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Freer, Richard William. "Growth and mechanistic investigation of novel precursors for chemical beam epitaxy growth applications." Thesis, University of Oxford, 1995. http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.294388.
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Witosch, Justine Martha. "Structural characterization of the Timeless-Tipin-RPA Complex and its interaction with ssDNA." Diss., Ludwig-Maximilians-Universität München, 2015. http://nbn-resolving.de/urn:nbn:de:bvb:19-179857.
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Witosch, Justine Martha Verfasser], and Elena [Akademischer Betreuer] [Conti. "Structural characterization of the Timeless-Tipin-RPA Complex and its interaction with ssDNA / Justine Martha Witosch. Betreuer: Elena Conti." München : Universitätsbibliothek der Ludwig-Maximilians-Universität, 2015. http://d-nb.info/1068460679/34.
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Bianco, Julien. "Rôle du complexe Claspine-Timeless-Tipin dans le maintien de la stabilité du génome au cours de la réplication." Thesis, Montpellier 1, 2010. http://www.theses.fr/2010MON1T009/document.
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Il a été montré récemment que l'instabilité génétique joue un rôle central dans les étapes précoces de la tumorigenèse. Celle-ci provoquerait une activation chronique des voies ATR/CHK1 et ATM/CHK2 dans les cellules précancéreuses, entrainant l'apoptose ou la sénescence des cellules concernées. Les mécanismes de checkpoint constituant une barrière contre la progression tumorale, toute mutation affectant ce checkpoint serait ainsi sélectionnée très tôt dans le processu s de tumorigenèse et faciliterait ensuite la progression tumorale. Ce modèle met en évidence le rôle central de l'instabilité génomique et du checkpoint dans la progression tumorale.Au cours de ma thèse, je me suis intéressé au complexe Claspine / Timeless / Tipin, initialement identifié comme médiateur de la voie ATR/CHK1 et qui est donc considéré comme ayant une fonction suppresseur de tumeur. Cependant, Claspine présente aussi des propriétés oncogéniques, puisque qu'elle est surexprimée dans de nombreuses lignées tumorales et cette surexpression est importante pour la prolifération cellulaire. Nous nous sommes donc demandé comment cette protéine pouvait être à la fois un oncogène et un suppresseur de tumeur. Chez la levure, l'homologue de Claspine est impliqué dans le maintien de la stabilité des fourches de réplication, indépendamment de sa fonction dans le checkpoint. Nous proposons que dans les cellules cancéreuses cette surexpression permette une meilleure stabilité des fourches, ce qui serait très important pour répliquer efficacement un génome soumis à un stress réplicatif constant. Au cours de ma thèse, nous avons construit et caractérisé un modèle de cellulescancéreuses HCT116 dans lesquelles nous avons diminué le niveau de Claspine ou deTimeless grâce à des shRNA, sans que cela n'affecte l'efficacité du checkpoint de réplication. Nous avons pu observer dans ces cellules un ralentissement de la progression des fourches de réplication et l'apparition d'une instabilité génétique. Il semblerait que spécifiquement dans le cas de Timeless, le ralentissement de la fourche de réplication et l'instabilité génomique se manifeste surtout dans les régions du génome répliquées tardivementThe correct execution of the replication program is essential for the maintenance of genome integrity during S phase. Indeed, replication fork progression is frequently challenged by DNA lesions and by a variety of natural pause sites. Arrested forks are unstable structures, which represent a major threat for the genome integrity if they are not promptly stabilized and restarted. In response to replicative stress, cells activated the replication checkpoint to prevent collapse of stalled forks and promote fork recovery. Recent evidence indicates that spontaneous replication stress occurs in precancerous lesions and promotes the development of cancer. Identifying the origin of this replication stress would represent a better understanding of the early stages of tumorigenesis. We study the function of Claspin, a mediator of the replication checkpoint, which plays a key role in the response to replication stress. It is therefore acting as a tumor suppressor, preventing genomic instability during DNA replication. Intriguingly, recent evidence indicates that Claspin is overexpressed in different cancers and can also acts as an oncoprotein. Studies on Mrc1p, the yeast homologue of Claspin, have shown that Mrc1 is permanently associated to forks, where it forms a complex with two partners called Tof1p and Csm3p (homologues of human Tim and Tipin respectively). We have shown by DNA combing that the replicative function of Mrc1p, is critical for viability in the presence of a replication stress. In l ight of our results in yeast, we propose that the Claspin/Tim/Tipin complex may also play a direct role for the replication of human cells. If confirmed, this replication function may account for the role of this complex in the cancer process and tumor resistance to genotoxic agents commonly used in anticancer therapy
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Grimmelsmann, Tim Albert [Verfasser]. "Biochemical and biophysical characterization of the human TIM/TIPIN/CRY complex - a potential direct link between the circadian clock and the cell cycle / Tim Albert Grimmelsmann." Mainz : Universitätsbibliothek der Johannes Gutenberg-Universität Mainz, 2020. http://d-nb.info/1223379086/34.
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Schütz, Jan-Hendrik. "Bioinspirierte Titin-analoge Polymere." Doctoral thesis, Niedersächsische Staats- und Universitätsbibliothek Göttingen, 2014. http://hdl.handle.net/11858/00-1735-0000-0023-993F-1.
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Bioinspirierte Polymere, die die Multidomänenstruktur des Muskelproteins Titin imitieren, wurden auf Grundlage von zuvor synthetisierten, zyklischen Präpolymeren, die Wasserstoffbrückenbindungen-tragende Monomere enthalten, hergestellt und hinsichtlich ihrer mechanischen Eigenschaften untersucht.
Zunächst wurde die Ringexpansionspolymerisation (REP) zur Erzeugung zyklischer Makromoleküle, die auf einer von Nishikubo et al. entwickelten, lebenden Gruppentransferpolymerisation von Thiiranmonomeren mit Acylgruppen-tragenden Initiatoren basiert, eingehend untersucht. Im Speziellen wurde ein System, bestehend aus dem zyklischen Initiator 2,4-Thiazolidindion (TZD) und Derivaten desselben, dem Katalysator Tetrabutylammoniumchlorid, verschiedenartig substituierten Thiiranmonomeren 2-(Phenoxymethyl)thiiran (PMT), 2-Methylthiiran (MT), 2-(tert-Butoxymethyl)thiiran (TBMT), 2-((o-Methylphenoxy)methyl)thiiran (MPMT) und dem Lösungsmittel N-Methylpyrrolidin-2-on verwendet. Bei der Insertion der Monomere MT, TBMT und MPMT in TZD, die unter guter Kontrolle des Polymerisationsgrads und der Dispersität stattfand, wurde eine Verschmelzung der Ringe zu größeren Ringstrukturen mit einem Verschmelzungsgrad von bis zu zwei, bei Verwendung von PMT sogar von bis zu vier beobachtet. Der Grad dieser Verschmelzung nahm im Fall von PMT mit zunehmender Monomerkonzentration, zunehmendem molaren Monomer-zu-Initiator-Verhältnis und zunehmender Reaktionstemperatur ab, während er bei den anderen Monomeren keine Konzentrations- und Temperaturabhängigkeit zeigte. Durch Anpassung der Molmassenverteilungen mittels einer Summe von Gauß-Funktionen im Fall der PMT-Polymere konnte die zeitliche Änderung der molaren Anteile der verschiedenen Ringspezies verfolgt werden. So wurden für Polymerkonzentrationen von 14 bis 52 Gew-% Geschwindigkeitskoeffizienten der Verschmelzung, die sich über Größenordnungen von 10^(−2) bis 10^(−6) L/mol/s erstrecken, ermittelt. Bei Verwendung von in 3-Position substituierten TZD-Derivaten wurde eine Zunahme der Anzahl verschmolzener Makrozyklen von bis zu sieben festgestellt. Die Bildung zyklischer Strukturen wurde mittels Massenspektrometrie und rasterkraftmikroskopischer (AFM) Aufnahmen gezeigt.
Neben den Homopolymerisationen wurden zyklische (AB)n-Multiblockcopolymere aus MT und PMT mit bis zu acht aus der Ringverschmelzung resultierenden Blöcken synthetisiert. Sie zeigten im Zugversuch, aufgrund der verschiedenen Topologien, im Vergleich zu linearen Diblockcopolymeren ähnlicher Zusammensetzung, deutliche Unterschiede in der maximalen Zugdehnung und der Zähigkeit.
