La grande complexité des échantillons biologiques peut compliquer l'identification des protéines et compromettre la profondeur et la couverture des analyses protéomiques utilisant la spectrométrie de masse. Des techniques de séparation permettant d’améliorer l’efficacité et la sélectivité des analyses LC-MS/MS peuvent être employées pour surmonter ces limitations. La spectrométrie de mobilité ionique différentielle, utilisant un champ électrique élevé en forme d'onde asymétrique (FAIMS), a montré des avantages significatifs dans l’amélioration de la transmission d'ions peptidiques à charges multiples, et ce, en réduisant les ions interférents. Dans ce contexte, l'objectif de cette thèse était d'explorer les capacités analytiques de FAIMS afin d'élargir à la fois la gamme dynamique de détection des protéines/peptides et la précision des mesures en protéomique quantitative par spectrométrie de masse. Pour cela, nous avons systématiquement intégré FAIMS dans des approches classiques en protéomique afin de déterminer les changements dynamiques du protéome humain en réponse à l’hyperthermie. Nous avons d’abord étudié les avantages de FAIMS par rapport à la quantification par marquage isobare (tandem mass tag, TMT). Cette approche permet le marquage d'ions peptidiques avec différents groupements chimiques dont les masses nominales sont identiques mais différant par leur distribution respective d'isotopes stables. Les ions peptidiques marqués par TMT produisent des ions rapporteurs de masses distinctes une fois fragmentés en MS/MS. Malheureusement, la co-sélection d'ions précurseurs conduit souvent à des spectres MS/MS chimériques et une approche plus lente basée sur le MS3 est nécessaire pour une quantification précise. Comme FAIMS améliore l’efficacité de séparation en transmettant sélectivement des ions en fonction de leur voltage de compensation (CV), nous avons obtenu moins de co-sélection de peptides. FAIMS a amélioré la quantification des peptides TMT au niveau MS2 et a permis d’obtenir 68% plus de peptides quantifiés par rapport aux analyses LC-MS/MS classiques, fournissant ainsi un aperçu plus vaste des changements dynamiques du protéome humain en réponse au stress thermique. De plus, nous avons étudié le marquage métabolique par incorporation d’acides aminés marqués par des isotopes stables en culture cellulaire (SILAC). Si des interférences co-éluent avec les isotopes SILAC, la quantification devient imprécise et les contreparties de SILAC peuvent être assignées de manière erronée aux ions interférants du chromatogramme, faussant ainsi le rapport SILAC. Le fractionnement post-ionisation FAIMS pourrait filtrer les ions appartenant au bruit de fond qui pourraient autrement être attribués à une paire ou à un triplet SILAC pour la quantification. Dans ce projet, FAIMS a été particulièrement bénéfique pour les espèces peu abondantes et s’est montré plus performant que le fractionnement par échange de cations (SCX). En outre, FAIMS a permis la séparation des phosphoisomères fréquemment observés dans les extraits complexes de phosphoprotéomes. Le troisième objectif de ce travail de recherche était d'explorer la séparation de l'état de charge et la transmission améliorée de peptides fortement chargés avec FAIMS et son application à l'analyse de peptides SUMOylés. FAIMS pourrait ainsi améliorer la transmission des peptides SUMOylés triplement chargés par rapport aux peptides tryptiques usuels, lesquels sont principalement doublement chargés. Ceci permettait l'enrichissement en phase gazeuse des ions peptides SUMOylés. FAIMS est une approche alternative plus simple pour fractionner les peptides SUMOylés, ce qui réduit les pertes d’échantillon et permet de simplifier le traitement des échantillons, tout en augmentant l’efficacité de séparation de manière plus automatisée et en ajoutant un ordre de grandeur de sensibilité. Le dernier objectif de cette thèse était d’améliorer l’instrumentation de FAIMS en le jumelant aux instruments à la fine pointe de la technologie. Avec un nouveau dispositif FAIMS, développé par nos collaborateurs chez Thermo Fisher Scientific, nous avons montré une amélioration dans la robustesse et la transmission des ions pour la nouvelle interface. Dans des expériences simples en protéomique shotgun, FAIMS a étendu la gamme dynamique d'un ordre de grandeur pour une couverture protéomique plus profonde par rapport aux analyses LC-MS/MS classiques. En outre, le fractionnement en phase gazeuse de FAIMS a généré moins d’analyses chimériques en MS2, ce qui a permis d’obtenir plus d’identifications et une meilleure quantification. Pour ce faire, nous avons directement comparé le LC-FAIMS-MS/MS au LC-MS/MS/MS en utilisant la sélection de précurseur synchrone (SPS) avec et sans fractionnement en phase inverse basique. Des