Submitted by Marco Antônio de Ramos Chagas (mchagas@ufv.br) on 2017-09-05T18:22:33Z No. of bitstreams: 1 texto completo.pdf: 525790 bytes, checksum: 4ae27d539a12d7e1df07619c08fa3326 (MD5) / Made available in DSpace on 2017-09-05T18:22:33Z (GMT). No. of bitstreams: 1 texto completo.pdf: 525790 bytes, checksum: 4ae27d539a12d7e1df07619c08fa3326 (MD5) Previous issue date: 2017-04-11 / Conselho Nacional de Desenvolvimento Científico e Tecnológico / Com o estímulo à produção e ao uso de biodiesel, o crambe é hoje uma das melhores opções para o fornecimento de matéria-prima, uma vez que apresenta valores expressivos de óleo em suas sementes. Entretanto, há carência de informações sobre o manejo da cultura, principalmente quanto ao sistema de produção de sementes de qualidade. Objetivou-se, com este estudo, avaliar as alterações físicas e fisiológicas em sementes de crambe colhidas em diferentes estádios de maturação e submetidas a diferentes temperaturas de secagem e armazenamento. Foram utilizadas sementes de crambe, cultivar FMS Brilhante, provenientes de área experimental localizada na região de Viçosa, Minas Gerais. No primeiro experimento, realizaram-se colheitas manuais quando as plantas estavam com 20, 40, 60, 80 e 100% de frutos marrons. Após as colheitas, as sementes foram beneficiadas e submetidas à secagem em diferentes temperaturas (ar natural e artificial a 30, 45 e 60 °C), até atingirem 10% de teor de água, com posterior avaliação das alterações físicas e fisiológicas nas sementes e, também, do acúmulo de óleo. Os dados foram submetidos à análise de variância. Os efeitos dos estádios de maturação foram estudados por análise de regressão e os efeitos das temperaturas de secagem foram estudados pelo teste de Tukey, a 5% de probabilidade. Com base nos resultados do primeiro experimento, no segundo experimento utilizaram- se sementes colhidas no estádio de maturação com 80% de frutos marrons. Após a colheita e o beneficiamento, as sementes provenientes dos diferentes tipos de secagem foram acondicionadas em embalagem de papel (saco de papel comum, com capacidade de 1 kg) e armazenadas por 12 meses em sala climatizada, com temperatura média de 20 oC e umidade relativa próximo aos 55%. No início do armazenamento e a cada 120 dias, foram determinados o teor de água, a germinação e o vigor das sementes (primeira contagem de germinação, emergência de plântulas e condutividade elétrica das sementes). Os efeitos das temperaturas de secagem foram estudados pelo teste de Tukey, a 5% de probabilidade, enquanto os efeitos dos períodos de armazenamento foram estudados por meio da análise de regressão. Quanto ao teor de óleo, houve efeito significativo apenas dos estádios de maturação. À medida que se prolongaram os estádios de maturação, houve incremento no teor de óleo das sementes, tendo o máximo conteúdo sido atingido com as colheitas realizadas a partir de 70% do total de frutos marrons. A temperatura de secagem de 60 °C foi prejudicial à qualidade fisiológica das sementes. A colheita de sementes de crambe, cultivar FMS Brilhante, visando à melhor qualidade fisiológica, deve ser realizada quando as plantas apresentarem entre 75 e 85% de frutos marrons. As temperaturas de 30 e 45 oC são indicadas para a secagem de suas sementes. As sementes de crambe apresentaram dormência pós-colheita, sendo totalmente superada durante o armazenamento. Constatou-se que o desempenho fisiológico das sementes decresce após oito meses de armazenamento. / As a result of increased production and biodiesel, crambe is today one of the best options of raw matter supply, since its seeds present expressive oil value. However, information on the management of this culture is scarce, mainly on quality seed production system. This study aims to evaluate the physical and physiological changes in crambe seeds harvested at different maturation stages and submitted to different drying and storage temperatures. Crambe cultivar FMS Brilhante seeds were used, originated from the experimental area located in the region of Viçosa, Minas Gerais. In the first experiment, manual harvests were performed when the plants presented 20, 40, 60, 80 and 100% of brown fruit. After the harvest, the seeds were processed and submitted to drying at different temperatures (natural and artificial air at 30, 45, and 60 °C), until reaching 10% of water content, followed by physical and physiological changes in the seeds, as well as oil accumulation. Data were submitted to variance analysis. The effects of the maturation stages were determined by regression analysis and the drying effects were analyzed by the Tukey test, at 5% probability. Based on the results obtained in the first experiment, the second experiment used seeds harvested at the maturation stage with 80% of brown fruits. After seeds were harvested and processed, the seeds originated from the different types of drying temperatures were placed in 1 kg capacity pa per bags, and stored for 12 months, in an acclimatized room with mean temperature of 20 oC and relative humidity close to 55%. At the start of storage, and at every 120 days, seed water content, germination, and vigor (first germination count, plantlet emergence and seed electric conductivity) were determined. The effects of the different drying temperatures