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Ang, Hwee Ngoh. "Modelling and characterisation of 2-terminal heterojunction phototransistors". Thesis, University of Surrey, 2005. http://epubs.surrey.ac.uk/843728/.
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A Heterojunction Phototransitor (HPT) is an attractive high-speed photodetector for optical communications, as it can provide high gain and high power. It can also be used to generate millimetre-wave signals using optical heterodyne for radio astronomy and wireless broad-band communications. Edge illuminated 2-terminal HPTs (2T-HPTs) integrated with an optical waveguide are designed and characterised. A small signal model is developed and it simulates the 2T-HPT frequency responses with good accuracy and supplements the measurement to determine its gain and cut-off frequency. This overcomes the requirement to measure the input photocurrent to the 2T-HPT using an exact replica of its PIN structure. The high frequency responses for the longer devices, which give higher saturation current, are limited by the loss of the transmission line. This high loss is also observed by the 2-port characterisation of the back-to-back configured 2T-HPT and gives a trade-off between the cut-off frequency and saturation current in the design. Additional analysis shows that the cut-off frequency is also limited by the large device capacitances. Using scaling of the model, the cut-off frequency is shown to increase to 59.4GHz with a gain of 39dB for a 1mum x 10mum 2T-HPT. The above result shows that the 2T-HPT could be best utilised in a periodic structure (P-TWHPT), with small device area sections connected by short transmission lines. This increases the saturation current level without reducing the cut-off frequency and gain. A P-TWHPT model is developed to simulate and analyse its frequency response. It is shown that the effects of phase matching and reverse input termination are not critical for 2T-HPT structure, as its 3dB bandwidth is limited by the base discharge time constant. A four 5mum x 10mum 2T-HPT section P-TWHPT is simulated with the phase mismatch and without reverse termination. It has a gain of 49dB and a cut-off frequency of 67.5GHz.
2
Shao, Jin. "Notch signalling pathway regulates the terminal differentiation of osteoblasts". Thesis, Queensland University of Technology, 2018. https://eprints.qut.edu.au/119172/2/Jin_Shao_Thesis.pdf.
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This project contributes to our understanding of bone cell biology and sheds light on the potential therapeutic application of Notch signalling pathway on bone-related diseases. The thesis was a step forward in answering how bone cells communicate with each other and determinate their own fates. It provides the first evidence demonstrating Notch signalling is critical in bone cell functions.
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Silva, Antônio Marcos Vargas da. "Disfunção endotelial na insuficiência renal terminal e no diabetes tipo 2". reponame:Biblioteca Digital de Teses e Dissertações da UFRGS, 2008. http://hdl.handle.net/10183/13140.
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Vários estudos envolvendo a avaliação da função endotelial em pacientes com insuficiência renal terminal (IRT) e em pacientes com diabetes tipo 2 (DM2) têm sido apresentados objetivando um melhor entendimento dos mecanismos fisiopatológicos e das condições que cercam essas patologias. As sessões de hemodiálise (HD) em pacientes com IRT e a microalbuminúria em pacientes com DM2 influenciam as respostas endoteliais e, diante disso, este trabalho constitui-se de dois estudos independentes com ambas as populações, sendo: o Estudo 1 objetivou avaliar a influência de uma sessão de HD na função endotelial venosa e no estresse oxidativo de nove pacientes com IRT comparados a um grupo controle (n=10). A função endotelial foi avaliada pela técnica de Dorsal Hand Vein e o estresse oxidativo pelas medidas de capacidade antioxidante total (TRAP) e de dano oxidativo à proteínas (Carbonilas). Antes da HD, os pacientes apresentaram reduzida venodilatação dependente do endotélio (VDE) na comparação com o controle (65,6 ± 10,5% vs. 109,6 ± 10,8%; P = 0,010). Após a HD houve um aumento na VDE (106,6 ± 15,7%; P = 0,045). A venodilatação independente do endotélio foi similar em todas as comparações realizadas. A HD reduziu o TRAP (402,0 ± 53,5 vs 157,1 ± 28,3 U of Trolox/μL plasma; P = 0,001) e não alterou as carbonilas (P = 0,389). O delta de VDE foi negativamente correlacionado com o delta de TRAP (r = -0,70; P = 0,037). Esses resultados sugerem que a sessão de HD melhora a função endotelial venosa associada a menor redução de antioxidantes. No Estudo 2 foram avaliados 28 pacientes com DM2, subdivididos em grupo normoalbuminúrico (n=16) e microalbuminúrico (n=12), com o objetivo de comparar entre os grupos a função endotelial no leito venoso e arterial. As funções endotelial venosa e arterial foram avaliadas pela técnica de Dorsal Hand Vein (venodilatação) e pela dilatação mediada pelo fluxo (FMD) da artéria braquial através de ultrasonografia de alta resolução, respectivamente. Pacientes microalbuminúricos apresentaram reduzida venodilatação (32,9 ± 17,4% vs. 59,3 ± 26,5%, respectivamente; P = 0,004) e FMD (1,8 ± 0,9% vs. 5,1 ± 2,4, respectivamente; P < 0,001), quando comparados a normoalbuminúricos. A venodilatação se correlacionou negativamente com albuminúria (r = -0,53; P = 0,004) e com HbA1c (r = -0,41; P = 0,032). O mesmo foi observado entre FMD e albuminúria (r = -0,49; P = 0,007) e HbA1c (r = -0,44; P = 0,019). Foi observada uma correlação positiva entre venodilatação e FMD (r = 0,50; P = 0,007). Assim, a função endotelial em ambos os leitos vasculares está prejudicada em pacientes com DM2 e microalbuminúria. Os dois métodos utilizados para avaliação da função endotelial se correlacionaram positivamente. Mesmo em um grupo de pacientes com bom controle metabólico, as respostas de vasodilatação se correlacionaram negativamente com HbA1c.Several studies were shown, involving endothelial function assessment in patients with endstage renal disease (ESRD) and in patients with type 2 diabetes (T2D), aiming a better understanding of physiopathological mechanisms and conditions surrounding these pathologies. Hemodialysis (HD) sessions in patients with ESRD and microalbuminuria in patients with T2D influence the endothelial responses and, therefore, this work was based on two independent studies, namely: Study 1 aimed at evaluating the influence of an HD session in venous endothelial function and oxidative stress of nine patients with ESRD compared to a control group (n=10). Endothelial function was assessed by dorsal hand vein technique and oxidative stress by total radical trapping antioxidant potential (TRAP) and protein oxidative damage (carbonyls). Before HD, the patients showed a reduced endothelium-dependent venodilation (EDV) compared with controls (65.6 ± 10.5% vs. 109.6 ± 10.8%; P = 0.010). After HD there was an increase in EDV (106.6 ± 15.7%; P = 0.045). The endotheliumindependent venodilation was similar in all comparisons performed. HD decreased TRAP (402.0 ± 53.5 vs 157.1 ± 28.3 U of Trolox/μL plasma; P = 0.001) and did not change the carbonyls (P = 0.389). The delta in EDV was negatively correlated with the delta in TRAP (r = -0.70; P = 0.037). These results suggest that an HD session improves endothelial venous function, in association with an antioxidant effect. In Study 2 28 patients with T2D were evaluated, subdivided into normoalbuminuric (n=16) and microalbuminuric group (n=12), aiming to compare the endothelial function in venous and arterial bed between the groups. Venous and arterial endothelial function were assessed by the dorsal hand vein technique (venodilation) and brachial artery flow-mediated vasodilation (FMD) by high-resolution ultrasonography, respectively. Microalbuminuric patients presented impaired venodilation (32.9 ± 17.4% vs. 59.3 ± 26.5%, respectively; P = 0.004) and FMD (1.8 ± 0.9% vs. 5.1 ± 2.4, respectively; P < 0.001), as compared to normoalbuminuric patients. Venodilation was negatively correlated with microalbuminuria (r = -0.53; P = 0.004) and HbA1c (r = -0.41; P = 0.032). The same was observed between FMD and albuminuria (r = -0.49; P = 0.007) and HbA1c (r = -0.44; P = 0.019). Venodilation was positively correlated with FMD (r = 0.50; P = 0.007). Thus, both venous and arterial endothelial function are impaired in patients with T2D and microalbuminuria. The two methods used for endothelial function evaluation were positively correlated. Even though patients had good metabolic control as a group, vasodilation responses were negatively correlated with HbA1c.
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Galal, Daria, i Martin Tillberg. "Security Test of iZettle's Reader 2 : A card terminal for safe payments?" Thesis, KTH, Skolan för elektroteknik och datavetenskap (EECS), 2020. http://urn.kb.se/resolve?urn=urn:nbn:se:kth:diva-277913.
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Ethical hacking and penetration testing are two methods often used when organizations and companies want to measure their level of information security, and find out if there are additional steps that can be taken in order to increase the security. This report describes a security test of the card terminal iZettle Reader 2, with the intention to examine its level of security based on the device’s frequent appearance in the society. The implementation is divided into three phases: prestudy and threat modelling, penetration testing and evaluation and conclusion of the security. The threat model was created using the two established models STRIDE & DREAD, which purpose is to identify the device’s various threats and attack vectors. From the threat model, a couple of attack vectors were selected to be penetration tested. By using conventional models and obtaining knowledge of common attacks such as Man-in-the-middle, Spoofing and Replay, the device and the payment solution could be tested with a systematical and reliable approach. A selection was made of the most prominent attack vectors, of which these were later tested; Man-in-the-middle of Bluetooth and HTTPS, and Reverse Engineering of the associated mobile application "iZettle Go". The result of the penetration tests indicated that the security around the device and surrounding systems is strong, but that it can be further supplemented with a couple of actions like certificate pinning and mutual authentication when communicating with TLS, as well as a more tamperproof software regarding the mobile application.Etisk hackning och penetrationstestning är två metoder som ofta tillämpas i sammanhang när organisationer och företag vill mäta sin nivå av informationssäkerhet, samt även ta reda på om eventuella åtgärder kan tas för att stärka säkerheten. Denna rapport beskriver ett säkerhetstest av kortterminalen iZettle Reader 2, med syftet att undersöka dess nivå av säkerhet grundat på enhetens frekventa uppträdande i samhället. Genomförandet är uppdelat i tre faser: förstudie och hotmodellering, penetrationstestning samt utvärdering och avgörande av säkerheten. Hotmodellen skapades med hjälp av de två vedertagna modellerna STRIDE & DREAD, vars syfte är att identifiera enhetens olika hot och attackvektorer. Utifrån hotmodellen valdes några attackvektorer som sedan penetrationstestades. Genom att använda etablerade modeller samt erhålla kännedom om konventionella attacker såsom Man-in-the-middle, Spoofing och Replay, kunde man testa enheten och betallösningen med ett systematiskt och pålitligt tillvägagångssätt. Ett urval gjordes av de mest lovande attackvektorerna, varav dessa senare testades; Man-in-the-middle av Bluetooth och Wi-Fi samt Reverse Engineering av den tillhörande mobilapplikationen "iZettle Go". Resultatet av testerna påvisade en stark säkerhet gällande enheten och dess omgivande system, men att säkerheten kan kompletteras ytterligare med ett par olika åtgärder som certificate pinning och mutual authentication vid kommunikation med TLS, samt manipuleringssäker mjukvara med avseende på mobilapplikationen.
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Prata, Henrique Moraes. "Enfermidade e infinito: direitos da personalidade do paciente terminal". Universidade de São Paulo, 2012. http://www.teses.usp.br/teses/disponiveis/2/2131/tde-15042013-111929/.
