Les membranes plasmiques et les membranes du trans-Golgi des cellules eucaryotes présentent une asymétrie des lipides qui les composent, avec les aminophospholipides (APLs : phosphatidylsérine et phosphatidyléthanolamine) enrichis dans le feuillet cytosolique. La dissipation de cette asymétrie est impliquée dans de nombreux processus (patho)physiologiques. Plusieurs études suggèrent que les ATPases P4 sont les candidats les plus probables pour le transport des APLs et le maintien de leur distribution asymétrique ; leur délétion dans la levure inhibe le trafic membranaire. En outre, des études ont montré que les ATPases P4 interagissaient avec les protéines de la famille CDC50 ; cette interaction est essentielle pour l'adressage et peut-être aussi la fonction des ATPases P4. Afin de contribuer à la compréhension du mécanisme de transport des lipides par les ATPases P4, l'objectif de ce travail a été de mettre au point la co-expression fonctionnelle, dans la levure, de l'ATPase P4 Drs2p et de sa protéine partenaire Cdc50p. Nous avons obtenu une fraction membranaire enrichie à 3% avec la protéine Drs2p, majoritairement en complexe avec Cdc50p. L'étude fonctionnelle du complexe nous a permis de mettre en évidence un rôle crucial du phosphatidylinositol-4-phosphate (PI(4)P), un important régulateur du trafic membranaire, au cours d'une étape particulière du cycle catalytique. Nous avons également développé un protocole de purification sur résine streptavidine du complexe Drs2p/Cdc50p. Enfin, comme un site potentiel d'interaction avec le PI(4)P est présent sur l'extrémité C-terminale de Drs2p, nous avons engendré différentes constructions de Drs2p, dans lesquelles une partie de l'extrémité C-terminale a été délétée ; dans une autre construction, l'extrémité N-terminale a également été délétée. Notre travail ouvre la voie à la caractérisation fonctionnelle et structurale détaillée du complexe Drs2p/Cdc50p, et à l'étude du rôle du transport de lipides dans le trafic membranaire.

This thesis aims at the study of small to large surface deformation that can be detected using the remote sensing interferometric synthetic aperture radar (InSAR) methods. The new developments of InSAR processing techniques allow the monitoring of surface deformation with millimeter surface change accuracy. Conventional InSAR use a pair of SAR images ("Master" and "Slave" images) in order to measure the phase difference between the two images taken at different times. The uncertainties in measurements using the conventional InSAR due to the atmospheric delay, the topographic changes and the orbital artifacts are the handicaps of this method. The idea of InSAR method is to measure the phase difference between tow SAR acquisitions. These measure refere to the ground movment according to the satellite position. In interferogram the red to blue colors refere to the pixel movement to or far from the satellite position in Line-Of-Sight (LOS) direction. In 2000's, Radar spacecraft have seen a large number of launching mission, SAR quisitions and InSAR applicability have seen explosion in differents geophysical studies due to the important SAR datas and facility of data accessibity. This SAR-mining needs other type and generation of InSAR processing.In 2001, Ferretti and others introduce a new method called Permanent Scatterer InSAR (PS) that is based on the use of more than one Slave image in InSAR processing with the same Master image. This method allows enhancing the LOS signal for each pixel (PS) by using the best time and/or space-correlated signal (from amplitude and/or from phase) for each pixel over the acquisitions. A large number of algorithms were developed for this purpose using thesame principle (variantes). In 2002, Berardino et al developed new algorithm for monitoring surface deformation based on the combination of stack of InSAR results from SAR couples respecting small baseline (SB) distance. Nowadays, these two methods represent the existing time series (TS) analysis of SAR images approaches. In addition, StaMPS software introduced by Hooper and others, in 2008 is able to combine these two methods in order to take advantages from both of this TS approaches in term of best signal correlation and reducing the signal noise errors. In this thesis, the time series studies of surface changes associate to differents geophysical phenomena will have two interest: the first is to highlight the PS and SBAS results and discuss the fiability of obtained InSAR signal with comparation with the previous studies of the same geophysical case or observations in the field and in the second time, the combined method will also validate the results obtained separately with differents TS techniques. The validation of obtained signal is assured by these two steeps: Both of PS and SBAS methods should give relatively the same interferograms and LOSdisplacement signal (in term of sign and values), in addition these results will be compared with the previous studies results or with observations on the field.In this thesis, the InSAR techniques are applied to different case-studies of small surface deformation [...]

