In Bolivia, tomato acreage is 6717 and has a yield of 12005 kg/ha and the total production is 80,636 TM. Departments that harvest tomato are Santa Cruz, Cochabamba and La Paz, Santa Cruz being the department that shows the highest rates of production with 40653 TM in comparison with La Paz which has a production of 3109 TM and Cochabamba of 2420 TM. The principle factors in affect are, the best climatic conditions in Santa Cruz, while Cochabamba and La Paz have differences in seasonal changes (National Institute of Statistics, 1998). The importance of the tomato harvest lies in consumption preference, for the nutritional properties, as they provide a rich source of Vitamins A and C, principally for its qualities of high productivity in terms of yield per area, being a factor of great importance in the economy of the farmer. The repeated production of tomato in the same area or locality tends to create problems phytopathologicals caused by fungi, bacteria and viruses, that at times become difficult to handle, thus becoming serious limiting factors that are able to seriously affect the yields, as such the investigation of sickness control is of extreme importance. The community of Carmen Pampa belonging to the municipality of Coroico, Nor Yungas, constituting a suitable area for the cultivation of tomato, but the attack of diseases caused by fungi, principally Phytophtora infestans, with an incidence of rate of 98%, which is increased by high temperature, humidity, precipitation and fog, all of which favor the spread of this fungus. For this reason farmers are forced to use chemical products that cause problems of resistance of the causal agent of the illnesses. The FAO (1992) estimates 3 million poisonings annually at a global level of farmers and families as a result of chemicals, which cause in turn a residual effect, environmental pollution and creates and additional cost in production. In the investigation of intoxication by agrochemicals in Bolivia, in a population of 870 persons studied mentioned that, 88% are unaware of the risks associated with the use and management of using them; the cases of poisonings are more frequent in tropical plains with 46%, the valleys with 26%, the inter-Andean valleys with 14% and the high plains with 12%, without mentioning those of suicide origin. For this reason, the object of the present investigation is to try to control the late blight disease (Phytophtora infestans) in the cultivation of the tomato (Lycopersicum sculentum), with biocides, to eliminate or diminish the use of agrochemical products.

Bridges are vital components of the U.S. transportation network. However, every year, the transportation agencies report a large number of aging bridges that are structurally damaged. Also, evolving traffic and particularly the overloaded traversing traffic can threaten the bridges' integrity and safety further. Bridge weight-in-motion (BWIM) is a system that takes the instrumented bridges as a scale and uses the structure response to compute the trucks' weights with no interruption in the traffic. In a particular type of BWIM, called nothing-on-road BWIM (NOR-BWIM), only a few weighing sensors should be installed under the bridge top slab. Since nothing will be installed on the road surface, NOR-BWIM addresses some of the main challenges of pavement-based WIM and traditional BWIM systems. These include lane closure, interruption to the traveling traffic, and sensitivity to daily tire impacts and harsh weather conditions. It also provides a portable solution with a less labor-intense installation process. Additionally, previous studies have shown that BWIM systems are versatile candidates for overcoming the critical challenges of structural health monitoring (SHM) across various types of bridges. The integration of the two systems is more cost-effective with improved performance; thus, it is more attractive to practitioners. However, the current BWIMs have serious shortcomings that make the integrated SHM-BWIM systems impractical in real-world long-span bridges. In the first two phases of this study, these shortcomings are addressed and a novel BWIM system is proposed. Then, the novel BWIM system is used for SHM in the third phase of the study. These shortcomings are explained as follows. Most studies are performed on short/medium-span T-beam and slab-on-girder bridges. However, longer span lengths, construction methods, different slab properties (e.g., stiffness), etc., can affect the efficacy of the NOR-BWIM. Thus, there is a need to further evaluate this technique on other bridges, such as concrete-box-girder bridges with longer spans, in an effort to ascertain whether or not NOR-BWIM systems would still work effectively on such bridges. Thus, the first phase presents an experimental investigation conducted for a long-span concrete-box-girder bridge (144 m span) called the Smart Road bridge. A total of 18 experimental tests were performed on the bridge. Moreover, a cost-effective sensor placement was developed. It was found that the number of axles is detectable with an accuracy of 100%. Moreover, the estimated mean-absolute-error for axle spacing, vehicle speed, and gross vehicle weight were 4.6%, 2.6%, and 4.6%, respectively. Lastly, it was also demonstrated that the developed cost-effective NOR-BWIM system is capable of lane identification and truck position detection. The second main issue with the existing BWIM approaches is their limited suitability for simultaneous multiple-vehicle cases on multiple-lane bridges. To address this limitation, in the second phase of this study, a novel BWIM approach is proposed. The approach is built around the removal of the non-localized portion of the strain response. Keeping the localized portion of the strain response, which is not sensitive to nearby loads, allowing for enhanced detection. The superiority of this approach stems from its capability to handle multiple-vehicle cases. These may present with an arbitrary number of trucks and light-weight vehicles, simultaneously passing the bridge in any arbitrary pattern or configuration. To show the applicability of the approach, a finite element (FE) model of a long-span concrete-box-girder bridge was simulated. The model was validated against the experimental data collected under known large events. The FE model was then used to consider single-truck events (for proof-of-concept) as well as complex multiple-truck traffic cases. These included in-one-row trucks, zigzag patterns, side-by-side trucks, and a combination of several trucks with several light-weight