mesures quantitatives comparables ont été obtenues pour toutes les méthodes, à l'exception du fait que FAIMS a parmi d’obtenir un nombre 2,5 fois plus grand de peptides quantifiables par rapport aux expériences sans FAIMS. Globalement, cette thèse met en évidence certains des avantages que FAIMS peut offrir aux expériences en protéomique en améliorant à la fois l'identification et la quantification des peptides. / The high complexity of biological samples can confound protein identification and compromise the depth and coverage of mass spectrometry-based proteomic analyses. Separation techniques that provide improved peak capacity and selectivity of LC-MS/MS analyses are often sought to overcome these limitations. High-field asymmetric waveform ion mobility spectrometry (FAIMS), a differential ion mobility device, has shown significant advantages by enhancing the transmission of multiple-charged peptide ions by reducing singly-charged interferences. In this context, the goal of this thesis was to explore the analytical capabilities of FAIMS to extend both the dynamic range of proteins/peptides detection and the precision of quantitative proteomic measurements by mass spectrometry. For this, we systematically integrated FAIMS in standard workflows to monitor the dynamic changes of the human proteome in response to hyperthermia. We first studied the merits of FAIMS to aid isobaric labeling quantification with tandem mass tags (TMT). This approach allows the labeling of peptide ions with different chemical groups of identical nominal masses but differing in their respective distribution of stable isotopes. TMT-labeled peptide ions produce reporter ions of distinct masses once fragmented by MS/MS. Unfortunately, the co-selection of precursor ions often leads to chimeric MS/MS spectra, and a slower MS3 centric approach is needed for precise quantification. Since FAIMS improves peak capacity by selectively transmitting ions based on their compensation voltage (CV), we obtained less peptide co-selection. FAIMS improved TMT quantification at the MS2 level and achieved 68 % more quantified peptides compared to regular LC-MS/MS, providing a deeper insight into the dynamic changes of the human proteome in response to heat stress. Further, we investigated stable isotope labeling by amino acids in cell culture (SILAC) quantification. If interferences co-elute simultaneously with SILAC isotopomers, quantification becomes inaccurate and SILAC counterparts can be missassigned to interfering ions in the highly populated chromatogram, thus skewing the SILAC ratio. FAIMS post-ionization fractionation could filter out background ions that can otherwise be attributed to a SILAC pair/triplet for quantification. In this work, FAIMS was especially beneficial for low abundant species and outperformed the standard strong cation exchange (SCX) fractionation workflow. In addition, FAIMS allowed the separation of phosphoisomers that are frequently observed in complex phosphoproteome extracts. The third aim of this work explored the charge state separation and enhanced transmission of highly charged peptides with FAIMS and its application for SUMOylated peptide analysis. FAIMS could enhance the transmission of triply charged SUMOylated peptides over typical tryptic peptide that are predominantly doubly charged, by applying more negative CVs with FAIMS. This allowed for gas-phase enrichment of SUMOylated peptide ions. FAIMS is an alternate and more straightforward approach to fractionate SUMOylated peptides that reduced sample loss, avoided sample processing, while increasing peak capacity in a more automated manner and added one order of magnitude in sensitivity. The last aim of this thesis was to improve the FAIMS instrumentation by interfacing it to the latest state-of-the-art instruments. With a new FAIMS device developed by our collaborators at Thermo Fisher Scientific, we demonstrate the robustness and the improved ion transmission for the new interface. In simple shotgun proteomics, FAIMS extended the dynamic range by one order of magnitude for deeper proteome coverage compared to regular LC-MS/MS. Moreover, fewer MS2 chimeric scans were generated with FAIMS gas-phase fractionation, which garnered more identifications and better quantification. For this, we directly compared LC-FAIMS-MS/MS to LC-MS/MS/MS using synchronous precursor selection (SPS) with and without basic reverse phase fractionation. Comparable quantitative measurements were obtained for all methods, except that FAIMS provided a 2.5-fold increase in the number of quantifiable peptides compared with non-FAIMS experiments. Overall, this thesis highlights some of the advantages that FAIMS can provide for proteomics experiments by improving both peptide identification and quantification.

