O presente trabalho trata do desenvolvimento de sensores eletroquímicos que possuam características descartáveis e ao uso destes dispositivos para a determinação de diferentes analitos em amostras biológicas, farmacêuticas e de interesse ambiental. O desenvolvimento e a aplicação dos sensores foram divididos em seis capítulos. O primeiro capítulo corresponde a fabricação de conjuntos de microeletrodos em suporte de CD-RW e placa fenolite utilizando impressão com tinta toner. Os conjuntos de microeletrodos foram fabricados por meio da deposição de duas máscaras de toner em um substrato de cobre ou ouro. Os eletrodos fabricados neste capítulo foram caracterizados e aplicados nos capítulos subsequentes. Os resultados da aplicação do conjunto de microeletrodos de cobre (DCRM) foram descritos no segundo capítulo. Os dispositivos foram aplicados para a determinação de peróxido de hidrogênio em amostras de antisséptico bucal e clareadores dentais. As determinações foram realizadas em solução de tampão fosfato (pH 7.0) por meio da técnica de amperometria (E = -0,2 V). Estes sensores foram também aplicados para determinação de ácido acetilsalítico (AAS) em amostras farmacêuticas em solução de hidróxido de sódio 0,1 mol L-1 por amperometria (E = 0,6 V). A determinação de nitrato em amostra de água de rio foi realizada por amperometria (E = -0,45V) em solução de sulfato de sódio 0,1 mol L-1 (pH = 2,0). Os resultados obtidos com o sensor demonstraram o sucesso das aplicações. As principais vantagens deste dispositivo dizem respeito à simplicidade de fabricação, baixo custo do equipamento e rapidez das análises. A caracterização eletroquímica do sensor e a determinação de ciclopirox olamina em solução de tampão BR 0,1 mol L-1 (pH = 5,0) utilizando o conjunto de microeletrodos de ouro (CD-RW) foi apresentada no terceiro capítulo. Os resultados obtidos mostraram que é possível realizar a determinação desta espécie de interesse em soluções oftalmológicas. O desenvolvimento, a caracterização e aplicação de um novo conjunto de microeletrodos de ouro fabricados a partir da redução eletroquímica da 5-bromo-1,10-fenantrolina em solução de dimetilformalmida (DMF) foi investidada no quarto capítulo. A superfície foi bloqueada com um filme isolante de 1,10-fenantrolina e o sensor foi caracterizado como um conjunto de microeletrodos de ouro. O sensor foi aplicado para a determinação de peróxido de hidrogênio, nas condições descritas anteriormente a fim de avaliar a aplicabilidade deste dispositivo. Os resultados obtidos foram promissores. A utilização de um eletrodo de microbanda impresso na configuração \"back-to-back\" foi descrita no quinto capítulo. A configuração faz uso da impressão de um novo eletrodo nas costas de um eletrodo impresso \"tradicional\", aumentando com isso a sensibilidade do sensor. O eletrodo impresso na configuração \"back-to-back\" foi utilizado para a determinação de íons Pb(II) em amostras de água potável por meio da técnica de voltametria de redissolução anódica por onda quadrada e os resultados obtidos foram concordantes com os encontrados utilizando espectrometria de emissão atômica por plasma acoplado. Os eletrodos de microbanda impressos na configuração \"back-to-back\" modificados com nanotubos de carbono para a determinação de capsaicina e dopamina e com ftalocianina de cobalto (II) para determinação de hidrazina foram investigados no sexto capítulo. Os resultados obtidos foram concordantes com aqueles descritos em outros trabalhos encontrados na literatura. / This work presents results on the fabrication of disposable electrochemical sensors and the use of such devices for the determination of different analytes in biological, pharmaceutical and environmental samples. The development and application of these sensors have been divided into six chapters. The first chapter describes the fabrication of a microelectrode ensemble (CD-RW) using ink toner. The sensor was fabricated by deposition of two toner pattern masks on copper and gold substrates. The electrodes fabricated according this procedure were characterized and applied in subsequent chapters. The second chapter describes the use of a disposable copper random microarrays (DCRM) for the amperometric determination of three analytes: hydrogen peroxide in real samples (oral antiseptic and dental whitening) at -0.2 V in phosphate buffer (pH 7.0) solution, acetylsalicylic acid (ASA) in pharmaceutical formulations at 0.6 V in 0.10 mol L-1 NaOH solution and nitrate in river samples at -0.45V in a 0.10 mol L-1 sodium sulfate solution (pH 2.0). The good results obtained with the DCRM demonstrated the successful application of this new sensor. The main advantages of the proposed manufacturing procedure are the simplicity, low cost of equipment and the high speed of production. The third chapter presents results on the use of a gold random microarray (GRM) for the determination of ciclopirox olamine in 0.10 mol L-1 Britton Robinson buffer solution (pH 5.0). Following the optimization of the experimental parameters, the proposed sensor presented excellent analytical properties for the amperometric detection of ciclopirox olamine at +0.85 V. The usefulness of the GRM sensor was confirmed by determining ciclopirox olamine in commercial products and the results obtained agreed well with those found by potentiometric titration and the labeled values. The fourth chapter describes the fabrication of a random assembly of microelectrodes (RAMs) by electrochemical reduction of 5-bromo-1,10- phenathroline in N,N-dimethylformamide (DMF), generating the 1,10-phenanthroline radical, which was covalently grafted on gold electrodes. After several potential cycles, the gold surface was partially blocked with an insulating film of 1,10-phenanthroline and the resulting modified electrode exhibited the characteristics of RAMs for the electrochemical reduction of the reversible probe 1,4-benzoquinone in DMF. This sensor was applied for hydrogen peroxide detection at -0.2 V in phosphate buffer (pH 7.0) solution. The fifth chapter reports on the use of screen-printed back-to-back microband electroanalytical sensors for quantification of lead(II) ions in drinking water samples in 0.01 mol L-1 HCl and the validation of the results by ICP-OES. The sixth chapter shows results on the use of back-to-back screen-printed microband electrodes modified with single-walled carbon nanotubes and cobalt phthalocyanine. The electroanalytical applications of this novel electrode configuration were exemplified towards the sensing of dopamine, capsaicin and hydrazine.

