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  • About
  • The Global ETD Search service is a free service for researchers to find electronic theses and dissertations. This service is provided by the Networked Digital Library of Theses and Dissertations.
    Our metadata is collected from universities around the world. If you manage a university/consortium/country archive and want to be added, details can be found on the NDLTD website.
11

Preparo e avaliação dos complexos de derivados de tiossemicarbazonas com(67/68 Ga) gálio, [99mTc] tecnécio e (111In)índio, como potenciais agentes para detecção de tumores / Preparation and evaluation of the thiosemicarbazone derivative complexes (67/68Ga)gallium, [99mTc]technetium and (111In)Indium as potential agents for tumor detection

Alyne Eloise Lafratta 06 June 2016 (has links)
Nas últimas décadas a medicina nuclear tornou-se uma grande aliada no auxílio ao diagnóstico de doenças e também para o tratamento do câncer. Parte deste sucesso está relacionada à constante pesquisa e desenvolvimento de novos radiofármacos. Uma classe de molécula que vem se mostrando promissora para o tratamento de tumores, tanto na sua forma orgânica quanto na forma de complexos organo-metálicos, é a tiossemicarbazona e seus derivados, os quais também podem formar complexos com radioisótopos metálicos dando origem a radiofármacos para diagnóstico e terapia. Neste trabalho foram preparados complexos com o ligante benzil-5-hidroxi-3-metil-5-fenil-4,5-diidro-1H-pirazol-1-carboditionato (H2bdtc) com os radioisótopos [99mTc]tecnécio, (67/68Ga)gálio e (111In)índio, e foram avaliados a pureza radioquímica, Log P e a estabilidade na presença de L-cisteína, L-histidina, soro albumina humana (SAH) e plasma de sangue humano; também foram avaliadas a taxa de captação dos radiofármacos in vitro em células de melanoma murino B16F10 e TM1M, além da avaliação da captação ex vivo e in vivo utilizando camundongos C57B/6 inoculados com as duas linhagens tumorais. Com o [99mT]tecnécio foram obtidos dois complexos diferentes, dependendo da concentração do PBS na solução, sendo que em um deles foi possível confirmar sua estrutura como [[99mTc]O(bdtc)(Hbdtc)] a partir do complexo de rênio [ReO(bdtc)(Hbdtc)], o outro complexo de [99mTc]tecnécio, bem como de (67/68Ga)gálio e (111In)índio não tiveram a estrutura caracterizada. A eficiência de marcação dos complexos foi superior a 90 %, com Log P maior que 1 para os complexos [[99mTc]O(bdtc)(Hbdtc)], [[99mTc]-bdtc] e [67/68Ga-bdtc] e 0,9 para [111In-bdtc]. Todos os complexos se mostraram com boa estabilidade na presença de L-cisteína e L-histidina, principalmente na primeira hora de incubação, mas não o foram na presença de SAH e plasma. A captação in vitro dos complexos em células B16F10 e TM1M variou entre 0,6 % e 1,8 %, e nos estudos de biodistribuição ex vivo foi obesrvada intensa e persistente captação hepática e no baço, superando 90 %, e captação no tumor variando de 0,2 % a 3 %, enquanto que nas imagens in vivo não foi possível observar de forma uma adequada captação nos tumores a ponto de permitir o uso como agente de diagnóstico. Os resultados permitem concluir que os complexos de derivados tiossemicarbazonas podem formar complexos com diferentes metais, mas novos derivados devem ser preparados para tentar melhorar o desempenho nos sistemas biológicos. Os experimentos com animais foram aprovados pela Comissão de Ética em Pesquisa da Faculdade de Medicina - USP, processo 372/12 / In recent decades, nuclear medicine has been used as diagnostic agent for disease and for the treatment of cancer. Part of this success is related to the constant research and development of new radiopharmaceuticals. Thiosemicarbazone and their derivatives have proven to be promising agent for the treatment of tumors, both in its organic form or as organo-metallic complexes. Also, they can to form complexes with metal radioisotopes giving radiopharmaceuticals for diagnosis and therapy. In this work we prepared complex of benzyl-5-hydroxy-3-methyl-5-phenyl-4,5-dihydro-1H-pyrazol-1-carboditionato (H2bdtc) with radioisotopes [99mTc]technetium (67/68Ga)gallium and (111In)indium and the radiochemical purity, Log P and stability in the presence of L-cysteine, L-histidine, human serum albumin (HSA) and human blood plasma were assessed; also were assessed the in vitro uptake rate of radiopharmaceuticals in murine melanoma cells B16F10 and TM1M, besides the evaluation of ex vivo uptake and in vivo using C57Bl/6 mice inoculated with both tumor lines. With [99mT] technetium two different complexes were obtained, depending on the concentration of the PBS in the solution, and one of them was had its structure to confirm as [[99mTc]O(bdtc)(Hbdtc)] from the standard rhenium complex [ReO(bdtc)(Hbdtc)], the other [99mTc] echnetium complex as well as (67/68Ga)gallium and (111In)indium not have characterized the structure. The labeling efficiency of compleos was higher than 90%, with log P higher than 1 for the complexes [[99mTc]O(bdtc)(Hbdtc)], [[99mTc]-bdtc] and [(67/68Ga)-bdtc] and 0.9 to [111In-bdtc]. All the complexes showed good stability in the presence of L-cysteine and L-histidine, especially in the first hour of incubation, but not in the presence of HSA and plasma. The uptake in vitro complexes in B16F10 and TM1M cells varied between 0.6% and 1.8%, and in ex vivo biodistribution studies was obesrvada intense and persistent liver uptake and spleen, exceeding 90%, and tumor uptake in changing from 0.2% to 3%, while in vivo imaging was not possible to observe a properly uptake in tumors, not allowing to use these molecules as a diagnostic agent. The results indicate that the thiosemicarbazone derivative complex can give complexes with different metals, but new derivatives should be prepared to try to improve performance in biological systems. The animal experimentation was approved by Comissão de Ética em Pesquisa da Faculdade de Medicina - USP, proccess 372/12
12