vehicles present. The results demonstrated that the proposed BWIM approach is capable of detecting the axle weights and gross vehicle weight (GVW) of the traversing trucks. Based on all complex multiple-truck cases, the overall mean absolute errors for GVW and axle weight estimations were 4.5% and 11.3%, respectively. In the last phase, a multiple-presence dual-purpose (MPDP) SHM approach was proposed to monitor the integrity of bridges using the BWIM system existing sensors. This approach centers on the influence line (IL) change and uses a developed multiple-presence IL (MP-IL) technique (in the second phase) for SHM application. This can effectively handle the multiple presence issue of the current integrated SHM-BWIM systems to make them more practical. Also, unlike many SHM-BWIM studies, noise and transverse position change (defined as false damage indicators) were included in the proposed procedure to provide a more realistic bridge health monitoring approach. To show the applicability of the approach, a similar FE model simulated in the second phase was used. The model was then used to evaluate the MPDP approach under single and multiple truck events. Eleven damage scenarios were simulated, and three SHM trucks (a 3-axle, a 4-axle, and a 5-axle) were used to improve the SHM accuracy. Also, an updated sensor placement was proposed to effectively work for both BWIM and SHM applications in both single and multiple-truck events. According to the results, the MPDP SHM procedure coupled with the novel MP-IL and the proposed sensor placement could effectively detect the damage scenarios in both single and multiple-truck events. Also, it was shown that using several independent SHM trucks can make the monitoring process more effective. / Doctor of Philosophy / Every year, the transportation agencies report a large number of aging bridges that are structurally damaged. Also, evolving traffic and particularly overloaded traffic can threaten the bridges' integrity and safety further. Bridge weight-in-motion (BWIM) is a traffic system that takes the instrumented bridges as a scale and uses the structure response to compute the trucks' weights with no interruption in the traffic. In a particular type of BWIM, called nothing-on-road BWIM (NOR-BWIM), only a few weighing sensors should be installed under the road surface. Since nothing will be installed on the road surface, NOR-BWIM addresses some of the main challenges of pavement-based WIM and traditional BWIM systems. These include lane closure, interruption to the traveling traffic, and sensitivity to daily tire impacts and harsh weather conditions. It also provides a portable solution with a less labor-intense installation process. Additionally, previous studies have shown that BWIM systems are versatile candidates for overcoming the critical challenges of structural health monitoring (SHM) across various types of bridges. The integration of the two systems is more attractive to practitioners because it brings improved performance at a lower cost. However, the current BWIMs have serious shortcomings that make the integrated SHM-BWIM systems impractical in real-world long-span bridges. In the first two phases of this study, these shortcomings are addressed and a novel BWIM system is proposed. Then, the novel BWIM system is used for SHM in the third phase of the study. These shortcomings are explained as follows. Most studies are performed on short/medium-span bridges with particular types of structures. However, longer span lengths, construction methods, different bridge components' properties, etc., can affect the efficacy of the NOR-BWIM. Thus, there is a need to further evaluate this technique on other bridges with longer spans and different structural systems to ascertain whether or not NOR-BWIM systems would still work effectively on such bridges. Thus, the first phase presents an experimental investigation conducted for a long-span concrete-box-girder bridge (a different structural system than the literature) with 144-m spans. A total of 18 experimental tests were performed on the bridge. Moreover, a cost-effective sensor placement was developed. It was found that the number of axles is detectable with no error. Moreover, the estimated error for axle spacing, vehicle speed, and gross vehicle weight were all low. Lastly, it was also demonstrated that the developed cost-effective NOR-BWIM system is capable of lane identification and truck position detection. The second main issue with the existing BWIM approaches is their limited suitability for simultaneous multiple vehicles on multiple-lane bridges. To address this limitation, in the second phase of this study, a novel BWIM approach is proposed. The superiority of this approach stems from its capability to handle multiple-vehicle cases. These may present with an arbitrary number of trucks and light-weight vehicles, simultaneously passing the bridge in any arbitrary pattern or configuration. To show the applicability of the approach, a model of the long-span bridge was simulated. The model was validated against the experimental data collected under known traffic events. The model was then used to consider single-truck events and complex multiple-truck traffic cases. The results demonstrated that the proposed BWIM approach can detect the axle weights and gross vehicle weight (GVW) of the traversing trucks. Based on all complex multiple-truck cases, the overall errors for GVW and axle weight estimations were 4.5% and 11.3%, respectively. In the last phase, a novel SHM approach was proposed to monitor the integrity of bridges using the existing sensors for BWIM. This approach uses the proposed BWIM system for SHM application. This can effectively handle the multiple presence issue of the current integrated SHM-BWIM systems to make them more practical. Also, unlike many SHM-BWIM studies, noise and transverse position change were included in the proposed procedure to provide a more realistic bridge health monitoring approach. A similar model simulated in the second phase was used to show the applicability of the approach. The model was then used to evaluate the MPDP approach under single and multiple truck events. Eleven damage scenarios were simulated. Also, an updated sensor placement was proposed to work effectively for both BWIM and SHM applications in single and multiple-truck events. According to the results, the proposed SHM procedure coupled with the novel BWIM and the proposed sensor placement could effectively detect the damage scenarios in both single and multiple-truck events.