Le sarcome de Ewing est la seconde tumeur pédiatrique de l’os la plus fréquente. Elle est caractérisée par une translocation chromosomique résultant à la fusion de EWSR1 avec un membre de la famille ETS. Chez 85% des patients, cette fusion conduit à l’expression de la protéine chimérique EWS-FLI1 qui est l’oncogène majeur de ce sarcome. Ce dernier agit principalement par son action transcriptionelle sur des cibles qui lui sont propres. Au niveau thérapeutique, le sarcome d’Ewing est traité par chimiothérapie, chirurgie locale et par radiothérapie. La survie à long terme des patients est de l’ordre de 70%, mais beaucoup plus basse pour les patients métastatiques et quasi nulle lors d’une récidive. Parmi maintes caractéristiques, certains cancers présentent une dérégulation énergétique. L’influence d’EWS-FLI1 sur cet aspect n’a fait l’objet d’aucune étude dans le contexte du sarcome d’Ewing. Nous avons donc étudié par profilage métabolomique des cellules de sarcome d’Ewing en présence ou en absence d’EWS-FLI1. En comparant ces deux conditions, des modulations du profil énergétique relatif au cycle de Krebs, des précurseurs de le glycosylation ainsi que des métabolites de la voie de la méthionine et du tryptophane ont été observés. En parallèle, grâce à un crible de banque de shRNAs réalisé dans des conditions expérimentales similaires à l’étude métabolomique (lignée d’Ewing avec ou sans EWS-FLI1), nous avons pu identifier des gènes présentant des caractéristiques « synthétique létales », c'est-à-dire tuant uniquement les cellules du sarcome d’Ewing en présence de son oncogène. / Ewing sarcoma, the second most commonly occurring pediatric bone tumor, is most often characterized by a chromosomal translocation between EWSR1 and FLI1. The gene fusion EWS-FLI1 accounts for 85% of all Ewing sarcoma and is considered the major oncogene and master regulator of Ewing sarcoma. EWS-FLI1 is a transcriptional modulator of targets, both directly and indirectly. Ewing sarcoma is aggressively treated with chemotherapy, localized surgery and radiation and has an overall survival of about 70%, however, survival for metastasis or relapsed cases remains low. One of the cancer hallmarks, metabolic deregulation, is most likely partly dependent on EWS-FLI1 in Ewing sarcoma cells. In order to get a better understanding of Ewing sarcoma biology and oncogenesis, it might be of high interest to investigate the influence of EWS-FLI1 in Ewing sarcoma cells. We therefore performed a global metabolic profiling of Ewing sarcoma cells with or without inhibition of EWS-FLI1. Several changes in the energy metabolism were observed throughout this study; the observed changes were consistent with an energy profile that moved from a cancer cell energy metabolism towards the energy metabolism of a more normal cell upon EWS-FLI1 inhibition, primarily based on the TCA cycle. Levels of TCA intermediates, glycosylation precursors, methionine pathway metabolites and amino acids, especially changes in the tryptophan metabolic pathway, were altered upon EWS-FLI1 inhibition. Parallel to this study, we performed a high-throughput synthetic lethality screen, in order to not only identify essential genes for cell survival and proliferation, but also to identify new synthetic lethal targets that could specifically target Ewing sarcoma cells carrying the EWS-FLI1 fusion gene.