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O presente trabalho apresenta uma nova perspectiva para as discussões jurídicas e bioéticas acerca dos direitos da personalidade dos pacientes terminais e encontra em nosso ordenamento jurídico, na afirmação de um direito geral da personalidade, a plenitude da tutela civil dos bens jurídicos personalíssimos do enfermo, sobretudo nas etapas finais da doença, ocasião em que a hipermedicalização do processo de morrer destaca-se como o principal fator gerador de lesões de diversas naturezas a esses bens. No caminho para chegarmos à proteção geral da personalidade, examinamos alguns direitos especiais que emergem ao final da existência humana, como o direito à morte em momento natural. No intuito de recuperar a centralidade da pessoa humana como fim único a que devem servir o Direito e a Medicina, construímos a trajetória do conceito de pessoa em seu desenvolvimento jusfilosófico para afirmar que todo ser humano é pessoa e sujeito de direito (ubi homo sapiens, ibi persona), ainda que não possua capacidade jurídica de fato, e, com isso, demonstrar a impossibilidade de pertença a uma classe de não pessoas independentemente de circunstâncias ou do desenvolvimento biopsíquico humano. Asseveramos, também, que o cuidar e o tratar em pacientes gravemente enfermos e terminais deve relacionar-se, antes, ao homem em sua dignidade e plenitude, em uma concepção biomédica, filosófica e metafísica conjugada da sua existência, e não se reduzir à simples obstinação prognóstica e terapêutica, visão reducionista que relaciona tratar a doença a um investimento no prolongamento estéril da vida humana. Nesse sentido, apresentamos perspectiva jurídica inovadora para a enfermidade e para a vivência dessa condição, do ponto de vista de pacientes terminais, cuidadores e equipes de saúde, à luz do pensamento de Emmanuel Lévinas e à centralidade que ele outorga à figura do Outro, que ilumina nossa hermenêutica do instituto dos direitos da personalidade. Concluímos que se faz necessária uma mudança do paradigma atual de cuidados de saúde em fim de vida também na esfera jurídica, com a aceitação, na escolha terapêutica, da naturalidade do evento morte ao final da existência: da busca da cura, para o cuidar; da quantidade para a qualidade da vida que resta.The thesis presents a new perspective of the legal and bioethical discussions regarding individual rights of terminal ill patients and finds in our legal system, in the assertion of a general individual right, the plenitude of the protection of the legal rights of the ill, especially at the last stages of the disease, when hipermedicalization of the dying process asserts itself as the major source of the various damages caused to individual rights. On the pathway to achieve the general protection of the personhood, we highlight some special rights which emerge at the end of human existence, as, for instance, the right for a death at a natural moment. To recover the centrality of the human person as the single and only end to which Law and Medicine should serve, we present herein a path of the concept of personhood in its juridical and philosophical development to affirm that every human being is an individual (ubi homo sapiens, ibi persona), even if he/she doesnt have legal capacity and, therewith, demonstrate the impossibility of belonging to a class of non-persons independently of circumstances or the bio-psychic development. We also argue that treating and caring of seriously ill and terminal patients should be related with person in its dignity and fullness, in a biomedical, philosophical and metaphysical conception of existence, irreducible to mere obstinacy in prognosis and treatment, as a result of a reductionist perspective which relates treating a disease to a futile investment of a sterile extension of human life. In this sense, we present a innovative juridical perspective to illness and the experience of this condition, from the point of view of terminal ill patients, caregivers and health care teams in light of the thought of Emmanuel Lévinas and the centrality that he grants to the figure of the Other, which illuminates our interpretation of individual rights. We conclude that a change in the extant paradigm of the end-of-life care in Brazil is imperative also in the legal realm, with the acceptance, in the therapeutic choice, of the natural path of death at the end of our existence: from the search for cure, to care; from quantity to quality of the remaining life.
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Chawla, Ayesha. ""C-Terminal Binding Protein 2" an emerging oncogene in colon and pancreatic cancers". VCU Scholars Compass, 2017. https://scholarscompass.vcu.edu/etd/5163.
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The C terminal binding proteins (CtBP) 1 and 2 are a family of transcriptional co-repressors overexpressed in a variety of cancers, and are frequently associated with poor prognosis and chemoresistance. CtBP has also been characterized in cell culture models as drivers of migration/invasion and epithelial-mesenchymal transition. CtBP mediates its transcriptional corepressor activity via its dehydrogenase domain, and inhibition of this domain interferes with CtBP oncogenic functions. The role of CtBP in APC mutant neoplasia remains obscure even though APC is responsible for degradation of both β-catenin and CtBP in suppressing colorectal tumorigenesis. Our prior work demonstrated that CtBP proteins can be effectively therapeutically targeted with substrate analogues of their intrinsic dehydrogenase domains. In addition, CtBP2 has been reported to play an important role in human colon cancer stem cells via its interaction with the transcription factor TCF4 on chromatin and promotes self-renewal of human colon tumor initiating cells (TICs) in vitro. To study CtBP2’s role in TIC activity in vivo, we studied TIC’s from Apc min/+ mice, which exhibit massive intestinal polyposis, in Ctbp2 wildtype or haploinsufficient backgrounds. Indeed, LGR5+, CD44+/CD24+, and CD133+ TIC populations were substantially decreased in Apc min/+ Ctbp2 +/- vs. Apc min/+ intestinal epithelia. Validating CtBP as a therapeutic target for TIC activity, we investigated intestinal TIC populations and polyposis in Apc Min/+ mice treated with the CtBP inhibitor 4-chloro-hydroxyimino phenylpyruvate (4-Cl-HIPP). Like Ctbp2 haploinsufficiency, 4-Cl-HIPP significantly decreased intestinal polyposis and downregulated LGR5+, CD44+/CD24+, and CD133+ TIC populations. To understand if CtBP2’s role in TIC activity and tumor progression extended to a cancer model, we studied the impact of Ctbp2 gene dosage in a mutant KRAS mouse pancreatic ductal adenocarcinoma (PDAC) model (CKP). Ctbp2 haploinsufficiency remarkably prolonged survival, abrogated peritoneal metastasis and ascites, and caused dramatic downregulation of c-Myc, a known critical dependency for TIC activity and tumor progression in PDAC. Overall, our data suggest a key role of CtBP2 in driving the TIC compartment and progression in both pre-malignant intestinal polyposis and aggressive murine PDAC models.
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Baker, Emma Louise. "The role of the long terminal repeat (LTR) in the pathogenesis of human immunodeficiency virus type 2 (HIV-2)". Thesis, University College London (University of London), 2004. http://discovery.ucl.ac.uk/1446725/.
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Recent data has indicated that the prolonged asymptomatic phase and freedom from clinical illness experienced by the majority of HIV-2 infected individuals results from a lower level of virus production during infection than that observed in either HIV-1 infection or in the small number of HIV-2 infected individuals displaying relatively rapid progression to disease. The rate at which viral gene products are transcribed is one mechanism by which the rate of virus production can be controlled and is mediated by the Long Terminal Repeat (LTR) regions of the HIV-2 genome. A limiting dilution sensitive nested PCR has been developed to amplify the HIV-2 LTR from clinically and phenotypically characterised infected sources, including a number of HIV-2 isolates and uncultured PBMC samples derived from Gambian HIV-2 infected long-term non-progressor (LTNP) and rapid progressor (RP) patients. Using a highly efficient cloning system LTR amplicons have been cloned into a firefly luciferase reporter vector. A dual luciferase reporter assay has been used to determine LTR-directed basal and Tat transactivated levels of transcription in physiologically relevant cell lines. LTRs derived from LTNP patients tended to direct lower levels of basal and Tat transactivated transcription when compared to LTRs derived from RP patients. The difference between the two groups was more pronounced in the T cell-like Jurkat cell-line. Nucleotide sequence analyses of the LTR clones has revealed that the rate of general and G-to-A mutations at single functional sites within the LTR is higher in sequences derived from LTNP patients compared to RP patients. Taken together our data implies a relationship between LTR activity, sequence variation, and overall levels of virus expression in HIV-2 as evidenced by higher levels of circulating peripheral HIV-2 RNA in the patients with progressive disease profiles. Therefore, different LTR responsiveness may relate to different rates of virus production and disease progression rates and hence be a determinant in viral pathogenesis.
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Leinenweber, Ariane [Verfasser]. "Regulation of Excitatory Amino Acid Transporter 2 (EAAT2) by Carboxy-terminal Domains / Ariane Leinenweber". Hannover : Bibliothek der Tierärztlichen Hochschule Hannover, 2010. http://d-nb.info/100962427X/34.
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Tang, Hui-yuan. "Role of C-terminal 18 amino acids for the biological activity of prostaglandin endoperoxide H synthase-2". Diss., Connect to online resource - MSU authorized users, 2007.
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Thesis (Ph. D.)--Michigan State University. Dept. of Biochemistry and Molecular Biology, 2007.Title from PDF t.p. (viewed Aug. 17, 2009). Includes bibliographical references (p. 114-125). Also issued in print.
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KOJIMA, KIYOHIDE, HIROMU NAKAMURA i SHONEN YOSHIDA. "Occurrence of a Terminal Deoxynucleotidyl Transferase-Like Activity in N-2-Fluorenylacetamide-treated Rat Liver". Nagoya University School of Medicine, 1985. http://hdl.handle.net/2237/17476.
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Abbenseth, Josh. "Synthesis of Terminal Transition Metal Pnictide Complexes by Activation of Small Molecules". Doctoral thesis, Niedersächsische Staats- und Universitätsbibliothek Göttingen, 2019. http://hdl.handle.net/21.11130/00-1735-0000-0003-C18F-2.
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Ly, Thu, Natalia Moroz, Christopher T. Pappas, Stefanie M. Novak, Dmitri Tolkatchev, Dayton Wooldridge, Rachel M. Mayfield, Gregory Helms, Carol C. Gregorio i Alla S. Kostyukova. "The N-terminal tropomyosin- and actin-binding sites are important for leiomodin 2's function". AMER SOC CELL BIOLOGY, 2016. http://hdl.handle.net/10150/621526.
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Leiomodin is a potent actin nucleator related to tropomodulin, a capping protein localized at the pointed end of the thin filaments. Mutations in leiomodin-3 are associated with lethal nemaline myopathy in humans, and leiomodin-2-knockout mice present with dilated cardiomyopathy. The arrangement of the N-terminal actin- and tropomyosin-binding sites in leiomodin is contradictory and functionally not well understood. Using one-dimensional nuclear magnetic resonance and the pointed-end actin polymerization assay, we find that leiomodin-2, a major cardiac isoform, has an N-terminal actin-binding site located within residues 43-90. Moreover, for the first time, we obtain evidence that there are additional interactions with actin within residues 124-201. Here we establish that leiomodin interacts with only one tropomyosin molecule, and this is the only site of interaction between leiomodin and tropomyosin. Introduction of mutations in both actin- and tropomyosin-binding sites of leiomodin affected its localization at the pointed ends of the thin filaments in cardiomyocytes. On the basis of our new findings, we propose a model in which leiomodin regulates actin poly-merization dynamics in myocytes by acting as a leaky cap at thin filament pointed ends.
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Garchar, Kimberly Kay. "A dying community : a Roycean critique of the medical community at the end of life /". view abstract or download file of text, 2006. http://proquest.umi.com/pqdweb?did=1232405801&sid=3&Fmt=2&clientId=11238&RQT=309&VName=PQD.
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Thesis (Ph. D.)--University of Oregon, 2006.Typescript. Includes vita and abstract. Includes bibliographical references (leaves 175-179). Also available for download via the World Wide Web; free to University of Oregon users.
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Kunert, Ilka. "Untersuchungen zur N-terminalen Glykierung und Bildung N-terminaler 2(1H)-Pyrazinonstrukturen in Lebensmitteln und in vivo". Doctoral thesis, Saechsische Landesbibliothek- Staats- und Universitaetsbibliothek Dresden, 2009. http://nbn-resolving.de/urn:nbn:de:bsz:14-qucosa-23410.
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Sowohl bei der Forschung der Maillard-Reaktion in Lebensmitteln als auch im menschlichen Körper lag das Hauptaugenmerk bislang auf der Reaktion der Carbonylfunktion mit den Aminofunktionen der Seitenketten wie Lysin oder Arginin, da sie in vielen Lebensmitteln oder physiologischen Proteinen die größte Quelle an Aminofunktionen darstellen. Dagegen wurde eine vergleichbare Reaktion mit dem N-Terminus von Aminosäuren, Peptiden oder Proteinen weniger beachtet, obgleich in lysinarmen oder peptidhaltigen Lebensmitteln die N-terminalen Aminofunktionen dominieren und die Seitenketten körpereigener Proteine räumlich für einen Angriff der Carbonylfunktion unzugänglich sein können.
Da in den HA-Nahrungen die allergieauslösenden Proteine hydrolytisch gespalten vorliegen, stehen für eine mögliche Amadori-Produktbildung gegenüber den konventionellen Säuglingsnahrungen quantitativ mehr alpha-Aminogruppen als epsilon-Aminogruppen zur Verfügung. Demzufolge sollte für die Beurteilung von HA-Nahrungen eine Methode entwickelt werden, mit deren Hilfe eine Aussage über die Amadori-Produktbildung auch am N-Terminus getroffen werden kann. Aufbauend auf den Ergebnissen der Furoylmethylderivate-Bestimmung (FMAA-Bestimmung) in peptidhaltigen Lebensmitteln, war es ein weiteres Ziel der vorliegenden Dissertation die entwickelte Methode auch auf ihre Anwendbarkeit auf die Beurteilung des Glykierungsstatus des Hämoglobin in vivo zu testen. Nach der N-terminalen Amadori-Produktbildung im Zuge der frühen Phase der Maillard-Reaktion lag im zweiten Teil der Dissertation das Hauptaugenmerk auf die fortgeschrittene Phase der Maillard-Reaktion am N-Terminus von Peptiden oder Proteinen. Der Schwerpunkt lag dabei auf der Bildung von 2-(1H)-Pyrazinonen im komplexen trockenen Lebensmittel und in vivo.
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Lei, Kui. "The Apoptotic Activity of c-Jun NH2-Terminal Kinase Signal Transduction: A Dissertation". eScholarship@UMMS, 2002. http://escholarship.umassmed.edu/gsbs_diss/246.
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Stress-induced JNK activity has been implicated in apoptosis. Gene disruption studies have established that JNK signaling is required for some forms of apoptosis. However, it was not clear whether and how JNK was able to deliver an apoptotic signal, because JNK and its regulated-downstream transcriptional factors control a variety of gene activities and multiple biological functions. I have studied this question by using constitutively activated JNK that is independent of upstream signaling. The results indicate that activated JNK is sufficient to deliver an apoptotic signal that causes cytochrome c release from mitochondria. Significantly, this apoptotic signal requires pro-apoptotic Bc12 proteins of Bax and Bak to mediate the downstream apoptotic program. This part of work established the apoptotic activity of JNK signal transduction and the key downstream components of JNK-stimulated apoptotic signal.
