The largest U.S. cancer health disparity exists in prostate cancer, with African American men having the highest incidence and mortality rates. The present study evaluated the effects of ZIC2 and the underlying mechanisms in the E006 parental African-American cell line that produces tumors at accelerated growth rates because of the increase of ZIC2 genes in African-American males. We analyzed the experimental research that the overexpression of ZIC2 contributes to progression of prostate cancer. E006AA cells with overexpressed or suppressed ZIC2 were analyzed to determine phenotypic differences, PCR, cell proliferation and immunoblot assays. The expression levels of ZIC2 were analyzed by CRISPR-Cas9, Western blot and proliferation growth curves. We discovered using these experimental techniques to knockout ZIC2, reduced cell proliferation occurred. This research investigated the role of ZIC2 in prostate cancer progression and the effects of the loss or gain of function of ZIC2 by using CRISPR-Cas 9 genome editing technology.

Na aviação, os procedimentos para situações anormais e de emergência, geralmente organizados em checklists compilados no Quick Reference Handbook (QRH), são elaborados e revisados como mecanismos de controle organizacional. Esta abordagem, no entanto, tem mostrado limitações em servir como solução para todos os tipos de situações, principalmente para problemas não estruturados. Neste cenário, o conceito ‘procedimentos como recursos para a ação’ tem sido visto como uma abordagem alternativa, embora tenha sido desenvolvida apenas de forma incipiente. Assim, o objetivo geral desta tese foi propor um protocolo para revisão dos procedimentos disponíveis em cockpits de aviões comerciais como apoio aos pilotos durante a gestão de anomalia. Para atingir o objetivo, a pesquisa adotou a Design Science Research e foi dividida em quatro etapas: compressão do problema, sugestão e desenvolvimento, avaliação e conclusão. Um estudo etnográfico cognitivo conduzido em uma companhia aérea brasileira propiciou melhor entendimento do problema por meio de observações participantes, entrevistas retrospectivas, entrevistas em grupo, dados secundários e documentos técnicos. Os resultados mostraram como fatores contextuais fora do escopo do QRH geraram demandas extras e requereram estratégias de adaptação dos sistemas cognitivos correlacionados. Fragmentos do QRH e de recursos adicionais foram intercalados para apoiar essas estratégias. As sugestões de melhorias envolveram a reorganização do QRH, dos checklists e dos recursos adicionais, a fim de melhor apoiar o reconhecimento de anomalias, o diagnóstico de problemas e o curso de ação. As sete etapas do protocolo foram desenvolvidas com base nos princípios teóricos e empíricos derivados do estudo e, em seguida, o protocolo foi avaliado de acordo com cinco critérios. Enquanto o artefato teve um bom desempenho em dois critérios, três deles revelaram a necessidade de ajustes, que podem ser superados com novas aplicações em diferentes contextos. Em conclusão, o estudo atingiu os objetivos geral e específicos, contribuiu para a classe de problemas ao operacionalizar o conceito ‘procedimentos como recursos para a ação’ e contribuiu para solucionar o problema prático ao proporcionar um artefato para ajudar as companhias aéreas a revisar seus procedimentos e outros recursos de modo a melhor apoiar os pilotos na gestão de anomalias. / In aviation, procedures for abnormal and emergency situations, generally organized in checklists compiled in the Quick Reference Handbook (QRH), are designed and redesigned as mechanisms of organizational control. This approach, however, has shown some drawbacks as a solution for any situation, specially for unstructured problems. In this scenario, the concept ‘procedures and resources for action’ has been seen as an alternative approach, although it has been incipiently developed. Thus, the general objective of this thesis was to propose a protocol for redesigning the procedures available in commercial aircraft cockpits as means of supporting pilots during anomaly management. To achieve the objective, the research adopted the Design Science Research approach and was divided into four stages: awareness of the problem, suggestion and development, evaluation and conclusion. A cognitive ethnographic study conducted in a Brazilian airline provided better understanding of the problem through participant observations, retrospective interviews, group interviews, secondary data and technical documents as sources of data. The results showed how contextual factors beyond the QRH scope generated extra demands and required adaptive strategies from the joint cognitive systems. Fragments from the QRH and from additional resources were interleaved to support these strategies. The design implications involved the reorganization of the QRH, the checklist and the additional resources in order to better support the anomaly recognition, the problem diagnosis and the course of action. The seven steps of the protocol were developed based on the theoretical and empirical principles derived from the study and, then, the protocol was evaluated according to five criteria. While the artefact performed well in two criteria, in three of them revealed opportunities of improvement, which can be overcame with more applications in different settings. In conclusion, the study achieved general and specifics objectives, contributed to the class of problems by operationalizing the concept ‘procedures as resources for action’ and contributed to solve the practical problem by providing an artefact that help airlines to redesign procedures and other resources in order to better support pilots during anomaly management.

