Le traitement et le diagnostic de maladies d'origine génétique suscite un grand intérêt à l'heure actuelle. De par leur spécificité d'appariement avec les acides nucléiques, les oligonucléotides possèdent un grand potentiel dans ce domaine. Ils se heurtent toutefois à des limitations majeures, dont leur faible stabilité en milieu physiologique et la difficulté qu'ils ont à franchir les membranes biologiques. De nombreuses équipes de recherche s'intéressent, afin de pallier ces limitations, à la conception et à la synthèse d'oligonucléotides chimiquement modifiés. Parmi ceux-ci, les Locked Nucleic Acids (LNA), présentant une modification qui consiste en l'insertion d'un pont −O−CH2− entre l'atome C2' et l'atome C4' du sucre, constituent une famille qui semble posséder les propriétés requises. Ils sont considérés comme des candidats très prometteurs en tant qu’agents thérapeutiques et qu’outils de diagnostic du génome. La caractérisation de la stabilité et de la sélectivité d'appariement entre les LNA et les acides nucléiques naturels est, dans ce contexte, important. Dans ce travail, nous avons étudié la stabilité, la sélectivité d'appariement ainsi que la dynamique de la structure double brin d'un oligonucléotide hybride LNA-DNA, et nous avons comparé ces propriétés à celles d'un oligonucléotide DNA-DNA de même séquence. Ce dernier est constitué de 11 paires de bases formées par l'appariement du brin 5'-GCGTGTGTGCG-3' avec le brin 3'-CGCACACACGC-5'. Dans le cas de l'hybride, les nucléotides du second brin sont tous remplacés par des LNA. La stabilité a été étudiée expérimentalement par différentes techniques : spectroscopie d'absorption UV, calorimétrie différentielle à balayage, résonance magnétique nucléaire et calorimétrie à titrage isotherme. Ces études montrent que la stabilité du duplexe hybride est plus importante que celle du naturel, et que ce phénomène s'explique par un terme entropique plus favorable pour la formation du duplexe LNA-DNA que pour la formation du duplexe DNA-DNA. La sélectivité d'appariement a été étudiée en comparant la stabilité des deux oligonucléotides étudiés avec celle d'oligonucléotides présentant un mésappariement dans la séquence. Nos résultats montrent que la sélectivité d'appariement du brin LNA n'est pas significativement différente de celle du brin DNA. Ce résultat ne doit cependant pas être généralisé car nous n'avons testé qu'une position centrale pour le mésappariement. L'étude de la dynamique de la structure des oligonucléotides a été effectuée par RMN et porte sur la caractérisation de la cinétique de l'ouverture individuelle des paires de bases. Nous observons que la durée de vie de l'état fermé des paires de bases G-C est supérieure dans l'oligonucléotide LNA-DNA, tandis que l'état fermé des paires A-T semble posséder une durée de vie supérieure dans l'oligonucléotide DNA-DNA. Au cours de ce travail de thèse nous avons pu caractériser les facteurs énergétiques à la base de la stabilité accrue des oligonucléotides chimiquement modifiés de type LNA. Nous avons montré que leur sélectivité d’appariement n’est pas toujours supérieure à celle des oligonucléotides naturels et dépend des séquences impliquées. Enfin, nous avons mis en évidence les différences entre la dynamique de la structure d’un oligonucléotide possédant des LNA et celle d’un duplexe DNA.

Eukaryotic protein kinases are one of the most important classes of human proteins, and a great deal of research has focused on the development of small molecule inhibitors as biological probes for the determination of their cellular function or as therapeutics for the treatment of disease, such as cancer. The need for new selective inhibitors and a better understanding of the selectivities of existing small molecules is readily apparent. Towards the goal of better understanding protein kinases and the molecules that inhibit them, I have developed a split-protein-based approach for the investigation of these kinase-small molecule interactions. Employing split-firefly luciferase as a reporter domain, we engineered a three-hybrid system capable of determining kinase inhibition through competitive interactions between an active site-directed ligand and a small molecule of interest. This method measures luciferase activity as a function of ligand binding, as opposed to the more traditional assays which quantify kinase activity directly, and alleviates the laborious process of protein purification. The model kinase PKA and the promiscuous ligand staurosporine were used in an initial test case to successfully validate the general design principles of our assay. The modular nature inherent to the assay's design enabled us to adapt it to roughly 300 additional protein kinases and two different ligands. We were able to establish a protocol for rapidly ascertaining the inhibition of a kinase by a library of 80 commercially available kinase inhibitors in a 96-well, high-throughput format. This protocol was then systematically applied to the AGC group of kinases to observe patterns of inhibition across similarly related kinases. We have further shown how these results might be correlated with the sequence identity between kinases to better anticipate inhibitor promiscuity. Finally, we were able to illustrate how a kinase-centric approach could be applied to correlate alterations to the kinase domain with changes in luminescence. This has use for the interrogation of different modes of inhibition as well as in identifying the specific determinants of inhibitor binding. In total, these efforts represent the optimization of a new, general platform for determining kinase inhibitor selectivity across the kinome, and it could potentially be applied universally to the interrogation of protein-ligand interactions.