De nombreuses applications industrielles spécifiques dans les secteurs tels que l’automobile, le médical et le spatial, requièrent un très haut niveau de fiabilité. Dans ce contexte, cette thèse traite de l’étude de la fiabilité des mémoires non-volatiles à grille flottante de type NOR Flash. Après une introduction mêlant l’état de l’art des mémoires non volatiles et la caractérisation électrique des mémoires Flash, une étude sur l’effet des signaux de polarisation a été menée. Un modèle a été développé afin de modéliser la cinétique de la tension de seuil durant un effacement. L’effet de la rampe d’effacement a été montré sur les cinétiques mais aussi sur l’endurance. Une étude sur la durée de vie de l’oxyde tunnel a ensuite montré l’importance de l’utilisation d’un stress dynamique. Nous avons caractérisé cette dépendance en fonction du rapport cyclique et du champ électrique appliqué. Enfin l’endurance de la cellule mémoire Flash a été étudiée et les effets de la relaxation durant le cyclage ont été analysés. / Many specific applications used in automotive, medical and spatial activity domains, require a high reliability level. In this context, this thesis focuses on the study of floating gate non-volatiles memories reliability more precisely in NOR Flash architecture. After an introduction mixing the state of art of non-volatiles memories and the electrical characterization of Flash memories, a study on the polarization signals effect has been led. A model has been developed in order to model the threshold voltage kinetic during an erase operation. The erasing ramp effect has been shown on kinetics and also on cycling. Then, a study on the tunnel oxide lifetime has shown the importance of relaxation during stress. This dependence has been characterized as a function of duty cycle and the electric field applied. Finally, Flash memory cell endurance has been explored and the relaxation effects during the cycling has been analyzed.

Conselho Nacional de Desenvolvimento CientÃfico e TecnolÃgico / A busca por novos derivados citotÃxicos da nor-β-lapachona à parte de uma crescente e contÃnua busca por novos compostos ativos. O presente estudo teve como objetivo avaliar o potencial citotÃxico de quatro derivados arilaminos (1-4) da nor-β-lapachona e os provÃveis mecanismos envolvidos na citotoxicidade da nor-β-lapachona e de seus derivados. TrÃs derivados (1, 3 e 4) e seu precursor apresentaram elevado potencial citotÃxico sobre todas as linhagens celulares tumorais humanas utilizadas. Em estudos com cÃlulas nÃo tumorais (CMSP), a nor-β-lapachona nÃo induziu citotoxicidade, porÃm seus derivados apresentaram efeitos antiproliferativos, cuja intensidade variou de moderado a fraco com valores de CI50 iguais a 5,02 ÂM (1), 12,02 ÂM (3) e 10,65 ÂM (4). AlÃm disso, os compostos nÃo apresentaram efeitos hemolÃticos (EC50 > 219,29 ÂM). Tanto a nor-β-lapachona quanto seus derivados (1, 3 e 4) induziram apoptose (via mitocondrial) em cÃlulas HL-60, como observado atravÃs dos ensaios de anÃlises morfolÃgicas e de citometria de fluxo, e distÃrbios sobre a progressÃo do ciclo celular de cÃlulas HL-60, apenas na maior concentraÃÃo (4 ÂM). O tratamento com os compostos induziu a formaÃÃo de EROS, assim como quebras das fitas da molÃcula de DNA em cÃlulas HL-60 (NQO1−) e DU-145 (NQO1+). A co-administraÃÃo de GSH reduziu a sensibilidade celular aos efeitos tÃxicos dos compostos estudados, e o prÃ-tratamento com agentes antioxidantes (NAC e IK) reduziu drasticamente a produÃÃo de radicais livres, o mesmo nÃo ocorrendo com culturas prÃ-tratadas com BH (agente depletor de GSH). PorÃm, o dicumarol (inibidor de NQO1) preveniu a formaÃÃo de EROS e os efeitos genotÃxicos apenas na linhagem DU-145, indicando que esses compostos possam ser metabolizados por outras redutases que nÃo a NQO1. As lesÃes ao DNA de cÃlulas DU-145 promovidas pela nor-β-lapachona e seus derivados (1, 3 e 4) foram, parcialmente, reparadas apÃs um perÃodo de tempo de 24 horas, o que corrobora com a sÃntese nÃo programada de DNA detectada apÃs a exposiÃÃo a esses compostos. AlÃm disso, todos os compostos ativos interferiram sobre os processos de reparo dos danos ao DNA induzidos pelo MMS, o que indica que a interferÃncia sobre esses processos contribui para seus efeitos citotÃxicos. A nor-β-lapachona e seus derivados arilaminos (1, 3 e 4) inibiram a taxa de proliferaÃÃo de cepas de S. cerevisiae defectivas na expressÃo de topoisomerases (Top1Δ, Top3Δ e Top1ΔTop3Δ) de maneira mais pronunciada do que observado na cepa selvagem (BY4741), indicando que a interferÃncia sobre a atividade das topoisomerases influencia, de algum modo, a citotoxicidade desses compostos. Nos estudos de genotoxicidade e mutagenicidade com fibroblastos de pulmÃo de hamster chinÃs (linhagem V79), todos os compostos citotÃxicos promoveram quebras nas fitas de DNA, oxidaÃÃo de bases nitrogenadas e induÃÃo de micronÃcleos, em concentraÃÃo (10 ÂM) muito superior do que as necessÃrias para induzir os mesmos eventos em cÃlulas tumorais. ReforÃando a participaÃÃo de EROS sobre os eventos mutagÃnicos, o prÃ-tratamento com NAC preveniu a formaÃÃo de cÃlulas micronucleadas e reduziu a sensibilidade celular aos efeitos tÃxicos dos compostos estudados. Esses resultados ressaltam as propriedades antitumorais da nor-β-lapachona e seus derivados arilaminos e que eles podem ser considerados como protÃtipos para o desenvolvimento de novos agentes anticÃncer. / The search for new cytotoxic derivatives of nor-β-lapachone is part of a growing and continuous search for new active compounds. The present study aimed to evaluate the cytotoxic potential of four arylamino-nor-β-lapachone derivatives (1-4) and the probable mechanism involved in the cytotoxicity of these compounds. Among the tested derivatives, only three of them (1, 3 and 4) and the precursor molecule elicited a significant antiproliferative effects in all human tumor cell lines used