Thesis (M.H.A.)--University of Michigan, 1969.

Thesis (M.E.T.)--University of Canterbury, 2006. / Typescript (photocopy). "June 2006." Includes bibliographical references (leaves 189-192). Also available via the World Wide Web.

Na primeira parte desta tese, estudamos os princípios operacionais das decisões celulares mediadas pelo sistema de sinalização Notch. Este sistema tem papel importante nas decisões celulares que ocorrem durante o desenvolvimento embrionário, cicatrização de feridas e na formação de tumores. O circuito de sinalização é ativado quando o receptor Notch de uma célula interage com um dos ligantes - Delta ou Jagged - de uma célula vizinha. O circuito Notch-Delta forma um comutador intercelular, e duas células vizinhas tendem a adotar estados diferentes - Emissor (muito ligante e pouco receptor) e Recebedor (pouco ligante e muito receptor). Neste manuscrito, apresentamos uma nova abordagem teórica que integra ambos Delta e Jagged no circuito Notch. Mostramos que o circuito Notch-Delta-Jagged permite um novo estado - um híbrido Emissor/Recebedor (E/R) com concentrações intermediárias de receptores e ligantes, e portanto o circuito é age como uma chave de três vias. Em seguida, observamos que a taxa de produção de ambos os ligantes, assim como a modulação assimétrica da afinidade de ligação do Notch com seus ligantes mediada pela glicosiltransferase Fringe, afeta severamente o intervalo de existência dos estados e sua relativa estabilidade - altos níveis de Jagged, mas não de Fringe ou Delta, promovem o estado híbrido E/R e o processo de indução lateral. Nós elucidamos o papel de Jagged na determinação dos estados celulares e discutimos sua possível implicação no entendimento da comunicação entre tumor e estroma, que frequentemente envolve comunicação via interações Notch-Jagged. Posteriormente, avaliamos a interação entre Notch, inflamação e a população de Células Cancerígenas Estaminais (CCE). Mostramos que inflamação pode expandir a população de CCE por meio do aumento dos níveis de produção de Jagged que posteriormente ativa o sistema de sinalização Notch em células vizinhas não-CCE. Nossos resultados sugerem que a inibição da produção de Jagged atenua o efeito da expansão de CCE devido a inflamação, indicando que inflamação cresce a população de CCE via interações Notch-Jagged. Nossos resultados são consistentes com observações em câncer de mama do subtipo basal (triplo negativo), onde a perda de Fringe e a ativação constitutiva do eixo NF-kB - Jag1 promove a expansão da população de CCE. Nossa abordagem computacional pode ser adaptada para incluir circuitos adicionais tais como p53 e hipóxia, que afetam a plasticidade celular, proporcionando assim uma plataforma útil para a projeção de novas terapias. Na segunda parte desta tese, introduzimos um novo método para seleção de características: Suvrel. Este é um método variacional, inspirado em aprendizado de relevância, para determinar tensores métricos para definição de distâncias baseadas em similaridades, para utilização em métodos de classificação. Nós introduzimos uma nova metodologia na qual o tensor métrico pode ser calculado analiticamente. O preprocessamento das características por uma transformação linear utilizando o tensor métrico calculado via Suvrel melhora a eficiência dos classificadores. Testamos nosso método para conjuntos de dados públicos, utilizando os classificadores mais comumente utilizados. Nós também aplicamos esta metodologia no estudo da relação entre parâmetros estruturais globais e o sistema de classificação de função enzimática. Por último, introduzimos uma nova metodologia para a identificação de genes diferencialmente expressos utilizando a tecnologia de microarranjos de DNA. Diferentemente das abordagens tradicionais, nossa metodologia evita passos intermediários de preprocessamento que são desnecessários e devido a isto não acumula erros destas análises, o que resulta em um método mais sensível e robusto. / In the first part of this thesis, we studied the operating principles of cell fate decisions mediated by Notch signaling pathway. This pathway have important role in cell fate determination during embryonic development, wound healing and tumorigenesis. Notch signaling is activated by binding of Notch receptor of one cell to either of its ligand- Delta or Jagged- of another cell. Notch-Delta circuit forms an intercellular toggle switch, and two neighboring cells tend to adopt different fates - Sender (high ligand, low receptor) and Receiver (low ligand, high receptor). Here, we present a new tractable theoretical framework that incorporates both Delta and Jagged in Notch signaling, and show that Notch-Delta-Jagged circuit enables an additional fate - hybrid Sender/Receiver (S/R) (medium ligand, medium receptor) and behaves as a three-way switch. Further, we found that production rates of both the ligands and the asymmetric modulation of binding affinity of Notch to its ligands by glycosyltransferase Fringe severely affects the parameter range of the existence of these states and their relative stability - high levels of Jagged, but not that of Fringe or Delta, promote hybrid S/R state and lateral induction. We elucidate the role of Jagged in cell fate determination and discuss its possible implications in understanding tumor-stroma crosstalk, which frequently entails Notch-Jagged communication. We further evaluate the interplay among Notch signaling, inflamation and Cancer Stem Cell population. We show that inflammation can expand the population of Cancer Stem Cells (CSCs) by increasing the levels of Jagged in cells that can further activate Notch signaling pathway in neighboring non-CSCs. Our results suggest that, inhibiting the production of Jagged dampens the effect of inflammation in expanding the CSC population, indicating that inflammatory signal function through Notch-Jagged signaling to increase CSCs. Our results are consistent with observations in basal-like breast cancer, where loss of Fringe and constitutive activation of NF-kB-Jag1 axis promotes CSC population. Our computational framework can be tailored to include additional signals such as p53 and hypoxia that affect this plasticity to gain stemness, thus providing a platform that can be useful in designing novel therapies. In the second part of the thesis, we introduce a new method for feature selection: Supervised Variational Relevance Learning (Suvrel). This is a variational method to determine metric tensors to define distance based similarity in pattern classification, inspired in relevance learning. We propose a new methodology where the metric tensor can be calculated analytically. Preprocessing the patterns by doing linear transformations using the metric tensor yields a dataset which can be more efficiently classified. We test our methods using publicly available datasets, for some standard classifiers. We also applied this methodology to study the relationship between global structural parameters and the Enzyme Commission hierarchy. Lastly, we propose a new methodology for identifying the differentially expressed genes using DNA microarray technology. Unlike traditional approaches, our methodology skips intermediate unnecessary preprocessing steps and therefore does not accumulate errors due to these analysis, resulting in a more sensitive and robust method.