Intrusion systems have been the subject of considerable research during the past 33 years, since the original work of Anderson. Much has been published attempting to improve their performance using advanced data processing techniques including neural nets, statistical pattern recognition and genetic algorithms. Whilst some significant improvements have been achieved they are often the result of assumptions that are difficult to justify and comparing performance between different research groups is difficult. The thesis develops a new approach to defining performance focussed on comparing intrusion systems and technologies. A new taxonomy is proposed in which the type of output and the data scale over which an intrusion system operates is used for classification. The inconsistencies and inadequacies of existing definitions of detection are examined and five new intrusion levels are proposed from analogy with other detection-based technologies. These levels are known as detection, recognition, identification, confirmation and prosecution, each representing an increase in the information output from, and functionality of, the intrusion system. These levels are contrasted over four physical data scales, from application/host through to enterprise networks, introducing and developing the concept of a footprint as a pictorial representation of the scope of an intrusion system. An intrusion is now defined as “an activity that leads to the violation of the security policy of a computer system”. Five different intrusion technologies are illustrated using the footprint with current challenges also shown to stimulate further research. Integrity in the presence of mixed trust data streams at the highest intrusion level is identified as particularly challenging. Two metrics new to intrusion systems are defined to quantify performance and further aid comparison. Sensitivity is introduced to define basic detectability of an attack in terms of a single parameter, rather than the usual four currently in use. Selectivity is used to describe the ability of an intrusion system to discriminate between attack types. These metrics are quantified experimentally for network intrusion using the DARPA 1999 dataset and SNORT. Only nine of the 58 attack types present were detected with sensitivities in excess of 12dB indicating that detection performance of the attack types present in this dataset remains a challenge. The measured selectivity was also poor indicting that only three of the attack types could be confidently distinguished. The highest value of selectivity was 3.52, significantly lower than the theoretical limit of 5.83 for the evaluated system. Options for improving selectivity and sensitivity through additional measurements are examined.

Abstract NEW SYNTHETIC STRATEGIES FOR IMPROVED GAS SEPARATION BY NANOPOROUS ORGANIC POLYMERS Suha S. Altarawneh, Ph.D. The emission of carbon dioxide (CO2) from fossil fuel combustion is a major cause of climate change. Therefore, the efficient separation of CO2 from mixtures of gases such as flue gas and impure sources of CH4 (e.g. natural gas and landfill gas) is an essential step in meeting the ever increasing demands on natural gas and creating a cleaner environment. Carbon capture and storage technology (CCS) is one of the methods employed for gas separation using chemisorption and/or physisorption processes. Several materials such as porous polymers and amine solutions have been used as gas adsorbents. However, the amount of energy required for the adsorbent regeneration is one of the main concerns that needs to be addressed. In this regard, porous organic polymers (POPs) with defined porosity and preferential binding affinity for CO2 over N2 and CH4 are some of the most attractive materials that could fulfill the above requirement and are also applicable for use in gas storage and separation. Suitable POPs that can be used for gas storage applications need to have high porosity and mechanical stability under high pressure conditions (~100 bar). Alternatively, the most effective POPs in gas separation are those that have preferential binding affinity for CO2 over other gases present at low pressure settings. In all cases, the chemical nature of POPs and their textural properties are key parameters, however, the modest surface area of most POPs limits their efficiency. With the above considerations in mind, the aim of our research is to develop benzimidazole–linked polymers (BILPs) that have variable porosity levels and chemical functionality to enhance gas separation (CO2/CH4, CO2/N2). We have established new synthetic routes that utilize polycondensation reactions between aryl-aldehydes and aryl-o-diamine building units to construct new BILPs with improved gas separation properties. Our strategy targeted structural and textural modifications of BILPs. We used longer linkers (building units) to improve porosity; however, the flexible linkers offered only low porosity due to network interpenetration. To overcome this challenge, a more controlled network growth rate was assessed by adjusting imine-bond formation rates through different acid loading. The acid, HCl, was used to catalyze imine-bond formation. The new resulting acid-catalyzed BILPs have shown an improved porosity up to 92% compared to the non-catalyzed BILPs. We