Despite the global effort to discover and improve ways to detect, treat, and monitor cancer, it still remains the second leading cause of death in the United States and poses a major health and economic burden worldwide. While traditional treatments like surgery, chemotherapy, radiation therapy, and hormone therapy have been successful and have decreased cancer mortality, cancer incidence in all sites continues to rise. Consequently, there is an immediate need to find new therapeutics for the treatment of cancer. In recent years, and with the continuing push towards personalized medicine, cancer biomarkers have become crucial to detect, treat, and monitor cancer. Thymidine kinase 1 (TK1) has been identified as a cancer biomarker with diagnostic, prognostic, and therapeutic potential. TK1 is a nucleotide salvage pathway enzyme responsible for maintaining a balance in the cell nucleotide pool and providing the cell with thymidine monophosphate, which upon further phosphorylation is incorporated into DNA during cell replication. TK1 has been found to be upregulated in the serum of cancer patients. Serum TK1 (sTK1) has been used as an early diagnostic and prognostic biomarker in many types of cancer and has been shown to be a better proliferation biomarker than Ki67. In this dissertation, we described the characterization of TK1 as a cancer biomarker that associates with the plasma membrane of hematological malignancies such as Burkitt's lymphoma, acute lymphoblastic leukemia, acute promyelocytic leukemia, acute T cell lymphoma, and solid malignancies such as lung, breast, and colon cancer. We also describe the different oligomeric TK1 forms that are found on the cell membrane and show that membrane TK1 has activity. We assess the clinical relevance of TK1 in all these malignancies, looking at tissue expression as well as gene expression from patients from The Cancer Genome Atlas database. We find that TK1 is not expressed on the surface of normal cells, whether they are proliferating or not, making TK1 a unique cancer biomarker, with the potential to be used in targeted therapy. We also find that TK1 expressed on the surface may be involved in the invasion potential of cancer cells. The knowledge gained from this study will help researchers working in clinical research and cancer immunotherapeutics to potentially use TK1 as a biomarker and cancer target, and thus providing another weapon against cancer. In this dissertation, we described the characterization of TK1 as a cancer biomarker that associates with the plasma membrane of hematological malignancies such as Burkitt's lymphoma, acute lymphoblastic leukemia, acute promyelocytic leukemia, acute T cell lymphoma, and solid malignancies such as lung, breast, and colon cancer. We also describe the different oligomeric TK1 forms that are found on the cell membrane and show that membrane TK1 has activity. We assess the clinical relevance of TK1 in all these malignancies, looking at tissue expression as well as gene expression from patients from The Cancer Genome Atlas database. We find that TK1 is not expressed on the surface of normal cells, whether they are proliferating or not, making TK1 a unique cancer biomarker, with the potential to be used in targeted therapy. We also find that TK1 expressed on the surface may be involved in the invasion potential of cancer cells. The knowledge gained from this study will help researchers working in clinical research and cancer immunotherapeutics to potentially use TK1 as a biomarker and cancer target, and thus providing another weapon against cancer.

Introduction: Immunochemical methods have significant importance in biomedical research. The benefit of immunochemical methods is their high sensitivity and accuracy. The aim of the work was to use immunochemical methods in investigation of cancer biomarkers and degenerative diseases. A total of four studies were performed. Two studies were focused on the search for new biomarkers of prostate cancer, the third study was focused on evaluation of FGF23 in patients with hyperparathyroidism, and the fourth study looked at the assessment of hyaluronic acid in synovial fluid of patients with knee gonarthrosis. Methods and patients: Study 1: Concentrations of Chromogranin A, Endoglin, TIMP-1 and thymidine kinase 1 (TK1) in serum and Endoglin, SPINK-1, Annexin, TIMP-1 in urine were measured in 58 patients with the (mean age 68 years, range 45 - 82 years) with clinically diagnosed prostate cancer and in 30 healthy individuals with the (mean age 64 years, range: 55 - 78 years) without clinically relevant urological history and PSA values in the reference range. Subsequently, serum TK1 levels were measured in 169 patients (mean age 62 years, range 45- 82 years) with prostate cancer and in a control group of 39 healthy men (mean age 61 years, range 54-78 years). The TK1 assay was also used to determine the...

A agricultura de precisão tem agregado alto valor para os agricultores por causa das tecnologias que estão ligadas a ela. Sistemas que extraem informações de imagens digitais são extremamente utilizados para que o agricultor tome decisões a fim de aumentar sua produtividade. Uma das técnicas de realizar o monitoramento é a construção de um mosaico de imagens aéreas, onde são utilizadas aeronaves voando em baixa altitude. Esta técnica pode levar dezenas de horas para ser concluída, dependendo da configuração do computador que a executa. Com o intuito de reduzir o tempo nessa construção e tornar possível o embarque a essa aplicação, este trabalho apresenta uma maneira simplificada de construir o mosaico de imagens aéreas baseada na técnica de georreferenciamento direto, no qual utiliza a computação heterogênea para acelerar o desempenho. Essa abordagem é composta por apenas três técnicas que também compõem a abordagem clássica para a construção de mosaicos (warping, extração de características e combinação de características), além de inserir em seus cálculos os dados fornecidos pelos sensores GPS e IMU com a finalidade de direcionar e posicionar cada imagem pertencente ao conjunto que formará o mosaico. A plataforma de computação heterogênea utilizada neste trabalho é a NVIDIA Jetson TK1 escolhida pelo fato de disponibilizar de uma GPU que suporta a linguagem de programação CUDA. Utilizando esta abordagem, a falta de correção da perspectiva do conteúdo (geometria) da imagem gera um resultado inesperado, pois os dados fornecidos pela IMU, ao contrário do que se imagina, apenas servem para corrigir a posição das coordenadas do GPS registradas no momento de captura de cada imagem que compõem o mosaico. O tempo de execução da aplicação desenvolvida é satisfatório tornando possível a adoção desta abordagem. / Accuracy agriculture has added value to farmers thanks to the new technologies that are linked to it. Systems that extract information from digital images are very usefull to help farmers making decisions in order to increase their productivity. One of the techniques to perform this kind of monitoring is the construction of an aerial imagery mosaic where aircrafts flies in low altitude. This technique may take hours to be completed, depending on computer\'s configuration. With the purpose of reducing time in this construction, this thesis presents a simplified way to make aerial imagery mosaic based on direct georeferencing. This approach is composed by three techniques that also make up the classic approach to building mosaics (warping, extraction of characteristics and combination of characteristics), the difference is with this technique here presented is also possible to insert into the calculations the data provided by the GPS and IMU sensors with the purpose of directing and positioning each image to the belonging set to form the mosaic. The heterogeneous computing platform used in this work is the NVIDIA JetsonTK1, this platform was chosen because it offers a GPU that supports the language of CUDA programming. If the images\' geometry errors weren\'t rectfyed, using this approach, an unexpected result happens, because the data provided by IMU, contrary to what is imagined, only serve to correct the position of the GPS coordinates recorded at the moment of capture of each image that composes the mosaic. The developing time in this application is satisfactory making the adoption of this approch favorable.