in the study. In experiments with peripheral blood mononuclear cells (PBMC), nor-β-lapachone did not induce cytotoxicity, however its derivatives showed antiproliferative effects whose intensity ranged from moderate to weak, with IC50 values equal to 5.02 ÂM (1), 12.02 ÂM (3) and 10.65 ÂM (4). Moreover, all the compounds showed no hemolytic effects (EC50> 219.29 ÂM). Nor-β-lapachone and its derivatives (1, 3 and 4) induced apoptosis (mitochondrial pathway) in HL-60 cells, based upon morphological and flow cytometric analysis, and interference on HL-60 cell cycle progression, only at the highest concentration (4 ÂM). Compounds exposure induced intracellular ROS generation, as well as DNA strand breaks in HL-60 (NQO1−) and DU-145 (NQO1+) cell lines. The co-administration of GSH reduced the cellular sensibility to the toxic effects of the studied compounds. Unlike cells pre-treated with BH (glutathione depletor agent), cells pre-exposed to antioxidants agents (NAC or KI) showed low production of free radicals. On the other hand, dicoumarol (NQO1 inhibitor) prevented the ROS formation and DNA strand breaks only in DU-145 cells, indicating that these compounds can be metabolized by other reductases than NQO1. The DNA damage induced by nor-β-lapachone and its derivatives (1, 3 and 4) in DU-145 cells were partially repaired after 24 h, which agrees with the data of unscheduled DNA synthesis. In addition, all active compounds interfere with DNA repair processes of DNA damage induced by MMS, indicating that this action contributes to compounds cytotoxic effects. All active compounds inhibited the proliferation rate of S. cerevisiae strains defective in the expression of DNA topoisomerases (Top1Δ, Top3Δ and Top1ΔTop3Δ) more pronounced than that observed in wild type strain (BY4741), suggesting that the interference on topoisomerases activities may contributes to the cytotoxicity of active compounds. Genotoxicity and mutagenicity studies with Chinese hamster lung fibroblast cell line (V79), showed that all cytotoxic compounds promoted DNA strand breaks, DNA bases oxidation and micronucleus formation in a concentration (10 ÂM) far higher than needed to induce the same events in tumor cells. Strengthening the ROS contribution on the mutagenic events, the pre-treatment with NAC prevented the formation of micronucleated cells and reduced the V79 cell sensibility to the cytotoxic effects of the studied compounds. These findings underscore the antitumor properties of nor-β-lapachone and its arylamino derivatives and they can be considered as prototypes for the development of new anticancer agents.

Les patients atteints de polyarthrite rhumatoide (PR) ont une diminution de l'espérance de vie de 10 à 15 ans. Cette augmentation de la mortalité semble liée à un processus athéromateux accéléré. La dysfonction endothéliale (DE) joue un rôle clé dans ce processus. L'arginase est une enzyme qui régule le niveau de NO par compétition avec la NO Synthase (NOS) pour leur substrat commun, la L-arginine.Nous avons montré que la vasodilatation Acétylcholine (ACh) dépendante était altérée dans le modèle d'Arthrite Induite à Adjuvant (AIA) chez le rat Lewis, témoignant d'une DE. L'incubation des anneaux aortiques avec la nor-NOHA un inhibiteur sélectif d'arginase a amélioré la réponse vasculaire à l'ACh chez les rats AIA. L'activité et l'expression vasculaire de l'arginase se sont révélées augmentées chez les rats AIA et corrélées positivement à la sévérité de l'arthrite.Nous avons caractérisé les mécanismes impliqués dans la DE du rat AIA. Nos résultats ont montré que la DE mettait enjeu une diminution de l'activité de la NO synthase, un déficit en EDHF, une suractivité de la COX-2, ainsi qu'une production excessive des anions superoxydes. Le traitement curatif des rats AIA par la nor-NOHA pendant 3 semaines, a permis de restaurer la fonction endothéliale. L'inhibition de l'arginase n'a pas modifié l'atteinte articulaire des rats AIA.Nos travaux ont permis de mieux comprendre la physiopathologie de la DE associée à la PR et ont déterminé pour la première fois le rôle délétère de l'arginase dans cette anomalie. Ils ouvrent des perspectives quant à l'utilisation des inhibiteurs d'arginase comme futurs traitements pharmacologiques de l'atteinte vasculaire du patient PR / Patients with RA are characterized by a decrease in life expectancy of 10 to 15 years. This increase in mortality seems to be related to an accelerated atheroma process. Endothelial dysfunction (ED) has a key role in these processes. The arginase is an enzyme which regulates the level of NO by competing with the NO synthase (NOS) to their common substrate, L-arginine.We showed that acetylcholine (ACh) dependent vasodilation was altered in the model of Adjuvant Induced Arthritis (AIA) in Lewis rats, indicating a endothelial dysfunction. The incubation of aortic rings with nor-NOHA has improved the vascular response to ACh in AIA rats. The activity and expression of vascular arginase are increased in AIA rats and positively correlated with the severity of arthritis.We characterized the mechanisms involved in DE in AIA rats. Our results showed that ED involved a decrease of activity of NO synthase, a decrease of EDHF, overactiviry of COX-2, thromboxane synthase and prostacyclin synthase, as well as excessive superoxide anions. The cure of AIA rats by a selective inhibitor of arginase, nor-NOHA for 3 weeks, has restored endothelial function. In contrast, inhibition of arginase activity did not change the weight, the diameter of ankles, radiological or histological articular damage in AIA rats.Our work has led to a better understanding of pathophysiology of ED associated with rheumatoid arthritis and determined for the first time the deleterious role of arginase in this vascular anomaly. These results open prospects for the use of arginase inhibitors as future pharmacological treatment of vascular patient PR.