were studied by the Tukey test at 5% probability, while the effects of the different storage periods were determined by regression analysis. As for oil content, there was a significant effect, only the maturation stages. As the maturation stages became longer, there was an increase in the oil content in the seeds, with the maximum content being reached at the harvests from 70% of the total of the brown fruits. The drying temperature of 60 °C was harmful to the physiological quality of the seeds. Aiming at a better physiological quality, Crambe cultivar FMS Brilhante seeds must be harvested when the plants present between 75 and 85% of brown fruit. Temperatures of 30 and 45 oC are indicated for seed drying. Crambe seeds presented post-harvest dormancy, which was totally overcome during storage. It was concluded that the physiological performance of the seeds decreases after 8 months of storage.

Le développement de nouvelles molécules capables d’intéragir avec l’ADN, leur mode d’intéraction et leur affinité est un domaine de recherche particulièrement important. Dans ce travail nous avons étudié les interactions avec l’ADN de la molécule Hoechst 33258 connu pour être un ligand du petit sillon ainsi que plusieurs de ces analogues.Dans un premier temps nous avons étudié la stabilité des complexes ADN-Hoechst 33258 en solution avec et sans DMSO comme co-solvant. Deuxièmement, les affinités de dérivés nouvellement conçus et synthétisés du Hoechst 33258 vis-à-vis de l'ADN ont été évaluées. Enfin, nous avons étudiés la capacité d’induction d’excimers en présence d’ADN de différentes molécules pyrénylées. Ces études ont été effectuées par différentes méthodes spectroscopiques, telles que l'absorbance UV-visible, la fluorescence, le dichroïsme circulaire, la spectroscopie de masse ESI et de la modélisation moléculaire. / The development of new DNA binders and the evaluation of their affinity toward DNA as well as their mode of binding is an area of research of prime importance. In this thesis we studied the interactions of Hoechst 33258, a well-known groove binder, as well as some of its newly synthesized derivatives with DNA. The stability of DNA-Hoechst 33258 complex in solution with and without DMSO as a co-solvent was evaluated.Secondly, the affinities of newly designed and synthesized derivatives of Hoechst 33258 toward DNA were evaluated. Finally, a set of pyrene derivatives able to induced excimer formation upon binding to DNA were studied. Different spectroscopic methods, such as UV-vis absorbance, fluorescence, circular dichroism, ESI mass spectroscopy and molecular docking were applied for the complete evaluation of the affinity of these ligands toward DNA.

This thesis consists of two major chapters, each with its own introduction, experimental section and discussion. The TG4T/daunomycin and G4/daunomycin complexes described in Chapter One are two out of only five crystallographic quadruplex/ligand structures reported to date. In both structures daunomycin molecules stack onto a terminal G quartet preventing the G4 quadruplex from destacking and unwinding. The number of interacting ligand molecules depends on the quadruplex structure itself. The G4 quadruplex can accommodate four daunomycin molecules within one layer, while the TG4T tetraplex only accommodates three. In both structures daunosamine moieties form hydrogen bonds with the quadruplex but only daunosamine moieties from the TG4T/daunomycin structure make slight incursions into the quadruplex grooves. Both structures are stabilised by π-π interactions, hydrogen bonds, Van der Waals contacts and electrostatic interactions. The daunomycin/TG4T complex is the first ever reported and the only structure where a ligand interacts directly with the quadruplex groove. Chapter Two describes nine crystal structures of Hoechst 33258 analogues with d(CGCAAATTTGCG)2 and d(CGCGAATTCGCG)2 oligonucleotides, and is divided into two sections. Section A includes seven structures with Halogenated Hoechst 33258 analogues that are potential agents in radiotherapy, phototherapy, radioimmunotherapy or photoimmunotherapy, and the structure of the precursor. In all of the examined complexes the ligand binds to the minor groove but not all halogen substituents refine to 100% occupancy. The refined occupancies of the halogen atoms reveal that the degree of carbon-halogen cleavage is highest for ortho and lowest for para substitution. Among meta substituents pointing outside the minor groove, bromine atoms had a higher occupancy than the larger iodines. The position of the halogen atom in the minor groove is influenced by additional substituents on the phenyl ring. In most cases the bulky halogen atom is facing outside of the minor groove. Only in the 3-iodo-5-isopropylHoechst complex is iodine positioned towards the floor of the groove allowing the big isopropyl group to face outside. Section B describes the structure of a carborane-containing ligand (JW-B) bound to the minor groove of d(CGCAAATTTGCG)2. The analysis shows that is possible to position boron-rich moieties close to the cell nucleus, and JW-B may have potential in Boron Neutron Capture Therapy. / Data file restricted at the request of the author, but available by individual request, use the feedback form to request access.

