O trabalho propõe um circuito para caracterização estatística do fenômeno Bias Temperature Instability (BTI). O circuito tem como base uma matriz de transistores para caracterização eficiente em larga escala de BTI. O design proposto visa o estudo da variabilidade de BTI dependente do tempo em dispositivos altamente miniaturizados. Para tanto se necessita medir centenas de dispositivos, a fim de se obter uma amostra estatisticamente significante. Uma vez que variações nos tempos de estresse e medida dos dispositivos podem gerar erros no processo de caracterização, o circuito implementa em chip (on-chip) o controle dos tempos de estresse e de medida, para que ocorra uma caracterização estatística precisa. O circuito de controle implementado faz com que todos dispositivos testados tenham os mesmos tempos de estresse e os mesmos tempos de recuperação (relaxamento). Desta forma, o circuito proposto melhora significantemente tanto a área utilizada quanto o tempo de medida, quando comparado a alternativas anteriormente implementadas. O leiaute do circuito foi realizado no novo nó tecnológico de 28 nanômetros do IMEC. / This work proposes an array-based evaluation circuit for efficient and massively parallel characterization of Bias Temperature Instability (BTI). This design is highly efficient when studying the BTI time-dependent variability in deeply-scaled devices, where hundreds of devices should be electrically characterized in order to obtain a statistically significant sample size. The circuit controls stress and measurement times for accurate statistical characterization, making sure all the devices characterized have the same stress and recovery times. It significantly improves both area and measurement time. The circuit layout is laid out in the new 28nm node IMEC technology.

O trabalho propõe um circuito para caracterização estatística do fenômeno Bias Temperature Instability (BTI). O circuito tem como base uma matriz de transistores para caracterização eficiente em larga escala de BTI. O design proposto visa o estudo da variabilidade de BTI dependente do tempo em dispositivos altamente miniaturizados. Para tanto se necessita medir centenas de dispositivos, a fim de se obter uma amostra estatisticamente significante. Uma vez que variações nos tempos de estresse e medida dos dispositivos podem gerar erros no processo de caracterização, o circuito implementa em chip (on-chip) o controle dos tempos de estresse e de medida, para que ocorra uma caracterização estatística precisa. O circuito de controle implementado faz com que todos dispositivos testados tenham os mesmos tempos de estresse e os mesmos tempos de recuperação (relaxamento). Desta forma, o circuito proposto melhora significantemente tanto a área utilizada quanto o tempo de medida, quando comparado a alternativas anteriormente implementadas. O leiaute do circuito foi realizado no novo nó tecnológico de 28 nanômetros do IMEC. / This work proposes an array-based evaluation circuit for efficient and massively parallel characterization of Bias Temperature Instability (BTI). This design is highly efficient when studying the BTI time-dependent variability in deeply-scaled devices, where hundreds of devices should be electrically characterized in order to obtain a statistically significant sample size. The circuit controls stress and measurement times for accurate statistical characterization, making sure all the devices characterized have the same stress and recovery times. It significantly improves both area and measurement time. The circuit layout is laid out in the new 28nm node IMEC technology.

