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1
Atris, Youssef H. "Design of RSD-cyclic and hybrid RSD-Cyclic/sigma-delta ADCs." Diss., Wichita State University, 2007. http://hdl.handle.net/10057/1421.
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In this research work two contributions to the area of analog to digital data converters
have been discussed. The area of focus is the RSD-Cyclic and sigma-delta ADC. First a novel
hybrid RSD-Cyclic-sigma-delta architecture is introduced which is a combination of the RSDCyclic
ADC and sigma-delta ADC architectures. The resolution obtained with this hybrid
architecture is n = n1 + n2 , where n1 = MSBrsd stands for the most significant bits obtained from
the RSD-architecture and n2 = LSBsdl stands for the least significant bits obtained from the
sigma-delta architecture. Since the sigma-delta block is required to achieve only an n2-bit
resolution (n2, n1 < n ) the over-sampling ratio required for the sigma-delta is not as high as the
over-sampling ratio required to achieve n-bit resolution. Also the requirements on the RSD-Cyclic
block are only the requirements to achieve n1-bit resolution, which means that the
requirements on the analog building blocks for the RSD-Cyclic part are more relaxed. Secondly,
in the RSD-Cyclic area we have introduced a circuit technique that allows an entire ADC system
to run on one operational amplifier without any loss of functionality. Therefore we will be saving
power and area, both very desirable features for mobile applications.Thesis (Ph.D.)--Wichita State University, College of Engineering, Dept. of Electrical and Computer Engineering
"July 2007."
2
Atris, Youssef H. Paarmann Larry D. "Design of RSD-cyclic and hybrid RSD-Cyclic/sigma-delta ADCs /." Diss., A link to full text of this thesis in SOAR, 2007. http://hdl.handle.net/10057/1421.
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Farhat, Farhat Agribi. "Performance of concrete structures retrofited with CARDIFRC RTM after thermal cycling." Thesis, Cardiff University, 2004. http://orca.cf.ac.uk/55930/.
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A new retrofitting technique using CARDIFRCRTM, a material compatible with concrete, has recently been developed at Cardiff University. It overcomes some of the problems associated with the current techniques based on externally bonded steel plates and FRP (fibre-reinforced polymer), which are due to the mismatch of their tensile strength and stiffness with that of concrete structure being retrofitted. This study investigates the effect of thermal cycles on the performance of reinforced concrete control and retrofitted beams. The concrete beams were heated to a maximum temperature of 90°C from the room temperature of about 25°C. The number of thermal cycles varied from 0 to 90 cycles. After the requisite number of thermal cycles, the beams were tested at room temperature in four-point bending. The tests indicate that the retrofitted beams are stronger, stiffer and more importantly failed in flexure. No visual deterioration or bond degradation was observed after thermal cycling of the retrofitted beams (the bond between the repair material and the concrete substrate remained intact) attesting to the good thermal compatibility between the concrete and CARDIFRCRTM. Therefore, this type of retrofit material can be successfully used in hot climates. The study also evaluates the performance of normal and high strength concretes repaired with CARDIFRCRTM using the wedge splitting test (WST). The main factors that could affect the bond between the repair material and concrete such as the surface roughness and thermal cycling are also investigated. It is shown that surface roughness plays a significant role in the overall bonding system, and no visual deterioration is observed after thermal cycling. Two analytical/computational models for predicting the ultimate moment capacity and the complete load-deflection behaviour of the retrofitted beams were applied. Both models predict very well the ultimate moment capacity of the retrofitted beams.
4
Reinmann, Andrew B. "Effects of Harvesting on Nutrient Cycling, Red Spruce Radial Growth, and Dendrochemistry 30 Years after Harvesting in Northern Maine, USA." Fogler Library, University of Maine, 2006. http://www.library.umaine.edu/theses/pdf/ReinmannAB2006.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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Maren, D. S. van. "Morphodynamics of a cyclic prograding delta : the Red River, Vietnam /." Utrecht : Royal Dutch Geographical Soc. [u.a.], 2004. http://www.gbv.de/dms/goettingen/396699715.pdf.
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Harrison, Kathryn Ann. "How browsing by red deer impacts on soil nutrient cycling in regenerating native woodland in the Scottish Highlands." Thesis, Lancaster University, 2003. http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.421618.
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McLatchie, Linda. "Block of the cyclic GMP-activated conductance of salamander rod photoreceptors." Thesis, University of Cambridge, 1994. http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.320405.
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Rix, Laura [Verfasser], Christian [Akademischer Betreuer] Wild, and Claudio [Akademischer Betreuer] Richter. "Carbon and nitrogen cycling by Red Sea coral reef sponges / Laura Rix. Betreuer: Christian Wild. Gutachter: Christian Wild ; Claudio Richter." Bremen : Staats- und Universitätsbibliothek Bremen, 2015. http://d-nb.info/1079652337/34.
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HOLTZCLAW, JOHN DAVID. "CHARACTERIZATION OF LIGHT SICKLE ERYTHROCYTES DERIVED FROM DENSE ERYTHROCYTES IN VITRO." University of Cincinnati / OhioLINK, 2001. http://rave.ohiolink.edu/etdc/view?acc_num=ucin990632508.
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Clayton, Russell Adrian. "Investigation of stabilized Berea Red soil with emphasis on tensile and cyclic triaxial tests." Master's thesis, University of Cape Town, 1989. http://hdl.handle.net/11427/8319.