Dominican mass-migration to the United States only started in the 1960s but Dominican Americans are now a sizable minority and in 2014 they became the largest Latino group in New York City. This thesis examines fictional works by Dominican American writers who migrated to the United States from the early 1960s to the 1990s which explore the predicament of Dominican Americans before and after the consolidation of Dominican-American communities. The novels under scrutiny here were published in English between 1991 and 2012 by Julia Alvarez (b. 1950), Loida Maritza Pérez (b. 1963), Junot Díaz (b. 1969), and Angie Cruz (b. 1972) and present us with characters whose search for a ‘home’ and for ways in which to articulate their individual and collective identity are shaped by continuous negotiations between the traditional values of their country of origin and the potentially transformative opportunities afforded by their new country. I will show how these texts powerfully challenge homogeneity, marginalisation, mainstream ideologies, nationalism, and discrimination while questioning the economic, social, religious, patriarchal, educational, and political structures of both the Dominican Republic and the United States in order to formulate diverse modalities of belonging to what Julia Alvarez has called a new “country that’s not on the map” and establish their own distinct position as Dominican American writers.

By tracking the intersection of contemporary fiction and the information technologies of the digital age, this thesis argues that the narratives being produced over the past ten years have evolved into a distinct genre of literature, one where the aesthetics of fragmentation and postmodern uncertainty must confront the new realities of a digitally saturated culture and society. In order to demonstrate this alteration in contemporary fiction, this thesis considers novels written within the past ten years that reflect on this new form of textuality, namely Don DeLillo’s Cosmopolis (2003) and David Eggers’ The Circle (2013). These texts demonstrate a paradigm shift in contemporary literature, a new kind of fiction in which American society, culture, economics, and politics, are all directly affected by various forms of digital mediatisation. These authors reflect an altered cultural zeitgeist within their fiction—writings which can be differentiated from the postmodern literary aesthetic—prompted by neoteric digital technologies coupled with the ubiquitous nature of the Internet. Although this topic is broad and covers multiple fields of scholarly interests, my thesis nonetheless concerns itself with a very specific line of questioning: will our authors have the imaginative wherewithal and social sensitivity to keep pace with changes brought forth by the explosion of information technologies? If so, what type of fiction is likely to emerge from this new digital environment? By taking a focused approach and using contemporary literature as representative of these massive social, economic, and political transformations, my research recalls Kurt Vonnegut’s “Canary in the Coal Mine” dictum: the writer has always been the first to notice the dramatic effects of technology on the individual and the culture at large.

This report is about control, design and implementation of a low voltage-fed quasi Z-source three-level inverter. The topology has been interesting for photovoltaic-systems due to its ability to boost the incoming voltage without needing an extra switching control. The topology was first simulated in Simulink and later implemented on a full-bridge module to measure the harmonic distortion and estimating the power losses of the inverter. An appropriate control scheme was used to set up a shootthrough and design a three-level inverter. The conclusion for the report is that the quasi Z-source inverter could boost the DC-link voltage in the simulation. But there should be more consideration to the internal resistance of the components for the implementation stage as it gave out a lower output voltage than expected.