No description available.

The subjects of film and theatre belong to an extensive hierarchical debate that has remained prominent within the realm of performing arts since the introduction of cinema in the late nineteenth century. A plethora of scholars choose to argue in favor of the former, suggesting that film surpasses theatre as superior in both aesthetics and overall execution of naturalism; however, the argument is purely subjective and cannot be applied to all films and their corresponding plays. As a counterclaim, theatre continues to thrive as a prominent source of artistic entertainment globally, not only offering a contemporary twist to preexisting texts, but also impacting an audience in methods that film will never be able to do so. Maria Friedman’s High Society is a primary example that reaffirms how theatre can triumph the continual debate when compared to its preceding film – The Philadelphia Story – directed by George Cukor, both artistically and through its overall execution of the profound topics represented within the original text. This thesis will primarily juxtapose Cukor’s iconic film with Friedman’s revival of the former that was performed in 2015 at London’s Old Vic theatre, offering an innovative rebuttal to the preexisting debate as well as to affirm the argument of how theatre compellingly transforms the mundane.

No description available.

Les technologies du numérique modifient profondément la manière dont les sociétés appréhendent et se représentent leur espace. La cartographie n’est pas à l’écart de ces changements et les cartes sont de plus en plus nombreuses et sont utilisées sous de nouvelles formes. C’est en particulier le cas de la consultation d’itinéraires uniques, rendue plus aisée par les évolutions techniques et technologiques. L’usage de ces itinéraires est aujourd’hui l’une des principales fonctionnalités des cartes numériques, dont un grand nombre sont issues de sociétés implantées aux États-Unis.Comment appréhender, dans le cadre d’une analyse diachronique et comparatiste, le rôle des cartes d’itinéraire dans la cartographie numérique? S’agit-il d’une nouveauté ou de la réactualisation d’une forme cartographique plus ancienne ? Quelle place tient ce type de représentations dans une perspective croisée?La thèse propose de répondre à ces questions par une analyse large à trois entrées : cartobibliographique, sémiologique et processuelle, en se basant sur des corpus de cartes issus de la Bibliothèque nationale de France et de laNewberry Library. Les principaux résultats de ce travail apportent un éclairage sur les changements en cours avec le passage d’une cartographie majoritairement papier à une cartographie majoritairement écran. Ils invitent finalement à penser ces changements à travers une redéfinition du statut de la carte à l’ère numérique. / Digital technologies deeply change the way in which societies grasp their environment and represent space Cartography is not exempt from these changes, maps are more widespread than ever and are being used for new purposes. Among them, the use of route specific maps, made easier by technical and technological developments. Many online maps are used for itineraries, and most of them come from United States-based corporations.These observations raise the questions of how to understand this specific use of maps when put in a chronological and comparative perspective ? Is this an innovation or rather an actualization of a previous type of mapping practice ? What is the status of these itineraries when studied in a multifaceted perspective ?This research addresses these questions using three main approches : cartobibliographical, semiological and processual, and relying on extensive map collections from the Bibliothèque nationale de France and the Newberry Library. The main results bring new insights on the changes taking place with the transition from a primarily paper cartography to a primarily on-screen cartography and call for a redefinition of the status of maps in the digital era.

