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Vicente-García, José Julio. "Identification of new activated Cdc42 kinase (ACK1) binding proteins and characterisation of the ACK1-STAT3 interaction." Thesis, University of Cambridge, 2009. http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.611738.
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Linderoth, E. "The role of Ack1 in TRAIL receptor signalling." Thesis, University College London (University of London), 2012. http://discovery.ucl.ac.uk/1369879/.
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The Tumour necrosis factor-related apoptosis-inducing ligand (TRAIL) is one of the most recently identified death inducing ligands of the TNF cytokine family. TRAIL induces apoptosis in most cancer cells, whereas the majority of normal cells are resistant. TRAIL receptor agonists are therefore considered to be a promising anti-cancer therapeutic. However, because many cancer cells develop resistance to TRAIL, understanding the mechanisms by which resistance is acquired will be critical for the therapeutic use of TRAIL in cancer therapy. We have discovered that Activated Cdc42-associated kinase 1 (Ack1) is required for TRAIL induced apoptosis in human epithelial cells. Ack1 is a non- receptor tyrosine kinase with numerous protein-protein interaction domains, suggested to have a role in several cellular processes such as trafficking, endocytosis and cell motility. Knockdown of Ack1 in various epithelial cell lines leads to significantly impaired TRAIL induced apoptosis as evident by reduced cleavage of Caspase-8 and -3 and surface exposure of phosphatidylserine. Exploring the underlying mechanism we found that Ack1 knockdown leads to impaired TRAIL induced clustering of TRAIL-R1 and a reduction in the recruitment of Caspase-8 to the DISC complex, essential for death inducing signal transduction. Translocation of the TRAIL receptors to lipid rafts in the plasma membrane have been suggested to be crucial for TRAIL receptor dynamics and downstream signalling following TRAIL ligand binding. In this work we show that Ack1 is required for the translocation of the TRAIL receptors to the lipid rafts. In this thesis, a novel regulatory role of Ack1 in apoptosis, death receptor signalling and lipid raft trafficking is presented, contributing further to the understanding of the molecular regulation of TRAIL receptor signalling.
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Svensson, Julia. "The Effects of ACK1 and Cell Density on ErbB3." Thesis, Uppsala universitet, Institutionen för biologisk grundutbildning, 2021. http://urn.kb.se/resolve?urn=urn:nbn:se:uu:diva-446027.
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The ErbB family of receptors are involved in signalling relating to cell proliferation and differentiation through activation of pathways such as PI3K and MAPK. Their overexpression is often found in different cancer types and therefore, their expression is under tight regulation. The ErbB family includes, EGFR, ErbB2, ErbB3, and ErbB4 where all but ErbB3 has a kinase domain, making ErbB3 a pseudokinase. Upon activation of the receptors, they are endocytosed through the formation of a clathrin-coated pit and are degraded in the lysosome. Interestingly, researchers have found that newly synthesised ErbB3 can also be degraded in the proteasome by protein Nrdp1. Suggesting that ErbB3 might work in a ligand-independent manner and needs additional regulatory mechanisms. ACK1 is a non-receptor tyrosine kinase that has a reported effect on EGFR by promoting receptor degradation in the autophagosome. However, their role in EGFR regulation is still debated. Therefore, this information alludes to the fact that ACK1 might influence other ErbB family members as well. This report aims to investigate whether ACK1 influences ErbB3 levels. Through RNAi mediated knockdown of ACK1 in MCF10A cells, a novel role of ACK1 acting as a regulator of ErbB3 is hinted at. Surprisingly, these results also show that ACK1 seems to act specifically on ErbB3 and not on its family members, EGFR and ErbB2. Moreover, this report shows that ErbB3 expression is linked to cell density.
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Krawczyk, Sylwia. "The roles of Ack1 in growth factor signalling and trafficking." Thesis, University of Birmingham, 2014. http://etheses.bham.ac.uk//id/eprint/4775/.
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Growth factor signalling controls multiple cellular functions, such as cell growth, proliferation, migration and cell survival, and misregulation of growth factor signalling has been shown to promote cancer development and progression. The study presented within this thesis focuses on the functions of a non-receptor tyrosine kinase Ack1 (Activated Cdc42-associated kinase 1, TNK2) in epidermal growth factor (EGF) receptor (EGFR) trafficking. This study reveals that Ack1 subcellular localization greatly depends on EGF availability. Furthermore, this work also identifies a potential role for Ack1 in a non-canonical degradative pathway through its associations with several autophagosomal proteins. Analyses of a panel of the Ack1 deletion mutants further reveal key mechanistic aspects of these associations and identify the Ack1 domains which are required for these to occur. Finally, a mass spectrometric approach has been applied which identifies novel post-translational modification sites within Ack1, and in combination with stable isotope labelling of amino acids in cell culture (SILAC), has allowed for characterisation of novel Ack1 interactors.
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Wu, Sijia. "Novel Mechanisms Regulating Dopamine Transporter Endocytic Trafficking: Ack1-Controlled Endocytosis And Retromer-Mediated Recycling." eScholarship@UMMS, 2001. http://escholarship.umassmed.edu/gsbs_diss/887.
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Dopamine transporters (DAT) facilitate high-affinity presynaptic dopamine (DA) reuptake in the central nervous system, and are required to constrain extracellular DA levels and maintain presynaptic DAergic tone. DAT is the primary target for addictive and therapeutic psychostimulants, which require DAT binding to elicit reward. DAT availability at presynaptic terminals ensures its proper function, and is dynamically regulated by endocytic trafficking. My thesis research focused on two fundamental questions: 1) what are the molecular mechanisms that control DAT endocytosis? and 2) what are the mechanism(s) that govern DAT’s post-endocytic fate? Using pharmacological and genetic approaches, I discovered that a non-receptor tyrosine kinase, activated by cdc42 kinase 1 (Ack1), stabilizes DAT plasma membrane expression by negatively regulating DAT endocytosis. I found that stimulated DAT endocytosis absolutely requires Ack1 inactivation. Moreover, I was able to restore normal DAT endocytosis to a trafficking dysregulated DAT coding variant identified in an Attention Deficit Hyperactivity Disorder (ADHD) patient via constitutively activating Ack1. To address what mechanisms govern DAT’s post-endocytic fate, I took advantage of a small molecule labeling approach to directly couple fluorophore to the DAT surface population, and subsequently tracked DAT’s temporal-spatial post-endocytic itinerary in immortalized mesencephalic cells. Using this approach, I discovered that the retromer complex mediates DAT recycling and is required to maintain DAT surface levels via a DAT C-terminal PDZ-binding motif. Taken together, these findings shed considerable new light on DAT trafficking mechanisms, and pave the way for future studies examining the role of regulated DAT trafficking in neuropsychiatric disorders.
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Wu, Sijia. "Novel Mechanisms Regulating Dopamine Transporter Endocytic Trafficking: Ack1-Controlled Endocytosis And Retromer-Mediated Recycling." eScholarship@UMMS, 2017. https://escholarship.umassmed.edu/gsbs_diss/887.
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Dopamine transporters (DAT) facilitate high-affinity presynaptic dopamine (DA) reuptake in the central nervous system, and are required to constrain extracellular DA levels and maintain presynaptic DAergic tone. DAT is the primary target for addictive and therapeutic psychostimulants, which require DAT binding to elicit reward. DAT availability at presynaptic terminals ensures its proper function, and is dynamically regulated by endocytic trafficking. My thesis research focused on two fundamental questions: 1) what are the molecular mechanisms that control DAT endocytosis? and 2) what are the mechanism(s) that govern DAT’s post-endocytic fate? Using pharmacological and genetic approaches, I discovered that a non-receptor tyrosine kinase, activated by cdc42 kinase 1 (Ack1), stabilizes DAT plasma membrane expression by negatively regulating DAT endocytosis. I found that stimulated DAT endocytosis absolutely requires Ack1 inactivation. Moreover, I was able to restore normal DAT endocytosis to a trafficking dysregulated DAT coding variant identified in an Attention Deficit Hyperactivity Disorder (ADHD) patient via constitutively activating Ack1. To address what mechanisms govern DAT’s post-endocytic fate, I took advantage of a small molecule labeling approach to directly couple fluorophore to the DAT surface population, and subsequently tracked DAT’s temporal-spatial post-endocytic itinerary in immortalized mesencephalic cells. Using this approach, I discovered that the retromer complex mediates DAT recycling and is required to maintain DAT surface levels via a DAT C-terminal PDZ-binding motif. Taken together, these findings shed considerable new light on DAT trafficking mechanisms, and pave the way for future studies examining the role of regulated DAT trafficking in neuropsychiatric disorders.