Quinones have been the subject of much interest due to their various biological activities, mainly as antitumor and as trypanocidal agents. Quinones are cytotoxic by two main mechanisms: the generation of ROS resulting in oxidative stress and alkylation of cellular nucleophiles, such as DNA and some enzymes such as topoisomerases. Their activity depends on bioreduction, similarly to what happens to nitroaromatic compounds. They also catalyze electron transfer reactions in biological processes and, after reduction generate radical anions (semiquinone radical anion and nitro), which depending on stability, can furnish their free electrons to acceptor molecules. In the present study, compounds with mixed functionalities derived from nor-β-lapachone, including a nitroaniline group were electrochemically studied in protic (acetate buffer) and aprotic (DMF+TBABF4, DMSO+TBAP and Acetonitrile+TBABF4) media, using glassy carbon and mercury as working electrodes. The compounds showed a complex redox behavior and the mechanism was elucidated using electron spin resonance. The electroreduced products of nor-β-lapachone and of the nitroquinones reacted with oxygen, indicative of the generation of reactive oxygen species, reactivity in the order of 2 > nor-β-lapachone > 3 > 1. We investigated their interaction with DNA, which was shown to be positive for nitroquinones and negative for the precursor nor-β-lapachone, in agreement with biological assays which had also shown that the nitroquinones cause DNA damage. The stability of the nitrosemiquinones, their half-life times were measured using mercury electrode, and the reaction rates for the electrochemical process-following-up-isproportionation reaction were measured. From these studies, a lower stability for the meta-substituted nitrophenylaniline (k2 = 5.188 x 103 L mol-1 s-1 and t1/2 = 0.06 s) was evidenced. Upon spectroelectrochemical reduction studies of the nitroquinones, the generation of radicalar intermediates (semiquinone radical anion and nitro radical anion) was observed, with differences between o- and m-derived compounds and the p-substituted one. To increase the solubility of the nitroquinones, in order to allow in vivo studies, the formation of inclusion complexes with β-cyclodextrin were evaluated. Positive results were obtained, leading to a viable formulation alternative for further biological studies with the compounds. / Conselho Nacional de Desenvolvimento Científico e Tecnológico / Quinonas despertam muito interesse devido às suas diversas atividades biológicas, principalmente como agentes antitumoral e tripanossomicida. A citotoxicidade de quinonas decorre de dois mecanismos principais: geração de EROs resultando no estresse oxidativo e alquilação de nucleófilos celulares, como o DNA e algumas enzimas, como as topoisomerases. Sua atividade depende de biorredução, similarmente ao que acontece com compostos nitroaromáticos. Eles também catalisam reações de transferência de elétrons biológicas e, após a redução geram ânions radicais (ânions radicais semiquinona e nitro), que dependendo da estabilidade, podem transferir seus elétrons livres a moléculas aceptoras. Neste trabalho, compostos de funcionalidade mista derivados da nor-β-lapachona, com um grupo nitroanilina, foram estudados eletroquimicamente nos meios prótico (tampão acetato) e aprótico (DMF + TBABF4, DMSO + TBAP e acetonitrila + TBABF4), utilizando carbono vítreo e mercúrio como eletrodos de trabalho. Os compostos apresentaram um comportamento redox complexo e o mecanismo elucidado por espectroeletroquímica. Os produtos da eletro-redução da nor-β-lapachona e nitroquinonas reagiram com oxigênio, indicativo da geração de EROs, na ordem de reatividade 2 > nor-β-lapachona > 3 > 1. Foi investigada a interação com DNA, que se mostrou positiva para as nitroquinonas e negativa para o precursor nor-β-lapachona, concordantes com ensaios biológicos que também evidenciou que as nitroquinonas causam dano ao DNA. A estabilidade do nitrosemiquinona, tempos de meia-vida e as taxas reacionais referentes à reação química de desproporcionamento acoplada ao processo eletroquímico para cada derivado foram determinadas usando eletrodo de mercúrio. A partir desses estudos, foi evidenciada a menor estabilidade para o nitrofenilamina meta-substituída (k2 = 15,188 x 103 L mol-1 s-1 and t1/2 = 0,06 s). Nos estudos por espectroeletroquímica das nitroquinonas, observou-se a geração de intermediários radicalares (ânions radicais semiquinona e nitro), com diferenças entre os nitroderivados o- e m-, assim como para o p- derivado. Com objetivo de aumentar a solubilidade das nitroquinonas, para posteriores estudos in vivo, foi avaliada a formação de complexos de inclusão com β-ciclodextrina. Foram obtidos resultados positivos, refletindo em alternativa viável para formulações posteriores com estes compostos e ensaios biológicos.

