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Thumshirn, Georgette. "Multivalente zyklische RGD-Peptide und RGD-Mimetika für den Einsatz in Tumordiagnostik und Tumortherapie." [S.l.] : [s.n.], 2003. http://deposit.ddb.de/cgi-bin/dokserv?idn=96988950X.
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Engrand, Philippe. "Calix[4]arènes fonctionnels pour ancrage sur polymère naturel et antennisation par le tripeptide RGD préparé par synthèse convergente." Thesis, Nancy 1, 2008. http://www.theses.fr/2008NAN10143/document.
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Ce travail porte sur la valorisation du calix[4]arène comme complexant de métaux de transition, immobilisé sur un matériau, et comme vecteur de principe actifs, aptes à interagir avec des récepteurs cellulaires. En premier lieu, la monofonctionnalisation sélective d’un calix[4]arène, sur sa partie haute ou sur sa partie basse est réalisée. Les fonctions nitro, amine, adéhyde, et alcène ont été incorporées sur la partie basse, via un bras espaceur, et un bras acide a été incorporé sur la partie haute. Ces calix[4]arènes monofonctionnalisés se déclinent en trois séries de composés, dépendant du degré et de la nature des substituants sur la partie basse : tétrol, triméthoxy et trisbipyridyle. Le second objectif est le greffage d’un calix[4]arène pourvu d’une fonction amine, sur un polymère naturel, cellulose ou dextran. Un mode opératoire reproductible a été mis au point, qui a permis d’obtenir un calix[4]arène complexant de l’ion Cu(I), immobilisé sur cellulose en poudre ou sur dextran. L'évaluation du taux de greffage par RMN et dosage UV-Vis en présence de Cu+ est décrite pour les dextrans. Enfin, nous avons incorporé sur la partie haute du calix[4]arène d'antennes de reconnaissance cellulaire de type RGD, préparées par synthèse convergente en solution. Une chimiothèque de tripeptides RGD, modulés sur les parties C- et N-terminales, a été obtenue avec de bons rendements. Ces peptides ont fait l’objet d’une évaluation biologique (adhésion cellulaire). Nous avons ainsi préparé des calix[4]arènes, de conformation conique, antennisés par le dipeptide GD et le tripeptide RGD, destinés à élaborer des modèles de vecteurs supramoléculaire de principes actifsThe aim of this present work is dedicated to the valorization of calix[4]arene as a transition-metal complexing agent, grafted on a polymeric material, and as a drug carrier, displaying a cell recognition peptidic sequence. We describe selective monofunctionalization of a calix[4]arene, at the upper rim or at the lower rim. Nitro, amino, aldehyde and alcene functions were incorporated on the calix[4]arene lower rim, via a spacer. In the same way, an acid arm was also incorporated on the calix[4]arne upper rim. We made those monofunctionalized calix[4]arenes available into three series, depending on the number and the nature of substituent on the three residual OH groups of the calix[4]arne carried function : tetrol, trimethoxy and trisbipyridyl. The second goal is dedicated to the grafting of an amino-fonctionalized calix[4]arene, on a natural polymer, such as cellulose or dextran. We have developped a method allowing to access to a new polymeric complexing agent. We also describe the grafting-ratio, calculated by NMR, UV-Vis and titration with Cu+. The third goal is dedicated to the grafting of the cell-recognizing RGD sequence, prepared in solution by a gram-scale convergent synthesis. A RGD analogue library, functionalized by variable groups on the C- and N- terminations, were obtained with interestly yields. Those peptides were involved into a biological evaluation (cellular adhesion). Thus, cone-conformed calix[4]arene incorporating the GD or RGD peptide sequence were elaborated as preliminary models for the access to new drug-carrier molecular devices
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Lee, Ted. "Triggerable ligand presentation using caged-RGD." Diss., Georgia Institute of Technology, 2013. http://hdl.handle.net/1853/52943.
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Cells rely on time-dependent binding and activation by the ECM to initiate downstream signal transduction. It is unknown whether adhesion to a ligand is required throughout various cell processes, or only during a specified time period ("temporal threshold”). Current approaches to ligand presentation often comprise of static, constant densities of ligands. In contrast, natural cell adhesive interactions with ECMs exhibit spatiotemporal patterns of binding and activation. Therefore, a key to future research in controlling cell-material interactions will be the development of materials that can respond to external stimuli.
The objective of this project is to engineer biomaterials that present a UV-labile caged-Arginine-Glycine-Aspartic Acid (RGD) ligand and evaluate the effects on cell activities. RGD is the minimal adhesive sequence of fibronectin. By dynamically modulating adhesive ligand presentation, the effects of temporal control on cell processes can be elucidated. In this caged-peptide, a photo-labile group adjacent to the aspartic acid residue of RGD effectively “masks” a cyclo(RGDfk) peptide. Upon UV irradiation (360 nm), the caging group is released thereby restoring the adhesive activity of the peptide.
By having unparalleled spatiotemporal control of RGD ligand presentation, we demonstrated two novel tools for discovery: 1) in vivo ligand presentation to probe downstream tissue behavior and cell infiltration to biomaterial implants, and 2) in vitro ligand presentation in situ using confocal-based live cell microscopy to investigate real-time vinculin recruitment and cell traction force generation. These studies represented the first demonstration of triggerable adhesive ligand presentation in vivo and demonstrated the utility of caged-compounds for probing specific receptor-ligand responses on highly defined PEG-based hydrogels. Triggerable in vitro ligand presentation, combined with traction force microscopy, demonstrated a new research tool for investigating focal adhesion formation and downstream force generation. Taken in whole, these results provide previously unknown insights into the importance of spatiotemporal control of adhesive ligands and created novel new research platforms for future discovery.
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McDonagh, Birgitte Hjelmeland. "Optimalised Carbodiimide Chemistry for RGD-coupled Alginate." Thesis, Norges teknisk-naturvitenskapelige universitet, Institutt for bioteknologi, 2012. http://urn.kb.se/resolve?urn=urn:nbn:no:ntnu:diva-16807.
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Alginate is a naturally ocurring polyanion of (1→4)linked β-d-mannuronic acid (M)and its C-5 epimer α-l guluronic acid (G). The polyanion, and particularly longstretches of guluronic acids, chelates and form hydrogels in the presence of divalentcations such as Ca2+ . Chelation occur at physiological conditions and the formed hy-drogels are biocompatible and stable. These properties nominates alginate hydrogelsas promising biomaterials in tissue engineering applications. Encapsulation of cells inalginate beads is easily prepared by mixing cells with high molecular weight alginate,and dripping the solution into a CaCl2 solution. When alginate comes into contactwith Ca2+ ions, alginate beads are immediately formed and the cells are captured ina three dimensional alginate matrix. Once inside the alginate capsule, the cells canbe transplanted into a host deficient in the particular cells. The alginate protectsthe cells against the immune system of the host, opening for allograf transplantationwithout immunosuppressiva. The pores in the alginate network are big enough toenable diffusion of waste and nutrition through the membrane, which is importantfor cell survival.Alginate is in itself not cell adhesive. However, alginate can be tailored into a celladhesive biomaterial by attachement of cell adhesive peptides, such as the RGDmotif found in extracellular matrix molecules such as fibronectin. Coupling of celladhesive peptides increase cell survival in three dimensional alginate matrices. Inthis study, RGD-alginate is tailored with a chemoenzymatic approach that ensuresRGD-coupling to non-gelling residues. This procedure starts with non-gelling man-nuronan that is chemically modified by attachement of the cell adhesive peptideGRGDYP by carbodiimide chemistry. Gelling residues are introduced to peptidecoupled mannuronan by a two step epimerisation catalyzed by the epimerases AlgE4and AlgE6.In this study, the carbodiimide chemsitry used for coupling GRGDYP to mannuro-nan is optimalised to create alginate with more than 0.2% bound peptide. Themodel molecules fluoresceinamine, 4-aminophenol and L-tyrosine-methyl ester areused for optimalisation, and the latter model molecule was found to give the bestrepresentation of peptide coupling to mannuronan. The carbodiimide mediated cou-pling to mannuronan is investigated by varying the pH, temperature and reactantconcentrations. The degrees of coupling for each intervention is assessed by 1 H NMRand UV/vis spectroscopy. The presence of covalently bound by-products, namedN-acylurea adducts, to mannuronan is assessed by 1 H NMR spectroscopy and acontrolled reduction of these unwanted compounds is attempted. The results from the optimalisation indicates that coupling of Me-O-Tyr and GRGDYP to mannuro-nan is concentration-dependent, as an increase in coupling was observed when theGRGDYP and Me-O-Tyr concentrations was increased. The highest peptide incor-poration described in this study was 3.4% GRGDYP coupled to mannuronan, whichis higher compared to similar studies.The optimalised carbodiimide chemistry is applied to a large scale batch of RGD-coupled alginate that is to be used for cell encapsulation of olfactory ensheating cellsfrom neonatal rat brain.High molecular weight alginate was coupled with 0.45% GRGDYP and filtratedwith active coal before cell encapsulation. The coal filtration removed a substantialamount of the unwanted N-acylurea adducts but also removed peptides, resultingin a GRGDYP coupling of 0.1% calculated from UV/vis spectroscopy, and 0.4%calculated from 1 H NMR spectroscopy. This indicates that peptides are associatedwith N-acylurea adducts and that active coal filtration is necessary to remove them.Encapsulation of olfactory ensheating cells to RGD-coupled alginate gave no mor-phology changes or enhanced cell viability compared to non-peptide coupled alginate.It is believed that the low enzymatic action of the AlgE6 epimerase, a low concen-tration of peptides or a combination of both, have influenced the cell viability andlack of morphology changes. Enhanced peptide incorporation can be achieved byincreasing the reactant concentrations of the peptides, but this would lead to a moreexpensive procedure. Increased efficacy, meaning a higher peptide coupling withlower adduct formation, at lower peptide concentrations was not achieved. However,the use of sodium borohydride in combination with periodate oxidised alginates forpeptide coupling should be assessed as a novel approach for increased peptide yieldsat lower peptide concentrations.
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Halie, Delphine. "Synthèse diastéréosélective de mimes du peptide RGD." Paris 5, 2006. http://www.theses.fr/2006PA05P639.
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Cressman, Sonya. "RGD-containing ligands for targeting liposomal nanoparticles." Thesis, University of British Columbia, 2007. http://hdl.handle.net/2429/31279.
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The use of a targeting ligand to enhance the delivery of liposomal nanoparticles (LNs) to specific cells in diseased tissue is an attractive strategy that has progressed very slowly since the idea originated over 25 years ago. The slow progress can be attributed, in part, to the difficulties involved in producing well-defined targeted LN systems. This work concerns the development of peptide-based ligands for targeting LNs to cells that overexpress the α[sub v]β₃ integrin, which is considered a unique marker of the tumor-associated endothelium. Initial work focused on using Fab' fragments of monoclonal antibodies as targeting ligands and employing literature techniques for coupling these proteins to lipids that can then be inserted in preformed LNs. However, it was found that the coupling procedures resulted in low yields of poorly defined lipid-ligand conjugates that were difficult to quantitate when incorporated into LN. Attention was then given to the development of a peptide-targeting agent that could be incorporated into an LN at the time that the LN is made. The RGD-containing cyclic peptide, eRGDfK, was employed as the targeting ligand. In order to characterize its binding to the α[sub v]β₃ integrin, a fluorescently labeled analogue, cRGDfK-488, was synthesized and capillary electrophoresis was employed for analysis. This procedure proved advantageous for studying receptor ligand interactions, since it allowed for the binding to be characterized in solution without the need for covalent modification of receptor or ligand. A 2:1 RGD ligand to integrin specific binding stoichiometry was revealed with the second binding event having a similar affinity as the first binding event. The next phase of these studies investigated the ability of cRGDfK-488 to bind to integrins on human umbilical vascular endothelial cells (HUVEC) and subsequently undergo endocytosis. This was compared to the binding and uptake properties of a fluorescently labeled monoclonal antibody, LM609X, which specifically binds α[sub v]β₃ integrin. Using flow cytometry and fluorescence microscopy, it is shown that the RGD ligand exhibited considerably greater uptake following incubation at endocytosis permitting temperatures (37°C) as compared to endocytosis inhibiting temperatures (4°C). A 7.4-fold increase in uptake of the RGD-lipid was observed following a one-hour incubation with HUVEC at 37°C, as compared to 4°C. In contrast, only a 1.9 fold increase in cell-associated fluorescence was observed on incubation with LM609X at 37°C as compared to 4°C. It is suggested that this ability of RGD ligands to stimulate endocytosis may be of utility for achieving enhanced intracellular delivery of ligand-associated drugs in anti-angiogenic applications. The cyclic peptide was then used to construct a fluorescently labeled RGD-spacer-lipid construct of defined molecular weight that could be incorporated into LN at the time of manufacture. It is shown that the resulting RGD-LNs bind to HUVEC with increasing avidity as the amount of RGD-spacer-lipid incorporated is increased. Further, these RGD-LNs are straightforward to make and can load and retain anti-cancer drugs such as doxorubicin. It is shown that RGD-LNs loaded with doxorubicin and incubated with HUVEC selectively deliver the drug to the cytosol while non-targeted LNs are not internalized by the cell, suggesting potential utility as targeted drug delivery systems in vivo.Medicine, Faculty of
Biochemistry and Molecular Biology, Department of
Graduate
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Zairi, Amel. "Elaboration et Caractérisation de revêtements à base de nitrure de chrome par pulvérisation cathodique magnétron en condition réactive : Propriétés mécaniques et tribologiques." Phd thesis, Ecole nationale supérieure d'arts et métiers - ENSAM, 2013. http://pastel.archives-ouvertes.fr/pastel-00996656.