Orientador: Prof. Dr. Michel Oliveira da Silva Dantas / Dissertação (mestrado) - Universidade Federal do ABC, Programa de Pós-Graduação em Engenharia Elétrica, 2016. / Sensores de vacuo sao amplamente utilizados tanto no ambito industrial como no da pesquisa cientifica, pois possuem aplicacoes em diversas tecnicas de fabricacao e de analise, como a microscopia eletronica de varredura (MEV), a litografia por feixe de eletrons, e a espectrometria de massa, entre outras. Dentre os diversos tipos de sensores de vacuo destacam-se os baseados em efeito de campo (FE - Field Emission Device), que sao dispositivos que emitem eletrons em vacuo na presenca de um elevado campo eletrico. A literatura destaca diversas vantagens destes dispositivos: operacao em temperatura ambiente, reducao de consumo de potencia e tensao de operacao, obtencao de altas densidades de correntes em areas reduzidas, e rapido tempo de resposta. Existem diversas tecnicas de microfabricacao que podem ser utilizadas para obtencao de dispositivos FE, destacando-se a tecnica HI-PS (gHydrogen Implantation . Porous Siliconh), que proporciona baixa complexidade e custo. No entanto, para obtencao de FEs com sistema anodo-catodo integrado, a tecnica HI-PS apresenta algumas limitacoes, como o elevado numero de etapas de processo, a necessidade de elevada temperatura e tempo de oxidacao, e principalmente a isolacao eletrica deficiente entre as estruturas do anodo e do catodo, propiciando a existencia de correntes de fuga pelo gcorpoh do dispositivo. Frente a estes problemas, este trabalho apresenta estrategias estudadas para aprimorar a tecnica HI-PS de microfabricacao de dispositivos de emissao de campo integrados. Visando a reducao do numero de etapas de processo e a eliminacao de defeitos, inicialmente, foi estudada a utilizacao de fotorresiste como mascara a implantacao ionica de hidrogenio. Esta estrategia se mostrou viavel, resultando na formacao seletiva de silicio poroso e na obtencao de micropontas (catodos) com altura em torno de 10 ¿Êm e diametro dos apices em torno de dezenas de nanometro, dimensoes estas atestadas por MEV. Tambem foi pesquisada a utilizacao de fotorresiste como camada dieletrica, que se mostrou inviavel para a aplicacao proposta devido aos valores de correntes de fuga relativamente elevados. Para melhorar a isolacao eletrica entre as estruturas do anodo e do catodo, a estrategia pesquisada foi a utilizacao de oxido de silicio poroso (Ox-PS) como camada dieletrica entre as referidas estruturas. Para obtencao do Ox-PS, foram estudados diferentes parametros de oxidacao, como temperatura, tempo de processo, gradiente de temperatura de oxidacao (pre-oxidacao), e processo de recozimento termico pos-oxidacao em ambiente Forming Gas. Para as caracterizacoes morfologicas do Ox-PS, foram analisados, por meio de microscopia otica, parametros como espessura, estabilidade estrutural, taxa de corrosao e oxidacao total da camada PS, sendo este ultimo realizado atraves da tecnica Fourier Transform Infrared Spectroscopy (FTIR). Para a caracterizacao eletrica da corrente de fuga, foram confeccionados dispositivos MOS, caracterizados eletricamente por aparato constituido por um analisador de parametros semicondutores. O Ox-PS obtido com T = 1000 ¿C, t = 1 h, e com recozimento termico pos-oxidacao em ambiente Forming Gas apresentou significativa reducao da corrente de fuga (de 30 nA para 0,125 nA), comprovando, deste modo, sua potencialidade para a aplicacao proposta. Ja na fabricacao do FE integrado, o Ox-PS obtido nestas condicoes apresentou elevada instabilidade estrutural, gerando a necessidade de implementar processos de pre-oxidacao para obtencao da estrutura anodo-catodo integrada. Atraves dos parametros adequados, foi finalmente comprovada a viabilidade da otimizacao da tecnica HI-PS atraves das estrategias estudadas, possibilitando a fabricacao do dispositivo FE integrado contendo micropontas de alturas de aproximadamente 10 micrometros e apices da ordem de dezenas de nanometros circundadas pela estrutura do anodo com distancias de separacao de aproximadamente 20 micrometros. Com a otimizacao dos processos de fabricacao, almeja-se futuramente