Dissertations / Theses on the topic 'NTCP'

Ce travail de thèse est centré sur l'établissement de modèles prédictifs de toxicité radio-induite et sur l’étude de leur intérêt en cas de radiothérapie par modulation d’intensité. Six modèles NTCP ont été implémentés et leur paramètres identifiés pour la prédiction des toxicités rectale et vésicale tardives dans le cancer de la prostate. Leur capacité prédictive a été démontrée pour les deux organes. Par ailleurs, le modèle LKB a été utilisé pour la prédiction de l’œsophagite aiguë en cas de radiothérapie du cancer bronchique non à petites cellules. Ensuite, le bénéfice tiré de l’incorporation du paramètre de dose équivalent uniforme (EUD) pour la planification inverse de la radiothérapie par modulation d’intensité (IMRT) a été évalué. L’évaluation de cette approche a montré une baisse significative de la dose dans les parois vésicale et rectale. L’incorporation de plusieurs modèles biologiques dans le processus d’optimisation de l’IMRT a aussi été réalisée. Des fonctions objectif ont été établies pour les différents facteurs biologiques comme le NTCP, l’EUD et le TCP. Les résultats dosimétriques obtenus montrent la supériorité de l’optimisation basée sur des facteurs biologiques sur celle reposant uniquement sur des facteurs physiques. Enfin, les modèles NTCP classiques ont été améliorés en intégrant un paramètre radiobiologique supplémentaire, le rapport α/β. Ce rapport α/β a été identifié pour différents types de toxicité. Avec ce nouveau paramètre, les modèles NTCP peuvent finalement être étendus à des patients traités suivant différents fractionnements, les traitements hypofractionnés étant de plus en plus utilisés
This thesis is focused on the predictive models of irradiation induced toxicities in intensity modulated radiotherapy. Six different NTCP models were implemented and their parameters were identified at predicting late rectal and bladder toxicities in prostate cancer. Their predictive skills have been demonstrated on both organs. Second, LKB model was used to predict the irradiation induced acute esophagitis after nun-small-cell lung cancer. Then, the benefit of using EUD in prostate cancer IMRT inverse planning was evaluated. The evaluation of the proposed approach proved that the use of EUD significantly decreased both the dose in the bladder and rectum walls. Then, the incorporation of different biological models in IMRT optimization process has been realized. Objective functions were established for different biological factors like NTCP, EUD and TCP. Obtained results show the superiority of the optimization based on biological factors over the optimization relying only on physical factors. Finally, classical NTCP models were corrected to deal with another radiobiological parameter, the α/β ratio. With this additional factor, NTCP models can be extended to predict toxicity for patients with different dose fractionation, these kinds of treatments being more and more clinically used

Orientador: Marco Antônio Rodrigues Fernandes
Resumo: O sucesso da radioterapia está intimamente ligado à razão terapêutica que representa o quociente entre a quantidade de tecido tumoral irradiado e o volume de tecido sadio atingido. A Probabilidade de Complicação em Tecidos Normais (NTCP) e a Probabilidade de Controle do Tumor (TCP) são parâmetros fornecidos por Sistemas de Planejamentos de Tratamentos (TPS) computadorizados, usados na rotina da radioterapia que auxiliam na interpretação da qualidade do tratamento. Neste trabalho são analisados os planejamentos de radioterapia de 03 pacientes portadores de câncer de próstata. Os planejamentos dos tratamentos foram realizados no TPS XiO, simulando as técnicas de radioterapia por intensidade modulada de feixe (IMRT) e radioterapia tridimensional conformada (3D-CRT). A dose de radiação preconizada para o volume de tratamento planejado (PTV) foi de 7.600 cGy, as simulações foram realizadas para um arranjo de 6 campos de radiação com feixes de raios X de megavoltagem e energia de 10 MV. Os volumes prostáticos variaram entre 107 cm3 e 143 cm3. A dose de cobertura D98% do PTV variou de 6.940 cGy a 7.570 cGy com IMRT e de 6.410 cGy a 7.250 cGy com 3D-CRT. Os valores obtidos para o TCP ficaram entre 73,5% a 81,1% com IMRT e entre 70,6% a 75,9% com 3D-CRT. Considerando os valores de NTCP para o reto e a bexiga, os maiores valores encontrados foram 6,9% para o reto e 6,1% para a bexiga, ambos planejados com a técnica de 3D-CRT. Para os casos analisados, os resultados mostram que a técnic... (Resumo completo, clicar acesso eletrônico abaixo)
Abstract: The success of radiotherapy is closely related to the therapeutic ratio which represents the ratio of the amount of irradiated tumor tissue to the volume of healthy tissue achieved. Normal Tissue Complication Probability (NTCP) and Tumor Control Probability (TCP) are parameters provided by computerized treatment planning systems (TPS), used in radiotherapy routine and also allow the interpretation of treatment quality. The aim of this work is analyze the planning of 03 cases of patients submitted to prostate cancer radiotherapy. The treatment plans were performed in TPS XiO, simulating the techniques of beam intensity modulated radiotherapy (IMRT) and tree-dimensional conformal radiation therapy (3D-CRT). The recommended radiation dose for the planned treatment volume (PTV) was 7600 cGy, the simulations were performed for an arrangement of 6 radiation fields with megavoltage X-ray beams and 10 MV energy. Prostatic volumes ranged from 107cm3 to 143cm3 . The D98% PTV coverage dose ranged from 6,940 cGy to 7,570 cGy with IMRT and from 6,410 cGy to 7,250 cGy with 3D-CRT. The values obtained for TCP were between 73.5% to 81.1% with IMRT and between 70.6% to 75.9% with 3D-CRT. Considering the NTCP values for the rectum and bladder, the highest values found were 6.9% for the rectum and 6.1% for the bladder, both planned using the 3D-CRT technique. For the analyzed cases, the results show that the IMRT technique presents better NTCP and TCP values than the 3D-CRT technique. These par... (Complete abstract click electronic access below)
Mestre

L’hépatite B est une maladie infectieuse grave et extrêmement contagieuse. Malgré l’existence d’un vaccin efficace plus de 240 millions de personnes souffrent d’une infection hépatique chronique et plus de 780 000 personnes meurent chaque année des conséquences aiguës ou chroniques de l’hépatite B. Les traitements actuels qui consistent en l’utilisation d’interféron et/ou d’inhibiteurs de la réplication virale sont encore insuffisants. De nouvelles thérapeutiques ciblant l’entrée virale sont en développement, notamment le Myrcludex B qui inhibe l’infection en empêchant l’entrée virale. Cependant, les mécanismes d’entrée du VHB dans l’hépatocyte sont encore mal connus. Récemment, l’identification du NTCP comme récepteur spécifique du VHB a permis de mieux comprendre le mécanisme d’attachement de ce virus. Ce récepteur constitue une nouvelle cible pour des antiviraux. C’est aussi un transporteur de sels biliaires fortement régulé par les cytokines pro-inflammatoires. Les objectifs de ce travail étaient : (i) d’étudier la fusion du VHB, étape cruciale de l’entrée d’un virus enveloppé, en établissant un modèle artificiel de fusion entre des particules virales purifiées et des liposomes, et (ii) d’étudier l’effet de l’interleukine 6 sur l’entrée virale. Nous n’avons pas pu mettre en évidence de fusion entre les particules virales et des liposomes suggérant l’incapacité de ce virus à fusionner avec une bicouche lipidique néanmoins il reste possible que des conditions particulières liées aux spécificités du VHB soient requises. Nos résultats ont également montré que l’interleukine 6 inhibait l’entrée virale en diminuant l’expression de NTCP
Hepatitis B is a severe and extremely contagious infectious disease. Despite an effective vaccine more than 240 million people are suffering from chronic infection and over 780 000 persons die each year from the consequences of acute and chronic hepatitis B. Current treatments consisting in the use of interferon and/or viral replication inhibitors are insufficient. New therapeutics targeting viral entry are in progress, such as Myrcludex B that has been shown to inhibit HBV infection by preventing HBV entry. However, the mechanism of HBV entry into hepatocytes is still poorly understood. Recently, the identification of NTCP as a specific HBV receptor allowed us to better understand the attachment of this virus. This receptor is now a target for antiviral molecules. It is also a carrier for bile salts known to be strongly regulated by pro inflammatory cytokines. The aims of our thesis were: (i) to study HBV entry by establishing an artificial model of fusion between purified viral particles and liposomes, and (ii) to study the interleukin 6 effect on viral entry. Our results with fusion assays suggest an absence of fusion in the entry process of this virus. However, fusion could require peculiar conditions related to HBV specificities. Our results also demonstrated that interleukin 6 inhibits virus entry by down-regulating NTCP expression

Certains problèmes scientifiques et techniques, imparfaitement résolus dans la mise en œuvre des traitements par ions légers ont été étudiés. La thèse développe successivement les trois approches suivantes : 1) La première partie de cette thèse travaille sur la définition de l'équipement (faisceaux fixes versus gantry) pour un centre de traitement et ainsi traiter la plus large variété possible de tumeurs pour un spectre élargi de situations cliniques caractéristiques chez l'adulte. Les tumeurs étudiées sont des tumeurs de la base du crâne, du rachis cervical haut, bronchiques, ganglionnaires thoraciques, ganglionnaires abdominales et de la prostate, l'on obtient ainsi un éventail assez large d'indications thérapeutiques. 2) La seconde partie met à contribution une partie des outils développés dans la première phase (traitement chez l'adulte). Le même design de salle de traitement est utilisé mais pour un ensemble de tumeurs intracrâniennes de la base du crâne et de la sphère ORL chez l'enfant et l'adulte jeune. Il peut être conclu que l'étude de multiples situations anatomo-pathologiques en thérapie protons n'a pas permis de dégager d'incidences faisceaulogiques originales et particulières à la gantry. 3) La dernière phase donne lieu à l'étude des caractéristiques physiques propres aux faisceaux d'ions carbones. Une comparaison est menée sur la base de simulations de données par l'utilisation de modèles de calcul du risque d'induction néoplasique après traitement chez l'adulte et plus spécifiquement chez l'enfant. La simulation semble indiquer que les ions carbones induiraient un phénomène de stérilisation cellulaire à doses intermédiaires & hautes dans les tissus & organes chez l'adulte et l'enfant
The question of the protontherapy is seen through a purely dosimetric aspect. The main question is to know if the multiplication of beam incidences thanks to a gantry allows obtaining an increase of the therapeutic benefit for the patient. These results suggest that a facility equipped with at least three fixed incidences of beam (horizontal, vertical from above and oblique around 50°) could probably treat properly most of the tumour locations. The second part focus on the pediatric cases in protontherapy. The protons as effective inducer of deterministic and stochastic effects in the paediatric tissues are gauged in the discussion. A thorough investigation on the limits and the possibilities offered by the protons for children is proposed. The third part introduces the study of the carbon-ions treatment. Their carcinogenic action is evaluated and compared against the photons, with consideration to the pediatric tissues and organs. The goal is to estimate by simulation if the carbon-ions bring a therapeutic advantage against the photon or proton treatments. The set of complex interactions within the tissues and organs are precisely explained and a simplified approach is brought. In conclusion, the set of complex radiobiological effects acting within tissues to induce different dose-responses of neoplasic risk can have contradictory actions. The standard and the repopulation models provide a comprehensive insight in spite of their purely theoretical aspect. They reveal some encouraging possibilities for the treatment of children by carbon-ions, especially when the choice of hypofractionation will be possible

The chief aim in developing radiation treatment plans is to maximise tumour cell kill while minimising the killing of normal cells. The acceptance by a radiation oncologist of a radiation therapy treatment plan devised by the radiation therapist, at present is largely based on the oncologists' previous clinical experience with reference to established patterns of treatment and their clinical interpretation of the dose volume histogram. Some versions of radiotherapy planning computer software now incorporate a function that permits biologically based predictions about the probability of tumour control (TCP) and/or normal tissue complications (NTCP). The biological models used for these probabilities are founded upon statistical and mathematical principles as well as radiobiology concepts. TCP and NTCP potentially offer the capability of being able to better optimise treatments for an individual patient's tumour and normal anatomy. There have been few attempts in the past to correlate NTCPs to actual treatment complications, and the reported complications have generally not shown any significant correlation. Thus determining whether either or both NTCPs and TCPs could be correlated with the observed clinical outcomes of prostate radiotherapy is the central topic of this thesis. In this research, TCPs and NTCPs were prospectively calculated for prostate cancer patients receiving radiation therapy, and subsequently assessed against the clinical results of the delivered treatments. This research was conducted using two different types of NTCP models, which were correlated against observed treatment-induced complications in the rectum and bladder. The two NTCP models were also compared to determine their relative efficacy in predicting the recorded toxicities. As part of this research the refinement of some of the published bladder parameters required for NTCP calculations was undertaken to provide a better fit between predicted and observed complication rates for the bladder wall which was used in this research. TCPs were also calculated for each patient using the best available estimate of the radiosensitivity of the prostate gland from recent research. The TCP/NTCP data was analysed to determine if any correlations existed between the calculated probabilities and the observed clinical data. The results of the analyses showed that a correlation between the NTCP and a limited number of toxicities did occur. Additionally the NTCP predictions were compared to existing parameters and methods for radiotherapy plan evaluation - most notably DVHs. It is shown that NTCPs can provide superior discriminatory power when utilised for prospective plan evaluation. While the TCP could not be correlated with clinical outcomes due to insufficient follow-up data, it is shown that there was a correlation between the TCP and the treatment technique used.