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Élaborer et optimiser des nouveaux matériaux restent toujours parmi les enjeux liés à l'amélioration de la performance de la durabilité des matériaux.Le domaine des traitements de surface et plus particulièrement les nanotechnologies utilisées pour produire des revêtements en couches minces plus précisément les dépôts physiques en phase vapeur (PVD), permet de synthétiser des nouveaux matériaux qui peuvent résister dans des conditions sévères de diverses applications.L'industrie des outils de coupe et plus précisément le bois dans notre cas, nécessitent de plus en plus la synthèse des nouveaux matériaux et nanomatériaux pour améliorer la tenue en service des outils de coupe.L'objectif de ce présent travail est de développer et caractériser des revêtements dont le matériau de base est le chrome et/ou le silicium en vue de les optimiser. L'élaboration a été réalisée par différentes méthodes à savoir la pulvérisation cathodique magnétron radio fréquence ou encore en mode courant direct. En outre, la RGPP (reactive gas pulsing process) a été exploité pour la première fois dans ce travail dont le but est de surmonter les difficultés rencontrées avec la pulvérisation réactive.Les différentes caractéristiques mécaniques et tribologiques des couches ont été étudiées et corrélées avec les caractéristiques physicochimiques et microstructurales.Il s'avère que la pulvérisation cathodique en mode courant direct prouve son importance par l'obtention des couches de meilleure qualité que celles obtenues en mode radio fréquence. Pour des contenus d'azote similaires on obtient des propriétés mécaniques et tribologiques plus importantes. On note que les propriétés mécaniques réalisent un gain de 60 % par rapport à celles obtenues en mode RF. En outre l'ajustement des paramètres de la méthode RGPP (le rapport cyclique et la période des pulses) influe considérablement les caractéristiques des couches obtenues et on montre une amélioration de la performance des couches. A l'issue de l'injection pulsée du gaz réactif, on montre que l'alternance entre l'ouverture et la coupure de la vanne du gaz réactif est indispensable pour la déposition dans un milieu réactif afin d'éliminer les composés métalliques sur les cibles obtenus lors de dépôt.Enfin, l'ajout de silicium au CrN mène à obtenir des solutions solides ou une structure nanocomposite selon la teneur de silicium dans la couche ce qui implique une amélioration des caractéristiques mécaniques et par la suite celles tribologiques.L'apport de ce travail de thèse est de présenter une étude globale sur la performance des couches CrN et CrSiN en corrélant ses caractéristiques mécaniques et tribologiques avec les paramètres physiques de dépôt et en adoptant plusieurs méthodes d'élaboration.
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Gibson, Christoph. "Kombinatorische Festphasensynthese und biologische Evaluation niedermolekularer RGD-Mimetika." [S.l.] : [s.n.], 2000. http://deposit.ddb.de/cgi-bin/dokserv?idn=959981314.
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Moncelet, Damien. "Propriétés d'agent de ciblage et de molécules cytotoxiques pour l'IRM et la thérapie de gliomes." Thesis, Bordeaux, 2014. http://www.theses.fr/2014BORD0166/document.
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L'objectif de cette thèse concerne la possibilité d'améliorer le diagnostic et la thérapie des gliomes par le ciblage des intégrines à l’aide du RGD et par le développement d'agents multimodaux de type alcoxyamine. L’étude de l’internalisation du RGD révèle une régulation par la densité cellulaire, paramètre histologique dans la catégorisation des gliomes. Dans notre modèle, la densité cellulaire impacte la contribution de l’endocytose clathrine-dépendante et le métabolisme mais n’influence pas le rôle du cytosquelette. La régulation de l’internalisation des peptides RGD par la densité cellulaire reste à mieux comprendre afin de perfectionner les agents utilisant ce ciblage pour l’imagerie et le diagnostic des gliomes. Dans le même temps, les propriétés multimodales des alcoxyamines ont été évaluées àdes fins théranostiques. Ces molécules s’homolysent spontanément pour libérer un nitroxyde et un radical alkylant cytotoxique pouvant en plus induire une réactivation immunitaire antitumorale. Le nitroxyde est un agent de contraste pour l’IRM rehaussée par effet Overhauser. Le fort rehaussement du signal observé à proximité du nitroxyde assure un suivi en temps réel de l’apparition de l’agent alkylant. L’adaptation des alcoxyamines pour une homolyse conditionnelle dans le gliome permettrait une action thérapeutique avec un contrôle spatial et un suivi temporel du composé cytotoxique. L’acheminement de molécules d’intérêt vers la cible est rendu difficile par la présence de barrières physiologiques. Dans ce travail, la progression de nanoparticules par la voie intratrachéale peut se substituer à celle intraveineuse avec une augmentation du temps de rétention dans le gliomeThe aim of this thesis is to improve the diagnostic and the therapy of glioma through both the integrin targeting by RGD and the development of Alkoxyamine as multimodal agent. The RGD internalization is regulated by the cellular density, a histologic parameterfor the glioma classification. In our model, the cellular density increases the contribution of both the clathrin-mediated endocytosis and the metabolism but not the one of the cytoskeletal. A better knowledge about the RGD internalization regulation by the cell density could help the MRI probe development for glioma diagnosis. Properties of alkoxyamine as multimodal agent were evaluated to perform theranostic. The spontaneous alkoxyamine homolysis give a nitroxide radical and a cytotoxic alkylating agent that could induce immune reactivation against the tumor. This nitroxide is an Overhauser enhanced MRI contrast agent. The strong signal enhancement in the nitroxide vicinity gives information in real-time about the release of the alkyl radical. Alkoxyamine adaptation for a conditional homolysis through specific glioma proteolysis activity could induce a localized alkyl therapeutic effect with a real-time monitoring. Physiological barriers limit the drug accumulation in the targeted sites. In this study, the intratracheal instillation of nanoparticles can substitute the intravenous administrationincreasing their intratumoral retention time
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Lu, Xinjie. "Structure and function studies of the RGD protein dendroaspin." Thesis, Imperial College London, 1996. http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.309313.
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Tai, By Lik Ren. "Synthesis of functional materials containing the RGD peptide sequence." Thesis, University of Leeds, 2009. http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.507877.
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Lee, Jowan. "A comparison of four tests of temporal resolution AFTR, RGDT, BFT and GIN /." Online access for everyone, 2004. http://www.dissertations.wsu.edu/Thesis/Summer2004/j%5Flee%5F060304.pdf.
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Cesana, Sonia. "Functionalization of poly(2-oxazoline)s with cyclic RGD peptides." [S.l. : s.n.], 2004. http://deposit.ddb.de/cgi-bin/dokserv?idn=974209643.
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Roberts, Jemma Natasha. "Enzyme-responsive RGD-functionalised substrates to influence mesenchymal stem cells." Thesis, University of Glasgow, 2013. http://theses.gla.ac.uk/4816/.
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Regenerative medicine is a rapidly expanding field of science with an exhaustive volume of literature published on the different strategies used to repair diseased or injured tissue. Recently, stem cells have emerged as a promising candidate in this regard owing to their involvement in embryogenesis, homeostatic turnover and normal tissue repair. Despite this potential, stem cell-based therapies have yet to be fully established in a clinical setting owing to complications associated with their limited numbers, immunogenicity, tumour formation and the ethical considerations surrounding their usage. Furthermore, the mechanisms underlying stem cell differentiation are complex and not fully understood, thus expanding stem cell numbers and predictably directing their commitment toward a desired lineage, represent a major challenge for tissue regeneration strategies. In an attempt to circumvent these problems there is currently a rising interest in biomimetic materials that aim to reproduce the physical architecture, chemical composition and plasticity of the in vivo extracellular environment in an in vitro setting. Furthermore, the need to expand stem cells while maintaining the stem cell phenotype has prompted many to look to the stem cell niche for answers. At the centre of most cellular responses to the physical cues embedded within the ECM are integrins. Integrins are mechanosensitive membrane spanning receptors that link the ECM to the cytoskeleton and thus transmit information from outside the cell into the nucleus, affecting gene transcription via a series of intracellular signalling cascades. To that end, many biomimetic systems incorporate integrin- binding ligands such as the tripeptide RGD. In this work glass surfaces functionalised with RGD were used to study changes in mesenchymal stem cell (MSC) responses to increased integrin binding by using an enzymatic ‘switch’ to reveal surface-bound RGD peptides that have been masked by a large chemical cap (Fmoc). The results of this work demonstrated that RGD- functionalised substrates can support MSC growth and influence them to commit to a particular fate. MSCs on surfaces where integrin-ligand binding was blocked developed a fibroblast-like phenotype whereas MSC grown on surfaces that were later enzymatically digested to reveal the underlying RGD ligands developed an osteoblast phenotype similar to RGD controls.
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Saraf, Poonam S. "RGD based peptide amphiphiles as drug carriers for cancer targeting." Scholarly Commons, 2014. https://scholarlycommons.pacific.edu/uop_etds/137.
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Specific interactions of ligands with receptors is one of the approaches for active targeting of anticancer drugs to cancer cells. Over expression of integrin receptors is a physiological manifestation in several cancers and is associated with cancer progression and metastasis, which makes it an attractive target for cancer chemotherapy. The peptide sequence for this integrin recognition is the Arg-Gly-Asp (RGD). Self-assembly offers a unique way of presenting ligands to target receptors for recognition and binding. This study focuses on development of integrin specific peptide amphiphile self-assemblies as carriers for targeted delivery of paclitaxel to α v β 3 integrin overexpressing cancers. Amphiphiles composed of conjugates of different analogs of RGD (linear, cyclic or glycosylated) and aliphatic fatty acid with or without 8-amino-3,6-dioxaoctanoic acid (ADA) as linker were synthesized and characterized. The amphiphiles exhibited Critical Micellar Concentration in the range of 7-30 μM. Transmission electron microscopy images revealed the formation of spherical micelles in the size range of 10-40 nm. Forster Resonance Energy Transfer studies revealed entrapment of hydrophobic dyes within a tight micellar core and provided information regarding the cargo exchange within micelles. The RGD micelles exhibited competitive binding with 55% displacement of a bound fluorescent probe by the cyclic RGD micelles. The internalization of fluorescein isothiocynate (FITC) loaded RGD micelles was significantly higher in A2058 melanoma cells compared to free FITC within 20 minutes of incubation at 37°C. The same micelles showed significantly lower internalization at 4°C and on pretreatment with 0.45M sucrose confirming endocytotic uptake of the RGD micellar carriers. The IC50 of paclitaxel in A2058 melanoma cells was lower when treated within RGD micelles as compared to treatment of free drug. On the other hand, IC50 values increased by 2 to 9 fold for micellar treatment in comparison to free drug in Detroit 551 cells. In A2058 melanoma xenograft mice model, the Paclitaxel-RGD micelles exhibited a significant inhibition of tumor growth in comparison to control treatment for both alternate day and twice weekly treatments. The studies showed the feasibility of using the non covalent peptide based self-assemblies as vehicles for targeted delivery in cancer.
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Thorendal, Victor. "Bioconjugation of RGD peptides on injectable PEGDMA for enhancing biocompatibility." Thesis, Uppsala universitet, Polymerkemi, 2019. http://urn.kb.se/resolve?urn=urn:nbn:se:uu:diva-396609.