Made available in DSpace on 2015-05-07T14:49:23Z (GMT). No. of bitstreams: 1 arquivototal.pdf: 2716493 bytes, checksum: 45124bd2a0783bf2deef175a9d510b95 (MD5) Previous issue date: 2012-02-24 / Coordenação de Aperfeiçoamento de Pessoal de Nível Superior - CAPES / Artificial chemical larvicides are a commonly used solution to control larvae of mosquitoes. However, these substances can have health and environmental impacts. We tested the efficacy of two biological methods to control mosquitoes larvae, the copepod (Mesocyclops oggunus) and entomotoxic bacteria Bacillus thuringiensis var, israelensis (Bti). These biological agents were used in isolation and consociated. We also interview endemic control agents that work with Aedes aegpty control in the city of João Pessoa-PB in order to access their perceptions about the uses of biological control against mosquito larvae. We found that the consociation between M. oggunus and Bti is more effective that each method in isolation to control larvae of A. albopictus (a species with similar biology with A. aegpity). Consequently the consociation between copepods and Bti represent a low operational cost and low environmental impact alternative to chemical larvicides in order to control mosquito larvae. Our interviews with endemic control agents involved with Aedes control showed that more efforts are need to inform them about the consequences and precautions associated to the use of chemical larvicides. / Larvicidas químicos artificiais são uma solução comumente utilizada para controlar as larvas de mosquitos. No entanto, essas substâncias podem causar impactos na saúde e no meio ambiente. Testamos a eficácia de dois controladores biológicos para controlar larvas de mosquitos, o copépodo (Mesocyclops ogunnus) e a bactéria entomotóxica Bacillus thuringiensis var. israelensis (Bti). Esses agentes biológicos foram utilizados isoladamente e em consorciação. Foram também realizadas entrevistas com os agentes de controle de endemias que trabalham no controle do Aedes aegypti na cidade de João Pessoa PB a fim de saber suas percepções sobre o uso de controladores biológicos no controle de larvas de mosquitos. Verificamos que a consorciação entre M. ogunnus e o Bti é mais eficaz do que a utilização dessas ferramentas isoladamente para controlar larvas de A. albopictus (uma espécie com a biologia semelhante ao A. aegypti). Dessa forma, a consorciação de copépodos com Bti representa uma alternativa de baixo custo operacional e baixo impacto ambiental a utilização de larvicidas químicos no controle de larvas de mosquitos. As entrevistas com agentes de controle de endemias mostraram que são necessários mais esforços para informá-los sobre as consequências e as precauções associadas ao uso de larvicidas químicos.

Mosquitoes are found in extremely large numbers in the lower parts of the River Dalälven. In the year 2000 the mosquito nuisance was especially high, resulting in foundation of the Biological mosquito control project. Since 2001 mosquito larvae are controlled by using a biological pesticide BTI (Bacillus thuringiensis ssp israelensis). The mosquito fauna in the area is dominated by flood water mosquitoes, a group of mosquitoes that are very aggressive and form new generations of mosquitoes during every single flooding event during the summer. To be able to efficiently control the mosquitoes it is essential to know the extension and locality of the flooding. A flooding event is evaluated by how high the water level will reach and at which time the top of the hydrograph is accruing. There is a need for a tool for short time prediction of flooding events in the Nedre Dalälven region. In this study a hydraulic model in the software HEC-RAS has been used, here called HEC-RAS NEDA. The hydraulic model came up with good results when predicting water surface levels. The validation process made from figures of a period with large amplitude in water levels showed that the modelled water level was within ± 0,05 m from the observed water stands. It is a stable model that can handle 100-year flows with quick changes in the flow. The correspondence is good concerning the water levels and it functions well when studying the top of the hydrograph. HEC-RAS NEDA is an accurate and easy to manage tool for prediction of flooding in the lake of Bysjön, Österviken and Färnebofjärden. Modelled results have been compared with the model made by Swedish meteorological and hydrological institute on the request of Räddningsverket. The results from the two models shows large discrepancies, probably because of low accuracy data entered into the model from Räddningsverket. Räddningsverket has used the Geographical Sweden Data height data bank´and I used the height data from a laser scanned digital terrain model. Area studies have also been made according to how the area of the water surface changes with the water stand. These studies show that during the flood in year 2000, 55 km2 was flooded based on laserscanning in Färnebofjärden. / Mygg förekommer i extremt stora antal i området kring nedre delen av Dalälven. År 2000 var myggplågan särskilt stor vilket medförde att projekt Biologisk Myggkontroll bildades. Myggbekämpning har bedrivits i Nedre Dalälven sedan 2001 med ett biologiskt bekämpningsmedel, Bacillus thuringiensis ssp israelensis (BTI). Områdets myggfauna domineras av så kallade översvämningsmygg, en grupp stickmyggor som är mycket aggressiva och bildar nya generationer efter varje enskild översvämning under sommaren. För en effektiv bekämpning av mygglarverna krävs att man vet översvämningens omfattning och lokalisering. En översvämning bedöms med avseende på hur högt vattenståndet når samt vid vilken tidpunkt hydrografens toppvärde inträffar. Det finns ett behov av ett verktyg som kan utföra korttidsprognoser av översvämningar i Nedre Dalälven. I denna studie har en hydraulisk modell i programvaran HEC-RAS använts, här kallad för HEC-RAS NEDA. Den hydrauliska modellen fungerar bra till att användas för prediktering av vattenstånd i Nedre Dalälven. Valideringen av modellen mot värden under en testperiod med stor amplitud i vattenståndet visade att modellerade vattenstånd var inom ± 0,05 m från de uppmätta värdena. Modellen är stabil och klarar av att hantera 100-årsflöden med snabba flödesfluktuationer. HEC-RAS NEDA är ett noggrant och lätthanterligt predikteringsverktyg för översvämningar i Bysjön, Österviken och Färnebofjärden. Överensstämmelsen är god gällande nivån av vattenståndet och den fungerar bra för att studera hydrografens topp temporärt. Modellerade resultat har jämförts med karteringar som Sveriges meteorologiska och hydrologiska institut har gjort på Räddningsverkets begäran. Resultaten skiljer sig betydligt mellan HEC-RAS NEDA och Räddningsverkets modell, troligen på grund av att Räddningsverket har stora svagheter i indata till modellen. Räddningsverket har använt Geografiska Sverige Data-Höjddata och modellen HEC-RAS NEDA är framtagen med höjddata från en digital terrängmodell baserad på laserscanning. Areella studier i GIS över hur arean av vattenspegeln förändras med vattenståndet visar att Färnebofjärden under augusti år 2000 lade 55 km2 under vatten.