Two pathways are known to mediate apoptosis in response to apoptotic stimulations: death receptor pathway and mitochondrial pathway. It has been established that JNK is required for the apoptosis mediated by mitochondria in response to ultraviolet irradiation and some genetic stress. However, the mechanisms are not fully understood. It is well known that Bax and Bak are indispensable downstream components leading to apoptotic mitochondrial changes and that other Bc12 family members can regulate the relative apoptotic activity of Bax and Bak. In conjunction with the first part of the research, I have investigated the hypothesis that JNK-mediated regulation of BH3-only Bc12 members contributes to its apoptotic activity. These results indicate that JNK-mediated phosphorylation of Bim and Bmf promotes the release of these proapoptotic BH3-only proteins from their sequestration and these factors become free to initiate apoptosis. This part of work established one mechanism of activated JNK-stimulated apoptosis. This mechanism may contribute to the phenomenon that Jnk1-/-Jnk2-/- fibroblasts are resistant to ultraviolet irradiation-induced apoptosis.
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Funakoshi, Yuuta. "Synthesis of Nitrogen-Containing Compounds from Terminal Alkynes and Sulfonyl Azides via N-Sulfonyl-1,2,3-triazoles". Kyoto University, 2017. http://hdl.handle.net/2433/227636.
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Weigelt, Johan. "Development of new NMR techniques and the structure of the N-terminal domain of Escherichia coli DnaB helicase /". Stockholm, 1999. http://diss.kib.ki.se/1999/91-628-3414-2.
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Opie, Shaun Rueben. "Characterization of mutations in the terminal repeats and capsid proteins of the adeno-associated virus type-2". [Gainesville, Fla.]: University of Florida, 2003. http://purl.fcla.edu/fcla/etd/UFE0000761.
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Shay, Daniel Travis. "Synthesis, structure, and reactivity of terminal cobalt imido complexes". Access to citation, abstract and download form provided by ProQuest Information and Learning Company; downloadable PDF file, 134 p, 2007. http://proquest.umi.com/pqdweb?did=1257806121&sid=6&Fmt=2&clientId=8331&RQT=309&VName=PQD.
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Caldwell, Rohm Mackenzie Smyth. "A terminal Middle Woodland ceramic complex from southern Illinois /". Available to subscribers only, 2008. http://proquest.umi.com/pqdweb?did=1594497441&sid=5&Fmt=2&clientId=1509&RQT=309&VName=PQD.
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Dowdy, Christopher R. "Runx1 C-terminal Domains During Hematopoietic Development and Leukemogenesis: A Dissertation". eScholarship@UMMS, 2012. https://escholarship.umassmed.edu/gsbs_diss/604.
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Runx1 is a master regulator of hematopoiesis, required for the initiation of definitive hematopoiesis in the embryo and essential for appropriate differentiation of many hematopoietic lineages in the adult. The roles of Runx1 in normal hematopoiesis are juxtaposed with the high frequency of Runx1 mutations and translocations in leukemia. Leukemia associated Runx1 mutations that retain DNA-binding ability have truncations or frame shifts that lose C-terminal domains. These domains are important for subnuclear localization of Runx1 and protein interactions with co-factors. The majority of leukemia associated Runx1 translocations also replace the C-terminus of Runx1 with chimeric fusion proteins. The common loss of Runx1 C-terminal domains in hematopoietic diseases suggests a possible common mechanism. We developed a panel of mutations to test the functions of these domains in vitro, and then developed mouse models to examine the consequences of losing Runx1 C-terminal domains on hematopoietic development and leukemogenesis in vivo.
We previously observed that overexpression of a subnuclear targeting defective mutant of Runx1 in a myeloid progenitor cell line blocks differentiation. Gene expression analysis before differentiation was initiated revealed that the mutant Runx1 was already deregulating genes important for maturation. Furthermore, promoters of the suppressed genes were enriched for binding sites of known Runx1 co-factors, indicating a non-DNA-binding role for the mutant Runx1.
To investigate the in vivo function of Runx1 C-terminal domains, we generated two knock-in mouse models; a C-terminal truncation, Runx1Q307X, and a point mutant in the subnuclear targeting domain, Runx1 HTY350-352AAA . Embryos homozygous for Runx1 Q307X phenocopy a complete Runx1 null and die in utero from central nervous system hemorrhage and lack of definitive hematopoiesis. Embryos homozygous for the point mutation Runx1HTY350-352AAA bypass embryonic lethality, but have hypomorphic Runx1 function. Runx1HTY350-352AAA results in defective growth control of hematopoietic progenitors, deregulation of B-lymphoid and myeloid lineages, as well as maturation delays in megakaryocytic and erythroid development.
Runx1 localizes to subnuclear domains to scaffold regulatory machinery for control of gene expression. This work supports the role of transcription factors interacting with nuclear architecture for greater biological control, and shows how even subtle alterations in that ability could have profound effects on normal biological function and gene regulation.
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Rodella, Umberto. "A novel model of Miller Fisher syndrome to study motor axon terminal regeneration". Doctoral thesis, Università degli studi di Padova, 2017. http://hdl.handle.net/11577/3422774.
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The neuromuscular junction (NMJ) is a ‘tripartite’ synapse, composed of the presynaptic motor axon terminal (MAT), the muscle fiber and perisynaptic Schwann cells (PSCs). NMJ functionality is essential for the execution of body movements and it is anatomically exposed, becoming an easy target of bacterial and animal neurotoxins, toxic chemicals, mechanical trauma, and autoimmune diseases.
In the Miller Fisher Syndrome (MFS) autoantibodies against specific gangliosides (>90% GQ1b) bind to MAT and in turn activate the complement system cascade at its surface, leading to nerve degeneration. Such damage is reversible, as the motor neuron is able to fully regenerate and restore neurotransmission.
PSCs are main supporters of NMJ regeneration: to date, however, the current understanding of PSCs role in this autoimmune neuropathy is mostly phenomenological, and molecular studies are needed. It was recently reported that the degenerating MAT release alarm signals (alarmins) able to activate the pro-regenerating phenotype of PSCs. Therefore, MAT can be considered an active player of its own regeneration. In addition, many other signals are thought to be generated by all the three main components of the NMJ, thus generating a complex inter-cellular communication network, which has been only partially identified.
In order to better elucidate the molecular and cellular events driving PSCs response to MAT damage in MFS, we recently developed a novel in vivo MFS model. The combination of FS3, a monoclonal antibody against gangliosides related to MFS, and normal human serum (NHS) as a source of complement, administered subcutaneously in LAL muscles and intramuscularly in soleus muscle in mice, causes the degeneration of MAT. Soon after MAT destruction, neuronal debris are engulfed and digested by PSCs. Within few days after injection MAT regrowth is morphologically and functionally complete, as assessed by immunofluorescence analysis and electrophysiological recordings. The effect is antibody- and complement-dependent, as no MAT degeneration takes place in the absence of FS3, nor when NHS is heat-inactivated.
To identify the neuronal alarmins responsible for PSCs activation and the signaling pathways engaged, we have parallely set up an in vitro MFS model consisting of administration of FS3 plus NHS to primary cerebellar neurons and spinal cord motor neurons, which causes a complement-dependent massive Ca2+ overload in neurite, together with the formation of neurite enlargements, named bulges. Bulges are sites of accumulation of swollen and dysfunctional mitochondria, and of localized hydrogen peroxide (H2O2) production. Hydrogen peroxide is an alarm signal for SCs. Indeed, in FS3 plus NHS attacked neurons-SCs co-cultures, neuron-derived H2O2 induces activation of the ERK1/2 pathway in SCs, a known crucial player of the switch toward a pro-regenerative phenotype of SCs.
In addition, we identified adenosine triphosphate (ATP) as an additional alarmin involved in SCs activation. Indeed, primary neurons exposed to FS3 plus NHS release ATP in the extracellular medium, which in turn evokes intracellular calcium spikes within SCs in co-cultures with neurons. These spikes were significantly abolished in the presence of the ATP-inactivating enzyme apyrase in the incubation medium.
Furthermore, experiments with a FRET-based cyclic AMP (cAMP) sensor show that, upon FS3 plus NHS addition in neurons-SCs co-cultures, cAMP levels rise in SCs, and this event eventually results in an ATP-dependent increased phosphorylation the transcription factor CREB (cAMP response element-binding protein).
In conclusion, the work performed during this PhD project has led to the development of novel in vitro and in vivo models of MFS, in order to study the molecular communication between MAT and PSCs. Hydrogen peroxide and ATP were found to be important neuronal alarmins, able to activate pro-regenerative pathways within SCs.
We believe these results throw light on the molecular and cellular events taking place in MFS, and may well be extended to other MAT affecting pathologies.La giunzione neuromuscolare (neuromuscular junction, NMJ) è una sinapsi ‘tripartita’, composta da un terminale assonico di un motoneurone (motor axon terminal, MAT), una fibra muscolare postsinaptica, e da cellule di Schwann perisinaptiche (perisynaptic Schwann cells, PSC). La funzionalità della NMJ è essenziale per l’esecuzione dei movimenti corporei. Tuttavia la sua anatomia la rende particolarmente esposta ad una vasta gamma di stimoli patologici, quali neurotossine animali e batteriche, sostanze tossiche, traumi meccanici e malattie autoimmuni. Nella sindrome di Miller Fisher (Miller Fisher Syndrome, MFS), auto-anticorpi riconoscono specifici gangliosidi (>90% GQ1b) presenti nel MAT e attivano la cascata del complemento alla sua superficie, causandone la degenerazione. Questo danno è reversibile, in quanto il MAT è in grado di rigenerare completamente e di ristabilire la trasmissione sinaptica. Le PSC sono tra i principali effettori della rigenerazione della NMJ. Ad oggi, tuttavia, l’attuale comprensione dei ruoli di queste cellule in questa neuropatia autoimmune è principalmente fenomenologica, e ulteriori studi molecolari. È stato riportato che il MAT in degenerazione rilascia segnali di allarme (alarmine) capaci di attivare il fenotipo di pro-rigenerazione delle PSC. Dunque si può dedurre che il MAT gioca un ruolo attivo nel processo della propria degenerazione. Inoltre è probabile che molti altri segnali siano generati da parte di tutti e tre i componenti della NMJ, che generano così un network complesso di comunicazione intercellulare, il quale è stato solo parzialmente compreso. Nel progetto di dottorato qui presentato è stato sviluppato un nuovo modello in vivo di MFS, allo scopo di chiarire gli eventi molecolari e cellulari che avvengono nelle PSC in seguito a danno del MAT osservato nella MFS. Ciò è stato permesso tramite l’utilizzo di FS3, un anticorpo monoclonale che riconosce gangliosidi associati alla MFS, e siero umano (normal human serum, NHS), utilizzato come fonte di proteine del complemento. La amministrazione subcutanea nel muscolo LAL, o intramuscolare nel muscolo soleo, della combinazione di questi due elementi induce la degenerazione del MAT, e i suoi frammenti vengono fagocitati e degradati dalle PSC. Entro pochi giorni dall’iniezione la rigenerazione del MAT è completa sia a livello morfologico che funzionale, come evidenziato da analisi di immunofluorescenza ed elettrofisiologiche. Gli effetti osservati sono strettamente dipendenti dall’anticorpo e dal sistema del complemento, in quanto non viene osservata neurodegenerazione in assenza di FS3 o quando il NHS viene inattivato al calore. Allo scopo di identificare le alarmine neuronali responsabili dell’attivazione delle PSC e le conseguenti risposte molecolari di quest’ultime, è stato parallelamente sviluppato un modello in vitro di MFS, che consiste nell’esposizioneì della combinazione di FS3 e NHS (FS3+NHS) a colture primarie di neuroni cerebellari o di motoneuroni da midollo spinale. Ciò causa un’entrata massiccia e incontrollata di calcio (Ca2+) a livello dei neuriti, associata alla formazione di protuberanze, o bulges, a livello dei neuriti stessi. Questi bulges sono siti di accumulo di mitocondri gonfi e disfunzionali, e di produzione di perossido di idrogeno (H2O2). Il perossido di idrogeno è un segnale di allarme per le cellule di Schwann (Schwann cells, SC). Infatti in co-colture di neuroni e SC, il H2O2 derivante dai neuroni attaccati da FS3+NHS induce l’attivazione nelle SC del pathway di ERK1/2, conosciuto per il suo importante ruolo di induzione del fenotipo pro-rigenerazione delle SC. Inoltre, tramite il modello in vitro di MFS, è stata identificata una seconda alarmina coinvolta nell’attivazione delle SC, l’adenosina trifosfato (ATP). Infatti, neuroni primari esposti al complesso FS3+NHS rilasciano nel mezzo extracellulare ATP, che a sua volta induce oscillazioni intracellulari di Ca2+ nelle SC. Queste oscillazioni sono abolite in presenza di apirasi, un enzima che degrada l’ATP, nel mezzo di incubazione. In aggiunta, esperimenti con un sensore FRET per l’AMP ciclico (cAMP) hanno mostrato che i livelli di SC aumentano in co-colture di neuroni e SC in seguito al danno neuronale esercitato da FS3+NHS. All’aumento di cAMP intracellulare osservata ne consegue un’aumentata fosforilazione (ovvero attivazione) del fattore di trascrizione CREB (cAMP response element-binding protein), anch’essa ATP-dipendente. In conclusione, il lavoro svolto in questo progetto di dottorato ha portato allo sviluppo di nuovo modelli in vivo e in vitro di MFS. Questi sono stati utilizzati per lo studio della comunicazione molecolare tra il MAT e le PSC. Il perossido di idrogeno e l’ATP sono stati identificati come importanti alarmine neuronali, capaci di attivare il fenotipo pro-rigenerazione delle SC. Crediamo che questi risultati contribuiscano a gettare luce sugli eventi molecolari e cellulari che avvengono alla NMJ nella MFS, e che queste conoscenze possano venire estese anche ad altre patologie che affliggono il MAT.