also used the “rational ligand design” approach to introduce new functionalities into BILPs (-OR) to alter the hydrophobic nature of their pores. In this regard, we have illustrated the applicability of this strategy to BILPs containing flexible aryl-o-diamine linkers. The bulky alkoxy groups were incorporated into the aryl-aldehyde building unit prior to polymerization. The resulting polymers have proven that the presence of the bulky pendant alkoxy-chains plays a significant role during the polymerization process which allows for increased control over network formation, and in turn, porosity. Sorption measurements, selectivity, and heats of adsorption data have confirmed the positive impact of the alkoxy-groups and shown that varying the pendant groups is a promising method for designing highly porous BILPs. In addition to pore functionalization with alkoxy-chains, we used pi-conjugated and N-rich building units to prepare new BILPs that have semiconducting properties in addition to their porous nature. This class of BILPs has shown that the extended-conjugated system improved BILPs electronic properties. The other studies performed in this research, involved the use of DFT theory to investigate CO2/BILPs interaction sites and binding affinities. The computational outcomes of DFT have shown that (C-H) bond of the aryl system is a possible site for CO2 interaction beside the free-N side and hydrogen bonding. All new polymers were characterized by spectral and analytical characterization methods and their sorption data were collected to evaluate their capability as candidates for gas separation applications.

Would you like a stranger more who shifts his/her attitudes to more closely align with yours? How would you feel if he/she aligned with everyone as opposed to just you? In Experiment 1, participants discussed with a partner disagreed upon social issues and received false feedback about whether the partner engaged in attitude alignment (shifted his/her attitude toward the participant’s attitude) following discussion. Participants also received false feedback about proportion of similarity (25%, 50%, or 75%) to the partner. Participants reported greater attraction toward partners who engaged in attitude alignment and who were more similar. However, similarity only predicted attraction in the absence of attitude alignment. Additionally, partner attitude alignment led to participant attitude alignment, and perceived reasoning ability marginally mediated the attitude alignment-attraction relationship. Similar to Experiment 1, participants in Experiment 2 received attitude alignment feedback, but they also received feedback about whether the partner engaged in attitude alignment with no others besides the participant (selective) or with many others besides the participant (unselective). Participants reported greater attraction toward partners who engaged in attitude alignment with them regardless of the partners’ attitude alignment with others. Perceived reasoning ability again mediated the attitude alignment-attraction relationship, and appeared to be more important in explaining this relation than cognitive evaluation or inferred attraction. Finally, participants reported greater trust and respect for partners who engaged in attitude alignment, but were no more willing to help those partners. This work extends our understanding of attitude alignment and its potential to affect interpersonal relationships, and it considers the influence of judgments about individuals outside of the dyad (i.e., alignment with others relative to alignment with the self).

To build novel electronic noses for mimicking biological olfactory systems that consist of olfactory receptor arrays with large surface area and massively-diversified chemical reactivity, three dimensional (3D) vertical aligned ZnO nanowire arrays were employed as active materials for gas detection. ZnO nanowire arrays share 3D structures similar to mammalian olfactory receptor arrays, with thousands of vertical nanowires providing a high reception area which can significantly enhance the sensors’ sensitivity. Meanwhile, with different material decorations (such as SnO2, In2O3, WO3 and polymers), each array of nanowires can produce a distinguishable response for each separate analyte, which would provide a promising way to improve the selectivity. Both patterned grown well-aligned and wafer size random-distributed 3D nanowire array sensing devices are investigated. Several different types of gas sensors have been investigated in this dissertation. Metal oxide semiconductor gas sensors based on 3D metal oxides/ZnO vertical nanowire arrays have detected NO2 and H2S down to ppb level, and five gases of NO2, H2S, H2, NH3, and CO have been discriminated. Active self-powered gas sensors based on 3D metal oxides/ZnO vertical nanowire arrays have been successfully fabricated and worked well for H2S and NO2 detection. With the decoration by mixture of PEDOT polymer with metal oxide nanoparticles, ZnO vertical nanowire array gas sensors have fast response and recovery time as well as good sensitivity to volatile organic gases of acetone, methanol and ethanol. A novel ionization sensor also has been built by ZnO vertical nannowire arrays, and this device could be able to ionize air under safety operation voltage.