Development of luminescent ruthenium complexes for in-vitro fluorescence imaging of angiogenesis with the RGD peptide

Victoria, Rosemary 01 May 2012 (has links)
Herein we report the synthesis of an RGD-ruthenium bipyridine [Ru(Bpy)2(BpyRGD)]2+ complex aimed at the detection of angiogenesis. Angiogenesis plays a critical role in many pathophysiological processes, such as tumor growth. The αv-integrins (αv[beta]3, αv[beta]5) are currently used as molecular targeting sites for anti-angiogenic therapies. The [Ru(Bpy)2(BpyRGD)]2+ complex is an organometallic luminescent probe, which enables noninvasive, in vitro imaging of αv[beta]3 expression. Peptides containing the arginine-glycine-aspartic acid (RGD) sequence have been shown to bind strongly to the αvb3 integrin. The RuBpy probes are soluble in water, display long lifetimes, and are photochemically stable. These properties enable the Ru(tris-bpy) complexes to be useful in numerous applications in biophysical and cell biology. The [Ru(Bpy)2(BpyRGD)]2+ complex was synthesized by combining the succinimidyl ester on the RuBpy complex with the lysine of the c(RGDfK) peptide. The results of the one-photon fluorescence bioimaging showed selective binding of the cyclic RGD to αv[beta]3 integrin, which supports previous literature. The high luminescence intensity, long lifetimes, and low cell toxicity levels of dye [Ru(Bpy)2(BpyRGD)]2+, illustrates the potential usage of this probe for future biological applications.
13

Feature selection based segmentation of multi-source images : application to brain tumor segmentation in multi-sequence MRI / Segmentation des images multi-sources basée sur la sélection des attributs : application à la segmentation des tumeurs cérébrales en IRM

Zhang, Nan 12 September 2011 (has links)
Les images multi-spectrales présentent l’avantage de fournir des informations complémentaires permettant de lever des ambigüités. Le défi est cependant comment exploiter ces informations multi-spectrales efficacement. Dans cette thèse, nous nous focalisons sur la fusion des images multi-spectrales en extrayant des attributs les plus pertinents en vue d’obtenir la meilleure segmentation possible avec le moindre coût de calcul possible. La classification par le Support Vector Machine (SVM), combinée avec une méthode de sélection d’attributs, est proposée. Le critère de sélection est défini par la séparabilité des noyaux de classe. S’appuyant sur cette classification SVM, un cadre pour suivre l’évolution est proposé. Il comprend les étapes suivantes : apprentissage des tumeurs cérébrales et sélection des attributs à partir du premier examen IRM (imagerie par résonance magnétique) ; segmentation automatique des tumeurs dans de nouvelles images en utilisant une classification basée sur le SVM multi-noyaux ; affiner le contour des tumeurs par une technique de croissance de région ; effectuer un éventuel apprentissage adaptatif. L’approche proposée a été évaluée sur 13 patients avec 24 examens, y compris 72 séquences IRM et 1728 images. En comparant avec le SVM traditionnel, Fuzzy C-means, le réseau de neurones, et une méthode d’ensemble de niveaux, les résultats de segmentation et l’analyse quantitative de ces résultats démontrent l’efficacité de l’approche proposée. / Multi-spectral images have the advantage of providing complementary information to resolve some ambiguities. But, the challenge is how to make use of the multi-spectral images effectively. In this thesis, our study focuses on the fusion of multi-spectral images by extracting the most useful features to obtain the best segmentation with the least cost in time. The Support Vector Machine (SVM) classification integrated with a selection of the features in a kernel space is proposed. The selection criterion is defined by the kernel class separability. Based on this SVM classification, a framework to follow up brain tumor evolution is proposed, which consists of the following steps: to learn the brain tumors and select the features from the first magnetic resonance imaging (MRI) examination of the patients; to automatically segment the tumor in new data using a multi-kernel SVM based classification; to refine the tumor contour by a region growing technique; and to possibly carry out an adaptive training. The proposed system was tested on 13 patients with 24 examinations, including 72 MRI sequences and 1728 images. Compared with the manual traces of the doctors as the ground truth, the average classification accuracy reaches 98.9%. The system utilizes several novel feature selection methods to test the integration of feature selection and SVM classifiers. Also compared with the traditional SVM, Fuzzy C-means, the neural network and an improved level set method, the segmentation results and quantitative data analysis demonstrate the effectiveness of our proposed system.
14