Weiterhin wurden die eingangs erwähnten bioinspirierten Polymere durch Kombination von zyklischen und linearen Segmenten hergestellt und auf ihre mechanischen Eigenschaften untersucht. Dazu wurden zyklische (ABC)n-Multiblockcopolymere, die zusätzlich einen kurzen Block des Monomers Ethyl-2-(4-(thiiran-2-ylmethoxy)benzamido)acetat (ETBAA) enthielten, der zur Ausbildung selbstkomplementärer Wasserstoffbrückenbindungen in der Lage ist, synthetisiert. Diese Präpolymere wurden mittels 1,3-dipolarer Cycloaddition in einer Polyadditionsreaktion mit einem niedermolekularen, bifunktionellen Verknüpfungsagens oder mit monofunktionellem Poly-n-butylacrylat (PBA) bzw. Polymethylacrylat (PMA), welche mittels RAFT-Polymerisation hergestellt wurden, verknüpft. So konnte im ersten Fall eine Poly-Ringpolymer-Topologie mit bis zu 19 nachgewiesenen Wiederholeinheiten und im zweiten Fall ein Polymer mit Kette–Ring–Kette-Topologie erhalten werden.
Untersuchungen der Proben im Zugversuch zeigten beim Kette–Ring–Kette-Polymer bis auf eine höhere Elastizität keine verbesserten Materialeigenschaften im Vergleich zum linearen PMA-Präpolymer. Die Poly-Ringpolymere hingegen zeigten im Gegensatz zu den Ringpolymeren ein einzigartiges Spannungs-Dehnungsverhalten, bessere Elastizitätseigenschaften und eine Erhöhung der anwendbaren Spannung bei gleicher Dehnung. Dies wurde durch den Einfluss inter- und intramolekular ausgebildeter physikalischer Bindungen durch die enthaltenen selbstkomplementären Wasserstoffbrückenbindungsmotive hervorgerufen. Eines der untersuchten Poly-Ringpolymere zeigte aufgrund der Ausbildung eines reversiblen physikalischen Netzwerkes sogar ein Formgedächtnis und die Fähigkeit zu einer partiellen Selbstheilung.
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Liversage, Alexander Duncan. "Investigations into titin/thick filament stoichiometry." Thesis, University of Bristol, 2000. http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.310804.
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Charton, Karine. "Etude de la physiopathologie de la dystrophie musculaire tibiale et de la dystrophie des ceintures 2J et stratégies thérapeutiques." Thesis, Evry-Val d'Essonne, 2010. http://www.theses.fr/2010EVRY0026/document.
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La titine est une protéine géante exprimée dans les muscles squelettiques et cardiaque. Un certain nombre de mutations pathogéniques ont été identifiées dans son dernier exon codant. La mutation la plus fréquente, FINmaj, conduit au remplacement de 4 acides aminés et est retrouvée chez de nombreux patients en Finlande. Cette mutation cause une dystrophiemusculaire tibiale (TMD) à l‟état hétérozygote et une dystrophie des ceintures de type 2J(LGMD2J) à l‟état homozygote.Pour obtenir une modèle d‟étude de la physiopathologie de ces maladies et évaluer des stratégiesthérapeutiques, nous avons introduit la mutation FINmaj dans le génome murin par une stratégiede Knock-In par recombinaison homologue. Ce modèle a été caractérisé et a permis de montrer qu‟il reproduit en grande partie les symptômes de la TMD et de la LGMD2J aux niveaux histologique et moléculaire. L‟étude de ce modèle murin a permis une meilleure compréhension de la physiopathologie de ces deux maladies et nous amené à étudier plus attentivement les interactions de la titine en C-ter avec ses partenaires afin de mieux comprendre l‟implication de la ligne M dans la vie du sarcomère. L‟ étude de la physiopathologie de la TMD et de la LGM2J a permis de montrer que la calpaïne 3 (une protéase à l‟origine d‟une autre dystrophie des ceintures), jouait un rôle majeur dans laTMD. Cette constatation nous a permis d‟envisager une approche thérapeutique pour cette dernière visant à diminuer les symptômes en régulant négativement la calpaïne 3. Une approche de thérapie génique a aussi été testée dans le but de traiter ces deux pathologies: le trans-épissage des derniers exons de la titine. En effet, étant donné la grande taille de l'ADNc de la titine (~100 kb), des stratégies classiques de transfert de gène n‟étaient pas envisageables. Pour s'affranchir de ce problème, nous avons testé une approche de trans-épissage de l‟ARN pour remplacer le ou les derniers exons du messager de la titine. Nous avons pu ainsi démontrer la faisabilité de la correction de la titine in vitroTitin is a giant protein expressed in both skeletal muscles and heart. Several pathogenic mutations were identified in its last coding exon. The most frequent mutation commonly referred to as FINmaj, results in the replacement of 4 amino acids and affects a subset of patients in Finland. The mutation causes a Tibial Muscular Dystrophy (TMD) when present on one allele and a Limb Girdle Muscular Dystrophy phenotype 2J (LGMD2J) when present on both alleles.To obtain a model for studying the physiopathology of these diseases and evaluating therapeutic strategies, we introduced the FINmaj mutation in the murine genome by a knock-in strategy by homologous recombination. This model was characterized and showed that it reproduces mainly the symptoms of both the human TMD and LGMD2J at histological and molecular levels.The study of this mouse model has allowed a better understanding of the pathophysiology of these two diseases and we have to study more carefully the interactions beyond titin C-ter with its partners to better understand the involvement of the M line in life of the sarcomere.The study of the pathophysiology of TMD and LGM2J showed that calpain 3 (a protease thatlind to an other limb-girdle muscular dystrophy), played a major role in TMD. This finding allowed us to consider a treatment approach for TMD to reduce symptoms by regulating negatively calpain 3. A gene therapy approach was also tested: the trans-splicing of the last exon of titin.Indeed, given the large size of the cDNA of titin (~ 100 kb), conventional strategies of genetransfer were not envisaged. To overcome this problem, we tested an approach to exchange the last exon or the last exons of the titin messenger. We were able to demonstrate the correction of titin in vitro
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Engberg, David. "Atom Probe Tomography of TiSiN Thin Films." Licentiate thesis, Linköpings universitet, Tunnfilmsfysik, 2015. http://urn.kb.se/resolve?urn=urn:nbn:se:liu:diva-122724.
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This thesis concerns the wear resistant coating TiSiN and the development of the analysis technique atom probe tomography (APT) applied to this materials system. The technique delivers compositional information through time-of-flight mass spectrometry, with sub-nanometer precision in 3D for a small volume of the sample. It is thus a powerful technique for imaging the local distribution of elements in micro and nanostructures. To gain the full benefits of the technique for the materials system in question, I have developed a method that combines APT with isotopic substitution, here demonstrated by substitution of natN with 15N. This alters the time-of-flight of ions with of one or more N and will thereby enable the differentiation of the otherwise inseparable isotopes 14N and 28Si. Signs of small-scale fluctuations in the data led the development of an algorithm needed to properly visualize these fluctuations. A method to identify the best sampling parameter for visualization of small-scale compositional fluctuations was added to an algorithm originally designed to find the best sampling parameters for measuring and visualizing strong compositional variations. With the identified sampling parameters, the nano-scale compositional fluctuations of Si in the metal/metalloid sub-lattice could be visualized. The existence and size of these fluctuations were corroborated by radial distribution functions, a technique independent of the previously determined sampling parameter. The radial distribution function algorithm was also developed further to ease in the interpretation. The number of curves could thereby be reduced by showing elements, rather than single and molecular ions (of which there were several different kinds). The improvement of the algorithm also allowed interpretation of signs regarding the stoichiometry of SiNy. With a combination of analytical transmission electron microscopy and APT we show Si segregation on the nanometer scale in arc-deposited Ti0.92Si0.0815N and Ti0.81Si0.1915N thin films. APT composition maps and proximity histograms generated from Ti-rich domains show that the TiN contain at least ~2 at. % Si for Ti0.92Si0.08N and ~5 at. % Si for Ti0.81Si0.19N, thus confirming the formation of solid solutions. The formation of relatively pure SiNy domains in the Ti0.81Si0.19N films is tied to pockets between microstructured, columnar features in the film. Finer SiNy enrichments seen in APT possibly correspond to tissue layers around TiN crystallites, thus effectively hindering growth of TiN crystallites, causing TiN renucleation and thus explaining the featherlike nanostructure within the columns of these films.
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Gomes, PatrÃcia Bezerra. "AvaliaÃÃo dos efeitos centrais e antinociceptivos das fraÃÃes isoladas da raiz de Petiveria alliacea L. (TIPI) em camundongos." Universidade Federal do CearÃ, 2006. http://www.teses.ufc.br/tde_busca/arquivo.php?codArquivo=271.
