International Telemetering Conference Proceedings / October 20-23, 2003 / Riviera Hotel and Convention Center, Las Vegas, Nevada / In our prior work [1] we proposed that network-centric data telemetry systems offer substantial improvements over traditional serial data telemetry systems. This paper is a follow up to that work and is also a companion to our experimentation paper [2]. In network-centric telemetry systems, there can be many infrastructure sites that form the network’s ad hoc communications paths, and there can be many fast-moving nodes, e.g., munitions, which enter the network, generate telemetry data, and exit the network. As the geographic size of such data telemetry networks grows, constraints on link margin will typically preclude a one-to-one matching of ground-based infrastructure sites to airborne, fast-moving nodes. That is, the fast-moving nodes will traverse distances that will require the mobile node to change which specific ground node it communicates with to transfer telemetry data. This paper describes an analytic model for the generic process of a fast moving node entering a wireless network and the associated handoffs of that node among ground stations as the fast mover traverses the spatial region covered by the wireless network. Our analysis and associated worst-case example demonstrate that wireless networking technology can handle the stress of rapidly managing connectivity to high-speed nodes for effective telemetry data extraction.

Chronic lymphocytic leukemia (CLL) is a cancer of B cells and is the most common leukemia in North America. Current therapies are fraught with challenges, and drug resistance and disease relapse remain common occurrences. Therefore, novel therapies and novel therapeutic strategies are needed to improve CLL therapy. Better yet, therapies targeted at specific weaknesses of CLL cells will ensure maximum efficacy and minimum adverse toxicity. To this end, this thesis focuses on targeting the susceptible BCR pathway and lysosome-mediated cell death pathway using gefitinib and lysosomotropic agents, respectively. Firstly, the novel use of the tyrosine kinase inhibitor gefitinib was explored. This drug was most effective in aggressive ZAP-70+ CLL cells and cell lines. A similar inhibitor, erlotinib, had no effect in CLL. Gefitinib inhibited phosphorylation of Syk and ZAP-70, prevented downstream kinase activation, and supressed the pro-survival BCR response. ZAP-70 is implicated in the mechanism of action of gefitinib as introduction of ZAP-70 into a B cell line increased their sensitivity to gefitinib. Secondly, the novel strategy of targeting lysosomes was explored. The lysosomotropic drugs siramesine, nortriptyline, desipramine, mefloquine, and tafenoquine were all found to induce cytotoxicity and lysosome permeabilization. Lysosome permeabilization was accompanied with lipid peroxidation and followed by loss of mitochondrial membrane potential. Compared with healthy B cells, CLL cells were more sensitive to this cell death pathway. This was potentially due to the overexpression of SPP1 and overproduction of sphingosine, which destabilized lysosomes. Lastly, this thesis explored the clinical utility of these targeted therapies. Both gefitinib and siramesine were more effective in CLL cells than patient T cells. Furthermore, they retained efficacy amid protective stromal cells. Clinical correlations revealed that gefitinib and siramesine were effective in CLL cells with poor prognostic features. Siramesine was more effective in male cells and in previously-treated cells. Gefitinib was most effective in young patients. Overall, work presented herein demonstrates the efficacy of the tyrosine kinase inhibitor gefitinib and lysosomotropic agents in primary CLL cells. This work investigates the altered biology of the BCR pathway and lysosomes in CLL cells, and takes advantage of these weaknesses using targeted therapies. / October 2016