Cancer is one of the most dreadful diseases due to its figure of morbidity and mortality and its strong social and economic impact in public healthy. The development of new chemotherapics is urgently required. Pharmoelectrochemical studies are important tools in pharmaceutical chemistry, pharmacology and biomedicine. In the present work, the cytotoxic activity of the nitroquinone 2,2–dimethyl–3-(3-nitrophenylamine)-2,3-dihydronaphtho[1,2-b]furan-4,5-dione, was performed, using electrochemical and pharmacological methods, in order to elucidate its mechanism of reduction and biological action. Additionally, electrochemical behaviour of cytotoxic arylamine and [1,2,3] triazolic naphthoquinones was investigated, in order to obtain reduction potentials, to correlate them with their biological activity. Studies were undertaken in aprotic medium (DMSO/TBAP and Acetonitrile/TBABF4) and protic medium (acetate buffer pH 4.5). The nitroquinone was further investigated, concerning its cytotoxicity, genotoxicity, cells morphological modification and immunomodulation effects in its presence, using, for that, dsDNA biosensors and flow cytometry, with the main goal of proposing its pharmacological mechanism of antitumour action. The nitroquinone is not genotoxic and it caused apoptosis, by an intrinsic (mithocondrial) pathway. The electrochemical behaviour of all the quinones, in aprotic and protic media, are typical of well-behaved quinones. The triazole ring worked as a highly electronwithdrawing group, shifting positively all the redox potentials. The nitroquinone has hybrid electrochemical behaviour due to the presence of two eletroactive groups in the molecule. The analysis by ESR allowed the definition of its reduction mechanism. Reduction potential values (EpIc) of the two sets of substances are not directly related to the pharmacological activities of the compounds. Log P values showed better correlation with the biological activity. With the aid of dsDNA biosensor, and ssDNA in a modified electrode, it was possible to analyse the positive and direct interaction of acridines with DNA. The adaptation of the methodology of ssDNA, enabling the study of these (insoluble) substances in ssDNA, demonstrated the contribution of pharmoelectrochemistry to the discovery of the mechanism of action of drugs. / Conselho Nacional de Desenvolvimento Científico e Tecnológico / O câncer é uma das doenças que mais causam temor na sociedade, devido ao seu potencial de morbidade e mortalidade, seu grande impacto econômico em saúde pública e, em todos os setores produtivos. O desenvolvimento de novos fármacos anticâncer é necessário e urgente. Estudos farmacoeletroquímicos constituem ferramentas importantes em química farmacêutica, farmacologia e biomedicina. No presente trabalho, avaliou-se o potencial citotóxico da nitroquinona 2,2–dimetil–3-(3-nitrofenilamino)-2,3-di-hidronafto[1,2-b]furan-4,5-diona, por meio de métodos farmacológicos e eletroquímicos, visando à elucidação de seu mecanismo de redução e de ação citotóxica. Investigou-se, adicionalmente, o comportamento eletroquímico e citotóxico de naftoquinonas [1,2,3]-triazólicas citotóxicas, com o intuito de determinar seus potenciais de redução para avaliar a possibilidade de correlação com a atividade biológica. Foram realizados estudos eletroquímicos em meio aprótico (DMSO/TBAP e Acetonitrila/TBABF4) e prótico (tampão acetato pH 4,5). A nitroquinona foi investigada detalhadamente quanto à citotoxicidade, à genotoxicidade, na avaliação de modificações morfológicas celulares, aspectos de imunomodulação, empregando biossensores de DNA e citometria de fluxo, com o intuito de propor o mecanismo de ação farmacológica da atividade antitumoral. Ela não se mostrou genotóxica e seu mecanismo de ação envolve a via apoptótica, dependente da mitocôndria. Todas as quinonas heterocíclicas apresentam comportamento eletroquímico típico de quinonas bem comportadas, em meio aprótico e prótico. O anel triazólico funcionou como um grupo altamente eletroatraente, deslocando positivamente os processos de redução desses compostos. A nitroquinona possui comportamento eletroquímico híbrido devido à presença de dois grupos eletroativos na molécula. A análise por ESR definiu o mecanismo de redução desta substância. Os potenciais de redução catódicos (EpIc) das duas séries de substâncias não estão diretamente relacionados às atividades farmacológicas dos compostos. Os valores de Log P correlacionam-se melhor com as atividades citotóxicas. As acridinas, estudadas em biossensor de DNA e em presença de ssDNA, mostram interação direta com o DNA. A adaptação da metodologia do biossensor de DNA possibilitou o estudo dessas substâncias (insolúveis) em ssDNA, demonstrando a contribuição da farmacoeletroquímica na descoberta do mecanismo de ação de fármacos.

