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Conselho Nacional de Desenvolvimento CientÃfico e TecnolÃgico / Em razÃo da crescente demanda de usuÃrios mÃveis por conteÃdos criados com formato especÃfico e personalizado, ou adaptado para atender suas necessidades e preferÃncias no uso da web, as redes convergentes sensÃveis ao contexto incorporam uma promissora tecnologia para permitir aplicaÃÃes de serviÃos personalizados a mÃltiplos usuÃrios. O projeto C-CAST (Context Casting) (C-CAST, 2012) foi estabelecido para arquiteturas de redes convergentes sensÃveis ao contexto para suportar sessÃes com qualidade de serviÃo (QoS - Quality of Service) de forma garantida a mÃltiplos usuÃrios, simultaneamente, independentemente de suas tecnologias de conexÃo sem fio. O mecanismo de controle do C-CAST Legado introduz questÃes de degradaÃÃo de desempenho, visto que a abordagem de sinalizaÃÃo adotada à direcionada por fluxo. Isto significa que a carga de sinalizaÃÃo aumenta exponencialmente com o nÃmero de admissÃes de fluxo. Este trabalho propÃe o C-CAST AvanÃado, o qual aperfeiÃoa o sistema do C-CAST Legado pela extensÃo de mecanismos inovadores que integram um controle dinÃmico da largura de banda sobreaprovisionada por classes de serviÃo e alocaÃÃo de Ãrvores overlay. Por meio dessa estratÃgia, busca-se reduzir taxas de sinalizaÃÃo de controle e alocaÃÃo de recursos em todo o sistema. A avaliaÃÃo do C-CAST AvanÃado à conduzida por meio de simulaÃÃo, demonstrando seus benefÃcios em relaÃÃo ao C-CAST Legado, por otimizar significativamente os nÃveis de desempenho de todo o sistema de rede, enquanto mantÃm usuÃrios com a melhor percepÃÃo de qualidade. / Due to the increase demand of mobile users for content created in a specific and customized way, or adapted to comply with the needs and preferences in web usage, converged networks which are context-sensitive have been incorporated to a promising technology and enabled applications of personalized services to multiple users. The C-CAST project (Context Casting) was established to converged network architectures to support context-sensitive sessions with quality of service (QoS - Quality of Service) in a manner to guarantee to multiple users simultaneously, regardless of their wireless technologies. The C-CAST control mechanism of the Legacy introduces issues of performance degradation, once the signaling approach adopted is directed per-flow, which means that the signaling load increases exponentially with the number of admissions flow. This work proposes the Advanced of C-CAST, which reconstruct the C-CAST legacy system by the extent of innovative mechanisms that integrate dynamic control of provisioned bandwidth by the service classes and allocation overlay trees. Through this strategy, it seeks to reduce rates of control signaling and allocating resources throughout the system. The C-CAST Advanced evaluation is conducted through simulation, demonstrating its benefits in relation to C-CAST Legacy, by significantly optimization the performance levels of the entire network system while keep the network users with the best quality perception.

O avanço crescente da tecnologia nos processos industriais atuais, bem como o elevado grau de interação de equipamentos e processos, provocou o aumento da sua sensibilidade a variações de energia, ou o aumento do grau de sensibilidade de algumas cargas industriais, o que gera interrupções de produção industrial. Essas, ocasionadas por problemas de qualidade de energia, levam a diversos fatores indesejáveis às indústrias, tais como: perdas de produção, perdas de faturamento, perda de matéria-prima, uso irracional de energia, dentre outros. Um processo têxtil apresenta grandes perdas de produção quando ocorrem esses eventos. Esta dissertação apresenta uma série seqüencial de procedimentos técnicos adotados experimentalmente em duas plantas de fiação sintética, para mitigar o impacto da qualidade de energia numa indústria química-têxtil. O problema de qualidade de energia estudado foi a variação de tensão de curta duração (VTCD), especificamente os afundamentos de tensão, sobre uma carga crítica. Quando esses eventos ocorriam, havia um grande volume de perdas no processo, em função da descontinuidade operacional provocada por esses afundamentos de tensão. Por meio de procedimentos foi possível identificar a carga crítica, no caso, os conversores estáticos de freqüência utilizados amplamente nesse processo. Uma vez identificada essa carga, foi possível a realização de intervenções objetivando reduzir a sua sensibilidade. Dois experimentos realizados através de um painel que simulou a situação do processo, com testes de afundamentos de tensão em conversores estáticos de freqüência, além de outros trabalhos experimentais utilizados como referências nessa dissertação, serviram como complemento para a conclusão. As intervenções realizadas tiveram como conseqüência a melhoria de qualidade do produto, aumento da produtividade, além de grande retorno financeiro. / The increasing evolution of technology in the current industrial processes, as well as the high interaction degree of equipment items and processes, have caused the increase in their sensitivity to voltage variations. The increase of sensitivity in some industrial loads generates interruptions in the industrial production. That happens due to power quality problems, which causes many undesired effects to the industries, such as losses in production, invoicing and raw material, unreasonable use of energy, among others. A textile process presents large