This master’s thesis deals with manufacturing and logistic issues of low voltage cabinets produced by ProCS, s.r.o. company. The aim is to design and evaluate manufacturing and assembling process rationalization proposal. The proposal is based on familiarization with technological process of cabinet's manufacturing. Becoming familiar with manufacturing and assembling process of marshalling and system cabinets made it possible to find an opportunity of rationalization through automation of selected assembling processes. Automation of striping and crimping process is possible through suitable crimping machine. Situation before and after rationalization is economically interpreted and evaluated using break even point analysis. Through mentioned rationalization arrangement it is possible to improve manufacturing flexibility, reduce lead times and cut down manufacturing costs.

Molecular self-assembly is the process of molecules able to associate into more ordered structures. Examples of self-assembling molecules is a class of ultrashort amphiphilic peptides with a distinct sequence motif, which consist of only three to seven amino acids. These peptides can self-assemble to form nanofibrous scaffolds, such as in form of hydrogels, organogels or aerogels, due to their amphiphilic structure which contains a dominant hydrophobic tail and a polar head group. Interestingly, these peptide scaffolds offer a remarkably similar fiber topography to that one found in collagen which is a dominant part of the extracellular matrix. The resemblance to collagen fibers brings a potential benefit in using these peptide scaffolds together with native human cells. Specifically, they can maintain high water content over 99 % weight per volume and are suitable for tissue engineering and regenerative medicine applications. Over the last decade, they have shown promising therapeutic potential in treating several diseases thanks to their high activity, target specificity, low toxicity, and minimal nonspecific and drug-drug interactions. This dissertation describes how to characterize and use ultrashort amphiphilic peptides for tissue engineering and biomedicine. The first chapter offers an overview of already reported self-assembling ultrashort peptides and their applications. As a proof-of-concept, ultrashort peptide scaffolds were used for osteogenic differentiation. Peptide nanoparticles were embedded into 5 peptide hydrogels with the goal to tune the stiffness of the peptide gels. Furthermore, the peptide scaffold was used for the generation of gold and silver nanoparticles after UV irradiation, which allowed the production of nanoparticles in the absence of any additional reducing agent. The mechanism of the generation of these nanoparticles was then investigated. The last chapter describes how tetrameric peptide solutions were utilized for 3D bioprinting applications. Compared to earlier reported self-assembling ultrashort peptide compounds, these tetrapeptides can form hydrogels at an extremely low concentration of 0.1% w/v in a relatively short time under physiological conditions. These promising findings suggest that the peptide solutions are promising bioinks for use in 3D bioprinting.