Flash Memories have been widely used as a storage media in electronic devices such as USB flash drives, mobile phones and cameras. Flash Memory offers a portable and non-volatile de- sign, which can be carried to everywhere without data loss. It is durable against temperature and humidity. With all these advantages, Flash Memory gets popular day by day. However, Flash Memory has also some disadvantages, such as erase-before restriction and erase limi- tation of each individual block. Erase-before restriction pushes every single writable unit to be erased before an update operation. Another limitation is that every block can be erased up to a fixed number. Flash Translation Layer - FTL is the solution for these disadvantages. Flash Translation Layer is a software module inside the Flash Memory working between the operating system and the memory. FTL tries to reduce these disadvantages of Flash Memory via implementing garbage collector, address mapping scheme, error correcting and many oth- ers. There are various Flash Translation Layer software. Some of them have been reviewed in terms of their advantages and disadvantages. The study aims at designing, implementing and simulating a NAND type FTL algorithm.

Phencyclidine (PCP) is a non-competitive NMDA receptor antagonist that has been shown to induce schizophrenia-like psychotic symptoms that are clinically indistinguishable from schizophrenia in patients. When administered to rodents, PCP produces an array of behaviours that are characteristic of schizophrenia. Schizophrenia is associated with continual and treatment resistant cognitive deficits which are now recognised as a core feature of the disease. The aim of the studies reported in chapter 3 were to establish a set of objects with equal preference in the NOR (novel object recognition) test. Furthermore, the inter-trial-interval (ITI) of the NOR test was investigated in an attempt to elucidate the effects of time and location of the rats during the ITI on the cognitive impairments following sub-chronic PCP treatment. The experiments in chapter 4 were designed to compare the performance of male and female rats in the NOR test following treatment with acute d-amphetamine (d-amph), PCP and sub-chronic PCP treatment. In chapter 5, validation of the cognitive deficits induced by sub-chronic PCP treatment was assessed using carefully selected pharmacological agents. The aim of the studies in chapter 6 was to determine the effects of isolation rearing on cognitive performance in the NOR test following increasing ITIs. Additionally, the sensitivity of isolation reared rats compared to social controls following acute administration of PCP and d-amph was assessed using the NOR test. Studies in chapter 8 utilised the 16-holeboard maze to determine the effects of acute treatment with d-amphetamine, PCP and scopolamine on working memory in the rat. NOR is a visual learning and memory test that measures recognition memory which is impaired in patients with schizophrenia. Studies presented in this thesis demonstrate the importance of careful pilot studies when selecting objects for use in the NOR test. Initial studies in sub-chronic PCP (2 mg/kg for 7 days followed by 7 days drug free) treated female hooded-Lister rats revealed a preference of the rats for the wooden cone object; subsequently this object was eliminated from further NOR experiments. Sub-chronic PCP treated rats were found to be highly susceptible to the disruptive influence of distraction during the short 1 min inter-trial-interval (ITI) in the NOR test. These results are consistent with clinical findings of the effects of distraction on cognition in schizophrenia patients. Following the initial validation experiments, a 1 min ITI in the home cage was selected for all subsequent NOR studies. Further experiments provided evidence to confirm that information presented in the acquisition trial is encoded but not retained in the retention trial of the NOR test by IV PCP-treated rats. Male rats were less sensitive to the recognition memory deficits induced by acute treatment with PCP and d-amphetamine compared with females. Following sub-chronic PCP treatment, both males and females showed object recognition deficits, however, the impairments were more robust in female rats. Female rats were therefore selected for all subsequent experiments. Pharmacological validation was carried out using carefully selected agents which were assessed for their ability to restore the sub-chronic PCP induced cognitive deficit in the object recognition test. It was found that the classical antipsychotic agents haloperidol and fluphenazine, the benzodiazepine anxiolytic chlordiazepoxide and the SSRI antidepressant fluoxetine were ineffective. Further studies showed that the atypical antipsychotic agents, clozapine and risperidone, the analeptic agent modafinil, the nAChR full agonist nicotine, and full agonist and positive allosteric modulator of the α7 nAChR (PNU-282987 and PNU120596 respectively) reversed the recognition memory deficit induced by sub-chronic PCP treatment in the NOR test. Isolation rearing of rats at weaning is an environmental stressor that has relevance for modelling the symptomatology and pathology of schizophrenia. Isolates had a significantly increased locomotor activity (LMA) response to a novel environment and enhanced sensitivity to time delay-induced recognition memory deficits, compared with their socially reared counterparts. Isolates were less sensitive to an acute PCP-induced recognition memory deficit but more sensitive to an acute d-amphetamine induced recognition memory deficit in the NOR test compared to social controls. Preliminary results from the 16-holeboard maze experiments reveal that acute administration of the mAChR antagonist scopolamine, d-amphetamine, PCP and sub-chronic PCP treatment reduced working memory scores compared to vehicle treated controls. Taken together, these findings suggest that sub-chronic treatment with PCP induces cognitive deficits in behavioural tests of relevance to cognition associated with schizophrenia. This may allow the detection of novel pharmacotherapies to alleviate these cognitive deficits and exploration of the nature of cognitive disturbances in these patients.