This thesis consists of two major chapters, each with its own introduction, experimental section and discussion. The TG4T/daunomycin and G4/daunomycin complexes described in Chapter One are two out of only five crystallographic quadruplex/ligand structures reported to date. In both structures daunomycin molecules stack onto a terminal G quartet preventing the G4 quadruplex from destacking and unwinding. The number of interacting ligand molecules depends on the quadruplex structure itself. The G4 quadruplex can accommodate four daunomycin molecules within one layer, while the TG4T tetraplex only accommodates three. In both structures daunosamine moieties form hydrogen bonds with the quadruplex but only daunosamine moieties from the TG4T/daunomycin structure make slight incursions into the quadruplex grooves. Both structures are stabilised by π-π interactions, hydrogen bonds, Van der Waals contacts and electrostatic interactions. The daunomycin/TG4T complex is the first ever reported and the only structure where a ligand interacts directly with the quadruplex groove. Chapter Two describes nine crystal structures of Hoechst 33258 analogues with d(CGCAAATTTGCG)2 and d(CGCGAATTCGCG)2 oligonucleotides, and is divided into two sections. Section A includes seven structures with Halogenated Hoechst 33258 analogues that are potential agents in radiotherapy, phototherapy, radioimmunotherapy or photoimmunotherapy, and the structure of the precursor. In all of the examined complexes the ligand binds to the minor groove but not all halogen substituents refine to 100% occupancy. The refined occupancies of the halogen atoms reveal that the degree of carbon-halogen cleavage is highest for ortho and lowest for para substitution. Among meta substituents pointing outside the minor groove, bromine atoms had a higher occupancy than the larger iodines. The position of the halogen atom in the minor groove is influenced by additional substituents on the phenyl ring. In most cases the bulky halogen atom is facing outside of the minor groove. Only in the 3-iodo-5-isopropylHoechst complex is iodine positioned towards the floor of the groove allowing the big isopropyl group to face outside. Section B describes the structure of a carborane-containing ligand (JW-B) bound to the minor groove of d(CGCAAATTTGCG)2. The analysis shows that is possible to position boron-rich moieties close to the cell nucleus, and JW-B may have potential in Boron Neutron Capture Therapy. / Data file restricted at the request of the author, but available by individual request, use the feedback form to request access.