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Includes bibliographical references.This dissertation investigates the soil mechanical properties of a sample of Berea Red soil and the most suitable methods of treatment to improve it. Special attention has been paid to lime stabilization and different curing techniques. Gradings, special indicators and California Bearing Ratios were determined on both natural and lime stabilized Berea Red soil. Consolidometer tests were performed on natural and lime or cement stabilized soil at various densities to establish the compressibility and collapse potential. A computer controlled Indirect Tensile Testing with data logging facilities was developed in apparatus order that some of the soil mechanical properties of Berea Red soil may be determined. Natural and stabilized Berea Red soil was tested in a monotonic and cyclic triaxial apparatus to determine the short and long stress strain characteristics.
12
Sunderman, Elizabeth R. "Single-channel kinetic analysis of the allosteric transition of rod cyclic nucleotide-gated channels /." Thesis, Connect to this title online; UW restricted, 1998. http://hdl.handle.net/1773/10526.
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Clements, Peter James Mackenzie. "Molecular genetic investigations of rod cyclic GMP phosphodiesterase beta subunit in canine Generalised Progressive Retinal Atrophy." Thesis, University College London (University of London), 1995. http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.307615.
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Cook, Terry Ann. "Function and regulation of the delta subunit of PDE6 /." Thesis, Connect to this title online; UW restricted, 2001. http://hdl.handle.net/1773/6287.
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Patel, Kishan. "Determination of the hydrogen peroxide concentration in rotenone induced dopaminergic cells using cyclic voltammetry and amplex red." Honors in the Major Thesis, University of Central Florida, 2012. http://digital.library.ucf.edu/cdm/ref/collection/ETH/id/600.
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Parkinson's disease (PD) is a neurodegenerative condition that affects millions of people worldwide. The exact etiology of PD is unknown. However, it is well established that environmental factors contribute to the onset of PD. In particular, chemicals such as the insecticide Rotenone have been shown to increase the death of dopaminergic (DA) neurons by increasing levels of reactive oxygen species (ROS). ROS such as hydrogen peroxide (H2O2) have been shown to be elevated above basal levels in PD patients. Currently, to measure H2O2 concentrations, a commercially available (Amplex® Red) fluorescent assay is used. However, the assay has limitations: it is not completely specific to hydrogen peroxide and can only measure extracellular ROS concentrations. This research focuses on testing an electrochemical sensor that uses cyclic voltammetry to quantitatively determine concentrations of H2O2 released from a cell culture. The sensor was first tested in normal cell culture conditions. Next, chemical interference was reduced and the sensor was optimized for accuracy by altering protein concentrations in the media. Finally, Rotenone was added to a cell culture to induce H2O2 production. Near real-time measurements of H2O2 were taken using the sensor and comparisons made to the fluorescent assay method. Overall, we are trying to determine if the electrochemical sensor can selectively and quantitatively measure H2O2 released from cells. Being able to track the production, migration and concentration of H2O2 in a cell can help researchers better understand its mechanism of action in cell death and oxidative damage, thus getting closer to finding a cure for PD.B.S.
Bachelors
Burnett School of Biomedical Sciences
Molecular and Microbiology
16
Becirovic, Elvir. "Role of the CNGB1a Subunit of the Rod Cyclic Nucleotide-Gated Channel in Channel Gating and Pathogenesis of Retinitis Pigmentosa." Diss., lmu, 2010. http://nbn-resolving.de/urn:nbn:de:bvb:19-119088.
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Hu, Bin. "Vesicle adhesion via interaction of integrin [alpha]IIb[beta]3 [alpha IIb beta 3] and cyclic-RGD-lipopeptide a model of cell adhesion processes /." [S.l. : s.n.], 2001. http://deposit.ddb.de/cgi-bin/dokserv?idn=962127124.
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Mikdar, Mahmoud. "Role of nucleotide metabolite transporters in erythropoiesis and red blood cell functions." Thesis, Université de Paris (2019-....), 2020. http://www.theses.fr/2020UNIP7099.
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De récents travaux ont montré que les voies métaboliques sont fortement impliquées dans la régulation de l’engagement et la différentiation des cellules souches hématopoïétiques (CSHs) vers les différentes lignées hématopoïétiques. Les nucléosides sont des métabolites et précurseurs indispensables pour la biosynthèse des nucléotides, et dont la disponibilité intracellulaire dépend de leur transport à travers la membrane plasmique. Cependant, le rôle des transporteurs de nucléosides et de nucléotides dans l’engagement érythroïde des CSHs reste mal défini. Au cours de ma thèse, l’analyse fonctionnelle des cellules sanguines de patients déficitaires de ENT1 ou ABCC4 a démontré pour la première fois que le transport des nucléosides (ENT1) et nucléotides (ABCC4) est essentiel pour maintenir (i) le métabolisme des nucléotides cycliques et désoxynucléotide, (ii) une morphologie et une déformabilité normales des globules rouges, (iii) la phosphorylation des protéines de la membrane érythrocytaire ainsi que l’organisation du cytosquelette, (iv) la physiologie plaquettaire et (v) l’érythropoïèse ex vivo. De plus, nos expériences mécanistiques ont démontré que ENT1 joue un rôle crucial dans l’engagement des CSHs vers la lignée érythroïde