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A cerebral aneurysm is a weakened area of an artery in the brain, creating an abnormal expansion. Recent research for treatment is utilizing a photopolymerizable hydrogel as a possible operation for injection in situ. This paper aimed to achieve bioconjugation of peptides on a PEGDMA polymer network (using the photoinitiator PEG-BAPO) to form a biocompatible photopolymerizable hydrogel, without compromise to any of its mechanical attributes. Achieving cell adhesion to the hydrogel surface is a critical requirement as that could drive the growth of endothelium between aneurysm and artery, to considerably enhance its sustainability and decrease the risk of inflammation. The hydrogel was synthesized by functionalizing RGD with a PEG-spacer and co-polymerize it with PEGDMA using UV-radiation to create an intertwined cross-linking network. Samples of various peptide concentrations were studied in cell culture to analyze cell adhesion, followed by mechanical tests to identify possible deviations. A subsequent study was established to create a dynamic prototype as a quantifiable replication of a hydrogel inside an aneurysm in vivo. The model was designed in SolidWorks and connected with an Ibidi sticky-Slide to roughly replicate a cerebral aneurysm connected to an artery with space to introduce a hydrogel sample.
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Boukalová, Iva. "Etický a sociální audit v RGP CZ s. r. o." Master's thesis, Vysoké učení technické v Brně. Fakulta podnikatelská, 2008. http://www.nusl.cz/ntk/nusl-221993.
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Master´s thesis Ethical and Social Audit of company RGP CZ s. r. o. deal about ethic audit in this company. The theoretical part is focused on the elementary prescription of the enterpreneurial ethics, it´s definition, evolution and reasons for ethical behaviour of enterprises. Important aspekt is also measurement of enterpreneurial ethic and consequently the tools of enterpreneurial ethic, which serve the purpose of realisation of ethical programme of the enterprise. The applied, practical part of this dissertation is the ethic audit of company RGP CZ s. r. o. and evaluation of this audit. Results are presented by recommendations for the company, how it shall proceed the improvements of the ethical behaviour of the company.
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Hofmann, Johannes [Verfasser], and Carsten [Akademischer Betreuer] Schmuck. "RGD-Receptor with Enhanced Water Solubility / Johannes Hofmann ; Betreuer: Carsten Schmuck." Duisburg, 2017. http://d-nb.info/1142113558/34.
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Kalinina, Sviatlana. "Novel technique in RGD-functionalisation of unstructured and structured inanimate surfaces." [S.l. : s.n.], 2007. http://digbib.ubka.uni-karlsruhe.de/volltexte/1000007975.
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Huang, Guofeng. "ENGINEERING RGD-MODIFIED LIPOSOMES FOR TARGETED DRUG DELIVERY TO ACTIVATED PLATELETS." Case Western Reserve University School of Graduate Studies / OhioLINK, 2006. http://rave.ohiolink.edu/etdc/view?acc_num=case1153187042.
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Kabashi, Agron, and Hassan El-Saabi. "Game software processes : with Focus on the Rapid Game Process (RGP)." Thesis, Blekinge Tekniska Högskola, Avdelningen för programvarusystem, 2006. http://urn.kb.se/resolve?urn=urn:nbn:se:bth-4903.
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The computer game industry has grown in a rapid rate over the past two decades becoming a billion dollar industry, even rivaling the movie industry. The greed for money caused the industry to grow large but the maturity did not grow in proportion. Compared to software engineering, game development is still a seed waiting to blossom. In this paper a development process (RGP) for games development using various software engineering paradigms is proposed. Furthermore a comparison between RGP and other game development processes will to some extent show the strengths and weaknesses of this process. The conclusions drawn are based on already validated software processes since the game process inherits a subset of these.
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Lussier, Carine. "Étude du système d'adhésion RGD dépendant dans la muqueuse intestinale humaine." Mémoire, Université de Sherbrooke, 2002. http://savoirs.usherbrooke.ca/handle/11143/3310.
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Les interactions cellule-matrice extracellulaire jouent un rôle important au niveau de processus tels la migration, la prolifération et la différenciation cellulaire. Les récepteurs principaux impliqués dans l'adhésion cellulaire sont les intégrines. Une sous-classe d'intégrines reconnaît de façon bien spécifique chez ses ligands la séquence peptidique RGD. La présente étude comporte, tout d'abord, une caractérisation de l'expression de différents membres de la famille RGD (récepteurs: sous-unités [alpha]8 et [alpha]v; ligand: ostéopontine) dans la muqueuse de l'intestin grêle au cours du développement, ainsi que dans les modèles cellulaires correspondants. Les patrons d'expression obtenus par immunofluorescence indirecte, immunobuvardage Western et RT-PCR, ont permis de déterminer que l'ostéopontine, ainsi que la sous-unité [alpha]8 des intégrines sont présents et agissent probablement au cours de la morphogenèse de la muqueuse intestinale. D'autre part, le récepteur épithélial de la ténascine-C n'ayant pas été identifié dans la muqueuse intestinale, la seconde partie du projet consistait à analyser, avec le modèle cellulaire HIEC-6, les différents récepteurs entrant en jeu dans l'interaction des entérocytes avec un fragment recombinant de la ténascine-C, le TNfn3. Cette adhésion s'est avérée RGD dépendante et effectuée par des intégrines présentant la sous-unité [alpha]v, ainsi que d'une autre intégrine, fort probablement [alpha]8[bêta]1. Pour vérifier le rôle de cette dernière dans l'adhésion sur la ténascine-C, des cellules HIEC-6 ont été infectées avec un vecteur rétroviral permettant l'expression d'un anti-sens de la sous-unité [alpha]8 ou de la sous-unité [alpha]8 complète. Ces cellules pourront permettre d'élucider le rôle d'[alpha]8[bêta]1 dans l'adhésion RGD dépendante des cellules cryptales intestinales sur la ténascine-C.
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Lopes, Rute. "Funcionalização de celulose bacteriana com peptídeo RGD para reparação tecidual de pele /." Araraquara, 2015. http://hdl.handle.net/11449/124406.
Full textAbstract:
Orientador: Reinaldo MarchettoCo-orientador: Sybele Saska Specian
Banca: Wilton Rogério Lustri
Banca: Ana Maria Minarelli Gaspar
Resumo: A celulose bacteriana (CB) apresenta ampla diversidade de aplicações. Neste trabalho o enfoque foi desenvolver um curativo temporário ou suporte para regeneração tecidual de pele, a partir da funcionalização de CB com peptídeo RGD, caracterizá-lo quanto às propriedades físico-químicas e avaliar in vitro a capacidade de estimular a adesão e a proliferação de fibroblastos, a citotoxicidade e a resposta imune. A finalidade do material desenvolvido consiste em promover a reparação tecidual de pele, visto que diversos fatores sistêmicos tais como diabetes, tabagismo e carência nutricional, podem dificultar o processo de cura. O uso de biomateriais como suporte de medicamentos ou curativos temporários, auxiliando ou acelerando o processo de reparação e cura, é uma necessidade nestes casos. A sequência peptídica RGD (Arginina-Glicina-Ácido Aspártico), encontrada em diversas proteínas da matriz extracelular (MEC), é frequentemente utilizada para promover a adesão celular, mediada por integrinas, em biomateriais. O peptídeo sintetizado foi escolhido por meio de estudo computacional. Foram sintetizados dois tipos de membranas, a CB-RGDAds, na qual o peptídeo RGD encontra-se adsorvido, e a CBRGDImz, na qual o peptídeo encontra-se ligado covalentemente à membrana, e, portanto, imobilizado. Estes materiais, juntamente com a membrana de CB pura, foram caracterizados a partir de análises de ângulo de contato, difratometria de raios-X (DRX), microscopia eletrônica de varredura (MEV), espectroscopia de absorção na região de infravermelho com Transformada de Fourier (FT-IR), termogravimetria (TG) e calorimetria diferencial exploratória (DSC). Posteriormente, as amostras foram submetidas a ensaios in vitro de viabilidade celular e morfologia celular utilizando a linhagem de fibroblastos L929; adicionalmente análises de determinação de citocinas TNF-α, IFN-γ e produção de óxido...
Abstract: Bacterial cellulose (BC) exhibits a broad diversity of applications. The aim of this study was to develop a scaffold or temporary dressing for skin tissue repair, whereof the BC would be functionalized with an RGD peptide. The synthesized materials were physicochemically characterized and submitted to in vitro analyses to assess their capacity of stimulating fibroblasts adhesion, proliferation and immune response. The developed materials would be applied in skin tissue repair that may be hampered by a series of sistemic factors, such as diabetes, smoking and nutritional deficiency. In theses cases, the usage of biomaterials as a drug delivery system or wound dressing, aiding or accelerating the repair and healing processes, becomes a necessity. The RGD peptide sequence (Arginine-Glycine-Aspartic Acid) is found in many extracellular matrix (ECM) proteins, and it is frequently used to promote cell adhesion, mediated by integrins, in biomaterials. The synthesized peptide sequence was chosen by means of computational analysis. Two types of membrane were synthesized, the BC-RGDAds in which the RGD peptide was adsorbed, and the BC-RGDImz in which the peptide was covalently bonded to the membrane, therefore, immobilized. These materials, together with the pure BC membrane, were characterized by contact angle analysis, x-ray diffractometry (XRD), scanning electron microscopy (SEM), Fourier transform infrared spectroscopy (FT-IR), thermogravimetric analysis (TGA) and differential scanning calorimetry (DSC). Subsequently, the samples were submitted to in vitro assays of cellular viability and cellular morphology, using the fibroblast lineage L929; moreover, to evaluate the immune and inflammatory response, the nitric oxide production assay as well as TNF-α and IFN-γ cytokines determination assays were performed using Balb/c mice cells. The results indicate that the BC-RGDAds and the BC-RGDImz membranes...
Mestre
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Lopes, Rute [UNESP]. "Funcionalização de celulose bacteriana com peptídeo RGD para reparação tecidual de pele." Universidade Estadual Paulista (UNESP), 2015. http://hdl.handle.net/11449/124406.
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000825911.pdf: 1735726 bytes, checksum: ac1e06d8b87ef7b2876cb9e6bf68776f (MD5)A celulose bacteriana (CB) apresenta ampla diversidade de aplicações. Neste trabalho o enfoque foi desenvolver um curativo temporário ou suporte para regeneração tecidual de pele, a partir da funcionalização de CB com peptídeo RGD, caracterizá-lo quanto às propriedades físico-químicas e avaliar in vitro a capacidade de estimular a adesão e a proliferação de fibroblastos, a citotoxicidade e a resposta imune. A finalidade do material desenvolvido consiste em promover a reparação tecidual de pele, visto que diversos fatores sistêmicos tais como diabetes, tabagismo e carência nutricional, podem dificultar o processo de cura. O uso de biomateriais como suporte de medicamentos ou curativos temporários, auxiliando ou acelerando o processo de reparação e cura, é uma necessidade nestes casos. A sequência peptídica RGD (Arginina-Glicina-Ácido Aspártico), encontrada em diversas proteínas da matriz extracelular (MEC), é frequentemente utilizada para promover a adesão celular, mediada por integrinas, em biomateriais. O peptídeo sintetizado foi escolhido por meio de estudo computacional. Foram sintetizados dois tipos de membranas, a CB-RGDAds, na qual o peptídeo RGD encontra-se adsorvido, e a CBRGDImz, na qual o peptídeo encontra-se ligado covalentemente à membrana, e, portanto, imobilizado. Estes materiais, juntamente com a membrana de CB pura, foram caracterizados a partir de análises de ângulo de contato, difratometria de raios-X (DRX), microscopia eletrônica de varredura (MEV), espectroscopia de absorção na região de infravermelho com Transformada de Fourier (FT-IR), termogravimetria (TG) e calorimetria diferencial exploratória (DSC). Posteriormente, as amostras foram submetidas a ensaios in vitro de viabilidade celular e morfologia celular utilizando a linhagem de fibroblastos L929; adicionalmente análises de determinação de citocinas TNF-α, IFN-γ e produção de óxido...
Bacterial cellulose (BC) exhibits a broad diversity of applications. The aim of this study was to develop a scaffold or temporary dressing for skin tissue repair, whereof the BC would be functionalized with an RGD peptide. The synthesized materials were physicochemically characterized and submitted to in vitro analyses to assess their capacity of stimulating fibroblasts adhesion, proliferation and immune response. The developed materials would be applied in skin tissue repair that may be hampered by a series of sistemic factors, such as diabetes, smoking and nutritional deficiency. In theses cases, the usage of biomaterials as a drug delivery system or wound dressing, aiding or accelerating the repair and healing processes, becomes a necessity. The RGD peptide sequence (Arginine-Glycine-Aspartic Acid) is found in many extracellular matrix (ECM) proteins, and it is frequently used to promote cell adhesion, mediated by integrins, in biomaterials. The synthesized peptide sequence was chosen by means of computational analysis. Two types of membrane were synthesized, the BC-RGDAds in which the RGD peptide was adsorbed, and the BC-RGDImz in which the peptide was covalently bonded to the membrane, therefore, immobilized. These materials, together with the pure BC membrane, were characterized by contact angle analysis, x-ray diffractometry (XRD), scanning electron microscopy (SEM), Fourier transform infrared spectroscopy (FT-IR), thermogravimetric analysis (TGA) and differential scanning calorimetry (DSC). Subsequently, the samples were submitted to in vitro assays of cellular viability and cellular morphology, using the fibroblast lineage L929; moreover, to evaluate the immune and inflammatory response, the nitric oxide production assay as well as TNF-α and IFN-γ cytokines determination assays were performed using Balb/c mice cells. The results indicate that the BC-RGDAds and the BC-RGDImz membranes...