production losses whenever these events in the process occur. This dissertation presents a sequence of technical procedures adopted experimentally in two yarn plants, to mitigate and reduce the impact of power quality problems in the chemical textile plant. The problem of power quality studied was short duration voltage variations, specifically the voltage sags. These events lead to a big volume of loss in the process, by operational disruption of sensitivity loads provoked by the voltage sags. By means of the proposed procedures it was possible to identify the critical load, in this case the ASD (Adjustable Speed Drive), a kind of load used extensively in the textile process; once identified this load, it was possible to carry out interventions aiming at the reduction of loads sensitivities. Two experiences were realized through a panel that simulated the process, by applying voltage sags to the drivers - ASD (Adjustable Speed Drive). Besides that other research works surveyed to complement and conclude this dissertation. The interventions realized have had as consequence the improvement in the product quality, increasing productivity, as well as an excellent payback.

Reverse engineering - defined as extracting information about a product from the product itself - is a design tactic commonly used in industry from competitive benchmarking to product imitation. While reverse engineering is a legitimate practice - as long as the product was legally obtained - innovative products are often reverse engineered at the expense of the pioneering company. However, by designing products with built-in barriers to reverse engineering, competitors are no longer able to effectively extract critical information from the product of interest. Enabling the quantification of barriers to reverse engineering, this dissertation presents a set of metrics and parameters that can be used to calculate the barrier to reverse engineer any product as well as the time required to do so. To the original designer, these numerical representations of the barrier and time can be used to strategically identify and improve product characteristics so as to increase the difficulty and time to reverse engineer them. On the other hand, these quantitative measures enable competitors who reverse engineer original designs to focus their efforts on products that will result in the greatest return on investment. In addition to metrics that estimate the reverse engineering barrier and time, this dissertation also presents a methodology to strategically plan for, select, design, and implement reverse engineering barriers. The methodology presented herein considers barrier development cost, barrier effectiveness in various product components, impact on performance, and return on investment. This process includes sensitivity analysis, modeling of the return on investment, and exploration of multiobjective design spaces. The effectiveness of the presented methodology is demonstrated by making a solar-powered unmanned aerial vehicle difficult to reverse engineer. In the example, the propeller is selected to be the critical component where a series of voids are introduced to decrease the propeller weight and increase the flutter speed (a desirable attribute in propellers). Our tenet is that the use of such a framework contributes greatly to the sustainability of technological, economical, and security advantages enjoyed by those who developed the technology. Designers benefit because (i) products do not readily disclose trade secrets, (ii) competitive advantages can be maintained by impeding competitors from reverse engineering and imitating innovative products, and (iii) the return on investment can be increased.

Le sujet de la thèse vise à développer un imageur neutron portable présentant des performances de détection compatibles avec les besoins de la recherche et de l’industrie nucléaire, notamment ceux du démantèlement. Cette thèse se décompose en trois axes principaux de recherche, précédés d’une phase de recherche bibliographique. Suite à cette dernière, l’approche de localisation retenue est l‘imagerie de neutrons rapides par encodage spatial. Les détecteurs de neutrons ont été étudiés et plusieurs choix, adaptés à cette problématique, ont été retenus pour la suite de l’étude. Le premier axe est consacré aux études sur le développement d’un détecteur de neutrons sensible à la position. Le deuxième axe est lié à la conception et au prototypage d’un imageur neutronique, se reposant sur un masque codé et un détecteur Timepix modifié par une couche de paraffine. Le dernier axe concerne le déploiement et la caractérisation expérimentale de ce prototype. / The subject of the thesis aims at developing a portable neutron imager with detection performance compatible with the needs of the nuclear research and industry, in particular those of decommissioning. This thesis is divided into three main areas of research, preceded by a bibliographic research phase. Following the latter, the localization approach adopted is spatial encoding fast neutron imaging. Neutron detectors were studied and several choices adapted to this challenge were selected for the continuation of the study. The first axis is dedicated to the studies on the development of a position-sensitive neutron detector. The second axis is related to the design and prototyping of a portable neutron imager, based on a coded aperture and a Timepix detector enhanced with a paraffin layer. The last axis concerns the deployment and experimental characterization of this prototype.