No description available.

Esta pesquisa se desenvolve no âmbito do ensino de ciências, no que tange à formação continuada de professores de Ciências e sequências didáticas. Objetivando-se obter um levantamento palpável sobre as concepções dos professores de Ciências sobre Ciência e Tecnologia (C&T), foram utilizadas duas ferramentas de coletas de dados: Uma enquete e sequências didáticas (SD) desenvolvidas pelos professores cursistas participantes do Curso de Especialização em Ensino de Ciências da Faculdade de Educação da USP no Programa Rede de Formação Docente (EEC-FEUSP-REDEFOR) durante o segundo ano de oferecimento, 2011-2012. O foco principal do presente estudo é sistematizar as concepções sobre C&T dos professores cursistas e observar como estas permeiam o desenvolvimento de SD, para que se obtenham subsídios e reflexões sobre os objetivos da educação científica, da formação de professores e do entendimento dos professores de ciências sobre as questões sócio científicas (QSC). A análise dos dados se desenvolveu utilizando duas abordagens, quantitativa e qualitativa, de forma a se complementarem. As análises estatísticas nomeadas análise multifatorial e de cluster, e abordagem qualitativa descritiva documental dos resultados sustentam a análise como um todo, interpretando os resultados obtidos, trazendo assim uma visão ampla do objeto de estudo que aponta a presença de dez tipos de concepções, 8 tipos de perfis de concepções sobre C&T que se traduzem nas SD em categorias sintéticas como: conhecimento científico prediz, reverte e evita problemas ambientais; conhecimento científico explica e viabiliza melhoria de vida; C&T beneficiam sociedade e ambiente; homem prejudica e desperdiça; preocupação simplória com a degradação ambiental; conteudismo; aproximação CTS e consciência de bem social global; funcionalidade e acesso ao conhecimento científico; conhecimento científico e visões alternativas, e finalmente, impactos do desenvolvimento científico e tecnológico no meio ambiente. A importância de se reconhecer tais variações e sentidos das concepções mais comumente expressas se revela à medida que configuram tópicos de discussão relevantes aos cursos de formação inicial e continuada de professores e a observação da forma como estas SD poderiam sintetizar concepções mais ricas de possibilidades de discussões em sala de aula. / This research develops in the scope of science teaching, in what concerns to in service formation science teachers and didactic sequences. In order to obtain a palpable survey on the conceptions of the teachers on Science and Technology (S & T), two data collection tools were used: a survey and didactic sequences (DS) developed by the teachers participating in the Specialization Course in Science Teaching of the Faculty of Education of USP in the Program of Teacher Education (EEC-FEUSP-REDEFOR), along the second year (2011-2012). The main focus of the present study is to systematize the conceptions about Science and Technology of the teachers and to observe how they permeate the development of DS, to obtain subsidies and reflections on the objectives of scientific education, teacher training and teachers\' understanding Sciences on socio-scientific issues (SSI). The analysis of the data was developed using two approaches: quantitative and qualitative, in order to complement each other. The statistical analyses named multifactorial and cluster analysis, and qualitative documentary descriptive approach of the results support the analysis as a whole, interpreting the results obtained, thus bringing a broad view of the object of study that points out the presence of ten types of conceptions, 8 types of profiles of S & T conceptions that translate into DS in synthetic categories such as: Scientific knowledge predicts, reverses and avoids environmental problems; Scientific knowledge explains and enables improvement in life; Society and Environment; Man harms and wastes; Simplistic concern with environmental degradation; Content; CTS approach and global social welfare awareness; Functionality and access to scientific knowledge; Scientific knowledge and alternative visions, and finally, Impacts of scientific and technological development on the environment. The importance of recognizing such variations and meanings of the most commonly expressed conceptions is revealed by the fact that they configure topics of discussion relevant to the initial and in service formation courses and the observation of how these DS could synthesize richer conceptions of possibilities for discussion In the classroom.