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Hansson, Annasara. "Développement et évaluation in vitro d’un dérivé de chitosan fonctionnalisé avec des peptides RGD pour la cicatrisation." Thesis, Lyon 1, 2012. http://www.theses.fr/2012LYO10182/document.
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L’objectif du travail présenté dans cette thèse était de développer des nanoparticulesfonctionnelles ayant la capacité d’induire l’adhésion et la migration de kératinocyteshumains normaux. L’utilisation de systèmes particulaires pour favoriser l’adhésion etla migration cellulaire dans les processus de cicatrisation constitue une nouvelleapproche de l’ingéniérie tissulaire. Dans cette optique, un dérivé hydrosoluble du chitosan rendu fonctionnel par l’ajoutde peptides RGD a été développé. Les nanoparticules furent développées parcoacervation complexe entre le dérivé cationique du chitosan et le sulfate dechondroïtine anionique. La capacité du système particulaire à induire unchangement cellulaire phénotypique a été évaluée in vitro.Lors de l’évaluation de ce nouveau polymère, le succès de la synthèse a été montrépar l’absence de cytotoxicité et par la préservation de son activité biologique médiéepar les séquences RGD. Aussi bien les polymères que les nanoparticules ont induitl’adhésion et la mobilité de fibroblastes dermiques humains, confirmant le conceptde nanoparticules bio-actives. Cependant, concernant l’étude des interactions entreles nanoparticules et les kératinocytes, aucune conclusion n’a pu être tirée etd’autres travaux sont nécessaires. Pour résumer, un système particulaire bio-actif a été développé. Le choix despeptides RGD pour induire la migration des kératinocytes doit être réévalué, etl’utilisation de concentrations plus importantes, de mélange de peptides d’adhésionou l’utilisation de peptides d’adhésion différents doit être envisagée pour laréalisation d’études ultérieuresThe aim of the work presented in this thesis, was to develop functionalizednanoparticles with the ability to induce adhesion and migration in normal humankeratinocytes. Using particulate systems to promote and support cell adhesion andmigration in epidermal restoration is a novel approach of tissue engineering.In this view, a water-soluble chitosan derivative functionalized with RGD peptideswas developed. Nanoparticles were formed through complex coacervation betweenthe cationic chitosan derivative and the anionic chondroitin sulfate. The particulatesystem was evaluated in vitro for its ability to change phenotype in cells.In the evaluation of the novel hybrid polymer, the successful synthesis wasconfirmed by the absence of cytotoxicity and a preserved bioactivity specific to theRGD-moieties. Both the polymer and the particles formed thereof induced celladhesion and spreading in human dermal fibroblasts, proving the concept ofbioactive nanoparticles. However, when investigating the interaction between thenanoparticles and keratinocytes, no clear conclusion could be drawn and furtherassays are required. To summarize, a bioactive particulate system was developed. The choice of RGDpeptides to induce migration in keratinocytes needs to be re-evaluated and higherconcentrations, mixtures of adhesion peptides or other adhesion peptides might beconsidered for further investigations
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Oliveira, Érica Aparecida de. "Estudo comparativo de radiofármacos para angiogênese na detecção de melanoma." Universidade de São Paulo, 2011. http://www.teses.usp.br/teses/disponiveis/85/85131/tde-31102011-092818/.
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Diagnóstico precoce e tratamento de melanoma, um tumor cutâneo com o pior prognóstico, é extremamente importante para um resultado clínico favorável. A biblioteca de peptídeos phage display é um recurso útil de triagem para identificar peptídeos bioativos que interagem com alvos em cânceres. O objetivo desse estudo foi a avaliação de dois traçadores de tecnécio-99m com sequências peptídicas RGD e NGR, conjugados com o quelante bifuncional MAG3. Os conjugados peptídicos (10 μL de uma solução μg/μL) foram marcados com tecnécio-99m usando tampão de tartarato de sódio. A avaliação radioquímica foi feita por ITLC e confirmada por CLAE. O coeficiente de partição foi determinado e ensaios de internalização foram realizados em duas linhagens celulares de melanoma (B16F10 e SKMEL28). A avaliação da biodistribuição dos traçadores foi realizada em animais sadios em diferentes tempos e também em camundongos portadores de células tumorais aos 120 min após a sua administração. Estudos de bloqueamento também foram conduzidos pela co-injeção de peptídeo frio. O desempenho dos conjugados peptídicos mostraram-se bastante parecidos em diversas avaliações. Eles foram radiomarcados com alta pureza radioquímica (>97%). Ambos são hidrofílicos, com excreção renal preferencial. A captação tumoral foi maior para células SKMEL28 do que para as células B16F10, especialmente para o 99mTc-MAG3-PEG8-c(RGDyK) (7,85±2,34 %DI/g) aos 120 min pós-injeção. O desempenho do 99mTc-MAG3-PEG8-c(RGDyk) foi superior que o do traçador com NGR, quanto à captação no melanoma humano podendo ser considerado como um promissor radiofármaco para diagnóstico de melanoma.Early diagnosis and treatment of melanoma, a cutaneous tumor with a serious prognosis, is extremely important for optimal clinical outcome. Phage display peptide libraries are a useful screening resource for identifying bioactive peptides that interact with cancer targets. The aim of this study was the evaluation of two technetium-99m tracers for angiogenesis detection in melanoma model, using cyclic peguilated pentapeptide with RGD and NGR motifs conjugated with bifunctional chelator MAG3. The conjugated peptides (10 μL of a μg/μL solution) were labeled with technetium-99m using a sodium tartrate buffer. Radiochemical evaluation was done by ITLC and confirmed by HPLC. Partition coefficient was determined and internalization assays were performed in two melanoma cells (B16F10 and SKMEL28). Biodistribution evaluation of the tracers was done in healthy animals at different times and also in mice bearing the tumor cells at 120 min post injection. Blocking studies were also conducted by co-injection of cold peptides. The conjugated showed the same profile in many evaluations. They were radiolabeled with high radiochemical purity (>97%). Both were hydrophilic, with preferential renal excretion. Tumor uptake was higher for human melanoma cells than for murinic melanoma cells, specially for 99mTc-MAG3-PEG8-c(RGDyK) (7.85±2.34 %ID/g) at 120 min post injection. The performance of 99mTc-MAG3-PEG8-c(RGDyk) was much better than NGR tracer concerning human melanoma uptake and might be considered in future investigations focusing radiotracers for melanoma diagnosis.
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Milner, Richard. "Characterisation of integrins on cells of the oligodendroglial lineage." Thesis, University of Cambridge, 1994. http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.360829.
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Antonow, Michelli Barcelos. "Desenvolvimento e caracterização físico-química de nanocápsulas multiparedes complexadas com zinco e funcionalizadas com RGD para reconhecimento por integrinas ανβ3 presentes em células tumorais." reponame:Biblioteca Digital de Teses e Dissertações da UFRGS, 2016. http://hdl.handle.net/10183/149502.
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A funcionalização de superfície nas nanocápsulas contendo doxorrubicina com o peptídeo RGD é uma estratégia promissora devido a ligação preferencial na integrina αvβ3 expressa em células tumorais. Este estudo objetivou o desenvolvimento, caracterização e estudos biológicos de nanocápsulas multiparedes com doxorrubicina e funcionalizadas com RGD. Para isso, na primeira etapa do trabalho foi realizada a síntese do peptídeo RGD. Os produtos obtidos foram caracterizados por análises de infravermelho e RMN de 1H. Na segunda etapa foram desenvolvidas formulações de nanocápsulas com doxorrubicina ou cloridrato de doxorrubicina, e, nanocápsulas multiparedes revestidas com quitosana, íons zinco, RGD ou fenilalanina. Essas suspensões foram caracterizadas através da determinação do pH, diâmetro de partícula por diferentes técnicas, potencial zeta, eficiência de encapsulação e eficiência de associação do RGD na superfície da nanopartícula. Na terceira etapa, foram realizados ensaios de viabilidade celular por MTT após 24 e 72h com as formulações desenvolvidas em células de câncer de mama (MCF7) e glioblastoma humano (U87MG). As formulações apresentaram diferentes valores de citotoxicidade e, utilizando o Gráfico de Pareto foi possível determinar os fatores que exercem maior influencia. Em células MCF7 foi a concentração de fármaco e tempo de tratamento e, nas células U87MG além desses fatores, a funcionalização mostrou-se determinante. Além disso, foi avaliada a captação das nanocápsulas funcionalizadas com RGD e fenilalanina após 24h nas células tumorais e células de queratinócitos humanos (HaCat), com diferentes níveis de expressão da integrina αvβ3. O estudo mostrou menores valores de captação nas células HaCat (sem expressão de integrina αvβ3) para as duas formulações testadas. Finalmente as nanocápsulas funcionalizadas com RGD apresentaram maior captação em células U87MG com maior expressão da integrina αvβ3.The surface functionalization in nanocapsules containing doxorubicin with RGD peptide is a promising strategy due to preferential binding in the αvβ3 integrin expressed on tumor cells. This study aimed the development, characterization, and biological studies of multiwall nanocapsules containing doxorubicin and functionalized with RGD. For this reason, in the first stage of this study the synthesis of RGD peptide was performed and the products characterized by infrared analysis and 1H NMR. Besides, nanocapsules formulations were developed containing doxorubicin or doxorubicin hydrochloride, and multiwall nanocapsules coated with chitosan, zinc ions, RGD or phenylalanine. These suspensions were characterized by pH determination, particle diameter by different techniques, zeta potential, encapsulation efficiency, and association efficiency of RGD on the surface of the nanoparticle. Additionally, it was performed cell viability assays by MTT after 24 and 72 hours with formulations developed in breast cancer (MCF7) and human glioblastoma cells (U87MG). Formulations showed different cytotoxicity values. The Pareto chart was possible to determine factors that have more influence. In MCF7 cells was drug concentration and treatment time, and U87MG cells, besides these factors, the functionalization was decisive. Furthermore, it was performed the cellular uptake of nanocapsules functionalized with RGD or phenylalanine after 24 hours in tumor cells and human keratinocyte cells (HaCaT), with different levels of expression αvβ3 integrin. The study showed less uptake in HaCaT cells (without expression αvβ3 integrin) for the two formulations applied, and the nanocapsules functionalized with RGD showed more uptake in U87MG cells, with higher expression of integrin αvβ3.
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Jatzová, Katarína. "Bioaktivní peptidy - nadějná složka kosmetických produktů." Master's thesis, Vysoké učení technické v Brně. Fakulta chemická, 2012. http://www.nusl.cz/ntk/nusl-216835.
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Ageing is a natural part of every human life cycle. During ageing there are lots of changes in the organism. One of the main pillars of the cosmetics industry is the development of active compounds that are fighting signs of skin ageing. The components as bioactive peptides are considered to be promising anti-ageing products, mainly because of the possibility to precisely define their chemical structure and therefore achieve more effective biological targeting. One of the signs of skin ageing is the weakening of the connections between epidermal cells and the extracellular matrix, decreasing expression of adhesion molecules and molecular components of dermo-epidermal connection. The most abundant adhesive receptors in the skin are integrins. Their ligands are extracellular matrix molecules, e. g. laminin or fibronectin. The minimal recognition sequence of integrins receptors is the amino acid motif arginine- glycine- aspartic acid (RGD). This sequence is also very interesting in terms of cosmetic applications because it provides the ability to create new and effective bioactive peptides. The subject of present work is basic safety testing of four peptides with RGD motif. A sequence of three peptides was modified by addition of glycine amino acids, or alanine. The expected effect was to improve interaction with integrin receptors. In each of the sample, levels of endotoxin was determined in order to exclude any possible interfering effects on the viability of cells. Subsequently, in NIH3T3 mouse fibroblasts viability was monitored by MTT assay and morphology. The quantity of obtained protein had been determined to increase data interpretation relevance.
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Fernandes, Helder. "Caractérisation des liens fonctionnels entre la protéine RhoGap Rgd1 et les protéines Wsc1 et Mid2, deux senseurs de l'état de la paroi chez la levure Saccharomyces cerevisiae : étude de la régulation post-traductionnelle de la protéine Rgd1." Bordeaux 2, 2005. http://www.theses.fr/2005BOR21305.