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CoordenaÃÃo de AperfeiÃoamento de Pessoal de NÃvel SuperiorAvaliaÃÃo dos efeitos centrais e antinociceptivos das fraÃÃes isoladas da raiz de Petiveria alliacea L. (tipi) em camundongos. PATRÃCIA BEZERRA GOMES. Orientador: Profa. Dra. Francisca ClÃa FlorenÃo de Sousa. DissertaÃÃo de Mestrado. Curso de PÃs-graduaÃÃo em Farmacologia. Departamento de Fisiologia e Farmacologia, UFC, 2006. Petiveria alliacea L. à um arbusto da famÃlia Phytolaccaceae, usada popularmente na medicina folclÃrica para o tratamento de uma ampla variedade de doenÃas nas AmÃricas do Sul e Central. As fraÃÃes acetato (FA), hexÃnica (FH), hidroalcoÃlica (FHA) e hidroalcoÃlica precipitada (FHAppt) da raiz do tipi foram estudadas para investigar suas propriedades farmacolÃgicas, nos modelos de nocicepÃÃo (contorÃÃes abdominais induzidas por Ãcido acÃtico, formalina a 1% e placa quente) e nos modelos comportamentais clÃssicos (campo aberto, labirinto em cruz elevado- LCE, rota rod, tempo de sono induzido por pentobarbital, nado forÃado e convulsÃes induzidas por pentilenotetrazol- PTZ). Foram analisados tambÃm os fitoconstituintes presentes no tipi, os efeitos farmacolÃgicos gerais e sua toxicidade aguda. As fraÃÃes foram administradas, via oral (v.o.) e/ou intraperitoneal (i.p.), nas doses de 100 e 200 mg/kg, em camundongos fÃmeas. A abordagem fitoquÃmica das fraÃÃes de Petiveria alliacea revelou a presenÃa de alcalÃides em FA, cumarinas em FA, FHA e FHAppt, saponinas e triterpenos em FA, FH, FHA e FHAppt. O extrato hidroalcoÃlico (500, 1000, 1500 e 2000 mg/kg, i.p.; 1000, 2000, 3000 e 4000 mg/kg, v.o.) do tipi apresentou uma baixa toxicidade e os parÃmetros mais visualizados foram analgesia, diminuiÃÃo da motilidade e passividade. Todas as fraÃÃes inibiram as contorÃÃes abdominais induzidas por Ãcido acÃtico. FA (200 mg/kg, i.p.), FH e FHAppt (100 e 200 mg/kg, i.p.), reduziram a nocicepÃÃo produzida pela formalina na 1 e 2 fases. FHA (100 e 200 mg/kg, i.p.) apresentou uma inibiÃÃo significativa na 1 fase deste teste, indicando um possÃvel efeito antinociceptivo. O efeito antinociceptivo produzido por FHAppt (200 mg/kg, i.p.) foi revertido pela naloxona (2mg/kg, s.c.), mostrando uma possÃvel participaÃÃo do sistema opiÃide neste processo. Nenhum efeito significativo foi observado no teste da placa quente. Todas as fraÃÃes do tipi induziram uma diminuiÃÃo significativa na atividade locomotora, rearing e grooming no teste do campo aberto, sugerindo uma possÃvel aÃÃo depressora central. Nenhum efeito significativo foi evidenciado na coordenaÃÃo motora dos animais no teste do rota rod. No LCE, FA (100 e 200 mg/kg, v.o.) reduziu o NEBA (n de entradas nos braÃos abertos) e o TPBA (tempo de permanÃncia nos braÃos abertos). FA, FH e FHA (100 e 200 mg/kg, i.p.), FHAppt (200mg/kg, i.p.) apresentaram uma significativa reduÃÃo do TPBA, indicando uma ausÃncia do efeito ansiolÃtico. As fraÃÃes da raiz de Petiveria alliacea promoveram um aumento significativo do tempo de imobilidade dos camundongos no teste do nado forÃado. AlÃm disso, corroborando estes resultados, as fraÃÃes causaram um prolongamento do tempo de sono induzido por pentobarbital, confirmando um provÃvel efeito sedativo e depressor central. Os efeitos neurofarmacolÃgicos de FHA (200 mg/kg, i.p.), observados nos testes do campo aberto e tempo de sono, nÃo foram revertidos com a administraÃÃo de flumazenil (2,5 mg/kg, i.p.), indicando que o mecanismo de aÃÃo de FHA, provavelmente, nÃo està relacionado com a participaÃÃo dos receptores GABAÃrgicos. Todas as fraÃÃes da raiz de Petiveria alliacea aumentaram a latÃncia da 1 convulsÃo e o tempo de morte das convulsÃes induzidas por PTZ nos animais, confirmando seu uso popular como anticonvulsivante. Os resultados mostraram que as diferentes fraÃÃes de Petiveria alliacea L. possuem significativo potencial antinociceptivo, sedativo, depressor e anticonvulsivante, devido à presenÃa destes constituintes, dando suporte ao uso da medicina folclÃrica desta planta.
Evaluation of the central and antinociceptive effects of isolated fractions from the root of Petiveria alliacea L. (tipi) in mice. PATRÃCIA BEZERRA GOMES. Supervisor: Profa. Dra. Francisca ClÃa FlorenÃo de Sousa. Master Dissertation. Course of Post-graduation in Pharmacology. Department of Physiology and Pharmacology, UFC, 2006. Petiveria alliacea L. a shrub from Phytolaccaceae family, is popularly used in folk medicine for treating a wide variety of disorders in South and Central America. The acetate (FA), hexanic (FH), hydroalcoholic (FHA) and precipitated hydroalcoholic (FHAppt) fractions from the root of tipi were studied to investigate its pharmacological properties in animals nocicepcion models (abdominal contractions induced by acetic acid, formalin 1% and hot plate tests) and in the classical behavioral models (open-field, elevated plus maze- EPM, rota rod, barbiturate-induced sleeping time, forced swimming and pentylenetetrazole (PTZ)-induced convulsions tests). Were analyzed the phytoconstituents presents in it, the general pharmacological effects and acute toxicity. The fractions were administered orally (p.o.) and/or intraperitoneally (i.p.), at single doses of 100 and 200 mg/kg, in female mice. The phytochemical approach of the fractions from Petiveria alliacea demonstrated the presence of alkaloids in FA, coumarins in FA, FHA and FHAppt, saponins and triterpenes in FA, FH, FHA and FHAppt. The hidroalcoholic extract (500, 1000, 1500 and 2000 mg/kg, i.p.; 1000, 2000, 3000 and 4000 mg/kg, p.o.) of the tipi presented a low toxicity and the parameters more visualized were analgesic, decrease in locomotor activity and passive behavior. All the fractions inhibited the abdominal contractions induced by acetic acid. FA (200 mg/kg, i.p.), FH and FHAppt (100 and 200 mg/kg, i.p.), reduced the nocicepcion produced by formalin in the 1st and 2nd phases. FHA (100 and 200 mg/kg, i.p.) presented a significant inhibition on the 1st phase, of this test, indicating a possible antinociceptive effect. The antinociceptive effect produced by FHAppt (200 mg/kg, i.p.) was reversed by naloxone (2 mg/kg, s.c.), showing the participation of the opioid system in this process. No significant effect was observed in the hot plate test. All the fractions of tipi induced a significant decrease in the locomotor activity, rearing and grooming in the open field test, suggesting a possible central depressant action. No significant effect was evident on motor coordination of the animals in the rota rod test. On LCE, FA (100 and 200 mg/kg, p.o.) decreased the NEOA (n of entries in the open arms) and the TPOA (time of permanence in the open arms). FA, FH and FHA (100 and 200 mg/kg, i.p.), FHAppt (200mg/kg, i.p.) presented a significant reduction of the TPOA, indicating an absence of anxiolytic effect. The fractions from the root of Petiveria alliacea promoted a significant increase in the immobility time of the mice in the forced swimming test. Moreover, corroborating these results, as caused a prolongation of the pentobarbital-induced sleeping time, confirmed a probable sedative and central depressant effect. The neuropharmacological effects of the FHA (200 mg/kg, i.p.), observed in the open field and barbiturate-induced sleeping time tests, werenât reverted with the administration of the flumazenil (2.5 mg/kg, i.p.), indicating that the mechanism of action of the FHA, probably didnât related with the participation of the GABAergic receptors. All the fractions of Petiveria alliacea increased the latency to the first convulsion and the lethal time of the PTZ-induced convulsions test in the animals, confirmed its popular use as anticonvulsant. Results showed that the different fractions of Petiveria alliacea L. have significant antinociceptive, sedative, depressant and anticonvulsant potentials, due to presence in this constituents, supporting folk medicine use of this plant.
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Schuster, Joseph M. "The contribution of titin to striated muscle shortening." Diss., Columbia, Mo. : University of Missouri-Columbia, 2008. http://hdl.handle.net/10355/5758.
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Thesis (M.S.)--University of Missouri-Columbia, 2008.The entire dissertation/thesis text is included in the research.pdf file; the official abstract appears in the short.pdf file (which also appears in the research.pdf); a non-technical general description, or public abstract, appears in the public.pdf file. "December 2008" Includes bibliographical references.