In this paper, top-down and bottom-up processing were studied regarding their effect on speech-in-noise. Three cognitive functions were also studied (divided attention, executive functioning, and semantic comprehension), and the effect they have on the speech processing and on each other. The research questions asked were if a difference in speech-in noise perception can be observed regarding the different levels of top-down and bottom-up support, if speech-in-noise is related to any of the researched cognitive abilities, and if there exists any correlation between these abilities. The method is a within-subject experimental design, consisting of four different tests: PASAT, to measure attention, LIT, to measure semantic comprehension, TMT, to measure executive functioning and SIN, to measure speech-in noise. The results showed a significant difference between top-down and bottom-up processing, a significant difference between top-down processing in decreasing and increasing conditions could also be seen. A negative correlation between the benefit of top-down support and the semantic comprehension task was found. Regarding the cognitive abilities a few correlations were found; the semantic comprehension task had a positive correlation to both the central executive task and the attentional task, the attentional task had a negative correlation to the central executive task, and both of the central executive subtasks had a positive correlation to each other. Most of the findings were expected, built on earlier cognitive hearing theories and studies.

Esta pesquisa se desenvolve no âmbito do ensino de ciências, no que tange à formação continuada de professores de Ciências e sequências didáticas. Objetivando-se obter um levantamento palpável sobre as concepções dos professores de Ciências sobre Ciência e Tecnologia (C&T), foram utilizadas duas ferramentas de coletas de dados: Uma enquete e sequências didáticas (SD) desenvolvidas pelos professores cursistas participantes do Curso de Especialização em Ensino de Ciências da Faculdade de Educação da USP no Programa Rede de Formação Docente (EEC-FEUSP-REDEFOR) durante o segundo ano de oferecimento, 2011-2012. O foco principal do presente estudo é sistematizar as concepções sobre C&T dos professores cursistas e observar como estas permeiam o desenvolvimento de SD, para que se obtenham subsídios e reflexões sobre os objetivos da educação científica, da formação de professores e do entendimento dos professores de ciências sobre as questões sócio científicas (QSC). A análise dos dados se desenvolveu utilizando duas abordagens, quantitativa e qualitativa, de forma a se complementarem. As análises estatísticas nomeadas análise multifatorial e de cluster, e abordagem qualitativa descritiva documental dos resultados sustentam a análise como um todo, interpretando os resultados obtidos, trazendo assim uma visão ampla do objeto de estudo que aponta a presença de dez tipos de concepções, 8 tipos de perfis de concepções sobre C&T que se traduzem nas SD em categorias sintéticas como: conhecimento científico prediz, reverte e evita problemas ambientais; conhecimento científico explica e viabiliza melhoria de vida; C&T beneficiam sociedade e ambiente; homem prejudica e desperdiça; preocupação simplória com a degradação ambiental; conteudismo; aproximação CTS e consciência de bem social global; funcionalidade e acesso ao conhecimento científico; conhecimento científico e visões alternativas, e finalmente, impactos do desenvolvimento científico e tecnológico no meio ambiente. A importância de se reconhecer tais variações e sentidos das concepções mais comumente expressas se revela à medida que configuram tópicos de discussão relevantes aos cursos de formação inicial e continuada de professores e a observação da forma como estas SD poderiam sintetizar concepções mais ricas de possibilidades de discussões em sala de aula. / This research develops in the scope of science teaching, in what concerns to in service formation science teachers and didactic sequences. In order to obtain a palpable survey on the conceptions of the teachers on Science and Technology (S & T), two data collection tools were used: a survey and didactic sequences (DS) developed by the teachers participating in the Specialization Course in Science Teaching of the Faculty of Education of USP in the Program of Teacher Education (EEC-FEUSP-REDEFOR), along the second year (2011-2012). The main focus of the present study is to systematize the conceptions about Science and Technology of the teachers and to observe how they permeate the development of DS, to obtain subsidies and reflections on the objectives of scientific education, teacher training and teachers\' understanding Sciences on socio-scientific issues (SSI). The analysis of the data was developed using two approaches: quantitative and qualitative, in order to complement each other. The statistical analyses named multifactorial and cluster analysis, and qualitative documentary descriptive approach of the results support the analysis as a whole, interpreting the results obtained, thus bringing a broad view of the object of study that points out the presence of ten types of conceptions, 8 types of profiles of S & T conceptions that translate into DS in synthetic categories such as: Scientific knowledge predicts, reverses and avoids environmental problems; Scientific knowledge explains and enables improvement in life; Society and Environment; Man harms and wastes; Simplistic concern with environmental degradation; Content; CTS approach and global social welfare awareness; Functionality and access to scientific knowledge; Scientific knowledge and alternative visions, and finally, Impacts of scientific and technological development on the environment. The importance of recognizing such variations and meanings of the most commonly expressed conceptions is revealed by the fact that they configure topics of discussion relevant to the initial and in service formation courses and the observation of how these DS could synthesize richer conceptions of possibilities for discussion In the classroom.