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La protéine Rgd1 est la RhoGAP de Rho3p et Rho4p chez la levure S cerevisiae. Un crible génétique a permis de mettre en évidence des interactions létales-synthétiques entre les gènes RGD1 et WSC1 ou MID2. La caractérisation de l'interaction génique entre RGD1 et WSC1 a révélé l'implication des protéines Rho3 et Rho4 dans les mécanismes conduisant à la létalité-synthétique du double mutant wsc1deltargd1delta. Les interactions géniques associant d'une part les gènes RGD1 et WSC1 et d'autre part les gènes RGD1 ET MID2 font intervenir des mécanismes différents. Nous proposons un modèle dans lequel Wsc1p et Rgd1p sont impliqués dans la régulation de la sécrétion polarisée. L'étude des mécanismes de régulation post-traductionnelle de Rgd1p a montré que cette protéine est phosphorylée de manière dynamique sur différents acides aminés. La phosphorylation de la protéine Rgd1 permet de réguler sa capacité à dimériser, à interagir avec les phospholipides et son activité RhoGAPRgd1p is a RhoGAP for Rho3p and Rho4p, two GTPases involved in a polarized growth in the yeast S. Cerevisiae. Using a genetic screen, synthetic lethal interactions between the RGD1 gene and WSC1 or MID2 were discovered. The WSC1 and MID2 genes code for cell sensors that regulate the activity of the cell integrity pathway. Characterization of the genetic interaction between RGD1 and WSC1 revealed the implication of Rho3p and Rho4p in the synthetic lethality. Functional interactions between RGD1 and WSC1 or RGD1 and MID2 where shown to be different. We propose a model in which Wsc1p and Rgd1p act together to regulate polarized secretion. Post-translational regulation studies of Rgd1p showed that this protein is multi-phosphorylated in a dynamic way. Phosphorylation of Rgd1p regulates its ability to form a dinner, to bind phospholipids and also modify its RhoGAP activity toward Rho3p and Rho4p
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Xu, Xiaolong. "Nanostructured W-O thin films by reactive sputtering : application as gas sensors." Thesis, Bourgogne Franche-Comté, 2018. http://www.theses.fr/2018UBFCA003/document.
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Cette thèse est dédiée à l’élaboration de couches minces d'oxydes de tungstène par pulvérisation cathodique réactive. Afin de jouer sur la composition des films, le procédé de pulsation du gaz réactif (RGPP) est mis en œuvre pour changer les concentrations en oxygène et en tungstène. En parallèle, la technique de dépôt sous incidence oblique (GLAD) est développée pour produire différentes architectures, à savoir des colonnes inclinées, des zigzags ou encore des spirales, et augmenter le rapport surface-volume dans les films. La co-pulvérisation GLAD est également étudiée en utilisant deux cibles inclinées et séparées de W et WO3. Les relations entre la microstructure, la composition, les propriétés électroniques et optiques des films d'oxydes de tungstène sont systématiquement étudiées. Ils sont finalement appliqués comme couches actives pour des capteurs résistifs afin d'améliorer la détection de vapeur de dodécane et d'ozone gazeux. La microstructure poreuse élevée des colonnes inclinées produite par GLAD combinée à une composition ajustée par RGPP conduit à définir une gamme de films d'oxydes de tungstène attractifs pour améliorer les performances capteursThis thesis is focused on the reactive sputter deposition of W-O thin films. In order to play with their composition, the Reactive Gas Pulsing Process (RGPP) is implemented and allows tunable oxygen and tungsten concentrations. Similarly, the GLancing Angle Deposition (GLAD) technique is developed to produce various architectures, namely inclined columns, zigzags and spirals, and increases the surface-to-volume ratio of the films. The GLAD co-sputtering approach is also investigated by means of two inclined and separated W and WO3 targets. Relationships between microstructure, composition, electronic and optical properties of W-O films are systematically studied. They are finally applied as active layers for resistive sensors in order to improve detection of dodecane vapor and ozone gas. The high porous microstructure of inclined columns produced by GLAD combined to the suitable composition adjusted by RGPP leads to define a range of W-O films attractive for sensing performances
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Lapertosa, Claudia Zanforlin. "Teste de detecção de intervalos aleatórios de silêncio em crianças com história de otite média recorrente." Pontifícia Universidade Católica de São Paulo, 2006. https://tede2.pucsp.br/handle/handle/12061.
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Previous issue date: 2006-07-31Coordenação de Aperfeiçoamento de Pessoal de Nível Superior
Introduction: otitis media is an inflammatory disease of middle ear that has greater occurrence on pediatric population, being considered a helth public problem all around the world. Peripheral ans fluctuanting hearing loss may be observed and this may cause a disturbance on the complex auditory stimuli perception, including speech. This altered auditory perception may cause difficulties on sound acoustics representation and on the auditory abilities related to speech in noise recognition, auditory memory, binaural interaction and temporal processing. Objective: to investigate the temporal auditory processing throug random gap detection test in a group of children with recurrent otitis media history on the early year of life. Method: 26 children, aged from 7 of 8 years old, according to one these criteria: otological history of 3 to 4 episodes of otitis media/year on the early years of life; 3 to 4 episodes of otitis media on their first moment life; type B ou C tympanometry at the moment of audiological evaluation. All the children were submited to the following procedures pure tone audiometry, speech audiometry, acoustic immitance measurement and to randm gap detection test (RGDT). Results: data showed RGDT hreshold longer for the frequency of 1000 Hz on the group of children with a type B timpanometry; the same happens with the group that showed abnormal acoustc reflex for 1000 Hz. Averange values for RGDT threshold ere 10 ms, sd of 2,7 ms, median of 10 ms, mode of 10 ms, minimum value was 5 ms an maximum was 15 ms. Compared to Dias (2004) values, the otitis media group showed longer threshold values. Conclusion: recurrent otitis media on early life years may produce a enlargement on the detection of silent intervals threshold
Introdução: A otite média é um processo inflamatório da orelha média de grande ocorrência na população infantil, sendo considerada um problema de saúde de caráter mundial. A presença de perda auditiva periférica e flutuante observada em alguns casos de otite média pode ocasionar alteração da percepção dos estímulos auditivos complexos, inclusive a fala. Esta alteração na percepção do sinal acústico pode causar prejuízo na representação de sons e nas habilidades auditivas que envolvem o reconhecimento da fala em ambientes ruidosos, memória auditiva, interação binaural e processos temporais. Objetivo: investigar o processamento auditivo temporal através do teste de detecção de intervalos de silêncio em crianças que tiveram otite média recorrente nos primeiros anos de vida. Método: Foram selecionadas 26 crianças com idade entre 7 e 8 anos que obedeciam aos seguintes critérios: ter histórico de 3 a 4 episódios de otite média/ano nos primeiros anos de vida, ter histórico de 3 a 4 episódios no primeiro anos de vida, ou ter timpanometria do tipo B ou C no momento da avaliação. As crianças foram submetidas à audiometria tonal, logoaudiometria, medida da imitância acústica e à pesquisa do limiar de intervalo de silêncio - RGDT (Random gap detection test). Resultado: Foi observado um aumento dos limiares do RGDT na freqüência de 1000 Hz nas crianças que tinham curva tipo B na timpanometria, assim como em relação ao reflexo do músculo estapédio contralateral alterado na mesma freqüência. Não houve correlação entre os valores do limiar do RGDT e o número de episódios de otite média. Os valores de média encontrados foram de 10 ms, desvio-padrão (dp)=2,7 ms, mediana=10 ms, moda=10ms, e valor mínimo encontrado igual a 5 ms e máximo igual a 15 ms. Comparados estes resultados com os de Dias (2004) estes valores foram maiores que os encontrados em crianças sem histórico de problema de ouvido ou de aprendizagem. Conclusão: a otite média recorrente nos primeiros anos de vida pode acarretar aumento na detecção de intervalos de silêncio o que pode explicar algumas das dificuldades de discriminação de ponto e modo articulatório encontradas nestas crianças
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Bohlin, Erik, and Jon Larsson. "Varför tillpassas det så få stabila linser i Sverige? : En enkätstudie om kontaklinsoptikers syn på RGP-linser." Thesis, Linnéuniversitetet, Institutionen för medicin och optometri (MEO), 2020. http://urn.kb.se/resolve?urn=urn:nbn:se:lnu:diva-96510.
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Bakgrund: Andelen stabillinstillpassningar (RGP-tillpassningar) i förhållande till totala tillpassningar är relativt låg i världen och Sverige är inget undantag. Anledningar till detta är många även om ett flertal nya RGP- linsdesigner som Orto-K och minisklerala blivit tillgängliga de senaste två decennierna. Syfte: Syftet med enkätundersökningen var att ta reda på varför andelen tillpassade stabila linser är relativt lågt i Sverige, samt för att undersöka varför de som inte jobbar med dessa linstyper, inte gör det. Metod: En enkät med ca 20 frågor som skickades till Optikerförbundets 1550 medlemmar via e-mail, samt en intervju utfördes med en synscentralsoptiker för att få insikt i hur optiker på syncentralen ser på detta. Därefter sammanställdes och analyserades svaren. Resultat: Utav de 1550 optiker i Optikerförbundet var det 359 som besvarade enkäten. Ungefär 30% utav dessa tillpassade RGP-linser, och majoriteten jobbade inom privatägda- eller franchisebutiker. De som kände sig bekväma med att tillpassa stabila linser sa att det beror på egen erfarenhet (49%), vana (15%) och kunskap (14%). De vanligaste anledningarna som angavs av de som inte tillpassar var att RGP-linser ”finns ej i butik”, eller beror på ” för litet kundunderlag” och ”ingen efterfrågan” samt på deras ”bristande kunskap”. Det var dock flera som ställde sig positiv till RGP-linser (76%) och kunde tänka sig tillpassa dem. Slutsats: Studien visar att användningen av RGP-linser är så liten i Sverige p.g.a. bristande kunskap, saknat utbud hos butiker och för litet kundunderlag enligt optiker.Background: The proportion of stable lens (RGP) fittings relative to total fitting is relatively low in the world, and Sweden is no exception. There are many reasons for this, despite that a few new RGP lens designs, such as the Ortho-K and mini-scleral lenses, have become available over the past two decades. Purpose: The aim of this study was to determine the reasons as to why the proportion of RGP lens-fittings is low in Sweden and to map the viewpoints of optometrists with licences to fit contact lenses, regarding why they choose not to fit this group of lenses. Method: A web-based survey with 20 questions was distributed to the 1550 members of the Swedish association of Optometrists via members-email. Questions focussed on fitting demographics, the reasons why those who did fit RGP-lenses felt comfortable doing this, and why those who did not fit this lens type choose not to. In addition, an interview with an optometrist working at a hospital eye-clinic was also conducted. Result: Among the 1550 members of the Swedish association of Optometrists, 359 responded to the survey. Approximately 34% of these fitted RGP-lenses and the majority worked in private self-owned or franchise stores. Those who felt comfortable fitting stable lenses said that it was because they had experience (49%), routine (15%) and knowledge (14%) within the field. The most common reasons given by those who did not fit RGP-lenses, as to why they did not fit RGP-lenses were that this lens type “was not available in the clinic”, that there were “too few customers” or “lack of demand” and that they “lacked essential knowledge”. There were however a majority of this group (76%) who were positive to fitting RGPlenses themselves Conclusion: Because of lack of knowledge, the missing of supply at stores and the lack of patients according to opticians, the amount of RGP-lens fitting in Sweden is low.
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Vieillemard, Aurélie. "Implication de la RhoGAP Rgd1p dans la polarité cellulaire chez les levures Saccharomyces cerevisiæ et Candida albicans." Thesis, Bordeaux 2, 2011. http://www.theses.fr/2011BOR21841/document.