Investigating the Application and Sustained Effects of Stochastic Resonance on Haptic Feedback Sensitivity in a Laparoscopic Task

Wilcox, Kara Liane 08 June 2023 (has links)
No description available.
15

PhD Dissertation-Chemistry-Aayush-2023

Aayush Aayush (15354604) 26 April 2023 (has links)
<p> </p> <p>Learning about ‘behavior’ has always been at the heart of my research endeavors. While my undergraduate work in evolution and ecology exposed me to the science behind why a behavior exists, in my graduate work, I intended to explore how to use something’s behavior to widen its applicability. In this thesis, <em>I will present three works that utilize some of the fundamental</em></p> <p><em>behaviors (i.e., properties) of elastin-like polypeptides (ELP) to improve existing protein purification methods or explore their applicability in bladder cancer imaging and immunotherapy. </em></p> <p>Bladder cancer has high recurrence rates (60-70 % annually) that necessitate multiple follow-up therapies making it one of the costliest cancers per patient. In this work, we have attempted to address two leading causes of the recurrence. First is a low sensitivity (62-84 %) and variable specificity (43-95 %) of white light cystoscopy used to diagnose and remove tumors. We aimed to address the heart of this problem, i.e., the non-specific mode of detection using white light. Only the trained eyes can discern abnormal from normal-appearing tissues even then, leaving up to 45% of tumors unresected to colonize and spread. <em>We developed and characterized near infrared dye-peptide-ligand conjugates (NIR-ELP-ligand) that undergo receptor-mediated binding and internalization to human bladder cancer cells in vitro and tissues ex vivo.</em> By using a molecular target-based probe in combination with NIR imaging, we can aid in improving the detection limit via selective binding to the tumor and reduction in background autofluorescence.</p> <p>Bacillus-Calmette Guérin (BCG) instillation in the bladder is the gold-standard</p> <p>immunotherapy used after surgical removal of bladder tumors. This was approved as a response to the inefficiency of surgery alone in improving cancer status. It has succeeded by reducing the recurrence rate to 30-50 %. But it comes with the complications of putting a live mycobacterium</p> <p>in the human body and giving a patient a urinary tract infection right after surgical tumor resection. <em>Thus, we aimed to deliver nucleic acid as immunotherapeutic cargo in a selective manner to elicit robust anti-tumor immune responses while minimizing the side effects due to its carrier.</em> Towards</p> <p>this goal, we have developed a highly modular and adaptable ELP-ligand fusion protein-based nucleic acid delivery carrier targeted toward bladder cancer. Before developing targeted peptide-based cancer imaging and nucleic acid delivery modalities, we addressed the Achilles heel of peptide-based approaches. The peptide and protein industry suffers</p> <p>through complex, time-consuming, inconsistent, and low-yielding purification methods. <em>We have developed a scalable, facile, and reproducible protein purification method that delivers ELP and ELP fusion proteins free of host cell proteins and nucleic acids and has low lipopolysaccharide</em></p> <p><em>content in just 3 h starting from a bacterial pellet. </em>Thus, for a coherent narrative, the thesis is structured as follows:</p> <p>1. Introduction</p> <p>2. ELP as a protein purification tag: Development of a rapid purification method for ELPs and ELP fusion proteins.</p> <p>3. ELP as a cancer imaging agent: Development of NIR-ELP-Ligand imaging probe targeting bladder cancer.</p> <p>4. ELP as a drug delivery agent: Utilizing ELP-ligand fusion protein in the formulation of targeted nucleic acid delivery carrier to bladder cancer.</p>

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