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White, Mary Kathryn. "Certified nursing assistants' feelings of preparedness in caring for nursing home residents at the end of life". Laramie, Wyo. : University of Wyoming, 2007. http://proquest.umi.com/pqdweb?did=1445048331&sid=8&Fmt=2&clientId=18949&RQT=309&VName=PQD.
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Gourmaud, Sarah. "Expression de c-Jun N-terminal kinase (JNK) dans la maladie d'Alzheimer : intérêts diagnostiques et thérapeutiques". Paris 7, 2014. http://www.theses.fr/2014PA077106.
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La maladie d'Alzheimer (MA) se caractérise par l'accumulation de peptides d'amyloïde-β42 (Aß₄₂), de protéine tau hyperphosphorylée (ptau) et une perte neuronale. Les niveaux d'Aß₄₂ et de tau au niveau du liquide céphalo-rachidien (LCR) des patients sont utilisés comme biomarqueurs diagnostique. Les protéines PKR et JNK sont des kinases impliquées dans la production d'AE342, la phosphorylation de tau et la mort neuronale. L'accumulation de leur forme active a été mise en évidence dans le cerveau de patients MA. Il existe trois isoformes de JNK. JNK1 et JNK2 sont ubiquitaires et JNK3 est presque exclusivement exprimée au niveau du cerveau. Aucune étude n'a étudié à ce jour les variations de JNK3 dans la MA. L'objectif de notre étude était d'analyser in vitro le lien entre PKR et JNK puis de mesurer l'expression des différents isoformes de JNK dans la MA chez l'homme. Nos résultats montrent que la protéine PKR intervient à la fois dans la voie d'activation et celle de désactivation de JNK en fonction des conditions de stress. Nous mettons également en évidence la diminution de l'apoptose neuronale due à l'Aß₄₂ grâce à un peptide inhibiteur de JNK. Nous avons mesuré une augmentation de la forme totale de JNK3 dans le cortex frontal et le LCR de patients Alzheimer. Le signal de JNK3 colocalise avec celui d'Ar342 au niveau des plaques séniles. Grâce au suivi clinique des patients nous avons montré que le niveau de JNK3 mesuré dans le LCR est corrélé au déclin cognitif chez les patients. JNK3 pourrait devenir un nouveau biomarqueur diagnostique et pronostique de la MA. Ces résultats, associés à ceux de la littérature, font de JNK3 et PKR d'intéressantes cibles thérapeutiquesAlzheimer's disease (AD) is characterized by the accumulation of amyloid-β42 peptide (Aß₄₂), hyperphosphorylated tau (ptau) proteins and neuronal loss. Cerebrospinal fluid (CSF) Aß₄₂and tau levels in patients are used as diagnostic biomarkers. PKR and JNK are kinases involved in the production of Ar342, tau phosphorylation and neuronal death. The accumulation of their active form was demonstrated in AD brains. There are three isoforms of JNK. JNK1 and JNK2 are ubiquitous and JNK3 is almost exclusively expressed in brain. No studies have examined changes in JNK3 in AD. The aim of our study was to analyze in vitro the relationship between PKR and JNK and then to measure the expression of JNK isoforms in AD patients. Our results showed that PKR is involved in both JNK activation and deactivation, according to stress conditions. We also showed a decrease of neuronal apoptosis due to Aß₄₂ with a JNK inhibitor peptide. We measured an increase of the total form of JNK3 in AD frontal cortex and CSF. JNK3 signal colocalizes with Aß₄₂ in senile plaques. Thanks to the clinical monitoring of patients we have shown that the CSF level of JNK3 correlates with the cognitive decline. JNK3 could become a new diagnostic and prognostic biomarker for AD. These results, together with those of the literature, make JNK3 and PKR interesting therapeutic targets
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Gleisner, Martin. "Interaction of he Epsin N-Terminal Homology domain (ENTH) with artificial membranes as a function of lateral tension". Doctoral thesis, Niedersächsische Staats- und Universitätsbibliothek Göttingen, 2016. http://hdl.handle.net/11858/00-1735-0000-0028-8821-2.
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Proteine formen während der Endozytose planare Membranen
zu gekrümmten Vesikeln um. Im ersten Schritt dieses Prozesses bindet das Protein
Epsin an das Rezeptorlipid Phosphatidylinositol-4,5-bisphosphat (PIP2) und ein
vorher ungeordneter Bereich am N-Terminus von Epsin, die epsin N-terminal
homology domain (ENTH), bildet eine α-Helix, welche in die Membran insertiert.
Im Rahmen dieser Arbeit wurde die Wechselwirkung von ENTH mit PIP2-haltigen
Lipiddoppelschichten unter Verwendung von bottom up Modellsystemen charakterisiert.
Die Affinität von ENTH zu PIP2 wurde für verschiedene Lipidzusammensetzungen
und Membrangeometrien untersucht, wobei unabhängig von
Lipidzusammensetzung und Membrantopologie ähnliche Bindungskonstanten
im hohen nanomolaren Bereich bestimmt wurden.
Ausgestülpte porenüberspannende Membranen wurden als Modellsystem etabliert,
um die Fähigkeit von ENTH zur Membrankrümmung als Funktion der Lipidzusammensetzung
zu charakterisieren. Die Höhe der ausgestülpten Membranen ist
durch die laterale Spannung begrenzt. Verursacht durch Insertion der ENTH Helix
wuchsen Membranen mit einem hohen Flächenkompressionsmodul. Im Gegensatz
dazu rissen Membranen mit einem niedrigen Flächenkompressionsmodul durch
die ENTH induzierte Bildung von Membrandefekten.
Entgegen der Eigenschaft von ENTH Membranen zu krümmen, wurde an hochgespannten
porenüberspannenden Membranen keine Membrantubulierung und
-vesikulierung beobachtet. Daher wurde untersucht, ob diese Fähigkeit durch eine
hohe laterale Spannung unterdrückt wird. Zu diesem Zweck wurden Riesenvesikel
auf einem Glassubstrat adhäriert, wobei die Adhäsionsstärke und in Folge die
laterale Spannung als Funktion der Mg2+ Konzentration eingestellt werden konnte.
ENTH-induzierte Membrantubulierung konnte für Vesikel mit niedriger Spannung
nachgewiesen werden und war bei höherer Spannung unterdrückt.
Unabhängig von der Membranspannung wurde ein Abflachen der Vesikel nach
ENTH-Zugabe beobachtet. Die Ursache hierfür wurde in der durch die insertierte
Helix hervorgerufene Reduktion des Flächenkompressionsmoduls gefunden. Die
insertierte Helix stört die hydrophoben Wechselwirkungen der Lipidfettsäureketten
und das reduzierte Flächenkompressionsmodul verringert die zur Membrankrümmung
benötigte Energie. In Kombination mit der durch die insertierte
Helix erzeugten lokalen Krümmung ist dies eine molekulare Erklärung für die
ENTH-initiierte Bildung eines Vesikels während der Endozytose.
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Reid, Jocelyn. "Fun[c]tions of the N-terminal extensions of the ubiquitin-specific processing protease-testis 1 and 2 isoforms". Thesis, McGill University, 2003. http://digitool.Library.McGill.CA:80/R/?func=dbin-jump-full&object_id=19440.
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Ubiquitin is a small, globular 8 kDa protein whose function is accomplished by its conjugation to targeted substrates. This conjugation is a multi-step process involving three different enzymes. Upon polyubiquitination of a target protein, the 26S proteasome is recruited, leading to the degradation of the substrate. The ubiquitination of proteins, and hence their degradation, can be prevented through the action of deubiquitinating enzymes (DUBs), cysteine proteases that cleave the isopeptide bond through which ubiquitin moieties are attached to their substrates. How DUBs recognize their substrates has been unclear. Two isoforms of a novel testis-specific deubiquitinating enzyme, UBP-tl and UBP-t2, which contain identical core regions but different N-termini, were identified 1. This thesis describes the further characterization of the function of the N-termini. Assessment of the kinetic parameters of UBP-tl, UBP-t2 and the core domain of the two enzymes alone (UBP-core) for the substrate ubiquitin-PEST revealed that the different N-termini increased the Km's of the enzymes, thereby diminishing their affinity towards the substrate. The Vmax of UBP-t2 and the core domain were similar, suggesting that the N-termini do not affect catalytic efficiency. As well, UBP-tl and UBP-t2 had lower activity than UBP-core against endogenously ubiquitinated testis proteins. Thus, the N-termini probably restrict the deubiquitinating activity of the core domain to specific substrates. The UBP-core deubiquitinating activity was not exclusive to testis proteins, as endogenously ubiquitinated proteins in liver, brain, and muscle extracts were also deubiquitinated, however at a slower rate than those in testis. UBP-testis appears to be specific for ubiquitinated proteins, as the enzymes could not remove Nedd8 (the ubiquitin-like protein most similar to ubiquitin) from endogenously neddylated proteins. Since the N-termini appeared to be involved in regulating substrate specificity, they were used as ligands in affinity columns to try to bind substrates and/or interacting proteins from testis extracts. AUFl, a protein regulating mRNA stability was found to be a possible interacting protein with the UBP-tl N-terminus.
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Holton, Janice Lesley. "Monoclonal antibodies in n-terminal peptide antisera in a study of the structure of desmosmal glycoproteins 2 and 3". Thesis, University of Southampton, 1991. http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.316030.
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Melo, Marcelo Maia Caixeta de. "?leo terminal de pacientes submetidos ? colonoscopia: aspectos endosc?picos, histol?gicos e cl?nicos". Faculdade de Medicina de São José do Rio Preto, 2007. http://bdtd.famerp.br/handle/tede/40.
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Made available in DSpace on 2016-01-26T12:51:18Z (GMT). No. of bitstreams: 1
marcelomaiacaixetamelo_dissert.pdf: 1810009 bytes, checksum: 1014c04abf9e0627459b0eaa88a963d8 (MD5)
Previous issue date: 2007-10-26The ileum is approximately the most distal three-fifths of the small intestine and is responsible for digestion and the absorption of foods. The diagnosis of diseases that affect this segment can be achieved by clinical evaluation and complementary examinations. Colonoscopy, not only allows macroscopical analysis, but also enables biopsies to be carried out for histological evaluation. Objective: The objective of this research was to study the terminal ileum of patients submitted to colonoscopy in respect to: 1) correlation of endoscopic and histological parameters; 2) compatibility between the initial histological results evaluation and a review of slides; 3) the chance of individuals with normal ileoscopy and abdominal pain and/or chronic diarrhea presenting with histological alterations. Casuistic and Method: Patients submitted to colonoscopy for varying reasons were prospectively studied. During this examination 47 (42.3%) male and 64 (57.7%) female patients, with ages ranging between 14 and 82 years old (mean 51.6 ? 15 years), were selected with the terminal ileum mucous smooth and without enanthema at endoscopic examinations. Biopsies of the ileal mucosa were obtained for these individuals with the slides being routinely examined during data collection and later reviewed. Results: The correlation between patients with normal xiii ileoscopy and histologically normal ileum was 34.2%. When patients with histologically normal ileum and mild ileitis were analyzed, the correlation was 99.1%. The agreement between the initial histological evaluation and review of slides in respect to normal ileum and mild or moderate ileitis according to the Kappa test was 0.10 (poor agreement). Considering the normal ileum together with mild ileitis and moderate ileitis Groups, the agreement was 0.21 (fair agreement). In patients with normal ileoscopy and abdominal pain and/or chronic diarrhea, the chance of presenting histological alterations by Odds Ratio calculation, was 2.5 times higher than for asymptomatic individuals or those with other symptoms. Conclusions: In patients with the terminal ileum mucosa smooth without enanthema, the correlation between endoscopic and histological findings was high. The concordance between the initial histological results evaluation and the review of slides was not good. The chance of individuals with normal ileoscopy and abdominal pain and/or chronic diarrhea, presenting histological alterations was greater than for asymptomatic individuals or those with other symptoms.