Signals via the T cell receptor (TCR) are critical for the development of T cells in the thymus, maintenance of a self-tolerant peripheral T cell repertoire and the activation of T cells in secondary lymphoid organs. A dynamic balance between tyrosine phosphorylation and dephosphorylation is essential for the maintenance of homeostasis and proper regulation of the immune system. The cytoplasmic phosphatase, PTPN22 (protein tyrosine phosphatase non-receptor type 22) is involved in negative modulation of signal transduction through the TCR and plays a central role in regulating lymphocyte homeostasis. Genome wide association studies reveal that point mutations in PTPN22 confer an increased risk of developing multiple autoimmune diseases in humans. The precise function of PTPN22 and how mutations contribute to autoimmunity is controversial. Loss-of-function mutations in PTPN22 are associated with elevated T effector cell expansion and autoreactive B cells in both humans and mice. A thorough dissection of the molecular involvement of PTPN22 and its allelic variant R619W is important to delineate its role in autoimmunity, to this end we utilised the Ptpn22-/- mice generated in our laboratory. In order to address whether R619W allelic variant is a gain- or loss-of-function mutation, we expressed both PTPN22WT and PTPN22R619W constructs in primary activated Ptpn22-/- T lymphocytes using lentiviral transduction. Surprisingly expression of either wild type or variant phosphatase showed no affect on cytokine production. Preliminary results from bone marrow chimeras generated by retroviral expression of PTPN22WT and PTPN22R619W in Ptpn22 deficient mice showed reduced T cell activation compared to Ptpn22-/- T cells. PTPN22WT appeared to be more suppressive of T cell responses than variant PTPN22R619W. Consistent with studies conducted in comparable knock-in mouse models, our data point to the variant PTPN22R619W as being a partial loss of function allele. To elucidate the mechanism of PTPN22 action in context of an autoimmune disease, we investigated the effect of Ptpn22 deficiency on the phenotype of SKG mice. The SKG mouse harbours a point mutation (W163C) within the carboxyl terminal SH2- domain of ZAP-70, which results in decreased TCR signalling and impaired thymocyte development with defective positive and negative selection. These mice are prone to developing CD4+ T cell mediated autoimmune arthritis that closely resembles rheumatoid arthritis in humans. We found that thymus differentiation was partially restored in SKG Ptpn22-/- thymocytes and Ptpn22 deficiency enhanced TCR mediated signalling in SKG Ptpn22-/- thymocytes relative to SKG thymocytes. Consistent with increased signalling observed in the thymocytes, there was improved in vitro proliferation and IL-2 production of CD4+ T lymphocytes from SKG Ptpn22-/- mice compared to SKG mice. By contrast to SKG mice, SKG Ptpn22-/- mice developed less severe mannan-induced arthritis and showed decreased proportions of Th17 and higher numbers of regulatory T cells. These results show that removal of PTPN22 can compensate, at least partially, for the deficient ZAP-70 activity in the SKG mouse, thus linking PTPN22 and ZAP-70 to the same signalling pathway. This study advances our understanding of how manipulating TCR signals impacts on downstream T cell functions, suggesting PTPN22 may be a valuable target for the treatment of autoimmune diseases. Further studies to determine physiological role of the phosphatase and its disease-associated variants could provide insight into mechanism of immune activation, tolerance and autoimmunity.

Introducción: Giardia intestinalis es el protozoario intestinal más común a nivel mundial y su diagnóstico parasitológico está basado en el examen microscópico, sin embargo, debido al carácter intermitente de la excreción del parásito en las heces el método puede revelar baja sensibilidad, esto ha motivado la búsqueda de nuevas alternativas de diagnóstico entre las que destacan aquellas que tiene como base la biología molecular. Objetivos: Evaluar 3 primeros para la detección molecular de G. intestinalis en muestras fecales. Diseño: Se realizó un estudio observacional, de corte transversal. Lugar: Instituto de Medicina Tropical “Daniel A. Carrión”, UNMSM. Procedimiento: Se evaluaron primers que amplifican las regiones de la beta-giardina y de la proteína de choque térmico 70 del ADN de G. intestinalis. Principales medidas de resultados: Se recolectó muestras fecales positivas y negativas a G. intestinales y a otros parásitos, las cuales fueron concentradas por centrifugación, luego almacenadas a -20°C y posteriormente analizadas mediante la técnica de PCR convencional. Resultados: Se estableció una temperatura de hibridación de 60°C para los primers de la beta-giardina y la proteína de choque térmico 70. La mezcla de reacción se estandarizó con las siguientes condiciones: Cl 2 Mg 1.5 mM, primers 0.6 µM, dNTPmix 0.3 mM y taq polimerasa 0.75 U. El límite de detección de los primeros fue de 87.3 ng/µL para beta-giardina, 359.5 ng/µL para GHSP70-1 y 24.1 ng/µL para GHSP70-2. Conclusiones: Se estableció una temperatura de hibridación y concentración de cloruro de magnesio común para los primers. Se observó un mejor límite de detección para el primer GHSP70-1 identificándose bandas en 7 diluciones con una sensibilidad y especificidad mayor que para el primer de la beta-giardina. / Introducción: Giardia intestinalis is the most common intestinal protozoan worldwide and its parasitologic diagnosis is based in microscopic examination; nonetheless, due to the intermittent parasites excretion in the feces, this method could reveal low sensitivity, this has motivated the search of new diagnostic alternatives such as those based on molecular biology. Goals: To assess 3 primers for the molecular detection of G. intestinalis in stool samples. Design: an observational, cross-sectional study was implemented. Settings: Tropical Medicine Institute “Daniel A. Carrión”, UNMSM. Procedures: We assessed primer that amplifies beta-giardin and heat-shock protein 70 of the G. intestinalis. Main measures of: Positives and negatives stool samples for G. intestinalis and for other parasites were collected and then concentrated by centrifugation and stored at -20°C for further analysis using conventional PCR. Results: A 60°C hybridization temperature was established for the primers of beta-giardin and the heat-shock protein 70. The master mix was standardized with the following conditions: 1.5mM Cl2Mg, 0.6 uM primers, 0.3mM dNTPmix and 0.75U Taq polimerasa. Limit detections were 87.3 ng/µL for beta-giardin, 359.5 ng/µL for GHSP70-1 and 24.1 ng/µL for GHSP70-2. Conclusions: We established a common hibridization temperature and a magnesium chloride common for the primers. A better detection limit was established for the primer GHSP70-1, identifying bands in seven dilutions with sensitivity and specificity higher for the beta-giardine primer. keywords: Giardia intestinalis, PCR, beta-giardina, heat-shock protein 70.