The liver is the major detoxifying organ, clearing the blood from drugs and other xenobiotics. The extent of hepatic clearance (CL) determines drug exposure and hence, the efficacy and toxicity associated with exposure. Drug-drug interactions (DDIs) that alter the hepatic CL may cause more or less severe outcomes, such as adverse drug reactions. Accurate predictions of drug CL and DDI risk from in vitro data are therefore crucial in drug development. Liver CL depends on several factors including the activities of transporters involved in the hepatic uptake and efflux. The work in this thesis aimed at developing new in vitro and in silico methods to predict hepatic transporter-mediated CL and DDIs in vivo. Particular emphasis was placed on interactions involving the hepatic uptake transporters OATP1B1, OATP1B3, and OATP2B1. These transporters regulate the plasma concentration-time profiles of many drugs including statins. Inhibition of OATP-mediated transport by 225 structurally diverse drugs was investigated in vitro. Several novel inhibitors were identified. The data was used to develop in silico models that could predict OATP inhibitors from molecular structure. Models were developed for static and dynamic predictions of in vivo transporter-mediated drug CL and DDIs. These models rely on a combination of in vitro studies of transport function and mass spectrometry-based quantification of protein expression in the in vitro models and liver tissue. By providing estimations of transporter contributions to the overall hepatic uptake/efflux, the method is expected to improve predictions of transporter-mediated DDIs. Furthermore, proteins of importance for hepatic CL were quantified in liver tissue and isolated hepatocytes. The isolation of hepatocytes from liver tissue was found to be associated with oxidative stress and degradation of transporters and other proteins expressed in the plasma membrane. This has implications for the use of primary hepatocytes as an in vitro model of the liver. Nevertheless, by taking the altered transporter abundance into account using the method developed herein, transport function in hepatocyte experiments can be scaled to the in vivo situation. The concept of protein expression-dependent in vitro-in vivo extrapolations was illustrated using atorvastatin and pitavastatin as model drugs.

Ce travail de thèse est centré sur l'établissement de modèles prédictifs de toxicité radio-induite et sur l'étude de leur intérêt en cas de radiothérapie par modulation d'intensité. Six modèles NTCP ont été implémentés et leur paramètres identifiés pour la prédiction des toxicités rectale et vésicale tardives dans le cancer de la prostate. Leur capacité prédictive a été démontrée pour les deux organes. Par ailleurs, le modèle LKB a été utilisé pour la prédiction de l'œsophagite aiguë en cas de radiothérapie du cancer bronchique non à petites cellules. Ensuite, le bénéfice tiré de l'incorporation du paramètre de dose équivalent uniforme (EUD) pour la planification inverse de la radiothérapie par modulation d'intensité (IMRT) a été évalué. L'évaluation de cette approche a montré une baisse significative de la dose dans les parois vésicale et rectale. L'incorporation de plusieurs modèles biologiques dans le processus d'optimisation de l'IMRT a aussi été réalisée. Des fonctions objectif ont été établies pour les différents facteurs biologiques comme le NTCP, l'EUD et le TCP. Les résultats dosimétriques obtenus montrent la supériorité de l'optimisation basée sur des facteurs biologiques sur celle reposant uniquement sur des facteurs physiques. Enfin, les modèles NTCP classiques ont été améliorés en intégrant un paramètre radiobiologique supplémentaire, le rapport α/β. Ce rapport α/β a été identifié pour différents types de toxicité. Avec ce nouveau paramètre, les modèles NTCP peuvent finalement être étendus à des patients traités suivant différents fractionnements, les traitements hypofractionnés étant de plus en plus utilisés.

The clinical introduction of proton therapy requires an extensive analysis of its benefits compared to conventional radiotherapy and a detailed analysis of possible uncertainties which might have serious consequences for patient treatment. In the first part of the presented thesis, the expected toxicities were evaluated for a treatment of head and neck cancer patients using a biologically adapted dose escalation schedule with photon and proton therapy. The feasibility of the dose escalation schedule could be demonstrated for both photon and proton therapy, since only a small increase in toxicity risk occurred for most toxicities. However, the expected toxicity risks were in most cases smaller with proton therapy. Furthermore, a higher benefit was found for patients with primary tumour locations in the upper head and neck area, who thus might be preferably referred to proton therapy. In the second part of this thesis, an extensive analysis of the impact of tumour motion in lung cancer treatment with active-scanning proton therapy was conducted. It could be shown, that dose degradations were small for tumour motion amplitudes below 5 mm. Parameters like the target volume concept, the optimisation approach, changes in the motion pattern and application sequence times had additional impact on the dose degradation. However, their magnitude was patient specific. Since not all parameters can be assessed before treatment, e.g. the motion pattern during treatment, prospective estimations should be supplemented by retrospective analyses
Die Einführung der Protonentherapie in die klinische Praxis erfordert umfassende Analysen ihrer Vor- und Nachteile im Vergleich zur konventionellen Photonentherapie sowie detaillierte Untersuchungen der Auswirkungen von Unsicherheiten in der Therapieapplikation. Im ersten Teil der vorliegenden Arbeit wurden die zu erwartenden Nebenwirkungen bei der Behandlung von Patienten mit Kopf-Hals-Tumoren mit einem biologisch-adaptierten Fraktionierungsschema inklusive Dosiseskalation mit Photonen- und Protonentherapie evaluiert. Dabei konnte gezeigt werden, dass die Dosiseskalation sowohl mit Photonen- als auch Protonentherapie angewandt werden kann, da die Wahrscheinlichkeit für das Auftreten von Nebenwirkungen in den meisten Fällen kaum erhöht wurde. Weiterhin wurden die Nebenwirkungswahrscheinlichkeiten mit der Protonentherapie im Vergleich zur Photonentherapie reduziert. Dies war vor allem für Patienten mit Tumoren im oberen Kopf-Hals-Bereich der Fall. Diese könnten daher bevorzugt zur Protonentherapie überwiesen werden. Darüber hinaus wurde im zweiten Teil der Arbeit eine umfassende Analyse des Einflusses der Tumorbewegung auf die Dosisverteilung bei Behandlung von Lungentumoren mit aktiver Protonenstrahlformierung durchgeführt. Dabei zeigte sich, dass Dosisdegradierungen bei Bewegungsamplituden unter 5mm gering sind. Parameter wie das Zielvolumenkonzept, Veränderungen des Bewegungsmusters oder der Applikationszeiten nehmen zusätzlich Einfluss auf die Dosisdegradierung, allerdings in unterschiedlichem Maß für individuelle Patienten. Da nicht alle Parameter vor Behandlung bekannt sein können, sollten prospektive Dosisabschätzungen durch retrospektive Analysen ergänzt werden

L’amortisseur thermique étudié dans le cadre de cette thèse a pour objectif de limiter les pics de température des composants électroniques fonctionnant en régime transitoire au moyen d’une structure composite consistant en un réseau de nanotubes de carbone (NTC) rempli de matériau à changement de phase (MCP) solide-liquide, le tout étant contenu dans un boîtier en silicium (Si). Ce système passif vise à augmenter l’inertie thermique volumique du composant grâce à la chaleur latente du MCP tout en maintenant une bonne conductance thermique grâce aux NTC. Un dispositif expérimental polyvalent a été développé spécifiquement pour caractériser les différentes générations d’échantillons fabriqués par les partenaires du projet THERMA3D. L’excitation thermique de l’échantillon est réalisée au moyen d’un laser en face amont et la réponse thermique est mesurée par caméra infrarouge simultanément sur les faces amont et aval. L’application d’une peinture sélectionnée sur l’échantillon permet d’accéder à sa température après un étalonnage dédié. Des méthodes d’estimation de paramètres ont été développées pour quantifier les deux caractéristiques essentielles de l’amortisseur thermique que sont sa capacité de stockage thermique et sa résistance thermique. Les sensibilités de la résistance thermique aux caractéristiques de la connexion Si/NTC et à la longueur des NTC ont été étudiées et les résistances thermiques d’interface Si/NTC ont été identifiées comme dominantes au sein du système. Des essais de cyclage thermique ont permis d’évaluer la fiabilité de l’ensemble de manière accélérée. Le comportement du MCP et la qualité du matériau de scellement ont été analysés par voie optique. Par ailleurs, la plus élevée des deux résistances thermiques d’interface Si/NTC a été localisée grâce à la visualisation infrarouge du réseau de NTC à travers le silicium semi-transparent. Enfin, une méthode de contrôle non destructif de la qualité de l’interface Si/NTC a été développée pour les amortisseurs thermiques de dernière génération
The purpose of the studied thermal damper is to smooth the temperature peaks of transient electronic components via a composite structure consisting of an array of carbon nanotubes (CNT) filled with solid-liquid phase change material (PCM), the whole being embedded in a silicon (Si) casing. This passive system is intended to increase the thermal inertia per unit of volume of the electronic component thanks to the latent heat of the PCM while maintaining a high thermal conductance thanks to the CNT. A versatile test bench was specifically developed in order to characterize the different generations of samples fabricated by the partners of the THERMA3D project. The thermal excitation of the front side of the sample is generated by a laser and the thermal response is measured simultaneously on the front and back sides by an infrared camera. A selected paint can be deposited on the sample in order to access its temperature by means of a dedicated calibration. Parameter estimation methods were developed in order to quantify both main characteristics of the thermal damper: its heat storage capacity and its thermal resistance. The sensitivities of the thermal resistance to the features of the Si/CNT connection and to the length of the CNT were studied and it was found out that the interfacial thermal resistances Si/CNT are dominant in the system. Thermal cycling tests enabled to assess the reliability of the thermal damper in an accelerated manner. The behavior of the PCM and the quality of the sealing material were optically analyzed. Besides, the infrared visualization of the CNT array through the semi-transparent silicon enabled to identify the highest of both Si/CNT interfacial thermal resistances. Finally, a non-destructive testing method for the evaluation of the quality of Si/CNT interfaces was developed for the latest generation of thermal dampers

Nitrogen is an essential building block of proteins and nucleic acids and, therefore, crucial for the biosphere. Nearly 79 % of the air consists of nitrogen, but in the form of nitrogen gas (N₂), which cannot be utilized by most organisms. Nitrogen-fixing microorganisms such as cyanobacteria have a central role in supplying biologically useful nitrogen to the biosphere. Therefore, it is important to achieve further understanding of control mechanisms involved in nitrogen fixation and related processes.