O emprego de mudas pré-brotadas (MPB) de cana-de-açúcar, no sistema canavieiro, cresceu imensamente nos últimos anos. Entretanto, a carência de informações no manejo com herbicidas no sistema pode comprometer a tecnologia. Com o objetivo de compreender melhor os efeitos causados por diferentes herbicidas aplicados em pré e pós-transplantes das MPBs de cana-de-açúcar da variedade CTC4, este estudo foi conduzido em duas etapas em diferentes condições. Os tratamentos foram definidos com base nos herbicidas mais usuais do setor. Ambos os experimentos foram conduzidos no centro de pesquisa da FMC em Paulínia (SP), onde efeitos como fitotoxicidade, altura, produtividade, número de perfilhos, número de colmos e germinação foram avaliados. Para o experimento de campo, observou-se que apesar de injúrias iniciais causadas por diversos herbicidas, apenas o sulfentrazone promoveu redução de produtividade, entretanto todos tratamentos aos 60 dias após à aplicação não apresentavam sintomas de fitotoxidez. A partir desse primeiro estudo, foi realizado em casa de vegetação outro experimento, buscando analisar os mesmos herbicidas em diferentes posicionamentos de aplicação e em dois tipos de solo. Quando posicionado em pré transplante os sintomas de injúrias foram mais elevados, comprometendo o desenvolvimento de alguns tratamentos. Neste caso, o diclosulam mostrou-se o menos seletivo independentemente do tipo de solo estudado, seguido pelo clomazone. Entretanto, a literatura mostra que resultados de seletividade variam de acordo com as condições empregadas e principalmente variedades da cultura, assim, repetições deste estudo devem ser realizadas para possibilitar uma melhor compreensão e validação dos dados. / The use of pre-sprouted seedlings (PSS) of sugarcane in the sugarcane\'s system has grown immensely in recent years. However, lack of information on herbicide management in the system may compromise the technology. In order to better understand the effects caused by different herbicides applied in pre and post-transplantation of sugarcane MPBs variety CTC4, this study was conducted in two stages under different conditions. The treatments were defined based on the herbicides most common in the industry. Both experiments were conducted at the FMC research center in Paulínia (SP), where effects such as phytotoxicity, height, yield, number of tillers, number of stems and germination were evaluated. For the field experiment, it was observed that in spite of initial insults caused by several herbicides, only sulfentrazone promoted a reduction of productivity, however all treatments at 60 days after application did not present phytotoxicity symptoms. From this first study, another experiment was carried out in a greenhouse, trying to analyze the same herbicides in different application positions and in two types of soil. When positioned in pretransplantation the symptoms of injuries were higher, compromising the development of some treatment. In this case, diclosulam showed to be the least selective independent of the type of soil studied, followed by clomazone. However, the literature shows that selectivity results vary according to the conditions employed and mainly the crop varieties, thus, repetitions of this study should be performed to enable better understanding and validation of the data.

Muscarinic acetylcholine receptors (mAChR) belong to the family of G-protein coupled receptors. There are five subtypes of mAChR denoted M1 to M5 that are widely and differentially distributed in both the central nervous system and periphery and play an important role in many specific physiological functions. Impairment of muscarinic neurotransmission occurs in serious disorders such as Alzheimer's disease, schizophrenia or Parkinson's disease that are accompanied by cognitive decline mainly due to the disruption of M1 receptor signaling in the brain. Unfortunately, the high degree homology of the orthosteric binding site among muscarinic receptor subtypes makes it very difficult to obtain subtype- selective agonists. One of the few known selective agonists is xanomeline that preferentially activates the M1 and M4 subtypes. Xanomeline exerts unique interactions with muscarinic receptors comprising reversible binding to the orthosteric domain, and wash-resistant allosteric interaction with a secondary binding site. The basis of xanomeline functional selectivity remains largely unknown. In an attempt to probe into such mechanisms we investigated the immediate and long-term effects of xanomeline on activation of muscarinic receptors, using intact Chinese hamster ovary (CHO) cells expressing individual...