<p>Structural metallic materials exposed to energetic particle bombardments often experience various types of irradiation-induced microstructural damage, thus degrading the mechanical properties of the materials in form of irradiation hardening and embrittlement. Nanostructured materials have shown better radiation resistance than their coarse-grained (CG) counterparts due to the existence of abundant defect sinks, such as grain boundaries, twin boundaries, and phase boundaries. However, recently developed nanocrystalline (NC) steels show limited room-temperature tensile ductility (< 1%), which may become a concern for their future application for nuclear reactors. The focus of this thesis is to explore the strength-ductility dilemma in modified 9Cr1Mo (T91) ferritic/martensitic (F/M) steel processed by thermomechanical treatment (TMT) and surface severe plastic deformation (SSPD) with an attempt to fabricate strong, ductile and radiation resistant F/M steels. </p> <p><b>Carbon partitioning</b> between the quenched martensite and the other phases (bainitic ferrite or retained austenite) is critical for enhancing the strength and ductility of T91 steel. The tensile properties of partially tempered (PT) T91 steel can be tailored through introducing bainitic ferrite with high-density nanoscale transition carbides and refined lath martensite. In addition, retained austenite was introduced by increasing the carbon concentration of T91 steel to 0.6 wt.%. The carbon-modified steel processed by quenching partitioning (Q-P) treatment exhibits an ultrahigh strength, ~ 2 GPa, with a uniform strain of ~ 5% due to the existence of coherent carbides, ultrafine martensite and retained austenite. </p> <p>Meanwhile, surface mechanical grinding treatment (SMGT) on T91 steel reveals that introducing <b>gradient structures</b> on the sample surface contributes to a higher strength and an improved plasticity than its homogeneously structured counterpart. The deformation mechanism of the gradient structures was investigated with the assistance of quasi <i>in situ</i> crystal orientation analyses. Furthermore, <i>ex situ</i> He ion irradiation on the gradient T91 steel indicates that radiation-induced damage, such as bubble-induced swelling and irradiation hardening, were gradually mitigated by grain refinement from the sample surface to the center, resulting in superior radiation resistance. The results obtained from this thesis may facilitate the design and fabrication of strong, ductile and radiation-tolerant F/M steels.</p>

With the rapid growth of industry 4.0 and the digital age, we can see that the use of digital tools, systems and solutions are becoming more standardized in all sectors. We are currently witnessing these tools becoming a much more integral part of future industry and therefore putting pressure on current organizations to adapt. Digital maturity is a phenomenon that has gained an abundance of exposure in recent years, and the importance of this phenomenon grows in relation to the growth of the digital environment. According to academia, questions about companies’ digital status have recently become topical. Digital maturity can act as a portal for possibilities and change. For example, exploiting opportunities, implementing technological processes and averting business risks that stem from advanced technologies. Academic research in this field mainly concentrates on the quantitative aspects and therefore we have engaged in a qualitative approach in order to fill the gap within this field of research. Moreover, we have identified that studies and contemporary assessment models do not consider the importance of management and aspect of change to the necessary extent. Academia mentions the importance of converting digital maturity assessments to company actions through a systematic engagement from managers. However, most studies in the field have focused on either giving overviews on different perspectives of assessments or answered questions regarding the success rate of digital transformations, we believe that management and change management are key components to digital maturity and transformational success. A qualitative approach is therefore suitable because of the exploratory nature of our interests. To gather data, we conducted interviews with participants chosen through a purposive sampling technique. The purposive sampling method was chosen to achieve a better and more qualitative result since the participants all had expertise within the field of digital development, digital maturity measurements and management. The interview questions were based on theories in our conceptual framework and served as a foundation for the interview guide. The intention was to see if our initial theories on digital maturity transformation would match the views of the participants. By using a thematic analysis method, we connected the participants answers to our identified framework themes, potentially altering our conceptual framework. The original components of our conceptual framework were: Importance of management and change management, which included theories of organizations, people, change kaleidoscope, the theory of constraints, PDSA-cycle and RACI-model. The result of the study showed that our predicted components of importance of management and change management were essential for the success of digital maturity. Our underlying theories also matched the participants views. However, new theories and components were added based on the empirical findings. These were: long term solutions and strategies, strong and motivating leadership, project triangle and communication plans. Our study indicates that management and change management can be success factors in the process of becoming more digitally mature.