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Bogomolovas, Julijus. "Titin role in muscle homeostasis : the kinase domain." Thesis, University of Liverpool, 2014. http://livrepository.liverpool.ac.uk/18355/.
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The giant muscle protein titin is a central player in cardiovascular health and disease. Titin molecules spanning half of the sarcomere form a filament system in striated muscles. The titin filament is not only an essential structural component of sarcomere, but also plays a central role in myofibril signaling through its kinase domain (TK) and numerous protein ligands. Thus, not surprisingly, mutations in this molecule might have detrimental effects. In this work a structure-driven approach was taken to re-evaluate titin kinase catalytic activity and the pathogenicity of two cardiomyopathy-associated titin mutations. Comparison of recombinant preparations from E.coli and insect cells revealed intrinsic inactivity of TK. It was demonstrated that previously reported phosphotransfer activity towards Tcap (a small Z-disc protein) is due to contaminant kinase activity from insect cells but not TK itself. Next, it was established that the eukaryotic host produces structurally indistinguishable TK from that produced in insect cells, albeit inactive towards Tcap, classical kinase substrates or extracts from mature or differentiating muscles. Structural analysis identified evolutionary conserved residue substitutions converting vertebrate TKs to pseudokinases. The structural context of dilated cardiomyopathy associated mutation was revealed in the crystal structure of TK enclosing neighboring domains A170 and M1. The mutation site resides in a conserved helix located in the linker region between TK and the binding site of ubiquitin E3 ligase MuRF1. Aspartate to valine substitution causes disruption of a conserved hydrogen bond and detachment of the affected helix from TK. In the context of the titin filament, this causes dissociation of the binding site from TK and increases interdomain flexibility. Structural alterations translate into increased MuRF1-mediated degradation of mutant titin fragments through the ubiquitin-proteasome pathway. Speculatively, haploinsufficiency of mutant titin could be a possible pathomechanism leading to dilated cardiomyopathy associated with the mutation under study. Comprehensive analysis of arrhythmogenic left ventricular cardiomyopathy associated titin mutation generated a novel model of pathogenesis. In contrast to previous reports, we demonstrate that mutation does not cause affected domain I10 unfolding, and is structurally compatible. Observed destabilization of the domain was attributed to a disrupted hydrogen bond, causing increased flexibility. A crystal structure of the affected domain flanked by adjacent domains I9-I11 demonstrated that threonine to isoleucine substitution might have detrimental effects on interdomain arrangement, resulting in exposure of a hydrophobic patch. Functionally, differential localization of mutant protein was observed in transgenic muscles. Speculatively, mutation could result in impaired folding of mutant protein and lead to accumulation of degradation-resistant aggregates or cause an increased stickiness to thin filaments as a novel pathomechanism. Results presented in this work demonstrate that TK is a catalytically inactive pseudokinase acting as a molecular scaffold. It was demonstrated that TK and MuRF1 signaling modules are structurally interconnected and genetic perturbation of this link might lead to dilated cardiomyopathy. In similar fashion, genetic alteration of interaction between immunoglobulin domains might cause arrhythmogenic left ventricular cardiomyopathy.
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Acerbi, Matteo. "Costruzioni modulari in linguaggi con tipi dipendenti." Master's thesis, Alma Mater Studiorum - Università di Bologna, 2014. http://amslaurea.unibo.it/6756/.
Full textAbstract:
In questa tesi si indaga come è possibile strutturare in modo modulare programmi e prove in linguaggi con tipi dipendenti. Il lavoro è sviluppato nel linguaggio di programmazione con tipi dipendenti Agda.
Il fine è quello di tradurre l'approccio Datatypes à la carte, originariamente formulato per Haskell, in Type Theory: puntiamo ad ottenere un simile embedding di una nozione di sottotipaggio per tipi ricorsivi, che permetta sia la definizione di programmi con side-effect dove i diversi effetti sono definiti modularmente, che la modularizzazione di sintassi, semantica
e ragionamento relativi a descrizioni di linguaggi.
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Bezerra, Josà Noberto Sousa. "ComposiÃÃo quÃmica,atividade fitonematicida e inseticida de Tipi (Petiveria alliaceae)." Universidade Federal do CearÃ, 2006. http://www.teses.ufc.br/tde_busca/arquivo.php?codArquivo=1570.
Full textAbstract:
Conselho Nacional de Desenvolvimento CientÃfico e TecnolÃgicoEste trabalho descreve o estudo dos componentes volÃteis e nÃo volÃteis das raÃzes de Petiveria alliaceae, incluindo as atividades nematicida e inseticida do Ãleo essencial. Para o estudo quÃmico, fitonematicida e inseticida utilizou-se as raÃzes da planta, das quais foram obtidos o Ãleo essencial e os constituintes nÃo-volÃteis. Do Ãleo essencial das raÃzes foram identificados os seguintes componentes: benzaldeido (61,5%) (constituinte majoritÃrio) dissulfeto de dibenzila (18,1%), transestilbeno (14,1%) e cinamaldeido (6,3%), sendo que esses dois Ãltimos compostos tambÃm foram isolados atravÃs de cromatografia em camada delgada preparativa e identificados por RMN 1H e 13C. O tratamento cromatogrÃfico dos extratos etanÃlico, acetato de etila e hexÃnico permitiu o isolamento de uma mistura de duas mercaptanas, dissulfeto de dibenzila e o trissulfeto de dibenzila, dissulfeto de dibenzila, uma alantoina e a sacarose, que pela primeira vez foram isoladas das raÃzes de Petiveria alliaceae. As mercaptanas isoladas sÃo conhecidas na literatura por suas atividades fungicidas e nematicida. O Ãleo essencial extraÃdo das raÃzes de P. alliaceae e seus constituintes foram submetidos aos ensaios de atividades nematicida contra larvas de Meloidogyne incÃgnita (nematÃide de galhas) e inseticida contra a Mosca branca (Bemisia tabaci) inseto do feijÃo (Callosobruchus maculatus). Os Ãleos essenciais obtidos de P. alliaceae coletadas nas duas localidades diferentes apresentaram significantes atividades inseticida e nematicida. Os constituintes isolados tiveram suas estruturas elucidadas atravÃs de mÃtodos espectromÃtricos de IV, EM, RMN 1H e 13C uni e bidimensionais (COSY, HMQC e HMBC).
This work describes the study of the volatile and the non-volatile components from the roots of Petiveria alliaceae, including the nematicidal and insecticidal activities of the essential oil. The following components were identified in the essential oil: benzaldehyde as the major constituent (61, 5 %), cinnamaldehyde (6, 3%), dibenzyl disulphide (18, 1%), transstilbene (14, 1%). The two last compounds were also isolated through a chromatography in a preparative thin layer identified by RMN 1H and 13C. The isolation of a mixture of two mercaptans, benzyl disulphide and dibenzyl trisulphide, saccharose and allantoin, which were isolated for the first time from the Petiveria alliaceae, was permitted by the chromatographic treatment of the ethyl acetate, hexane, and ethanolic extracts. The isolated mercaptans are known in literature for their fungicide and insecticide activities. The constituents of the essential oil, extracted from the roots of Petiveria alliaceae, were submitted to the nematicidal activities against Meloidogyne incognita larva, insecticide against white fly (Bemisa tabaci) and insect of the beans (Callosobruchus maculatos). Significant insecticidal and nematicidal activities were present in the essential oil from the P. alliaceae, collected in two different localities. The isolated constituents had their structure elucidated through spectrometric methods of IV, EM, RMN 1H and 13C uni and bi-dimensional (COSY, HMQC and HMBC)
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Anderson, Brian R. "The Biophysics of Titin in Cardiac Health and Disease." Diss., The University of Arizona, 2014. http://hdl.handle.net/10150/319877.
Full textAbstract:
The giant protein titin is the third myofilament in the cardiac sarcomere. It is responsible for generating passive forces in stretched myocardium and maintaining sarcomere structure. The force generation properties of titin are determined by titin's elastic springlike elements, and this dissertation focuses on the determination of the physical properties of these springlike elements using atomic force microscopy. The primary project of this dissertation investigates the link between a single point mutation in one of titin's subdomains and arrhythmogenic cardiomyopathy.
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Roberts, Angharad Margaret. "Titin : an analysis of genetic variation and cardiac phenotype." Thesis, Imperial College London, 2014. http://hdl.handle.net/10044/1/26990.