This thesis is aimed on fringe benefits which are very popular part of employee's remuneration these days. The supply of benefits is very wide and it depends on the employer what he chooses. It is important to take into consideration what influence the benefits have on employees' satisfaction and what are their tax impacts. The objective of this thesis is to consider all mentioned aspects and to analyse the system of fringe benefits in the company Murr CZ s.r.o. For analysis of the present employee's satisfaction with the system, questionnaire method was used. Then some changes were recommended which could improve the benefit system regarding satisfaction and also regarding tax impacts. The employees could be divided into two groups according their position in the company. First one would be management and the second one would be team leaders and workers. Following this concept the company could adapt benefits with regard to specifics of each group. The company should think over the new benefits including pension insurance contribution and the alternative between transport allowances and culture or sport vouchers.

published_or_final_version / Social Work / Master / Master of Social Work

published_or_final_version / Sociology / Master / Master of Philosophy

The Large Binocular Telescope Interferometer uses a near-infrared camera to measure the optical path length variations between the two AO-corrected apertures and provide high-angular resolution observations for all its science channels (1.5-13 microns). There is however a wavelength dependent component to the atmospheric turbulence, which can introduce optical path length errors when observing at a wavelength different from that of the fringe sensing camera. Water vapor in particular is highly dispersive and its effect must be taken into account for high-precision infrared interferometric observations as described previously for VLTI/MIDI or the Keck Interferometer Nuller. In this paper, we describe the new sensing approach that has been developed at the LBT to measure and monitor the optical path length fluctuations due to dry air and water vapor separately. After reviewing the current performance of the system for dry air seeing compensation, we present simultaneous H-, K-, and N-band observations that illustrate the feasibility of our feedforward approach to stabilize the path length fluctuations seen by the LBTI nuller.

This work began as an investigation of tufting within fashion design. It is in- teresting because there is a lack of tufting within fashion design, especially of long tufted fringes. How can a technique that is usually used for interior design, for example rugs, be brought successfully into a fashion context? The question how to create longer fringes than usual for tufting emerged after experiments made in various materials. In order for the machine to create long fringes, lighter materials like plastic were tested and also differ- ent ways of using the machine. Since the tufted expression became very organic with the long plastic fringes, tufted try-outs were made in geometric shapes to see what hap- pened at the front of the garment. Would the geometric shape totally disappear? It was decided to take the plastic material further together with more tra- ditional materials for tufting like wool and linen, in order to get the expres- sion of both lengths and materials in the fringes and to investigate how they could be combined in interesting ways on the human body. During the way it was found that the long plastic fringes together with the traditional materials needed a flat contrast, and that is when the plain tuft- ing weave was introduced as an important part of the garment with differ- ent placements of the tufted areas, which give great shape and volume to the garments. There are great possibilities to find new expressions through tufting with long fringes within fashion design, shown in this work. If the technique is developed with fashion in mind, could it be a technique used to replace parts of the fur industry? / Program: Modedesignutbildningen

This thesis explores the initiatives possible for corporations interested in providing child care services to their employees. It also attempts to explain why corporations are becoming increasingly interested in providing this benefit to employees.A needs assessment survey was designed to discover the child care related needs of employees and to determine how child care responsibilities impact the work environment. An exploratory study was conducted of a sample of employees (N=127) at General Telephone in Fort Wayne, Indiana.Most employees, parents and non-parents, in this sample believed that child care responsibilities adversely affected productivity within their company. They also felt that company-sponsored child care assistance could improve productivity. Using the chi-square test of significance, child care responsibilities were significantly related to increased rates of absenteeism, work interruptions and turnover. There was substantial interest among employees in a corporate sponsored child care center and/or financial assistance to reduce the cost of child care expenses.

A technique using diffractive elements for finding the absolute shape of a large-scale object is proposed. An accurate projected fringe profilometry can be built by applying the holographic technique in this system. The advantages of using the presented technique for projected fringe profilemetry are : (1) a large depth of field ; (2) very low fringe distortion ; (3) a compact design for the measurement system ; (4) high accuracy ; (5) fast measurement speed.