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Krishnan, Kadalmani. "Characterisation of the G protein controlled tyrosine kinase, ACK1 and its interaction with nucleolar partner proteins." Thesis, University of Cambridge, 2012. http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.610698.
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Cebula, Patricia Verfasser], Johannes [Akademischer Betreuer] Bode, and Dieter [Akademischer Betreuer] [Willbold. "HCV interferiert mit Ack1-abhängigen Signalwegen durch Herabregulation der TC-PTP / Patricia Cebula. Gutachter: Johannes Bode ; Dieter Willbold." Düsseldorf : Universitäts- und Landesbibliothek der Heinrich-Heine-Universität Düsseldorf, 2011. http://d-nb.info/1015434118/34.
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Cebula, Patricia [Verfasser], Johannes Akademischer Betreuer] Bode, and Dieter [Akademischer Betreuer] [Willbold. "HCV interferiert mit Ack1-abhängigen Signalwegen durch Herabregulation der TC-PTP / Patricia Cebula. Gutachter: Johannes Bode ; Dieter Willbold." Düsseldorf : Universitäts- und Landesbibliothek der Heinrich-Heine-Universität Düsseldorf, 2011. http://d-nb.info/1015434118/34.
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Guillet, Stéphanie. "Monogenic predisposition to systemic lupus erythematosus and efferocytosis Impaired efferocytosis and Systemic Lupus Erythematosus in patients with autosomal recessive ACK1 and BRK Kinases deficiencies." Thesis, Sorbonne Paris Cité, 2019. http://www.theses.fr/2019USPCB003.
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Le Lupus Erythemateux disséminé (LED) est un ensemble de maladies auto-immunes caractérisées par la présence d'anticorps anti-nucléaires. La pathogenèse du lupus est inconnue à ce jour et les mécanismes de la maladie pourraient être multiples. Dans ce travail nous reportons l'identification de variants autosomaux récessifs, pertes de function, dans le domaine kinase de ACK1 et BRK respectivement, chez des patients atteints de LED de 2 familles non apparentées. Utilisant des macrophages dérivés d'iPSCs similaires aux macrophages résidents exprimant TIM4, nous montrons que la forme sauvage de ACK1 et BRK n'est pas requise pour la phagocytose de bactéries et de champignons, mais est nécessaire pour une efferocytose efficace, incluant la phagocytose mediée par l'actin de cellules apoptotiques par des macrophages humains et l'expression précoce de gène anti-inflammatoire induit par STAT3 et AKT et déclenché par l'exposition à des cellules apoptotiques. Ces résultats indiquent que l'activité kinase de ACK1 et BRK sont nécessaires pour la clearance immunologiquement silencieuse des cellules apoptotiques par les macrophages. Enfin ces données définissent un sous-groupe de patients atteints de LED avec un déficit génétique d'efferocytose qui pourrait bénéficier de thérapie ciblée dans le futureSystemic Lupus Erythematosus (SLE) is a collection of autoimmune diseases characterized by auto-antibodies against nuclear antigens. Pathogenesis of SLE remains unclear and disease mechanisms may be multiple. Here we report the identification of autosomal recessive loss-of-function variants in the kinase domain of ACK1 and BRK, in patients from two families with SLE. Using patients and controls iPSC-derived Tim4+ resident-like macrophages we find that wild-type ACK1 and BRK are dispensable for phagocytosis of bacteria and fungi, but are both required for efficient efferocytosis, including actin-mediated engulfment of apoptotic cells by human macrophages, and an early cell-autonomous anti-inflammatory gene expression program driven by AKT and STAT3 and triggered by apoptotic cells. These results indicate that ACK1 and BRK kinases activity are required for the immunologically silent clearance of apoptotic cells by macrophages and define genetic efferocytosis deficiency in a subset of SLE patients who may benefit from personalized therapy in the future
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Masdeu, Camara Maria del Mar. "Papel de la tirosina quinasa Ack1 en la neuritogénesis y señalización regulada por neurotrofinas y moléculas de guía axonal." Doctoral thesis, Universitat de Barcelona, 2014. http://hdl.handle.net/10803/145719.
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Ack1 es una proteína tirosina quinasa citoplasmática que pertenece a la familia de proteínas Ack que está formada por 9 miembros. Ack1 está compuesta por varios dominios de interacción proteína-proteína y un dominio catalítico tirosina quinasa cuya autofosforilación regula parcialmente la función de la proteína (Lougheed et al., 2004). Ack1 se encuentra altamente expresada en cerebro (Urena et al., 2005; La Torre et al., 2006), principalmente en las zonas del hipocampo, corteza cerebral, bulbo olfativo y cerebelo (Urena et al., 2005). Además, se ha demostrado que Ack1 se localiza tanto en dendritas como en regiones presinápticas y su expresión se regula a la alza por un incremento de actividad neuronal (Urena et al., 2005).
Las funciones fisiológicas de Ack1 son bastante desconocidas. En conjunto, los datos publicados hasta la actualidad destacan la capacidad de la proteína Ack1 para interaccionar con una gran variedad de proteínas, que indica que Ack1 puede participar en diferentes rutas de transducción de señales, y por tanto, participar en diferentes procesos fisiológicos de las células. Por ejemplo, se ha descrito que puede participar en la regulación del citoesqueleto de actina (Burbelo et al., 1995), en los procesos de endocitosis (Teo et al., 2001), en las cascadas de señalización que resultan de la adhesión celular (Bourdoulous et al., 1998), en la migración celular (Modzelewska et al., 2006), en la proliferación (Nur et al., 2005) y en la supervivencia (Mahajan et al., 2005).
La mayoría de funciones de Ack1 conocidas se deducen de las interacciones moleculares de ésta y hasta la actualidad se dispone de muy pocos datos respecto a las competencias biológicas de esta proteína, especialmente a nivel de SNC. Por eso, en esta tesis hemos intentado determinar el papel de la tirosina quinasa Ack1 en las funciones del SNC mediante 5 capítulos de resultados.
En el capítulo I explicamos la producción de un anticuerpo monoclonal contra Ack1 que produjimos con el objetivo de poder estudiar la proteína Ack1 a nivel funcional. Este anticuerpo lo produjimos contra la región rica en prolinas de Ack1 con el fin que nos permitiera aumentar la especificidad de nuestros experimentos.
En el capítulo II caracterizamos la proteína Ack1 a nivel más funcional. Demostramos que Ack1 es un componente de la vía de señalización de las neurotrofinas, siendo fosforilada en respuesta a neurotrofinas e interaccionando con sus receptores Trk. Además, también describimos que cambios de expresión de Ack1 alteran la neuritogénesis en células PC12 y los patrones de ramificación axonal y dendrítico en neuronas de hipocampo y células granulares de cerebelo.
En el capítulo III examinamos la interacción de Ack1 con las proteínas de la densidad postsináptica CaMKII y PSD-95, su fosforilación en respuesta a los estímulos excitadores NMDA y glutamato, y la afectación de los botones axonales de las ramas colaterales de Schaffer por una falta de expresión de Ack1. Los resultados obtenidos en este capítulo apuntan a una posible implicación de Ack1 a nivel de terminales sinápticos.
En el capítulo IV nos centramos en estudiar la interacción de Ack1 con la proteína FAK y su participación en procesos de quimioatracción mediados por Netrina-1. Los datos obtenidos sugieren una interacción entre ambas proteínas, que Ack1 se fosforila en respuesta a Netrina-1 y una implicación de la proteína Ack1 en los procesos de quimioatracción mediados por Netrina-1 en células de hipocampo.
Finalmente, siendo las proteínas Ack1 y FAK unas proteínas que dependen de su estado de fosforilación para regular su actividad, en el capítulo V de resultados de esta tesis estudiamos las dianas de fosforilación y posibles proteínas de interacción de ambas proteínas, mediante la técnica de espectrometría de masas en muestras de cerebro de ratón en desarrollo, de cerebro de ratón adulto y de cerebro de ratón adulto hiperestimulado.
- Bibliografía
Bourdoulous S, Orend G, MacKenna DA, Pasqualini R, Ruoslahti E (1998) Fibronectin matrix regulates activation of RHO and CDC42 GTPases and cell cycle progression. The Journal of cell biology 143:267-276.
Burbelo PD, Drechsel D, Hall A (1995) A conserved binding motif defines numerous candidate target proteins for both Cdc42 and Rac GTPases. The Journal of biological chemistry 270:29071-29074.
La Torre A, del Rio JA, Soriano E, Urena JM (2006) Expression pattern of ACK1 tyrosine kinase during brain development in the mouse. Gene Expr Patterns 6:886-892.