Made available in DSpace on 2014-06-12T17:38:03Z (GMT). No. of bitstreams: 2 arquivo3823_1.pdf: 1925092 bytes, checksum: c28739759fef3b35a51684329d53f339 (MD5) license.txt: 1748 bytes, checksum: 8a4605be74aa9ea9d79846c1fba20a33 (MD5) Previous issue date: 2008 / Petróleo Brasileiro S.A. / As transformações de fase de um aço estrutural foram estudadas a partir do resfriamento contínuo num substrato metálico capaz de simular as transformações microestruturais de diferentes pontos de uma ZTA (Zona Termicamente Afetada). O Material estudado foi o Aço API 5L Grau X-70, muito utilizado em tubulações nas Industriais Petroquímicas pela sua elevada resistência mecânica e baixo peso, constituindo-se num dos chamados aços ARBL (Alta Resistência e Baixa Liga). Neste contexto, o estudo térmico realizado simula as transformações microestruturais no metal de base nos processos de soldagem SMAW (Shield Metal Arc Welding) ou Eletrodo Revestido e GTAW (Gas Tungsten Arc Welding) ou TIG (Tungstem Insert Gas), assumindo por isso uma grande importância para levantamento das propriedades físicas e mecânicas de diferentes pontos da zona termicamente afetada. O Simulador Térmico de Soldas desenvolvido e aqui denominado de Gleeble mostrou-se capaz de reproduzir as diferentes condições termodinâmicas de pontos de uma ZTA, possibilitando o levantamento de curvas do ciclo térmico em função das condições impostas. Para o aquecimento dos corpos de prova foram utilizados dois fornos de resistência elétrica de alta potência para realização de aquecimento rápido e durante o resfriamento dos corpos de prova no Gleeble a temperatura era registrada por meio de termopar com registrador de temperatura digital gerando as curvas de resfriamento em microcomputador. Assim sendo, foram levantadas curvas de resfriamento para corpos de prova resfriados em Gleeble a partir de diferentes temperaturas utilizando-se Software (aplicativo) comercial para aquisição dos dados. Os resultados obtidos no Gleeble foram comparados aos resultados simulados num outro aplicativo comercial (SOLDASOFT) capaz de reproduzir ciclos térmicos e repartições térmicas em função dos parâmetros de soldagem, fornecidos como dados de entrada. Para comparação das microestruturas resultantes do Gleeble foram feitas soldas reais realizadas pelos processos ER (Eletrodo Revestido) e TIG. A caracterização microestrutural foi feita por microscopia ótica