?leo compreende cerca de 3/5 distais do intestino delgado, sendo respons?vel pela digest?o e absor??o de alimentos. O diagn?stico de doen?as que afetam esse segmento pode ser feito por meio de avalia??o cl?nica e exames complementares. A colonoscopia, al?m da possibilidade de an?lise macrosc?pica, permite realiza??o de bi?psias para avalia??o histol?gica. Objetivo: O objetivo desta pesquisa foi estudar o ?leo terminal de pacientes submetidos ? colonoscopia considerando: 1) correla??o endosc?pica e histol?gica; 2) concord?ncia entre resultados da avalia??o histol?gica inicial e revis?o de l?minas; 3) chance de indiv?duos com ileoscopia normal, portadores de dor abdominal e ou diarr?ia cr?nica apresentarem altera??es histol?gicas. Casu?stica e M?todo: Foram estudados prospectivamente pacientes submetidos ? colonoscopia por diversas indica??es. Durante esse exame foram selecionados 111 pacientes, sendo 47 (42,3%) do sexo masculino e 64 (57,7%) do feminino, com idade entre 14 e 82 anos (51,6 ? 15 anos), que apresentaram ao exame endosc?pico do ?leo terminal mucosa lisa, sem enantema. Foram realizadas bi?psias da mucosa ileal nesses indiv?duos, sendo as l?minas examinadas rotineiramente durante coleta de dados e revisadas posteriormente. Resultados: A correla??o entre pacientes com ileoscopia normal e ?leo histologicamente normal foi 34,2%. Quando a somat?ria dos pacientes com xi ?leo histologicamente normal e ile?te leve foi analisada, constatou-se correla??o de 99,1%. A concord?ncia entre avalia??o histol?gica inicial e revis?o de l?minas considerando-se ?leo normal, ile?te leve e ile?te moderada pelo teste de Kappa foi 0,10 (concord?ncia pobre). Considerando os grupos ?leo normal-ile?te leve e ile?te moderada, a concord?ncia foi 0,21 (concord?ncia razo?vel). Nos pacientes com ileoscopia normal, portadores de dor abdominal e ou diarr?ia cr?nica, a chance de apresentarem altera??es histol?gicas, pelo c?lculo da Odds Ratio, foi 2,5 vezes maior em rela??o ?queles assintom?ticos e ou com outros sintomas. Conclus?es: Nos pacientes com mucosa do ?leo terminal lisa, sem enantema, a correla??o entre achados endosc?picos e histol?gicos foi elevada. A concord?ncia entre resultados da avalia??o histol?gica inicial e revis?o de l?minas n?o foi satisfat?ria. A chance de indiv?duos com ileoscopia normal, portadores de dor abdominal e ou diarr?ia cr?nica, apresentarem altera??es histol?gicas foi maior em rela??o ?queles assintom?ticos e ou com outros sintomas.
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Le, Hingrat Quentin. "Impact de la variabilité génétique dans la région Long Terminal Repeat et le gène de l'intégrase sur la réplication du VIH-2". Thesis, Université de Paris (2019-....), 2019. https://theses.md.univ-paris-diderot.fr/LE_HINGRAT_Quentin_va.pdf.
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Le VIH-2 est souvent considéré comme un modèle d’infection rétrovirale atténuée, du fait de sa faible réplication virale, des faibles taux de transmission et de la progression plus lente vers le stade SIDA des patients infectés. Les mécanismes causaux de cette moindre physiopathologie sont encore mal connus. Dans ce travail, nous nous sommes intéressés à la diversité du VIH-2, notamment dans deux régions génomiques : l’intégrase et la région Long Terminal Repeat (LTR). Nous avons tout d’abord amélioré la technique classique d’isolement de souches virales afin de disposer de davantage de souches de VIH-2, en purifiant les échantillons de patients avec des billes anti-CD44. Ensuite, nous avons utilisé ces souches pour étudier la sensibilité aux inhibiteurs de transfert de brin de l’intégrase, ou INSTI. Au cours de ce travail, nous avons mis en évidence un nouveau mécanisme de résistance aux INSTI chez le VIH-2, l’insertion de 5 acides aminés après le codon 231 du gène de l’intégrase. Cette insertion est responsable d’une résistance importante au raltegravir (RAL), à l’elvitegravir (EVG), au cabotegravir (CAB), ainsi qu’une résistance modérée au dolutegravir (DTG). La sensibilité au bictegravir (BIC) était conservée pour certains isolats porteurs de cette insertion. Une insertion de deux acides aminés a aussi été observée transitoirement chez un patient. Nous avons confirmé ces observations phénotypiques en construisant des virus porteurs de ces insertions par mutagénèse dirigée. L’insertion, qu’elle soit de 2 ou de 5 acides aminés, n’était pas responsable d’une perte de capacité réplicative, à l’exception du mutant avec l’insertion GIRGK.En revanche, la structure prédite de l’intégrase est fortement modifiée, avec notamment la perte d’un des deux feuillets bêta composant le tonneau bêta du domaine C-terminal.La sensibilité phénotypique des mutants a été déterminée, pour les insertions de 5 acides aminés, les résultats étaient similaires à ceux obtenus avec les isolats cliniques. Nous avons aussi pu déterminer la sensibilité du mutant avec l’insertion GK, qui était sensible au BIC et au DTG, mais déjà pleinement résistant à RAL et au CAB. Dans la dernière partie de notre travail, nous avons étudié la variabilité dans la région LTR des provirus de 66 patients naïfs d’antirétroviraux, inclus dans la cohorte ANRS CO5 VIH-2. La variabilité génétique était plus importante dans les séquences du groupe B, du fait notamment de nombreuses insertions et délétions dans la sous-région «régulatrice» comprenant l’ensemble des sites de fixation de facteurs de transcription cellulaire. Ces virus du groupe B présentaient une délétion de quelques nucléotides dans la région contenant les sites de fixation PuB1 et pets, causant une perte de ce dernier site de fixation. De plus, 4 provirus du groupe B présentaient une délétion du premier site de fixation du facteur de transcription ubiquitaire Sp1. Cette variabilité entraînait des conséquences sur l’activité transcriptionnelle de ces LTR. Les LTR du groupe A et du groupe B présentaient la même activité transcriptionnelle basale mais, dans les cellules Jurkat, après activation cellulaire, l’activité transcriptionnelle des LTR du groupe B et d’un LTR de groupe A dans lequel la zone contenant la délétion de pets a été insérée était 10 fois plus faible que celle du LTR de groupe A. La délétion du premier site de fixation de Sp1 diminuait l’activité transcriptionnelle basale dans les cellules Jurkat et la réponse à la transactivation par la protéine virale Tat dans les cellules HEK293THIV-2 is oftenconsidered as an attenuated model of HIV-1 infection. Indeed, HIV-2 is characterized by its lower viral replication, reduced transmission rates and a slower progression towards AIDS of infected-patients. Mechanisms implied in HIV-2 reduced pathogenicity are not entirely understood. In our work, we have focused on HIV-2 diversity, especially in two genomic regions: the integrase and the Long Terminal Repeat (LTR) region.We have improved the culture method, by purifying clinical samples using anti-CD44 paramagnetic beads. This allowed us to increase the number of viral strains in our collection. Then, we used those strains to study phenotypic susceptibility to integrase strand transfer inhibitors (INSTI). During this study, we identified a new molecular mechanism of resistance to INSTI, a 5 amino-acids insertion after codon 231 of HIV-2 integrase. This insertion was responsible for a high level of resistance to raltegravir (RAL), elvitegravir (EVG), cabotegravir (CAB), and a slight increase in the resistance todolutegravir (DTG). Certain isolates harboring this insertion remained susceptible to bictegravir (BIC).A 2 amino-acids insertion was also transiently observed in one patient. We have confirmed those phenotypic data by constructing HIV-2 mutants by site-directed mutagenesis. Whether the insertion was composed of 2 or 5 amino-acids, replicative capacitywas similar to the wild-type virus, except for the mutant with a GIRGK insertion. However, the predicted structure of mutated HIV-2 integrases was modified, notably in the C-terminal domain, due to the loss of one of the two beta sheets composing the beta barrel. Phenotypic susceptibility of mutants was determined and results for HIV-2 mutants witha 5 amino-acids insertion were similar to those obtained with clinical isolates.We also determined the susceptibility of the mutant with a GK insertion. It was susceptible to BIC and DTG, but already resistant to RAL and CAB. In the last part of our work, we have characterized genetic variability within LTR region in 66 antiretroviral-naïve patients, included in the French ANRS CO5 HIV-2 cohort.Genetic variability was higher among group B sequences, due to a high number of insertions and deletions in the «regulatory» sub-region that encompasses all transcription factor binding sites. All group B viruses presented a short deletion in the region encompassing PuB1 andpets binding sites, causing the loss of the pets binding site.Furthermore, 4 group B viruses had also a deletion of the first binding site of Sp1 transcription factor. This variability impacted LTR transcriptional activity. Group A and B LTRs presented asimilar basal transcriptional activity but, in Jurkat cells, after cellular activation, transcriptional activities of group B LTR and a group A LTR in which the deletion of pets binding site has been introduced were 10-fold lower than the transcriptional activity of an intact group A LTR. The deletion of the first Sp1 binding site reduced the basal transcriptional activity in Jurkat cells and the response to transactivation by the viral protein Tat in HEK293T
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Nakao, Kayoko. "Knowledge, preferences, and arrangement of end-of-life care and decision-making among Japanese American older adults". Diss., Restricted to subscribing institutions, 2009. http://proquest.umi.com/pqdweb?did=1872935931&sid=1&Fmt=2&clientId=1564&RQT=309&VName=PQD.
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Kugler, Neil. "When curing stops and caring begins : a study of the need for end-of-life care education of future health care workers /". ProQuest subscription required:, 2003. http://proquest.umi.com/pqdweb?did=990270731&sid=1&Fmt=2&clientId=8813&RQT=309&VName=PQD.
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Litteral, Vaughn. "mdm2 Amplification in NIH3T3L1 Preadipocytes Leads to Mdm2 Elevation in Terminal Adipogenesis". Wright State University / OhioLINK, 2008. http://rave.ohiolink.edu/etdc/view?acc_num=wright1216825497.
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Nishino, Noriko. "Mechanistic studies of atmospheric chemical reactions of hydroxyl radicals with aromatic hydrocarbons, including 2-ring polycyclic aromatic hydrocarbons, and terminal alkenes". Diss., UC access only, 2009. http://proquest.umi.com/pqdweb?index=94&did=1907248571&SrchMode=1&sid=1&Fmt=7&retrieveGroup=0&VType=PQD&VInst=PROD&RQT=309&VName=PQD&TS=1270251046&clientId=48051.
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Xu, Chao. "NMR structural studies of apolipoprotein E amino-terminal domain and amyloid beta peptide /". Available to subscribers only, 2006. http://proquest.umi.com/pqdweb?did=1136079871&sid=15&Fmt=2&clientId=1509&RQT=309&VName=PQD.
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Thesis (M.S.)--Southern Illinois University Carbondale, 2006."Department of Molecular Biology, Microbiology and Biochemisty." Includes bibliographical references (leaves 105-113). Also available online.
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Maya, Vladkova Georgieva. "TrkA COOH-terminal tail: its relevance on receptor stability and signaling for cell differentiation and survival". Doctoral thesis, Universitat de Lleida, 2010. http://hdl.handle.net/10803/8106.
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El receptor del factor de creixement nerviós TrkA contribueix a la supervivència i a ladiferenciació de diferents poblacions neuronals. Tot i que les principals vies de senyalització i
molècules adaptadores activades després de la unió del lligant al receptor estan ben
estudiades, recentment un creixent nombre de proteïnes que interaccionen amb TrkA han
estat descrites com a nous mecanismes de regulació del receptor. La trans-autofosforilació
del receptor, a més d'activar les cascades de senyalització rellevants per la diferenciació i
supervivència cel·lular, com són les vies de les MAPKs i PI3K-Akt, també indueix un augment
transitori de la concentració de calci citoplasmàtic. En conseqüència la proteïna sensora de
Ca2+ calmodulina (CaM) també participa en la senyalització per TrkA. El nostre grup estava
interessat en discernir la relació entre CaM i TrkA, i vàrem descobrir que CaM interacciona
directament i de manera Ca2+-dependent amb l'extrem carboxi-terminal de TrkA. A partir
d'aquests resultats ens vàrem plantejar de buscar la posició exacta del domini d'unió a
calmodulina en la seqüencia de TrkA. Donat que els programes de predicció no van trobar una
seqüència candidata d'unió a CaM en el domini intracel·lular del TrkA, vàrem centrar-nos en el
extrem COOH-terminal del receptor, un domini ric en aminoàcids hidrofòbics en posicions
conservades. Vàrem introduir mutacions en dos aminoàcids del domini candidat, Leu784 i
Val790 substituint-los per Ala. Els assajos d'unió van mostrar que els mutants TrkA-L784A i
TrkA-L784A-V790A no perdien la unió a CaM, per tant no formaven part del domini d'unió a
CaM de TrkA. Tanmateix, vàrem demostrar que aquests aminoàcids hidrofòbics són importants
per a la unió i la regulació de la lligasa d'ubiquitina Nedd4-2. Vàrem observar una forta
interacció dels dos receptors mutants amb Nedd4-2, que es corroborava amb una augmentada
co-localització de les dues proteïnes detectada per immunofluorescència. Com a conseqüència
s'observà una intensa multimonoubiquitinització basal dels receptors mutants mitjançada per
Nedd4-2. Aquests resultats correlacionen amb un important descens en la quantitat de
receptor a causa d'un direccionament d'aquest cap als endosomes tardans/lisosomes. Tot
plegat resultava en un increment en la degradació dels receptors mutats. Malgrat la reducció
en la quantitat de receptors de membrana, els receptors TrkA mutats van ser capaços
d'activar vies de senyalització, i fins i tot eren més eficients en promoure l'extensió de
neurites que els receptors TrkA normals. Els nostres resultats demostren que la composició de
l'extrem COOH-terminal de TrkA participa en la regulació de la unió i activitat de Nedd4-2.