Submitted by PPG Administra??o e Neg?cios (ppgad@pucrs.br) on 2018-10-31T17:22:35Z No. of bitstreams: 1 JOSIANE_BRIETZKE_PORTO_TES.pdf: 2215776 bytes, checksum: fc5d237ed433a12756eb499883e32497 (MD5) / Approved for entry into archive by Sheila Dias (sheila.dias@pucrs.br) on 2018-11-01T13:25:18Z (GMT) No. of bitstreams: 1 JOSIANE_BRIETZKE_PORTO_TES.pdf: 2215776 bytes, checksum: fc5d237ed433a12756eb499883e32497 (MD5) / Made available in DSpace on 2018-11-01T13:33:16Z (GMT). No. of bitstreams: 1 JOSIANE_BRIETZKE_PORTO_TES.pdf: 2215776 bytes, checksum: fc5d237ed433a12756eb499883e32497 (MD5) Previous issue date: 2018-08-30 / Coordena??o de Aperfei?oamento de Pessoal de N?vel Superior - CAPES / Smart city is an approach to managing and coping with urban challenges in search for innovative solutions leading to better quality of life and sustainability in cities. Several initiatives have been undertaken, with a significant worldwide growth trend in the coming years. Such initiatives, however, may require non-trivial public investment, and failures resulting from them can have important consequences such as monetary loss, loss of reputation, reduced confidence and lack of public value. This research aims at setting a methodology in smart cities composed of a reference model and an assessment method from the Public Value perspective. These artifacts were evaluated based on the perception of 23 representatives of the Quadruple Helix (government, industry, university and citizens) and on the results of the applicability in practice, through an initial pilot evaluation, in the city of Nova Santa Rita. It follows Design Science as its epistemological paradigm and Design Science Research as its method, uniting theoretical and methodological rigor as well as practical utility for society. The results showed that the artifacts developed in this research can help in the design and assessment of smart cities in a gradual way, bringing together best practices considered intelligent and that allow for the expansion and/or generation of Public Value, consisting of a prescriptive scientific contribution. Among the contributions are the protocol, contingency and construction heuristics, which detail how these artifacts were rigorously designed and developed, under the Design Science paradigm, to solve the problem identified in this research. They are specific and useful knowledge, generated from this research, aimed at the practice and resolution of real problem, and can be used for future evolutions of the artifacts developed in the research and/or design of new artifacts, in different contexts and classes of problems. / Smart city corresponde a uma abordagem para gerenciamento e enfrentamento de desafios urbanos, em busca de solu??es inovadoras para melhor qualidade de vida e sustentabilidade nas cidades. Em raz?o disso, diversas iniciativas v?m sendo feitas, com tend?ncia de crescimento significativo nos pr?ximos anos, em ?mbito mundial. Entretanto, tais iniciativas podem requerer investimentos p?blicos n?o triviais e falhas podem ter consequ?ncias importantes como perda monet?ria, preju?zo em rela??o ? reputa??o, redu??o de confian?a e aus?ncia de valor p?blico para as partes interessadas. Este trabalho desenvolveu uma metodologia em smart cities, sob a perspectiva de Valor P?blico, composta por um modelo de refer?ncia e um m?todo de avalia??o, avaliados com base na percep??o de 23 representantes da Qu?drupla H?lice (governo, ind?stria, universidade e cidad?os) e nos resultados da aplicabilidade na pr?tica, por meio de uma primeira avalia??o piloto, na cidade ga?cha de Nova Santa Rita. Adota Design Science como paradigma epistemol?gico e Design Science Research como m?todo de pesquisa, unindo rigor te?rico-metodol?gico e utilidade pr?tica para a sociedade. Os resultados mostraram que os artefatos desenvolvidos nessa pesquisa podem ajudar na concep??o e na avalia??o de smart cities de um modo gradual, reunindo melhores pr?ticas consideradas inteligentes, que possibilitam amplia??o e/ou gera??o de Valor P?blico, consistindo numa contribui??o cient?fica de car?ter prescritivo. Entre as contribui??es t?m-se tamb?m o protocolo, as heur?sticas contingenciais e de constru??o, que detalham como esses artefatos foram projetados e desenvolvidos com rigor, sob o paradigma de Design Science, para a resolu??o do problema identificado nessa pesquisa. Constituem conhecimento espec?fico e ?til, gerado a partir da pesquisa, voltado ? pr?tica e ? resolu??o de um problema real, podendo ser usado para futuras evolu??es dos artefatos desenvolvidos na pesquisa e/ou no projeto de novos artefatos, em diferentes contextos e classes de problemas.