The private equity industry has experienced a decade marked by substantial growth. However, as the investment landscape for capital providers has become more complex, the leadership team of private equity firms plays a more crucial role in navigating significant challenges. Focused on two themes, this dissertation explores the background of top management teams (TMTs) in private equity firms, its correlation with fund performance, and the backgrounds of deal lead partners and their risk assessment of leveraged buyout (LBO) investments. The first essay investigates TMT diversity, emphasizing its multi-dimensional connection with fund performance. The study differentiates between socio-demographic and occupational diversity, uncovering various effects on fund outcomes. The second essay constructs a diversity index based on a comprehensive methodology to maximize the correlation between TMT diversity and private equity fund performance. The third essay explores the risk profiles of private equity partners in LBO investment decisions, establishing a link between socio-demographic backgrounds and distinct risk assessment archetypes. This dissertation contributes to the literature in the intersection of private equity and TMT, providing insights for scholars and practitioners alike.

<p>  </p> <p>Many viewers—especially those from the continental United States—have praised Disney for such recent actions as casting Pacific Islanders in the animated feature film <em>Moana</em> (2016) and assembling a group of cultural advisors (named the Oceanic Story Trust) to guide the filmmakers’ creative decisions. However, my project contends that Disney continues to play a significant role in the maintenance of settler colonialism in Hawai‘i, despite these seemingly progressive attempts at challenging Hollywood’s whitewashing. In this project, I argue that Disney creates and replicates the structures of settler colonialism in Hawai‘i through a mechanism that I term <em>imagineered imperial tourism</em>. In my formulation, imagineered imperial tourism involves commodifying historical narratives of colonization to serve the Disney brand by “innocently” repackaging them for the purpose of settler tourist consumption. To signal a Disney-specific branding and reproduction of settler colonial tropes and ideologies, I use the term “imagineered”—a play on Disney’s trademarked term <em>Imagineering</em>, which names the work of the creative team tasked with engineering the company’s most innovative devices, built environments, and technologies.</p> <p>Through a sustained study of Disney’s relevant productions—from the feature films <em>Lilo & Stitch</em> (2002) and <em>Moana</em> to its built environments at the Walt Disney World Resort in Orlando, FL, and Aulani, A Disney Resort & Spa in Ko Olina, Hawai‘i—I suggest that over time, Disney has normalized a version of Native Hawaiian people and history in US popular culture that reproduces common settler colonial discourses which have structured popular perceptions of Hawai‘i. The company’s almost century-long history of media production has cemented these discourses into a set of public pedagogies that have been reproduced across generations. Disney’s Pacific Island-themed productions and attractions are rife with tropes of native primitivism and imperialist nostalgia. They also reveal the primacy of the discursive framework of hegemonic multiculturalism vis-à-vis the commodified “spirit of aloha,” a sentiment which is superficially rooted in Native Hawaiian epistemologies and branded as a key selling point by the tourism industry. Furthermore, Disney has actively colonized Hawaiian lands since 2007, capitalizing on the Islands’ exploitative tourist industry while also obscuring longstanding battles over land ownership and denying Native Hawaiians sovereignty over their stolen lands. Ultimately, I suggest that Disney’s ostensibly “innocent” repackaging contributes to the violent erasure of Native Hawaiian history in popular culture. </p>