No description available.

The retinoblastoma family of phosphoproteins consisting of the retinoblastoma protein (pRB) and the two structurally related proteins p130 and p107 play an important role in the negative regulation of cell cycle progression. Hypophosphorylated pocket proteins interact with the different members of the E2F family and repress the transcription of E2F-dependent genes and consequently suppress cell cycle progression through the G0/G1 transition and the restriction point in G1. Mitogenic stimulation results in sequential activation of cyclin/CDK complexes in mid to late G1, leading to subsequent hyperphosphorylation at multiple Ser/Thr sites of pocket proteins triggering dissociation of pocket protein/E2F complexes. This disruption leads to de-repression of many E2F dependent genes whose products are essential for cell cycle progression. The traditional view has been that pocket proteins continue to be hyperphosphorylated through the S and G2 phases and following cyclin/CDK inactivation during mitotic exit become dephosphorylated by action of PP1. However, our lab observed that upon treatment of asynchronously growing cells with the CDK inhibitor Flavopiridol or CHX, pocket proteins, are rapidly dephosphorylated correlating with the inactivation of G1/CDKs and down regulation of D-type cyclins, respectively. Pocket protein dephosphorylation was prevented by pre-treating these cells with phosphtase inhibitors at a concentration selective for PP2A, implicating PP2A or PP2A-like serine/threonine phosphatase in this iii process. The involvement of PP2A on pocket protein dephosphorylation was further strengthened by the observation that SV40 small t antigen (ST) delays/prevents p107 dephosphorylation. Moreover, a physical association between PP2A/C and p130/p107 was observed throughout the cell cycle that was not affected by CHX treatment, strongly suggesting that CHX-induced dephosphorylation is not the result of increased pocket protein targeting by PP2A, but rather that a dynamic equilibrium between CDKs and PP2A is shifted to dephosphorylation when CDK activity is compromised. This dynamic equilibrium operates throughout the cell cycle. PP2A is a trimeric enzyme complex consisting of a catalytic C, a structural A and substrate specific B subunit. There are four families of regulatory B subunits designated B, B’, B’’ and B’’’, each with several members encoded by genes with multiple splice variants that mediate substrate specificity and subcellular localization. It has been reported recently that in excess of 200 functional distinct PP2A holoenzymes can assemble with distinct specificities. Therefore, to gain insight into the mechanisms that regulate the steady state phosphorylation of pocket proteins throughout the cell cycle, it was essential to identify the specific holoenzyme complexes involved. To this end, it was identified that a PP2A trimeric holoenzyme containing B55α specifically targets and dephosphorylates p107/p130 both in vitro and in mammalian cells. B55α associates directly with the spacer of p107 and this interaction seems to be indirectly enhanced by the C-terminus of p107. The decreased association of p107 with PP2A/C of the B55α/PP2A holoenzyme complex upon treatment with ST further confirmed the role of B55α in mediating p107-PP2A/C interaction. Our data also revealed an interaction between B55α and p130, but not pRb, which appears to prefer a PR70, suggesting selectivity in the interaction of pocket proteins with distinct PP2A holoenzymes. In accordance with this, recombinant purified B55α dephosphorylates p107 in vitro. Limited ectopic expression of B55α but not other subunits, result in ST sensitive dephosphorylation of p107 and p130 in cells. Further shRNA mediated knockdown of B55α results in hyperphosphorylation of p107 and p130. This suggests that the cellular levels of B55α are critical in modulating the phosphorylation status of p107/p130 rather than just catalyzing the dephosphorylation of these proteins when the activity of CDKs is compromised. Since ST disrupts the B55α/PP2A holoenzyme complex by binding to the PP2A-A-C dimer and leads to hyperphosphorylation of pocket proteins it is conceivable that ST mediates its effects on cell proliferation at least in part, via inactivation of the PP2A holoenzymes that activates pocket proteins. Given the sensitivity of p107 phosphorylation to the cellular levels of B55α, future analyses should ascertain if deregulation of B55α leads to hyperphosphorylation of pocket proteins and abnormal cell cycle progression. / Molecular Biology and Genetics

This thesis describes a performance measurement tool that allows a user to measure network performance using a handheld device. The measurement tool consists of a client program that runs on a Microsoft Pocket PC device and a server program that runs on a regular Microsoft Windows computer. Both programs are Windows applications implemented in C/C++ using the Microsoft Embedded Visual Tool and Microsoft Visual Studio. The use of a Pocket PC device provides mobility to users, which can save time and energy when performing experiments. The thesis describes the design of the performance measurement application, implementation issues, and tests conducted using the tool. / Master of Science

