contenção de uma usina nuclear são o RELAP5 e o COCOSYS. Esses códigos computacionais são ferramentas de análise que preveem as condições termohidráulicas dentro de um prédio de contenção de um reator refrigerado à água leve. A contenção da planta tipo Pressurized Water Reactor (PWR) é um edifício de concreto revestido internamente por metal e tem limites de pressão que devem ser respeitados durante a ocorrência de um acidente. Os dados de entradas necessários para esta simulação são: adição de massa e energia geradas do estudo de um acidente do tipo LBLOCA com o código RELAP5 da planta em questão. Os resultados da análise do comportamento da contenção da planta nuclear Angra 2 durante os acidentes base de projetos estudados rupturas do tipo guilhotina do circuito primário nas pernas fria e quente foram satisfatórios quando comparados com os apresentados no Relatório de Análise de Segurança (RFAS/A2) da planta e as distribuições de pressão ficaram bem abaixo do valor de pressão de projeto da contenção (6,3bar). / This work aims to verify the integrity of Angra 2 reactor containment by using a more realistic approach for the possibility of containing all radionuclides generated during a Large Break Loss of Coolant Accident (LBLOCA). In addition, this information is used for a more realistic calculation of the Peak Cladding Temperature (PCT) of the hottest area in the reactor during this accident. This study will contribute to the safety of the population from the surrounding areas after the occurrence of a design basis accident. Some of the programs used to analyze the containment of a nuclear plant are RELAP5 and COCOSYS. These computers codes are tools for analysis used for predicting the physical conditions and distributions of radionuclides inside a containment building following the release of material from the primary system in a light-water reactor accident. The containment of the type PWR plant is a concrete building coated internally with metal and has pressure limits to be respected during the occurrence of an accident. The simulation should be performed to ensure that the radionuclides originating from accidents in the plant are not released into the environment. The input data required for this simulation are: mass addition and energy generated from the simulation of an accident of the type Loss of Coolant Accident (LOCA) using RELAP5 code. The results of the analysis of the containment behavior of the Angra 2 nuclear plant during the design basis accidents studied - guillotine-type ruptures of the primary circuit in the cold and hot legs - were satisfactory when compared to those presented in the Final Safety Analysis Report (FSAR) of the plant; moreover, the pressure distributions were below the contention design pressure value (6.3bar).

Orientador: José Moacir Marin / Banca: Everlon Cid Rigobelo / Banca: Maria de Fátima Martins / Banca: Cleber Jacob Silva de Paula / Banca: Mônica Hitomi Okura / Resumo: A indústria avícola brasileira gera grandes quantidades de resíduos orgânicos, como a cama de frango, utilizada frequentemente na agricultura. Entre as bactérias presentes neste fertilizante orgânico estão os membros da família Enterobacteriaceae. O objetivo deste estudo foi analisar o perfil de fatores de virulência e resistência antimicrobiana de isolados de Escherichia coli da cama de frango na produção comercial de aves de corte. Foi montado um sistema de fermentação similar ao utilizado nas granjas comerciais de frango de corte, sendo coletadas amostras desta cama 5, 10, 15, 30 e 60 dias após o início do tratamento. Um total de 47 cepas de Escherichia coli foi isolado e testado por meio da reação em cadeia da polimerase para detectar genes de virulência característicos de APEC (hlyF, iss, ompT, iroN e iutA). Além disso, foram realizados testes de susceptibilidade a 14 antimicrobianos. Os resultados indicaram que as cepas apresentaram genes característicos de E. coli patogênica aviária (APEC), sendo os genes hlyF, iss e ompT os mais prevalentes. Os isolados apresentaram alta resistência (˃50%) à tetraciclina, gentamicina, cefotaxima, nitrofurantoína e ampicilina. Estes resultados sugerem que as estirpes possuem genes de virulência e resistência que podem ser disseminados no ambiente, representando um potencial risco zoonótico para os seres humanos. / Abstract: The Brazilian poultry industry generates large amounts of organic waste, such as chicken litter, which is often used in agriculture. Among the bacteria present in organic fertilizer are members of the Enterobacteriaceae family. The objective of this study was to analyze the profile of virulence factors and antimicrobial resistance of Escherichia coli isolates from poultry litter in commercial plants production. A fermentation system similar to that used in commercial chicken farms was set up, and samples of this litter were collected 5, 10, 15, 30 and 60 days after the start of treatment. A total of 47 Escherichia coli strains were isolated and tested through Polymerase chain reaction to detect virulence genes característicos de APEC (hlyF, iss, ompT, iroN e iutA). Antimicrobial susceptibility testing was performed using 14 antimicrobials. The results indicated that our strains harbored genes characteristic of Avian Pathogenic E. coli (APEC), with the hlyF, iss and ompT genes being the most prevalent. The isolates showed high resistance (˃50%) to tetracycline, gentamicin, cefotaxime, nitrofurantoin and ampicillin. These findings suggest that our strains harbored virulence and resistance genes which can be spread in the environment and are a potential zoonotic risk for humans. / Doutor