This thesis concerns different molecular aspects of the transcription factor NtcA from the heterocystous cyanobacterium Anabaena PCC 7120. Apart from performing oxygenic photosynthesis, Anabaena PCC 7120 is also capable of fixing nitrogen. NtcA is a protein regulating transcription of a wide range of genes and in particular genes involved in cyanobacterial global nitrogen control. NtcA binds as a dimer to the promoter regions of target genes such as those involved in nitrogen fixation and heterocyst differentiation.

NtcA from Anabaena PCC 7120 was heterologously expressed in E. coli and a high yield of recombinant protein was achieved through purification by Ni-IMAC chromatography. The purified NtcA was used to examine DNA binding motifs preferred by NtcA in vitro using a semi-random library of DNA sequences. The preferred binding sequence for NtcA is TGTA – N₈ – TACA and at least five of the bases in the palindromic binding site are necessary for binding. Differences in the consensus sequence in vivo may reflect variations in the structural conformation of NtcA under various physiological conditions.

Since an earlier study suggested redox-regulated NtcA-DNA binding the role of the two cysteine residues of NtcA were investigated. Binding studies using three mutants, Cys157Ala, Cys164Ala, and Cys157Ala / Cys164Ala, demonstrated that all these NtcA variants bind to DNA with a slightly higher affinity in the presence of the reducing agent DTT. The studies indicate that the binding mechanism is not dependent on a conformational change of NtcA caused by breaking of intra-molecular disulfide bonds.

Crystallization followed by structural studies rendered a partial crystal structure of NtcA. The structure verifies that NtcA is a dimeric protein. Each subunit has three domains: the N-terminal domain, a dimerization helix connecting the N-terminal domain with the C-terminal domain, as well as making up the dimer interface, and a C-terminal domain including the DNA binding helix-turn-helix motif.

Furthermore, an NtcA binding site was found in the promoter region of the hupSL gene, encoding an uptake hydrogenase in Nostoc punctiforme (ATCC 29133), indicating that yet another gene is transcriptionally controlled by NtcA, thereby further emphasizing the multifaceted role of NtcA in cyanobacteria.

Materiais cerâmicos à base de óxidos de manganês, de níquel e de cobalto foram preparados por meio de mistura de óxidos seguida de homogeneização e sinterização controlada em 1250 °C. Os óxidos foram caracterizados por meio das técnicas de difração de raios X, fluorescência de raios X, termogravimetria e determinação de distribuição de tamanho de partículas por espalhamento laser. A caracterização dos corpos sinterizados foi feita por meio de análise por microscopia eletrônica de varredura, difração de raios X e fluorescência de raios X. O comportamento termistor foi estudado por meio de medidas de resistividade elétrica pela técnica dc de duas pontas de prova entre temperatura ambiente e 220 °C. Os principais resultados mostram ser possível a preparação de termistores em ampla faixa de resposta elétrica por meio da variação da composição relativa dos óxidos de manganês, de níquel e de cobalto.
Ceramic tliermistors based on manganese, nickel and cobalt oxides were prepared by mixing these oxides followed by pressing and sintering at 1250 °C range. The oxides were characterized by X-ray diffraction, X-ray fluorescence, thermogravimetry and differential thermal analysis, and by the determination of particle size distribution by laser scattering. After sintering. X-ray diffraction. X-ray fluorescence and scanning electron microscopy analyses were carried out. The thermistor behavior was studied by two-probe dc electrical resistivity measurements in the room temperature-220 °C range. The main results show the possibility of designing thermistors with the required electrical response by suitable choice of the relative concentrations of the precursor oxides.

With its enormous potential Voice over Internet Protocol is one of the latest buzzwords in information technology. Despite the numerous advantages of Voice over IP, it is a major technical challenge to achieve a similar call quality as experienced in the ordinary Public Switched Telephone Network. This thesis introduces standardized Internet protocols for Voice over IP, such as Session Initiation Protocol (SIP), Real-time Transport Protocol (RTP), in its background chapter. In order to provide better Quality of Service (QoS) Voice over IP applications should support a feedback mechanism, such as the Real-time Control Protocol (RTCP), and use accurate timing information, provided by the Network Time Protocol (NTP). Additionally this thesis considers synchronization issues in calls with two and more peers. After a rather academic overview of Voice over IP, the open source real-time application “minisip”, a SIP user agent, and its operation and structure for handling audio streams will be introduced. Minisip was extended by an implementation of NTP and RTCP to provide a test platform for this thesis. A clear conclusion is that the addition of global time helps facilitate synchronization of multiple streams from clients located any where in the network and in addition the ability to make one-way delay measurements helps SIP user agents to provide better quality audio to their users.
Röst över IP, eller Internettelefoni baserad på “Voice over Internet Protocol” (VoIP), har med sin stora potential blivit ett av de senaste modeorden inom informationsteknologin. Vid sedan av ett antal fördelar med VoIP så innebär det en stor teknisk utmaning att uppnå en likadan samtalskvalitet som i det vanliga, fasta, telenätet. I den här uppsatsen beskrivs hur tjänstevalitet för VoIP kan förbättras genom att noggrant tidssynkronisera de (två eller flera) klienter som deltar i ett telefonsamtal. För detta krävs dels en återkopplingsmekanism, såsom “Real-time Control Protocol” (RTCP), samt en gemensam tidsuppfattning i de inblandade klienterna, vilket kan uppnås med hjälp av “Network Time Protocol” (NTP). Dessa protokoll, liksom de övriga Internet-standarder som VoIP baseras på (såsom “Session Initiation Protocol” (SIP) och “Real-time Transport Protocol” (RTP), beskrivs inledningsvis i uppsatsen. För studien har en SIP-klient baserad på öppen källkod använts (“Minisip”), och utökats med NTP och RCTP funktionalitet för att testa den föreslagna förbättringen av VoIP. En tydlig slutsats är att kännedom om en “global tid” möjliggör synkronisering av multipla ljudströmmar från klienter som befinner sig på olika nätverk. Möjligheten att mäta paketfördröjningen (envägs) bidrar också till en förbättrad ljudkvalitet.

Made available in DSpace on 2016-08-17T14:52:51Z (GMT). No. of bitstreams: 1 Michel Valenca Gabriel.pdf: 465513 bytes, checksum: 942d92f812d9d94a2f9910b710ac55f2 (MD5) Previous issue date: 2004-01-30
In this work we present a study on the sensitivity of anemometers based on thermoresistive sensors heated to a constant temperature. The configurations that makes the thermoresistive sensor heated to a constant temperature are composed of a Wheatstone bridge using a feedback operational amplifier. The substitution measurement method is used, where an electrical quantity, the operational amplifier output voltage, varies in accordance to the variation of the quantity of interest, in such a way that the electrical quantity compensates the effect of the former in the sensor. In our case, the quantity to be measured is the speed of the wind and the quantity of substitution is operational amplifier output voltage. Studies were carried out considering two types of sensors, the metallic PTC and the thermistor NTC. An analysis of the measurement circuits was carried out for each sensor type, taking into account the constants and variables that influence the measurement process. For these circuits, simulation results are presented which make possible to evaluate the measurement system behavior. An analysis of the sensitivity of the measurement circuits output voltage with respect to the wind speed is also carried out. This analysis made possible the development of a procedure for determining the operation point for the NTC-based circuit that yields the maximum sensitivity. From the analysis of the measurement configurations sensitivity, it was observed that the NTC-based configuration presents higher sensitivity compared to the PTC-based configuration, for relatively low operating temperatures, above the ambient temperature. The equivalent sensitivity for the PTC-based configuration occurs only for temperatures much higher than that for achieving the maximum sensitivity for the NTC. This characteristic can be used for implementing anemometers that operates at a temperature much closer to the ambient temperature.
Neste trabalho apresentamos um estudo sobre a sensibilidade de anemômetros baseados em sensores termo-resistivos aquecidos a temperatura constante. A configuração que faz com que o sensor termo-resistivo seja aquecido a uma temperatura constante é composta de uma ponte de Wheatstone realimentada usando um amplificador operacional [1]. O método de medição utilizado é o de substituição, em que uma grandeza elétrica, a tensão de saída do amplificador operacional, varia de acordo com a variação da grandeza de interesse, de forma a compensar seu efeito no sensor. Neste caso, a grandeza a ser medida é a velocidade do vento e a grandeza de substituição é a tensão de saída do amplificador operacional. Foram feitos estudos considerandos dois tipos de sensores, o PTC metálico e o termistor NTC. Faz-se uma análise dos circuitos de medição para cada tipo de sensor, levando em conta as constantes e as variáveis que interferem no processo de medição. Para tais circuitos são apresentados resultados de simulações em computador que nos possibilitaram avaliar o comportamento do sistema de medição. Para os circuitos de medição, faz-se uma análise da sensibilidade da tensão de saída do amplificador operacional com relação à velocidade do vento. Essa análise possibilitou desenvolvimento de um método para cálculo do ponto de maior sensibilidade e ponto de operação do circuito baseado no NTC. Observou-se que a configuração com NTC apresenta uma maior sensibilidade do que a configuração com PTC para temperaturas de operação do sensor relativamente baixas, mas acima da temperatura ambiente. A sensibilidade equivalente da configuração com o PTC ocorre para temperaturas bem acima do ponto de máxima sensibilidade do NTC. Essa característica pode ser aproveitada para implementações de anemômetros aquecidos que operam com temperaturas mais próximas da temperatura ambiente.

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Carbon nanotubes are among the most promising nanomaterials with special features for use both as biomedical engineering. Several studies on the toxicity and feasibility are performed to assess its application in humans for delivery of drugs. In this study, we performed the evaluation of the hepatotoxic effect of carbon nanotubes multi-wall (MWCNT) by biochemical markers (albumin (ALB), total protein (TP), transaminases (ALT / AST), alkaline phosphatase (ALP), lactate dehydrogenase (LDH)) after administration via the intraperitoneal and intragastric in female mice at a dose of 1.5 mg / kg suspended in saline. Blood samples were analyzed one day, 7 and 30 days after treatment with MWCNT. The results after intraperitoneal administration showed a rise in serum total protein after 1 and 7 days. Serum albumin showed an increase in concentration after 7 days and 30 days after reduction. The activity of ALT levels increased only after 1 day, whereas the activity of AST showed an increase after 7 and 30 days. The LDH activity also increased significantly after 7 and 30 days. The FAL showed an increase in its activity after 1 and 7 days and a reduction after 30 days. The results obtained after intragastric administration of MWCNT showed an increase in serum total protein after 7 days and 30 days after reduction. Albumin did not show significant variations. The ALT activity increased significantly after 1 day and a reduction after 30 days. AST activity showed no significant differences in this way. The activity of LDH showed an increase after 7 days, no significant difference after 1 day and 30 days. The activity of ALP showed an increase after only one day. Serum albumin and total protein indicate an acute inflammatory process by both intraperitoneal and through activities of liver enzymes intragastric. As intraperitoneally showed severe liver injury while intragastrically showed mild reversible liver damage.
Nanotubos de carbono estão entre os nanomateriais mais promissores, com características especiais tanto para uso biomédico quanto para engenharia. Vários estudos sobre a sua toxicidade e viabilidade são realizados para avaliar sua aplicação em seres humanos para entrega de fármacos. Neste estudo, realizamos a avaliação do efeito hepatotóxico de nanotubos de carbono de parede múltipla (NTCPM) através de marcadores bioquímicos albumina (ALB), proteínas totais (PT), transaminases (ALT/AST), fosfatase alcalina (FAL), lactato desidrogenase (LDH)), após administração via intraperitoneal e via intragástrica em camundongos fêmeas na dose de 1,5mg/Kg suspensos em solução salina. As amostras de sangue foram analisadas 1 dia, 7 e 30 dias após o tratamento com NTCPM. Os resultados obtidos após administração intraperitoneal demonstraram uma elevação na concentração sérica de proteínas totais após 1 e 7dias. A albumina sérica apresentou um aumento na sua concentração após 7 dias e uma redução após 30 dias. A atividade de ALT apresentou aumento somente após 1 dia, enquanto que a atividade da AST apresentou aumento após 7 e 30 dias. A atividade de LDH também apresentou um aumento significativo após 7 e 30 dias. A FAL apresentou aumento em sua atividade após 1 e 7 dias e uma redução após 30 dias. Os resultados obtidos após a administração via intragástrica de NTCPM apresentaram um aumento na concentração sérica de proteínas totais após 7dias e uma redução após 30 dias. A albumina não apresentou variações significativas. A atividade de ALT apresentou um aumento significativo após 1 dia e uma redução após 30 dias. A atividade da AST não apresentou diferenças consideráveis por esta via. A atividade de LDH apresentou um aumento após 7dias, não apresentando diferença após 1 dia e 30 dias. A atividade da FAL apenas apresentou aumento após 1 dia. Os valores séricos de albumina e proteínas totais indicam um processo inflamatório agudo tanto pela via intraperitoneal quanto pela via intragástrica.As atividades das enzimas hepáticas por via intraperitoneal indicaram lesão hepática grave enquanto que por via intragástrica indicaram lesão hepática leve reversível.