<p>The aim of this work has been to characterize the effects of conditioned medium (CM) on insect cell productivity and physiology in order to get a better understanding about the mechanisms that regulate productivity in serum-free media. Two cell lines have been investigated, Spodoptera frugiperda (Sf9) and Trichoplusia ni (T. ni, BTI-Tn-5B1-4). The baculovirus expression vector system (BEVS) was used for protein expression, using the ligand-binding domain of the human glucocorticoid receptor as a model protein. Addition of CM at inoculation led to a shorter lag phase and that the cells reached the maximum cell density faster than cells in fresh medium for both Sf9 and T. ni cells. Sf9 cells passed a switch in growth kinetics after 30-40 passages. At this point, CM lost its stimulating effect on proliferation. CM also affected the cell size and cell cycle progression. Sf9 and T. ni cells became smaller when CM was added at inoculation because they had a minor arrest in the cell cycle after inoculation and therefore started to divide earlier than cells in fresh medium. For Sf9 cells, this was illustrated by a smaller arrest in G2/M in the beginning of culture and the cells were consequently less synchronized. For T. ni cells, the initial decrease in the S phase population was followed by an earlier increase of the S phase population for the cells with CM than for the cells in fresh medium.</p><p>Addition of 20 % CM or CM filtrated with a 10 kDa cut-off filter to Sf9 cultures had a negative effect on the specific productivity. However, addition of CM to Sf9 cells that had passed the switch in growth kinetics had no negative effect on productivity. This indicates that CM not affects the protein production per se, but rather through its effects on cell physiology. Instead, the degree of cells synchronized in G2/M is important for high productivity and the gradually decreasing degree of synchronization during the course of a culture might be the explanation behind the cell density dependent decrease in productivity for Sf9 cells. This was further supported by the positive effects on productivity achieved by synchronizing Sf9 cells in G2/M by yeastolate limitation, which counteracted the cell density-dependent drop in productivity and hence a higher volumetric yield was achieved. Addition of 20 % CM to T. ni cultures had a positive effect on productivity. The specific productivity was maintained at a high level longer than for cells in 100 % fresh medium. The product concentration was 34 % higher and the maximum product concentration was obtained 24 hours earlier for the cells with the addition of CM. These results show that the effects of CM on productivity are not the same for the two cell lines and that the mechanism regulating productivity are quite complex.</p>

京都大学 / 0048 / 新制・課程博士 / 博士(情報学) / 甲第19862号 / 情博第613号 / 新制||情||106(附属図書館) / 32898 / 京都大学大学院情報学研究科通信情報システム専攻 / (主査)教授 佐藤 高史, 教授 小野寺 秀俊, 教授 髙木 直史 / 学位規則第4条第1項該当 / Doctor of Informatics / Kyoto University / DFAM