本研究的主要目的有二：一為探討多媒體軟體使用者介面的螢幕標示效果 與使用者反應時間之間的關係，另一為探討多媒體軟體使用者介面的螢幕 標示效果與使用者主觀態度之間的關係。實驗中根據物件文字標示與表徵 圖文字標示兩個變數，分為實驗組與控制組，其中實驗組具備物件文字標 示與表徵圖文字標示，而控制組則不具備物件文字標示與表徵圖文字標示 。本實證研究中，對二百零三位大學商學院一、二年級生進行測試，包括 線上雛型系統軟體測試與使用者主觀評估問卷兩部份。其中線上雛型系統 軟體測試的主要收集資料為使用者反應時間，而使用者主觀評估問卷則收 集系統內記憶性問題及使用者主觀態度等資料。研究進行方法如下：．依 學生隨機安排在電腦教室內上機，由預先安裝好的軟體來決定實驗組與控 制組。．首先系統將顯示中文之遊戲說明，以及各功能鍵所代表之意義， 使用者按滑鼠鍵即可進入遊戲。．於遊戲結束後，系統以自動方式展示一 段與先前系統不同的示範，在實驗組中，系統提供的是不具圖件文字標示 ╱表徵圖文字標示的展示，而在控制組中，系統提供的是具備圖件文字標 示╱表徵圖文字標示的展示。 ．自動展示停止之後，使用者始填答問 卷。 ．進行問卷評估與線上資料收集。實證研究結果顯示，在使 用者反應時間方面，實驗組與控制組之間確實有顯著差異 (P = 0.01)， 而在使用者性別與使用者年級方面， 使用者反應時間的差異性則並不明 顯 ( P of GRADE = 0.3348, P of GENDER = 0.2975)。至於主觀評 估問卷方面，大部分受測者皆肯定螢幕上圖件文字標示與表徵圖文字標示 存在的必要性，認為確實對系統進行有幫助，其中又以對於表徵圖文字標 示表示肯定者較多。

Language-play can briefly be described as the wilful manipulation of the peculiarities of a linguistic system in a way that draws attention to these peculiarities themselves, thereby causing a communicative and cognitive effect that goes beyond the conveyance of propositional meaning. Among the various phenomena answering this description are the different kinds of puns, but also more strictly form-based manipulations such as rhymes and alliteration, in addition to a host of other, sometimes even fuzzier, subcategories. Due to its unusual nature, and especially its frequently strong dependence on the idiosyncrasies of a particular language, language-play can generally be assumed to constitute a significant challenge in a translation context. Furthermore, given its non-negligible effects, the translator is not free to simply ignore the language-play (provided it has been recognized as such in the first place) without having taken an active stance on its treatment. However, the difficulties in finding a suitable target-language solution are possibly exacerbated if the source text is a complex multimedia product such as a film, the translation of which, normally in the form of dubbing or subtitling, is subject to additional constraints. In view of these intricacies, it has been the aim of this study to analyze and measure how language-play in film has actually been treated in authentic dubbing and subtitle versions. As a prerequisite, the concept of language-play has been elaborated on, and more than a dozen subcategories have been described, developed, and employed. For the purpose of carrying out a meaningful analysis of the dubbing and subtitling of language-play, a corpus has been compiled, comprising 18 family films and 99 of their various target versions, most on DVD, and yielding nearly 800 source-text instances of language-play and thousands of translation solutions. The results indicate that especially two sets of factors, among the many that are likely to influence a translation, play a prominent role: the type of the language-play, and the identity and working conditions of the translator. By contrast, the mode of translation (dubbing vs. subtitling), the target language, or the general properties of the films, could not be shown to have a sizeable impact.