Full textAbstract:
Non ischaemic dilated cardiomyopathy (DCM) is an important cause of heart failure leading to chronic morbidity and death and as such is a major health burden. DCM is familial in up to 50% of cases but is genetically heterogeneous, hindering both genotype-phenotype studies and the application of genetic information for stratified patient management. TTN truncating variants (TTNtv) cause severe and familial DCM, but sometimes occur in healthy individuals, posing challenges for the interpretation of these variants. In this PhD thesis, the power of quantitative cardiac MRI (CMR) is integrated with targeted resequencing of TTN in order to assess the relationship between TTN genotype, cardiac phenotype and clinical outcomes. A prospectively recruited DCM cohort was established following CMR assessment in 374 patients (88% Caucasian, 72% male, mean age 54 ± 35 years, mean left ventricular ejection fraction (LVEF) 38% ± 24.5%, mean indexed end-diastolic volume 129 ± 141 mm). Following several iterations of design, refinement and testing an NGS assay was produced that captures all TTN coding exons and splice sites. Optimal parameters for sequencing and analysis of variants were established and genotype data compiled from 374 prospective, unselected cases, 155 end-stage retrospective cases, and 308 MRI phenotyped healthy volunteers. These data were integrated with that from 3603 population subjects and together used to identify molecular signatures that aid interpretation of TTN truncations both in DCM and as incidental findings. Overall, TTNtv were identified in 1.4% of controls, 13% of unselected and 22% of end-stage DCM cases (OR = 13, P= 2.8x10-43, DCM vs controls) confirming TTN as the commonest cause of genetic DCM in all patient groups. TTNtv-containing exons in DCM have higher usage than those in controls (P=2.5x10-4) and these are estimated to have >93% probability of pathogenicity (likelihood ratio 14). Compared to TTNtv-ve DCM, TTNtv+ve patients had lower LVEF (P=0.02), thinner LV walls (P=0.02), and a higher incidence of sustained ventricular tachycardia (P=0.001). C-terminus TTNtv were also associated with lower LVEF versus N-terminus (β=-18±7%, p=0.006) and were more common in end-stage disease. Together these data provide the first insight into genotype-phenotype correlations and will be of benefit in variant interpretation and patient stratification in TTN-based DCM.
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Taylor-Burt, Kari. "Shiver me titin! Elucidating titin's role in organism-level performance." Thesis, Northern Arizona University, 2013. http://pqdtopen.proquest.com/#viewpdf?dispub=1543984.
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The frequency of oscillatory behaviors, like shivering, depends on the animal size and the properties of the muscles driving them. Titin and other muscular proteins play an important role in determining muscle properties, such as stiffness. Because the frequency of oscillatory behaviors depends on muscle properties, we predict that changes in titin's structure would affect these behaviors. The muscular dystrophy with myositis ( mdm) mouse model is characterized by a deletion in the N2A region of titin. Homozygous mdm mutants are substantially smaller (body mass is ½ to ⅓), have a stiffer gait, and have reduced lifespans compared to their wildtype and heterozygous siblings. In addition, we observed that mutants were heterothermic while wildtypes and heterozygotes were homeothermic when exposed to ambient temperatures ranging from 20-37 °C. We measured the relationship between metabolic rate and the differential between body and ambient temperatures for all three genotypes. As the temperature differential increased, metabolic rates increased more rapidly in the mutants than in wildtype or heterozygous mice, indicating that the mutants have a much higher conductance than their age-matched siblings. We measured shivering frequency in the mdm mice. The frequency of tremor during shivering is expected to be directly proportional to (k/ m)0.5 where k is stiffness and m is body mass. Using an allometric relationship between body mass and shivering frequency, we calculated expected values for all three genotypes based on body mass alone. These predicted values allowed us to take into account the much lower body masses of the mdm mutants. The difference between expected and observed values was significantly larger for mutant mice than wildtypes or heterozygotes. Together, the heterothermy in mutants, the very high conductance, and the decreased tremor frequency demonstrate the thermoregulatory challenges faced by mice with the mdm mutation. Previous work at the whole-muscle level showed that despite the higher passive stiffness observed in mdm mutant muscles, these muscles are more compliant when activated compared to muscles from wildtype mice. The lower tremor frequencies in mutants are consistent with a reduced active muscle stiffness in vivo. These observations suggest that titin affects the tuning of shivering frequency by playing a role in setting active muscle stiffness.
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Au, Yunghan. "The interaction of alpha-actinin-2 with ZASP and titin." Thesis, University College London (University of London), 2004. http://discovery.ucl.ac.uk/1446765/.
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Z-band Alternately Spliced PDZ-containing protein (ZASP) is a sarcomeric Z- disk protein expressed in human cardiac and skeletal muscle that is involved in a dominant familial dilated cardiomyopathy. ZASP interacts with the last 150 amino acids of alpha-actinin-2, the major component of the Z-disk, via an N-terminal PDZ domain. ZASP and alpha-actinin-2 are thought to play an important structural role, probably by forming a ternary complex with titin Z-repeats. We have determined the structure of ZASP PDZ and characterised its interaction with alpha-actinin-2. We show that ZASP PDZ is a classical class 1 PDZ domain that recognises with micromolar affinity the carboxy- terminal sequence of an alpha-actinin-2 calmodulin-like domain. We also characterised the ternary complex ZASP/alpha-actinin-2/titin and the role of each component, showing that the alpha-actinin-2/ZASP PDZ interaction involves a binding surface distinct from that involved in the recognition of the titin Z repeats. Finally, we used the ZASP PDZ structure to model other members of the enigma family by homology and to predict their abilities to bind alpha-actinin-2.
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Zhang, Jian Qiao. "Comparative studies with titin from tropical and temperate fish muscle." Thesis, University of Nottingham, 1992. http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.316940.
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Slater, Rebecca E., and Rebecca E. Slater. "Modulation of Cardiac Titin Stiffness in Physiological and Pathophysiological States." Diss., The University of Arizona, 2016. http://hdl.handle.net/10150/623160.
Full textAbstract:
The giant sarcomeric protein titin spans the length of the half sarcomere and contains an I-band spanning region that functions as a molecular spring that develops passive force during diastole. Titin stiffness is modulated both by isoform switching and post-translational modifications including phosphorylation. Modulation of titin stiffness occurs in physiological and pathophysiological states including Heart Failure with Preserved Ejection Fraction (HFpEF) which is marked by increased diastolic stiffness. Here, I investigated the effects of titin phosphorylation by two kinases, ERK2 and CaMKIIδ, at the level of the protein and the myocardium. Additionally, I used mouse models of HFpEF to test if modulating titin stiffness could ameliorate increased diastolic stiffness. Specifically, I used the TAC/DOCA model (surgical) and the N2B KO model (genetic) of HFpEF to test the effects of metformin on titin stiffness and diastolic function. HFpEF mice treated with metformin had improved diastolic function, reduced passive stiffness, and increased PKA phosphorylation compared to non-treated HFpEF animals. Interestingly, these results were only found in animals with an intact N2B-element indicating an underlying mechanism that arises from the N2B element and that includes an increase in PKA-phosphorylation. Additionally, I used the TtnΔIAjxn mouse model, as a mechanical analog of the increased diastolic stiffness in HFpEF, to test the therapeutic effects of exercise and heart rate reduction. Exercise induced hypo-phosphorylation of the PEVK element of titin consistent with reduced passive tension while heart-rate reduction had no effect on passive stiffness. These studies build on the increasing understanding of how titin's stiffness can be modulated and the ways to take advantage of titin in a beneficial manner for diastolic function.
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Hallett, Peter C. "Scanning force microscopy of striated muscle proteins." Thesis, University of Bristol, 1996. http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.296600.
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Çakmaktepe, Şükrü Kökçe Ali Babayev Arif. "Kane tipi yarıiletken kuantum çubuklarında yük taşıyıcılarının enerji spektrumları /." Isparta: SDÜ Fen Bilimleri Enstitüsü, 2006. http://tez.sdu.edu.tr/Tezler/TF01039.pdf.
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Lugo, Mendez Anastasia M. "By Proxy: A Radiocarbon Perspective on Prehistoric Mobility Using Summed Probability Distributions and Paleoenvironmental Reconstructions in Wyoming and Montana." DigitalCommons@USU, 2019. https://digitalcommons.usu.edu/etd/7447.
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Stone circles are among the most common and understudied archaeological features in the Rocky Mountains and High Plains. Their widespread availability coupled with increased archaeological research accompanying oil and natural gas exploration in the region has expanded the availability and size of the region’s radiocarbon database. The dates as data approach uses radiocarbon ages as variables from a larger sample. This thesis compiles radiocarbon ages associated with tipi ring sites in Wyoming and Montana and creates a summed probability distribution from these ages to serve as a proxy for prehistoric mobility. The distribution is corrected for taphonomic bias, or data loss, and compared to two paleoenvironmental proxies from northwestern Wyoming lakes to determine whether prehistoric mobility meets the expectations of the patch choice model. Running correlation windows provide statistical comparisons between datasets. Although a weak statistical relationship is apparent between mobility and the paleoenvironmental reconstructions over the 5000-year study period, no statistically significant correlations were identified at 150-or 200-year scales. Moderate strength correlations between the environmental data and mobility proxy when mobility is lagged suggest a delayed relationship between the datasets. Future research must include expanding the radiocarbon database and obtaining finer-scale paleoenvironmental reconstructions.