en contrôlant le métabolisme des nucléotides cycliques et l’activation des facteurs de transcriptions érythroïdes. Ce travail a également montré qu’une mutation compensatoire dans le gène ABCC4, retrouvée chez deux patients ENT1null, diminuait les altérations érythroïdes chez ces patients, ce qui confirme le rôle de ces deux transporteurs dans la régulation intracellulaire de l’AMP cyclique. De plus, ce résultat a été confirmé par un modèle souris Ent1-/- puisque le traitement de ces souris avec un inhibiteur de ABCC4 augmente l’engagement érythroïde des CSHs, l’érythropoïèse et l’hématocrite. En outre, une étude protéomique et génomique sur des sujets PEL-négatif a montré qu’une large délétion dans le gène ABCC4 est responsable de ce groupe sanguin. L’inactivation du gène ABCC4 dans une lignée cellulaire par CRISPR-Cas9 a confirmé que l’antigène de groupe sanguin PEL est portée par la protéine ABCC4. Contrairement à ENT1, l’absence totale de ABCC4 est associée à une altération de la fonction plaquettaire sans anomalie de la lignée érythroïde et dont le mécanisme de compensation n’implique pas ENT1. En conclusion, mon travail de thèse dévoile un nouveau mécanisme moléculaire régulant l’érythropoïèse, et démontre le rôle important du métabolisme des nucléotides dans l’engagement des CSHs et dans la biologie érythroïde. Nos résultats ouvrent de nouvelles perspectives pour le développement de stratégies thérapeutiques pour le traitement de l’anémie basées sur la disponibilité intracellulaire des nucléosides et des nucléotidesRecently, metabolic pathways have emerged as critical components in the regulation of hematopoietic stem cell (HSC) renewal, as well as in lineage commitment and differentiation. Nucleosides are major metabolite precursors for nucleotide biosynthesis and their availability in HSCs is dependent on their transport through specific membrane transporters. However, the role of nucleoside and nucleotide transporters in the differentiation of HSCs to the erythroid lineage remains undefined. In the present work, we demonstrate for the first time that nucleoside (ENT1) and nucleotide (ABCC4) transport is essential for the (i) metabolism of cyclic nucleotides and deoxynucleotides (ii) erythrocyte morphology and deformability, (iii) erythrocyte membrane protein phosphorylation and skeleton organization, (iv) platelet function, and (v) ex vivo erythropoiesis. Interestingly, functional and mechanistic experiments showed that the equilibrative nucleoside transporter 1 (ENT1) controls the nucleotide metabolism and the activation of erythroid transcription factors. This finding explains the role of ENT1 in maintaining the optimal erythroid commitment and differentiation of HSCs. On the other hand, although the downregulation of the ABC nucleotide transporter ABCC4 attenuates the erythroid disorders in ENT1null patients, its total loss results in abnormal platelet function without erythroid disorders. Importantly, we demonstrate that a large deletion in ABCC4 gene is associated with the PEL-negative null blood phenotype. The loss of PEL expression on ABCC4-CRISPR-Cas9 K562 cells and its overexpression in ABCC4-transfected cells provided evidence that ABCC4 is the gene underlying the PEL blood group antigen. Targeting ENT1 and ABCC4 transporters either by knockout or pharmacological inhibition in mice lead to a marked change in blood cells counts. Specifically, the genetic deletion of Ent1 in mice results in a decreased RBC production and macrocytosis. While mice treated with ABCC4 inhibitor increased the erythroid commitment of HSCs, and enhanced erythropoiesis as demonstrated by the increase of circulating erythrocytes and reticulocytes. Overall, our findings reveal a new molecular mechanism regulating erythropoiesis and highlight the important role of nucleotide metabolism in the lineage commitment of HSCs and erythroid biology. Our findings open new avenues for the development of novel therapeutic strategies for the treatment of anemia
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Victoria, Rosemary. "Development of luminescent ruthenium complexes for in-vitro fluorescence imaging of angiogenesis with the RGD peptide." Honors in the Major Thesis, University of Central Florida, 2012. http://digital.library.ucf.edu/cdm/ref/collection/ETH/id/633.
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Herein we report the synthesis of an RGD-ruthenium bipyridine [Ru(Bpy)2(BpyRGD)]2+ complex aimed at the detection of angiogenesis. Angiogenesis plays a critical role in many pathophysiological processes, such as tumor growth. The αv-integrins (αv[beta]3, αv[beta]5) are currently used as molecular targeting sites for anti-angiogenic therapies. The [Ru(Bpy)2(BpyRGD)]2+ complex is an organometallic luminescent probe, which enables noninvasive, in vitro imaging of αv[beta]3 expression. Peptides containing the arginine-glycine-aspartic acid (RGD) sequence have been shown to bind strongly to the αvb3 integrin. The RuBpy probes are soluble in water, display long lifetimes, and are photochemically stable. These properties enable the Ru(tris-bpy) complexes to be useful in numerous applications in biophysical and cell biology. The [Ru(Bpy)2(BpyRGD)]2+ complex was synthesized by combining the succinimidyl ester on the RuBpy complex with the lysine of the c(RGDfK) peptide. The results of the one-photon fluorescence bioimaging showed selective binding of the cyclic RGD to αv[beta]3 integrin, which supports previous literature. The high luminescence intensity, long lifetimes, and low cell toxicity levels of dye [Ru(Bpy)2(BpyRGD)]2+, illustrates the potential usage of this probe for future biological applications.B.S.
Bachelors
Sciences
Biology
20
Akasov, Roman. "Novel 3D in vitro models based on multicellular tumor spheroids to test anticancer drugs and drug delivery vehicles." Thesis, Strasbourg, 2017. http://www.theses.fr/2017STRAF013/document.