The Aryl hydrocarbon receptor (AhR) is a ligand-activated transcription factor and member of the basic helix-loop-helix Per/ARNT/Sim (bHLH/PAS) family of chemosensors and developmental regulators. As a member of the PAS domain family of transcription factors responsive to exogenous signals, the AhR exerts influence on many processes relating to cellular fate. The activation of AhR is widely associated with toxic endpoints related to dioxin exposure. However, the AhR also activates endogenous gene programs related to development, cellular growth, and differentiation. The AhR is able to bind a variety of ligands, leading to a wide range of biological outcomes. Recent reports have shown that the AhR can mediate tumor suppressive effects. As a ligand-activated transcription factor, the AhR has the potential to actuate a variety of transcriptional programs that are dependent on the AhR ligand. Our central hypothesis is that AhR ligands can be identified that are capable of initiating tumor suppressive functions of the AhR. We utilized complementary cell-based and in silico virtual screening approaches to identify potential AhR ligands. We developed homology models of the AhR ligand-binding domain (LBD) for virtual ligand screening (VLS) of small molecule libraries. This led to the identification of new AhR ligands 5,7- dihydroxyflavanone!and 5-hydroxy-7-methoxyflavone. Additional small molecule libraries were screened in parallel that led to identification of flutamide as a putative AhR ligand. Flutamide is clinically approved for the treatment of prostate cancer due to its ability to antagonize androgen receptor mediated transcription. We investigated the biological effects of flutamide in AhR positive cancer cells that do not express the androgen receptor and found that flutamide inhibited the growth of HepG2 cells. Suppression of AhR expression reversed the anti-proliferative effects of flutamide. We tested 15 structural analogs of flutamide, including the flutamide metabolite 2-hydroxyflutamide for activation of AhR transcriptional activity. Flutamide is unique in its ability to activate the AhR, and suppresses hepatoma cell growth. These data suggests that flutamide-induced AhR transcriptional activity is required to initiate the tumor suppressive effects. We examined changes in cell cycle checkpoint proteins after flutamide treatment and discovered increased expression of cell cycle inhibitory proteins p27[superscript Kip1] and p15[superscript INK]. We also found that transforming Growth Factor β1 (TGFβ1), which regulates both p27[superscript Kip1] and p15[superscript INK], is upregulated by flutamide. We demonstrate that TGFβ1 is upregulated by flutamide in an AhR-dependent manner and is required for suppression of proliferation by flutamide. We identify specific and unique transcriptional signatures of the AhR upon activation by flutamide, that are distinct from the potent AhR agonist 2,3,7,8-Tetrachlorodibenzo-p-dioxin (TCDD). In summary, we characterize flutamide as an AhR ligand and demonstrate its AhR-dependent tumor suppressive effects in hepatoma cells. We provide the first direct evidence that AhR regulates TGFβ signaling in a ligand dependent manner. We demonstrate that the AhR-induced downstream transcriptional signature and subsequent biological effects are specific to the AhR ligand. Our studies have broad impact for characterizing the AhR as a new therapeutic target in hepatocellular carcinoma. / Graduation date: 2013 / Access restricted to the OSU Community at author's request from March 28, 2013 - March 28, 2015

Cool molecular hydrogen H2 may be the ultimate possible constituent to the Milky-Way missing baryon. We describe a new way to search for such transparent matter in the Galactic disc and halo, through the diffractive and refractive effects on the light of background stars. By simulating the phase delay induced by a turbulent medium, we computed the corresponding illumination pattern on the earth for an extended source and a given passband. We show that in favorable cases, the light of a background star can be subjected to stochastic fluctuations of the order of a few percent at a characteristic time scale of a few minutes. We have searched for scintillation induced by molecular gas in visible dark nebulae as well as by hypothetical halo clumpuscules of cool molecular hydrogen (H2_He) during two nights, using the NTT telescope and the IR SOFI detector. Amongst a few thousands of monitored stars, we found one light-curve that is compatible with a strong scintillation effect through a turbulent structure in the B68 nebula. Because no candidate were found toward the SMC, we are able to establish upper limits on the contribution of gas clumpuscules to the Galactic halo mass. We show that the short time-scale monitoring of a few 10^6 star _ hour in the visible band with a >4 m telescope and a fast readout camera should allow one to interestingly quantify or constrain the contribution of turbulent molecular gas to the Galactic halo.