Ce travail de thèse s’inscrit dans le cadre d’une collaboration entre Sanofi à Vitry-sur-Seine et le Laboratoire Hétérochimie Fondamentale et Appliquée (LHFA) à Toulouse, et a pour but de développer de nouveaux nanovecteurs à base de conjugués polymériques biodégradables et biocompatibles capables d’encapsuler, de transporter et de libérer des agents thérapeutiques. Les travaux précédemment réalisés au laboratoire, ont montré que la libération de principes actifs hydrophobes, tels que le Cabazitaxel de la famille des taxanes, pouvait être contrôlée grâce à l’architecture de conjugués de nature PEG-PLA. Dans le premier chapitre, une étude a été menée afin d’améliorer la cinétique de libération du principe actif, en tirant profit de la différence de pH qui réside entre les tissus sains et les tissus cancéreux. Différents liens (reliant le principe actif au copolymère) ayant un comportement pH dépendant ont été étudiés, comme l’hydrazone, l’acétal et le β-thiopropionate. La liaison ester boronique, dynamique en fonction du pH, a aussi été étudiée dans le but de déstructurer la NP et permettre indirectement d’améliorer la libération du principe actif. La synthèse et l’évaluation des divers conjugués ont montré que la structure polymérique amphiphile des conjugués inhibait considérablement le comportement pH dépendant attendu. Dans le second chapitre, plusieurs technologies comme le ciblage, permettant de diriger la NP dans l’organisme, ou l’imagerie permettant de les visualiser, ont été étudiées. L’influence de la structure des conjugués de forme Y et L sur les propriétés de reconnaissance et d’imagerie a été analysée. La structure Y offre quelques avantages quant à la quantité de ligand requise pour obtenir un ciblage actif optimal ainsi qu’une meilleure visualisation, en comparaison des résultats obtenus avec les conjugués L. La méthode de co-nanoformulation a permis de faire varier la quantité de ligand ou de sonde d’imagerie au sein des NPs. Dans le troisième chapitre, la synthèse et l’efficacité de sels de (bi)pyridinium comme catalyseurs pour la ROP de l’ε-caprolactone sont présentées. Un phénomène de coopérativité avec des bipyridiniums, dications donneurs de deux liaisons hydrogènes (IHBD) a été mis en évidence pour l’activation de l’ε-caprolactone, avec des activités en ROP plus importante en comparaison des systèmes impliquant la participation d’une seule liaison H. Les meilleurs systèmes ont pu être évalués plus en détail et ont permis d’accéder à des polymères de masses définies allant jusqu’à 13 000 g/mol. / This PhD thesis is based on a joint between Sanofi in Vitry-sur-Seine and LHFA. This work consists in the development of new nanovectors based on biodegradable and biocompatible polymerics conjugate that enable to encapsulate, transport and deliver therapeutic agents. Previous works in the laboratory have shown that the release of hydrophobic drugs, such as Cabazitaxel, a taxane derivative, could be controlled by the architecture of the conjugated PEG-PLA. In the first chapter, a study was realized to improve the release kinetics of the drug, taking advantage of the difference of pH between healthy and cancerous tissue. Different linkers (linking the drug to the copolymer) having a pH dependent behavior have been studied, such as hydrazone, acetal and β-thiopropionate. The boronic ester bonding, dynamic function of pH, was also studied in order to destroy the NP and indirectly improve the release of drug. The synthesis and the evaluation of various conjugates have shown that the amphiphilic polymeric structure of the conjugates significantly inhibited the expected pH-dependent behavior. In the second chapter, several technologies such as targeting or imaging were studied. The influence of the Y and L-shape on the recognition and imaging properties was analyzed. The Y-shape offers advantages like the amount of ligand required for optimal active targeting and better visualization, in comparison with the results obtained with the L conjugates. The method of co-nanoformulation allowed to adjust the ligand amount or imaging probe within the NPs. In the third chapter, the synthesis and efficiency of (bi)pyridinium salts as catalysts for the ROP of ε-caprolactone are presented. A collaborative behavior with dication bipyridiniums is bearing two hydrogen bonds (IHBD) was demonstrated for the activation of the ε-caprolactone, with greater ROP activities compared to systems involving the participation of only one H bond. The best systems were evaluated in more details and allowed access to polymers with a molecular weight of up to 13 000 g / mol.