The process of tax decentralization and the growing participation of municipal governments in the set of tax resources of Brazil, amplify its expansion in the management of public services dedicated to the population, creating conflicts in the structure of this level of government. The expansion and the improvement of the public services dedicated to the population require a larger structure and that is the reason that it requires more expenditure to municipalities. Although the municipalities public revenue receives an increase of financial resources, it has been demonstrated insufficient in order to afford these expansions. Between the tributes that the municipalities adopt, there are the IPTU and also ISSQN. These taxes could represent a stimulus on the tributes, making it sufficient to support the public expenditure. The taxes belong to the federal constitution, it is governed by a complementary municipality s law and it has as first generator of tributes, the inclusion in owns register of all buildings, residential and commercial. The presented work demonstrates the possibilities of using mobile computing in the simplification of the collection and data processing, detailing two systems in the area of urban management that use technology GPS with connection wireless Bluetooth and also it allows the update and the insertion of new information in the data base. / O processo de descentralização fiscal e a crescente participação dos governos municipais no conjunto dos recursos tributários do Brasil ampliaram sua expansão na gestão dos serviços públicos de atendimento à população, criando conflitos na estrutura desse nível de governo. A ampliação e melhoria dos serviços públicos prestados à população requerem uma estrutura maior, e geram por isso mais despesas para o município. Dessa forma, embora a receita pública municipal tenha recebido um incremento de recursos financeiros, tem se mostrado insuficiente para bancar essas expansões. Assim, entre os tributos de arrecadação própria que os municípios possuem, estão os Impostos IPTU e ISSQN. Esses impostos podem representar um estímulo nas arrecadações, suficientes para atender às despesas públicas, estão previstos na constituição federal. Ambos são regidos por lei complementar municipal, e possuem como primeiro fato gerador de arrecadação a inscrição em cadastro próprio de todos os imóveis residenciais e comerciais existentes. Este trabalho mostra a possibilidade de se utilizarem sistemas computacionais móveis na simplificação de coleta e processamento de dados à campo, detalhando dois sistemas na área de gestão urbana, que utilizam tecnologia GPS com conexão sem fio Bluetooth, e permitem a atualização e inserção de novas informações no banco de dados.

La maladie du sommeil ou trypanosomiase africaine humaine fait partie des maladies tropicales négligées sévissant en Afrique sub-saharienne. Elle est causée par le parasite mono-flagellé, Trypanosoma brucei, véhiculé par la mouche tsé-tsé (Glossina spp.). Le flagelle de ce parasite prend naissance au niveau du corps basal et émerge de la cellule en traversant une structure appelée poche flagellaire (FP). Cette poche est formée par l’invagination de la membrane plasmique autour de la base proximale du flagelle. Elle est essentielle à la survie du parasite, car elle constitue l’unique site d’endo- et d’exocytose de la cellule. Cette structure est maintenue autour du flagelle via un constituant du cytosquelette appelé, collier de la poche flagellaire (FPC). Ce collier décrit une structure en anneau ou en fer-à-cheval à la zone de sortie du flagelle. Le premier composant identifié au niveau du FPC est une protéine appelée BILBO1. BILBO1 est essentielle et nécessaire à la biogenèse du FPC et de la FP. Une analyse protéomique et un crible en double-hybride réalisé contre une banque génomique de T. brucei ont permis d’identifier plusieurs partenaires potentiels de BILBO1. Nous avons pu identifier et caractériser de nouvelles protéines du FPC, localisées comme BILBO1 dans une structure en anneau. Nous avons étudié leur fonction chez le parasite, en caractérisant les effets de la surexpression de ces protéines ou de leur ARN interférence sur la croissance et la morphologie cellulaire. / The Human African Trypanosomiasis is a Sub-Saharan Neglected Tropical Disease, caused by Trypanosoma brucei, a mono-flagellate protozoan transmitted by the tsetse fly (Glossina spp.). The T. brucei flagellum originates from a cytoplasmic basal body then grows, to emerge from the cell, by traversing an unusual and essential structure called the Flagellar Pocket (FP). This pocket is an invagination of the pellicular membrane at the base of the flagellum. The FP is essential for the survival of the parasite, because it is the unique site for endo- and exocytosis. The Flagellar Pocket Collar (FPC) is a cytoskeletal component of the FP, and is located at the neck of the FP where it maintains a ring/horseshoe structure at the exit site of the flagellum. The FPC contains numerous uncharacterised proteins, including the first protein identified as FPC component - BILBO1. BILBO1 is essential and required for FPC and FP biogenesis. A proteomic analysis and a private two-hybrid genomic screen experiment on T. brucei have revealed a number of potential BILBO1 partners. We found several proteins localize to the FPC like BILBO1 in a ring-like structure. We characterise these new FPC proteins and their function in the parasite. We have characterised the effects of the GFP fusion protein over-expression and RNAi on cell growth and morphology in T. brucei.