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Carbon nanotubes are among the most promising nanomaterials with special features for use both as biomedical engineering. Several studies on the toxicity and feasibility are performed to assess its application in humans for delivery of drugs. In this study, we performed the evaluation of the hepatotoxic effect of carbon nanotubes multi-wall (MWCNT) by biochemical markers (albumin (ALB), total protein (TP), transaminases (ALT / AST), alkaline phosphatase (ALP), lactate dehydrogenase (LDH)) after administration via the intraperitoneal and intragastric in female mice at a dose of 1.5 mg / kg suspended in saline. Blood samples were analyzed one day, 7 and 30 days after treatment with MWCNT. The results after intraperitoneal administration showed a rise in serum total protein after 1 and 7 days. Serum albumin showed an increase in concentration after 7 days and 30 days after reduction. The activity of ALT levels increased only after 1 day, whereas the activity of AST showed an increase after 7 and 30 days. The LDH activity also increased significantly after 7 and 30 days. The FAL showed an increase in its activity after 1 and 7 days and a reduction after 30 days. The results obtained after intragastric administration of MWCNT showed an increase in serum total protein after 7 days and 30 days after reduction. Albumin did not show significant variations. The ALT activity increased significantly after 1 day and a reduction after 30 days. AST activity showed no significant differences in this way. The activity of LDH showed an increase after 7 days, no significant difference after 1 day and 30 days. The activity of ALP showed an increase after only one day. Serum albumin and total protein indicate an acute inflammatory process by both intraperitoneal and through activities of liver enzymes intragastric. As intraperitoneally showed severe liver injury while intragastrically showed mild reversible liver damage.
Nanotubos de carbono estão entre os nanomateriais mais promissores, com características especiais tanto para uso biomédico quanto para engenharia. Vários estudos sobre a sua toxicidade e viabilidade são realizados para avaliar sua aplicação em seres humanos para entrega de fármacos. Neste estudo, realizamos a avaliação do efeito hepatotóxico de nanotubos de carbono de parede múltipla (NTCPM) através de marcadores bioquímicos albumina (ALB), proteínas totais (PT), transaminases (ALT/AST), fosfatase alcalina (FAL), lactato desidrogenase (LDH)), após administração via intraperitoneal e via intragástrica em camundongos fêmeas na dose de 1,5mg/Kg suspensos em solução salina. As amostras de sangue foram analisadas 1 dia, 7 e 30 dias após o tratamento com NTCPM. Os resultados obtidos após administração intraperitoneal demonstraram uma elevação na concentração sérica de proteínas totais após 1 e 7dias. A albumina sérica apresentou um aumento na sua concentração após 7 dias e uma redução após 30 dias. A atividade de ALT apresentou aumento somente após 1 dia, enquanto que a atividade da AST apresentou aumento após 7 e 30 dias. A atividade de LDH também apresentou um aumento significativo após 7 e 30 dias. A FAL apresentou aumento em sua atividade após 1 e 7 dias e uma redução após 30 dias. Os resultados obtidos após a administração via intragástrica de NTCPM apresentaram um aumento na concentração sérica de proteínas totais após 7dias e uma redução após 30 dias. A albumina não apresentou variações significativas. A atividade de ALT apresentou um aumento significativo após 1 dia e uma redução após 30 dias. A atividade da AST não apresentou diferenças consideráveis por esta via. A atividade de LDH apresentou um aumento após 7dias, não apresentando diferença após 1 dia e 30 dias. A atividade da FAL apenas apresentou aumento após 1 dia. Os valores séricos de albumina e proteínas totais indicam um processo inflamatório agudo tanto pela via intraperitoneal quanto pela via intragástrica.As atividades das enzimas hepáticas por via intraperitoneal indicaram lesão hepática grave enquanto que por via intragástrica indicaram lesão hepática leve reversível.

Thesis (Ph.D.)--Michigan State University. Dept. of Biochemistry and Molecular Biology, 2008.
Title from PDF t.p. (viewed on Apr. 2, 2009) Includes bibliographical references. Also issued in print.

The growing market of portable devices and smart wearables has contributed to innovation and development of systems with longer battery-life. While Near Threshold Computing (NTC) systems address the need for longer battery-life, they have certain limitations. NTC systems are prone to be significantly affected by variations in the fabrication process, commonly called process variation (PV). This dissertation explores an intriguing effect of PV, called choke points. Choke points are especially important due to their multifarious influence on the functional correctness of an NTC system. This work shows why novel research is required in this direction and proposes two techniques to resolve the problems created by choke points, while maintaining the reduced power needs.

Sustainable harvesting of non-timber forest products (NTFPs) and associated livelihood security can be compromised by changes in the broader ecosystem. This study investigates mistletoe infection of Amla, Phyllanthus emblica and Phyllanthus indofische7i, an NTFP of significant livelihood importance, in the Biligiri Rangaswarny Temple (BRT) Wildlife Sanctuary in southern India. Infection patterns of the Loranthaceae mistletoe, Taxillus tomentosus, were characterised across the Amla population and their underlying mechanisms explored. Two alternative management approaches were investigated, and traditional ecological knowledge documented and assessedfo r its concordance and additionality to scientific data. A high prevalence of infection, and the apparent greater susceptibility of the more significant resource species, suggests that mistletoe infection has serious implications for Amla sustainability. Traditional knowledge provided novel information on infection spread, and highlighted failings in current population assessments, emphasising the importance of a multidisciplinary approach to assessing sustainability. Traditional approaches to management conflict with current institutional perspectives, but may be somewhat more effective and require further investigation. However, existing data, both from scientific studies and traditional knowledge, are insufficient to prescribe with certainty the best approach to mistletoe control. The participatory implementation of an active adaptive management programme may offer benefits over alternative management options for securing Amla as a viable NTFP harvesting system.

Detta arbete behandlar en specifik typ av överbelastningsattack som blir allt mer populär. Dessa attacker utförs genom öppna reläer med syftet att få ut en avsevärt mycket högre effekt än den som annars är uppnåbar. Granskning av attacker utförda genom tjänsterna DNS och NTP har utförts med syftet att ge en klar bild av hur allvarligt hotet är och även klargöra hur en systemadministratör kan säkra tjänsterna för att skydda både sina egna och andras resurser. Resultaten av undersökningar visar att en attack utförd genom en DNS-tjänst ger under optimala förhållanden en amplifikationsfaktor av "102.4" och en attack genom en NTP-tjänst ger under optimala förhållanden en amplifikationsfaktor av "229.16". Resultaten visar även att problemet kan lösas helt eller delvis genom att begränsa tillåtna nätverk eller stänga av rekursion i DNS och kommandon i NTP.
This work concerns a specific type of Denial of Service attack which is becoming increasingly popular. These attacks are carried out through open relays with the purpose of getting a significantly higher effect than otherwise achievable. Examination of attacks carried out through the services DNS and NTP have been conducted with the purpose of providing a clear picture of how serious the threat is and also clarify how a system administrator can secure the services to protect both their own and others resources. The results of our studies show that an attack performed through a DNS service gives under optimal conditions a amplification factor of "102.4" and an attack through a NTP service gives under optimal conditions a amplification factor of "229.16". The results also show that the problem can be solved in whole or in part by limiting the allowed network or disable recursion in DNS and commands in NTP.

Thesis (M.S. in Management)--Naval Postgraduate School, June 1990.
Thesis Advisor(s): Liao, Shu S. Second Reader: Matthews, Danny G. "June 1990." Description based on title screen as viewed on March 23, 2010. DTIC Identifier(s): Communications Networks, Naval Operations, Cost Effectiveness, Digital Communications, Economic Impact, Theses, DMS (Defense Message System), AUTODIN (Automatic Digital Network), Message Delivery, Naval Telecommunications Center (California), Monterey (California). Author(s) subject terms: Defense Message System, NTCC Monterey. Includes bibliographical references (p. 53-56). Also available in print.

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Coordenação de Aperfeiçoamento de Pessoal de Nível Superior
O Network Time Protocol (NTP) é um protocolo para sincronização de relógios de computadores em rede que tem quase duas décadas de existência e está em contínua evolução. Com algoritmos robustos para tratamento de fase e freqüência, com um bom disciplinador de relógio local e tendo implementações para as mais diversas plataformas e sistemas operacionais de computadores e equipamentos de rede, o NTP tornou-se um padrão de fato. Entretanto, esse protocolo ainda tem problemas que precisam ser solucionados para ser operacionalmente eficaz, pois seu desempenho depende de boas condições de rede para a troca das informações de sincronização, sofrendo bastante em caso de congestionamento. Devido a esses problemas, em vários países (incluindo o Brasil) esse protocolo é considerado inadequado para prover informação de horário de forma confiável, fazendo com que registros de hora em sistemas que o utilizam não tenham valor legal. Além disso, muitas aplicações necessitam de um sistema de controle de relógios confiável para funcionar corretamente (por exemplo, sistemas bancários e servidores de bancos de dados distribuídos). Isso obriga muitas empresas a utilizar sistemas legados tradicionais e mais caros para poder funcionar de forma correta e legal. Com o advento da Qualidade de Serviço em redes de computadores, esse problema pode ser abordado elegantemente e resolvido. Várias arquiteturas de Qualidade de Serviço foram propostas, mas a arquitetura de Serviços Diferenciados (DiffServ), devido a sua facilidade de implementação e ao fato de ter sido a mais estudada e implementada experimentalmente, mostrou-se a mais forte candidata à implantação mundial e no menor prazo. Essa arquitetura adequou-se bem ao problema de sincronização de relógios, embora a solução não seja trivial. Essa dissertação sugere um arcabouço para lidar com a sincronização de relógios através do NTP em domínios DiffServ com ou sem corretores de banda. Tendo-se Serviços Bem Definidos (Well Defined Services WDS) e baseado na idéia de que as aplicações devem conhecer o tipo de tratamento necessário ao seu tráfego, esse arcabouço consiste na adoção de políticas para o tratamento de tráfego NTP nos equipamentos de rede e na adoção de uma política para a marcação de pacotes por parte da aplicação. A proposta é validada com um estudo de caso feito com medição real do desempenho da aplicação sobre um ambiente de rede emulado