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Les sphéroïdes multicellulaires tumoraux (SMT) constituent un outil prometteur dans le domaine de l’étude biologique des tumeurs. Le but de la thèse était de développer une technique de la formation de SMT et de démontrer la disponibilité de ces sphéroïdes comme modèle in vitro 3D pour tester l’efficacité de principes actifs anticancéreux ainsi que celle de formulations de délivrance de médicaments. L'effet d’auto-assemblage de cellules induit par une addition des peptides RGD cycliques a été étudié pour 16 lignées cellulaires de différentes origines. Le peptide cyclique RGDfK et sa modification avec le cation triphenylphosphonium (TPP) ont permis de mettre en évidence l’induction de formation de sphéroïdes. Les sphéroïdes ont été employés comme modèles pour évaluer la cytotoxicité de principes actifs antitumoraux (doxorubicine, curcumine, temozolomide) et un certain nombre de formulations nano- et micrométriques (microréservoirs, nano-émulsions et micelles)Multicellular tumor spheroids (MTS) are a promising tool in tumor biology. The aim of the Thesis was to develop a novel highly reproducible technique for MTS formation, and to demonstrate the availability of these spheroids as 3D in vitro model to test anticancer drugs and drug delivery vehicles. Cell self-assembly effect induced by an addition of cyclic RGD-peptides directly to monolayer cultures was studied for 16 cell lines of various origin. Cyclo-RGDfK peptide and its modification with triphenylphosphonium cation (TPP) were found to induce spheroid formation. The spheroids were used as a model to evaluate the cytotoxicity of antitumor drugs (doxorubicin, curcumin, temozolomide) and a number of nano- and micro- formulations (microcontainers, nano-emulsions and micelles)
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Jusot, Maud. "Description de l'espace conformationnel de peptides cycliques de la famille RGD par une approche inspirée de la robotique et par des simulations de dynamique moléculaire." Electronic Thesis or Diss., Sorbonne université, 2018. http://www.theses.fr/2018SORUS201.
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Les petits peptides cycliques représentent une classe émergente et prometteuse de molécules thérapeutiques. Cependant le manque de connaissance de leur espace conformationnel rend difficile leur conception et la prédiction de leur structure. Afin de pouvoir améliorer les connaissances sur ces molécules aux propriétés uniques, nous avons voulu développer une approche alternative à celles existantes permettant la caractérisation la plus précise possible de leur espace conformationnel. Pour cela, nous avons développé une méthode EGSCyP, s'appuyant sur une représentation multi-niveaux du peptide : une représentation mécanique et l'utilisation d'algorithme issus du domaine de la robotique permettant une approche globale puis une amélioration de la précision en modèle tout atome. EGSCyP a été développé pour gérer les résidus modifiés tels que les résidus de forme D et N-méthylés. Cette méthode a été comparée à des simulations de dynamique moléculaire par échange de répliques et des données expérimentales pour la valider. Elle a été appliquée à un ensemble de pentapeptides cycliques RGD dérivés de la Cilengitide, un anticancéreux. Notre approche a montré de bonnes performances notamment en ce qui concerne la complétude de l'espace conformationnel de ces peptides et a permis d'évaluer l'impact des modifications chimiques telles que les résidus en forme D ou N-méthylés sur ce paysage conformationnelSmall cyclic peptides represent an emerging and promising class of therapeutic molecules. However, the lack of knowledge on their conformational space makes their design difficult as well as the prediction of their structure. In order to improve knowledge on these molecules with unique properties, we wanted to develop an alternative approach to those existing allowing the most exhaustive characterization of their conformational space. For that, we have developed EGSCyP method, based on a multi-level representation of the peptide: a mechanical representation and the use of robotics inspired algorithms allowing a global search and then a refinement in an all atom model. EGSCyP was developped to deal with D-amino acids and N-methylated residues. This method has been compared to replica exchange molecular dynamics simulations and experimental data to validate the approach. It has been applied to a set of cyclic pentapeptides RGD derived from Cilengitide, an anticancer drug. Our method has shown good performances, particularly with regard to the completeness of the conformational space of these peptides, and has made possible to evaluate the impact of the chemical modifications like the D-amino acids or N-methylated ones on this conformational landscape
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Choi, Jungyoon. "Développement de molécules théranostiques ciblantes contre le cancer de la prostate Targeting tumors with cyclic RGD-conjugated lipid nanoparticles loaded with an IR780 NIR dye: In vitro and in vivo evaluation." Thesis, Université Grenoble Alpes (ComUE), 2017. http://www.theses.fr/2017GREAV025.
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Depuis leur découverte en 1987, les peptides RGD ont été largement testés comme agents anti-angiogéniques et comme agents de contraste pour la détection et l’imagerie des tumeurs. En particulier pour l’imagerie optique, plusieurs vecteurs à base de RGD sont testés en préclinique car ils ciblent en même temps les tumeurs et leurs vaisseaux récemment formés.Le premier objectif de ma thèse était de développer un agent de contraste fluorescent dans le proche infra-rouge pour guider la prise de biopsies dans la prostate par imagerie optique. En tant que partenaire d’un programme ANR, notre objectif était de créer une nanoémulsion lipidique conjuguée avec des peptides RGD cycliques, chargée avec un fluorophore proche infra-rouge, et de les tester dans un modèle de cancer de la prostate chez la souris. Comme la plupart des nanoparticules qui présentent un diamètre de 50 nm, les nanoémulsions lipidiques (LNPs) peuvent s’accumuler passivement dans les tumeurs par effet EPR (Enhanced permeability and retention effect). Dans cette étude, nous développons des LNPs PEGylées en surface, chargées avec de l’oleyl-IR780 pour l’imagerie de fluorescence proche infra-rouge et greffées avec des peptides cRGD dans le but de cibler l’intégrine αvβ3. Sur les lignées cellulaires HEK293-β3, HEK293-β3-αvRFP, DU145 et PC3, nous démontrons un ciblage spécifique du récepteur avec les cRGD-LNPs mais pas avec les LNPs-cRAD et LNPs-standards. Nous démontrons aussi que les LNPs-cRGD se lient à l’intégrine αvβ3, interfèrent avec