<b>Background</b>: In order to protect the poor from health shocks, the Government of India launched Rashtriya Swasthya Bima Yojna (RSBY) in 2008. The objectives of this study are: a) to assess the changes in the financial burden of health care on the poor population; b) to estimate the effects of RSBY in reducing the financial burden on the poor; and c) to examine the impact of RSBY on the labour supply of the poor. <b>Methods</b>: The study is based on data from the National Sample Survey Organisation (NSSO). The sample size is between 100-125 thousand households at the all-India level. The study uses pooled cross-section regression analysis to assess the changing pattern of out-of-pocket (OOP) payments on healthcare. The impact of RSBY on financial risk protection and labour force participation rate in India were estimated using the difference-in-differences (DID) method. <b>Findings</b>: My thesis consists of three papers. The findings in the first paper, changing pattern of out-of-pocket payments, reflect that the poorest 20% of households, compared to the richest 20%, realised a slower increase in out-of-pocket as a share of the household’s total expenditure (-0.5%) and catastrophic payments (-2%) during the period of 2000-2012. However, during the same period, Scheduled caste/tribe and Muslim households reported an increased burden of out-of-pocket. The second paper finds reduction in the probability of incurring ‘any inpatient expenditure’ and ‘catastrophic inpatient expenditure’ after RSBY intervention but marginal increase in the ‘per person monthly inpatient expenditure’ and insignificant change in ‘inpatient expenditure as a share of households’ total expenditure’. The effects of the scheme on the total out-of-pocket payment are negligible and non-drug expenditure reflected significant increase. The third paper finds that women’s labour supply increased (3% per annum) but the elderly labour supply declined (1.5%). Further, men switched from self-employment to casual work while women moved to wage-paid regular and casual jobs at the cost of being self-employed. <b>Discussion and conclusion</b>: The poor and other less advantaged population groups realised an increasing OOP burden mainly on account of two factors: i) outpatient care is not covered under RSBY; and ii) the benefit package under the scheme is very modest. Women’s labour supply increased and the elderly labour supply declined in favour of leisure because of possible improvements in health. However, the overall labour supply did not change. The Indian government needs to consider broadening the benefit package and including outpatient coverage under RSBY.