Lougheed JC, Chen RH, Mak P, Stout TJ (2004) Crystal structures of the phosphorylated and unphosphorylated kinase domains of the Cdc42-associated tyrosine kinase ACK1. The Journal of biological chemistry 279:44039-44045.
Mahajan NP, Whang YE, Mohler JL, Earp HS (2005) Activated tyrosine kinase Ack1 promotes prostate tumorigenesis: role of Ack1 in polyubiquitination of tumor suppressor Wwox. Cancer research 65:10514-10523.
Modzelewska K, Newman LP, Desai R, Keely PJ (2006) Ack1 mediates Cdc42-dependent cell migration and signaling to p130Cas. The Journal of biological chemistry 281:37527-37535.
Nur EKA, Zhang A, Keenan SM, Wang XI, Seraj J, Satoh T, Meiners S, Welsh WJ (2005) Requirement of activated Cdc42-associated kinase for survival of v-Ras-transformed mammalian cells. Mol Cancer Res 3:297-305.
Teo M, Tan L, Lim L, Manser E (2001) The tyrosine kinase ACK1 associates with clathrin-coated vesicles through a binding motif shared by arrestin and other adaptors. The Journal of biological chemistry 276:18392-18398.
Urena JM, La Torre A, Martinez A, Lowenstein E, Franco N, Winsky-Sommerer R, Fontana X, Casaroli-Marano R, Ibanez-Sabio MA, Pascual M, Del Rio JA, de Lecea L, Soriano E (2005) Expression, synaptic localization, and developmental regulation of Ack1/Pyk1, a cytoplasmic tyrosine kinase highly expressed in the developing and adult brain. The Journal of comparative neurology 490:119-132.Ack1 is a cytoplasmic tyrosine kinase highly expressed in Central Nervous System (Urena et al., 2005; La Torre et al., 2006) that has several protein-protein interaction domains and a catalytic domain that is autophosphorylated, and this process regulates, at least in part, the action of this protein (Lougheed et al., 2004). Moreover, it has been demonstrated that Ack1 is localized in dendrites and presynaptic regions and that its expression is up-regulated by an increase of neuronal activity (Urena et al., 2005). Most of the known functions of Ack1 have been elucidated from interactions of Ack1 with several proteins. But, most of the physiologically functions of Ack1 remain to be described, especially in CNS. For this reason, the aim of this thesis has been to unravel some of these functions on CNS that are described through 5 chapters. In the 1st chapter we have explained the production of a monoclonal antibody against Ack1 that allowed us to improve the specificity of our experiments and to study Ack1 at a functional level. In the 2nd chapter we have demonstrated that Ack1 is a component of the neurotrophin pathway, because it is phosphorylated as a response to neurotrophins and interacts with Trk receptors. Moreover, we also have described how changes in Ack1 expression alter neuritogenesis and axonal and dendritic ramification. In the 3th chapter we have analyzed the interaction of Ack1 with the postsynaptical proteins CaMKII and PSD-95, its phosphorylation in response to excitatory stimulus such as NMDA or glutamate and we have described that a lack of Ack1 expression decrease the size of axonal buttons. These data suggest an implication of Ack1 at a synaptic level. In the 4th chapter we focused on the determination of the interaction of Ack1 and FAK, the Ack1 phosphorylation in response to Netrin-1 and the effect of Ack1 in chemoattraction regulated by Netrin-1. Finally, in the 5th chapter we studied the phosphorylation sites and the possible interacting proteins of FAK and Ack1 by mass spectrometry in samples of mice brain in development, of adult mice brain and of adult mice overstimulated brain. - Bibliography La Torre A, del Rio JA, Soriano E, Urena JM (2006) Expression pattern of ACK1 tyrosine kinase during brain development in the mouse. Gene Expr Patterns 6:886-892. Lougheed JC, Chen RH, Mak P, Stout TJ (2004) Crystal structures of the phosphorylated and unphosphorylated kinase domains of the Cdc42-associated tyrosine kinase ACK1. The Journal of biological chemistry 279:44039-44045. Urena JM, La Torre A, Martinez A, Lowenstein E, Franco N, Winsky-Sommerer R, Fontana X, Casaroli-Marano R, Ibanez-Sabio MA, Pascual M, Del Rio JA, de Lecea L, Soriano E (2005) Expression, synaptic localization, and developmental regulation of Ack1/Pyk1, a cytoplasmic tyrosine kinase highly expressed in the developing and adult brain. The Journal of comparative neurology 490:119-132.
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Vangadasalam, Sandra. "Physical and functional interaction between DOM-B and ACF1." Diss., lmu, 2011. http://nbn-resolving.de/urn:nbn:de:bvb:19-140100.
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Thorne, Nicholas James. "Firmware and gateway for the ACE1 reconfigurable accelerator card." Master's thesis, University of Cape Town, 2011. http://hdl.handle.net/11427/10926.
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This thesis describes the continued work on the in-house designed FPGA based co-processor daughtercard referred to as ACE1. The aim: to create an ecosystem incorporating firmware, bootstrapping code, drivers and a development environment to create a seamless environment. Challenges in setting up and debugging the interface that connects the coprocessor daughtercard to the host server include: problems with the power network, the edge connectors and timing problems with the primary protocol which prevented host-based communications. The options include allowing the daughtercard to function in a stand-alone fashion and we present a gateware solution that allows users to select from a number of alternatives for each of the layers in the Open Systems Interconnect networking model.
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Dial, John Michael Borchers Christoph H. "Inhibition of the Cdh1-dependent anaphase-promoting complex by Acm1." Chapel Hill, N.C. : University of North Carolina at Chapel Hill, 2007. http://dc.lib.unc.edu/u?/etd,967.
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Thesis (Ph. D.)--University of North Carolina at Chapel Hill, 2007.Title from electronic title page (viewed Dec. 18, 2007). "... in partial fulfillment of the requirements for the degree of Doctor of Philosophy in the Department of Biochemistry & Biophysics." Discipline: Biochemistry and Biophysics; Department/School: Medicine.
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Acke, Fabian [Verfasser], Wolf-Dieter [Akademischer Betreuer] Fessner, and Felix [Akademischer Betreuer] Hausch. "Entwicklung promiskuitiver Aldolasen / Fabian Acke ; Wolf-Dieter Fessner, Felix Hausch." Darmstadt : Universitäts- und Landesbibliothek Darmstadt, 2020. http://d-nb.info/1218692340/34.
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Nicholl, Sarah. "Characterisation of AAE7/ACN1 and aconitase isoforms from Arabidopsis thaliana." Thesis, Bangor University, 2011. http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.536471.
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Hong, Lingzi. "Act1-Mediated RNA Metabolism in IL-17-Driven Inflammatory Diseases." Case Western Reserve University School of Graduate Studies / OhioLINK, 2021. http://rave.ohiolink.edu/etdc/view?acc_num=case162673878106271.
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Acke, Fabian Verfasser], Wolf-Dieter [Akademischer Betreuer] Fessner, and Felix [Akademischer Betreuer] [Hausch. "Entwicklung promiskuitiver Aldolasen / Fabian Acke ; Wolf-Dieter Fessner, Felix Hausch." Darmstadt : Universitäts- und Landesbibliothek Darmstadt, 2020. http://nbn-resolving.de/urn:nbn:de:tuda-tuprints-118212.
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Swaidani, Shadi. "THE ROLE OF ACT1 IN IL-25 DEPENDENT TH2 RESPONSES AND ALLERGIC AIRWAY INFLAMMATION AND AIRWAY HYPERRESPONSIVENESS." Case Western Reserve University School of Graduate Studies / OhioLINK, 2010. http://rave.ohiolink.edu/etdc/view?acc_num=case1270240862.
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Kullgren, Carina. "Ack Värmeland regionalitet i diskurs och praktik /." Göteborg : Etnologiska institutionen, Göteborgs universitet, 2000. http://catalog.hathitrust.org/api/volumes/oclc/45065007.html.
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Elliot-Smith, Andrea Elizabeth. "Biochemical studies of the Cdc42-ACK interaction." Thesis, University of Cambridge, 2004. http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.615807.
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Fudal, Isabelle. "Etude du gène d'avirulence ACE1 de Magnaporthe grisea, agent pathogène du riz : analyse de l'expression du gène ACE1 et évolution dans les populations de Magnaporthe grisea." Paris 11, 2004. http://www.theses.fr/2004PA112008.