implementar o dispositivo FE integrado obtido por HI-PS no desenvolvimento de sensores compactos e de baixo custo e complexidade de fabricacao. / Vacuum sensors are widely used in industry and in scientific research, because they can be applied in several fabrication and analysis techniques, such as Scanning Electron Microscopy (SEM), electron beam lithography and mass spectrometry, for example. Among the large number of vacuum sensors, we can highlight the Field Emission Devices (FE), which are devices that emit electrons in vacuum environment when submitted to a high electric field. The literature reports several advantages of these devices: operation at room temperature, low power consumption, high current densities in small areas, and fast response times. Several microfabrication techniques allow obtaining FE devices, including the HI-PS (Hydrogen Implantation ¿ Porous Silicon) technique, which is remarkable due to its low complexity and cost. However, HI-PS presents some limitations when applied to obtain FE with integrated anode-cathode system: high number of process steps, high temperature and oxidation times, and mainly the poor electrical insulation between anode-cathode structures, which results in leakage currents through the bulk of these devices. In this context, this work shows strategies to improve the HI-PS technique for microfabrication of integrated FE devices. First, we use photoresist as mask for hydrogen ion implantation aiming at defects elimination and reduction of process steps. This strategy resulted in the selective formation of porous silicon and in obtaining microtips (cathodes) with 10 ìm height and apex around tens of nanometers, as verified by Scanning Electron Microscopy (SEM). In addition, photoresist was tested as dielectric between anodecathode structures, but the high leakage current measured hindered the use of this material for the proposed application. The main strategy researched to improve the electrical insulation between anode-cathode structures was the use of oxidized porous silicon (Ox-PS) as dielectric. To obtain Ox-PS, we studied oxidation parameters such as temperature, time, pre-oxidation, and post-oxidation annealing. Optical Microscopy and Fourier Transform Infrared Spectroscopy (FTIR) were applied to analyze morphological aspects such as thickness, stability, etch rates and full oxidation of PS layers. A semiconductor parameter analyzer was used to characterize the leakage current from fabricated MOS devices. The Ox-PS obtained with T = 1000 °C, t = 1 h, and post-oxidation annealing in Forming Gas environment showed remarkable decrease of leakage current in comparison to the other oxidation conditions (from 30 nA to 0,125 nA), which demonstrates potentiality for the proposed application. Additionally, a pre-oxidation process was introduced to improve structural stability of Ox-PS layers. After this implementation, the optimization viability of HI-PS technique was finally proved, allowing obtaining an integrated FE device with microtips with 10 micrometers height and apex about tens of nanometers surrounded by the anode structure. The separation distance between anode-cathode structures was about 20 micrometers. With the optimization of fabrication process, we intend to implement hereafter the integrated FE device obtained by HI-PS technique in the development of compact sensors with low cost and low fabrication complexity.

Made available in DSpace on 2014-12-17T14:20:21Z (GMT). No. of bitstreams: 1 LucianaCC_TESE.pdf: 4454358 bytes, checksum: acd9ca889a0f174c8d5f49b94bbd79be (MD5) Previous issue date: 2011-04-01 / Coordena??o de Aperfei?oamento de Pessoal de N?vel Superior / This research looks at the collective imagination in which it keeps alive the issue of heroin wise. Two wise women appear in the narratives of popular history and the History of Donzela Theodora and History Imperatriz Porcina, collated by Lu?s da C?mara Cascudo in his Five Books of the People. The universality, mobility and circularity of these narratives are discussed by authors such as Bakhtin and Guinzburg. The research is developed from three key categories: Knowledge Magic as the knowledge