Oral cancer drugs are branded and expensive medications that generally do not have generics available. The restrictions of the Medicare Part D program, including the coverage gap and high cost-sharing, and the high cost of oral chemotherapy may lead to patients’ non-adherence to medication. Few studies have examined the cost and utilization of oral anti-cancer medications. This study will be the first to examine the costs associated with the use of oral anti-cancer medications and the impact of cost-sharing and type of prescription drug subsidy on medication discontinuation in the Medicare Part D elderly population. Objectives: To determine the usage and costs of oral cancer treatment in elderly Medicare Part D beneficiaries and to examine the relationship between out of pocket costs and medication discontinuation or delay. Methods: A cross-sectional study of the spending and usage of oral cancer drugs in the Medicare Part D population was conducted. A 5% random sample of 2008 Medicare beneficiaries was used. The study sample included all members of this group who: 1) were 65 years of age and older and 2) filled at least one prescription for imatinib, erlotinib, anastrozole, letrozole, or thalidomide. We examined the average costs patients paid per day, the cost that the Part D plan paid per day, and the total cost that patients paid for the entire year for each drug. The demographic characteristics and type of prescription drug subsidy of Part D beneficiaries who used oral cancer drugs were reported in frequency counts and percentages. We also determined the percentage of enrollees who entered the Part D coverage gap, the time and duration that they fell into the coverage gap, the number of beneficiaries who discontinued treatment and the association between OOP costs and medication discontinuation or delay, controlling for polypharmacy, prescription coverage and socio-demographic factors. Results: Prescription drug subsidy was categorized in four groups: 1) Dual Eligible (DE), 2) full Low Income Subsidy (LIS), 3) partial LIS, and 4) no subsidy. Mean out-of-pocket (OOP) costs per day were between $0.03 and $0.09 for DE beneficiaries, between $0.04 and $0.23 for full LIS beneficiaries, between $1.17 and $6.34 for partial LIS beneficiaries and between $2.93 and $36.84 for beneficiaries who did not receive a subsidy. On average, the beneficiaries who used oral cancer medications were between 75 and 76 years of age. Over half of oral cancer medication users were Caucasian and female. Over two-thirds of oral cancer medication users received no subsidies for their prescription coverage. About 99% of users of the more expensive drugs - imatinib, erlotinib and thalidomide - entered the coverage gap and the majority of these entered the coverage gap at the time of their first fill. In contrast, beneficiaries who filled the less expensive drugs - anastrozole and letrozole - entered the coverage gap later. Less than 7% entered the coverage gap at the time of the first fill of their prescriptions. Beneficiaries who used imatinib, erlotinib, or thalidomide spent approximately a month in the coverage gap. Over the course of a year, the majority of their time was spent in the catastrophic phase. Approximately 33-60% of total oral cancer drug users discontinued their therapies. About 50% of these discontinued during the coverage gap for anastrozole and letrozole and about 80% discontinued during the catastrophic phase for imatinib, erloinib and thalidomide. OOP costs were associated with medication discontinuation for all five oral cancer drugs. The odds of discontinuation and delay increased 101%, 170%, and 264% for each $100 increase in OOP spending for imatinib, erlotinib and thalidomide users, respectively. The odds of discontinuation and delay increased 9%-10%, and 6-8% for every $10 increase in OOP spending for anastrozole and letrozole users, respectively. Conclusions: About 33-60% of all users discontinued their therapies. Beneficiaries receiving subsidies had low OOP costs, averaging between $0.03 and $6.34 per day. Beneficiaries on the more expensive drugs and not having subsidies had high OOP costs, averaging between $15.66 and 36.84 per day. Higher OOP costs were associated with an increased likelihood of discontinuation or delay.

Made available in DSpace on 2015-04-22T22:14:09Z (GMT). No. of bitstreams: 1 Dissertacao Samuel Lungareze.pdf: 4572476 bytes, checksum: 70070d60dc879fec996a32a20cdd90c1 (MD5) Previous issue date: 2010-01-15 / Coordenação de Aperfeiçoamento de Pessoal de Nível Superior / The Periodontal disease (DP) is very strongly associated with the dental biofilm and may evolve the formation of a periodontal pocket. The propolis has been used as a medicinal product since 300 b.C, and has the following characteristics: anti-cancer activities, antioxidant, anti-inflammatory, antimicrobial, and antifungal. The propolis antimicrobial activity in face of periodontalpatogens has been investigated though in vitro and in vivo tests, mainly with the etanolic extracts. The following paper had as an objective