This thesis examines how women perform as leaders within male-dominated professions, including law, business, politics, the military, and the academy. In studying women's performances in terms of the corporeal and spectacular, the investigation seeks to understand how particular women enact leadership through their materiality within specific times and places. Drawing on Gilles Deleuze and Felix Guattari's (1988) theorising of the processes of 'becoming', woman-as-leader is studied as an entity that passes from one incomplete and multiple assemblage to another, rather than as a singular 'developing' identity. The research is located within and between the paradoxes that complicate the performances of leadership for women. One key paradox serving as a rationale for this investigation is that, while 'equity' has become a truism of contemporary leadership, it is clear from formal reports (for example, the 2002 Equal Opportunity for Women in the Workplace Agency (EOWA) report), that many women continue to be marginalised and under-represented as leaders and senior managers. Moreover, those few women who have achieved success often acknowledge themselves as both legitimately and differently - and sometimes awkwardly, located as leaders in the everyday enactments of their work. The investigation of leadership within and between such paradoxes is problematic for a neo-liberal order of thinking, and even for socially critical theory, because of the assumptions that modernist literature makes about women's struggle for political legitimacy (ie, a narrative of progress, emancipation, and/or linear cumulative historical development). It is for this reason that the conceptual tools used in this study are drawn from post-feminist and post-structuralist theory. Such theorising refuses literal categories in favour of 'ironic categories' (Rorty, 1989) where two apparently oppositional ideas are understood to be both necessary and true. To explore women 'becoming' leaders (Deleuze & Guattari, 1988), 'woman-as-leader' is interrogated using Jean François Lyotard's (1984) notion of 'performativity,' Mary Russo's (1994) theorising of the embodied spectacle of 'the female grotesque', and Richard Rorty (1989) and Donna Haraway's (1991) insistence on partiality, doubt, and the importance of 'undoing' the fixity of modernist categories - in this instance, for women. One ironic category of importance to the study is Haraway's theorising of a 'cyborgian identity', a technological assemblage that is part-human/part-machine. This allows acknowledgement that women leaders inhabit realms beyond the boundaries imposed by the same/difference, human/machine, present/past, and real/virtue binaries. Using these tools, the performances of a number of women leaders is examined in an empirical study that focuses on a few individual women located in male-defined and male dominated settings. The empirical work has two key components. First, it provides a reading of three moments in time where a female individual dys-appears (Leder, 1990) in the public gaze, erupting as a unique spectacle in spaces that are both enabling and constraining. It foregrounds the unique complexities of three public performances in which women made a spectacle of themselves, while the analysis refuses to either celebrate the individuals involved, or to bemoan the conditions under which they did so. The analysis demonstrates the value of re-thinking leadership in terms of its complexity for the female as embodied public 'performer'. It then moves on to focus specifically on the (embodied, spectacular) tactics being deployed by women leaders in contemporary professional work. This analysis is located in the professions of law, business, politics, the military, and the academy. The data-as-evidence emerging from the analysis show women leaders to be both and neither enacting and troubling 'proper' (ie, traditional and/or known) leadership conventions. The analysis provides a reading of how, through certain tactical shifts, women work to 'de-territorialise' both the 'forms of content' and 'forms of expression' (Deleuze & Guattari, 1988) constituting leadership performances. It makes visible the tactical assemblages these women deploy, and the ways in which such tactics separate, combine, and compound the same/difference, equality/inequality, either/or binaries. The specific tactical manoeuvres for achieving legitimacy in the public gaze cluster around four identifiable ironic categories: (i) legitimate cross-dressing (ii) assertive defence (iii) proper blasphemy, and (iv) humanly-machinic. When taken together, the two components of the empirical study compel a re-theorising of 'woman-as-leader' as both insider and outsider, an entity engaging in the on-going work of diss-assembling and re-assembling a leaderly self. Woman is shown 'to be not one, not multiple, but multiplicities', simultaneously (Deleuze & Guattari, 1988). This re-theorising provides a more nuanced account of women leaders working to maintain legitimacy, credibility, and propriety as leaders than mainstream theorising of leadership and management currently allows.