This investigation was an analysis of the interaction of adolescent exposure to methylphenidate (MPH; trade name: Ritalin) on nicotine sensitization and conditioned place preference (CPP) in a rodent model and underlying mechanisms of this effect. Animals were treated IP with 1 mg/kg MPH or saline using a ―school day‖ regimen of five days on, two days off, from postnatal day (P) 28-50. During the final two weeks of MPH treatment, animals were either behaviorally sensitized to nicotine (0.5 mg/kg free base) or saline for 10 days, or conditioned to nicotine or saline using the CPP behavioral paradigm. In addition, three days after behavioral sensitization was complete, animals were analyzed for stress behavior using the forced swim stress behavioral test. In addition, 24 hours after post-test conditioning animals were analyzed for the effect of a clinically relevant dose of pre-exposed MPH (1mg/kg) and nicotine treatment on the expression of BDNF in the nucleus accumbens and dorsal hippocampus. Behavioral results revealed that adolescent pre-exposure to MPH blunted nicotine behavioral sensitization in both male and female rats during the first week of testing. However, MPH enhanced nicotine CPP in both adolescent male and female rats. Interesting, animals administered MPH demonstrated a significantly decreased latency to immobility in the forced swim stress behavioral test. In addition, pre-exposure to a 1 mg/kg dose of MPH appears to have sensitized the BDNF response to nicotine in females as compared to all other groups.

Protein identification using tandem mass spectrometry (MS/MS) has proven to be an effective way to identify proteins in a biological sample. An observed spectrum is constructed from the data produced by the tandem mass spectrometer. A protein can be identified if the observed spectrum aligns with the theoretical spectrum. However, data generated by the tandem mass spectrometer are affected by errors thus making protein identification challenging in the field of proteomics. Some of these errors include wrong calibration of the instrument, instrument distortion and noise. In this thesis, we present a pre-processing method, which focuses on the removal of noisy data with the hope of aiding in better identification of proteins. We employ the method of binning to reduce the number of noise peaks in the data without sacrificing the alignment of the observed spectrum with the theoretical spectrum. In some cases, the alignment of the two spectra improved.

This present study was intended to identify the reliability and validity of the Vert™ device when compared to a Switch mat. Vert is a wireless device intended to measure jump count and jump height through an application on a smartphone or tablet and the Switch mat provides jump height using wireless sensors. Jump height is an important factor in many sports such as volleyball and basketball and it is important to have devices that coaches and trainers can use for testing that they can rely on. If this device is found to be valid and reliable, coaches and trainers could potentially use it in more practical settings such as practice and games due to the portability and small size. This study consisted of 6 subjects who volunteered. The switch mat was connected to the device to display the jump height immediately after the jump. The Vert sensor was clipped onto the subject’s hip near the center of mass and the jump count and height were then displayed on an app. The subjects completed a series of warm-ups followed by 3 sets of 5 repetition countermovement jumps while using both devices to collect the data. The total 15 jump heights from these 3 sets of 5 were then analyzed using Pearson correlation analysis as well as a paired sample T-test. The jump height recorded from the Vert was consistently about 10 cm off from the jump height of the switch mat, which for a volleyball player, could be the difference between blocking and missing the ball. The results of this study showed that the Vert device is reliable but not practically valid. If technical improvements were made to the device to correct the height components the device could potentially be used in place of a force plate or switch mat when conducting athlete testing but the device is not currently valid for practical use.