of tradition (Almeida), sensitive knowledge (Levi-Strauss), thought mythical / magical / symbolic (Morin); Wise Women as carriers of this knowledge, which merge and overlap with the imagery of witches and healers; and Mythical Elements which corresponds to the archetypal images (Jung and Silveira), symbols and other images that relate to the magic universe, the magical beliefs and practices considered, ie belonging to the imaginary magic (Bethencourt). Porcina and Theodora are understood as bearers of knowledge of M?tis (Detienne and Vernant), or the cunning intelligence, the manipulation of ph?rmakon (Derrida), the healing potion, which may be the word or ointment of the herb. The route takes us to meet the great archetype of the Wise Woman as psychic power of the feminine, the anima. Narratives are medicinal balms (Estes) and is the clash between the anima and its embodiments by wise women, and animus, his opponents, which gives the transmutation of the psyche, a work comparable to that of alchemyThe Knowledge Magic, operating through the female, myth and nature can recover from its essential value to the emerging paradigm that suggests a more complete human science and a more plural / A presente pesquisa se volta para o imagin?rio coletivo no qual se mant?m viva a tem?tica da hero?na s?bia. Duas mulheres s?bias aparecem nas narrativas populares Hist?ria da Donzela Teodora e a Hist?ria da Imperatriz Porcina, cotejadas por Lu?s C?mara Cascudo em sua obra Cinco Livros do Povo. A universalidade, a mobilidade e a circularidade dessas narrativas s?o discutidas a partir de autores como Bakhtin e Guinzburg. A pesquisa se desenvolve a partir de tr?s categorias chaves: o Saber M?gico como saberes da tradi??o (Almeida), saberes sens?veis (L?vi-Strauss), pensamento m?tico/m?gico/simb?lico (Morin); Mulheres S?bias como as operadoras desse saber, que se confundem e se imbricam com o imagin?rio das bruxas e curandeiras; e Elementos M?ticos que corresponde ?s imagens arquet?picas (Jung e Silveira), s?mbolos e demais imagens que remetam ao universo m?gico, ?s cren?as e pr?ticas consideradas m?gicas, ou seja, pertencentes ao imagin?rio da magia (Bethencourt). Teodora e Porcina s?o compreendidas como portadoras do saber da m?tis (Detienne e Vernant), ou seja, da intelig?ncia astuta, da manipula??o do ph?rmakon (Derrida), a po??o de cura, que pode ser a palavra ou o ung?ento de erva. O percurso nos leva ao encontro do grande arqu?tipo da Mulher S?bia enquanto pot?ncia ps?quica do feminino, a anima. As narrativas s?o b?lsamos medicinais (Est?s) e ? no embate entre a anima e suas personifica??es atrav?s de mulheres s?bias, e o animus, seus oponentes, que se d? a transmuta??o da psique, um trabalho compar?vel ao da alquimia. O Saber M?gico, operando atrav?s do feminino, do mito e da natureza pode recuperar seu valor indispens?vel junto ao paradigma emergente que aponta um humano mais completo e uma ci?ncia mais plural

Submitted by Automa??o e Estat?stica (sst@bczm.ufrn.br) on 2016-06-06T22:31:08Z No. of bitstreams: 1 GelsaPedroCampelo_DISSERT.pdf: 1791157 bytes, checksum: cf1c75f51f8ae22fe8b7222adbf3e1b3 (MD5) / Approved for entry into archive by Arlan Eloi Leite Silva (eloihistoriador@yahoo.com.br) on 2016-06-09T20:33:03Z (GMT) No. of bitstreams: 1 GelsaPedroCampelo_DISSERT.pdf: 1791157 bytes, checksum: cf1c75f51f8ae22fe8b7222adbf3e1b3 (MD5) / Made available in DSpace on 2016-06-09T20:33:03Z (GMT). No. of bitstreams: 1 GelsaPedroCampelo_DISSERT.pdf: 1791157 bytes, checksum: cf1c75f51f8ae22fe8b7222adbf3e1b3 (MD5) Previous issue date: 2015-07-31 / Condi??es de trabalho desfavor?veis constituem um dos fatores que podem contribuir para o desencadeamento de transtornos ps?quicos e comportamentais nos trabalhadores. Nesse sentido, esta pesquisa objetivou caracterizar as condi??es de trabalho dos servidores t?cnico-administrativos, especificamente dos auxiliares e assistentes em administra??o do campus central da Universidade Federal do Rio Grande do Norte - UFRN, Natal, Brasil, bem como, identificar a incid?ncia de sofrimento ps?quico nesse grupo de servidores. Enquanto estrat?gia, optou-se por um estudo de caso do tipo multim?todo, de