Les travaux de cette thèse portent sur la simulation de la dégradation des paramètres électriques des transistors MOS et bipolaires sous stress statiques et dynamiques. Cette étude a été menée à l’aide d’un outil de simulation de fiabilité développé en interne. Selon la technologie MOS ou bipolaire, les mécanismes étudiés ont été successivement : Hot Carrier Injection, Bias Temperature instability, Mixed Mode et Reverse base emitter bias. L’investigation a été aussi étendue au niveau circuit. Nous nous sommes ainsi intéressés à l’effet de la dégradation des transistors sur la fréquence d’un oscillateur en anneau et les performances RF d’un amplificateur faible bruit. Les circuits ont été soumis à des contraintes DC , AC et RF. La prédictibilité, établie de ces dégradations, a été validée par des essais de vieillissement expérimentaux sur des démonstrateurs encapsulés et montés sur PCB. Les résultats de ces études ont permis de valider la précision du simulateur et la méthode de calcul quasi-statique utilisée pour calculer les dégradations sous stress dynamiques. Ces travaux de recherche ont pour but d’inscrire cette approche prédictive dans un flot de conception de circuits afin d’assurer leur fiabilité. / The work of this thesis focuses on the simulation of the electrical parameters degradation of MOS and bipolar transistors under static and dynamic stresses. This study was conducted using an in-house reliability simulation tool. According to the MOS or bipolar technology, the studied mechanisms were successively: Hot Carrier Injection, Bias Temperature instability, Mixed Mode and Reverse base emitter bias. The investigation was then extended to circuit-level. The effect of transistors degradation on a ring oscillator frequency and the RF performances of a low noise amplifier were investigated. The circuits were subjected to DC, AC and RF constraints. Predictability of these degradations has been validated by experimental aging tests on encapsulated and PCB-mounted demonstrators. The results of these studies proved the accuracy of the simulator and validated the quasi-static calculation method used to predict the degradation under dynamic stress. The goal of this research is to embed this predictive approach into a circuit design flow to ensure its reliability.

Bacillus thuringiensis sérotype israelensis (Bti) produit quatre toxines entomocides utilisées à grande échelle pour le biocontrôle des populations de diptères nuisibles et vecteurs de maladies : Cry4Aa, Cry4Ba, Cry11Aa et Cyt1Aa. Chacune de ces toxines présente un effet létal sur différents insectes mais, lorsqu’elles sont combinées, on observe un effet synergique et l’absence de résistance. Bien que cette synergie soit bien documentée par des tests de toxicité, il existe très peu d’information sur son mécanisme aux niveaux cellulaire et moléculaire. À l’aide d’intestins isolés des larves du moustique Aedes aegypti, le principal vecteur du paludisme, et de microélectrodes, nous avons observé une dépolarisation membranaire en présence de Cyt1Aa et de Cry4Aa individuellement. Cette dépolarisation se produit cependant plus rapidement lorsque la Cyt1Aa est utilisée en même temps que la Cry4Aa. D’autre part, des expériences réalisées avec la sonde calcique Fura-2 sur une lignée cellulaire provenant d’Anopheles gambiae (Ag55), ont révélé une forte activité lytique de la Cyt1Aa, mais très peu d’effets des autres Cry, et ce même en combinaison. Nous avons dissocié les cellules de l’épithélium intestinal isolé du moustique pour des expériences de Fura2. Nos résultats, quoique préliminaires, montrent les effets variables de ces toxines lorsqu’elles sont administrées seules sur les cellules dissociées : une augmentation du calcium intracellulaire, ou une fuite de la sonde se traduisant par une perte du signal fluorescent, ou la lyse cellulaire. On observe également en présence de Cyt1Aa et de Cry4Ba, que les effets sont presque instantanés. / Bacillus thuringiensis var israelensis (Bti) produces four insecticidal toxins used around the world to control disease-borne and harmful dipterans populations: Cry4Aa, Cry4Ba, Cry11Aa and Cyt1Aa. They each present their lethal effect on different dipterans, but combined, they generate a synergistic activity and a reduced resistance is observed. Though these synergies are well documented and supported by toxicity bioassays, little is known regarding the cellular and molecular mechanisms of these synergies. Here, by using freshly isolated midguts from the mosquito Aedes aegypti, an important malaria vector, and glass microelectrodes, we measured the electrical potential of the apical membrane when exposed to these toxins alone or in combination. We observed a depolarisation when treated with Cyt1Aa and Cry4Aa. Toxin mixture assays only revealed a faster depolarisation of the membrane when the above two toxins were combined together, and a variety of responses with other toxin mixtures. Microspectrofluometry using the calcium probe Fura-2 on an immortal cell line from Anopheles gambiae (Ag55) showed massive effect of Cyt1Aa, but very little effect of the Cry toxins alone or in mixture. Microspectrofluometry experiments were also conducted on freshly dissociated cells from Aedes aegypti. Though these experiments are innovative and the results preliminary, it was observed that some cells responded differently to Cyt1Aa and Cry4Ba, showing the various ways these toxins affect cells, by inducing either intracellular calcium change, or by entirely losing the probe, or by cell lysis. The mixture of these toxins is very efficient and almost instantaneous.