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Les isolats de Magnaporthe grisea possédant le gène d'avirulence ACE1 sont spécifiquement reconnus par les variétés de riz possédant le gène de résistance Pi33. ACE1 code pour une enzyme du métabolisme secondaire (un hybride polycétide synthase/peptide synthétase). L'activité enzymatique d'Ace1 étant nécessaire à l'avirulence, le signal reconnu par les plantes résistantes possédant Pi33 pourrait être le métabolite secondaire dont la biosynthèse dépend d'Ace1. ACE1 est exclusivement exprimé dans les appressoria pendant l'étape de pénétration, aussi bien sur plante que sur certaines membranes artificielles. Aucune expression n'a été détectée dans les appressoria du mutant déficient en mélanine bufl, incapable de développer une pression appressoriale. L'ajout de solutions osmotiques sur des appressoria de bufl rétablit l'expression d'ACE1. Nos résultats suggèrent que l'expression d'ACE1 est dépendante d'un stade de développement atteint juste avant la pénétration et de la pression appressoriale. Des délétions du promoteur d'ACE1 ont révélé une région de 200 bp nécessaire à la transcription dans l' appressorium. L'analyse de l'allèle ACE1 dans le descendant virulent 2/0/3 a révélé l'insertion d'un nouveau retroposon (MINE) dans la POL d'ACE1. La majorité des isolats récoltés dans le monde sont avirulents pour Pi33 et possèdent tous le même allèle ACE1 (ACE1-GUY11. 1). Les isolats virulents ont été majoritairement trouvés en Asie et Amérique du Sud, son génétiquement liés et peuvent être classés en trois groupes en fonction de leur génotype ACE1. Un groupe possède l'allèle virulent (ACE1-GUY11. 2) qui présente 99 % d'identité avec ACEl-GUY11. 1. Le deuxième groupe possède l'allèle virulent (ACE1-CM28) qui présente 88 % d'identité avec ACE1-GUY11. 1. Le troisième groupe possède les allèles virulents ACEl-GUYll. 2 et ACEl-CM28. Ces allèles sont localisés sur des chromosomes différents, indiquant que ces isolats normalement haploi͏̈des sont partiellement diploi͏̈des au locus ACElIsolates of the rice blast fungus Magnaporthe grisea that carry the avirulence gene ACE1 are specifically recognized by rice cultivars carrying the resistance gene Pi33. ACE1 encodes an enzyme of the secondary metabolism (a hybrid polyketide synthase/non-ribosomal peptide synthase). Since Acel enzymatic activity is required for avirulence, the signal recognized by rice cultivars carrying Pi33 should be a secondary metabolite. ACE1 is expressed exclusively in appressoria during the penetration process, either on plant or artificial surfaces. ACE1 was not expressed in appressoria differentiated on Mylar or in appressoria from the melanin-deficient mutant bufl, unable to build up appresorial turgor. Addition of hyper-osmotic solutions to bufl appressoria restored ACE1 expression. Our results suggest that ACE1 expression requires an appressorial developmental stage reached before penetration and turgor. Deletion analysis of ACE1 promoter revealed a 200-bp region required for appressorium specific transcription. Characterization of ACE1 structure in the virulent progeny 2/0/3 revealed an insertion of a new retroposon (MINE) into ACE1 ORF. Most worldwide M grisea isolates were avirulent towards Pi33 and carried the same ACE1 avirulent allele (ACE1-GY11. 1). Isolates virulent towards Pi33 were mostly detected in Asia and South America and classified into three groups according to their ACE1 genotypes. The first group has a virulent allele (ACE1-GY11. 2) that is 99% identical to ACEl-GY11. 1. The second group has a virulent allele (ACE1-CM28) that is 88% identical to ACE1-GY11. 1. The third group has two virulent ACE1 alleles (ACE1-GY11. 1 and ACE1-CM28). These two alleles are localized on different chromosomes, indicating that these normally haploid isolates are partially diploid for ACE1. Typing of isolates from these groups using neutral markers (micro-satellites, SNIPS) revealed that they are genetically related, suggesting that they derive from a single complex event
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Velichko, Sharlene, Xu Zhou, Lingxiang Zhu, Johnathon David Anderson, Reen Wu, and Yin Chen. "A Novel Nuclear Function for the Interleukin-17 Signaling Adaptor Protein Act1." PUBLIC LIBRARY SCIENCE, 2016. http://hdl.handle.net/10150/621947.
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In the context of the human airway, interleukin-17A (IL-17A) signaling is associated with severe inflammation, as well as protection against pathogenic infection, particularly at mucosal surfaces such as the airway. The intracellular molecule Act1 has been demonstrated to be an essential mediator of IL-17A signaling. In the cytoplasm, it serves as an adaptor protein, binding to both the intracellular domain of the IL-17 receptor as well as members of the canonical nuclear factor kappa B (NF-kappa B) pathway. It also has enzymatic activity, and serves as an E3 ubiquitin ligase. In the context of airway epithelial cells, we demonstrate for the first time that Act1 is also present in the nucleus, especially after IL-17A stimulation. Ectopic Act1 expression can also increase the nuclear localization of Act1. Act1 can up-regulate the expression and promoter activity of a subset of IL-17A target genes in the absence of IL-17A signaling in a manner that is dependent on its N- and C-terminal domains, but is NF-kappa B independent. Finally, we show that nuclear Act1 can bind to both distal and proximal promoter regions of DEFB4, one of the IL-17A responsive genes. This transcriptional regulatory activity represents a novel function for Act1. Taken together, this is the first report to describe a non-adaptor function of Act1 by directly binding to the promoter region of IL-17A responsive genes and directly regulate their transcription.
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Valentine, Lisa Gallagher. "Molecular characterisation and regulation of acyl-CoA oxidase 1 (ACX1) in Arabidopsis thaliana." Thesis, University of Glasgow, 2001. http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.394810.
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Wu, Ling. "A HYPER TH17 RESPONSE CONNECTS THE PSORIASIS-ASSOCIATED ACT1 VARIANT TO SKIN INFLAMMATION." Case Western Reserve University School of Graduate Studies / OhioLINK, 2015. http://rave.ohiolink.edu/etdc/view?acc_num=case1409866338.
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Benatti, Luciana Benjamim 1978. "Atributos bioquímicos e fisiológicos de AC1 : um cafeeiro naturalmente descafeinado." [s.n.], 2012. http://repositorio.unicamp.br/jspui/handle/REPOSIP/315471.
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Orientador: Paulo MazzaferaTese (doutorado) - Universidade Estadual de Campinas, Instituto de Biologia
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Resumo: Em 2004, Silvarolla e colaboradores descobriram três plantas (AC1, AC2 e AC3) de Coffea arabica, provenientes da Etiópia, com baixa quantidade de cafeína nas sementes. Esta pequena concentração (0,76 mg/g) em AC1, quando comparada com grãos de C. arabica com cafeína (em torno de 12 mg/g), foi verificada ser de origem constitutiva da planta, sendo esta denominada como naturalmente descafeinada. Neste trabalho a planta de AC1 foi estudada, já que esta é a mais adequada para a transferência genética do traço "sem cafeína" para cultivares com alta produtividade. Ao analisar o desenvolvimento das sementes de AC1, foi observado que endospermas maduros da planta com baixas quantidades de cafeína perderam menos massa do que os de Mundo Novo (MN) e que estes, no final do desenvolvimento, eram maiores do que os de AC1. Entretanto, apesar deste fato, os conteúdos de aminoácidos, açúcares solúveis, ácidos orgânicos, ácidos clorogênicos e trigonelina foram similares nas sementes de frutos de MN e AC1. Foi constatado que em todos os estádios fenológicos as sementes de AC1 apresentaram baixas quantidades de cafeína. Além disso, foi observado que não só sementes e folhas apresentaram esta característica, mas também flores e internódios. Experimentos com o fornecimento de [2-14C] adenina e análises enzimáticas de teobromina sintase e cafeína sintase nas sementes de AC1 confirmaram que, assim como em folhas, a síntese de cafeína é bloqueada na metilação de teobromina a cafeína, acumulando altas taxas de teobromina. Experimentos de análise de expressão gênica indicaram que, apesar dos genes responsáveis pela síntese das três metiltransferases envolvidas na síntese de cafeína ser expressos nos endospermas de AC1, suas expressões são menores se comparadas com o controle MN, principalmente ao analisar a expressão do gene CCS1, que codifica para a cafeína sintase. Os compostos fenólicos apresentaram valores próximos ao longo de todo o desenvolvimento do endosperma, sendo que a quantidade equivalente encontrada nestes grãos parcialmente explica a atividade antioxidante similar encontrada nos grãos maduros de MN e AC1. Análises de proteínas de reserva em endospermas maduros foram similares em MN e AC1
Abstract: In 2004, Silvarolla and co-workers discovery three plants (AC1, AC2 and AC3) of Coffea arabica, originated from Ethiopia, with low amount of caffeine in the seeds. This low concentration (0,76 mg/g) was found to be constitutive plant origin, this being referred to as naturally decaffeinate. In this work only the seeds of AC1 were studied, since this plant has shown to be the most suitable for gene transfer trace "without caffeine" for cultivars with high productivity. By analyzing the development of the seed AC1, it was observed that the mature endosperm of the plant with low amounts of caffeine lost less weight than those of MN, and also at the end of development, they were greater than those of AC1. However, despite this fact, the contents of amino acids, organic acids, chlorogenic acids and trigonelline were similar to MN and AC1 seeds and fruits. Soluble sugars were also similar in most part of the development despite the sucrose in the endosperm AC1 cherry stage, having it's significantly less than the one found in the endosperm MN at the stage. It was found that in all growth stages seeds AC1 presented low amounts of caffeine. Furthermore, it was observed that not only seeds and leaves showed this characteristic, but also flowers and internodes. Experiments with the supply of [2-14C] adenine and enzymatic analyzes of theobromine synthase and caffeine synthase in AC1 seeds confirmed that as leaves, caffeine synthesis are blocked in the methylation of theobromine to caffeine, accumulating high levels of theobromine. Experiments of the gene's expression analysis indicated that, although the genes responsible for the synthesis of the three methyltransferases involved in caffeine synthesis are expressed in AC1 endosperm, presented minor expressions compared to the control MN, especially when analyzing the expression of the gene CCS1, which synthesizes caffeine synthase. Phenolic compounds had similar values throughout the development of the endosperm, the equivalent amount found in these grains partly explains the similar antioxidant activity found in the MN and AC1 mature grains. The reserve proteins assays of mature endosperms were also similar in both endosperms
Doutorado
Biologia Vegetal
Doutora em Biologia Vegetal
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THANGARAJ, ARUNA. "PERFORMANCE ANALYSIS OF PRIORITIZED TCP ACK SCHEMES IN THE IEEE 802.11e WLANs." University of Cincinnati / OhioLINK, 2007. http://rave.ohiolink.edu/etdc/view?acc_num=ucin1195571967.