Despite generous universal social health insurance with little formal restrictions of outpatient utilisation, Austria exhibits high rates of avoidable hospitalisations, which indicate the inefficient provision of primary healthcare and might be a consequence of the strict regulatory split between the Austrian inpatient and outpatient sector. This paper exploits the considerable regional variations in acute and chronic avoidable hospitalisations in Austria to investigate whether those inefficiencies in primary care are rather related to regional healthcare supply or to population characteristics. To explicitly account for inter-regional dependencies, spatial panel data methods are applied to a comprehensive administrative dataset of all hospitalisations from 2008 to 2013 in the 117 Austrian districts. The initial selection of relevant covariates is based on Bayesian model averaging. The results of the analysis show that supply-side variables, such as the number of general practitioners, are significantly associated with decreased chronic and acute avoidable hospitalisations, whereas characteristics of the regional population, such as the share of population with university education or long-term unemployed, are less relevant. Furthermore, the spatial error term indicates that there are significant spatial dependencies between unobserved characteristics, such as practice style or patients' utilization behaviour. Not accounting for those would result in omitted variable bias.

Self-stabilizing system is a concept of fault-tolerance in distributed computing. A distributed algorithm is self-stabilizing if, starting from an arbitrary state, it is guaranteed to converge to a legal state in a finite number of states and remains in a legal set of states thereafter. The property of self-stabilization enables a distributed algorithm to recover from a transient fault regardless of its objective. Moreover, a self-stabilizing algorithm does not have to be initialized as it eventually starts to behave correctly. In this thesis, we focus on extensions and refinements of self-stabilization by studying two non-traditional aspects of self-stabilization. In traditional self-stabilizing distributed systems [13], the inherent assumption is that all processes run predefined programs mandated by an external agency which is the owner or the administrator of the entire system. The model works fine for solving problems when processes cooperate with one another, with a global goal. In modern times it is quite common to have a distributed system spanning over multiple administrative domains, and processes have selfish motives to optimize their own pay- off. Maximizing individual payoffs under the umbrella of stabilization characterizes the notion of selfish stabilization . We investigate the impact of selfishness on the existence and the complexity of stabilizing solutions to specific problems in this thesis. Our model of selfishness centers on a graph where the set of nodes is divided into subsets of distinct colors, each having their own unique perception of the edge costs. We study the problems of constructing a rooted shortest path tree and a maximum flow tree on this model, and demonstrate that when processes are selfish, there is no guarantee that a solution will exist. We demonstrate that the complexity of determining the existence of a stabilizing solution is NP-complete, carefully characterize a fraction of such cases, and propose the construction of stabilizing solutions wherever such solutions are feasible. Fault containment and system availability are important issues in today's distributed systems. In this thesis, we show how fault-containment can be added to weakly stabilizing distributed systems. We present solutions using a randomized scheduler, and illustrate techniques to bias the random schedules so that the system recovers from all single faults in a time independent of the size of the system, and the effect of the failure is contained within constant distance from the faulty node with high probability (this probability can be controlled by a user defined tuning parameter). Using this technique, we solve two problems: one is the persistent-bit problem, and the other is the leader election problem.

<p>To minimize the damage in the event of a security breach it is desirable to limit the privileges of remotely available services to the bare minimum and to isolate the individual services from the rest of the operating system. To achieve this there is a number of different containment strategies and process privilege security models that may be used. Two of these mechanisms are Solaris Containers (a.k.a. Solaris Zones) and Type Enforcement, as implemented in the Fedora distribution of Security Enhanced Linux (SELinux). This thesis compares how these technologies can be used to isolate a single service in the operating system.</p><p>As these two technologies differ significantly we have examined how the isolation effect can be achieved in two separate experiments. In the Solaris experiments we show how the footprint of the installed zone can be reduced and how to minimize the runtime overhead associated with the zone. To demonstrate SELinux we create a deliberately flawed network daemon and show how this can be isolated by writing a SELinux policy.</p><p>We demonstrate how both technologies can be used to achieve isolation for a single service. Differences between the two technologies become apparent when trying to run multiple instances of the same service where the SELinux implementation suffers from lack of namespace isolation. When using zones the administration work is the same regardless of the services running in the zone whereas SELinux requires a separate policy for each service. If a policy is not available from the operating system vendor the administrator needs to be familiar with the SELinux policy framework and create the policy from scratch. The overhead of the technologies is small and is not a critical factor for the scalability of a system using them.</p>