Heart failure (HF) induced by aortic pressure over-load is associated with increased coronary artery stiffness. Perivascular adipose tissue (PVAT) and advanced glycation end products (AGE) both promote arterial stiffness. However, the mechanisms by which coronary PVAT promotes arterial stiffness and the efficacy of exercise to prevent coronary stiffness are unknown. The present study hypothesized both chronic continuous and interval exercise training would prevent coronary artery stiffness associated with inhibition of PVAT secreted AGE. Yucatan mininature swine were divided into four groups: control-sedentary (CON), aortic-banded sedentary heart failure (HF), aortic-banded HF continuous exercise trained (HF+CONT), and aortic-banded HF interval exercise trained (HF+IT). Coronary artery stiffness was assessed by ex vivo mechanical testing and coronary artery elastin, collagen and AGE-related proteins were assessed by immunohistochemistry. HF promoted coronary artery stiffness with reduced elastin content and greater AGE accumulation which was prevented by chronic continuous and interval exercise training. HF PVAT secreted higher AGE compared with CON and was prevented in the HF+CONT and HF+IT groups. Young healthy mouse aortas cultured in HF PVAT conditioned media had increased stiffness, lower elastin content and AGE accumulation compared with CON, which was prevented by PVAT from the HF+CONT and HF+IT groups. HF coronary PVAT secreted greater interleukin-6 (IL-6) and IL-8 compared to CON which was prevented by both continuous and interval exercise training regimens. We conclude chronic continuous and interval exercise is a potential therapeutic strategy to prevent coronary artery stiffness via inhibition of PVAT-derived AGE secretion in a pre-clinical mini-swine model of pressure overload-induced HF.

Protein–lipid binding interactions play crucial roles in various physiological and pathological processes, making it very important to study these interactions at the molecular level. However, investigation of these interactions is complicated by several issues, including the inherent complexity of membranes as well as the diverse mechanisms by which proteins interact with the membrane surfaces. As a result, many of these interactions remain poorly characterized. Synthetic probes are useful tools employed for studying protein–lipid binding interactions. This thesis will detail the design and synthesis of metabolically stabilized analogues of various signaling lipids, which mimic the natural species and are not easily modified by enzymes present in biological systems. A modular approach is employed for synthesizing these lipid probes, giving access to a wide range of derivatized lipid probes that can then be used for several studies. Although a wide variety of metabolically stabilized lipid analogues have been synthesized, their activity has not yet been characterized and quantified in detail. So, there is a great need to synthesize biologically active phosphorothioate and phosphonate analogues of various signaling lipids in order to properly characterize and compare the binding affinities and activity of these analogues. Synthesis of metabolically stabilized lipid analogue would take us one step closer towards understanding protein–lipid interactions in biological systems and in trying to find answers to the myriad of questions pertaining to these systems.

Managing projects in an organization, especially a project-oriented organization, is a challenging task. Project data has a large volume and is complex to manage. It is different from managing a single project, because one needs to integrate and synthesize information from multiple projects and multiple perspectives for high-level strategic business decisions, such as aligning projects with business objectives, balancing investment and expected return, and allocating resources. Current methods and tools either do not well integrate multiple aspects or are not intuitive and easy to use for managers and executives. In this dissertation project, a multidimensional and visual exploration approach was designed and evaluated to provide a unique and intuitive option to support decision making in project portfolio management. The research followed a general design science research methodology involving phases of awareness of problem, suggestion, development, evaluation and conclusion. The approach was implemented into a software system using a prototyping method and was evaluated through user interviews. The evaluation result demonstrates the utility and ease-of-use of the approach, and confirms design objectives. The research brings a new perspective and provides a new decision support tool for project portfolio management. It also contributes to the design knowledge of visual exploration systems for business portfolio management by theorizing the system.

The alternative fuel biodiesel is produced from the transesterification of vegetable oils or animal fat to fatty acid methyl esters. Pomona has a reactor on campus that can be used to run this reaction and produce biodiesel. The use of biodiesel has been found to lower air pollutant and greenhouse gas emissions, but can be potentially harmful to the engines if it contains impurities. This paper proposes a method using high-performance liquid chromatography to test the quality of biodiesel. This method utilizes instrumentation and materials that are available in Pomona College's Chemistry Department, requires very little sample preparation, and is relatively safe, as long as general lab safety practices are followed. This method can also be used to optimize the procedure used to make the biodiesel. An optimized production procedure and a test method to assess the final product will ensure high quality fuel that can be used with confidence in diesel engines. This will likely add strength to proposals to increase the use of the on-campus reactor and produce biodiesel for campus grounds equipment from waste vegetable oil.