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Sem, Kai-Ping. "Characterization of a Drosophila homologue of ACK (activated Cdc42-associated kinase)." Thesis, National Library of Canada = Bibliothèque nationale du Canada, 2001. http://www.collectionscanada.ca/obj/s4/f2/dsk3/ftp04/MQ61605.pdf.
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Bansal, Dushyant. "Third-Party TCP Rate Control." Thesis, University of Waterloo, 2005. http://hdl.handle.net/10012/803.
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The Transmission Control Protocol (TCP) is the dominant transport protocol in today?s Internet. The original design of TCP left congestion control open to future designers. Short of implementing changes to the TCP stack on the end-nodes themselves, Internet Service Providers have employed several techniques to be able to operate their network equipment efficiently. These techniques amount to shaping traffic to reduce cost and improve overall customer satisfaction. The method that gives maximum control when performing traffic shaping is using an inline traffic shaper. An inline traffic shaper sits in the middle of any flow, allowing packets to pass through it and, with policy-limited freedom, inspects and modifies all packets as it pleases. However, a number of practical issues such as hardware reliability or ISP policy, may prevent such a solution from being employed. For example, an ISP that does not fully trust the quality of the traffic shaper would not want such a product to be placed in-line with its equipment, as it places a significant threat to its business. What is required in such cases is third-party rate control.
Formally defined, a third-party rate controller is one that can see all traffic and inject new traffic into the network, but cannot remove or modify existing network packets. Given these restrictions, we present and study a technique to control TCP flows, namely triple-ACK duplication. The triple-ACK algorithm allows significant capabilities to a third-party traffic shaper. We provide an analytical justification for why this technique works under ideal conditions and demonstrate via simulation the bandwidth reduction achieved. When judiciously applied, the triple-ACK duplication technique produces minimal badput, while producing significant reductions in bandwidth consumption under ideal conditions. Based on a brief study, we show that our algorithm is able to selectively throttle one flow while allowing another to gain in bandwidth.
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Ho, Ka Ming. "Cross-layer design of FDD-OFDM system based on ACK/NAK feedbacks /." View abstract or full-text, 2007. http://library.ust.hk/cgi/db/thesis.pl?ECED%202007%20HO.
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Pinkoski, Nathan. "Postmodern Aristotles : Arendt, Strauss, and MacIntyre, and the recovery of political philosophy." Thesis, University of Oxford, 2017. https://ora.ox.ac.uk/objects/uuid:b4d728b9-8bb4-47e6-ac01-16dcc9f6f314.
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What is political philosophy? Aristotle pursues that question by asking what the good is. If Nietzsche's postmodern diagnosis that modern philosophical rationalism has exhausted itself is true, it is unclear if an answer to that question is possible. Yet given the prevalence of extremist ideologies in 20th century politics, and the politically irresponsible support of philosophers for these ideologies, there is an urgent need for an answer. This thesis examines how, in these philosophical circumstances, Hannah Arendt, Leo Strauss, and Alasdair MacIntyre conclude that a key resource in the recovery of political philosophy, and in showing its contemporary relevance, lies in the recovery of Aristotle's political philosophy. This thesis contends that how and why Arendt, Strauss, and MacIntyre turn to Aristotle, and what they find in Aristotle, depends on their varying critiques of modernity. Convinced that the philosophical tradition is shattered irreversibly after the events of totalitarianism, Arendt argues for a retrieval of Aristotle and his understanding of politics from the fragments of that tradition. Strauss is impelled to turn to the political philosophy of Aristotle because of the crisis of radical historicism, to recover classical rationalismâs answer to what the good is. MacIntyre turns to Aristotle to find the moral justification for rejecting Stalinism that contemporary philosophical traditions fail to provide; he reconstructs an Aristotelian tradition that can answer the question of what the good is better than his contemporary rivals. Although these thinkers may appear disparate, this thesis argues that each addresses the question of what the good is by offering a vision of political philosophy as a way of life, which Aristotle helps form. This way of life probes the relationship between philosophy and politics as permanent problem for human existence. In recovering this tradition of thinking with Aristotle about the character of political philosophy, this thesis aims to contribute to the understanding of each of these thinkers, as well as to the practice of political philosophy in modern, post-Nietzschean times.
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Gritten, Daniel John. "The profession and practice of screenwriting in British cinema, the 1920s and 1930s." Thesis, University of Bristol, 2007. http://hdl.handle.net/1983/19c45812-ac51-4daf-b5dc-a1a310b6475e.
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Ghalamkari, Hossein Hooman. "Factors affecting the extended role of the community pharmacist." Thesis, University of Bristol, 1999. http://hdl.handle.net/1983/7be8f49e-200b-40c9-ac81-9a137e0c8be7.
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In recent years health care personnel have seen changes to their roles and responsibilities. A number of reports both from within the occupation and from government have recommended changes in the roles of community pharmacists so that they become more active in the provision of health care. The new roles and services suggested have become known as "extended roles" and include health promotion, treatment of minor ailments, provision of advice on prescribed medicines to the public and to other health care personnel. The aim of this study was to investigate the factors affecting the extended roles of the community pharmacist. The investigation initially took an exploratory approach and used unstructured interviews with pharmacists to ascertain influences on every day practice which could have implications on implementation of extended roles. The findings from the initial qualitative stage were incorporated into a national survey of community pharmacists. A number of interrelated factors were found to be important including work practices, financial considerations, people's expectations, relationships with GPs and pharmacists' own definitions of their roles. These findings are explained in terms of the progressive division of labour in the market for the provision of health care. Recommendations are made for extending the role of the community pharmacist
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Metcalf, Sara J. "The palaeoenvironment and palaeoecology of a Middle Jurassic vertebrate-bearing fen-type paleosol in a coastal carbonate regime." Thesis, University of Bristol, 1995. http://hdl.handle.net/1983/955beb87-8c25-4857-ac91-c3451390ff62.
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Parcero, Osiris J. "The optimal country's policy to attract an MNC new production plant." Thesis, University of Bristol, 2005. http://hdl.handle.net/1983/b06d7a7b-5c4d-4c6d-aca1-7a4f98970e6c.
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Al-Yazeedi, Fatema. "Applying computer-assisted assessment to auto-generating feedback on project proposals." Thesis, Brunel University, 2016. http://bura.brunel.ac.uk/handle/2438/13626.