This thesis consists of two major chapters, each with its own introduction, experimental section and discussion. The TG4T/daunomycin and G4/daunomycin complexes described in Chapter One are two out of only five crystallographic quadruplex/ligand structures reported to date. In both structures daunomycin molecules stack onto a terminal G quartet preventing the G4 quadruplex from destacking and unwinding. The number of interacting ligand molecules depends on the quadruplex structure itself. The G4 quadruplex can accommodate four daunomycin molecules within one layer, while the TG4T tetraplex only accommodates three. In both structures daunosamine moieties form hydrogen bonds with the quadruplex but only daunosamine moieties from the TG4T/daunomycin structure make slight incursions into the quadruplex grooves. Both structures are stabilised by π-π interactions, hydrogen bonds, Van der Waals contacts and electrostatic interactions. The daunomycin/TG4T complex is the first ever reported and the only structure where a ligand interacts directly with the quadruplex groove. Chapter Two describes nine crystal structures of Hoechst 33258 analogues with d(CGCAAATTTGCG)2 and d(CGCGAATTCGCG)2 oligonucleotides, and is divided into two sections. Section A includes seven structures with Halogenated Hoechst 33258 analogues that are potential agents in radiotherapy, phototherapy, radioimmunotherapy or photoimmunotherapy, and the structure of the precursor. In all of the examined complexes the ligand binds to the minor groove but not all halogen substituents refine to 100% occupancy. The refined occupancies of the halogen atoms reveal that the degree of carbon-halogen cleavage is highest for ortho and lowest for para substitution. Among meta substituents pointing outside the minor groove, bromine atoms had a higher occupancy than the larger iodines. The position of the halogen atom in the minor groove is influenced by additional substituents on the phenyl ring. In most cases the bulky halogen atom is facing outside of the minor groove. Only in the 3-iodo-5-isopropylHoechst complex is iodine positioned towards the floor of the groove allowing the big isopropyl group to face outside. Section B describes the structure of a carborane-containing ligand (JW-B) bound to the minor groove of d(CGCAAATTTGCG)2. The analysis shows that is possible to position boron-rich moieties close to the cell nucleus, and JW-B may have potential in Boron Neutron Capture Therapy. / Data file restricted at the request of the author, but available by individual request, use the feedback form to request access.

This thesis consists of two major chapters, each with its own introduction, experimental section and discussion. The TG4T/daunomycin and G4/daunomycin complexes described in Chapter One are two out of only five crystallographic quadruplex/ligand structures reported to date. In both structures daunomycin molecules stack onto a terminal G quartet preventing the G4 quadruplex from destacking and unwinding. The number of interacting ligand molecules depends on the quadruplex structure itself. The G4 quadruplex can accommodate four daunomycin molecules within one layer, while the TG4T tetraplex only accommodates three. In both structures daunosamine moieties form hydrogen bonds with the quadruplex but only daunosamine moieties from the TG4T/daunomycin structure make slight incursions into the quadruplex grooves. Both structures are stabilised by π-π interactions, hydrogen bonds, Van der Waals contacts and electrostatic interactions. The daunomycin/TG4T complex is the first ever reported and the only structure where a ligand interacts directly with the quadruplex groove. Chapter Two describes nine crystal structures of Hoechst 33258 analogues with d(CGCAAATTTGCG)2 and d(CGCGAATTCGCG)2 oligonucleotides, and is divided into two sections. Section A includes seven structures with Halogenated Hoechst 33258 analogues that are potential agents in radiotherapy, phototherapy, radioimmunotherapy or photoimmunotherapy, and the structure of the precursor. In all of the examined complexes the ligand binds to the minor groove but not all halogen substituents refine to 100% occupancy. The refined occupancies of the halogen atoms reveal that the degree of carbon-halogen cleavage is highest for ortho and lowest for para substitution. Among meta substituents pointing outside the minor groove, bromine atoms had a higher occupancy than the larger iodines. The position of the halogen atom in the minor groove is influenced by additional substituents on the phenyl ring. In most cases the bulky halogen atom is facing outside of the minor groove. Only in the 3-iodo-5-isopropylHoechst complex is iodine positioned towards the floor of the groove allowing the big isopropyl group to face outside. Section B describes the structure of a carborane-containing ligand (JW-B) bound to the minor groove of d(CGCAAATTTGCG)2. The analysis shows that is possible to position boron-rich moieties close to the cell nucleus, and JW-B may have potential in Boron Neutron Capture Therapy. / Data file restricted at the request of the author, but available by individual request, use the feedback form to request access.

Thesis (Ph. D.)--Virginia Polytechnic Institute and State University, 1993. / Vita. Abstract. Includes bibliographical references (leaves 184-187). Also available via the Internet.