<p>Sammanfattning</p><p>I min undersökning har jag haft som syfte att undersöka läroplan för de frivilliga skolformerna Lpf 94 och där visa på hur ämnet ensemble beskrivits i styrdokumenten mot bakgrund av tidigare forskning. Därtill har jag genom fyra kvalitativa intervjuer undersökt hur de intervjuade lärarna sätter upp mål, tolkar undervisningens syfte och planerar undervisningen i jämförelse med vad som står i läroplanen. Frågeställningarna var: Hur har ensemble beskrivits som aktivitet/ämne i styrdokumentet Lpf 94 mot bakgrund mot traditioner som funnits i tidigare läroplaner? Hur planerar, lägger fokus, sätter upp mål och tolkar lärarna ensembleundervisningens syfte i jämförelse med vad som står i läroplanen? Det som framgår i Lpf 94 är bristen på en tydlig anvisning om hur mycket/lite, ensemble som ska ingå i musikundervisningen vid gymnasieprogrammen. Endast Estetiska programmet inriktning musik beskrivs ensemblelektionernas riktlinjer och innehåll lite tydligare. Decentraliseringen av skolan från statlig styrning till kommunstyrt är en orsak till Lpf 94 otydliga anvisningar i musikundervisningen. Enligt skolverkets undersökning av den kommunala styrningen lämnar de flesta kommuner det mesta av ansvaret till skolan. I en del skolor förekommer otydligt formulerade målbeskrivningar av ämnet. Detta kan innebära att lärare håller fast vid äldre tiders traditionella undervisning och äldre mer styrande läroplaner. Av mina intervjuade arbetade två av musiklärarna på estetiska programmet och de andra två på gymnasiets övriga program. Likheter mellan de intervjuade musiklärarnas i upplägg och planering låg i hur de ville att ensemblespelandet skulle låta, att grupperna fungerande och att låtarna skulle passa gruppen alternativt att gruppen skulle passa till låtarna. Skillnaderna låg i hur lärarna såg på sin egen roll, elevens roll och ämnets roll. Tre av musiklärarna har ett essentialistiskt förhållningssätt och en lärare har ett progressivistiskt synsätt. Lärarna i intervjun anser sig inte ha någon särskild användning av läroplanen, till de är de för grovt skrivna och generella i sitt upplägg. I min undersökning kan jag se att de intervjuade lärarna trots sin egen utsaga om läroplanens oanvändbarhet utgår ifrån innehållet i läroplanen om än tolkat utifrån sina egna mål och syften.</p>

ITC/USA 2014 Conference Proceedings / The Fiftieth Annual International Telemetering Conference and Technical Exhibition / October 20-23, 2014 / Town and Country Resort & Convention Center, San Diego, CA / Accurate reproduction of RF transmissions for test and development has been out of reach for some time. The testing of RF equipment, multipath generation and downstream TM processing systems has been done in the past with varying levels of accuracy. In the past the techniques of checking TM equipment worked, but lacked realism that real TM transmissions provide. This paper describes the development of an IF recorder for range TM. We discuss the usage of a recorder with multiple channels, time correlation, channel skew capability, IF over IP capabilities and file management will allow repeatable, realistic testing of TM systems.

The purpose of this study is to examinehowdemocracy andstudent participation hasbeen developed inthethree curricula for upper secondary school. To find this out, I have used the following questions:•Howare the conceptsof democracy and student participationformulated in the various curricula Lgy70, Lpf94 and Gy11? •What changes with regard to these formulations have been made between the curricula Lgy70, Lpf94 and Gy11?The essay is written so that I have interpreted my empirical material to make a discourse analysis in which I analysethe three curricula of upper secondaryschool with the intention to highlight how the ideal of student participation was supposed to look like. The source material that I use in the essay arethe three curricula;Lgy70 , Lpf94 and Gy11 .Student participationhas had a major role in allthecurricula,but ithas changed in how it was madeand how it would be implemented. Lgy70stresses thatformal and collective participation is important, but there are indications of ashift to a more personal and informal participation forthe students. With Lpf94 and Gy11itcan be seenthat it is precisely this change that has taken place in the curriculum. The students' own responsibility to implement and take controlhas increased.

Sammanfattning I min undersökning har jag haft som syfte att undersöka läroplan för de frivilliga skolformerna Lpf 94 och där visa på hur ämnet ensemble beskrivits i styrdokumenten mot bakgrund av tidigare forskning. Därtill har jag genom fyra kvalitativa intervjuer undersökt hur de intervjuade lärarna sätter upp mål, tolkar undervisningens syfte och planerar undervisningen i jämförelse med vad som står i läroplanen. Frågeställningarna var: Hur har ensemble beskrivits som aktivitet/ämne i styrdokumentet Lpf 94 mot bakgrund mot traditioner som funnits i tidigare läroplaner? Hur planerar, lägger fokus, sätter upp mål och tolkar lärarna ensembleundervisningens syfte i jämförelse med vad som står i läroplanen? Det som framgår i Lpf 94 är bristen på en tydlig anvisning om hur mycket/lite, ensemble som ska ingå i musikundervisningen vid gymnasieprogrammen. Endast Estetiska programmet inriktning musik beskrivs ensemblelektionernas riktlinjer och innehåll lite tydligare. Decentraliseringen av skolan från statlig styrning till kommunstyrt är en orsak till Lpf 94 otydliga anvisningar i musikundervisningen. Enligt skolverkets undersökning av den kommunala styrningen lämnar de flesta kommuner det mesta av ansvaret till skolan. I en del skolor förekommer otydligt formulerade målbeskrivningar av ämnet. Detta kan innebära att lärare håller fast vid äldre tiders traditionella undervisning och äldre mer styrande läroplaner. Av mina intervjuade arbetade två av musiklärarna på estetiska programmet och de andra två på gymnasiets övriga program. Likheter mellan de intervjuade musiklärarnas i upplägg och planering låg i hur de ville att ensemblespelandet skulle låta, att grupperna fungerande och att låtarna skulle passa gruppen alternativt att gruppen skulle passa till låtarna. Skillnaderna låg i hur lärarna såg på sin egen roll, elevens roll och ämnets roll. Tre av musiklärarna har ett essentialistiskt förhållningssätt och en lärare har ett progressivistiskt synsätt. Lärarna i intervjun anser sig inte ha någon särskild användning av läroplanen, till de är de för grovt skrivna och generella i sitt upplägg. I min undersökning kan jag se att de intervjuade lärarna trots sin egen utsaga om läroplanens oanvändbarhet utgår ifrån innehållet i läroplanen om än tolkat utifrån sina egna mål och syften.