Així mateix, s'evidencia que la ubiquitinització de TrkA per Nedd4-2 promou el tràfic
endosomal de TrkA cap als endosomes tardans/lisosomes augmentant d'aquesta manera la
degradació del receptor. Per altra banda, s'observa que la multimonoubiquitinització de TrkA
no interfereix en l'activació de les vies de senyalització, tanmateix potencia la senyalització del
receptor conduent a la diferenciació cel·lular.
El receptor del factor de crecimiento nervioso TrkA contribuye a la supervivencia y
diferenciación de varias poblaciones neuronales. A pesar del buen conocimiento de las
principales vías de señalización y las proteínas adaptadoras activadas después de la unión del
ligando al receptor, últimamente se ha descrito un número creciente de proteínas que
interaccionan con el receptor participando en su regulación. La trans-autofosforilación del
receptor, adicionalmente a la activación de vías de señalización relevantes para la
diferenciación y la supervivencia celular, como son las vías de las MAPKs y PI3K-Akt, también
conlleva un aumento transitorio del calcio citoplasmático. En consecuencia la proteína sensora
de calcio calmodulina (CaM) también participa en la señalización por TrkA. Nuestro grupo tenía
interés en estudiar la relación entre CaM y TrkA y descubrió que la CaM interacciona de forma
directa y calcio dependiente con el extremo COOH-terminal del receptor TrkA. A partir de
estos resultados nos plantemaos buscar la posición exacta del sitio de unión a calmodulina
dentro de la secuencia de TrkA. Puesto que los programas de predicción no encontraron
ninguna secuencia candidata de unión a calmodulina en el dominio intracelular de TrkA, nos
centramos en el extremo COOH-terminal, dominio rico en ácidos hidrofóbicos en posiciones
conservadas. Introducimos mutaciones puntuales en el sitio candidato de unión a CaM
cambiando la L784 y la V790 por Ala. Los ensayos de unión a CaM realizados mostraron que
los mutantes TrkA-L784A y TrkAL784A-V790A no perdían la unión a CaM, por lo tanto no
formaban parte del dominio de unión a CaM de TrkA. Sin embargo, hemos demostrado que
estos aminoácidos son importantes para la unión y la regulación de la ligasa de ubiquitina
Nedd4-2. . Observamos una mayor interacción de los dos mutantes del extremo COOHterminal
con Nedd4-2, resultado que era corroborado por una mayor colocalización de las dos
proteínas detectada por immunofluorescencia. Como consecuencia observamos una intensa
multimonoubiquitinización basal de los receptores mutados mediada por Nedd4-2. Estos
resultados correlacionan con un importante descenso de la cantidad de receptor a causa de
un direccionamiento de este hacia los endosomas tardíos/lisosomas. Todo ello resultaba en un
incremento en la degradación de los receptors mutados. A pesar de la reducción en la cantidad
de receptor en membrana, los mutantes de TrkA mostraron ser capaces de activar las vías de
señalización e incluso ser más eficientes promoviendo el crecimiento de neuritas comparando
con el receptor normal. Estos resultados demuestran que la composición del extremo COOHterminal
de TrkA regula la unión y la actividad de la ligasa de ubiquitina Nedd4-2. Además, la
ubiquitinización de TrkA mediada por Nedd4-2 promueve el direccionamiento de los receptores
mutados hacia los endosomas tardíos/lysosomas dando lugar a una mayor degradación del
receptor. Por otro lado, se observa que la multimonoubiquitinización de TrkA no interfiere con
la activación de las vías de señalización, sino más bien potencia la señalización del receptor
que conduce a la diferenciación celular.
The nerve growth factor receptor TrkA contributes to the survival and
differentiation of several neuronal populations. Although main signaling pathways
and adaptor molecules activated after ligand binding to the receptor are well studied,
recently a growing number of TrkA interacting proteins have been described as novel
mechanisms of receptor regulation. Receptor trans-autophosphorylation, additionally
to activating signaling cascades relevant for cell differentiation and survival, such as
MAPKs and PI3K-Akt, also induces a transient increase in intracellular calcium
concentration. Therefore, the Ca2+ sensor calmodulin (CaM) also participates in TrkA
signaling. Our group was interested in elucidating the relationship between CaM and
TrkA, and discovered that CaM interacts directly with the C-terminal tail of TrkA in a
Ca2+ dependent manner. Consequently, we sought to find the exact position of the
calmodulin binding site on TrkA sequence. Since available prediction software was
unable to find a putative CaM binding site in TrkA intracellular domain, we focused
on the C-terminal tail, a domain rich in hydrophobic amino acids in conserved
positions. We introduced point mutations on Leu784 and Val790 by switching them
to Ala, located on our predicted CaM binding site. However, TrkA-L784A and TrkAL784A/
V790A mutants did not lose CaM binding, therefore they were not involved on
CaM binding. Nonetheless, we demonstrated that these hydrophobic aminoacids are
important for the binding and regulation of Nedd4-2 Ub ligase. We observed a
stronger interaction of both C-terminal mutant receptors with Nedd4-2, corroborated
with a higher colocalization of both proteins by immunofluorescence. Consequently,
we observed an enhanced basal multimonoubiquitination of mutant receptors by
Nedd4-2. These results correlated with a decrease in TrkA abundance due to a faster
late endosome/lysosome targeting, leading to a higher degradation rate of mutant
receptors. Despite the reduction in the amount of membrane receptor caused by the
C-terminal changes, TrkA mutants were able to activate signaling cascades and were
even more efficient in promoting neurite outgrowth than the wild-type receptor. Our
results demonstrate that the C-terminal tail conformation of TrkA regulates Nedd4-2
binding and activity. Moreover, TrkA ubiquitination by Nedd4-2 promotes TrkA
endosomal trafficking to late endosome/lysosome leading to receptor degradation. In
addition, TrkA multimonoubiquitination does not interfere with the activation of
signaling cascades, but rather potentiates receptor signaling leading to
differentiation.
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El, Barbry Houssam. "Découverte du rôle crucial du résidu en position 2 des séquences MTS d’adressage mitochondrial". Electronic Thesis or Diss., Sorbonne université, 2023. http://www.theses.fr/2023SORUS035.
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Les mitochondries sont des organites complexes impliquant un millier de protéines, la plupart codées dans le génome nucléaire. Leur biogenèse a nécessité au cours de l’évolution la mise en place de systèmes efficaces d’adressage et d’import protéique, et des défaillances de ces systèmes sont associées à des pathologies graves, neuropathies, troubles cardiovasculaires, myopathies, maladies neurodégénératives ainsi que cancers. De nombreuses protéines mitochondriales possèdent en N-terminal une séquence d’adressage appelée MTS (Mitochondrial Targeting sequence) qui forme une hélice alpha amphiphile essentielle pour leur import mitochondrial. La séquence des divers MTSs est néanmoins très variables et leur caractéristiques critiques ne sont pas encore bien comprises. Le point de départ de ma thèse est la découverte, chez les levures, d’une surreprésentation en position 2 des séquences MTSs de 4 acides aminés hydrophobes (F, L, I, W). Au cours de mes années de thèse, j’ai pu confirmer, par des expériences de mutagenèse dirigée, le rôle critique de la nature du résidu en position 2 des MTSs. En effet, grâce au développement d’un système novateur de criblage des défauts d’import basé sur le sauvetage fonctionnel de la toxicité d’une protéine mitochondriale, j’ai pu observer que seuls les résidus surreprésentés en position 2 des protéines mitochondriales permettaient un import efficace. Mon travail a ainsi démontré l'existence de fortes contraintes évolutives s’exerçant au niveau de la position 2 des MTSs dont la compréhension pourrait à terme être utile pour optimiser l’adressage mitochondrial de protéines thérapeutiques chez des patients atteints de maladies mitochondrialesMitochondria are complex organelles involving a thousand proteins, most of which are encoded in the nuclear genome. Their biogenesis has required the evolutionary development of efficient protein addressing and import systems, and failures of these systems are associated with serious pathologies, neuropathies, cardiovascular disorders, myopathies, neurodegenerative diseases and cancers.Many mitochondrial proteins have an N-terminal addressing sequence called MTS (Mitochondrial Targeting Sequence) which forms an amphiphilic alpha helix essential for their mitochondrial import. However, the sequence of the various MTSs is highly variable and their critical characteristics are not yet well understood. The starting point of my thesis was the discovery in yeast of an overrepresentation of 4 hydrophobic amino acids (F, L, I, W) at position 2 of the MTSs sequences. During my thesis, I was able to confirm the critical role of the nature of the residue in position 2 of the MTSs through directed mutagenesis experiments. Indeed, thanks to the development of an innovative system for screening import defects based on the functional rescue of the toxicity of a mitochondrial protein, I was able to observe that only residues overrepresented at position 2 of mitochondrial proteins allowed efficient import. My work has thus demonstrated the existence of strong evolutionary constraints at position 2 of MTSs, the understanding of which could ultimately be useful for optimising the mitochondrial addressing of therapeutic proteins in patients suffering from mitochondrial diseases
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NADAL, WOLLBOLD FLORENCE. "Activation et regulation des map kinases extracellular signal-regulated kinase 2 et c-jun nh2-terminal kinase 1 dans les plaquettes humaines". Paris 7, 2000. http://www.theses.fr/2000PA077163.
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Les map kinases sont des serine/threonine kinases regroupees en trois familles : les extracellular signal-regulated kinases (erks), les c-jun nh2-terminal kinases (jnks) et les p38 m a p k s. Principalement activees par les recepteurs a activite tyrosine kinase, les recepteurs couples aux proteines g heterotrimeriques et les integrines, elles jouent un role important dans la proliferation, la differenciation, la migration et l'apoptose. Si l'activation, la regulation, et le role des map kinases sont tres etudiees dans les cellules proliferatrices, tres peu de travaux sont realises dans les cellules anuclees comme les plaquettes sanguines ou leur fonction est encore inconnue. Outre la presence des proteines erk1/2 et p38 m a p k dans les plaquettes humaines, nous avons mis en evidence la presence de la proteine jnk1 dans ces cellules. Nous avons par ailleurs, etudie l'activation des kinases erk2 et jnk1 dans les plaquettes humaines stimulees par la thrombine. Nos resultats montrent que l'activation de la proteine jnk1 est plus precoce que celle de erk2, et suggerent que erk2 et jnk1 ne sont pas impliquees dans les evenements precoces de l'activation plaquettaire. De plus, l'activite de erk2, retrouvee dans la fraction soluble et dans le cytosquelette, est dependante de l'activation des pkcs conventionnelles et independante de l'activation des kinases de la famille rafs. Enfin et pour la premiere fois, nos resultats mettent en evidence que dans un modele d'adhesion cellule/cellule telle que l'agregation plaquettaire, une integrine et particulierement l'integrine iib3 peut reguler negativement les map kinases erk2 et jnk1. D'autre part, nous avons montre que ces deux map kinases sont regulees positivement par le phenomene d'agitation.
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FODERA', Emanuele. "The peculiar processing of LRP8 and its significance for Alzheimer's disease". Doctoral thesis, Università degli studi del Molise, 2022. https://hdl.handle.net/11695/115827.
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La malattia di Alzheimer (AD) è la forma più comune di demenza e ad oggi non esiste una terapia efficace per guarire. L'ipotesi della cascata amiloide afferma che i peptidi β-amiloidi, derivanti dall’aberrante processing della Proteina Precursore dell’Amilode (o APP) da parte degli enzimi β- (BACE 1) e γ-secretasi, sono responsabili dell’amiloidosi, perdita neuronale e demenza. Oltre alle forme sporadiche, l' AD familiare è causata dalla iperespressione o mutazione nel gene APP, o da mutazioni nei geni delle Preseniline, componenti chiave del complesso enzimatico (γ-secretasi) che scinde APP. Lo scenario è ulteriormente complicato dal fatto che soggetti portatori dell' allele Apolipoproteina e4 (ApoEe4), il principale fattore di rischio dell’AD, possono sviluppare AD, anticipando l'insorgenza della malattia. Il fallimento degli studi clinici per il trattamento dell’amiloide ha messo in dubbio la validità dell' ipotesi della cascata amiloide; d’altro canto, studi su topi KO condizionali per le Preseniline suggeriscono che una perdita di funzione di γ-secretasi spiegherebbe meglio il fenotipo neurodegenerativo. In questo scenario, abbiamo deciso di esplorare un'ipotesi diversa, partendo dalla considerazione che APP, Preseniline e ApoEe4 fanno parte di un unico pathway, ancora poco chiaro, il cui fallimento porta alla neurodegenerazione. Abbiamo quindi focalizzato i nostri studi sul recettore LRP8, noto anche come ApoER2, il quale: 1) interagisce con APP, 2) è il recettore per ApoE e 3) è processato da γ-secretasi. Inoltre LRP8, mediando il segnale della Reelina, è coinvolto in processi come migrazione neuronale e arborizzazione dendritica.