l’adhésion des cellules à la vitronectine et sont co-internalisées avec αvβ3 dans les cellules en moins d’une heure. Nous avons ensuite étudié leur biodistribution et leur capacité de ciblage dans les souris porteuses de tumeurs DU145 ou M21. Nous n’avons observé aucune différence significative au niveau de l’accumulation/rétention entre les LNP-cRGD et les LNP non-ciblées. Ceci suggère que, malgré une bonne formulation des NPs, le ciblage cRGD n’augmente pas la quantité totale de LNPs qui s’accumulent passivement dans les tumeurs sous-cutanées via l’effet EPR. Dans un second temps, nous avons essayé d’augmenter ce ciblage et avons travaillé sur une nanoparticule faite d’une matrice de silice couverte par un peptide cRGD combiné à un autre peptide ATWLPPR qui cible la neuropilin-1 (NRP1). NRP1 est un corécepteur de VEGFR2, aussi impliqué dans la néoangiogenèse et dans la croissance tumorale. Le double-ciblage cRGD/ATWLPPR devrait assurer un meilleur ciblage tumoral ainsi qu’une meilleure activité anti-angiogénique comparé aux NPs présentant uniquement le cRGD. Cependant, nous avons plutôt trouvé un effet antagoniste avec les NP-cRGD mais sans synergie apparente ou effet additionnel lorsque le deuxième ligand était présent. Au contraire, nos résultats préliminaires suggèrent que le double-ciblage déclencherait plutôt la prolifération cellulaire. Ceci mérite une investigation plus poussée pour mieux comprendre les mécanismes mis en jeu. De plus, l’utilisation de telles particules mais qui seraient aussi capables de délivrer des agents cytotoxiques pourrait entrainer une activité anti-tumorale puissanteSince the discovery of RGD peptides in 1987, they have been largely tested as anti-angiogenic agents as well as targeted contrast agents for tumor detection and imaging. In particular, several RGD-based optical contrast agents are currently being tested in preclinical studies because they target tumors and newly formed blood vessels at the same time.The first aim of my thesis work was to develop a near-infrared (NIR) fluorescent contrast agent for optically guided prostate biopsy. As partners of an ANR program, our objective was to provide a cRGD-targeted lipid nanoemulsion labeled with a NIR dye, which would target prostate tumors in a mouse model. Like several 50 nm-large nanocarriers, lipid nanoparticles (LNPs) can passively accumulate in tumors through the Enhanced Permeability and Retention (EPR) effect. In this study, we developed PEGylated LNPs loaded with oleyl-IR780 dye as a contrast agent for NIR fluorescence imaging, and modified them with cyclic RGD peptides in order to target integrin αvβ3. We demonstrate a specific targeting of the receptor with cRGD-LNPs but not with cRAD-LNP and standard LNP, using HEK293-β3, HEK293-β3-αvRFP, DU145 and PC3 cell lines. We also demonstrate that cRGD-LNPs bind to αvβ3, interfere with cell adhesion to vitronectin, and co-internalize with αvβ3 within one hour. We then investigated their biodistribution and tumor targeting in mice bearing DU145 or M21 tumors. We observed no significant differences between cRGD-LNP and non-targeted ones regarding their biodistribution and accumulation/retention in tumors. This suggested that despite an efficient formulation of the cRGD-LNPs, the cRGD-mediated targeting did not increase the total amount of LNP that could already accumulate passively in the subcutaneous tumors via the EPR effect.In a second objective, we tried to improve this targeting and worked on second generation nanoparticles made of a silica matrix covered by a cRGD peptide combined with another peptide, ATWLPPR, which targets Neuropilin-1 (NRP1). NRP1, a co-receptor of VEGFR2, is also involved in neo-angiogenesis and tumor growth. Dual-targeted cRGD/ATWLPPR-SiNPs were thus expected to provide a better tumor targeting as well as an improved anti-angiogenic activity as compared to cRGD-only-SiNPs. However, we found a possible antagonistic effect only with cRGD-SiNPs without synergy or additive effect despite the presence of the two ligands. In contrast, our preliminary results suggest that the dual-targeted SiNPs may trigger a cell proliferation and tumor-promoting effect. This should be further investigated, but one interesting consequence would be that the delivery of selected therapeutic agents using our dual-targeted SiNPs may provide an interesting antitumor activity
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Foster, Kristi A. "Field Ecology Patterns of High Latitude Coral Communities." NSUWorks, 2011. http://nsuworks.nova.edu/occ_stuetd/82.
Full textAbstract:
Some climate models predict that, within the next 30-50 years, sea surface temperatures (SSTs) will frequently exceed the current thermal tolerance of corals (Fitt et al. 2001; Hughes et al. 2003; Hoegh-Guldberg et al. 2007). A potential consequence is that mass coral bleaching may take place (i) during warm El Niño-Southern Oscillation (ENSO) events which are predicted to occur in some regions more frequently than the current 3-7 year periodicity (Hoegh-Guldberg 1999; Sheppard 2003) or (ii) perhaps as often as annually or biannually if corals and their symbionts are unable to acclimate to the higher SSTs (Donner et al. 2005, 2007). Global data also indicate an upward trend toward increasing frequencies, intensities, and durations of tropical hurricanes and cyclones (Emanual 2005; Webster et al. 2005). As coral communities have been shown to require at least 10-30 years to recover after a major disturbance (e.g. Connell 1997; Ninio et al. 2000; Bruno & Selig 2007; Burt et al. 2008), it is possible that future coral communities may be in a constant state of recovery, with regeneration times exceeding the periods between disturbances. Life history traits (e.g. reproduction, recruitment, growth and mortality) vary among species of hard corals; thus, gradients in community structures may have a strong influence on susceptibilities to disturbance and rates of recovery (Connell 1997; Ninio & Meekan 2002). Taxa which are more susceptible to bleaching and mechanical disturbance (e.g. tabular and branching acroporids and pocilloporids) may experience continual changes in population structure due to persistent cycles of regeneration or local extirpation, while the more resistant taxa (e.g. massive poritids and faviids) may display relatively stable population structures (Woodley et al. 1981; Hughes & Connell 1999; Baird & Hughes 2000; Marshall & Baird 2000; Loya et al. 2001; McClanahan & Maina 2003). Determining whether resistant coral taxa have predictable responses to disturbances, with consistent patterns over wide spatial scales, may improve predictions for the future affects of climate change and the composition of reefs (Done 1999; Hoegh-Guldberg 1999; McClanahan et al. 2004).