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Through different learning portals, computer-assisted assessment (CAA) tools have improved considerably over the past few decades. In a CAA community, these tools are categorised into types of questions, types of testing, and types of assessment. Most of these provide the assessment of multiple-choice questions, true and false questions, or matching questions. Other CAA tools evaluate short and long essay questions, each of which different grading methods and techniques in terms of style and content have. However, due to the complexity involved in analysing free text writing, the development and evaluation of accurate, easy to use, and effective tools is questionable. This research proposes a new contextual framework as a novel approach to the investigation of a new CAA tool which auto-generates feedback on project proposals. This research follows a Design Science Research paradigm to achieve and evaluate the accuracy, ease of use, and effectiveness of the new tool in the computer science domain in higher education institutes. This is achieved in three interrelated cycles:(1) based on the existent literature on this topic and an exploratory study on the currently available approaches to the provision of feedback on final year project proposals, a proposed framework to auto-generate feedback on any electronically submitted coursework is constructed in order to gain a clear understanding on how such a CAA tool might work; (2) a contextual framework based on the proposed framework for final year project proposals is constructed by considering both the style and content of the free text and using different text mining techniques; and (3) the accuracy, easy to use, and effectiveness of the implemented web-based CAA application named Feedback Automated Tool (FEAT)is evaluated based on the contextual framework. This research applies CAA and text mining techniques to identify and model the key elements of the framework and its components in order to enable the development and evaluation of a novel CAA contextual framework which can be utilised for auto-generating accurate, easy to use, and effective feedback on final year project proposals.
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Jain, Dhawal [Verfasser], and Peter B. [Akademischer Betreuer] Becker. "Effects of nucleosome remodeling factor ACF1 on in vivo chromatin organization / Dhawal Jain. Betreuer: Peter B. Becker." München : Universitätsbibliothek der Ludwig-Maximilians-Universität, 2015. http://d-nb.info/1082504742/34.
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Börner, Kenneth [Verfasser], and Peter [Akademischer Betreuer] Becker. "Roles of nucleosome remodeling factors ACF1 and Domino during Drosophila melanogaster oogenesis / Kenneth Börner ; Betreuer: Peter Becker." München : Universitätsbibliothek der Ludwig-Maximilians-Universität, 2017. http://d-nb.info/1127527789/34.
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Francis, Breeson. "Enhancing TCP Congestion Control for Improved Performance in Wireless Networks." Thèse, Université d'Ottawa / University of Ottawa, 2012. http://hdl.handle.net/10393/23254.
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Transmission Control Protocol (TCP) designed to deliver seamless and reliable end-to-end data transfer across unreliable networks works impeccably well in wired environment. In fact, TCP carries the around 90% of Internet traffic, so performance of Internet is largely based on the performance of TCP. However, end-to-end throughput in TCP degrades notably when operated in wireless networks. In wireless networks, due to high bit error rate and changing level of congestion, retransmission timeouts for packets lost in transmission is unavoidable. TCP misinterprets these random packet losses, due to the unpredictable nature of wireless environment, and the subsequent packet reordering as congestion and invokes congestion control by triggering fast retransmission and fast recovery, leading to underutilization of the network resources and affecting TCP performance critically. This thesis reviews existing approaches, details two proposed systems for better handling in networks with random loss and delay. Evaluation of the proposed systems is conducted using OPNET simulator by comparing against standard TCP variants and with varying number of hops.
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Farooq, Muhammad Ali. "Iron Citrate Toxicity Causes aco1Δ-induced mtDNA Loss in Saccharomyces cerevisiae." ScholarWorks@UNO, 2013. http://scholarworks.uno.edu/honors_theses/34.
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Aconitase is an enzyme of the Krebs cycle that catalyzes the isomerization of citrate to isocitrate. In addition to its enzymatic activity, Aco1 has been reported to bind to mitochondrial DNA (mtDNA) and mediate its maintenance in the budding yeast S. cerevisiae. In the absence of Aco1, cells rapidly lose mtDNA and become “petite” mutants. The purpose of this study is to uncover the mechanism behind mtDNA loss due to an aco1 deletion mutation. We found that an aco1 mutation activates the mitochondria-to-nucleus retrograde (RTG) signaling pathway, resulting in increased expression of citrate synthases (CIT) through the activation of two transcription factors Rtg1 and Rtg3. Increased activity of CIT leads to increased iron accumulation in cells, which is known to raise reactive oxygen species (ROS). By deleting RTG1, RTG3, genes encoding citrate synthases, orMRS3 and MRS4, encoding two irontransporters in the mitochondrial inner membranes, mtDNA loss can be prevented in aco1 deletion mutant cells. We further show that the loss of SOD1, encoding the cytoplasmic isoform of superoxide dismutase, but not SOD2, encoding the mitochondrial isoform of superoxide dismutase, prevents mtDNA loss in aco1 mutant cells. Altogether, our data suggest that mtDNA loss in aco1 mutant cells is caused by the activation of the RTG pathway and subsequent iron accumulation and toxicity in the mitochondria.
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Berruyer, Romain Paul Emile. "Etude des interactions riz-Magnaporthe grisea : Caractérisation et clonage du gène de résistance Pi33." Montpellier, ENSA, 2003. http://www.theses.fr/2003ENSA0003.
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La résistance des plantes aux agents pathogènes suit souvent la théorie gène-pour-gène. Contrairement aux autres gènes d'avirulence, le gène ACE1 de Magnaporthe grisea (responsable de la pyruculariose du riz) code pour une grosse protéine qui n'est pas sécrétée. Au cours de cette thèse, le gène de résistance correspondant à ACE1 a été cartographié sur le bras court du chromosome 8 à l'aide de couples de souches isogéniques. Ce gène de resistance dominant est différent de ceux déjà connus. Il a été nommé Pi33 puis finement cartographié en utilisant une population de 889 lignées et des marqueurs moléculaires. Une cartographie physique a été réalisée sur deux banque BAC, l'une, ordonnée, de la variété Nipponbare (sensible) l'autre, non ordonnée, de la variété IR64 (résistante). L'étude des séquences disponibles dans la zone n'a permis de détecter aucun homologue de gènes de résistance connus. Enfin, le polymorphisme autour de Pi33 et son origine parmi les parents d’IR64 ont été étudiésWe identified the resistance gene corresponding to the avirulence gene ACE1 using pairs of isogenic strains of Magnaporthe grisea differing only by their ACEl allele. This resistance gene was mapped on the rice chromosome 8. Allelism tests permitted us to distinguish this gene from other known resistance genes. This single dominant gene was designated as Pi33. Finally, Pi33 was finely mapped between two molecular markers that are separated by a distance of 1. 6 cM. Using this fine map, we physically mapped Pi33 using the ordered BAC library of the cultivar Nipponbare (susceptible). We then used the markers found during this walk to physically map Pi33 in the IR64 (resistant) unordered BAC library. No resistance gene homologues (RGA) were found in the available sequence data in the area of Pi33. Finally, we studied the polymorphism around Pi33 and the origin of this gene amongst the parents of the IR64 cultivar. Pi33 is probably an ancestral gene that appeared before rice domestication
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Hartupee, Justin Curtis. "Regulation of mRNA Stability in Chemokine Gene Expression." Case Western Reserve University School of Graduate Studies / OhioLINK, 2008. http://rave.ohiolink.edu/etdc/view?acc_num=case1212426414.
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Dudek, Débora Nakadomari. "Deleção parcial do fator de transcrição ACE1 para otimização da produção de celulases por trichoderma reesei RUT-C30." Universidade Estadual do Oeste do Paraná, 2017. http://tede.unioeste.br/handle/tede/2954.