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La polarité cellulaire est un phénomène biologique essentiel du monde vivant. Chez la levure Candida albicans, sa capacité à croître sous une forme hyperpolarisée semble être un élément déterminant de sa pathogénicité. Nous avons entrepris d’identifier les éléments moléculaires d’une structure essentielle à cette croissance hyphale, le Spitzenkörper, afin de mieux comprendre le rôle de ce corps apical dans la croissance polarisée. Nous nous sommes également intéressés à la régulation des protéines Rho3 et Rho4 impliquées dans la croissance polarisée de C. albicans, à travers l’identification et l’étude de la protéine RhoGAP commune à ces deux protéines Rhos, la protéine Rgd1.Chez la levure Saccharomyces cerevisiæ, les protéines Rho3 et Rho4 sont également impliquées dans le contrôle de la croissance polarisée, et sont régulées par la protéine Rgd1. Le laboratoire, à l’origine de la découverte de ce régulateur commun, étudiait des aspects de croissance polarisée contrôlée par les protéines Rho3 et Rho4, à travers l’étude de la régulation de la protéine Rgd1. Nous avons notamment mis en évidence que Rgd1p est modifiée au niveau post-traductionnel par des phosphorylations. La kinase Ipl1 de la famille des kinases Aurora est un des acteurs de cette modification. Différents éléments indiquent que le complexe phosphatase Glc7-Bud14 serait également impliqué dans le contrôle de l’état de phosphorylation de Rgd1p, de façon antagoniste à la kinase Ipl1Cell polarity is an essential process for living organisms. In the yeast Candida albicans, its ability of hyperpolarized growth seems to be a decisive element for its pathogenicity. We undertook to identify molecular elements of an essential structure for hyphal growth, named Spitzenkörper, to better understand the role of this apical body in polarised growth. We also studied regulation of Rho3 and Rho4 proteins implicated in C. albicans polarised growth, through identification and study of a shared RhoGAP protein, named Rgd1.In the yeast Saccharomyces cerevisiæ, Rho3 and Rho4 proteins are also implicated in polarised growth control, and are regulated by Rgd1 protein. The laboratory, which identified this shared regulator, studied polarised growth aspects controlled by Rho3 and Rho4 proteins, through study of Rgd1p regulation. We showed that Rgd1p is post-translationally modified, by phosphorylations. The Ipl1 kinase, an Aurora family member, is implicated in this modification. Several elements indicate that the Glc7-Bud14 phosphatase complex would be also implicated in the control of Rgd1 phosphorylation state, antagonistically to Ipl1p
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Kojetinsky, Corina. "Untersuchungen zur Nachstarprävention in vitro mittels des zyklischen RGD-Peptids cRGD D FV." [S.l.] : [s.n.], 2001. http://deposit.ddb.de/cgi-bin/dokserv?idn=964899817.
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Kojetinsky, Corina. "Untersuchungen zur Nachstarprävention in vitro mittels des zyklischen RGD-Peptids cRGD D FV." Doctoral thesis, Humboldt-Universität zu Berlin, Medizinische Fakultät - Universitätsklinikum Charité, 2002. http://dx.doi.org/10.18452/14747.
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Hintergrund: RGD-Peptide hemmen kompetitiv die Adhäsionsmoleküle von Linsenepithelzellen (LEC). Ziel unserer Untersuchungen war es herauszufinden, ob diese Peptide in der Lage sind, auch nach Kurzzeitinkubation eine suffiziente Inhibition der Adhäsion bzw. eine Ablösung adhärenter Zellen und damit eine ausreichende Prävention des Nachstars zu bewirken. Außerdem wurde überprüft, ob das von uns verwendete RGD-Peptid eine Toxizität für die Hornhaut aufweist. Material und Methoden: Kulturen boviner und humaner LEC, boviner Hornhautendothelzellen, humane und bovine Linsenkapselexzidate und humane explantierte Hornhäute wurden verwendet. Wir untersuchten die Inhibition der Adhäsion und die Ablösung konfluenter LEC-Layer mittels des zyklischen RGD-Peptids cRGDDFV (Inkubationszeiten von 1 Stunde bzw. 5-7 Tagen und Konzentrationen von 10-4 M, 10-3 M und 2x10-3 M wurden angewandt). Ergebnisse: Wir fanden nach nur einstündiger Inkubation in der Kulturschale eine Adhäsionsinhibition von 48% für bovine LEC und von 100% für humane LEC. Die Differenz zwischen Kontrollpeptid und cRGDDFV war statistisch signifikant (pPurpose: RGD-peptides competitively inihibit adhesion molecules of the lens epithelial cells (LEC). The purpose of our study was to investigate whether this peptide could be able to inhibit adhesion sufficiently after short term incubation resp. to detach adherent cells and so to prevent posterior capsule opacification (PCO). Also there was proofed if there is any toxicity for the cornea. Methods: Cultures of bovine and human LEC, bovine cornea endothelial cells, humane and bovine fragments of the lens capsule and explanted humane corneas were used. The inhibition of adhesion and the detachment of confluent LEC-layer by the cyclic RGD-peptide cRGDDFV were studied (incubation time was 1 hour resp. 5-7 days and concentrations of 10-4, 10-3 M and 2x10-3 M were used). Results: After one hour incubation time in a culture dish inhibition of adhesion was 48% for bovine LEC resp. 100% for humane LEC. There was a statistically significant difference between the control-peptide-group and cRGDDFV (p
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Garanti, Tanem. "RGD-targeted solid lipid nanoparticles containing asiatic acid for the treatment of cancer." Thesis, University of Central Lancashire, 2016. http://clok.uclan.ac.uk/16565/.
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Selective anti-cancer treatment and targeting is needed to help minimise unwanted side-effects from conventional chemotherapy. Advanced drug delivery systems (DDSs) that have the potential for passive and active targeting have been of significant interests in the past decades, particularly with the use of nano-based drug carriers. The concept of targeting to the tumour vasculature or angiogenic blood vessels has continued to be of interests in cancer research since 1970s, as it offers promising therapeutic applications for many solid tumours. Active targeting of DDSs relies on specific interactions between the ligand (generally conjugated onto the surface of DDSs) and its receptor, which is overexpressed on target tumour tissues. In this study, arginine-glycine-aspartic acid (RGD) tripeptide was used to target the αvβ3 integrin receptor that is overexpressed by both tumour endothelial cells and various tumour tissues, potentially providing a double-killing (by targeting tumour and tumour endothelial cells) effect. Asiatic acid (AA) is an extract from a medical plant, Centella Asiatica and has demonstrated potential anti-inflammatory, as well as anti-angiogenic and anti-cancer properties. However, its poor water solubility (0.03 mg/mL) is one of the major limitations for its progression for clinical applications. To help overcome the solubility issue of AA and also to improve its therapeutic efficacy, AA was incorporated into RGD-containing solid lipid nanoparticles (SLNs) after optimisation of the SLN preparation comprised of glyceryl monostearate, glyceryl distearate and glyceryl tristearate lipids and subsequent characterisation on their physicochemical properties. The targeting ability of these AA-containing RGD-conjugated SLNs and their apoptotic / necrotic induction on cancer cells were assessed using U87 MG glioma cells and ECV-304 bladder cancer endothelial-like cells, which are known to express αvβ3 integrin. Moreover, the efficacy of both AA and AA-loaded SLNs were tested for the first time on in vitro 3D U87 MG tumour spheroids. Besides the anti-tumour efficacy, AA-containing RGD-SLNs were also investigated for their potential anti-angiogenic effect using various cellular assays of ECV-304 endothelial-like cells. Results obtained from this study showed that RGD-targeted SLN formulations improved the cellular uptake of nanoparticles compared to non-RGD containing SLNs and thus enhanced drug accumulation and cytotoxic effect seen on U87 MG and ECV-304 cells. Furthermore, AA-containing SLNs showed prevention of spheroid formation, inhibition of spheroid growth and cytotoxic effect on U87 MG spheroids, where RGD-SLNs also showed improved spheroid penetration compared to non-RGD containing SLNs. In addition, AA-loaded RGD-SLNs showed potential anti-angiogenic effect by demonstrating concentration-dependent inhibition of cell adhesion, migration and invasion, as well as disruptions in tube network of endothelial cells in in vitro angiogenesis assay. To conclude, AA-loaded RGD-targeted SLNs showed promising anti-cancer and anti-angiogenic effects in vitro, which supports its development for future clinical applications and warrants further investigation on an appropriate in vivo angiogenesis model to maximise its clinical potential.
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Theisen, Maíra. "Estudo computacional via dinâmica molecular de poli(vinil álcool) funcionalizado com tripetídeo RGD." reponame:Biblioteca Digital de Teses e Dissertações da UFRGS, 2017. http://hdl.handle.net/10183/171735.
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Hidrogéis são redes poliméricas tridimensionais ligadas entre si por reticulações químicas ou físicas, e podem absorver água ou fluidos biológicos. A estrutura permite que estes materiais tenham altos níveis de hidrofilicidade e biocompatibilidade, que em conjunto com as demais propriedades, fazem com que os hidrogéis sejam vistos como promissores biomateriais. Devido a estas características, hidrogéis possuem diversas aplicações voltadas as áreas médica e farmacêutica. Alguns hidrogéis apresentam um comportamento responsivo a variações de alguma condição do ambiente, são os chamados hidrogéis responsivos ou hidrogéis inteligentes. Neste trabalho foi escolhido o polímero poli (vinil álcool) funcionalizado com o tripeptídeo RGD. A investigação foi desenvolvida através de simulações de dinâmica molecular a fim de primeiramente observar a formação do hidrogel. Para então observar a influência do tripeptídeo, da temperatura e do pH na capacidade do polímero de absorver água e em sua estrutura. Para isso, foram realizadas análises de desvio quadrático médio estrutural, raio de giro e ligações de hidrogênio. As análises de função de distribuição radial mostraram indícios da formação de ligações de hidrogênio, tanto de interações intramolecular como intermolecular. Enquanto as demais análises mostraram que pode ocorrer comportamento responsivo para a temperatura de 310 K. Quando a pH do meio passa de neutro para ácido, ocorrem mudanças nas ligações de hidrogênio e na estrutura. Estudos experimentais de hidrogéis ainda possuem algumas limitações, visto que certas características do material não podem ser determinadas com precisão. Através de métodos computacionais medidas como a quantidade e localização de reticulações e de peptídeo podem ser determinadas. Assim, estudos computacionais prévios ou posteriores podem ajudar a esclarecer dados obtidos experimentalmente.Hydrogels are three-dimensional polymeric network crosslinked to each other by chemical or physical crosslinks, and can imbibe water or biological fluids. The materials structure allows it to have high levels of hydrophilicity and biocompatibility, which together with the other properties make them promising biomaterials. Due to these two characteristics hydrogels have numerous biomedical and pharmaceutical applications. Some hydrogels have a responsive behavior due to changes in their environment, the so-called stimuli-responsive hydrogels, or “smart” hydrogels. For this work the poli(vinyl alcohol) polymer functionalized with RGD peptide was chosen. The work was developed using molecular dynamics simulations in order to observe the hydrogel formation and also the influence of tripeptide, temperature and pH in water imbibe capacity and polymer structure. For this analysis of root-mean-square deviation, radius of gyration and radial distribution function was performed. The analysis of radial distribution function showed signs of hydrogen bond formation of both intramolecular and intermolecular interactions. Other analysis showed that thermoresponsive behavior may occur for 310 K. When the environment pH value is modified from neutral to acidic, changes occur in hydrogen bonds and structure. Experimental studies of hydrogels have some limitations because some characteristics of the material can’t be precisely determinated. With computational methods the amount and the location of crosslinks and peptide can be determinated. Therefore, previous or posterior computational studies can help to elucidate experimental data.
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Welsh, Daniel J. "Dendritic and self-assembling linear RGD peptides : from integrin binding to responsive hydrogels." Thesis, University of York, 2011. http://etheses.whiterose.ac.uk/2350/.
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Several studies exist in the literature which utilise either dendritic (covalent) or self-assembling (non-covalent) strategies to achieve multivalent binding to a biological target, but rarely are the two explored together. Herein, we compare and contrast dendritic and self-assembling approaches to organise a multivalent array of ligands to bind the protein, integrin αvβ3. In the first instance, linear RGD (Arg-Gly-Asp) peptides were covalently attached to first and second generation dendritic frameworks, and a positive (monovalent) and negative control were synthesised. A fluorescence polarisation (FP) competition assay was used to quantify the binding. The first generation dendron (2.16) was the most effective binder, with an EC50 of 125 μM (375 μM per peptide unit); significantly better than the monovalent ligand (2.19), the binding of which could not be quantified in our assay, even at 1 mM concentration; whilst the second generation dendron (2.17) was somewhat less effective, indicating that there is an optimum number of ligands that can be displayed before the multiple ligand array becomes disadvantageous to the binding. To explore the non-covalent approach, the linear RGD peptide was conjugated to either a single hydrophobic C12 aliphatic chain (3.2), an aromatic pyrene (3.4), a C22 aliphatic chain (3.6), or two C12 aliphatic chains (3.18), which gave rise to amphiphilic peptides which were able to self-assemble to differing degrees and into markedly different morphologies, as shown by a Nile Red encapsulation study and TEM imaging. Spherical micelles were formed by amphiphiles 3.2 and 3.4, whereas 3.6 and 3.18 produced cylindrical, rod-like micelles. Compounds 3.2 and 3.4 were the most effective integrin binders at concentrations of 200 μM and 110 μM, respectively, whilst 3.6 and 3.18 failed to produce a quantifiable binding concentration. The results therefore show that not only does the micellar self-assembly approach yield multivalent ligand displays with improved efficiency of binding compared with the dendritic method, but the morphology of the self-assembled system can also be detrimental to the recognition of the protein, at least in our FP assay and using purified integrin in solution. Finally, we report on a family of linear RGD peptide conjugate hydrogelators. Of particular interest was the novel bolaamphiphile C12-[urea-RGD]2 (4.4), comprised of linear RGD peptide head groups connected to either end of a hydrophobic C12 aliphatic chain via urea linkages. The molecule undergoes thermoreversible chiral self-assembly in water and generates a sample-spanning nanofibrous gel network, as determined by circular dichroism spectroscopy and TEM/SEM imaging, respectively. Gels were formed at a minimum gel concentration (MGC) of 0.06 wt % (0.6 mg/ml, 0.5 mM), one of the lowest MGCs reported and represents a “super” hydrogel. We report on its responsiveness (breakdown) towards charge dense basic anions such as phosphate and acetate, but its stability in the presence of more charge diffuse halide and nitrate anions. Furthermore, we demonstrate the passive diffusion of encapsulated low MW additives out of the gel phase, whereas high MW, protein-sized molecules remain trapped within the fibrous network.