The work presented in this dissertation describes the spatial and temporal patterns in community structures for high latitude coral assemblages that have experienced the types of natural disturbances which are predicted to occur in tropical reef systems with increasing frequency as a result of climate change. The primary area of focus is the southeastern Arabian Gulf, where the coral communities are exposed to natural conditions that exceed threshold limits of corals elsewhere in the world, with annual temperature ranges between 14-36°C (Kinzie 1973; Shinn 1976) and salinities above 40 ppt. Two additional regions are included in this study for comparisons of high latitude coral community structures. The northwestern Gulf of Oman is adjacent to the southeastern Arabian Gulf (i.e. the two bodies of water are connected by the Strait of Hormuz); however, the environmental conditions are milder in the Gulf of Oman such that the number of coral taxa therein is threefold that found in the southeastern Arabian Gulf (i.e. 107 coral species in the Gulf of Oman compared to 34 species in this region of the Arabian Gulf (Riegl 1999; Coles 2003; Rezai et al. 2004)). Broward County, Florida is geographically remote from the Gulfs and, therefore, serves as a benchmark for testing whether consistent patterns in community structures exist despite different climatic and anthropogenic influences.
The coral communities within the southeastern Arabian Gulf, the northwestern Gulf of Oman, and Broward County, Florida have been exposed to recurrent elevated sea surface temperature (SST) anomalies, sequential cyclone and red tide disturbances, and frequent hurricanes and tropical storms, respectively. These disturbances and other impacts (e.g. bleaching episodes, disease outbreaks, anthropogenic stresses) have affected the more susceptible acroporids and pocilloporids, resulting in significant losses of coral cover by these families and shifts towards massive corals as the dominant taxa. During the post-disturbance scarcity or absence of branching and tabular corals, the resistant massive taxa have become the crux of the essential hard coral habitat for fish, invertebrates and other marine organisms.
Because recovery to pre-disturbance community structures may take decades or may not occur at all, it is vital that scientists and resource managers have a better understanding of the spatial and temporal ecology patterns of the corals that survive and fill in the functional gaps that are created by such disturbances. To aid in this understanding, this dissertation presents spatial and temporal patterns for the coral assemblages which have developed after the respective disturbances. Spatial ecology patterns are analyzed using graphical descriptions (e.g. taxa inventories, area cover, densities, size frequency distributions), univariate techniques (e.g. diversity indices), distributional techniques (e.g. k-dominance curves) and multivariate techniques (e.g. hierarchical clustering, multidimensional scaling). Temporal comparisons at monitoring sites within the southeastern Arabian Gulf and northwestern Gulf of Oman describe the coral population dynamics and are used to create size class transition models that project future population structures of massive corals in the recovering habitats.
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Tang, James Y. "Nitrogen fixation and cycling in a mixture of young red alder and Douglas-fir." Thesis, 1997. http://hdl.handle.net/1957/34068.
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Lavery, John Meredith. "The influence of red alder in adjacent conifer stands : nutrient cycling and light transmission." Thesis, 2000. http://hdl.handle.net/2429/11314.
Full textAbstract:
Red alder (Alnus rubra(Bong.)) is an important successional deciduous species in British
Columbia with expanding commercial markets. Alder is a pioneer species which grows rapidly
on disturbed sites and in riparian areas of coastal British Columbia. Alder's impressive early
height growth and ability to increase the rate of cycling of nitrogen and other nutrients lead to a
challenge in managing alder with conifers. Managing alder in mixedwood stands requires
finding an appropriate balance between competition for light and the improvement in N status of
a site, which would lead to improved conifer growth over time. Light transmission to the
understory of adjacent alder and conifer stands was measured along a transect between the two
stands using photodiode and quantum sensors, as well as hemispherical photography. Light
varied with age and site, but alder stands generally had more light in the understory than the
adjacent conifer stands. This difference was more marked in younger stands. Modeling using
SLIM and LITE correlated well with the sensor information, and further modelling of the alder
stands suggests that the amount of light available to conifers adjacent to an alder stand is of
adequate quantity to sustain conifer growth within 5m of the alder/conifer stand boundary. The
assessment of nutrient cycling in alder stands involved independent studies of litterfall, soil
qualities, and a bioassay of the soils using Douglas-fir seedlings. Higher concentrations of N and
several other nutrients were found in alder litter, but the conifer litter had very high levels of
several micronutrients. The alder litterfall made significant contributions to nutrient inputs up to
15m into the conifer stands. The soil showed elevated N, and Total C, C:N and pH were
influenced by alder presence in the oldest stands. This series of experiments also showed the
influence of alder on the concentration of N in the shoots of the seedlings, as well as an influence
on boron. The influence of alder litterfall, soil and bioassay N at points along the transects was
correlated at the oldest and middle aged sites, suggesting that red alder produces a significant
change in the nutrient cycling in adjacent conifer stands. Implications for managers and
suggestions for management are discussed.
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Cesana, Sonia [Verfasser]. "Functionalization of poly(2-oxazoline)s with cyclic RGD peptides / Sonia Cesana." 2004. http://d-nb.info/974209643/34.
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Dose, Andrea Christina. "Molecular characterization of the cyclic nucleotide-gated cation channel of bovine rod outer segments." Thesis, 1995. http://hdl.handle.net/2429/4785.