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Coordenação de Aperfeiçoamento de Pessoal de Nível Superior - CAPES
Second generation bioethanol employs lignocellulosic materials in its preparation. One of the steps for these materials degradation utilizes cellulases produced by microorganisms. Among these, Trichoderma reesei fungus is one of the main cellulases producers used in industry. This fungus genetic modification can lead to enzimes production optimization, reducing cost and improving biofuels manufacture. Thus, the present work objective was delete the sequence encoding zinc fingers motifs of cellulase ACE1repressor transcription factor from T. reesei RUT-C30 fungus, seeking enzymatic production optimization. In primers construction for amplification ACE1 regions 5’ and 3' and the hph selection marker, which confers hygromycin B resistance, Joint Genome Institute - JGI site and the BioEdit ® program were used. The deletion cassette with pRS426 vector construction was mediated by Saccharomyces cerevisiae SC9721 yeast. After the cassette construction, T. reesei RUT-C30 transformation was made by protoplast and this transformation confirmation was effected by part of the hph using hphNestF and hphNestR amplification primers. After transformation with mutants obtained, endoglucanase, exoglucanase and total cellulase activity was quantified with carboxymethylcellulose substrates (CMC), microcrystalline cellulose (Avicel®) and Whatman paper filter (PF), respectively. The enzymatic production and biomass hydrolysis efficiency were performed comparing RUT-C30 strain for mutants. After deletion cassette construction, a 3501 bp fragment amplification confirmed the cassette formation. Posteriorly, RUT-C30 strain transformation, a 989 bp amplification was observed, confirming the 3 mutants target sequence deletion. With cellulase activity assay, 3 transformed strain showed higher enzymatic production when compared to RUT-C30 strain. In this comparison, a significant statistical difference was observed of RUT-C30Δace1-1 strain with Avicel® and PF (p <0.001) CMC (p <0.01), RUT-C30Δace1-2 strain with CMC (p<0,01) e PF (p<0,05), and RUT-C30Δace1-3 strain with Avicel (p<0,001), CMC and PF (p<0,01). The mutants also showed greater efficiency in biomass hydrolysis, with release sugar increase between 21 and 42%. Based on this study, mutants are promising for most efficient and viable ethanol production. Nevertheless, additional tests must be carried out to better understand these fungi applicability in the industrial level.
O bioetanol de segunda geração emprega materiais lignocelulósicos na sua elaboração. Uma das etapas para a degradação destes materiais utiliza celulases produzidas por microrganismos. Dentre estes, o fungo Trichoderma reesei é um dos principais produtores de celulases utilizadas na indústria. A modificação genética deste fungo pode levar à otimização da produção de suas enzimas, diminuindo o custo e melhorando a fabricação de biocombustíveis. Desta forma, o objetivo do trabalho foi deletar a região dos motivos dedos de zinco no gene que codifica o fator de transcrição repressor de celulase ACE1 do fungo T. reesei RUT-C30, buscando a otimização na produção enzimática. Na construção dos primers para amplificação das regiões 5’ e 3’ de ace1 e do marcador de seleção hph, que confere resistência à higromicina B, utilizou-se o site Joint Genome Institute – JGI e o programa BioEdit®. A construção do cassete de deleção com o vetor pRS426 foi mediado pela levedura Saccharomyces cerevisiae SC9721. Posteriormente, a construção do cassete, a transformação de T. reesei RUT-C30 foi realizada através de protoplasto e a confirmação desta transformação foi efetuada por amplificação de parte do hph utilizando os primers hphNestF e hphNestR. Após a transformação, com os mutantes obtidos, a atividade de endoglucanase, exoglucanase e celulase total foi quantificada com os substratos carboximetilcelulose (CMC), celulose microcristalina (Avicel®) e papel de filtro Whatman (PF), respectivamente. A produção enzimática e a eficiência na hidrólise da biomassa foram realizadas comparando-se a linhagem RUT-C30 aos mutantes. Após a construção do cassete de deleção, a amplificação de um fragmento de 3501 pb confirmou a formação do cassete. E, posteriormente à transformação da linhagem RUT-C30, o amplificado de 989 pb foi observado, confirmando a deleção da sequência alvo em 3 mutantes. Com o ensaio de atividade de celulases, as 3 linhagens transformadas mostraram maior produção enzimática quando comparadas à linhagem RUT-C30. Nessa comparação, foi observada diferença estatística significativa da linhagem RUT-C30Δace1-1 com Avicel® e PF (p<0,001), da linhagem RUTC30Δace1- 2 com CMC (p<0,01) e PF (p<0,05) e da linhagem RUT-C30Δace1-3 com Avicel (p<0,001), CMC e PF (p<0,01). Os mutantes também apresentaram maior eficiência na hidrólise da biomassa, com aumento na liberação de açúcar entre 21 e 42%. Com base nos dados deste estudo, os mutantes apresentam-se promissores para a produção mais eficiente e viável de etanol. Apesar disso, testes adicionais devem ser realizados para melhor entendimento da aplicabilidade destes fungos a nível industrial.
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Pellnor, Joachim. "Ack Värmland, du värdefulla kulturmiljö! : -Natur- och kulturmiljöers uppkomst och användning i Värmlands län." Thesis, Uppsala universitet, Institutionen för ABM, 2015. http://urn.kb.se/resolve?urn=urn:nbn:se:uu:diva-254179.
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Kulturhistoriska platser har allt mer börjat benämnas som kulturmiljöer, vilket är hela områden som har påverkats av människan på ett eller annat sätt. I dessa områden fanns andra värderingar än endast det kulturhistoriska, oftast formulerade som hållbarhet och utveckling. Båda dessa begrepp är grundpelare i uppsatsens teoretiska utgångspunkt, resiliensteorin. Resiliensteorin är en förgrening till systemteori, i vilken samhället ses som en helhet. Enligt resiliensteorin är samhället likt ett socio-ekologiskt system uppbyggt av flera variabler i samhället, dessa variabler är; sociala, politiska, miljömässiga och ekonomiska. Dessa variabler består i sin tur av flera variabler som bygger upp deras helhet. Variablerna har olika tröskelvärden, det vill säga hur mycket en variabler klara av olika former av påfrestning innan systemet delvis förändras eller förstörs. Kulturmiljön är en av variablerna som bygger upp samhället. I uppsatsen undersöks vad som händer med kulturmiljöer när de definieras som variabler inom resiliensteorin, vilken roll de är tänkt att fylla på en beslutsmässig nivå; från internationell nivå till regional nivå. Frågeställningarna är: Varför ser dagens kulturarbete kring natur- och kulturmiljön ut som den gör idag? Vilka aktörer finns och förvänts finnas i anknytning till kulturmiljön? Vilka är resonemangen kring värdefulla kulturmiljöer? Vägs alla resiliensteoretiska aspekter i kulturmiljön lika tungt i beslutsprocesser och användningen av den? Källmaterialet i uppsatsen är från forskning kring kulturlandskapet och resiliens-forskning, med olika undersökningar och publikationer som grund. För undersökning kring de beslutsfattande leden har olika propositioner, motioner, FOU-publikationer från staten samt publikationer från Länsstyrelsen i Värmlands län undersökts. Undersökningsmetoden har varit text- och diskursanalys. Undersökningen visar hur kultur- och naturmiljön skapats utefter en rad vetenskapliga och politiska diskurser. Den rådande diskursen, formad av resiliensteorin, har nu gjort det möjligt att legitimera ett sökande efter nya värden i kulturmiljön annat än det traditionella bevarandet. Vilket öppnat upp för nya värden, värderingar och bruk av kulturmiljön och potentiellt förändra rollen av kulturarv i samhället. I en rådande majoritet av framtidsplanerna kring kulturmiljöer i Värmlands län är detta bruk ekonomiskt och besöksnärings bejakande.
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White, M. D. "Cycles in edge-coloured graphs and subgraphs of random graphs." Thesis, University of Oxford, 2011. http://ora.ox.ac.uk/objects/uuid:95ef351e-acb1-442c-adf5-970487e30a4d.
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This thesis will study a variety of problems in graph theory. Initially, the focus will be on finding minimal degree conditions which guarantee the existence of various subgraphs. These subgraphs will all be formed of cycles, and this area of work will fall broadly into two main categories. First to be considered are cycles in edge-coloured graphs and, in particular, two questions of Li, Nikiforov and Schelp. It will be shown that a 2-edge-coloured graph with minimal degree at least 3n/4 either is isomorphic to the complete 4-partite graph with classes of order n/4, or contains monochromatic cycles of all lengths between 4 and n/2 (rounded up). This answers a conjecture of Li, Nikiforov and Schelp. Attention will then turn to the length of the longest monochromatic cycle in a 2-edge-coloured graph with minimal degree at least cn. In particular, a lower bound for this quantity will be proved which is asymptotically best possible. The next chapter of the thesis then shows that a hamiltonian graph with minimal degree at least (5-sqrt7)n/6 contains a 2-factor with two components. The thesis then concludes with a chapter about X_H, which is the number of copies of a graph H in the random graph G(n,p). In particular, it will be shown that, for a connected graph H, the value of X_H modulo k is approximately uniformly distributed, provided that k is not too large a function of n.
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Lyon, P. C. "Targeted release from lyso-thermosensitive liposomal doxorubicin (ThermoDox®) using focused ultrasound in patients with liver tumours." Thesis, University of Oxford, 2016. https://ora.ox.ac.uk/objects/uuid:4817361a-e7f8-4773-ac81-8445ace05301.
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Simmons, David Edward. "On the performance of constrained amplify-and-forward networks." Thesis, University of Oxford, 2016. https://ora.ox.ac.uk/objects/uuid:788cdfdd-8a80-4223-ace1-37b6a8095fd7.