natureza descritiva com etapas quantitativa e qualitativa sequenciais. Para isso, foi realizada inicialmente pesquisa documental atrav?s do levantamento de dados epidemiol?gicos relativos ?queles servidores lotados no campus central, visando identificar as principais enfermidades apresentadas durante o per?odo de janeiro de 2011 a junho de 2014. Em seguida, procedeu-se a etapa de diagn?stico dos aspectos relacionados ao trabalho, atrav?s da aplica??o online e in loco do Question?rio de Condi??es de Trabalho (j? validado por Borges et al., 2013a) em 11 setores selecionados de acordo com os seguintes crit?rios: maior n?mero de servidores por unidade organizacional e maiores e menores percentuais de afastamentos para tratamento de sa?de por CID-F (conforme registros da Diretoria de Aten??o ? Sa?de do Servidor ? DAS). No tratamento dos dados foram utilizados os softwares editor de planilhas Microsoft Office Excel; estat?stico SPSS? Statistical Package for the Social Sciences e realizou-se an?lise de conte?do de tipo classificat?rio das quest?es abertas. Participaram do estudo de caso 174 servidores e os resultados obtidos mostram predomin?ncia de afastamentos por transtornos mentais ou comportamentais (CID F), doen?as do sistema osteomuscular (CID M) e do aparelho respirat?rio (CID J). Entre os fatores que apresentaram signific?ncia est?o ? jornada de trabalho (contratuais e jur?dicas); exig?ncia de esfor?o f?sico (M=2,59) e espa?o de trabalho (M=2,58) ? condi??es f?sicas e materiais; est?mulo ? colabora??o (M=3,5) - processos e caracter?sticas do trabalho; e participa??o (M=1,78) - ambiente sociogerencial. Logo se infere a exist?ncia de rela??o entre esses fatores e alguns dos motivos de afastamento relatados pelos participantes. Sugere-se ainda a amplia??o da presente investiga??o com estudos envolvendo outras categorias profissionais (incluindo bolsistas e terceirizados) e setores espec?ficos. / Unfavorable working conditions constitute one of the factors that may contribute to cause psychic suffering and behavioral disorders in workers. This research aimed to characterize the working conditions public servant technical- administrative , specifically the auxiliaries and assistants in administration of the Federal University of Rio Grande do Norte ? UFRN, Natal, Brasil, as well to identify the incidence of psychic suffering in this group of public servants. As a strategy, we chose a case study of multi-method type, descriptive with quantitative and qualitative sequential steps. For this, it initially performed desk research by surveying epidemiological data for these public servants working in central campus, to identify the major diseases presented in the period from January 2011 to June 2014. Then, we proceeded to diagnostic step of the aspects related to work, by applying online and in loco of Working Conditions Survey (already validated by Borges et al., 2013a) in 11 sectors selected according to the following criteria: high number of workers public servants and major and minor percentage of absences for health care for ICD-F (according to records of Sector of Workers Health Care - DAS). In the treatment of the data the spreadsheet editor software Microsoft Office Excel and statistical SPSS Statistical Package for Social Sciences were used and made qualifying type of content analysis of open questions. Applied to this study 174 public servants and the results show a predominance of absenteeism due to mental or behavioral disorders (ICD F), musculoskeletal diseases (ICD M) and respiratory system (ICD J). Among the factors that were significant are the working hours (contractual and legal); Physical Effort (M = 2.59) and workspace (M = 2.58) - physical and material conditions; encouraging collaboration (M = 3.5) - processes and characteristics of the work; and participation (M = 1.78) - social-management environment. Therefore, it infers the existence of a relationship between these factors and some of the reasons for absenteeism reported by participants. It is suggested the expansion of this research with studies involving other professionals (including scholarship workers and contractors) and specific sectors.