De forma sustentável o setor sucroalcooleiro nacional apresenta grande potencial para o desenvolvimento tecnológico de fontes alternativas de energia. A partir das novas concepções de emprego de energias alternativas, o resíduo industrial do processamento da cana-de-açúcar passa a ser uma matéria-prima com grande potencial e valor. De forma ilustrativa da potencialidade deste material, os dados de produção de bagaço de cana e suas aplicações estão destacados na parte introdutória, compreendendo a possível integração das usinas com as biorrefinarias. A utilização do bagaço de cana-de-açúcar como combustível para co-geração de energia atende à necessidade de mercado, sendo que a rentabilidade de energia elétrica é altamente viável. Porém, considerando-se que esta matéria-prima apresenta características peculiares para a biorrefinaria, objetivou-se o fracionamento da biomassa. As metodologias são investigadas por abranger a conversão da biomassa(bagaço e palha de cana-de- açúcar) para uma variedade de produtos de maior valor agregado (energia, biomateriais e produtos químicos). As etapas de fracionamento, ou seja, de pré-tratamentos foram: préhidrólise, deslignificação e branqueamento. A pré-hidrólise apresentou-se seletiva para a remoção das hemiceluloses, já para a etapa de deslignificação, mostrou-se mais seletiva para a remoção de ligninas, embora houvesse grande remoção também das hemiceluloses. Para a etapa de branqueamento, a remoção residual de lignina foi atingida, porém também foi removido celulose. A avaliação das etapas de pré-tratamentos foi realizada pela determinação dos rendimentos de processos, da seletividade reacional, bem como pela quantificação dos produtos e resíduos obtidos. Os materiais obtidos nas etapas de pré-tratamentos foram caracterizados e posteriormente submetidos ao processo de hidrólise ácida. São apresentados os resultados de rendimento de obtenção de glicose a partir de celulose, em base celulose inicial e em base celulose reagida. Na primeira parte, discutiram-se os rendimentos gravimétricos das reações de hidrólise ácida que para o material in natura resultaram em maiores rendimentos de hidrólise. Os maiores rendimentos obtidos no estudo de hidrólise de celulose foram obtidos para substratos derivados do bagaço integral na concentração de ácido de 0,14%. Os resultados da quarta, relativa a obtenção de coprodutos, HMF e furfural revelou a geração de baixas concentrações desses inibidores da fermentação etanólica. De forma conclusiva, a associação dos resultados dos processos de pré-tratamentos com os resultados obtidos nas reações de hidrólise poderá ser empregada para compreender as vantagens e desvantagens de cada etapa, mostrando caminhos para um melhor aproveitamento da biomassa vegetal, em especial o bagaço de cana de açúcar. Considerando-se a produção de etanol de segunda geração, determinaram-se também as quantidades de inibidores de fermentação etanólica. / Sustainably the Brazilian sugarcane sector presents great potential for technological development of alternative sources of energy. From the new concepts of employment of alternative energy sources, industrial waste from processing of sugarcane becomes a raw material with great potential and value. Illustratively of the potential of this material, the production data of sugarcane bagasse and their applications are highlighted in the introductory section, including the possible integration of the sugarcane mills to biorefineries. The utilization of crushed sugarcane as fuel for co-generation of energy meets the market need, and the profitability of electricity is highly feasible. However, considering that this raw material has peculiar characteristics to the biorefinery, this work aimed at the fractionation of biomass. The methodologies are investigated for covering the conversion of biomass (bagasse and straw from sugarcane). For a variety of products with higher added value (energy, biomaterials and chemicals). The steps of fractionation, or pre-treatments were pre-hydrolysis, delignification and bleaching. The pre-hydrolysis showed up selective removal of hemicelluloses. On the other hand, the delignification step was more selective for the removal of lignin, although there was also large removal of hemicelluloses. For the bleaching stage, the removal of residual lignin was achieved, but some cellulose was also removed from the pulps. The evaluation of the pre-treatments steps were performed by determined the yields of the processes, the selectivity and the quantification of the reaction products and wastes obtained. The materials obtained by the pre-treatment steps were characterized and further submitted to acid hydrolysis. It were presented the results of glucose yields of production base on initial cellulose and reacted cellulose. The first part of the work discusses the gravimetric yield of the acid hydrolysis reaction that produced the highest yield for the in natura material. The highest yields obtained in this study of cellulose hydrolysis were obtained for substrates derivates from integral bagasse at acid concentration of 0.14%. The results of the fourth step, concerning the production of HMF and furfural, revealed the production of low concentrations of these inhibitors of ethanol fermentation. Conclusively, the association of the results obtaining in the pre-treatment processes with that ones obtained by the hydrolysis processes can be used to understand the advantages and disadvantages of the individual steps, showing trends towards a better utilization of vegetal biomass, especially crushed sugarcane. In terms of second generation ethanol, it was presented the results of the quantification of potential inhibitors of ethanolic fermentation.