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Ting, Lok Yin. "Calcium dependence of titin-regulated passive force in skeletal muscle fibers." Thesis, McGill University, 2012. http://digitool.Library.McGill.CA:80/R/?func=dbin-jump-full&object_id=110598.
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AbstractRationale: There is evidence that the passive forces produced by titin in skeletal muscles may be regulated by Ca2+. Studies have shown an upwards shift in the passive force-sarcomere length (SL) relation when muscle fibres are tested with a high concentration of Ca2+ and the myosin-actin interaction is abolished.Objective: To test the hypothesis that there is a direct relation between the concentrations of Ca2+ and the cross-bridge independent increase in passive forces.Hypothesis: There is an upward shift in passive force-sarcomere length relation with increase calcium concentration.Methods: Single fibres were isolated from the rabbit psoas muscle and transferred into an experimental chamber, between a force transducer and a motor arm. Fibres were activated in a range of Ca2+ concentrations (pCa2+ between 4.5 and 9.0), before and after administration of the myosin inhibitor blebbistatin. The fibres were submitted to a protocol in which they underwent consecutive step-stretches, starting at an initial SL of 2.5µm (amplitude of stretch: 5% initial SL, duration 300 ms, pauses between stretches: 30 sec).Results: We observed similar passive force-sarcomere length curves in all calcium concentrations. Different pCa2+ did not affect the amount of passive force produced. Conclusions: The results suggest that the passive forces in skeletal muscles are not regulated by calcium concentrations.RésuméPréambule: Il existe des preuves que les forces passives produites par titine des muscles squelettique sont liées avec la concentration de Ca2+. Plusieurs études montrent qu'il existe un lien positif entre la longueur des sarcomères et la force passive générée lorsque les tests sont faits dans des hautes concentrations de Ca2+ et lorsque les interactions actine-myosine sont abolies. Objectifs: Tester l'hypothèse qu'il y a un lien positif entre la concentration de Ca2+ et l'augmentation de la force passive lorsque les pontages croisés sont abolis. Hypothèse: La force passive augmente parallèlement avec l'augmentation de la concentration de calcium.Méthodologie: Les fibres musculaires psoas des lapins sont d'abord isolées et transférées dans une chambre expérimentale fixées entre un transducteur de force et un bras moteur du système. Ces fibres sont activées dans une solution de calcium entre pCa2+4.5 et pCa2+9.0 avant et après l'administration de l'inhibiteur de myosine, blebbistatin. Les fibres sont étirées consécutivement débutant à une longueur de sarcomère 2.5m. (À une amplitude d'étirement de 5% de LS initiale, une durée de 300ms et 30s de pause entre chacun des étirements. Résultats: La force passive est semblable pour chacun des concentrations de calcium, donc il n'y a aucuns effets de calcium sur la production de la force passive.Conclusions: Les résultats nous suggèrent que la force passive n'est pas liée à la concentration de calcium.
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陈美翩 and Meipian Chen. "Effects of iron overload on apoptosis and titin proteolysis in cardiomyocytes." Thesis, The University of Hong Kong (Pokfulam, Hong Kong), 2013. http://hdl.handle.net/10722/193425.
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Iron is one of the essential elements involved in various fundamental biological activities. However, excess iron may bypass the negative feedback regulatory systems, leading to the formation of iron overload. The increase of iron deposition generates cellular toxicity and subsequently damages vital organs. Primary and secondary iron overload are affecting patients worldwide. Iron overload cardiomyopathy is the primary cause of cardiac dysfunction and cardiovascular mortality in β-thalassaemia major patients. Current effective therapy includes chelation treatment with conventional and new iron chelators, while potential new therapies are currently under development.
The pathophysiology of iron overload cardiomyopathy remains unclear. Controversial findings on the mechanism of excessive iron entry into cardiomyocytes exist. Using novel real-time approach to trace iron entry into HL-1 cardiomyocytes, the only beating cardiac cell line with mature cardiac phenotype available currently, we visualized the patterns of iron entry following ferric iron incubation with and without ascorbate. Iron entry could be partly blocked by pretreatment with L-type calcium channel blockers but not T-type calcium channel blocker. Such blockage effect by L-type calcium channel blockers occurred in ferric iron overload. This finding suggested a role of L-type calcium channels for ferric iron uptake into cardiomyocytes under iron overload condition.
For the pathophysiology of iron cardiac toxicity, we assessed the iron overload induced apoptosis using both in vitro and in vivo approaches. The results demonstrated that iron-overloaded mouse HL-1 atrial cardiomyocytes and human embryonic stem cell derived ventricular cardiomyocytes underwent apoptosis via the mitochondria-mediated caspase-3 dependent pathway. Supportive data was found in iron-overloaded mouse myocardium by an increase in DNA fragmentation. However, despite the blockage of iron entry, L-type calcium channel blockers did not significantly prevent iron induced apoptosis in vitro.
The mechanism of cardiac contractile dysfunction caused by iron overload on cardiomyopathy has not yet been fully characterized. Given the central role of titin, the giant myofilament protein, as the main determinant in myocardial passive tension, stiffness, diastolic and systolic cardiac function, as well as myocardial twisting and untwisting motion, we investigated its expression in iron-overloaded cardiomyocytes in vitro and in vivo. Our results indicated that significant degradation of cardiomyocytes titin was induced by iron overload. This was associated with the cleavage at the elastic domain. Its potential upstream protease, calpain, was further identified to be activated under iron overload. The specific role of titin proteolysis in iron-overloaded cardiomyocytes merited further investigation.
The findings in this project provided new insights to the pathophysiology of iron overload cardiomyopathy, in terms of the route for iron entry, iron induced cardiac apoptosis, and titin proteolysis. Novel therapeutic approaches for prevention and treatment of iron overload cardiomyopathy can focus on inhibiting excessive iron uptake, as well as by targeting pathways involved in cardiac apoptosis and titin proteolysis.published_or_final_version
Paediatrics and Adolescent Medicine
Doctoral
Doctor of Philosophy
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Head, Jared G. "Structure and function of the #beta#-sheet proteins, titin and CD2." Thesis, University of Bristol, 1998. http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.265387.
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Engel, Frank, and Frank Usbeck. "Die Tipis der alten Nordamerika-Sammlungen im Leipziger Museum für Völkerkunde." VWB, 2013. https://tud.qucosa.de/id/qucosa%3A29282.
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Borgia, Madeleine Bridget Windsor. "Studies of the aggregation and misfolding of titin Ig-like domains." Thesis, University of Cambridge, 2011. http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.609256.
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Engel, Frank, and Frank Usbeck. "Die Tipis der alten Nordamerika-Sammlungen im Leipziger Museum für Völkerkunde." Saechsische Landesbibliothek- Staats- und Universitaetsbibliothek Dresden, 2016. http://nbn-resolving.de/urn:nbn:de:bsz:14-qucosa-199111.
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Bezerra, José Noberto Sousa. "Composição química,atividade fitonematicida e inseticida de Tipi (Petiveria alliaceae)." reponame:Repositório Institucional da UFC, 2006. http://www.repositorio.ufc.br/handle/riufc/10868.