Einleitung Der intensive Einsatz von Pflanzenschutzmitteln in der konventionellen Landwirtschaft kann zum Eintrag von Rückständen in die Nahrungskette führen. Milchliefernde Rinder nehmen Pflanzenschutzmittelrückstände mit dem Futter auf, die durch aktive Sekretion in die Milch eine Gefährdung für sensible Bevölkerungsgruppen, wie Kinder, verursachen könnten. Die in nationalen Rückstandskontrollen untersuchten Milchproben unterschreiten zwar in der Regel die gesetzlich festgelegten Höchstgrenzen (Maximum Residue Level, MRL), jedoch kann eine andauernde Belastung mit Pflanzenschutzmitteln die Entstehung chronischer Erkrankungen, wie Morbus Parkinson und Kinderleukämie, fördern. Im Rindereuter stellt der ATP-binding cassette Transporter der Subfamilie G2 (ABCG2) den wichtigsten Transportweg für Fremdstoffe in die Milch dar. Mit seinem breiten Substratspektrum ist der bovine ABCG2-Transporter (bABCG2) in der Lage, unterschiedliche Substrate in die Kuhmilch zu transportieren. Jedoch ist bislang unklar, ob auch Pflanzenschutzmittel bABCG2-vermittelt in die Milch sezerniert werden können und ob die gleichzeitige Aufnahme mehrerer Rückstände die bABCG2-Effluxaktivität beeinflusst. Ziele der Untersuchungen Ziel dieser Arbeit war die Identifikation von Pflanzenschutzmitteln als mögliche Substrate des bovinen Effluxtransporters. Weiterhin wurde untersucht, ob zwischen zwei Wirkstoffen synergistische oder antagonistische Effekte am bABCG2-Transporter auftreten. Material und Methoden Es wurden 14 häufig in der konventionellen Landwirtschaft eingesetzte Pflanzenschutzmittel in 0,1-, 1- und 10-facher MRL-Konzentration, in Bezug auf essbare Gewebe von Rindern, untersucht. Weiterhin wurden sechs Kombinationen aus jeweils zwei Wirkstoffen ausgewählt. Im WST-1 (Water Soluble Tetrazolium 1) Assay wurden MDCKII-bABCG2-Zellen in aufsteigender Konzentration mit den Pflanzenschutzmitteln inkubiert (72 h) und die Zellvitalität ermittelt. Nach Inkubation der MDCKII-bABCG2- und MDCKII-Mock-Zellen mit den ausgewählten Pflanzenschutzmitteln oder den Kombinationen (4 h) wurde der Hoechst 33342-Akkumulationsassay durchgeführt. Dabei führt eine Interaktion des Pflanzenschutzmittels mit dem bABCG2-Transporter zu einer intrazellulären Anreicherung des Hoechst 33342-Farbstoffes. Für die Identifikation signifikanter Unterschiede wurden jeweils mindestens zwölf Monolayer auf Normalverteilung (Shapiro-Wilk-Test) überprüft und eine Einweg-Varianzanalyse mit Holm-Šidák post hoc Test (p ≤ 0,05) durchgeführt. Ergebnisse Nachdem eine Beeinträchtigung der Zellvitalität durch die ausgewählten Pflanzenschutzmittel in 0,1- bis 10-facher MRL-Konzentration ausgeschlossen wurde, konnte im Hoechst 33342-Assay für Chlorpyrifos-methyl und Tebuconazol ab 0,1-facher MRL-Konzentration eine signifikante Zunahme der intrazellulären Hoechst 33342-Gehalte im Vergleich zur unbehandelten Kontrolle nachgewiesen werden. Für Diflufenican, Glyphosat, Methiocarb, Prochloraz, Rimsulfuron sowie Thiacloprid konnte in 1- und 10-facher MRL-Konzentration und für Iprodion sowie Ioxynil in 10-facher MRL-Konzentration eine signifikant erhöhte Hoechst 33342-Anreicherung detektiert werden. Darüber hinaus führte eine gleichzeitige Applikation von Methiocarb und Chlorpyrifos-methyl in 1-facher MRL-Konzentration, sowie von Glyphosat und Rimsulfuron in 10-facher MRL-Konzentration zu einer synergistischen Steigerung der Farbstoffakkumulation. Schlussfolgerung Es konnte festgestellt werden, dass das MDCKII-Zellmodell in Kombination mit dem Hoechst 33342-Assay eine valide Methode darstellt, um Wechselwirkungen einzelner und kombinierter Pflanzenschutzmittel zu