Full textAbstract:
The cyclic nucleotide-gated (CNG) cation channel of rod photoreceptors plays an
important role in the perception of light. The channel gating is the final step in the visual
transduction cascade. The cloning (Kaupp et al., 1989) of what is now known to be the
CNG channel α subunit facilitated its molecular characterization. A heterologous
expression system was developed to examine molecular aspects of the α and β subunits
of the CNG channel. Expression in mammalian cells helped resolve confusion regarding
the JVL of the rod CNG channel a subunit. Although the cDNA codes for an 80 kDa
protein, the a subunit exists in the rod outer segment as a 63 kDa protein suggesting the
existence of a processing mechanism. PCR was used to construct cDNA clones which
code for both the 63 and 80 kDa forms of the a subunit of the rod CNG channel. A
polyclonal antibody, generated to specifically label the 80 kDa α subunit, was used in
conjunction with a monoclonal antibody specific for the 63 kDa α subunit in labeling
studies. These antibodies were shown to be mono-specific, capable of differentiating
between the two size forms of the a subunit. Immunohistochemical studies
demonstrated that the 63 kDa α subunit is the predominant species in the rod outer
segment while the 80 kDa form is present in very low quantities. Rod outer segment
(ROS) purification on sucrose gradients also showed that the 80 kDa form co-sediments
with the 63 kDa α subunit indicating that the two size forms coexist in the outer
segment. Examining the α subunits of the photoreceptors of another species
demonstrated similar processing of the CNG α subunit polypeptides, however, an
olfactory a subunit did not appear to undergo similar processing.
The cloned CNG channel β subunit cDNA codes for a protein with a predicted
molecular mass of 155 kDa (Korschen et al, 1995). Heterologous expression of the β
subunit cDNA yielded a 240 kDa protein, positively identifying the 240 kDa protein in
ROS which co-purifies with the a subunit as the CNG β subunit. Construction and expression of a truncated form of the (3 subunit demonstrated that it is the glutamic acidrich
N-terminal portion of the (3 subunit that is responsible for its anomalous migration
on an SDS gel. Co-expression of both subunits in mammalian cells indicated that the 3
subunit was not responsible for the processing of the α subunit. As seen for the subunits
of the native CNG channel the heterologously expressed α and β subunits coimmunoprecipitated.
The subunit interaction was not dependent on the 92 N terminal
amino acids of the 80 kDa α subunit or on the glutamic acid-rich portion of the P
subunit. A method for reconstitution of the heterologously expressed CNG channel was
also developed. The expressed a subunit reconstituted alone did not generate functional
cGMP-gated channels. Reconstitution of the heterologously expressed channel complex
comprising the 80 kDa α and complete β subunits generated functional channels.
Compared to the native CNG channel, 10% of the heterologously expressed channel
complex exhibited cGMP-gated channel activity. This is the first example of
reconstitution of a heterologously expressed cation channel into lipid vesicles for Ca²⁺ efflux measurements. The system presented here will be useful to further define CNG α
and β subunit interactions and to carry out structure-function studies on the channel
using a biochemical efflux assay.
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Wang, I. Hsiu, and 王怡琇. "Proteomic analysis of a novel compound─cyclic RGD in breast carcinoma cell line MCF-7." Thesis, 2004. http://ndltd.ncl.edu.tw/handle/46231910293949373346.
Full textAbstract:
碩士國立臺北科技大學
化學工程系碩士班
92
Synthetic peptides containing the RGD (Arg-Gly-Asp) motif have been extensively used as inhibitors of integrin-ligand interactions in studies of cell adhesion, migration, growth, differentiation, and apoptosis. The RGD motif is an integrin-recognition motif found in many ligands, so the RGD-containing peptides can be used to probe integrin functions in various biological systems. A linear RGD is tripeptide consists of a flexible structure that makes the motif binding to acceptor with inefficient chelating affinity. Therefore, we designed a cyclic-RGD peptide (Tpa-RGDWPC, cRGD) with rigid skeleton to bind closely to its acceptor. The cRGD was obtained by solid phase peptide synthesis method using Rink amide resin. We showed that the cRGD exerts more potency than that of liner RGD on inhibiting cell growth of MCF-7. This has stimulated us to address the question of how cRGD inhibits cell growth of MCF-7 cells. To uncover what molecular mechanism involved in the RGD motif exert in MCF-7 cells is also of considerable importance. We used proteomics and bioinformatics to survey global changes in proteins after cRGD treatment in MCF-7 cells. The classification of these proteins according to the different biological processes in which they are involved is shown. It is of interest that most of the proteins which appear to be strongly influenced by cRGD treatment are mostly involved in metabolism, cell growth, responsive to external stimulus, cell communication, reproduction and cell death. This is the first report which monitored the protein expression profile of MCF-7 cells in response to treatment with cRGD in a time-course analysis. The clustering data indicated temporal patterns of altered protein expression that can be classified as early, intermediate and late response proteins. These patterns of protein expression may be important for predicting response to cRGD. Taken together, these results demonstrated the molecular explanation for the properties of cRGD in breast cancer cells and provide a valuable in-depth impact in breast cancer therapy.
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Huang, Tsui-Chin, and 黃翠琴. "Cyclic RGD-Induced Cell Death in Human Breast Carcinoma (MCF-7) Cells: The Influence of Caspase Pathway." Thesis, 2005. http://ndltd.ncl.edu.tw/handle/pz2t5r.