The aim of this work has been to characterize the effects of conditioned medium (CM) on insect cell productivity and physiology in order to get a better understanding about the mechanisms that regulate productivity in serum-free media. Two cell lines have been investigated, Spodoptera frugiperda (Sf9) and Trichoplusia ni (T. ni, BTI-Tn-5B1-4). The baculovirus expression vector system (BEVS) was used for protein expression, using the ligand-binding domain of the human glucocorticoid receptor as a model protein. Addition of CM at inoculation led to a shorter lag phase and that the cells reached the maximum cell density faster than cells in fresh medium for both Sf9 and T. ni cells. Sf9 cells passed a switch in growth kinetics after 30-40 passages. At this point, CM lost its stimulating effect on proliferation. CM also affected the cell size and cell cycle progression. Sf9 and T. ni cells became smaller when CM was added at inoculation because they had a minor arrest in the cell cycle after inoculation and therefore started to divide earlier than cells in fresh medium. For Sf9 cells, this was illustrated by a smaller arrest in G2/M in the beginning of culture and the cells were consequently less synchronized. For T. ni cells, the initial decrease in the S phase population was followed by an earlier increase of the S phase population for the cells with CM than for the cells in fresh medium. Addition of 20 % CM or CM filtrated with a 10 kDa cut-off filter to Sf9 cultures had a negative effect on the specific productivity. However, addition of CM to Sf9 cells that had passed the switch in growth kinetics had no negative effect on productivity. This indicates that CM not affects the protein production per se, but rather through its effects on cell physiology. Instead, the degree of cells synchronized in G2/M is important for high productivity and the gradually decreasing degree of synchronization during the course of a culture might be the explanation behind the cell density dependent decrease in productivity for Sf9 cells. This was further supported by the positive effects on productivity achieved by synchronizing Sf9 cells in G2/M by yeastolate limitation, which counteracted the cell density-dependent drop in productivity and hence a higher volumetric yield was achieved. Addition of 20 % CM to T. ni cultures had a positive effect on productivity. The specific productivity was maintained at a high level longer than for cells in 100 % fresh medium. The product concentration was 34 % higher and the maximum product concentration was obtained 24 hours earlier for the cells with the addition of CM. These results show that the effects of CM on productivity are not the same for the two cell lines and that the mechanism regulating productivity are quite complex. / QC 20101125

The aim of this thesis is to numerically evaluate democratic consolidation in Eastern European countries of the former Eastern Bloc. To compare these countries with each other and decide which of these countries can be considered as consolidated democracies. Secondary aim is to find which factors supported this consolidation or at least correlate with it. Theoretical basis of this work is Wolfgang Merkel's theory of democratic consolidation. He divides democratic consolidation into four levels: constitutional consolidation, representative consolidation, behavioral consolidation and democratic consolidation of the political culture. Each level of democratic consolidation is numerically expressed, with usage of Bertelsmann's transformation index data, separately for all states in two-year intervals since 2005 to 2015. Based on that, overall democratic consolidation is calculated. Therefore, we can compare countries between each other and in time. Correlation between factors supporting consolidation and overall democratic consolidation is expressed by Pearson correlation coefficient. This work is beneficial in creating and describing method, which can be used for numerical expression of democratic consolidation in any state since 2005 to 2015 without author's subjective influence. Another benefit is...