detektieren. Insgesamt konnten unterhalb gesetzlich festgelegter MRL-Werte acht Pflanzenschutzmittel als potentielle bABCG2-Substrate identifiziert, sowie additive Effekte von Wirkstoffkombinationen nachgewiesen werden. Durch die Aufnahme von Pflanzenschutzmitteln mit dem Futter könnten diese aktiv in die Milch sezerniert werden und somit eine Gefahr für den Verbraucher darstellen:1 Einleitung 1 2 Literaturübersicht 4 2.1 Überblick über Membrantransporter 4 2.2 ABCG2-Effluxtransporter 5 2.2.1 Überblick 5 2.2.2 Struktur 6 2.2.3 ABCG2-Transportmechanismus 8 2.2.4 Spezifität der ABCG2-Substrate und Inhibitoren 9 2.2.5 Gewebeexpression 11 2.2.6 Bedeutung 12 2.2.7 Regulation der ABCG2-Transportaktivität 14 2.3 Fremdstoffsekretion der bovinen Milchdrüse 16 2.3.1 Funktionelle Anatomie 16 2.3.2 Transportmechanismen 16 2.3.3 Fremdstofftransporter 17 2.3.4 Bedeutung des ABCG2-Transporters 19 2.4 Pestizide 20 2.4.1 Überblick 20 2.4.2 Einsatz von Pflanzenschutzmitteln 21 2.4.3 Rechtliche Regelungen 21 2.4.4 MRL-Wert-Festsetzung von Pestiziden 22 2.4.5 Exposition des Verbrauchers 23 2.4.6 Gesundheitliche Risiken 24 2.4.7 Pestizide als endokrine Disruptoren 25 2.4.8 Mehrfachrückstände 26 2.4.9 Risikobewertung von Mehrfachrückständen 27 2.5 Problemstellung und Zielsetzung 29 3 Material und Methoden 30 3.1 Material 30 3.1.1 Pestizide 30 3.1.2 Chemikalien 32 3.1.3 Kit 32 3.1.4 Puffer und Lösungen 32 3.1.5 Zellkultur 33 3.1.6 Geräte 34 3.2 Methoden 35 3.2.1 Allgemeine zellbiologische Methoden 35 3.2.1.1 Kultivierung 35 3.2.1.2 Passagieren 35 3.2.1.3 Bestimmung der Zellzahl 35 3.2.1.4 Kryokonservierung 36 3.2.2 Bestimmung der Zellvitalität mittels WST-1 Zytotoxizitätstest 36 3.2.3 Quantitative Proteinbestimmung mittels BCA-Assay 38 3.2.4 Ermittlung von Interaktionen am bABCG2-Transporter 38 3.2.4.1 Aussaat und Vorbehandlung 39 3.2.4.2 Durchführung des Hoechst 33342-Assays 40 3.2.5 Detektion von Pestizidwechselwirkungen am bABCG2-Transporter 41 3.3 Statistik 42 4 Ergebnisse 43 4.1 Auswahl der Pestizide und ihrer Konzentrationen 43 4.2 Auswahl der Pestizidkombinationen 46 4.3 Einfluss der Pestizide auf die Zellvitalität 48 4.4 Interaktionen von Pestiziden am bABCG2-Transporter 53 4.5 Pestizidwechselwirkungen am bABCG2-Transporter 56 5 Diskussion 60 5.1 Zellmodell 60 5.2 Zellvitalitätsstudien in MDCKII-bABCG2-Zellen 61 5.3 Pestizide als potentielle bABCG2-Substrate 64 5.4 Wechselwirkungen von Pestiziden am bABCG2-Transporter 75 5.5 Risiken potentieller bABCG2-Substrate 79 6 Zusammenfassung 80 7 Summary 82 8 Literaturverzeichnis 84 9 Anhang 106 10 Danksagung 111

The American Heart Association (AHA) estimates that at least one American will die from a coronary event every minute, costing over $150 billion in 2008 alone. Regenerating the myocardium of patients that survive the initial infarction has proven to be an elusive goal. A variety of factors - including the loss of contractile cells, inflammatory response following infarction, cardiac hypertrophy, and lack of suitable cues for progenitor cells - causes fibrosis in the heart and loss of cardiac function. This dissertation examines three drug delivery strategies aimed at improving conditions for cardiac regeneration: polyketal microspheres as non-inflammatory drug delivery vehicles; surface functionalization of microparticles with nitrilotriacetic acid-nickel (NTA-Ni) for non-covalent tethering of proteins; and using Hoechst-inspired ligands for targeting extracellular DNA in necrotic tissue.

Thesis (M.S.)--Virginia Polytechnic Institute and State University, 1992. / Vita. Abstract. Includes bibliographical references (leaves 131-139). Also available via the Internet.