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This thesis examines the effects of resource constraints on amplify-and-forward (AF) networks. Chapters 3 and 4 are the first research chapters. Chapter 3 studies the outage probability performance of a two-hop two-way AF peak power constrained orthogonal frequency division multiplexing (OFDM) network. Its performance is then optimized. Chapter 4 focuses on the one-way special case of the system studied in Chapter 3. It begins with an analysis of the network when nonlinear distortion produced by signal clipping dominates the additive noise in the system. To conclude Chapter 4, the theoretical study performed throughout Chapters 3 and 4 is used to optimize the performance of a one-way real world test bed. Chapter 5 studies the n-hop multiple-input multiple-output (MIMO) AF relay network. Novel techniques are developed using random dynamical system (RDS) theory and Lyapunov exponents to establish capacity and power scaling laws for the network as n grows large. One of the main conclusions is that the average transmit power must grow at an exponential rate if capacity decay across the network is to be avoided. Chapter 6 constitutes the final research chapter. In it, the techniques used to study peak-power constrained OFDM-based networks are combined with those developed in Chapter 5, which were used to study capacity and power scaling for multihop AF networks. The conclusion of this is that incorporating OFDM into peak-power constrained multihop AF relay networks will cause the capacity along each of the network's eigenchannels to decay exponentially. Finally, we show that the effects of distortion can be circumvented by ensuring the number of antennas at each node scales at a super-linear rate with the number of hops within the network.
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Funnell, Timothy. "Characterisation of the human two-pore channels." Thesis, University of Oxford, 2011. http://ora.ox.ac.uk/objects/uuid:8c148321-5c6d-4942-ac31-3a4ca3791077.
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The Ca²⁺-mobilising messenger NAADP has been shown to play a key role in the regulation of mammalian physiology. Recently, the two-pore channels (TPCs) have been proposed as an NAADP-gated Ca²⁺ channel. Chapter 1 introduces the TPCs as the major candidates in governing NAADP-mediated Ca²⁺-release from acidic stores. Chapter 2 explains the methodologies developed and used. Chapter 3 demonstrates the successful immunopurification of HsTPC2 and its incorporation into an artificial lipid bilayer. K⁺ and Ca²⁺ currents were seen in reponse to nM - μM concentrations of NAADP; with the open probability (P₀) fitting a bell-shaped concentration-response curve. Ligand sensitivity was shown to be regulated by luminal [Ca²⁺], whereby a 20-fold increase in [Ca²⁺] lumen (10 μM to 200 μM) caused a 100-fold reduction in the EC50 from ≈ 500 nM to 5 nM. Furthermore, a reduction in luminal pH from 7.2 to 4.8 reduced the P₀ but 1 μM Ned-19 inhibiting all channel activity. Chapter 4 investigates the in situ properties of HsTPC2 by the purification and patch clamp of intact lysosomes from cells overexpressing HsTPC2. Three methods of purification were compared: differential centrifugation, whole lysosome immunoprecipitation and magnetic chromatography. Techniques involving lysosomal swelling and whole cell homogenisation were also optimised to ensure minimal contamination by non-lysosomal proteins. Whole lysosome patch clamping revealed NAADP-induced, Ca²⁺-specific currents in response to NAADP, but not cADPR, IP₃ or Ned-19. High concentrations of NAADP (mM) and Ned-19 (μM) showed prolonged ≈ 5 minutes) inhibition of channel activity. Chapter 5 explores the protein-protein interactions of the purified HsTPC2 and identifies a heterodimeric interaction between HsTPC1 and HsTPC2 was further dissected by coimmunoprecipitation, colocalisation and FRET studies. Despite clear evidence that both isoforms independently form homodimers, it is likely that heterodimerisation is a dynamic interaction only seen in a subset of the channel population. Chapter 6 discusses the results obtained in the wider context of cell physiology.
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Howard, Newton. "Approach to study the brain : towards the early detection of neurodegenerative disease." Thesis, University of Oxford, 2014. http://ora.ox.ac.uk/objects/uuid:2f81e9d4-ac91-444f-b966-ce1fc665b065.
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Neurodegeneration is a progressive loss of neuron function or structure, including death of neurons, and occurs at many different levels of neuronal circuitry. In this thesis I discuss Parkinson’s Disease (PD), the second most common neurodegenerative disease (NDD). PD is a devastating progressive NDD often with delayed diagnosis due to detection methods that depend on the appearance of visible motor symptoms. By the time cardinal symptoms manifest, 60 to 80 percent or more of the dopamine-producing cells in the substantia nigra are irreversibly lost. Although there is currently no cure, earlier detection would be highly beneficial to manage treatment and track disease progression. However, today’s clinical diagnosis methods are limited to subjective evaluations and observation. Onset, symptoms and progression significantly vary from patient to patient across stages and subtypes that exceed the scope of a standardized diagnosis. The goal of this thesis is to provide the basis of a more general approach to study the brain, investigating early detection method for NDD with focus on PD. It details the preliminary development, testing and validation of tools and methods to objectively quantify and extrapolate motor and non-motor features of PD from behavioral and cognitive output during everyday life. Measures of interest are categorized within three domains: the motor system, cognitive function, and brain activity. This thesis describes the initial development of non-intrusive tools and methods to obtain high-resolution movement and speech data from everyday life and feasibility analysis of facial feature extraction and EEG for future integration. I tested and validated a body sensor system and wavelet analysis to measure complex movements and object interaction in everyday living situations. The sensor system was also tested for differentiating between healthy and impaired movements. Engineering and design criteria of the sensor system were tested for usability during everyday life. Cognitive processing was quantified during everyday living tasks with varying loaded conditions to test methods for measuring cognitive function. Everyday speech was analyzed for motor and non-motor correlations related to the severity of the disease. A neural oscillation detection (NOD) algorithm was tested in pain patients and facial expression was analyzed to measure both motor and non-motor aspects of PD. Results showed that the wearable sensor system can measure complex movements during everyday living tasks and demonstrates sensitivity to detect physiological differences between patients and controls. Preliminary engineering design supports clothing integration and development of a smartphone sensor platform for everyday use. Early results from loaded conditions suggest that attentional processing is most affected by cognitive demands and could be developed as a method to detect cognitive decline. Analysis of speech symptoms demonstrates a need to collect higher resolution spontaneous speech from everyday living to measure speech motor and non-motor speech features such as language content. Facial expression classifiers and the NOD algorithm indicated feasibility for future integration with additional validation in PD patients. Thus this thesis describes the initial development of tools and methods towards a more general approach to detecting PD. Measuring speech and movement during everyday life could provide a link between motor and cognitive domains to characterize the earliest detectable features of PD. The approach represents a departure from the current state of detection methods that use single data entities (e.g.one-off imaging procedures), which cannot be easily integrated with other data streams, are time consuming and economically costly. The long-term vision is to develop a non-invasive system to measure and integrate behavioral and cognitive features enabling early detection and progression tracking of degenerative disease.
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Kasprzyk, Kalina. "Inequality, redistribution and mobility of agricultural incomes in Scotland." Thesis, University of Dundee, 2014. https://discovery.dundee.ac.uk/en/studentTheses/5362a34d-91a5-4970-ac21-adf6dd91eeba.
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The purpose of this thesis is to analyse different aspects of the distribution of agricultural incomes in Scotland. More specifically, the thesis will first investigate the impact of agricultural income support on inequality through the analysis of its redistributive effect. Decomposition of the redistributive effect allows to determine if agricultural support has been progressive or regressive in absolute terms and whether discrimination between farms with equal pre-support incomes exists. Such assessment is performed both for actual data with the historic model of the Single Farm Payment (SFP) in place, as well as for counter-factual data generated by two hypothetical regional model distributions of the SFP; the latter is particularly informative in the context of the new Common Agricultural Policy (CAP) reform that will require all Member States to adopt area-based entitlements. In addition, the thesis will study the evolution of agricultural income distribution through the analysis of income mobility. The first focus of this dynamic analysis is to investigate the transition process underlying the evolution of agricultural income inequality over time. This is achieved by decomposing changes in inequality over time into the part which measures if income growth was progressive or regressive (vertical mobility) and the part which measures the resulting reshuffling of individuals within the income order (reranking mobility). The characterisation of the expected income growth process will indirectly examine the validity of Gibrat’s law in Scottish agriculture. Furthermore, the determinants of vertical mobility will be investigated in order to analyse the impact of structural change and transitory shocks. The second focus of the dynamic analysis is to investigate whether the inequality in Scottish agricultural incomes is a transitory or structural problem, and to what extent structural inequality is caused by differences in the economic size of farms.