evaluate the histological response of the inflammatory DP induced on the rats periodontal tissue after the use of a watery suspension of propolis (SAP), at 0,1%, 1%, and 10%, for subgingival irrigation. Was used 84 wistar rats (Rattus novergicus), weighting between 210 and 290g with eight weeks old. They were distributed in the following experimental groups: group I (n= 14, SAP at 0,1%), group II (n=14, SAP at 1%), group III (n=14, SAP at 10%), group IV (n=14, Tween`s solution 80 at 5%), group V (positive control, n=14, with induced DP and without treatment), group VII (n=14, chlorhexidine at 2%) and group VI (n=84, negative control, not induced contralateral teeth and not treated on animals of groups I, II, III, IV, V e VII). The inflammatory DP was induced with the technique that uses the ligation with cotton yarn during a period of 15 days on the cervical of the first left inferior molar. After the removal of the yarn the periodontal pocket was irrigated 3 times (1st, 4th and 7th days) with the tests solution and the sacrifice was done on the 15th and 30th day after treatment. Was done the test exact of Fisher (p-value 0,05). Analyzing comparatively the results you may suggest that the propolis suspension on the concentration of 0,1% is efficient considering the short term inflammatory response (15 days), associated to the presence of dense gingival fibers, blood vessels without congestion, no dental reabsorption and bone loss. There for may be used as an alternative treatment for the periodontal disease, needing further studies to demonstrate the biological viability on the use as supporting on the periodontal therapeutic. / A doença periodontal (DP) está intimamente associada com a formação de biofilme dental, podendo progredir para formação de uma bolsa periodontal. A própolis tem sido utilizada como produto medicinal desde 300 a.C., e apresenta como características: atividades anticancerígena, antioxidante, anti-inflamatória, antimicrobiana e antifúngica. A atividade antimicrobiana da própolis frente aos periodontopatógenos já foi investigada através de testes in vitro e in vivo, principalmente através de extratos etanólicos. O presente trabalho teve como objetivo avaliar histologicamente a resposta da DP inflamatória induzida no tecido periodontal de ratos após a utilização de suspensões aquosas de própolis (SAP) a 0,1%, 1% e 10%, para irrigação subgengival. Foram utilizados 84 ratos wistar (Rattus novergicus), pesando entre 210 e 290g, com oito semanas de idade, distribuídos nos seguintes grupos experimentais: grupo I (n=14, SAP a 0,1%), grupo II (n=14, SAP a 1%), grupo III (n=14, SAP a 10%), grupo IV (n=14, Solução de Tween 80 a 5%), grupo V (controle positivo, n=14, com DP induzida e sem tratamento), grupo VII (n=14, clorexidina a 2%) e grupo VI (n=84, controle negativo, dentes contralaterais não induzidos e não tratados nos animais dos grupos I, II, III, IV, V e VII). A DP inflamatória foi induzida através da técnica da ligadura com fios de algodão durante um período de 15 dias na cervical do 1º molar inferior esquerdo. Após a remoção do fio a bolsa periodontal foi irrigada 3 vezes (1º, 4º e 7º dias) com as Soluções testes e o sacrifício foi realizado com 15 e 30 dias após o tratamento. Foi realizado teste exato de Fisher (p-valor 0,05). Analisando comparativamente os resultados pode-se sugerir que a SAP foi eficiente considerando principalmente a resposta inflamatória em curto prazo (15 dias) e na concentração de 0,1%, associada à presença de fibras gengivais densas, vasos sanguíneos sem congestão, ausência de reabsorções dentárias e perdas ósseas, podendo ser uma alternativa de tratamento da DP necessitando de estudos futuros para demonstrar a viabilidade biológica na utilização como coadjuvante na terapêutica periodontal.

O objetivo principal deste estudo é a análise do balanço de sedimentos arenosos na enseada de Balneário Camboriú, localizada no litoral centro-norte do Estado de Santa Catarina. Para alcançar os objetivos deste trabalho a enseada foi compartimentada em células e utilizadas diferentes metodologias que envolveram a análise de diversos parâmetros, tais como: sedimentologia e morfologia da praia e antepraia; estabilidade da praia em planta e perfil; perfil de equilíbrio da enseada; transporte de sedimentos por ondas e correntes e perda de sedimentos para fora da praia através dos banhistas. A praia de Balneário Camboriú é composta de areia fina a muito fina, de composição quartzosa, bem a moderadamente classificados. A distribuição das fácies sedimentares da enseada de Balneário Camboriú demonstra a inexistência de trocas de sedimentos arenosos da praia com a região da antepraia, sendo esta dominada principalmente por sedimentos finos (silte e argila). A estabilidade da praia em planta encontra-se em equilíbrio dinâmico na porção norte e sul da enseada. A morfologia praial em valores de variação de volume e largura demonstrou que os perfis localizados na porção norte, que corresponde a região mais exposta da praia, apresentam maiores variações do que os demais perfis localizados