Full textAbstract:
碩士國立臺北科技大學
生物科技研究所
93
Synthetic peptides containing the arginine-glycine- aspartate (RGD) motif have been used extensively as inhibitors of integrin-ligand interactions in studies of cell adhesion, migration,growth and differentiation, because the RGD motif is an integrin-recognition motif found in many ligands. we designed a cyclic-RGD peptide (Tpa-RGDWPC, cyclic-RGD) with rigid skeleton to bind closely to its acceptor. The cyclic-RGD was obtained by solid phase peptide synthesis method using Rink amide resin via a strategy .we previously reported that cyclic RGD caused cell death in MCF-7 cell line.Apoptosis was observed by 4'', 6-diamidine-2`-phenylindole dihydrochloride (DAPI) staining for morphological changes for biochemical alterations. On the basis of cDNA microarray data, we suggest that the caspase 8 and FADD-like apoptosis regulator, the caspase 9 and inhibitor of apoptosis protein formed the positive and negative feedback control system. These results indicate that cyclic-RGD peptide can induce apoptosis by caspase pathway. The mRNA expression levels of all caspases in MCF-7 treated with cyclic RGD were analyzed and confirmed by real-time quantitative PCR technique.
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Chen, Wan-Jou, and 陳宛柔. "Study on Tricarbonyl 99mTechnetium(I) Labeled HYNIC-Cyclic RGD Peptide as a Specific Marker of αvβ3 Integrin for Tumor Imaging." Thesis, 2004. http://ndltd.ncl.edu.tw/handle/18431640966629012345.
Full textAbstract:
碩士國立清華大學
原子科學系
92
The αvβ3 integrin is an important cell adhesion receptor involved in tumor-induced angiogenesis and tumor metastasis. The high binding specificity to αvβ3 integrins of peptides containing Arg-Gly-Asp (RGD) residue suggests that the radiolabeled RGD peptides be useful as tumor specific imaging agents. Recently, several radionuclides were used to detect αvβ3 integrins and were suitable for noninvasive determination of tumor status, therapy monitoring and possibility of tumor metastasis. Since 99mTc is characteristic of excellent radionuclide with a high-resolution 140.5 keV γ, a half-life 6 h, economically and conveniently available from 99Mo-99mTc generator and extensively used in nuclear medicine, it will be significant to develop 99mTc labeled RGD peptide for clinical use in nuclear medicine. Synthesis of NHS-HYNIC, conjugation of RGD peptide with NHS-HYNIC and preparation of [99mTc(CO)3(OH2)3]+ were carried out respectively according to the previous reports [Abrams et al. J Nucl Med 31(1990) 2022, Su et al. Bioconjugate Chem 13(2002) 561 and Alberto et al. J Am Chem Soc 120(1998) 7987]. RGD peptide was labeled with [99mTc(CO)3(OH2)3]+ via hydrazinonicotinamide as a bifunctional chelator. 99mTc(I)-HYNIC-RGD was prepared by mixing the [99mTc(CO)3(OH2)3]+ solution with HYNIC-RGD in PBS buffer at room temperature. Radiochemical characterization for 99mTc(I)-HYNIC-RGD were conducted by thin layer chromatography, electrophoresis, and HPLC. According to the results, the radiochemical purity for 99mTc(I)- HYNIC-RGD was around 60%. The synthesis and labeling work for 99mTc(I)-HYNIC-RGD has been established in this study. Furthermore in vitro and in vivo tests for 99mTc(I)-HYNIC-RGD for tumor angiogenesis imaging study are underway.
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Lin, Ke-chen, and 林哿塵. "Pluripotency and Proliferation of Amniotic Fluid-Derived Stem Cells Cultured on Biomaterials Grafted with Oligopeptides and Cyclic RGD Having Optimal Elasticity." Thesis, 2015. http://ndltd.ncl.edu.tw/handle/47685738900298538091.
Full textAbstract:
碩士國立中央大學
化學工程與材料工程學系
103
Human amniotic fluid-derived stem cells (AFSCs) are pluripotent fetal cells capable of differentiating into multiple lineages, including representatives of the three embryonic germ layers. Stem cells which derived from human amniotic fluid may become a more suitable source of stem cells in regenerative medicine and tissue engineering. However, stem cell characteristics, such as proper differentiation and maintenance of pluripotency, are regulated not only by the stem cells themselves but also by their microenvironment. On the other hand, the stem cell fates of pluripotency and differentiation can influence by biological cues (i.e. extracellular matrix (ECM)) and physical cues (i.e. elasticity) of cell culture biomaterials. Here we investigated the maintenance of pluripotency and differentiation ability of AFSCs cultured on poly(vinylalcohol-co-itaconic acid), PVA-IA films grafted with several ECM-derived oligopeptides and combined with cyclic RGD having different elasticity. AFSCs cultured on soft PVA-IA films (19.6 kPa) grafted with ECM-derived oligopeptides showed high pluripotency, as assessed by the pluripotent gene expression (Oct4, Sox2, and Naong). AFSCs grow on stiff PVA-IA films (30.4 kPa) grafted with the combination of oligopeptides derived from collagen type I (oligoCOL) and cyclic RGD peptide showed higher pluripotency than that grafted with oligoCOL. Surprisingly, AFSCs cultured on PVA-IA films showed higher pluripotency also expressed higher level of early differentiation markers for three germ layers (Nestin, Runx2, Sox17) in expansion medium. This result suggests that AFSCs are heterogenous and that this population contains highly pluripotent stem cells and stem cells that can be easily differentiated. It is suggested that physical cues such as stiffness of culture biomaterials and biological cues such as ECM-derived peptides can guide pluripotency and differentiation ability of stem cells.
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Becirovic, Elvir [Verfasser]. "Role of the CNGB1a subunit of the rod cyclic nucleotide gated channel in channel gating and pathogenesis of retinitis pigmentosa / Elvir Becirovic." 2010. http://d-nb.info/1006625305/34.
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Hu, Bin [Verfasser]. "Vesicle adhesion via interaction of integrin αIIbβ3 [alpha IIb beta 3] and cyclic-RGD-lipopeptide : a model of cell adhesion processes / Bin Hu." 2001. http://d-nb.info/962127124/34.
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