The research described in this thesis reviewed previous uses of Interactive Voice Response (IVR), developed appropriate software, and employed IVR to obtain self-report of sensitive issues in surveys and conduct brief public health interventions. Chapter 1 introduces IVR and describes a systematic critical review of the use of IVR. IVR is a telephone interviewing technique where the human speaker is replaced by a high quality recorded interactive script to which the respondent provides answers by pressing the keys of a touch-telephone (touchphone). IVR has numerous advantages, including: economy, autonomy, confidentiality, access to certain population groups, improved data quality, standardised interviewing, multi-lingual interfaces, and detailed longitudinal assessments. Despite this, there have been few survey applications of IVR compared to alternative methods such as Computer-Assisted Telephone Interview (CATI). There has not been any evaluation of the use of IVR for asking sensitive questions in surveys or as a tool for health promotion at the community level. A literature review, described in Chapter 2, was conducted to identify other methods of asking sensitive questions. The literature review identified 19 different methods. Those methods that were most successful were those that provided the greatest degree of anonymity to the respondent. It was suggested that IVR may be a suitable method for community surveys. As described in Chapter 3, a custom software called Generalized Electronic Interviewing System (GEIS) was developed. This provided both CATI and IVR interviewing modes. As described in Chapter 4, it was found that the response rate obtained using IVR was unacceptably low, and an alternative interviewing method, the Hybrid method was developed. In the Hybrid method the interview was initiated by the interviewer but completed using IVR with GEIS. As described in Chapter 5, the IVR, CATI and Hybrid methods were used to investigate self-reported rates of alcohol and drug consumption within a telephone household survey of 2880 households. The self-report rates were compared to the National Drug Strategy Household Survey (NDSHS). Response rates did not differ significantly between the CATI and Hybrid methods, however the response rate for IVR was significantly less than the other methods. The Hybrid and IVR methods obtained significantly higher self-report consumption rates for alcohol and marijuana, and significantly higher hazardous drinking scores using Alcohol Use Disorders Identification Test (AUDIT). In Chapter 6 a pilot of an IVR cervical screening brief advice interface is described. A total of 5000 households were contacted by the IVR system. The system randomly selected an eligible woman aged 18-69 per household and determined her cervical screening status. A total of 661 women listened to the IVR message. The IVR call was shown to be acceptable and inexpensive compared to a mail pamphlet intervention. In Chapter 7 a randomized controlled trial of an IVR cervical screening brief advice involving 17,008 households is described. Cervical screening rate data were obtained from the Health Insurance Commission (HIC) for a period spanning six months before and following the intervention. The cervical screening rate was increased in the intervention postcodes by 0.43% compared to the control postcodes, and the increase was greater for older women at 1.34%. This was a desirable outcome since this group is considered to be an at-risk group. The overall conclusion was that IVR technology could be feasibly used to contact women to deliver brief interventions aimed at increasing cervical screening rates, but the cost per screen was likely to be high. It is suggested that an IVR system could be linked to cervical screening registers to more directly and economically contact women, and provide an efficacious complementary approach to the existing letter reminder system. / PhD Doctorate

<p>The gastric mucosa is frequently exposed to endogenously secreted hydrochloric acid of high acidity. Gastric mucosal defense mechanisms are arranged at different levels of the gastric mucosa and must work in unison to maintain its integrity. </p><p>In this thesis, several mechanisms underlying gastric mucosal resistance to strong acid were investigated in anesthetized rats and mice. The main findings were as follows:</p><p>Only when acid secretion occurred did the pH gradient in the mucus gel withstand back-diffusion of luminal acid (100 mM or 155 mM HCl), and keep the juxtamucosal pH (pH_jm) neutral. Thus, when no acid secretion occurred and the luminal pH was 0.8-1, the pH gradient was destroyed. </p><p>Bicarbonate ions, produced concomitant with hydrogen ions in the parietal cells during acid secretion and blood-borne to the surface epithelium, were carried transepithelially through a DIDS-sensitive transport. </p><p>Prostaglandin-dependent bicarbonate secretion seemed to be less important in maintaining a neutral pH_jm. </p><p>Removal of the loosely adherent mucus layer did not influence the maintenance of the pH_jm. Hence, only the firmly adherent mucus gel layer, approximately 80µm thick, seemed to be important for