Submitted by Amanda Silva (amanda.osilva2@ufpe.br) on 2015-03-11T13:42:17Z No. of bitstreams: 2 TESE Adriana da Silva Andrade Pereira.pdf: 6828087 bytes, checksum: 9d66e9700be0a70e927b955ee06cb850 (MD5) license_rdf: 1232 bytes, checksum: 66e71c371cc565284e70f40736c94386 (MD5) / Made available in DSpace on 2015-03-11T13:42:17Z (GMT). No. of bitstreams: 2 TESE Adriana da Silva Andrade Pereira.pdf: 6828087 bytes, checksum: 9d66e9700be0a70e927b955ee06cb850 (MD5) license_rdf: 1232 bytes, checksum: 66e71c371cc565284e70f40736c94386 (MD5) Previous issue date: 2014-02-17 / CNPq; CAPES / Schistosoma mansoni, é um dos mais importantes parasitas que infectam seres humanos. No nordeste do Brasil, a esquistossomose é historicamente endêmica e considerada como um problema de saúde pública. No estado de Pernambuco, particularmente no litoral e zona da Mata, predomina a cepa São Lourenço da Mata (SLM). Estudos ultraestruturais desta cepa até então ainda não foram realizados, embora análises morfométricas e morfológicas de outras cepas existentes no Brasil já tenham sido publicadas na literatura. Os vermes são bem adaptados ao hospedeiro, tendo a sua longevidade vista como uma conseqüência do eficaz escape do sistema imune. Na circulação sanguínea os vermes devem obter lipídios a partir do hospedeiro, já que eles não sintetizam tais compostos, sendo as lipoproteínas plasmáticas a possível fonte de tais lipídios, além de poderem atuar mascarando o reconhecimento do verme pelo sistema imune. Neste trabalho, microscopia eletrônica de varredura (SEM) foi utilizada para a análise morfológica e morfométrica de cercárias e vermes adultos de S. mansoni cepa SLM, bem como para estudar a interação da lipoproteína de baixa densidade (LDL) com o tegumento do parasito. Também foram usadas diferentes técnicas para a localização e identificação das proteínas envolvidas no processo de absorção e/ou transporte de lipoproteínas no verme adulto de S. mansoni. As cercárias foram obtidas de caramujos Biomphalaria glabrata e os vermes adultos de camundongos machos Mus musculus e Swiss, ambos infectados pela cepa SLM de S. mansoni. Os resultados da SEM mostraram que os corpos da cercárias são cobertos por espinhos, com uma ventosa ventral, uma ventosa oral com receptores sensoriais, e um par de glândulas de penetração na cabeça. Seu comprimento total variou de 174 a 290μm. O comprimento dos vermes adultos machos foi de 4mm e das fêmeas 5mm. O comprimento da região anterior do macho foi de 470μm e 271μm para o sexo feminino. Todos os parâmetros foram realizados em dez amostras. Os valores encontrados na morfometria da cepa SLM foram menores que em outras cepas de S. mansoni já descritas. Através da microscopia eletrônica de transmissão (TEM), os experimentos de imunomarcação mostraram partículas de ouro localizadas dentro do tegumento, na região muscular e espículas dos machos e em torno das células vitelínicas das fêmeas. A utilização de técnicas tais como imunoblotting e “liquid chromatography–mass spectrometry” (LC-MS) proporcionaram a identificação no S. mansoni de duas formas diferentes da chaperona Hsp 70, proteínas envolvidas na interação com a apo-B e o seu transporte para o retículo endoplasmático, sendo responsável também pela ruptura das interações clatrina-clatrina na endocitose humana. Com a descoberta destas proteínas, novos estudos serão necessários para esclarecer o papel funcional das mesmas no S. mansoni.