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BEZERRA, J. N. S. Composição química,atividade fitonematicida e inseticida de Tipi (Petiveria alliaceae). 2006. 121 f. Dissertação (Mestrado em Química Orgânica) - Centro de Ciências, Universidade Federal do Ceará, Fortaleza, 2006.Submitted by José Jairo Viana de Sousa (jairo@ufc.br) on 2014-10-10T18:53:22Z No. of bitstreams: 1 2006_dis_jnsbezerra.pdf: 6462938 bytes, checksum: a3066d6d4b93361ed9f4c6ca281f1d98 (MD5)
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This work describes the study of the volatile and the non-volatile components from the roots of Petiveria alliaceae, including the nematicidal and insecticidal activities of the essential oil. The following components were identified in the essential oil: benzaldehyde as the major constituent (61, 5 %), cinnamaldehyde (6, 3%), dibenzyl disulphide (18, 1%), transstilbene (14, 1%). The two last compounds were also isolated through a chromatography in a preparative thin layer identified by RMN 1H and 13C. The isolation of a mixture of two mercaptans, benzyl disulphide and dibenzyl trisulphide, saccharose and allantoin, which were isolated for the first time from the Petiveria alliaceae, was permitted by the chromatographic treatment of the ethyl acetate, hexane, and ethanolic extracts. The isolated mercaptans are known in literature for their fungicide and insecticide activities. The constituents of the essential oil, extracted from the roots of Petiveria alliaceae, were submitted to the nematicidal activities against Meloidogyne incognita larva, insecticide against white fly (Bemisa tabaci) and insect of the beans (Callosobruchus maculatos). Significant insecticidal and nematicidal activities were present in the essential oil from the P. alliaceae, collected in two different localities. The isolated constituents had their structure elucidated through spectrometric methods of IV, EM, RMN 1H and 13C uni and bi-dimensional (COSY, HMQC and HMBC)
Este trabalho descreve o estudo dos componentes voláteis e não voláteis das raízes de Petiveria alliaceae, incluindo as atividades nematicida e inseticida do óleo essencial. Para o estudo químico, fitonematicida e inseticida utilizou-se as raízes da planta, das quais foram obtidos o óleo essencial e os constituintes não-voláteis. Do óleo essencial das raízes foram identificados os seguintes componentes: benzaldeido (61,5%) (constituinte majoritário) dissulfeto de dibenzila (18,1%), transestilbeno (14,1%) e cinamaldeido (6,3%), sendo que esses dois últimos compostos também foram isolados através de cromatografia em camada delgada preparativa e identificados por RMN 1H e 13C. O tratamento cromatográfico dos extratos etanólico, acetato de etila e hexânico permitiu o isolamento de uma mistura de duas mercaptanas, dissulfeto de dibenzila e o trissulfeto de dibenzila, dissulfeto de dibenzila, uma alantoina e a sacarose, que pela primeira vez foram isoladas das raízes de Petiveria alliaceae. As mercaptanas isoladas são conhecidas na literatura por suas atividades fungicidas e nematicida. O óleo essencial extraído das raízes de P. alliaceae e seus constituintes foram submetidos aos ensaios de atividades nematicida contra larvas de Meloidogyne incógnita (nematóide de galhas) e inseticida contra a Mosca branca (Bemisia tabaci) inseto do feijão (Callosobruchus maculatus). Os óleos essenciais obtidos de P. alliaceae coletadas nas duas localidades diferentes apresentaram significantes atividades inseticida e nematicida. Os constituintes isolados tiveram suas estruturas elucidadas através de métodos espectrométricos de IV, EM, RMN 1H e 13C uni e bidimensionais (COSY, HMQC e HMBC).
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Laurel, Antoinette. "The Study of Titin in A/I Knockout Mice During Cardiac Failure." Thesis, The University of Arizona, 2011. http://hdl.handle.net/10150/144556.
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Polack, Christopher [Verfasser]. "Function of Titin in Striated Muscles in Health and Disease / Christopher Polack." Berlin : Freie Universität Berlin, 2015. http://d-nb.info/108017110X/34.
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Nyaboke, Roseline Nyaboke. "The Role of N2A and N2B Titin Isoforms in Muscle Cell Development." Youngstown State University / OhioLINK, 2016. http://rave.ohiolink.edu/etdc/view?acc_num=ysu1471612545.
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Sandberg, Emil, and Simon Ternström. "Samvetsgrannhet: Nyckeln till akademisk motivation? : En studie om förhållandet mellan personlighet och akademisk motivation hos studenter på en högskola i Mellansverige." Thesis, Högskolan i Gävle, Avdelningen för socialt arbete och psykologi, 2015. http://urn.kb.se/resolve?urn=urn:nbn:se:hig:diva-20104.
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The purpose of this study was to investigate the relationship between students’ academic motivation and personality in different classes at a university in central Sweden. The study was conducted on students of economics and nursing, who were asked to answer a paper questionnaire. The questionnaire of consisted two parts, the first part was a TIPI test which measured personality traits using the Big Five theory and the second part was an AMS test that measured academic motivation. A total of 106 students participated in the study, including 50 from economics and 56 from nursing. The main result showed that the strongest significant correlation was between the personality trait conscientiousness and internal motivation. This relationship was found to completely rely on the nursing students replies, giving an indication that the nursing students who were self-disciplined and targeted were motivated by internal factors. This relationship was not found in the replies from the economics students. There was some difference between the two study specializations.Syftet med studien var att undersöka förhållandet mellan akademisk motivation och personlighet hos studenter med olika studieinriktningar på en högskola i Mellansverige. Studien genomfördes på studenter från ekonom- och sjuksköterskeprogrammet som fick besvara en pappersenkät. Enkäten bestod av två delar, varav den första var ett TIPI-test som mätte personlighetsdimensioner med hjälp Big Five-teorin och den andra var ett AMS-test som mätte akademisk motivation. Totalt deltog 106 studenter i undersökningen, varav 50 från Ekonomprogrammet och 56 från Sjuksköterskeprogrammet. Huvudresultatet visade att det starkaste signifikant sambandet var mellan personlighetsdimensionen samvetsgrannhet och intern motivation. Detta samband visade sig helt bäras av sjuksköterskestudenternas svar, vilket gav en indikation på att de sjuksköterskestudenter som var självdisciplinerade och målinriktade motiverades av interna faktorer. Detta samband återfanns över huvudtaget inte hos ekonomstudenterna. Det förelåg en viss skillnad mellan de två olika studieinriktningarna.
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Müller, Anna-Eliane [Verfasser]. "Modulation of cardiac titin stiffness in diabetic and exercised hearts / Anna-Eliane Müller." Düsseldorf : Universitäts- und Landesbibliothek der Heinrich-Heine-Universität Düsseldorf, 2015. http://d-nb.info/1066359237/34.
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Bodmer, Nicholas. "Molecular Investigations into the Titin-Telethonin Complex: A study in Protein-Protein Interactions." University of Cincinnati / OhioLINK, 2015. http://rave.ohiolink.edu/etdc/view?acc_num=ucin1439307071.
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Javidialesaadi, Abdolreza. "Computer Simulations of Titin I27 and Knotted Protein Remodeling by Clp Biological Nanomachines." University of Cincinnati / OhioLINK, 2018. http://rave.ohiolink.edu/etdc/view?acc_num=ucin1523628577990709.
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Tonino, Paola, Balazs Kiss, Josh Strom, Mei Methawasin, John E. Smith, Justin Kolb, Siegfried Labeit, and Henk Granzier. "The giant protein titin regulates the length of the striated muscle thick filament." NATURE PUBLISHING GROUP, 2017. http://hdl.handle.net/10150/626066.
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The contractile machinery of heart and skeletal muscles has as an essential component the thick filament, comprised of the molecular motor myosin. The thick filament is of a precisely controlled length, defining thereby the force level that muscles generate and how this force varies with muscle length. It has been speculated that the mechanism by which thick filament length is controlled involves the giant protein titin, but no conclusive support for this hypothesis exists. Here we show that in a mouse model in which we deleted two of titin's C-zone super-repeats, thick filament length is reduced in cardiac and skeletal muscles. In addition, functional studies reveal reduced force generation and a dilated cardiomyopathy (DCM) phenotype. Thus, regulation of thick filament length depends on titin and is critical for maintaining muscle health.
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Guerra, Andrea. "LTIQ Un Calcolo Lineare per Q#." Master's thesis, Alma Mater Studiorum - Università di Bologna, 2021. http://amslaurea.unibo.it/22959/.
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Il teorema di non duplicazione della meccanica quantistica afferma che uno stato quantistico non possa mai essere duplicato o cancellato. Diversi linguaggi di programmazione quantistici, ovvero basati sui principi della meccanica quantistica, garantiscono a tempo di compilazione, grazie ai sistemi di tipi lineari, che i loro programmi non violino mai il teorema di non duplicazione. Non è questo il caso del linguaggio specifico di dominio Microsoft Q#: l’esecuzione di un programma Q# può portare ad errori a tempo di esecuzione dovuti a violazioni del teorema di non duplicazione causando uno spreco di risorse quantistiche. Per ovviare a questo problema, in questo lavoro di tesi viene formalizzato il core computazionale di Q# introducendo il calcolo fondazionale Linearly Typed Idealized Q# (abbreviato in LTIQ). Dopo aver provvisto LTIQ di una sintassi e una semantica operazionale viene definitio un sistema di tipi lineare per esso.
Il risultato principale di questo elaborato, assieme alla definizione del sistema di tipi, è la dimostrazione del teorema di sicurezza rispetto ai tipi (type safety). Da questo segue che in un programma ben tipato nessun dato tipato linearmente verrà duplicato o cancellato durante l’esecuzione del programma. Avendo i dati quantistici tipo lineare,
nessun programma ben tipato violerà quindi il teorema di non duplicazione durante la sua esecuzione.
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Olsson, Anna. "Olika personlighetsdrag och dess förhållande till prosocialt beteende. : En enkätundersökning mellan TIPI och PTM." Thesis, Karlstads universitet, Institutionen för sociala och psykologiska studier, 2014. http://urn.kb.se/resolve?urn=urn:nbn:se:kau:diva-31564.