the pH_jm. </p><p>Staining of the mucus gel with a pH-sensitive dye revealed that secreted acid penetrated the mucus gel from the crypt openings toward the gastric lumen only in restricted paths (channels). One crypt opening was attached to one channel, and the channel was irreversibly formed during acid secretion. </p><p>Gastric mucosal blood flow increased on application of strong luminal acid (155 mM HCl). This acid-induced hyperemia involved the inducible but not the neural isoform of nitric oxide synthase. These results suggest a novel role for iNOS in gastric mucosal protection and indicate that iNOS is constitutively expressed in the gastric mucosa. </p><p>It is concluded that a pH gradient in the gastric mucus gel can be maintained during ongoing acid secretion, since the acid penetrates the mucus only in restricted channels and bicarbonate is carried from the blood to the lumen via a DIDS-sensitive transporter.</p>

<p>The field of forensic genetics is growing fast and the development and optimisation of more sensitive, faster and more discriminating forensic DNA analysis methods is highly important. In this thesis, an evaluation of the use of novel DNA technologies and the development of specific applications for use in forensic casework investigations are presented.</p><p>In order to maximise the use of valuable limited DNA samples, a fast and user-friendly Real-time PCR quantification assay, of nuclear and mitochondrial DNA copies, was developed. The system is based on the 5’ exonuclease detection assay and was evaluated and successfully used for quantification of a number of different evidence material types commonly found on crime scenes. Furthermore, a system is described that allows both nuclear DNA quantification and sex determination in limited samples, based on intercalation of the SYBR Green dye to double stranded DNA. </p><p>To enable highly sensitive DNA analysis, Pyrosequencing of short stretches of mitochondrial DNA was developed. The system covers both control region and coding region variation, thus providing increased discrimination power for mitochondrial DNA analysis. Finally, due to the lack of optimal assays for quantification of mitochondrial DNA mixture, an alternative use of the Pyrosequencing system was developed. This assay allows precise ratio quantification of mitochondrial DNA in samples showing contribution from more than one individual.</p><p>In conclusion, the development of optimised forensic DNA analysis methods in this thesis provides several novel quantification assays and increased knowledge of typical DNA amounts in various forensic samples. The new, fast and sensitive mitochondrial DNA Pyrosequencing assay was developed and has the potential for increased discrimination power.</p>

The cardiac sodium-calcium exchanger (NCX) is an important membrane protein which regulates cellular calcium necessary for the optimal contractile function of the heart. NCX has become a focal point in ischemic heart disease (IHD) research as evidence suggests that reactive oxygen species (ROS) produced during IHD can cause NCX to malfunction resulting in an intracellular calcium overload leading to cardiac contractile abnormalities. Therefore, I hypothesized that NCX function is mediated by ROS increasing NCX1 activity during cardiac ischemia-reperfusion. To research this hypothesis, I investigated cellular mechanisms which may play a role in NCX dysfunction and also examined methods to correct NCX function. I found that reactive oxygen species directly and irreversibly modify NCX protein, increasing its activity, thereby worsening the calcium overload which is deleterious to cardiac function. I also elucidated the molecular means by which NCX protein modification occurs. Exploring pharmacological means by which to decrease NCX function to relieve the calcium overload and reduce the damage to the heart, I discovered that ranolazine (Ranexa), indicated for the treatment of angina pectoris inhibits NCX activity directly, thereby further reducing the calcium overload-induced injury to the heart. Furthermore, many IHD patients are also co-morbid for type-2 diabetes. These patients are prescribed sulfonylurea (SU) agents which act at the ATP sensitive K+ channel (KATP). One agent such as glibenclamide is known to have cardiotoxic side effects. Therefore, SUs devoid of any cardiac side effects would beneficial. Interestingly, patients possessing the genetic variant E23K-S1369A KATP channel have improved blood glucose levels with the use of the SU gliclazide. Therefore, I determined the functional mechanism by which gliclazide has increased inhibition at the KATP channel. These findings have implications for type-2 diabetes therapy, in which 20% of the type-2 diabetic population carries the KATP channel variant. In summary, the findings presented in this thesis have implications on treatment strategies in the clinical setting, as a NCX inhibitor can be beneficial in IHD and possibly type-2 diabetes. Moreover, a pharmacogenomic approach in treating type-2 diabetes may also provide a positive outcome when considering co-morbid cardiac complications such as atrial fibrillation and heart failure.