TRAIL (TNF-related apoptosis inducing ligand) est une protéine anti-tumorale capable de se lier spécifiquement aux récepteurs agonistes de mort (TRAIL-Rl ou DR4 et TRAIL-R2 ou DR5) des cellules cancéreuses et d'induire leur apoptose sans être toxique pour les cellules saines. Grâce à leurs propriétés exceptionnelles, notamment leur biocompatibilité, les nanotubes de carbone et surtout les SWCNTSs sont utilisés dans un large éventail d'applications et sont considérés très prometteurs pour révolutionner la thérapie anticancéreuse en nanomédecine. Les SWCNTSs sont connus par leur diffusion rapide dans un milieu aqueux tel que le sang, ouvrant la voie de développement de nouveaux nanovecteurs de médicaments. L'objectif principal de nos travaux de thèse a consisté à fonctionnaliser TRAIL sur des SWCNTSs pour mimer sa fonction membranaire en induisant une forte agrégation des récepteurs et déclencher l'apoptose (mort cellulaire programmée). Dans un premier temps, la fonctionnalisation des SWCNTSs avec TRAIL a été réalisée: adsorption non covalente des molécules de PSE sur les nanotubes via 1t-1t stacking, puis greffage du TRAIL au complexe SWCNTS-PSE pour former le nanovecteur (nommé NPT). Ensuite, nous avons caractérisé notre NPT par différentes méthodes (RAMAN, XPS, IR, MET, STEM ... ) afin d'estimer le taux de greffage du TRAIL sur le NPT, qui était environ de 80%. Dans un deuxième temps, nous avons étudié les paramètres thermodynamiques tels que le pH et la température du NPT en comparaison avec TRAIL seul par une approche chromatographique d'affinité (CHLP). Les résultats obtenus montrent une meilleure affinité du nanovecteur par rapport à TRAIL seul avec le récepteur TRAIL-R2 immobilisé sur la colonne chromatographique. En outre, des calculs de docking ont montré également que le complexe NPT couplé aux homotrimères de TRAIL est le plus stable une fois docké au récepteur TRAIL-R2. Ainsi, nous avons montré que les interactions de type Van der Waals et des liaisons hydrogène régissent l'association NPT-DR5 pour un pH supérieur à 7,4 (comme pour TRAIL seul). Enfin, notre nanovecteur s'est avéré plus efficace que TRAIL seul dans des différents tests menés in vitro sur des plusieurs types de lignées tumorales. Le NPT a permis une augmentation du potentiel pro­apoptotique de TRAIL avec un gain de fonction apoptotique estimé entre 10-20 fois par rapport à celui obtenu avec TRAIL seul. Dans ce travail, nous fournissons ainsi une preuve de concept que les nanovecteurs basés sur la fonctionnalisation du TRAIL avec les SWCNTSs peuvent être utiles pour les futurs traitements anti-cancéreux en nanomédecine
TRAIL (TNF-related apoptosis inducing ligand) is a protein involved in immune anti-tumor surveillance. This cytokine is able to bound specifically to agonist death receptors (TRAIL-Rl or DR4 and TRAIL-R2 or DR5) of cancer cells, inducing apoptosis without being taxie to healthy cells. Thanks to their exceptional properties such as biocompatibility, carbon nanotubes and especially single-walled carbon nanotubes (SWCNTSs) are used in a wide range of applications and are considered to be very promising for cancer therapy in nanomedicine. The SWCNTSs are known to rapidly diffuse in aqueous media such as blood, opening the way for the development of new drug nanovectors or nanocarriers. The main purpose of this work is to functionalize SWCNTSs with TRAIL to mimic the membrane function of TRAIL by inducing a strong aggregation of death receptors and then induce apoptosis. First of all, the choice of SWCNTS functionalization with TRAIL was considered the first key in this thesis: non-covalent adsorption of PSE molecules on the nanotubes via 1t-1t stacking and TRAIL was next attached to a SWCNTS-PSE to form our nanovector, called NPT. Then, the NPT was characterized by various methods (Raman, XPS, IR, TEM, STEM, ... ) in order to estimate the grafted degree of TRAIL on the NPT surface (about 80%). Secondly, we investigated the ef:fects of the thermodynamic parameters such as pH and temperature on NPT versus TRAIL by a chromatographie approach (HPLC). The results showed a better affinity for NPT compared to TRAIL alone with the TRAIL-R2 receptor immobilized on the chromatographie colurnn. In addition, docking calculations have also shown that the NPT complex coupled to TRAIL homotrimers is the most stable when docked to DR5. Thus, we have demonstrated that Van der Waals interactions and hydrogen bonds govem the NPT-DR5 association for pH > 7.4 (as for TRAIL). Finally, our TRAIL-based SWCNTSs nanovectors (NPT) proved to be more efficient than TRAIL alone towards death receptors in triggering cancer cell killing in vitro. These NPTs increased the pro-apoptotic potential of TRAIL by nearly 10 to 20-fold in different Human tumor cell lines tested including colorectal, non-small cell lung cancer, or hepatocarcinomas. We provide in this work a proof of concept that nanovectors based on SWCNTS functionalization with TRAIL may be useful for future cancer treatments in nanomedicine

Vattenfall and Svenska Kraftnät perform start-up tests, where hydropower generators are used to power up the electrical grid in case of a blackout. To monitor the electrical grid, Phasor Measurement Units (PMU) are used. Each PMU is individually equipped with a GPS-receiver to precisely timestamp the data relative to the official time UTC. During the test, it is also of interest to timestamp the measurement signals from individual hydropower generators to later compare with PMU-data, and thus study the power grids impact on the generator.

 

The aim is to work out an appropriate method to make these measurements and to build a data acquisition system, capable of timestamp data relative to UTC, from a generator in one of Vattenfalls hydroelectric power stations. The problem is that the generator is located in an underground station which hampers the reception of GPS-signals and wiring should be avoided if possible.

 

Time synchronization has been solved by using Vattenfalls network, which is synchronized by the network protocol NTP. The network includes the concerned hydropower stations and thus can wiring from the surface be avoided. The maximum error for the server in the specific hydroelectric power station is bounded within [-4.62, 3.18] ms relative to UTC. The conclusion is that Vattenfalls NTP-network meets the requirements to distribute time. A platform from National Instruments, programmed with the graphical language LabVIEW, has been used for data acquisition. The platform is programmed to synchronize its internal clock to a NTP-server, timestamp the input signals and save the data on the internal hard drive.

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Conselho Nacional de Desenvolvimento Científico e Tecnológico (CNPq)
Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP)
In the present work epoxy/ MWCNT/ mineral fillers nanocomposites were obtained using ultrasonication and calendering. The effect of addition of mineral filler (calcium carbonate, montmorillonite and sepiolite) in electrical, mechanical and thermal properties of epoxy/ MWCNT were analyzed. Two different CNT were studied, with different aspect ration and purity, however only Nanocyl CNT’s presented improvement in the nanocomposites electrical properties and for that reason was employed for hybrid epoxy/ MWCNT/ mineral nanocomposites production. The electrical percolation threshold was determined as 0.04 wt% and for 0.3 wt% the electrical conductivity reached 1.29X10-2 S/m. The addition of calcium carbonate and montmorillonite improved electrical conductivity for epoxy nanocomposites produced with 0.05 wt% CNT and the same behavior was observed for epoxy/ MWCNT / sepiolite nanocomposites at 0.1 wt% CNT. The epoxy/ MWCNT nanocomposite at 0.05% CNT when produzed via calendering presented improvement in the electrical conductivity compared to the same nanocomposite produced via ultrasonication. For epoxy/ MWCNT at 0.05 wt% of CNT, the addition of calcium carbonate in the nanocomposite led to an electrical conductivity 1 decade higher than the epoxy/ 0.05 wt% CNT nanocomposite produced via calendering. The mineral fillers also modified thermal and mechanical behavior of the nanocomposites, and improvements in flexural modulus, thermal stability and Tg were observed.
Neste trabalho produziu-se nanocompósitos híbridos de resina epóxi/ NTCPM/ cargas minerais utilizando-se sonicação de alta energia e calandragem, e estudou-se a influência da adição de diferentes cargas minerais (carbonato de cálcio, montmorilonita e sepiolita) nas propriedades elétricas, térmicas e mecânicas de nanocompósitos epóxi/NTCPM. Neste trabalho foram utilizados dois diferentes tipos de nanotubos de carbono, com razões de aspecto e purezas diferentes, e verificou-se que somente um deles apresentou melhoria nas propriedades elétricas dos nanocompósitos epóxi/NTCPM, o qual foi empregado na produção de nanocompósitos híbridos epóxi/ NTCPM/ cargas minerais. A percolação elétrica dos nanotubos de carbono foi determinada em aproximadamente 0,04% em massa, e para um teor de 0,3% em massa de nanotubos de carbono, a condutividade elétrica atingiu 1,29X10-2 S/m. Nos nanocompósitos processados via sonicação de alta energia, observou-se elevação da condutividade elétrica com a adição de montmorilonita sódica e carbonato de cálcio para os teores de 0,05% em massa de NTCPM e com a adição de sepiolita somente para o teor de 0,1% em massa de NTCPM. Nos nanocompósitos processados via calandragem, o nanocompósito de resina epóxi/ 0,05% NTCPM apresentou condutividade elétrica duas vezes superior ao mesmo nanocompósito processado via sonicação de alta energia e a adição de carbonato de cálcio elevou a condutividade elétrica do nanocompósito de resina epóxi/ 0,05% NTCPM/ carbonato de cálcio em uma ordem de grandeza quando comparado ao nanocompósito epóxi/ 0,05% NTCPM processado via calandragem. A adição de NTCPM e cargas minerais também modificou os comportamentos mecânico e térmico dos nanocompósitos, elevando-se o módulo elástico em flexão, resistência térmica e Tg.
FAPESP: 2014/16299-8

In this study reliable film type NTCR thermistors based on NiMn(_2)O(_4)+δ were produced and their electrical properties were studied in detail. Electron-beam evaporation procedures have been applied to produce thin film NTCR thermistors. Phase pure NiMn(_2)O(_4)+δ target material was produced via a traditional ceramic precursor oxide route and thin films were deposited in an optimised procedure. The thickness distribution of evaporated films showed good agreement with a theoretical model, derived from evaporation theory and the sticking coefficient of the vapour on the substrates was approximately 80% ± 1.5%. The composition of electron-beam evaporated films was found to be not controllable in terms of the phase purity and the Ni : Mn ratio. In order to avoid these problems thick film NiMn(_2)O(_4)+δ NTCR thermistors were developed using direct screen-printing techniques. Detailed Rietveld refinement analysis was carried out for the source powder used for screen-printing. The main focus of the work was the measurement of resistance-temperature (R-T) characteristics of thin and thick films and pellets. In the temperature range of concern (77 K -550 K) conduction was found to be by variable-range hopping (VRH) and nearest-neighbour hopping (NNH); R ~ exp (TʆT)(^p), where the index p depends on the mode of hopping. Detailed analysis of R-T data showed that screen-printed films and pellets exhibited a p-value of 0.5, which was identified with VRH with a parabolic density of states (DOS) with an exponential dependence of resistance: R ~ exp (TʆT)(^0.5). For electron-beam evaporated films the mechanisms detected were NNH: R ~ exp (TʆT); and VRH with a constant DOS {p = 0.25) following: R ~ exp (TʆT)(_0.25). For screen-printed films with incorporated glass phase the electrical conduction mechanism was analysed using a.c. impedance spectroscopy and at low frequencies the hopping conduction was in agreement with the d.c. behaviour. The time constant of this mechanism could be described by an equivalent circuit containing a RC element. For higher frequencies a second mechanism was found, best described by a CRL element.

Drug-induced liver injury (DILI) is the major cause of pharmaceutical withdrawal from the market and cholestasis is one of the most common DILI observed. Cholestasis stem from abnormalities in the activity of bile acid transporters, namely the sodium-dependent taurocholate co-transporting polypeptide, Ntcp (Slc10a1), and the bile salt export pump, Bsep (Abcb11). The nuclear receptors, pregnane X receptor (PXR) and farnesoid X receptor (FXR), have been implicated in the regulation of Ntcp and Bsep. The aim of this study was to establish the relative roles of FXR and PXR in the regulation of Ntcp and Bsep, in the rat liver and sandwich cultured rat hepatocytes (SCRH) to establish the usefulness of SCRH as a good model for bile acid transport studies. For this purpose, male Sprague Dawley rats were treated with FXR and PXR ligands and siRNAs. Intraperitoneal (IP) injection of FXR ligand, CDCA, resulted in induction in FXR mRNA levels whereas siRNA treatment knocked down FXR transcript levels. FXR induction decreased Ntcp transcript levels that were reversed in FXR knockdown animals. CDCA treatment resulted in greater than 2-fold increase in Bsep mRNA levels that was absent in FXR knockdown animals. The PXR ligand, PCN, showed an induction in PXR mRNA levels while siRNA treatment resulted in the knockdown in PXR transcript levels. PXR induction did not cause any change in Ntcp and Bsep transcript levels. Furthermore, sandwich cultured rat hepatocytes were used to ascertain if the above in vivo findings are reproducible in vitro. Treatment of hepatocytes with FXR ligand, CDCA, and PXR ligand, PCN, caused greater than 5-fold increase in the respective mRNA levels whereas respective siRNA treatment caused >79% knocked in their transcript levels. FXR induction decreased Ntcp mRNA levels that were ablated in FXR knockdown cultures. FXR induction resulted in a 6-fold increase in Bsep mRNA levels that disappeared in FXR knockdown cultures. On the contrary, PXR induction did not influence the expression levels of Ntcp and Bsep. Taken together these data demonstrate that both FXR and PXR are inducible at mRNA and protein levels in vivo and their expression can be knocked down in the rat liver. Moreover, FXR negatively regulate Ntcp and positively regulate Bsep while PXR does not influence Ntcp and Bsep expression. Finally, the data shows that these in vivo findings can be successfully reproduced in sandwich cultured rat hepatocytes. To conclude, sandwich cultured rat hepatocytes mimic the in vivo situation and provide a good model for bile acid transport studies.