Studi preliminari sulla localizzazione di LRP8 hanno evidenziato, attraverso esperimenti di Immunoistochimica, una riduzione sia a livello neuronale che parenchimale dei livelli di LRP8 e un parallelo aumento del segnale nucleare in pazienti con AD. Da esperimenti di SDS-PAGE e Western Blot (WB) abbiamo inoltre riscontrato una riduzione della proteina intera di LRP8 (~ 100 kDa) e un concomitante incremento dei suoi frammenti C-terminali (denominati LICD) nei pazienti con AD rispetto ai casi controllo.
Pertanto, la nostra ipotesi è che LRP8 nell’AD subisce un processing diverso e che i frammenti LICD, traslocando nel nucleo, possono avere un ruolo trascrizionale.
In questa tesi abbiamo esplorato in vitro il processing e la localizzazione nucleare di LRP8, e degli LICD, in diverse condizioni. Per tale motivo abbiamo utilizzato cellule Neuro 2A (N2A), trasfettate stabilmente con un plasmide codificante per LRP8 umano contenente una coda ddk-myc all' estremità C-terminale; inoltre, per mimare in vitro la "perdita di funzione" di γ-secretasi, abbiamo usato il DAPT, uno specifico inibitore di γ-secretasi. Inizialmente abbiamo osservato, sia attraverso esperimenti di WB che di Immunocitochimica, un aumento nucleare degli LICD nelle cellule trattate col DAPT.
Abbiamo quindi esplorato il coinvolgimento di altri enzimi, oltre γ-secretasi, nella formazione degli LICD. Usando l' Actinonina, un inibitore specifico dell' enzima Meprin β (noto per generare peptidi Aβ troncati all’estremità N-terminale, e la cui espressione è aumentata nel cervello di pazientiAD), abbiamo notato che l' Actinonina riduce la formazione degli LICD e la loro traslocazione a livello nucleare. Infine, investigando il presunto ruolo trascrizionale degli LICD, abbiamo determinato mediante RT-PCR che la presenza nucleare degli LICD è associata a un incremento dell’ mRNA di BACE1.
In conclusione, i nostri dati evidenziano che il processing di LRP8 è alterato nei pazienti AD e che, in vitro, questa condizione è mimata dal blocco di γ-secretasi. Resta da definire il significato della riduzione di LRP8, e l’ aumento degli LICD, nei pazienti con AD e la correlazione con ApoEe4. Tuttavia, i nostri studi indicano che un incremento degli LICD e la loro localizzazione nucleare possono innescare un meccanismo patogenico, attraverso un incremento dei livelli di BACE 1, un aumento del processing di APP e la formazione dell’ amiloide.Alzheimer’s disease (AD) is the most common form of dementia and at present there are no effective therapies. The cause of the neurodegeneration is unclear and the amyloid cascade hypothesis states that short amyloid β-peptides, derived from the aberrant processing of Amyloid Precursor Protein (or APP) by β- (BACE1) and γ-secretases, are the neurotoxic triggers that cause amyloidosis, neuronal loss, and dementia. Besides the sporadic forms, familial AD is caused by overexpression or mutation into the APP gene, or by mutations into Presenilins genses, which are key components of the enzymatic complex (γ-secretase) that cleaves APP. The scenario is further complicated by the fact that subjects carriers of the Apolipoprotein e4 allele (ApoEe4) may develop AD, anticipating the onset of the disease, being ApoEe4 the major risk factor for AD. Recent literature and the failure of clinical trials to treat amyloid-β peptide, pose at risk the amyloid hypothesis. Further, studies in conditional KO mice for presenilins suggest that a “loss of function” of γ-secretase may more effectively explain a neurodegenerative phenotype. In this scenario, we decided to explore a different hypothesis, starting by the pivotal consideration that APP, presenilins and ApoEe4 are part of a single pathway, still unclear, whose failure leads to neurodegeneration. We therefore focused our studies on the LRP8 receptor, also known as ApoER2, which: 1) interacts with APP, 2) is the receptor for ApoE, and 3) is processed by γ-secretase. Moreover, LRP8, mediating the Reelin signal, takes part in processes such as neuronal migration and dendritic arborization. In our initial studies on LRP8 localization, we determined that in the brain cortex of AD patients, LRP8 levels are reduced at neuronal and parenchymal level and, in parallel, we observed an increment of nuclear staining in Immunohistochemistry experiments. By SDS-PAGE and Western Blot (WB) experiments we evidenced a reduction of LRP8 full-length (~ 100 kDa) protein and a parallel increment of C-terminal fragments (named LICDs), which is more evident in AD patients than in control cases. Thus, our hypothesis is that LRP8 undergoes a different processing in AD, and we speculated that LICDs could translocate into the nucleus with a putative transcriptional function. In this thesis, we explored in vitro the processing and the nuclear localization of LRP8, and its LICDs, in different conditions. To investigate the LRP8 processing we decided to use Neuro 2A (N2A) cells, stably transfected with a plasmid encoding for human LRP8 bearing the ddk-myc tag in the C-terminal extremity, and to recreate in vitro a “loss of function” of γ-secretase, we used DAPT, a specific γ-secretase inhibitor. We initially observed that DAPT-treated cells showed an increase of nuclear LICDs, both in WB and Immunocytochemistry experiments. We therefore explored the involvement of other enzymes, beside γ-secretase, in the formation of LICDs. Using Actinonin, a specific inhibitor of the Meprin β enzyme (known to generate the N-terminus of Aβ peptides, and whose expression is enhanced in AD brain), we determined that Actinonin reduces LICDs formation and nuclear translocation in N2A LRP8-ddk-myc cells. Finally, exploring a putative transcriptional role for LICDs, we determined by RT-PCR that the presence of LICDs into the nucleus is associated with an increment of BACE1’s mRNA level. In conclusion, our data show that LRP8 processing is altered in AD patients, and that, in vitro, this condition is mimicked upon γ-secretase block or “loss of function”. The significance of an increment of LICDs, or rather by the reduction of LRP8 full length receptor, in AD patients and the correlation with ApoEe4 or familial conditions is still to be defined. However, our studies indicate that an increment of LICDs and their nuclear localization may trigger a cyclic pathogenic pathway through an increment of BACE1 levels, enhancing APP processing and amyloid-β formation.
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Möhwald, Jiří. "Ukázka řízení otáček motoru frekvenčním měničem". Master's thesis, Vysoké učení technické v Brně. Fakulta strojního inženýrství, 2009. http://www.nusl.cz/ntk/nusl-228651.
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The following diploma thesis deals with the management of asynchronous motor revolutions by a frequency converter MICROMASTER 440 via the programmable controller S7-200. At the beginning, I researched the company documentation of Siemens, which is the producer of the frequency converter and the programmable controller mentioned above. As my work proceeded, I also started to study the company documentation of Mitsubishi Electric, which produces the operating pannel. The first part of my thesis provides a general description of the stated devices and the second part deals with the solution of the task itself. My task was to design a way of communication between the converter and the controller. I chose a USS protocol via serial port RS-485. The operation of the controller was performed by using an operating terminal type GOT1000 which was connected to the controller. In summary, my diploma thesis primarily deals with the construction of an operating programme for the controller and with creating of a graphical control on the terminal. In the end, I evaluated the knowledge gained during the work on this subject and suggested further procedures.
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Nagar, Bhushan. "X-ray crystallographic analysis of 1) the two N-terminal domains of epithelial cadherin and 2) C3d, a fragment of the complement protein C3". Thesis, National Library of Canada = Bibliothèque nationale du Canada, 2001. http://www.collectionscanada.ca/obj/s4/f2/dsk3/ftp05/NQ63590.pdf.
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Price, Anna Helen. "Biomarkers for cardiovascular risk prediction in people with type 2 diabetes". Thesis, University of Edinburgh, 2017. http://hdl.handle.net/1842/28785.
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Introduction: Type 2 diabetes continues to be one of the most common non-communicable diseases worldwide and complications due to type 2 diabetes, such as cardiovascular disease (CVD) can cause severe disability and even death. Despite advances in the development and validation of cardiovascular risk scores, those used in clinical practice perform inadequately for people with type 2 diabetes. Research has suggested that particular non-traditional biomarkers and novel omics data may provide additional value to risk scores over-and-above traditional predictors. Aims: To determine whether a small panel of non-traditional biomarkers improve prediction models based on a current cardiovascular risk score (QRISK2), either individually or in combination, in people with type 2 diabetes. Furthermore, to investigate a set of 228 metabolites and their associations with CVD, independent of well-established cardiovascular risk factors, in order to identify potential new predictors of CVD for future research. Methods: Analyses used the Edinburgh Type 2 Diabetes Study (ET2DS), a prospective cohort of 1066 men and women with type 2 diabetes aged 60-75 years at baseline. Participants were followed for eight years, during which time 205 had a cardiovascular event. Additionally, for omics analyses, four cohorts from the UCL-LSHTM-Edinburgh-Bristol (UCLEB) consortium were combined with the ET2DS. Across all studies, 1005 (44.73%) participants had CVD at baseline or experienced a cardiovascular event during follow-up. Results: In the ET2DS, higher levels of high sensitivity cardiac troponin (hs-cTnT) and N-terminal pro-brain natriuretic peptide (NT-proBNP) and lower levels of ankle brachial pressure index (ABI) were associated with incident cardiovascular events, independent of QRISK2 and pre-existing cardiovascular disease (odds ratios per one SD increase in biomarker 1.35 (95% CI: 1.13, 1.61), 1.23 (1.02, 1.49) and 0.86 (0.73, 1.00) respectively). The addition of each biomarker to a model including just QRISK2 variables improved the c-statistic, with the biggest increase for hs-cTnT (from 0.722 (0.681, 0.763) to 0.732 (0.690, 0.774)). When multiple biomarkers were considered in combination, the greatest c-statistic was found for a model which included ABI, hs-cTnT and gamma-glutamyl transpeptidase (0.740 (0.699, 0.781)). In the combined cohorts from the UCLEB consortium, a small number of high-density lipoprotein (HDL) particles were found to be significantly associated with CVD: concentration of medium HDL particles, total lipids in medium HDL, phospholipids in medium HDL and phospholipids in small HDL. These associations persisted after adjustment for a range of traditional cardiovascular risk factors including age, sex, blood pressure, smoking and HDL to total cholesterol ratio. Conclusions: In older people with type 2 diabetes, a range of non-traditional biomarkers increased predictive ability for cardiovascular events over-and-above the commonly used QRISK2 score, and a combination of biomarkers may provide the best improvement. Furthermore, a small number of novel omics biomarkers were identified which may further improve risk scores or provide better prediction than traditional lipid measurements such as HDL cholesterol.
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Soumya, R. Deo. "Characterization of the terminal region RNAs of the West Nile virus genome and their interaction with the small isoform of 2' 5'-oligoadenylate synthetases (OAS)". Plos.org, 2014. http://hdl.handle.net/1993/30733.
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2'-5'-oligoadenylate synthetases (OAS) are interferon-stimulated proteins that act in the innate immune response to viral infection. Upon binding to viral double-stranded RNAs, OAS enzymes produce 2'-5'-linked oligoadenylates that stimulate RNase L and ultimately slow viral propagation. Studies have linked mutations in the OAS1 gene to increased susceptibility to West Nile virus (WNV) infection, highlighting the importance of the OAS1 enzyme. Here I report that the 5'-terminal region (5'-TR) of the WNV genome, comprising both the 5'-untranslated region (5'-UTR) and initial coding region, is capable of OAS1 activation in vitro. This region contains three RNA stem loops (SLI, SLII, and SLIII), whose relative contribution to OAS1 binding affinity and activation were investigated using electrophoretic mobility shift assays and enzyme kinetics experiments. Stem loop I (SLI) is dispensable for maximum OAS1 activation, as a construct containing only SLII and SLIII was capable of enzymatic activation. Mutations to the RNA binding site of OAS1 confirmed the specificity of the interaction. Solution conformations of both the 5'-TR RNA of WNV and OAS1 were then elucidated using small-angle x-ray scattering. I also report that the 3' terminal region (3'-TR) is able to mediate specific interaction with and activation of OAS1. Binding and kinetic experiments identified a specific stem loop within the 3'-TR that is sufficient for activation of the enzyme. The solution confirmation of the 3'-terminal region was determined by small angle X-ray scattering, and computational models suggest a conformationally restrained structure comprised of a helix and short stem loop. Structural investigation of the 3'-TR in complex with OAS1 is also presented. Finally, we show that genome cyclization by base pairing between the 5'- and 3'-TRs, a required step for replication, is not sufficient to protect WNV from OAS1 recognition. The purity, monodispersity and homogeneity of all samples subjected to SAXS analysis were evaluated using dynamic light scattering and/or analytical ultra-centrifuge. These data provide a framework for understanding recognition of the highly structured terminal regions of a flaviviral genome by an innate immune enzyme.October 2015
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Tjhen, Richard June. "Structure and dynamics of ribonucleoproteins by X-ray crystallography and NMR: Structural basis of Piwi PAZ domain binding preference for 2'-O-methylated 3' terminal ssRNAs". Diss., Search in ProQuest Dissertations & Theses. UC Only, 2010. http://gateway.proquest.com/openurl?url_ver=Z39.88-2004&rft_val_fmt=info:ofi/fmt:kev:mtx:dissertation&res_dat=xri:pqdiss&rft_dat=xri:pqdiss:3398888.