Dans le contexte du handicap, certaines solutions technologiques permettent de pallier des déficiences pour lesquelles la pharmacologie et la chirurgie sont impuissantes. Les neuroprothèses font partie de ces solutions technologiques. Il s'agit de dispositifs s'interfaçant avec le système nerveux (périphérique ou central), soit pour agir sur celui-ci (stimulation électrique fonctionnelle par exemple), soit pour y recueillir des signaux destinés à commander un dispositif extérieur tel qu'une prothèse robotisée.Le travail présenté dans ce manuscrit s'inscrit dans ce second contexte du recueil de signaux neuronaux sur un nerf périphérique. Aujourd'hui, le seul dispositif utilisable de manière chronique sur l'être humain est l'électrode Cuff tripolaire. Celle-ci recueille l'activité globale du nerf et manque singulièrement de sélectivité. Des dispositifs plus sélectifs, comme les électrodes intrafasciculaires, existent, mais présentent l'inconvénient d'être traumatisants pour le nerf et extrêmement délicats à mettre en place. Notre objectif, au cours de ce travail de thèse, a donc été de développer un dispositif associant la sélectivité d'une électrode intrafasciculaire à la faible invasivité d'une électrode Cuff.Nous avons donc commencé par étudier, en simulation, le potentiel d'action extracellulaire d'un axone myélinisé. Nos simulations nous ont permis de mettre en évidence un "phénomène local", évoqué dans plusieurs publications d'expérimentations antérieures à nos travaux et propre aux axones myélinisés, décroissant très rapidement quand augmente la distance de l'axone à l'électrode. Nous avons donc étudié et dimensionné un dispositif simple, spécifiquement sensible à ce phénomène local.A partir de ce dispositif, nous avons proposé une architecture d'électrode extraneurale qui possède un indice de sélectivité très supérieur à celui de la plus sélective des électrodes extraneurales publiées à ce jour.Malheureusement, ce gain en sélectivité se paie par une dégradation du rapport signal sur bruit. Nous avons donc étudié les solutions permettant de réduire le niveau de bruit ramené au niveau de l'électrode, et nous exposons les grandes lignes d'un dispositif électronique d'acquisition multi-voie faible bruit à température ambiante.Enfin, nous avons construit un modèle d'axone artificiel qui nous a permis de valider expérimentalement nos modèles de simulation ainsi que l'existence du phénomène local. / In the context of sensory or motor deficiencies, some technologic solutions can be proposed in case pharmacology and surgery are inefficient. Neuroprostheses are one of these technologic solutions. It consists in devices interfacing the (peripheral or central) nervous system, either acting on it (functional electric stimulation, neuromodulation...), or recording neuro-signals (automated prosthesis control, closed-loop stimulation...).The work presented in this manuscript focuses on the latter, and more precisely, on recording neuro-signals from peripheral nerves. Today, the only implantable device that can be used for chronic recording on human peripheral nervous system is the tripolar cuff electrode.Unfortunately, it is sensitive to the nerve global activity and exhibits a very low selectivity. More selective devices, like intrafascicular electrodes, exist, but has the drawback to be more traumatizing for the nerve.Therefore, the objective of this thesis was to develop a device associating the selectivity of intrafascicular electrode together with the low invasivity of cuff electrode.We thus started to perform simulations of the extracellular action potential of myelinated axons, putting in evidence a "local phenomenon", already described in some previous publications, and decreasing very quickly with the distance. Then, we have designed and studied a simple neural interface based on the characteristics of this local phenomenon, and specifically sensitive to it.The results have allowed us to propose an extraneural electrode, promising a selectivity index far higher than today's state of the art.Unfortunately, the gain in selectivity leads also to the degradation of signal-to-noise ratio. We have thus studied solutions to reduce noise at the electrode interface, and presented the architecture of a low-noise multi-channel acquisition circuit fitting our requirements.Finally, we have built the artificial model of an axon in order to experimentally validate simulation results, as well as the the local phenomenon characteristics.