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Genom webbaserade enkäter har data insamlats för att undersöka huruvida det finns en korrelation med de olika personlighetsdragen inom The Big Five och olika dimensioner av prosocialt beteende. Till detta utformades en enkät genom sammanslagning av Ten Item Personality Inventory (TIPI) och Prosocial Tendency Measure (PTM), där index togs ut för alla olika dimensioner. Respondenter rekryterats genom ett tillgänglighetsurval (N= 79, varav 24 stycken män, M= 39,6 år, SD= 13.6, 55 stycken kvinnor, M= 40.1 år, SD= 13.6 ). Totalt av urvalet var 13,8 procent uppvuxna i en storstad, 28,8 procent uppvuxna i småstad och 57,5 procent inom landsbygd. Inom urvalet hade 10 procent en grundskoleutbildning, 38,8 procent gymnasieutbildning, och 51,3 högskole- eller universitetsutbildning. Resultatet visar att det finns samvariationer mellan de olika personlighetsdragen och olika dimensioner av prosocialt beteende.
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Methawasin, Mei Methajit. "The Role Of Titin In Cardiac Function: Studies With The Mouse Model Deficient In The Splicing Factor RBM20." Diss., The University of Arizona, 2014. http://hdl.handle.net/10150/337266.
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In the first half of this work, titin's role in cardiac function was studied using intact cardiac myocytes. The development of a carbon fiber based cell-attachment system allowed diastolic and systolic function of the isolated intact myocyte to be investigated. Addition of actomyosin inhibitor to the intact myocyte revealed that the majority of the cell's diastolic stiffness is due to titin but that actomyosin interaction exists as well and contributes ~ 30% of total diastolic stiffness. The details of this study are provided in chapter 1. Heart failure with preserved ejection fraction (HFpEF) accounts for up to 50% of total heart failure cases and is characterized by increased diastolic stiffness. An effective treatment for HFpEF does not exist. Reducing titin stiffness as a therapeutic strategy for lowering left ventricular (LV) chamber stiffness in HFpEF is currently under consideration. To understand the functional consequence of reduced titin stiffness on global cardiac function a Rbm20 Δᴿᴿᴹ mouse model was created. The Rbm20 Δᴿᴿᴹ model has deficiency in titin splicing that results in expression of very large and compliant titin isoforms in the sarcomeres. Study of Rbm20 Δᴿᴿᴹ cells revealed that cellular diastolic stiffness was inversely related to the size of titin and was reduced in a graded manner in Rbm20 Δᴿᴿᴹ heterozygous (+/-) and homozygous (-/-) cells. Importantly, reduced titin-based stiffness manifested in vivo as reduced LV chamber stiffness, which could be observed by echocardiography and pressure volume (PV) analysis. The systolic function of Rbm20 Δᴿᴿᴹ was studied by measuring the Frank-Starling mechanism (FSM), first at the intact myocyte level. The FSM was reduced in Rbm20 Δᴿᴿᴹ +/- and -/- with the largest reduction in -/- cells. PV analysis demonstrated a reduced FSM at the LV chamber level, consistent with the result at the cellular level. Surprisingly, exercise testing showed an enhanced exercise performance in cardiac specific Rbm20 Δᴿᴿᴹ +/- mice (relative to wild-type mice). Thus, this work indicates that increasing titin compliance improves diastolic function but negatively impacts systolic function. Importantly, findings suggest that the beneficial effect of improving diastolic function is a dominant effect. This work is described in Chapter 2.
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Bull, Mathew Michael. "Experimentally Altering the Compliance of Titin's Spring Region." Diss., The University of Arizona, 2016. http://hdl.handle.net/10150/613257.
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Chapter 1 of this work focuses on alternative splicing of titin as a proof of concept therapy for treating diastolic dysfunction and restrictive filling in a genetic murine model (Ttn^(ΔIAjxn)). The Ttn^(ΔIAjxn) mouse has increased strain on the spring region of titin and acts as a mechanical analogue of the titin-based increase in passive myocardial stiffness found in patients with heart failure and preserved ejection fraction (HFpEF). HFpEF is a complex disease characterized by diastolic dysfunction, exercise intolerance, and concentric hypertrophic remodeling. Approximately half all of heart failure patients suffer from diastolic dysfunction, however, no effective therapy exists for treating this pervasive syndrome. Titin, the largest known protein and molecular spring in the heart, has emerged as a prime candidate for therapeutic targets aimed at restoring compliance to the sarcomere in order to improve diastolic function. Titin has two main cardiac isoforms that are regulated by alternative splicing; the smaller N2B isoform (~3.0 MDa) and the larger more compliant N2BA isoform (~3.3 MDa). Diastolic stiffness of the left ventricle is dependent upon the N2BA:N2B isoform ratio. In the first half of this work, we modified these two primary isoforms by inhibiting the known titin splicing factor Rbm20. We demonstrate that Rbm20 reduction restores diastolic function, improves exercise tolerance and attenuates afterload induced pathologic remodeling of the left ventricle in Ttn^(ΔIAjxn) mice.The work in chapter 2 is focused on studies using the previously published N2B knock out (KO) murine model. The N2B spring element found in cardiac titin's I-band region has been proposed as a sensor and signaling "hot spot" in the sarcomere. This study investigates the role of titin's cardiac specific N2B element as a mechano-sensor for stress and strain induced remodeling of the heart. The N2B KO mouse was subjected to a variety of stressors including transverse aortic constriction (TAC), aortocaval fistula (ACF), chronic swimming, voluntary running and isoproterenol stimulation. Our data revealed that the N2B element is essential in preload stimulated cardiac hypertrophy as well as remodeling due to beta-adrenergic stress. Cardiac hypertrophy is a common maladaptive feature of heart failure patients and the mechanical triggers that determine pathologic growth are not well understood. My work in the N2B KO mouse reveal titin's important role in cardiac remodeling.
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Borgiani, Edoardo. "Misura delle sollecitazioni nel femore umano con diversi tipi di protesi d'anca." Bachelor's thesis, Alma Mater Studiorum - Università di Bologna, 2012. http://amslaurea.unibo.it/4310/.
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Person, Veronika. "Die Rolle von Titin in der Sarkomerogenese Untersuchungen an adulten Kardiomyozyten der Ratte in Langzeitkultur /." [S.l.] : [s.n.], 2000. http://deposit.ddb.de/cgi-bin/dokserv?idn=960462864.
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Bergmann, Nora [Verfasser], Ulf [Akademischer Betreuer] Stahl, and Michael [Akademischer Betreuer] Gotthardt. "Smooth muscle titin in embryo implantation and angiogenesis / Nora Bergmann. Betreuer: Ulf Stahl ; Michael Gotthardt." Berlin : Technische Universität Berlin, 2010. http://d-nb.info/1066546274/34.
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Schütz, Jan-Hendrik [Verfasser], Philipp [Akademischer Betreuer] Vana, and Michael [Akademischer Betreuer] Buback. "Bioinspirierte Titin-analoge Polymere / Jan-Hendrik Schütz. Gutachter: Philipp Vana ; Michael Buback. Betreuer: Philipp Vana." Göttingen : Niedersächsische Staats- und Universitätsbibliothek Göttingen, 2014. http://d-nb.info/1062770684/34.
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Roos, Viola Corinne [Verfasser], Wolfgang [Akademischer Betreuer] Linke, and Katrin [Akademischer Betreuer] Marcus. "Titin-Degradationsprodukte als potentielle Biomarker für Herzerkrankungen / Viola Corinne Roos. Gutachter: Wolfgang Linke ; Katrin Marcus." Bochum : Ruhr-Universität Bochum, 2016. http://d-nb.info/1089006594/34.
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Zelinka, Lisa M. "PROTEIN EXPRESSION AND CHARACTERIZATION OF THE MAJOR AUTOANTIGEN (TITIN DOMAIN) ASSOCIATED WITH AUTOIMMUNERIPPLING MUSCLE DISEASE." Kent State University / OhioLINK, 2015. http://rave.ohiolink.edu/etdc/view?acc_num=kent1416852571.
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Schütz, Jan-Hendrik Verfasser], Philipp [Akademischer Betreuer] Vana, and Michael [Akademischer Betreuer] [Buback. "Bioinspirierte Titin-analoge Polymere / Jan-Hendrik Schütz. Gutachter: Philipp Vana ; Michael Buback. Betreuer: Philipp Vana." Göttingen : Niedersächsische Staats- und Universitätsbibliothek Göttingen, 2014. http://nbn-resolving.de/urn:nbn:de:gbv:7-11858/00-1735-0000-0023-993F-1-5.
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Coviello, Anna Chiara. "Esistenza del minimo globale per certi tipi di problemi vincolati in R^n." Bachelor's thesis, Alma Mater Studiorum - Università di Bologna, 2010. http://amslaurea.unibo.it/1558/.
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