This dissertation describes the development of temperature and pH-responsive interfaces, where the emphasis is placed on tuning the responsivities within a physiological temperature range. This tuning is achieved through the utilization of polymeric building blocks, where each component is specifically synthesized to have a unique responsivity. The assembly of these components onto surfaces permits the fabrication of stimuli-responsive interfaces. In addition, this dissertation explores the use of a self-assembling peptide as a modular building block to modify the interface of hydrogel microparticles, resulting in the formation of a new biosynthetic construct. Hydrogels are three-dimensional, crosslinked polymer networks that swell in water. Over the years, hydrogels have been extensively explored as biomaterials due to their high water content, tunable mechanics, and chemical versatility. Two areas where hydrogels have received considerable interest are drug delivery and extracellular matrices. Unfortunately, developing structurally and functionally complex hydrogels from the top down is challenging because many parameters cannot be independently tuned in a bulk material. An alternative route would be to develop a library of building blocks, where each is tailored for a given function, and assemble these components into composite structures. The building block synthesized and utilized in this dissertation is a microgel. Microgels are a colloidal dispersion of hydrogel microparticles, ranging in size from 100 to 1000 nm in diameter. The microgels were prepared from environmentally responsive polymers, sensitive to both temperature and pH. Microgels have been used in the fabrication of polyelectrolyte layer-by-layer films, where the microgel serves as the polyanion and a linear polycation is used to “stitch” the particles together. In Chapters 3 and 4, stimuli-responsive interfaces are prepared from environmentally responsive microgel building blocks. In particular, Chapter 3 demonstrates tuning of the film response temperature by preparing several different microgels with differing ratios of two thermoresponsive polymers. Chapter 4 evaluates the influence of the pH environment on the thermoresponsivity of microgel films. While the pH environment was found to substantially affect some films, it is possible to prepare microgel films that behave independently of pH. The swelling/de-swelling of the films was also investigated by atomic force microscopy (AFM) as a function of both pH and temperature. It was determined that the AFM imaging parameters can drastically affect the measured film thicknesses (Appendix A) due to the soft, deformable nature of microgel films. The studies in these chapters illustrate the advantages of preparing composite structures from discrete components, where the functionality of the composite is dictated by the constituent particles. In Chapter 5, attention is placed on modifying the surface of microgel particles. Many of the traditional routes used to modify microgels involve the incorporation of co-monomers into the network or the addition of polymer shells. However, a new core/shell construct is presented, where a microgel core is coated with a self-assembling peptide shell. In this scenario, the peptide shell serves as a modular scaffold, where surface-localized functional groups can participate in reactions. Although there are still a number of questions remaining in regard to the assembly process and stability of the construct, initial experiments suggests that this is an interesting and promising structure to study. Finally, a discussion of future directions and possible experiments is provided in Chapter 6. Hopefully, this will serve as a guide for further exploration of the research presented herein. Microgels remain a rich class of materials to study and employ. While their synthesis is rather straightforward, their use often results in complex behavior and interesting phenomena. Understanding their behavior is a crucial step in realizing their full potential.

published_or_final_version / Industrial and Manufacturing Systems Engineering / Doctoral / Doctor of Philosophy

L’objectif de ce travail de thèse est de développer de nouveaux agents tensioactifs, capables de s’auto-assembler sous forme de micelles permettant de solubiliser les principes actifs insolubles, en vue de leur administration par voie intraveineuse. Cette étude a permis la synthèse, la caractérisation physico-chimique ainsi que l’évaluation toxicologique in vitro et in vivo de nouveaux agents tensioactifs d’origine naturelle. Au cours de cette étude, différentes familles de tensioactifs ont été évaluées. Ces nouveaux agents tensioactifs sont composés d’une partie hydrophobe de type cholestérol, sels biliaires ou lipides, associée via une fonction amide à une partie hydrophile dérivée d’acides aminés tels que la lysine, la glutamine ou l’acide glutamique.Ces travaux expérimentaux ont permis d’étudier l’influence de la flexibilité de la partie hydrophobe sur la capacité de solubilisation des tensioactifs. Cette étude a montré que l’efficacité de solubilisation est reliée à la flexibilité de la partie hydrophobe. L’utilisation d’agents tensioactifs composés d’une chaîne lipidique saturée flexible a permis de solubiliser efficacement le principe actif insoluble avec un taux de charge de 46 % (m/m). Les tensioactifs composés de lipides saturés sont donc plus efficaces en termes de solubilisation que les dérivés de stéroïdes ou de lipides polyinsaturés, moins flexibles. Les études de toxicité ont mis en évidence la relation ente la structure chimique des tensioactifs et leur toxicité, en particulier vis-à-vis des membranes cellulaires. L’introduction de doubles liaisons en configuration cis dans la partie lipidique des tensioactifs permet de diminuer leur interaction avec les membranes cellulaires et donc leur toxicité mais diminue également leur capacité de solubilisation. Le développement de nouveaux agents tensioactifs nécessite donc de trouver un compromis entre la capacité de solubilisation et la toxicité des tensioactifs. / The aim of this thesis was to develop novel surfactants, able to self-assemble into micelles and to solubilize insoluble drugs intented for intravenous injection. Natural-based surfactants were synthesized and their physico-chemical properties were evaluated. In addition, their in vitro and in vivo toxicity were evaluated. Their drug solubilization abitity was also investigated. Three surfactant classes were evaluated. They were composed of a hydrophobic moiety, such as cholesterol, bile salts or lipids, bonded to a hydrophilic moiety, deriving from amino acids, such as lysine, glutamine or glutamic acid, via an amide bond.The influence of surfactant hydrophobic moiety flexibility on drug solubilization ability was evaluated. This study evidenced that solubilization efficiency is related to the surfactant hydrophobic moiety flexibility. The use of surfactants with flexible and saturated lipidic moieties increased drug water solubility with a drug loading of 46 % (w/w). Saturated lipid-based surfactants exhibited a better solubilization efficiency, in comparison with steroid-based surfactants or poly-unsaturated-based surfactants. Toxicity studies evidenced the relation between surfactant chemical structure and their toxicity, in particular with cell membranes. The introduction of double bond in cis configuration in surfactant lipidic moiety decreased their interaction with cell membranes and thus their toxicity. In addition, this chemical modification also decreased their solubilization ability. To develop novel surfactants, it is thus necessary to take into account drug solubilization ability and toxicity of surfactants.