Orientador: Carlos Alberto Luengo
Dissertação (mestrado) - Universidade Estadual de Campinas, Instituto de Fisica Gleb Wataghin
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Resumo: Desde a sua descoberta em 1991, os Nanotubos de Carbono (NTC) têm atraído muito a atenção da comunidade científica, devido as suas propriedades. Neste trabalho é apresentada uma breve revisão das pesquisas em NTC e algumas definições básicas relevantes para a sua estrutura e propriedades. Em vista da utilização deste material em uma futura aplicação e devido ao interesse do grupo na área de energia, é apresentado o estado da arte do armazenamento de Hidrogênio e, em particular, no armazenamento em sólidos de grande área superficial, classe a qual os NTC pertencem. Apresentam-se as modificações realizadas em um Reator de Arco Elétrico (Forar II) para se realizar a Síntese de NTC, são relatadas as experiências e a caracterização das amostras obtidas utilizando-se Microscopia Eletrônica de Varredura e Espectroscopia Raman.
Abstract: Since their discovery in 1991 Carbon Nanotubes (CNT) have received increasing attention by the scientific community due to their properties. Here is presented a brief review of ongoing CNT research, and basic definitions useful to understand their structure and significant properties. Because of future applications in the energy area, are presented developments in Hydrogen storage, more specifically its adsorption in solids with large internal surface areas, a characteristic of CNT materials. Modifications of the existing FORAR II to obtain CNT by the electric arc method are presented, and a description of the routines employed to obtain CNT. The characterization of catalysts and CNT by Scanning Electron Microscopy and Raman Spectroscopy are presented and discussed.
Mestrado
Física da Matéria Condensada
Mestre em Física

Orientadores: Júlio Roberto Bartoli, Elizabeth Grillo Fernandes
Dissertação (mestrado) - Universidade Estadual de Campinas, Faculdade de Engenharia Química
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Resumo: Nanotubos de carbono (NTCs) apresentam características interessantes para aplicações em eletrodos transparentes. Quando dispersos em escala nanométrica são transparentes ao espectro da luz visível e são capazes de conduzir eletricidade após atingirem percolação em matrizes poliméricas isolantes. Neste trabalho, é descrito o uso de nanotubos de carbono de camadas múltiplas (NTCMs) na produção de filmes poliméricos flexíveis transparentes e condutores como alternativa ao uso do óxido de índio dopado com estanho (ITO) em células solares orgânicas. Os nanotubos foram dispersos e purificados em solução aquosa de dodecil sulfato de sódio (SDS) pelos processos de sonicação e centrifugação, e a dispersão monitorada por espectroscopia UV-Vis e potencial ?. Os nanocompósitos foram produzidos via polimerização in situ do monômero metacrilato de metila (MMA) na presença de 0 a 1% p/p NTCs e os filmes depositados através da técnica de revestimento por rotação a alta velocidade (spin coating). A reação de polimerização foi acompanhada pela calorimetria exploratória diferencial (DSC). Verificou-se que na presença de NTCs, a taxa de conversão do monômero é acelerada. A cinética de degradação térmica foi avaliada pelo método de Broido utilizando a análise termogravimétrica (TGA). Foi observado que os NTCs aumentam a estabilidade térmica do PMMA, retardando a degradação por despolimerização. Estudos por espectroscopia FT-IR mostraram uma banda de absorção em 1601 cm-1, (C=C), a qual não é característica do PMMA, indicando que os NTCs participam da polimerização do PMMA. Para concentrações de até 1% p/p de NTCs, os filmes PMMA/NTC apresentaram excelentes propriedades ópticas. Ou seja, baixo coeficiente de absorção, na ordem de 103 cm-1, altos valores de gap óptico (Eopt), entre 3,2 e 4,14 eV, e alta transparência por todo espectro visível, entre 88 e 93%. Nas mesmas concentrações, foi observada uma diminuição substancial na resistividade elétrica dos filmes em 8 ordens de grandeza (de 1016 para 108 ?/quadrado), comparados ao filme de PMMA puro. Entretanto, a faixa de resistividade alcançada ainda é típica de materiais isolantes. Estudos de otimização poderiam originar filmes PMMA/NTC como uma alternativa promissora para ITO em OPVs
Abstract: Carbon nanotubes (CNTs) have interesting features for applications in transparent electrodes. When dispersed at the nanoscale, they become transparent within the visible range and are able to conduct electricity after reaching the percolation threshold in an insulating polymer matrix. In this work, the use of multi-walled carbon nanotubes (MWCNTs) is described for the production of flexible transparent conducting polymer films as an alternative to the use of indium-tin oxide (ITO) in organic solar cells. The nanotubes were dispersed and purified in an aqueous solution of sodium dodecyl sulfate (SDS) by the process of sonication and centrifugation, and the dispersion monitored by UV-Vis spectroscopy and ? potential. The nanocomposites were produced via in situ polymerization of the monomer methyl methacrylate (MMA) in the presence of 0 to 1 %wt. of CNTs. The films were deposited by the spin-coating technique. The polymerization reaction was monitored by differential scanning calorimetry (DSC). It was found that in the presence of CNTs, the conversion rate of the monomer is accelerated. The kinetics of thermal degradation was measured according to the Broido's method by using thermogravimetric analysis (TGA). It was observed that CNTs increase the thermal stability of PMMA, slowing degradation by depolymerization. FT-IR data showed an absorption band at 1601 cm-1 (C = C), which is not characteristic of PMMA, indicating that the CNTs takes place in the polymerization of PMMA. For concentrations up to 1wt% of CNTs, the PMMA/CNT films had excellent optical properties, i.e., a low absorption coefficient in the order of 103 cm-1, wide optical gap (Eopt) between 3.2 and 4.14 eV, and high transparency within the whole visible range, between 88 and 93%. In the same concentrations, the electrical resistivity of the films dropped by 8 orders of magnitude (from 1016 to 108 ?/sqr), compared to the pure PMMA film. Even though this electrical resistivity value is typical of insulating materials, further optimization studies could provide PMMA/CNT films as a promising alternative to ITO in OPV
Mestrado
Ciencia e Tecnologia de Materiais
Mestre em Engenharia Química

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Coordenação de Aperfeiçoamento de Pessoal de Nível Superior (CAPES)
A medição de vazão volumétrica ou velocidade de escoamento de um fluido em regime laminar ou turbulento encontra várias aplicações na engenharia. Assim, pesquisas científicas para o desenvolvimento de arquiteturas e técnicas de medição para essas grandezas são de grande relevância e se encontram em constante expansão. Dentre as arquiteturas existentes para aplicações anemométricas em um regime de escoamento indistinto, a térmica denota diversas vantagens como excelente largura de banda, resolução espacial e baixo custo. Essa é formada basicamente por um termistor conectado em um dos braços de uma ponte de Whetstone modificada. Embora detenha simples configuração, ela possui algumas limitações impostas pela relação não linear entre a temperatura e a grandeza aplicada ao sensor. Além disso, contribuem como limitantes não idealidades do amplificador operacional que compõe a arquitetura. Diante disso, propõem-se o projeto e a implementação de uma arquitetura de anemômetro térmico com linearização por realimentação de tensão, empregando um sensor termorresistivo do tipo NTC. Essa técnica permite obter uma relação linear entre a temperatura e a grandeza utilizada como entrada. Promovem-se também comparações entre o clássico anemômetro e o preconizado neste trabalho. A validação da arquitetura proposta é conduzida através de simulações, bem como comparação experimental com a clássica e um instrumento comercial.
The velocity or volumetric flow measurement of laminar or turbulent flow flows meet various engineering applications. Thus, scientific research for the development of architectures and measurement techniques for these magnitudes is of great relevance and is constantly expanding. Among the existing architectures for anemometric applications in an indistinct flow regime, thermal denotes several advantages such as large bandwidth, spatial resolution and low cost. This is basically a thermistor connected to one of the arms of a modified Whetstone bridge. Although it has a simple configuration, it has some limitations imposed by the non-linear relation between the temperature and the signal applied to the sensor. In addition, it contributes as a limitation the physical parameters of the operational amplifier that composes the architecture. Therefore, it is proposed the design and implementation of a thermal anemometer architecture with voltage feedback linearization, using a thermoresistive sensor of the NTC type. This technique allows to obtain a linear relation between the temperature and the quantity used as input. Comparisons between the classic anemometer and the one advocated in this work are also promoted. The validation of the proposed architecture is conducted through simulations, as well as experimental comparison with classic and commercial instrument.