Le développement des nanotechnologies dans le domaine médical a suscité un engouement considérable ces dernières années, notamment l’utilisation de nanoparticules pour la vectorisation de principes actifs. Les nanoparticules offrent des perspectives uniques pour la vectorisation et la délivrance de principes actifs qu’ils soient des gènes (thérapie génique),des anti-cancéreux (chimiothérapie) ou encore des agents photosensibilisateurs (photothérapie dynamique, TPD). Le défi majeur reste cependant l’acheminement des molécules thérapeutiques jusqu’à leur site d’action, tout en gardant leur intégrité ainsi que leur effet thérapeutique.L’axe de recherche de cette thèse est l’utilisation des nanocapsules lipidiques comme plateforme multifonctionnelle pour la délivrance de principes actifs. Un des objectifs étant le développement de nanocapsules lipidiques, stables de point de vue physico-chimique, et fonctionnalisées avec du polyéthylèneimine capables de délivrer efficacement un plasmide ADN et un anti-cancéreux (paclitaxel) dans le cadre d’une thérapie combinée. Les applications de ces nanovecteurs pour la transfectionde gènes et la vectorisation de chimiothérapeutique in vitro ont été réalisées.Par ailleurs, l’aptitude de nanocapsules lipidiques à vectoriser des agents photosensibilisants pour la thérapie photodynamique a été aussi étudiée in vitro, et les résultats ont montré que l’encapsulation de deux molécules de PS dans les nanocapsules permet une synergie de l’effet photodynamique tout en gardant les propriétés physico-chimiques de chaque PS. Enfin, l’encapsulation d’un agoniste au canal ionique TRPM8, le menthol, fait l’objet du dernier chapitre. L’étude par imagerie calcique du relargage de cette molécule lipophile in vitro a permis de confirmer le potentiel des NCL comme nanovecteurs de principes actifs. / The development of nanotechnology in the medical field has attracted considerable interest in recent years, including the use of nanoparticles for drug delivery. Nanoparticles offer unique opportunities for delivery of active drugs such as genes (gene therapy), anti-cancer (chemotherapy) or photosensitizers (photodynamic therapy, PDT). The major challenge, however, remains the delivery of therapeutic molecules to their site of action while keeping their integrity and their therapeutic effect.The research focus of this thesis is the use of lipid nanocapsules as a multifunctional platform for the delivery of drugs. One goal is the development of stable lipid nanocapsules, functionalized with polyethyleneimine and capable of effectively delivering a plasmid DNA and an anti-cancer (paclitaxel) as part of a combination therapy. The applications of these nanocarriers for transfection and delivery of chemotherapeutic were performed in vitro.Moreover, the ability of lipid nanocapsules to encapsulate photosensitizers for photodynamic therapy has been studied in vitro, and the results showed that the encapsulation of two molecules of PS in the nanocapsules allows a synergy photodynamic effect while protecting the PS from photo degradation.Finally, encapsulating an ion channel TRPM8 agonist (menthol) is the subject of the last chapter. The study by calcium imaging of the release of this lipophilic molecule in vitro confirmed the potential of lipid nanocapsules as nanocarriers of drugs.

Indiana University-Purdue University Indianapolis (IUPUI) / Paper spray - mass spectrometry (PS-MS) has been developed as a rapid and direct ionization method for qualitative and quantitative analysis of complex samples at trace levels. In this work, different sampling devices for PS-MS were investigated to improve the assay’s simplicity and sensitivity over traditional approaches. In particular, chapter two characterizes an alternate paper substrate to enhance drug detection on surfaces like asphalt, cloth, concrete, aluminum, and glass. Analysis occurs on a single spray ticket coated with pressure-sensitive adhesive (PSA), also known as Post-it notes to detect and quantify drug residues. A PS-MS method utilizing PSA paper was developed to detect a mixture of ten drugs off of various surfaces to evaluate the qualitative and quantitative capabilities of the aforementioned substrate. After the method development on a conventional linear ion trap mass spectrometer, the assay was translated for use on a portable mass spectrometer to evaluate the suitability of the pressure-sensitive adhesive paper substrate in the field in chapter three. Chapter four introduces a sampling device combined with a snap-in solid-phase extraction (SPE) column. The new cartridge design not only inherits the functions from the first iteration SPE cartridge, including extraction and preconcentration from complex samples, but also exhibits greater flexibility in volume control and ease of use for on-site sample collection.