O celulossomo é um complexo multienzimático extracelular utilizado por bactérias anaeróbias para a degradação de biomassa vegetal. Ele é composto por escafoldinas, estruturas alongadas que abrigam diversos módulos cohesina, às quais se ligam dockerinas, seus parceiros de interação específica de alta afinidade, fusionados às enzimas celulolíticas. Os módulos cohesina e dockerina compõem o elemento central da interação entre todos os componentes que integram o celulossomo. Esses módulos são divididos em tipos, de acordo com sua sequência primária. Essa divisão reflete efeitos funcionais distintos, sendo o tipo I responsável pela ligação de enzimas às escafoldinas, enquanto o tipo II medeia a ligação de escafoldinas à célula. O celulossomo de Ruminococcus flavefaciens é o mais complexo conhecido, e na classificação por tipos, suas sequências divergem, formando o tipo III, que foi posteriormente subdividido em 6 grupos para significância funcional. Nesse sistema, o principal responsável pela integração de enzimas ao sistema é a escafoldina primária ScaA, a qual interage com escafoldina adaptadora ScaB. A especificidade dessa ligação - dockerina de ScaA (Rf-DocA) com cohesinas de ScaB (Rf-CohB1-7) - é classificada como único membro do grupo 5, na divisão de grupos que compõem o tipo III. Assim, essa interação é de suma importância para a organização do celulossomo desse organismo, tendo sido estudada por meio de experimentos biofísicos e bioquímicos. Porém a falta de uma estrutura cristalina resolvida desses componentes limita a compreensão que podemos ter sobre a interação. 1-2 Nesse trabalho, apresentamos as estruturas cristalográficas de Rf-DocA, em complexo com a Rf-CohB4, além da estrutura dessa cohesina isolada, e ainda, a Rf-CohB1, e alguns de seus mutantes pontuais. Com isso, esclarecemos aspectos estruturais desses módulos, como a presença de dois sítios funcionais de ligação a cálcio em Rf-DocA. Também é observável pelos modelos gerados, detalhes da ligação entre eles, como os resíduos participantes da interação. Estudos de afinidade entre esses módulos foram conduzidos para a elucidar algumas propriedades da ligação entre esses módulos, de forma que descobrimos que ela ocorre de uma única maneira, e que há um loop na cohesina cuja flexibilidade afeta a afinidade da ligação. Isso sugere um mecanismo de alteração conformacional que regula a ligação à dockerina. Adicionalmente, buscamos o emprego desses módulos em uma aplicação tecnológica, desenhando redes automontáveis de proteínas, visando a construção de um nanomaterial. Essas redes são formadas por características intrínsecas das proteínas que os compõem, sendo o principal fator considerado sua simetria rotacional.3 Nesse sentido, as dockerinas e cohesinas foram utilizadas para ligação entre proteínas de diferentes simetrias. Utilizamos proteínas de simetrias C3, C4 e C6 com fusão a dockerinas, que se conectam às cohesinas fusionadas a proteínas de simetria C2, as quais formam o elemento linear da ligação entre os diferentes módulos. Esse desenho experimental permite a expressão e purificação independentes dos componentes, o que facilita a obtenção das redes, a partir da mistura dos dois componentes. Através de análises preliminares por microscopia eletrônica de transmissão, observamos a formação de filmes bidimensionais extensos e nanotubos com a construção testada. / The cellulosome is an intricate multienzyme extracelular complexes evolved by anaerobic bacteria for degradation of cellulosic biomass. It is composed of scaffoldins, elongated structures, which bare numerous cohesin modules, which bind to dockerin modules, their high affinity and specificity partners, borne by cellulolytic enzymes. The cohesin and dockerina modules constitute the central element of the interaction between every component of the cellulosome. These modules are categorized in types, according to their primary sequence. That distribution reflects distinct functions, in which the type I is responsible for integration of enzymes to scaffoldins, while type II mediates anchoring of scaffoldins to the cell wall. The cellulosome of Ruminococcus flavefaciens is the most intricate known to date, which is categorized into a third type of cohesins and dockerins, due to sequence diversion. The type III was further divided into 6 groups to impart functional significance. In that system, the main enzyme integrating component is the primary scaffoldin ScaA, which interacts to the adaptor scaffoldin ScaB. The specificity of this interaction - dockerina of ScaA (Rf-DocA) to ScaB cohesins (Rf-CohB1-7) - is sorted as a single member of group 5, in the subtypes of type III. Thus, this interaction is essential for cellulosome organization, having been studied by biophysical and biochemical experiments. However, the lack of a solved crystalline structure of these components narrows our understanding on this interaction. In the present study, we present the structures of Rf-DocA, complexed to Rf-CohB4, besides the structure of this isolated cohesin, and also Rf-CohB1 and its point mutants. Due to these data, we clarify structural aspects of these modules, such as the occurrence of two functioning calcium binding sites in Rf-DocA. We also identified details of their binding, such as the interacting residues. Through binding affinity studies, we concluded that the interaction between these modules occurs in a single mode, and that there is a loop in the cohesin module whose flexibility has direct effects on the binding affinity to dockerin. Additionally, we sought to utilize these modules in a downstream application, by designing self-assembling arrays of proteins, aiming for the construction of a nanomaterial. These arrays are constructed from the intrinsic properties of its constituent proteins, in which the main factor is rotational symmetry. In this context, dockerina and cohesin modules were used of binding different symmetry proteins. We utilized C3, C4 and C6 point symmetry proteins fused to dockerin modules, which bind to the cohesin modules fused to C2 point symmetry proteins, which establish the linear connection between the distinct components. This experimental design allows for the independent expression and purification of the components, which facilitates the achievement of the arrays, by simple mixture of the two components. Through preliminary analysis by transmission election microscopy, we observed the construction of two-dimensional films and nanotubes.