Oregon State University has hosted an International Atomic Energy Agency (IAEA) International Collaborative Standard Problem (ICSP) through testing conducted on the Multi-Application Small Light Water (MASLWR) facility. The MASLWR facility features a full-time natural circulation loop in the primary vessel and a unique pressure suppression device for accident scenarios. Automatic depressurization system (ADS) lines connect the primary vessel to a high pressure containment (HPC) which dissipates steam heat through a heat transfer plate thermally connected to another vessel with a large cool water inventory. This feature drew the interest of the IAEA and an ICSP was developed where a loss of feedwater to the steam generators prompted a depressurization of the primary vessel via a blowdown through the ADS lines. The purpose of the ICSP is to evaluate the applicability of thermal-hydraulic computer codes to unique experiments usually outside of the validation matrix of the code itself. RELAP5-3D 2:4:2 was chosen to model the ICSP. RELAP5-3D is a best-estimate code designed to simulate transient fluid and thermal behavior in light water reactors. Modeling was conducted in RELAP5-3D to identify the strengths and weaknesses of the code in predicting the experimental trends of the IAEA ICSP. This extended to nodalization sensitivity studies, an investigation of built-in models and heat transfer boundary conditions. Besides a qualitative analysis, a quantitative analysis method was also performed. / Graduation date: 2013

The aim of this paper is to evaluate the performance of two divergent methods for delineating commuting regions, also called labour market areas, in a situation that the base spatial units differ largely in size as a result of an irregular population distribution. Commuting patterns in Sweden have been analyzed with geographical information system technology by delineating commuting regions using two regionalization methods. One, a rule-based method, uses one-way commuting flows to delineate local labour market areas in a top-down procedure based on the selection of predefined employment centres. The other method, the interaction-based Intramax analysis, uses two-way flows in a bottom-up procedure based on numerical taxonomy principles. A comparison of these methods will expose a number of strengths and weaknesses. For both methods, the same data source has been used. The performance of both methods has been evaluated for the country as a whole using resident employed population, self-containment levels and job ratios for criteria. A more detailed evaluation has been done in the Goteborg metropolitan area by comparing regional patterns with the commuting fields of a number of urban centres in this area. It is concluded that both methods could benefit from the inclusion of additional control measures to identify improper allocations of municipalities. / <p>Open Access</p>

Many geoenvironmental applications make use of granular drainage layers. Design guidelines for these drains recommend a granular soil that provides for filtration of the adjacent base soil. Filtration criteria have been developed through laboratory studies in which fine soils under a concentrated gradient of water are protected from erosion by a filter soil. The primary objective in these studies has been the geotechnical stability of earth-fill structures, while drainage was a secondary consideration. Granular drainage layers have therefore been constructed using fine sand. The subsequent migration of fine soil into these drains has resulted in significant loss in permeability. The main research objective was to develop design criteria for granular drains to be used for long term operation in environmental applications. The secondary objective was to investigate the relationships between grain size distribution of drain materials and clogging by fines. This was done through a laboratory study where changes in permeability were measured in granular soils infiltrated with fines. Lastly, the effect of salinity on fines deposition was also investigated. The hypothesis of the current study is that coarser granular drains minimize the impact of clogging and provides a better alternative to traditional drain designs for long term environmental applications. The laboratory study was performed with three granular drainage soils: a French Drain sand designed using the traditional filter design method, a coarser uniform sand, and a coarser graded sand with approximately 40% gravel sized particles. Three fine soils were used to infiltrate the drainage soils; however, their particle size distributions were not significantly different from one another. The results indicate that the permeability of all three drainage soils could be reduced by approximately one order of magnitude with continuous flow of a high concentration of fines (5 g/L). The permeabilities of the sands were reduced to a lesser extent with a lower concentration of fines. Permeabilities of the graded soils decreased more slowly with a lower concentration of fines, when considering pore volumes of flow. However, the rate of permeability decrease was ultimately influenced by the amount of fines delivered to the sample. A lower concentration of fines did not significantly slow the rate of permeability reduction in the uniform sand. All three sands retained a similar mass of fines (samples were split and fines content measured following each test). Salinity in the pore water did not significantly affect deposition, likely due to the fact that the fines contained a small amount of clay sized particles. When considering that all three drainage soils became clogged with fines during the tests, the coarse soils maintained a relatively high permeability due to the fact that their pre-test permeabilities were high. This information, along with the results from the literature review, has led to the development of recommended new design criteria for granular drains to be used for long-term geoenvironmental applications. Test results from an earlier study found that dispersive soils subject to high gradients can be successfully protected by a filter coarser than the coarse graded soil used in the current study. It therefore follows that a granular soil intended for groundwater collection applications can be made to be coarser than the current accepted practice. A proposed granular drain design band is presented in the current study.