De nos jours, alors que la société est toujours plus interconnectée, une synchronisation temporelle sûre et précise devient de plus en plus critique pour de nombreuses applications. Les dispositifs informatiques utilisent souvent des oscillateurs à cristal de faible précision pour conserver le temps en local. Cette imprécision engendre une dérive entre les machines. La solution pour assurer une synchronisation précise de l’heure entre elles est d’utiliser une horloge de référence avec une source précise de temps, puis de diffuser le temps sur le réseau. Un des protocoles qui assurent la synchronisation temporelle est Network Time Protocol (NTP). Bien que NTP ait bien fonctionné pour un usage général pendant de nombreuses années, sa sécurité et sa précision sont mal adaptées aux défis futurs. De nombreux mécanismes de sécurité dépendent du temps dans le cadre de leur fonctionnement. Par exemple, avant d’utiliser un certificat électronique,il est nécessaire de confirmer sa validité temporelle. Une machine avec une horloge imprécise pourrait accepter des certificats expirés ou révoqués.Cette thèse présente d’abord le contexte de la synchronisation temporelle en commençant par la définition de certains concepts fondamentaux tels que le modèle d’horloge, le problème de la synchronisation d’horloge et certaines notions comme l’exactitude, la précision et la stabilité des horloges.Nous étudions les protocoles de synchronisation temporelle les plus courants des réseaux de communication, et entre autres NTP.Ensuite, nous considérons la sécurité de la synchronisation temporelle en présentant les possibles menaces de sécurité contre les protocoles de synchronisation temporelle et les exigences de sécurité de ces protocoles. Nous nous concentrons sur la sécurité du protocole NTP tel que décrit par le standard, et les travaux connexes qui ont tenté de l’améliorer sur ce point. Nous discutons également de l’importance d’avoir un compromis bien équilibré entre sécurité et performance.Dans notre première contribution, nous proposons d’aller plus loin que NTP avec Secure Time Synchronization Protocol (STS), un nouveau protocole de synchronisation de l’heure, qui est authentifié et sécurisé, et adapté aux larges déploiements. Nous décrivons le fonctionnement de STS et prouvons sa conception sécurisée, à l’aide d’une analyse formelle faite par deux outils de vérification de protocole de sécurité : Proverif et Tamarin. Nous présentons l’implémentation de STS basée sur le projet OpenNTPD, et évaluons ses performances en comparant la précision de STS avec celle de NTP non authentifié. Nous soulignons la dépendance circulaire entre la validation du certificat et la synchronisation temporelle.En réalité, une synchronisation temporelle fiable nécessite des matériaux cryptographiques qui ne sont valables que sur des intervalles de temps désignés, mais ces intervalles de temps ne peuvent être comparés à l’heure actuelle que lorsque les hôtes participants sont synchronisés de manière fiable. Nous présentons une solution qui fournit, lors de l’amorçage, une synchronisation approximative basée sur le blockchain Bitcoin, pour rompre cette dépendance circulaire.Dans notre deuxième contribution, nous proposons une méthode pour améliorer l’exactitude du protocole NTP, en tenant compte des délais de transmission asymétriques dus à une bande passante ou à un routage différent sur le chemin d’aller et de retour. En fait, l’asymétrie est assez répandue sur Internet, ce qui dégrade la performance de NTP qui fait l’hypothèse de délais symétriques. Cette méthode s’appuie sur l’utilisation d’un client NTP synchronisé par GPS, pour mesurer le délai unidirectionnel minimal aller et retour jusqu’à son serveur de temps. Ainsi, il est possible de calibrer NTP en prenant en compte cette asymétrie
Nowadays, as society has become more interconnected, secure and accurate time-keeping becomes more and more critical for many applications. Computing devices usually use crystal clocks with low precision for local synchronization. These low-quality clocks cause a large drift between machines. The solution to provide precise time synchronization between them is to use a reference clock having an accurate source of time and then disseminate time over a communication network to other devices. One of the protocols that provide time synchronization over packet-switched networks is Network Time Protocol (NTP). Although NTP has operated well for a general-purpose use for many years, both its security and accuracy are ill-suitedfor future challenges. Many security mechanisms rely on time as part of their operation. For example, before using a digital certificate, it is necessary to confirmits time validity. A machine with an inaccurate clock canaccept an expired or revoked certificate.This thesis first provides a background on time synchronization starting with the definition of some fundamental concepts such as the clock model, the problem of clock synchronization, and some notions like accuracy, precision, and stability of clocks. We study the most common time synchronization protocols used in packet-switched networks, and among others NTP.Then,we consider the security of time synchronization by presenting the possible security threats against time synchronization protocols and the security requirements of these protocols. We zoom in the securityof the NTP protocol as described by the standard NTP and other related work that tried to enhance NTP security. We also discuss the importance of having a well-balanced trade-off between security and performance.In our first contribution, we propose to go further in the support of NTP security with Secure Time Synchronization protocol (STS), a new secure authenticated time synchronization protocol suitable for widespread deployments. We describe the operation of STS and prove its design secure with a formal analysis using two security protocol verification tools: Proverif and Tamarin. We present the implementation of STS based on the OpenNTPD project, and evaluate its performance by comparing the STS precision with unauthenticated NTP. We point out the circular dependency between certificate validation and time synchronization. In fact, reliable time synchronization requires cryptographic materials that are valid only over designated time intervals, but time intervals can be only enforced when participating hosts are reliably synchronized. We present a solution for bootstrapping time synchronization based on the Bitcoin blockchain to break this circular dependency.In our second contribution, we propose a method for improving the accuracy of the NTP protocol by taking into account asymmetric transmission delays due to different bandwidth or routing on the forward and backward paths. In fact, asymmetry is quite prevalent in the Internet, which leads to low accuracy ofNTP that relies on the symmetric delay assumption to compute the clock offset. This method builds on using an NTP client synchronized with GPS to measure precisely the one-way transmission delay on the forward and backward path with his time server. In this way, it is possible to calibrate NTP to take into account asymmetry

This  report  is  a  part  of  a  master  thesis  project  done  at  Ericsson  Linköping  incooperation with Linköpings Tekniska Högskola (LiTH). This project is divided intwo different parts.  The first part is to create a measurement node that collectsand processes data from network time protocol servers.   It is used to determinethe  quality  of  the  IP  network  at  the  node  and  detect  potential  defects  on  usedtimeservers or nodes on the networks.The second assignment is to analyze the collected data and further improve theexisting synchronization algorithm.  Ip communication is not designed to be timecritical and therefore the NTP protocol needs to be complemented with additionalsignal processing to achieve required accuracy.  Real time requirements limit thecomputational complexity of the signal processing algorithm.

El presente proyecto de investigación propone la implementación de la ISO/NTC-29110 en una empresa MYPE consultora de Software Vision-xtrema S.A. para mejorar sus procesos de gestión de proyectos e implementación de software y poder acceder a mercados nacionales e internacionales que exigen una certificación. Este proyecto se sustenta en la publicación “La implementación de la norma ISO/IEC 29110 Guías de Gestión e Ingeniería para las organizaciones pequeñas” de Claude Y. Laporte, Editor del proyecto de ISO/IEC 29110 Standards and Guides en ISO/IEC JTC1 SC7 Working Group 24 del SubComité 7 (SC7) del Comité Técnico Conjunto 1 (JCT1) de la Organización Internacional de Normalización (ISO) y la Comisión Electrónica Internacional (IEC), en el que se señalan los beneficios de la norma ISO/IEC 29110 para las organizaciones pequeñas: Trabajo estandarizado, con mejor calidad y resultados consistentes en todos los proyectos. Mejor administración y seguimiento del proyecto. Mejor comunicación dentro del equipo. Proporciona mayores posibilidades para acceder a mercados internacionales. Como objetivos específicos del presente proyecto, se busca: Determinar el perfil de implementación para la MYPE. Crear un plan para Implementar la Gestión de proyectos en base a la Norma ISO/NTC-29110. Crear un plan para Implementar Software en base a la Norma ISO/NTC-29110. En el presente trabajo de investigación se propone roles, un mapa de procesos, se describen y diagraman los procesos, y se sugieren un conjunto de artefactos los cuales van a evidenciar los requisitos que exige la ISO-29110.
This research project proposes the implementation of ISO/NTC-29110 in a MYPE consulting company of Software Vision-xtrema S.A. to improve your project management and software implementation processes and gain access to national and international markets that require certification. This project is based on the publication “The implementation of ISO / IEC 29110 Management and Engineering Guides for small organizations” by Claude Y. Laporte, Editor of the ISO / IEC 29110 Standards and Guides project in ISO / IEC JTC1 SC7 Working Group 24 of Subcommittee 7 (SC7) of Joint Technical Committee 1 (JCT1) of the International Organization for Standardization (ISO) and the International Electronic Commission (IEC), in which the benefits of ISO / IEC 29110 for small organizations: Standardized work, with better quality and consistent results in all projects. Better administration and monitoring of the project. Better communication within the team. Provides greater possibilities to access international markets. The specific objectives of this project are: Determine the implementation profile for the MYPE. Create a plan to implement project management based on the ISO / NTC-29110 standard. Create a plan to Implement Software based on the ISO / NTC-29110 Standard. In this research work, roles are proposed, a process map, the processes are described and diagrammed, and a set of artifacts are suggested which will demonstrate the requirements required by ISO-29110.
Tesis

El presente proyecto de fin de carrera responde a la necesidad creada a causa de las normativas publicadas por la Oficina Nacional de Gobierno Electrónico e Informática (ONGEI) que declaran de uso obligatorio las Normas Técnicas Peruanas NTP-ISO/IEC 27001:2008 y NTP-ISO/IEC 17799:2007 (con fechas de publicación mayo 2012 y julio 2011 respectivamente) a una lista de empresas del estado peruano que pertenezcan y/o estén involucradas en la Administración Pública con la finalidad de establecer un modelo integral para el desarrollo de los planes de seguridad de la información de la misma. Esta necesidad, a causa del carácter obligatorio de las normas mencionadas, es reconocida como la atención a la falta de procedimientos que permitan realizar auditorías que verifiquen el cumplimiento de la NTP-ISO/IEC 17799 como parte del proceso de cumplimiento integral de la NTP-ISO/IEC 27001 en las empresas del estado peruano. La elaboración de estos procedimientos estarán basados en COBIT 5.0, publicado en mayo de 2012, nuevo estándar de facto para Tecnologías de Información reconocido internacionalmente. Estos procedimientos estarán acompañados de la declaración de aplicabilidad para la norma NTP-ISO/IEC 17799 para poder definir los controles que serán establecidos e implementados por la institución, un Inventario de activos de información comúnmente relacionados con los controles presentes en la NTPISO/ IEC 17799 y un Mapeo del marco COBIT 5.0 frente a la norma NTP 17799 identificando la correspondencia de los dominios de COBIT hacia los controles de la NTP.
Tesis

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In this work it was characterized the microstructure and the electrical parameters of NTC temperature sensors, based on the mechanical mixing of niquel and cobalt oxides. Different proportions of this two materials (mol), was prepared and sintered at 1150C, 1200C, 1250C and 1300C. The microstructure was characterized by x-ray diffraction, MEV and EDS referring to the fases formed during the sintering, as well as, regarding grain size, the distribution of the chemical elements of this two oxides and the porosity of the final ceramic product. For the proportions of 10, 20, 30, 40, 50, 60, 80 e 90 (mol) of NiO on C3O4, and sintered on the four temperarures, it was obtained solid solution between niquel and cobalt oxides. Spinel phase, NiC2O4, was formed in the composition with 70 NiO (mol) at 1250C and 1300C, with segregation of CoO phase between the grain boundaries. The one phase composition with 60 (mol) NiO, sintered at 1250°C, and the composition with 70 (mol) NiO, sintered at 1300C, showed the best thermistor characteristics, by DC characterization. The values of beta factor, sensitivity and activation energy for the conductivity process (Ea), of the composition with 70 NiO was respectively 6203 K-1; -4,0 at (120C) and 0,53 eV.
No presente trabalho foi caracterizada a microestrutura e os parâmetros elétricos de sensores de temperatura do tipo NTC, a partir de mistura mecânica de óxidos de níquel e cobalto. Foram preparadas diferentes composições ( em mol ) entre os dois materiais e sinterizados nas temperaturas de 1150, 1200, 1250 e 1300C. A microestrutura foi caracterizada pela técnica de raios X, por MEV e EDS, no que se refere às fases formadas durante a sinterização, assim como, com respeito ao tamanho de grão, distribuição dos elementos e da porosidade do corpo cerâmico final. Para as composições de 10, 20, 30, 40, 50, 60, 80 e 90 em mol de NiO em C3O4, e sinterizadas nas quatro temperaturas, obteve-se a formação de soluções sólidas entre os óxidos de níquel e de cobalto. A composição de 70 em mol de NiO apresentou a formação da fase do espinélio NiC2O4, nas temperaturas de 1250 e 1300 C, com a segregação da fase de CO na região intergranular. As melhores características termistoras, obtidas pela caracterização elétrica DC, foram encontradas para a composição monofásica de 60 em mol de NiO, sinterizada a 1250C, e para a composição de 70 em mol de NiO sinterizada a 1300C. A composição de 70 de NiO apresentou uma constante termistora de 6203 K-1, sensibilidade igual a -4,0 (a 120C) e energia de ativação (Ea) para o processo de condução eletrônica de 0,53 eV.