"Many assembly machines for consumer products suffer from the fact that the mechanisms used to impart the necessary assembly motions to the product are orders of magnitude more massive than the product payloads that they carry. This characteristic subsequently limits the operating speed of the machine. If the follower train could be made less massive without sacrificing accuracy and control, it would therefore allow higher speeds. It is well-known that structures that carry only tensile loads can be much less massive than those that must also carry compressive loads. This concept is demonstrated in many structures, such as the suspension bridge. This master’s project set out to investigate the feasibility of a tension-member follower train for a generic cam-driven pick and place mechanism. This system was first dynamically simulated using a computer model, and then tested by constructing a proof of concept prototype. A cam-driven, low-mass tension member (in this case a spring steel strip over pulleys) under spring preload was used to replace the bellcranks and connecting rods typical of a conventional follower train. The system was determined to be feasible and will allow for increased operating speeds at potentially lower costs as an additional benefit."

Thesis (M.S.)--Massachusetts Institute of Technology, Alfred P. Sloan School of Management, 1980. / MICROFICHE COPY AVAILABLE IN ARCHIVES AND DEWEY. / Bibliography: leaves 128-129. / by Bruce William Lamar. / M.S.

Thesis (M.S.)--Massachusetts Institute of Technology, Dept. of Electrical Engineering and Computer Science, 1980. / MICROFICHE COPY AVAILABLE IN ARCHIVES AND ENGINEERING. / Bibliography: leaves 160-163. / by Mostafa Hamed Ammar. / M.S.