O ensino de inglês em uma escola técnica é voltado para atender às necessidades dos alunos e do curso. Atuando como professora de inglês para fins específicos no CEFET UnED Itaguaí, deparei-me com um curso novo no estado do Rio de Janeiro, o Curso Pós-Médio Técnico em Portos. Em vista disto, este estudo propõe-se a investigar como o documento portuário, NOR, Notice of Readiness, ou ainda, Aviso de Prontidão, fundamental em uma operação portuária e, consequentemente, material importante para o curso de Portos, se estrutura em estágios para transmitir significados. Objetivamente, este trabalho responde as seguintes questões: em que situação o gênero NOR se constitui? e que linguagem medeia a atividade social nessa situação?. Para tanto, no desenvolvimento da pesquisa, são utilizados os pressupostos da Linguística Sistêmico-funcional (HALLIDAY, 1985; HALLIDAY; HASAN, 1989), que tem a função e a semântica como base da linguagem e da atividade comunicativa, sendo a língua influenciada pelo contexto social. Dessa forma, adota-se uma concepção de gênero a partir de uma perspectiva funcionalista: o gênero é visto como uma atividade direcionada por objetivos e propósitos, realizada em estágios e na qual os falantes são engajados como membros da nossa cultura (MARTIN, 1992). Adota-se, ainda, a noção de configuração contextual (CC) de um gênero, que faz referência às variáveis de registro localizadas no contexto situacional: o campo, a relação e o modo, que possibilitam perceber os elementos obrigatórios e opcionais que compõem a estrutura potencial de um gênero (EPG), assim como verificar seus traços estruturais, lexicais, gramaticais e semânticos (HALLIDAY; HASAN, 1989). O corpus desta pesquisa é constituído de dez exemplares do documento NOR, coletados em duas empresas que possuem terminais portuários na região da Costa Verde, no Rio de Janeiro. A fim de analisar os exemplares do documento, fizemos uma pesquisa de base qualitativa para identificar os seus estágios obrigatórios e opcionais a partir das marcas léxico-gramaticais no texto, mapeando suas funções, conforme a proposta de Hasan (1989). Os resultados da análise dos dez documentos sugere que há quatro estágios obrigatórios nestes textos, ou seja, o documento NOR possui quatro estágios que cumprem certas funções importantes na atividade social em que se insere. Estes estágios ocorreram em todos os exemplares pesquisados e são portanto determinantes para caracterizar o gênero NOR. Nestes estágios, foram identificados padrões da léxico-gramática que sinalizam as respectivas funções dos segmentos textuais que compõem o NOR, mostrando a estreita relação entre texto (representado por suas características lexico-gramaticais) e contexto (representado pela configuração contextual postulada para o NOR). Assim, esta análise aponta vantagens para o contexto portuário uma vez que propõe um modelo para facilitar a leitura e escrita do documento NOR, levando o profissional da área a se tornar um participante mais competente. Além do aporte à área portuária, esta dissertação pode auxiliar na análise de outros gêneros, nos quais seus pesquisadores tenham como premissa um modelo que considera o meio social onde o texto é produzido / The teaching of English as a foreign language in a technical school is designed to meet students' and the courses needs. Acting as a teacher of English for Specific Purposes at CEFET Itaguaí, I came across a new course in Rio de Janeiro state, the Technical Course of Cargo shipping. Considering this, the present study aims to investigate how the cargo shipping document, NOR, or Notice of Readiness, which is a crucial cargo shipping operation and, consequently, an important material for the course at CEFET, is structured in stages to transmit meanings. Objectively, this paper answers the following research questions: "what is the situation in which the NOR is produced? " and "what are the main features of the language that mediates social activity in this situation?". To answer these questions the theoretical assumptions of Systemic functional linguistics (SFL) (HALLIDAY, 1985, HALLIDAY; HASAN, 1989) were drawn upon: SFL sees function and semantics as the basis of language and of communicative activity, and thus considers language to be influenced by social context. The concept of gender adopted comes from the same functionalist perspective: genre is here seen as an activity driven by goals and purposes, held in stages and in which speakers are engaged as members of a particular culture (MARTIN, 1992). The notion of a contextual configuration (CC) for a genre is also adopted, and it refers to the variables located in the situational context (field, tenor and mode) that enable one to realize the obligatory and optional elements that make up a genres structure potential (GSP), as well as investigate their structural features, lexical, grammatical and semantic (HASAN, 1989). The corpus for this study consists of ten exemplars of the document NOR, collected in two companies with cargo shipping terminals in the region of Costa Verde in Rio de Janeiro. In order to examine these documents, a qualitative research was carried out to identify their obligatory and optional stages on the basis of the identification of lexico-grammatical signals in the text, thus mapping their functions, as Hasan (1989) proposed. The results of the analysis of the ten documents suggest that there are four obligatory stages in these texts: the NOR document has four stages that fulfill certain important functions in the social activity in which it operates. These stages occurred in all samples studied and are therefore crucial to characterizing the genre. This research contributes to the pedagogy in the area of cargo shipping negotiations as it establishes a suggested model to facilitate the reading and writing of the document NOR, which might lead to professionals in the field becoming more competent participants in the social activity under discussion. Apart from its contribution to the area of cargo shipping , this research may help in the analysis of other genres, in which researchers adopt a model that considers the social environment in which the text is produced