Tese (doutorado)—Universidade de Brasília, Faculdade de Ciências da Saúde, 2008.
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A pesquisa aborda o tema da Saúde do Trabalhador sob a perspectiva do direito constitucional, na seara dos direitos fundamentais, articulado em mecanismos de peso-e-contrapeso com outros dois: livre-iniciativa e meio ambiente do trabalho. O aparente conflito de constitucionalidade entre esses três direitos é desfeito ao se evidenciar que, na essência, as distorções e anacronismos do atual sistema protetivo acidentário, dito esgotado, são de natureza infraconstitucionais, cujos vícios ideológicos, administrativos, políticos, econômicos, epistemológicos, teóricos e práticos suscitam a precedência do vértice liberal, de cunho individualista, sobre os demais. A tese mitiga essa protuberância da livre-iniciativa no triângulo distorcido dos direitos fundamentais ao sugerir um novo marco regulatório estatal. De um lado, o financiamento flexível e dinâmico do Seguro Acidente do Trabalho - SAT, conforme a regra de mercado, inspiradora do FAP, que vincula a doença ao prejuízo e a saúde ao lucro sob o prisma da regra espelho do poluidor-pagador; de outro lado, no campo social, passa o ônus da prova ao empregador quando da concessão pelo Instituto Nacional de Seguro Social - INSS dos benefícios acidentários, presumidos pelo NTEP. Tal regulação se fundamenta no retorno econômico dos empregadores como potente propulsor do saneamento do meio ambiente do trabalho. A tese, no âmbito do objetivo geral, propõe uma nova configuração da Saúde do Trabalhador ao aproveitar, dialeticamente, as forças liberal, social e ambiental em um sistema cineticamente autobalanceável com resultantes positivas às empresas, ao Estado e à sociedade, no médio-longo prazo. Todo estudo é alimentado por dois grandes repositórios de dados institucionais, pertencentes ao Ministério da Previdência ocial - MPS: Sistema Único de Benefício – SUB e Cadastro Nacional de informações Sociais – CNIS. O CNIS provê os dados populacionais e arrecadatórios e o SUB, os dados relativos à casuística, cuja indexação se dá por duas variáveis: CNAE (Classificação Nacional de Atividades Econômicas), exposição, representante populacional, como figura ontológica, de isomorfia coercitiva, mimética e normativa, de representações sociais, epidemiológicas, econômicas, jurídicas e geodemográficas, de natureza sintética e a CID (Classificação Internacional de Doenças), desfecho clínico incapacitante, representante da casuística, sob o prisma anatomoclínico e fisiopatológico, de natureza analítica. Nos objetivos específicos, este estudo elabora três metodologias, a saber: 1) Aferição da insalubridade dos ambientes de trabalho por intermédio do NTEP, que consiste na sugestão de nexo de causalidade entre a classe de atividade econômica da empresa empregadora – dada pela CNAEClasse – e o grupo de doença incapacitante (Agrupamento-CID), que haja produzido benefício pago pelo INSS, do tipo auxílio-doença previdenciário (B31), auxílio-doença acidentário (B91), aposentadoria por invalidez previdenciária (B32) e aposentadoria por invalidez acidentária (B92). Esses benefícios totalizaram 12.464.713 casos para os 174 Agrupamento-CID da casuística - excluídos aqueles dos capítulos 15, 16, 17, 18, 20 e 21 da CID, bem como o agrupamento HIV-AIDS (B20-B24) – oriundos da população média sob estudo de 24.269.946 vínculos empregatícios, distribuída nos 675 CNAE-Classe, cuja taxa de rotação média ficou em 36%. A coorte previdenciária de sete anos, censitária, dinâmica, não-concorrente, iniciada em 01/01/2000 e seguida até 31/12/2006, acumulou 139.136.758 vínculos-ano e apresentou prevalência geral 848 (x 10.000), sendo 80,2% da espécie B31 (previdenciário); e, 8,7% de B91(acidentário). O NTEP só é estabelecido quando cumulativamente os três seguintes requisitos são atendidos: i) Limite Inferior do Intervalo de Confiança para 99% (LIIC) da Razão de Chances (RC) maior que um (=1%); ii) Tamanho Amostral (n) maior que Quantidade Média de Vínculos (Qt) para um poder estatístico (1-) de 95% e iii) Amplitude Relativa da Razão de Chances (ARRC) menor que três. Além do NTEP, esta coorte produz indicadores epidemiológicos - medidas de freqüência, de associação e de impacto, bem como prevalências gerais e específicas de CNAE - norteadores de políticas públicas e privadas e de novos e aprofundados estudos científicos, no campo da promoção à saúde do trabalhador. Por exemplo, indicamse a Razão de Chances (RC), a Fração Etiológica entre os Expostos (FEExp) e a Fração Etiológica Populacional (FEpop) para os CNAE de Curtimento de couro com Agrupamento-CID de Traumatismos do punho e da mão (RC= 3,15; FEExp = 63,25% e FEpop = 0,27%) ; Produção de ferro-gusa e Queimaduras e corrosões (RC= 34,98; FEExp = 96,67% e FEpop = 1,57%); Fabricação de automóveis e Transtornos dos tecidos moles (RC= 6,68; FEExp = 79,47% e FEpop = 1,47%); e, Banco Múltiplos, com Carteira e Transtorno dos Nervos (RC= 4,37; FEExp = 69,72% e FEpop = 2,79%). 2) Gradação tributária dos grupos de riscos leve, médio e grave (cluster) atribuíveis ao SAT para os 675 CNAE-Classe, que apresentam 16,2 ocorrências acidentárias (x 10.000), com perda de 27,7 dias para 1.000 dias trabalhados, ao custo de R$1.976,86 pagos, a cada R$ 1.000,00 recolhidos aos cofres públicos. A gradação é feita com uso da técnica multivariada de análise de discriminantes (conglomeração) que consiste em agrupar os CNAE pela similaridade da distância euclidiana quadrática no espaço tridimensional das variáveis padronizadas dos coeficientes de freqüência, gravidade e custo, segundo o critério de ward combinado ao k-means. A freqüência é carregada por todos os benefícios acidentários (B91, B92, B93), acrescidos daqueles (B31 e B32) que possuam NTEP. O processamento é feito pelo pacote computacional SPSS, cuja convergência para os três clusters acontece com a seguinte configuração: 345 CNAE-Classe no grau leve (51%); 173 de grau médio (26%) e 157 de grau grave (23%). 3) Dosimetria tributária para as empresas pertencente a uma CNAE-Classe mediante aplicação do fapímetro, cujo número, FAP, multiplica as alíquotas de 1%, 2% ou 3% do SAT, dentro do intervalo contínuo fechado [0,5000; 2,000], de forma a reduzi-las até 50% ou majorá-las em até 100%. O fapímetro opera por interpolação linear simples e leva em conta o score apurado por empresa ao compará-lo ao score médio da CNAE, segundo as três variáveis (coeficientes padronizados de freqüência, gravidade e custo). Por exemplo, para as 28 primeiras empresas, em ordem decrescente de score, do CNAE 2910 (Fabricação de Automóveis) verifica-se que em apenas duas delas houve o FAP máximo (FAP=2,0); nove ficaram com FAP entre 1,0 e 2,0 e as outras 17 receberam o FAP entre de 0,50 e 1,0. ________________________________________________________________________________________ ABSTRACT
The research approaches the subject of the Health of the Worker under the perspective of the constitutional law, according to the basic rights, articulated in elements of balance-and-counterbalance of weight with others two: free-initiative and environment of the work. The apparent conflict of constitutionality between these three rights is undone by the moment that is evident that, in essence, the distortions and anachronisms of the recent accidental protector system insults to if to evidence that, in the essence, such biases of the current accidental protector system, depleted, are infraconstitutional. The thesis mitigates this lump of the freeinitiative in the distorted triangle of the basic rights when suggesting a new landmark of regulatory state. In one hand, the flexible and dynamic financing of the Work Accident Insurance - SAT, as the market principles, inspirer of the FAP, this ties the illness to the damage and the health to the profit under the prism of the rule mirror of the polluting agent-payer. In the other hand, in the social field, it is transferred the responsibility of the test to the employer when the concession for the National Social Security Institute - INSS of the accidental benefits is established, presumed by the NTEP. Such regulation is based on the economic return of the employers as powerful propellant of the sanitation of the environment of the work. The thesis, in the scope of the general objective, considers a new configuration of the Health of the Worker when taking advantage, dialectically, the liberal, social and ambient forces in a kinetically system with positive resultants to the companies, the State and the society, in the medium-long stated period. All the study is fed by two great repositories of institutional data, pertaining to the Ministry of Social Security - MPS: National Social Security Unified Benefits System (SUB) and Cadastre National of Social Information - CNIS. The CNIS provides the population and collectors and the relative SUB, the amount of cases data, which indexation is based on two of variables: CNAE (exposition), populational representative, as ontological figure, of coercive isomorphy, mimetic and normative, of social representations, epidemiologists, economic, legal of synthetic nature; the CID (International Classification of Diseases), representative of the amount of cases, under the anatomoclinical and fisiopatologic prism, of analytical nature. In the specific objectives, this study elaborates three methodologies, 1) Gauging of the unhealthy of the environments of work by intermediate of the NTEP, which consists in the suggestion of causality nexus among the Class of economic activity of the company employer - given for the National Classification of Economic Activities (CNAE-Class) - and the group of handicap illness, diagnosed according to grouping CID, which has paid benefit for the INSS, of the type social security sick (B31), accidental benefits sick (B91), retirement for social security disability (B32) and retirement for accidental benefits disability (B92). These benefits totalized 12.464.713 cases for the 174 Grouping of the amount of cases - excluded those of chapters 15, 16, 17, 18, 20 and 21 of the CID, as well as grouping SIDA (B20-B24) - deriving of the average population under study of 24.269.946 employment bonds, distributed in the 675 CNAE-Class, which tax of average rotation was in 36%. Cohort of Social Security of seven years, dynamic, not-competitor, from 01/01/2000 to 31/12/2006, accumulated 139.136.758 bond x year and presented general prevalence 848 (x 10,000), being 80.2% of the B31 species (Social Security); 8.7% of B91 (accidental benefits). The NTEP alone is established when cumulatively the three following requisites are: i) Low Limit of the Reliable Interval for 99% (LIIC) of the Odds Ratio (RC) bigger than one (=1%); II) Size bigger Amostral (n) bigger than Average Amount of Bonds (Qt) for a statistic power (1-) of 95% and III) Relative Amplitude of the Odds Ratio (ARRC) lesser than three. Beyond the NTEP, this cohort produces pointers epidemiologists - measure of frequency, association and impact, as well as general and specific prevalence of CNAE - guide of public and private politics and new and deepened scientific studies, in the field of promotion to the health of the worker. For example, the Odds Ratio (RC) is indicated, the Etiological Fraction between Exposed (FEExp) and the Populational Etiological Fraction (FEpop) for the CNAE of leather Tanning with Grouping de Traumatism of the fist and hand (RC= 3,15; FEExp = 63.25% and FEpop = 0.27%); Production of iron and burnings (RC= 34,98; FEExp = 96.67% and FEpop = 1.57%); Manufacture of automobiles and Troubles with soft fabrics (RC= 6,68; FEExp = 79.47% and FEpop = 1.47%); Commercial bank, with Wallet and Upheaval of Nerves (RC= 4,37; FEExp = 69.72% and FEpop = 2.79%). 2) Gradation tax of the groups of light risks, average and serious (to cluster) attributable to the SAT for the 675 CNAE-Class, which presents 16,2 accidental benefits occurrences (x 10,000), with loss of 27,7 days for 1.000 days worked, at the cost of R$1.976,86 paid , to each R$ 1,000, 00 collected to the public coffers. The gradation is made by the use of the multivaried technique of analysis of discriminants (conglomeration) that consists in grouping the CNAE for the Euclidean similarity of the quadratic distance in the three-dimensional space of the standardized 0 variable of the coefficients of frequency, gravity and cost, according to criterion of agreed Ward to k-means. The frequency is loaded for all the accidental benefits (B91, B92, B93), increased of those (B31 and B32) that possess NTEP. The processing is made by computational package SPSS, which convergence for three clusters occurs with the following configuration: 345 CNAEClass in the light degree (51%); 173 of average degree (26%) and 157 of serious degree (23%). 3) Doses control tax for the companies pertaining to a CNAE-Class by means of application of fapimeter, which number, FAP, multiplies the aliquots of 1%, 2% or 3% of the SAT, inside of the closed continuous interval [0,5000; 2,000], in order to reduce them until 50% or to increase them to 100%. Fapimeter operates for simple linear interpolation and considers the appropriate score for company when comparing its score average of the CNAE, according to three variables (standardized coefficients of frequency, gravity and cost). For example, for the 28 first companies, in sequence decreasing of score, CNAE 2910 (Manufacture of Automobiles) it is verified that in only two of them it had the maximum FAP (FAP=2,0); nine had been with FAP between 1,0 and the 2,0 and others 17 had received the FAP between from 0,50 and 1,0.