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Sperling, Adam Samuel Abdur-Rahim. "The function of the histone H3 N terminal tail in the formation of heterochromatin in the budding yest, Saccharomyces cerevisiae". Diss., Restricted to subscribing institutions, 2009. http://proquest.umi.com/pqdweb?did=1905641821&sid=1&Fmt=2&clientId=1564&RQT=309&VName=PQD.
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Maimari, Theopisti [Verfasser], Kristina [Gutachter] Lorenz, Andreas [Gutachter] Schlosser i Karoline [Gutachter] Kisker. "The influence of N-terminal peptides of G-protein coupled receptor kinase (GRK) 2, 3 and 5 on β-adrenergic signaling / Theopisti Maimari ; Gutachter: Kristina Lorenz, Andreas Schlosser, Karoline Kisker". Würzburg : Universität Würzburg, 2020. http://d-nb.info/1204006369/34.
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De, Loayza Tantalean Leonora Raquel, i Vasquez Milagros Del Pilar Esquen. "Calidad de vida de los pacientes con enfermedad renal crónica en estadio terminal por diabetes mellitus tipo 2 en terapia de reemplazo renal atendidos en un hospital de Essalud en el año 2018-2019". Bachelor's thesis, Universidad Católica Santo Toribio de Mogrovejo, 2021. http://hdl.handle.net/20.500.12423/3321.
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Objetivos: Describir la calidad de vida así como los factores sociodemográficos de pacientes en hemodiálisis y diálisis peritoneal por diabetes mellitus tipo 2. Metodología:
Estudio descriptivo transversal. Se aplicó el instrumento SF-36 que evalúa la calidad de vida, y el cuestionario APEIM versión modificada 2011-2012 para evaluar el nivel socioeconómico a 59 pacientes con diagnóstico de enfermedad renal crónica terminal por diabetes mellitus tipo 2 en terapia dialítica, seleccionados según criterios de inclusión. Resultados: En hemodiálisis (HD) se incluyeron a 35 pacientes, de los cuales, 21 refieren una mejor calidad de vida global. En el grupo de diálisis peritoneal (DP), 14 de los 24 pacientes mostraron una peor calidad de vida global. En el nivel socioeconómico no se registraron pacientes en las categorías alto y medio; sin embargo, el mayor porcentaje de la población se encontró en la categoría bajo inferior para ambos grupos. Según el sexo, 39 pacientes son varones. De los 20 varones en HD, 16 perciben una mejor calidad de vida global. Podemos observar también, que de 19 varones en diálisis peritoneal, 10 refieren una peor calidad de vida global.
Conclusión: La mayor cantidad de pacientes en hemodiálisis perciben una mejor calidad de vida en las dimensiones salud general, función social, salud mental y global SF-36, por otro lado, la mayoría de los pacientes en diálisis peritoneal perciben una peor calidad de vida global. Además se observa que la mayor parte de los pacientes entrevistados tienen un nivel socioeconómico bajo inferior.
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Shasha, Adelle. "Metal-Catalysed Hydroamination". Science. School of Chemistry, 2007. http://hdl.handle.net/2123/1710.
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Doctor of Philosophy(PhD),This thesis describes the synthesis of terminal and internal amino and amidoalkynes and their hydroamination (cyclisation) catalysed by the complex (bis(N-methylimidazol-2-yl)methane)dicarbonylrhodium(I) tetraphenylborate (1). A series of analogous palladium complexes were also prepared and investigated for catalytic hydroamination. The scope of the rhodium(I) complex (1) for the intramolecular hydroamination of more complex amino and amidoalkyne substrates was investigated. This was made possible with the synthesis of aliphatic substrates, namely, 4 pentyn 1 amide (3) and 5 hexyn 1 amide (4) and a number of aromatic substrates, namely, 1, 4 diamino-2, 5 diethynylbenzene (5), 1, 4-diamino-2, 5 bis(phenylethynyl)benzene (6), 2, 3-diamino-1, 4-diethynylbenzene (7), 2, 3-diamino-1, 4-bis(phenylethynyl)benzene (8), 1, 5-bis(acetamido)-2, 4-diethynylbenzene (9), N-(acetyl)-2-ethynylbenzylamine (10) and N-(acetyl)-2-(phenylethynyl)benzylamine (11). The rhodium(I) complex (1) catalytically cyclised the aliphatic 4 pentyn 1 amide (3) regioselectively to the 6 membered ring, 3, 4 dihydro 2 pyridone (64) as the sole product. Attempts to cyclise 5 hexyn 1 amide (4) to produce either the 6 or 7 membered ring were unsuccessful. Compounds 5, 6, 7 and 8 were doubly cyclised to 1, 5 dihydro pyrrolo[2, 3 f]indole (71), 1, 5-dihydro-2, 6-diphenyl-pyrrolo[2, 3 f]indole (73), 1, 8-dihydro-pyrrolo[2, 3 g]indole (74) and 1, 8-dihydro-2, 7-diphenyl-pyrrolo[2, 3 g]indole (75) respectively. The aromatic amides with terminal acetylenes 9 and 10 cyclised to give 1, 7 diacetyl pyrrolo[3, 2 f]indole (76) and N (acetyl) 1, 2 dihydroisoquinoline (77) respectively. However, attempts to cyclise 11 were unsuccessful. Thus the rhodium(I) complex (1) successfully catalysed via hydroamination both terminal and internal acetylenic amine and amide substrates, to give pyridones, indoles and isoquinolines. Cationic and neutral palladium complexes incorporating the bidentate heterocyclic nitrogen donor ligand bis(N-methylimidazol-2-yl)methane (bim; 2) were synthesised: [Pd(bim)Cl2] (15), [Pd(bim)2][BF4]2 (17) [Pd(bim)(Cl)(CH3)] (14), [Pd(bim)(CH3)(NCCH3)][BF4] (16). All of the complexes were active as catalysts for the intramolecular hydroamination reaction, using the cyclisation of 4 pentyn 1 amine (21) to 2 methyl 1 pyrroline (22) as the model test reaction. Percentage conversions, turnover numbers and reaction profiles for each complex were compared to the rhodium(I) complex (1). These studies have shown that the catalytic activity was not significantly dependent on the bim donor ligand or the choice of metal. Substitution of the bim (2) ligand with the COD ligand and the use of methanol as the solvent did impact significantly on the efficiency of the hydroamination reactions.
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Shasha, Adelle. "Metal-Catalysed Hydroamination". Thesis, The University of Sydney, 2006. http://hdl.handle.net/2123/1710.
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This thesis describes the synthesis of terminal and internal amino and amidoalkynes and their hydroamination (cyclisation) catalysed by the complex (bis(N-methylimidazol-2-yl)methane)dicarbonylrhodium(I) tetraphenylborate (1). A series of analogous palladium complexes were also prepared and investigated for catalytic hydroamination. The scope of the rhodium(I) complex (1) for the intramolecular hydroamination of more complex amino and amidoalkyne substrates was investigated. This was made possible with the synthesis of aliphatic substrates, namely, 4 pentyn 1 amide (3) and 5 hexyn 1 amide (4) and a number of aromatic substrates, namely, 1, 4 diamino-2, 5 diethynylbenzene (5), 1, 4-diamino-2, 5 bis(phenylethynyl)benzene (6), 2, 3-diamino-1, 4-diethynylbenzene (7), 2, 3-diamino-1, 4-bis(phenylethynyl)benzene (8), 1, 5-bis(acetamido)-2, 4-diethynylbenzene (9), N-(acetyl)-2-ethynylbenzylamine (10) and N-(acetyl)-2-(phenylethynyl)benzylamine (11). The rhodium(I) complex (1) catalytically cyclised the aliphatic 4 pentyn 1 amide (3) regioselectively to the 6 membered ring, 3, 4 dihydro 2 pyridone (64) as the sole product. Attempts to cyclise 5 hexyn 1 amide (4) to produce either the 6 or 7 membered ring were unsuccessful. Compounds 5, 6, 7 and 8 were doubly cyclised to 1, 5 dihydro pyrrolo[2, 3 f]indole (71), 1, 5-dihydro-2, 6-diphenyl-pyrrolo[2, 3 f]indole (73), 1, 8-dihydro-pyrrolo[2, 3 g]indole (74) and 1, 8-dihydro-2, 7-diphenyl-pyrrolo[2, 3 g]indole (75) respectively. The aromatic amides with terminal acetylenes 9 and 10 cyclised to give 1, 7 diacetyl pyrrolo[3, 2 f]indole (76) and N (acetyl) 1, 2 dihydroisoquinoline (77) respectively. However, attempts to cyclise 11 were unsuccessful. Thus the rhodium(I) complex (1) successfully catalysed via hydroamination both terminal and internal acetylenic amine and amide substrates, to give pyridones, indoles and isoquinolines. Cationic and neutral palladium complexes incorporating the bidentate heterocyclic nitrogen donor ligand bis(N-methylimidazol-2-yl)methane (bim; 2) were synthesised: [Pd(bim)Cl2] (15), [Pd(bim)2][BF4]2 (17) [Pd(bim)(Cl)(CH3)] (14), [Pd(bim)(CH3)(NCCH3)][BF4] (16). All of the complexes were active as catalysts for the intramolecular hydroamination reaction, using the cyclisation of 4 pentyn 1 amine (21) to 2 methyl 1 pyrroline (22) as the model test reaction. Percentage conversions, turnover numbers and reaction profiles for each complex were compared to the rhodium(I) complex (1). These studies have shown that the catalytic activity was not significantly dependent on the bim donor ligand or the choice of metal. Substitution of the bim (2) ligand with the COD ligand and the use of methanol as the solvent did impact significantly on the efficiency of the hydroamination reactions.
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Pachas, Vargas Miguel Francisco. "Momento de inicio de la hemodiálisis y su impacto en la mortalidad en pacientes con insuficiencia renal terminal en el Hospital Nacional 2 de Mayo, en el periodo junio 2005-mayo 2006". Bachelor's thesis, Universidad Nacional Mayor de San Marcos, 2006. https://hdl.handle.net/20.500.12672/16040.
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El momento óptimo del tratamiento para pacientes con enfermedad renal crónica previene complicaciones serias y urémicas, sin embargo, todas las formas de terapia de reemplazo renal ocasionan problemas importantes. El presente trabajo tiene el fin de estimar el impacto sobre la mortalidad que tiene el inicio precoz versus tardío de la terapia de diálisis en pacientes con insuficiencia renal terminal en el Hospital Nacional 2 de Mayo. El estudio de tipo retrospectivo, observacional y descriptivo tuvo como población de estudio a todos los pacientes mayores de 15 años que fueron atendidos en el Servicio de Emergencia de dicho hospital. De acuerdo a criterios de inclusión se obtuvo una muestra total de 79 pacientes que se sometieron a hemodiálisis durante su estancia hospitalaria. De estos, 51 pacientes fueron considerados como Iniciadores Tardíos y 28 como Iniciadores Precoces. Dentro de las condiciones comórbidas, la hipertensión arterial y la diabetes mellitus son la causa más frecuente de insuficiencia renal crónica terminal primando la primera condición. El nivel de hemoglobina promedio para ambos grupos (7.1 +/- 2.1 g/dL) se le categoriza como anemia severa. Se concluye que la mortalidad intrahospitalaria de los pacientes sometidos a la terapia dialítica es la misma tanto para el grupo de iniciadores precoces como tardíos, y que la mortalidad en tales pacientes es menor que la mortalidad en los pacientes que no son dializados. También, el paciente en promedio que inicia la diálisis tiene mayor comorbilidad y parámetros de enfermedad renal avanzada y que ello puede influir en la sobrevida del paciente.
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FU, TZU-HSIU, i 傅子修. "Satisfaction Analysis of Airport Terminal Sign System – A Case of Taoyuan International Airport Terminal 2". Thesis, 2019. http://ndltd.ncl.edu.tw/handle/6f84vf.
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碩士開南大學
觀光運輸學院碩士在職專班
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Summary Symbols and signs have become an indispensable facility for human life and activities, especially at the Taoyuan International Airport, where most of the country's main entrances and exits are available. High dependence to assist in quickly finding directions during the immigration process. The goodness of the marking system not only makes passengers more convenient, but also an important indicator of the level of airport service. This study studies the satisfaction of the exit marking system of the second terminal of Taoyuan International Airport, discusses the satisfaction of the marking system service of Taoyuan International Airport, and discusses the planning and design of the airport marking system based on the user's perspective, and then proposes improvement suggestions for the marking system. . The results of the study show that in the non-regulated regional facilities, the highest percentage of unused recycling counters are the tax refund counters and the customs service desks. The lowest proportions that have never been used are the restrooms and check-in counters. The marked areas in the control area have never been used. The room, followed by the smoking room (area), the lowest percentage of unused options are the boarding gate and the restroom. The highest satisfaction rate is used. The non-regulated area is the check-in counter and the self-check-in counter. The control area is the security check/license check and boarding gate; the smoking room (area) mark is the lowest satisfaction. On the whole, except for a small number of facilities, the satisfaction of the use of most other facilities will vary with the characteristics of individual social and social characteristics, and the number is too small to be the most important source of dissatisfaction, among which elevators and restrooms are considered by passengers. Those that are important but are currently less satisfied, and should be prioritized for improvement. Keywords: Sign System, Satisfaction, Satisfaction-importance Analysis