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Thoreau, Fabien. "Conception, synthèse et activité biologique de vecteurs peptidiques pour le ciblage et/ou la thérapie du cancer." Thesis, Université Grenoble Alpes (ComUE), 2017. http://www.theses.fr/2017GREAV006/document.
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Ces travaux de thèse portent sur la conception, la synthèse et l'étude biologique de vecteurs peptidiques pour des applications en diagnostic et/ou thérapie du cancer.Nous avons utilisé des châssis cyclodécapeptidiques fonctionnalisés de façon chimiosélective par des éléments de ciblage et des effecteurs. Ces châssis, dotés de quatre ligands c[RGDfK], possèdent une forte affinité pour les récepteurs intégrine avB3 qui sont surexprimés dans de nombreux cancers et par les cellules endothéliales de l'environnement tumoral. Ils sont en revanche peu exprimés par les tissus sain. La présentation multivalente des ligands -RGD- permet également au châssis d'être internalisé par les cellules tumorales.Nous avons donc mis au point des molécules composées du châssis peptidique, de quatre ligands -RGD- pour le ciblage tumoral, et de différents effecteurs pour plusieurs applications. A travers de multiples collaborations, nous avons relié ce vecteur à un agent hautement toxique (cryptophycine), un photosensibilisateur (DHP), un peptide pro-apoptotique (BAX), un complexe de Gallium 68 (pour une étude clinique de phase I pour une application en imagerie TEP). Nous avons également greffé ces châssis présentant quatre motifs -RGD- à des polymères ou à des nanoparticules de silice, tous deux fluorescents.Le projet principal de cette thèse était la conception de vecteurs ciblant deux récepteurs tumoraux de manière simultanée. En plus de cibler l'intégrine avB3, nous avons ciblé le récepteur NRP1 qui est lui aussi surexprimé lors de l'angiogenèse tumorale. Nous avons exploité divers réactions chimiosélectives (oxime, cycloaddition de Huisgen, amidation) pour concevoir des vecteurs fluorescents ciblant l'un des deux récepteurs ou les deux à la fois. Des tests biologiques in vitro et in vivo ont été réalisés. Il s'avère que les composés à double ciblage permettent une très bonne détection de la tumeur, mais non supérieure à des composés à mono ciblage. En revanche, la réponse cellulaire déclenchée par les composés à double ciblage est unique, et totalement différente d'une co-injection. Nous avons plusieurs éléments qui tendent à prouver qu'un complexe NRP1-vecteur-Intégrine se formerait et resterait ancré au niveau de la membrane cellulaire, bloquant son internalisationThis thesis work is about conception, synthesis and biological activities of peptide vectors for diagnostic and/or therapeutic applications against cancer.We used cyclodecapeptidic scaffolds chemoselectively handled with targeting elements and effectors. Those scaffolds presenting four c[RGDfK] ligands have a strong affinity for integrin avB3 receptors, wich are overexpressed in various cancers and by endothelial cells from the tumor surrounding. They are poorly expressed in healthy tissues. The multivalent presentation of -RGD- motifs higly increases the internalisation of the scaffold by tumor cells. Thus we developed molecules composed by four -RGD- motifs for tumor targeting, and different effectors for various applications. Thanks to multiple collaborations, we linked the vector to a highly cytotoxic compound (cryptophycine), a photosensitiser (DHP), a pro-apoptotic peptide (BAX), a DOTA complex (for 68-Ga complexation, for PET applications). We also grafted the cyclodecapeptide bearing four -RGD- motifs to polymers or silica nanoparticles, both fluorescent.The main project of this thesis was the conception of dual targeting vectors. Our objective was to simultaneously target two receptors overexpressed in the tumor periphery. Beside the targeting of avB3, we decided to target the NRP1 receptor, which is also overexpressed during tumor angiogenesis. We exploited various chemoselective reactions (oxime, huisgen cycloaddition, peptide coupling) to synthesise fluorescent vectors targeting one of the two receptors, or both. In vitro and in vivo biological experiments were realised. We discovered that dual targeting compounds allow a really good tumor detection, but inferior to mono targeting ones. Nevertheless, the cellular answer triggered by dual targeting compounds is totally different from those obtained with other compounds, including co-injection. We found different elements that tend to show that a NRP1-vector-integrin could be formed, and would be blocked inside the cellular membrane, resulting in its internalisation's blocking
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Oliveira, Érica Aparecida de. "Desenvolvimento de radiotraçadores angiogênicos para diagnóstico de glioma: estudo em modelo animal." Universidade de São Paulo, 2014. http://www.teses.usp.br/teses/disponiveis/85/85131/tde-02122014-143353/.
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A imagem molecular oferece a perspectiva de detectar doenças bem antes de os sintomas surgirem. A vasculatura tumoral é vital no crescimento do tumor e na disseminação de metástases, sendo assim alguns radiofármacos são dirigidos para a angiogênese. O glioma, tumor cerebral de baixa incidência porém alta mortalidade, requer um diagnóstico precoce para favorecimento da abordagem terapêutica. O objetivo desse estudo foi o desenvolvimento de novo radiofármaco para diagnóstico por imagem de glioma, baseado em peptídeos angiogênicos (GX1 e GX1-RGD) marcados com o radioisótopo tecnécio-99m. O desempenho dos conjugados peptídicos mostraram-se bastante parecidos em diversas avaliações. Eles foram radiomarcados com alta pureza radioquímica (>96%) e estáveis em soro até pelo menos 4h. Ambos são hidrofílicos e com baixa ligação às proteínas plasmáticas. A biodistribuição em animais sadios demonstrou alta excreção renal e depuração sanguínea rápida para ambos os radiotraçadores. Nos estudos in vitro, o 99mTc-HYNIC-PEG4-c(GX1) apresentou picos de ligação aos 60 min e o 99mTc-HYNIC-E-[c(RGDfk)-c(GX1)]) aos 120 min, nas células endoteliais HUVEC, usadas como controle, e nas células tumorais das linhagens U87MG e T98G. A captação tumoral nos animais foi mais acentuada para células U87MG, especialmente para o 99mTc-HYNIC-E-[c(RGDfk)-c(GX1)]) (2,87 ± 0,53% DI/g) aos 60 min p.i., com boa visualização em imagens adquiridas por gama-câmara e micro-SPECT/CT. Estudos realizados com os peptídeos conjugados à nanopartículas magnéticas para visualização em ressonância magnética também demonstraram especificidade dos produtos em tecidos tumorais. O desempenho do 99mTc-HYNIC-E-[c(RGDfk)-c(GX1)]) foi superior que o do traçador GX1, quanto à captação no glioma humano, podendo ser considerado como um promissor radiofármaco para diagnóstico de gliomas.Molecular imaging offers the prospect of detecting diseases well before the symptoms appear. The tumor vasculature is vital in the tumor growth and dissemination of metastasis, thus some radiopharmaceuticals are directed to angiogenesis. The glioma, a brain tumor of low incidence but high mortality, requires an early diagnosis for favoring therapeutic approaches. The aim of this study was the development of a new radiopharmaceutical for imaging diagnosis of glioma, based in angiogenic peptides (GX1 and RGD-GX1) radiolabeled with technetium-99m radioisotope. The peptidic conjugates showed very similar performance in several evaluation. They were radiolabeled with high radiochemical purity (>96%) and are stable in the blood serum at least for four hours. Both are hydrofilic and had minimal binding to plasma protein. The biodistribution in healthy mice at many times, showed high renal excretion and fast blood clearance for both radiotracers. At in vitro studies, the 99mTc-HYNIC-PEG4-c(GX1) exhibit binding peaks at 60 min and the 99mTc-HYNIC-E-[c(RGDfk)-c(GX1)]) at 120 min, at HUVEC endotelial cells, used as control, and at tumor cell lines U87MG and T98G. The animal tumor uptake was more pronounced for U87MG cells, specially for 99mTc-HYNIC-E-[c(RGDfk)-c(GX1)]) (2.87 ± 0.53% DI/g) at 60 min p.i., with good visualization in images acquired with gama-camara and micro-SPECT/CT. Studies performed with peptides conjugate to magnetonanoparticles for MRI visualization also demonstred the peptides specificity in tumor tissue.The 99mTc-HYNIC-E-[c(RGDfk)-c(GX1)]) performance was superior to the GX1 tracer, regarding the glioma uptake, and may be consider as a promisser radiopharmaceutical for glioma diagnosis.
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Leiß, Michael. "Genetic analyses of fibronectin functions in vivo and in vitro." kostenfrei, 2009. http://www.opus-bayern.de/uni-regensburg/volltexte/2009/1414/.
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Miksch, Christian. "Verwendung von alpha-(Alkylthio)glycinen zur Festphasensynthese modifizierter Peptide und Synthese von RGD-Cyclopeptiden." Diss., lmu, 2001. http://nbn-resolving.de/urn:nbn:de:bvb:19-2806.
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Hersel, Ulrich. "Monomere und multimere RGD-Peptide für die integrinvermittelte Zelladhäsion auf Biomaterialien und zur Tumordiagnose." [S.l.] : [s.n.], 2003. http://deposit.ddb.de/cgi-bin/dokserv?idn=968944876.
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Bozon, Aurelie. "Le RAFT-RGD radiomarqué avec un émetteur °- comme nouvel agent de radiothérapie interne vectorisée." Phd thesis, Université de Grenoble, 2013. http://tel.archives-ouvertes.fr/tel-00820235.
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Le RAFT-RGD radiomarqué avec un émetteur β- comme nouvel agent de radiothérapie interne vectorisée. L'intégrine αvβ3 est fortement impliquée en oncogenèse à travers son rôle dans la néoangiogenèse tumorale, dans la prolifération et la survie des cellules cancéreuses et dans le processus métastatique. L'intégrine αvβ3 est exprimée faiblement dans la plupart des tissus. Par contre, elle est fortement exprimée par les cellules endothéliales activées lors de l'angiogenèse et par les cellules de nombreux types de cancers invasifs. Ces caractéristiques font de l'intégrine αvβ3 une excellente cible pour l'imagerie et la thérapie de ces tumeurs. Le RAFT-RGD (Regioselectively Addressable Functionalized Template-(cyclo-[RGDfK])4) est un derivé polypeptidique constitué de quatre peptides cyclo-RGD (spécifiques de l'intégrine αvβ3) fixés sur un groupe porteur RAFT. Le RAFT-RGD cible spécifiquement l'intégrine αvβ3 in vitro et in vivo et permet la détection par imagerie nucléaire ou par fluorescence de tumeurs exprimant αvβ3 sur des modèles précliniques. Le RAFT-RGD un excellent vecteur potentiel pour cibler les tumeurs exprimant αvβ3 et pour y délivrer des traitements, que ce soit des molécules de chimiothérapie ou des radionucléides de thérapie. Cette étude est la première à évaluer le potentiel thérapeutique du RAFT-RGD radiomarqué avec un émetteur β- sur un modèle de souris Nude porteuses de tumeurs exprimant l'intégrine αvβ3. Une injection de 37 MBq de 90Y-RAFT-RGD ou de 177Lu-RAFT-RGD permet de ralentir significativement la croissance de tumeurs exprimant l'intégrine αvβ3 par rapport aux souris contrôles non traitées ou traitées avec la même activité de la molécule de contrôle non spécifique de la cible, le RAFT-RAD. En comparaison, une injection de 30 MBq de 90Y-RAFT-RGD ne permet pas de ralentir la croissance de tumeurs n'exprimant pas l'intégrine αvβ3. Le RAFT-RGD présente un bon potentiel pour le traitement de tumeurs exprimant l'intégrine αvβ3 lorsqu'il est radiomarqué avec des émetteurs β-. Mots clés : intégrine αvβ3, RAFT-RGD, ciblage tumoral, radiothérapie interne vectorisée.