nas porções mais protegidas. Verificou-se um processo de rotação praial entre os perfis, havendo acresção em alguns enquanto ocorre erosão em outros, mostrando uma troca de sedimentos entre eles. O volume de sedimentos ganho pela praia entre 1994 e 2005 foi de aproximadamente 49.000 m3 que foram adicionados artificialmente por uma obra de alimentação executada pela prefeitura municipal. A profundidade de fechamento apresenta um comportamento gradacional, com diminuição dos valores de norte para o sul da enseada, em acordo com os padrões de distribuição do fluxo de energia das ondas e correntes. Os valores definidos para a profundidade de fechamento variam entre 4 m e 1,7 m. Este limite de profundidade é também demonstrado na variação faciológica entre a praia e antepraia. Os cenários de refração, difração de ondas e transporte de sedimentos associado demonstrou que a praia se comporta como uma célula fechada, não havendo troca significativa de sedimentos entre esta e a região de antepraia. Portanto, gerando um balanço arenoso nulo entre estes dois ambientes. Verificou-se, que o volume sedimentar removido da praia pelos banhistas não causou grande impacto no balanço de sedimentos durante o período amostral. Por outro lado, sugere-se que em longo prazo, esta retirada de areia possa representar um déficit mais significativo, da ordem de 970m³. O cálculo do balanço de sedimentos arenosos para a praia e enseada de Balneário Camboriú apresentou um valor negativo de 152 m3/ano. Este valor pode ser considerado mínimo quando comparado ao volume total de sedimentos da praia, e corresponde a metade do valor calculado para a perda anual de sedimentos causadas pelos banhistas Com isso pode-se concluir que a enseada de Balneário Camboriú está em equilíbrio quanto ao balanço sedimentar, sem perdas e ganhos de sedimentos consideráveis. / The overall goal of this study is the sandy sediment budget analysis in the Balneário Camboriú bay, located in central-northern coast of Santa Catarina State. To achieve the objectives of this work the bay was compartments in cells and used different methodologies that involved the analysis of various parameters such as: the beach and bay sedimentology and morphology; planform and profile beach stability; equilibrium beach profile; sediment transport by waves and currents and loss of sediment through the beach users. The Balneário Camboriú beach is composed of the fine and very fine sand, quartz and to moderately classified. The sedimentary facies distribution shows there are no exchanges of sediment from the sandy beach with the bay, dominated mainly by fine-grained sediments (silt and clay). The planform beach stability is in dynamic equilibrium in the north and south beach portion. The beach morphology change in volume and width values showed that the profiles located in the northern portion, more exposed to the beach, have more variations than the other profiles located in portions more protected. There was a process of beach rotation between the profiles, there was accretion in some profiles and erosion in others, showing an exchange of sediment between them. The sediment volume gain the beach between 1994 and 2005 was approximately 49,000 m3 which were artificially added to the beach for nourishment implemented by Municipality. The depth of closure presents a gradational behavior, with declining values of north to the south of the bay, in accordance with the waves and currents flow of energy distribution patterns. The values defined for the depth of closure ranging from 4 m to 1.7 m. This limit of depth is also shown in facies variation between the beach and shoreface. The waves refraction and diffraction scenarios and sediment transport showed that the beach is behaving like a closed cell, with no exchange between beach and shoreface. Therefore, generating a null balance between these two sandy environments. It was found that the sediment volume removed by users beach causes no major impact on the coastal sediment sampling during the period (summer 2003/2004). Moreover, it is suggested that a long-term Balneário Camboriú, the sand removal could present a more significant deficit in the coastal sediment, as this beach is mostly populated flow in twenty years where the sediment volume would be withdrawn from 970m³ . The beach and shoreface Balneário Camboriú sandy sediment balance calculation presented a negative value of 152 m3/year. This quantities can be considered minimal when compared to the total sediment volume from the beach. The estimated value is half the value calculated for the loss of sediment removed by users. This can be concluded that the inlet of Balneário Camboriú bay is totally balanced on the sediment, with no considerable sediment losses and gains.

Thesis (Ph.D.)--Kent State University, 2005. / Advisors: Alicia R. Crowe, Shawn Fitzgerald. Keywords: teacher education; mobile computing; handheld computing; social studies education; attitudes. Includes survey instrument. Includes bibliographical references (leaves 102-128). Also available via the World Wide Web.