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Genes, Nicholas G. "Chondrocyte Adhesion to RGD-bonded Alginate: Effect on Mechanotransduction and Matrix Metabolism: a Dissertation." eScholarship@UMMS, 2003. https://escholarship.umassmed.edu/gsbs_diss/89.
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The mechanism of mechanotransduction in chondrocyte matrix metabolism is not well understood, in part because of the density of cartilage and in part because of limitations in in vitroculture systems. Using alginate covalently modified to include the integrin adhesion ligand R-G-D (arginine-glycine-aspartate) represents a unique approach to studying mechanotransduction in that it allows for exploration of the role of integrin adhesion in mediating changes to chondrocyte behavior.
The hypothesis of this research was that chondrocytes will form a cytoskeletal adhesion to RGD-alginate mediated integrins, that this attachment will enable chondrocyte sensation of mechanical signals, and this signaling will alter chondrocyte matrix metabolism. The first aim of this research was to characterize chondrocyte attachment to RGD-alginate, and assess the role of substrate mechanics on chondrocyte attachment kinetics and morphology. Secondly, the effect of chondrocyte attachment to RGD-alginate in 3D culture on matrix biosynthesis was assessed, as were changes in substrate mechanics. Finally, this research aimed to determine the metabolic response of chondrocytes to changes in intrinsic and extrinsic mechanics.
It was found that the RGD ligand functionalized the alginate scaffold, enabling chondrocytes to sense the mechanical environment. Attachment kinetics, morphology, and proteoglycan metabolism were found to adapt to hydrogel matrix stiffness when an integrin adhesion was present. Externally applied compression was transmitted through this integrin attachment, causing changes in proteoglycan synthesis. Components of media serum were found to modulate the effects of integrin mechanotransduction.
These results were obtained by analyzing a novel approach with established techniques, such as the DMB dye assay for sulfated GAG content. The conclusions conform to diverse data from cartilage explant loading and monolayer culture studies, yet were accomplished using one versatile system in a straightforward manner. The potential of this system extends further, into identification of intracellular signaling pathways and extracellular modulation of matrix components. Seeded RGD-alginate is well suited for studying consequences of integrin attachment.
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Carpentier, Emilie. "EP1 et PME1 : deux protéines pariétales à motif RGD, quels rôles chez le lin ?" Rouen, 2005. http://www.theses.fr/2005ROUES025.
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Chez les animaux, l'adhérence cellulaire dépend d'interactions intégrines/protéines de matrice extracellulaire via un motif RGD. Chez les plantes, les mécanismes d'adhérence sont méconnus, bien que certaines protéines possèdent le motif RGD. Nous avons caractérisé 2 protéines pariétales de lin possédant ce motif. La première, une pectine méthylestérase (PME), catalyse la dé-méthylation des pectines. PME1 est maturée au cours de sa sécrétion et une fois mise en place dans la paroi de cals la surexprimant. Son pro-peptide n'a pas d'impact sur sa localisation. La seconde, EP1, glycoprotéine homologue aux Extracellular Protein, présente des similarités avec les lectines à mannose dans sa région N-terminale. In vitro, EP1 recombinante permet l'adhérence de cellules animales sans qu'elles forment de pseudopodes. De plus, la régulation positive de son expression par l'acide salicylique implique cette protéine dans la réponse aux pathogènesIn animals, cellular adhesion was widely studied, particularly interactions between integrins and extracellular matrix proteins, via the RGD motif. In plants, mechanisms involved in adhesion are still unknown, although some proteins contain a RGD motif. We characterized 2 flax cell wall proteins with this motif. The first one, a pectin methylesterase (PME) catalyzes the pectin de-methylation. PME1 is matured during its secretion and after its deposition in wall of callus overexpressing this protein. Its pro-peptide has no impact on its cell wall localization. The second one EP1, glycoprotein homologous to the Extracellular Protein shares, in N-terminal region, similarities with mannose lectins. In vitro, recombinant EP1 allows cells to adhere but not to spread like they do with adhesion proteins as fibronectin. Finally, the positive regulation of its expression by salicylic acid suggests that this protein is involved in the pathogen response
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Petitprin, Aurélie. "Le RAFT-RGD radiomarqué avec un émetteur °- comme nouvel agent de radiothérapie interne vectorisée." Thesis, Grenoble, 2013. http://www.theses.fr/2013GRENS002/document.
Full textAbstract:
Le RAFT-RGD radiomarqué avec un émetteur β- comme nouvel agent de radiothérapie interne vectorisée. L'intégrine αvβ3 est fortement impliquée en oncogenèse à travers son rôle dans la néoangiogenèse tumorale, dans la prolifération et la survie des cellules cancéreuses et dans le processus métastatique. L'intégrine αvβ3 est exprimée faiblement dans la plupart des tissus. Par contre, elle est fortement exprimée par les cellules endothéliales activées lors de l'angiogenèse et par les cellules de nombreux types de cancers invasifs. Ces caractéristiques font de l'intégrine αvβ3 une excellente cible pour l'imagerie et la thérapie de ces tumeurs. Le RAFT-RGD (Regioselectively Addressable Functionalized Template-(cyclo-[RGDfK])4) est un derivé polypeptidique constitué de quatre peptides cyclo-RGD (spécifiques de l'intégrine αvβ3) fixés sur un groupe porteur RAFT. Le RAFT-RGD cible spécifiquement l'intégrine αvβ3 in vitro et in vivo et permet la détection par imagerie nucléaire ou par fluorescence de tumeurs exprimant αvβ3 sur des modèles précliniques. Le RAFT-RGD un excellent vecteur potentiel pour cibler les tumeurs exprimant αvβ3 et pour y délivrer des traitements, que ce soit des molécules de chimiothérapie ou des radionucléides de thérapie. Cette étude est la première à évaluer le potentiel thérapeutique du RAFT-RGD radiomarqué avec un émetteur β- sur un modèle de souris Nude porteuses de tumeurs exprimant l'intégrine αvβ3. Une injection de 37 MBq de 90Y-RAFT-RGD ou de 177Lu-RAFT-RGD permet de ralentir significativement la croissance de tumeurs exprimant l'intégrine αvβ3 par rapport aux souris contrôles non traitées ou traitées avec la même activité de la molécule de contrôle non spécifique de la cible, le RAFT-RAD. En comparaison, une injection de 30 MBq de 90Y-RAFT-RGD ne permet pas de ralentir la croissance de tumeurs n'exprimant pas l'intégrine αvβ3. Le RAFT-RGD présente un bon potentiel pour le traitement de tumeurs exprimant l'intégrine αvβ3 lorsqu'il est radiomarqué avec des émetteurs β-. Mots clés : intégrine αvβ3, RAFT-RGD, ciblage tumoral, radiothérapie interne vectoriséeΒ- emitters radiolabeled RAFT-RGD as new agents for internal targeted radiotherapy. The αvβ3 integrin is known to play an important role in tumor-induced angiogenesis, tumor proliferation, survival and metastasis. Because of its overexpression on neoendothelial cells such as those present in growing tumors, as well as on tumor cells of various origins, αvβ3 integrin is an attractive molecular target for diagnosis and therapy of the rapidly growing and metastatic tumors. A tetrameric RGD-based peptide, regioselectively addressable functionalized template-(cyclo-[RGDfK])4 (RAFT-RGD), specifically targets integrin αvβ3 in vitro and in vivo. RAFT-RGD has been used for tumor imaging and drug targeting. This study is the first to evaluate the therapeutic potential of the β- emitters radiolabeled tetrameric RGD peptide RAFT-RGD in a Nude mouse model of αvβ3-expressing tumors. An injection of 37 MBq of 90Y-RAFT-RGD or 177Lu-RAFT-RGD in mice with αvβ3-positive tumors caused a significant growth delay as compared with mice treated with 37 MBq of 90Y-RAFT-RAD or 177Lu-RAFT-RAD or untreated mice. In comparison, an injection of 30 MBq of 90Y-RAFT-RGD had no efficacy for the treatment of αvβ3-negative tumors. 90Y-RAFT-RGD and 177Lu-RAFT-RGD are potent αvβ3-expressing tumor targeting agents for internal targeted radiotherapy. Keys words : integrin αvβ3, RAFT-RGD, tumour targeting, internal targeted radiotherapy
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Guven, Sinan. "Integrated Biomimetic Scaffolds For Soft Tissue Engineering." Master's thesis, METU, 2006. http://etd.lib.metu.edu.tr/upload/3/12607436/index.pdf.
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Tissue engineering has the potential to create new tissue and organs from cultured cells for transplantation. Biodegradable and biocompatible scaffolds play a vital role in the transfer of the cultured cells to a new tissue. Various scaffolds for soft tissue engineering have been developed, however there is not any structure totally mimicking the natural extracellular matrix (ECM), ready to use.
In this study biodegradable and biocompatible scaffolds were developed from natural polymers by tissue engineering approach and tested in vitro. Scaffolds (SCAF) were prepared with freeze drying and composed of chitosan, gelatin and dermatan sulfate. Polymer solutions were treated with different stirring rates (500 rpm and 2000 rpm), freezing temperatures (-20 °C and -80 °
C) and molding (cylindrical mold and petri dish) to achieve porous structure in order to provide sufficient space for cell growth and extracellular matrix production. Among the prepared scaffolds at different conditions, the scaffolds prepared at 500 rpm and frozen at -80 °
C, (SCAF-1), was chosen for further studies. These scaffolds achieved 0.512 MPa tensile strength, with 9.165 MPa tension modulus and 3.428 MPa compression modulus. Besides in lysozyme containing degradation medium they conserved their integrity and lost about 30 % of their initial weight in 30 days period. Mechanical and enzymatic degradation tests showed that scaffolds have physical integrity for the tissue engineering applications. To mimic the natural tissue and enhance cell growth, biologically active arginine &
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glycine - aspartic acid - serine (RGDS) peptides and platelet derived growth factor-BB (PDGF-BB) were immobilized on the SCAF-1. Fibroblast cells were seeded on the scaffolds containing RGDS, (SCAF-1-RGDS), and PDGF-BB, (SCAF-1-RGDS-PDGF), and incubated in media either free of serum or containing serum. Scaffolds immobilized with RGDS and PDGF-BB had the highest attached cell number by the day 15. Florescence microscopy studies also indicated that RGDS and RGDS-PDGF modified scaffolds were more suitable than controls, (SCAF-1), for cell growth and proliferation. According to scanning electron microscopy (SEM) results, modified scaffolds demonstrated better cell morphology and attachment of cells. Based on the obtained results, it can be concluded that RGDS-PDGF immobilized chitosan-gelatin-dermatan sulfate systems have a great potential to be used as a scaffold for soft tissue engineering applications.
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Silva, Gustavo de Carvalho. "RGPD aplicado nas PME portuguesas." Master's thesis, 2020. http://hdl.handle.net/10362/94888.
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Dissertation presented as the partial requirement for obtaining a Master's degree in Information Management, specialization in Knowledge Management and Business IntelligenceO Regulamento Geral sobre a Proteção de Dados (RGPD) regula a proteção das pessoas singulares no que diz respeito ao tratamento de dados pessoais e à livre circulação desses dados, com entrada em aplicação a 25 de maio de 2018. Vem introduzir não só novas regras como também elevadas coimas em caso de incumprimento, o que exige uma atenção cuidada das organizações que lidam e possuem à sua guarda dados pessoais. As PME, dado as suas características dimensionais, poderão encontrar muitas dificuldades na implementação do novo regulamento. É preciso compreender como as PME lidam com dados pessoais e de que forma se adaptaram para cumprir o regulamento durante este primeiro ano de implementação Para esta dissertação, foi conduzido um inquérito às PME portuguesas com o objetivo de avaliar que tipo de dados estas tratam, o conhecimento que têm do regulamento e como se adaptaram as novas regras.
The General Data Protection Regulation (RGPD) regulates the protection of individuals regarding the processing of personal data and the free movement of such data, which entered into force on 25 May 2018. It introduces not only new rules but also high fines in case of non-compliance, which requires the careful attention of the organizations that handle and keep individual’s personal data. SMEs, given their dimensional characteristics, may encounter many difficulties in implementing the new regulation. We need to understand how SMEs handle personal data and how they have adapted to comply with the regulation during this first year of implementation. For this dissertation, a survey was conducted on Portuguese SMEs to assess what type of data they deal with, their knowledge of the regulation and how the new rules have been adapted.