209 research outputs found

    Description of the pragmatic functions of attitudinal boosters that express the degree of a certain quality (ADCQS) in a parallel corpus from a translation approach

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    El propósito de esta tesis fue el de describir las funciones pragmáticas de los Acentuadores Actitudinales que Expresan el Grado de Cierta Cualidad (AEGC) en un corpus paralelo ubicados en subtítulos transcritos. Nuestra revisión de literatura reveló una escasez de información en relación a la acentuación dentro de este género de discurso, especialmente en relación en la Traductología y con el par de idiomas inglés-español. El marco teórico se construyó teniendo en cuenta al enfoque funcional, la Traductología, la acentuación y la situación comunicativa. Se propone un diseño metodológico que detalla la delimitación del corpus de análisis. La metodología de análisis permitirá analizar la información derivada de la teoría presentada en el diseño metodológico. Siguiendo cada paso de la metodología, hay un breve resumen de los resultados de cada fase de la investigación. Finalmente, se presentan los resultados, la discusión y las conclusiones; recapitulando los objetivos, los pasos para alcanzarlos y la respuesta que este trabajo obtuvo a la pregunta de investigación; así como sugerencias y recomendaciones en torno a estudios futuros.The purpose of this thesis was to describe the pragmatic functions of attitudinal boosters that express the degree of a certain quality (ADCQs) in a parallel subtitle transcript corpus. Our review of literature revealed a dearth of information regarding accentuation in this genre of discourse, especially as it related to traductology, and with the EnglishSpanish language pair. In the conceptual framework, supportive theory was expounded regarding the functional approach to traductology, accentuation, and the communicative situation. Further, a methodological design which would permit the delimitation of the corpus of analysis was proposed. The analysis methodology which would later permit the analysis of extracted data was derived from the theory presented in the methodological design. Following each step of the methodology is a brief summary of the results of each phase of the investigation. Finally, the results, discussion, and conclusions are presented, recapitulating the objectives, the steps taken to reach them, and the answer that this investigation provided in response to the research question. Lastly, suggestions and recommendations related to the present, and future studies, are given

    Determination of the Membrane Topology of the Small EF-Hand Ca2+-Sensing Proteins CaBP7 and CaBP8

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    The CaBPs represent a subfamily of small EF-hand containing calcium (Ca2+)-sensing proteins related to calmodulin that regulate key ion channels in the mammalian nervous system. In a recent bioinformatic analyses we determined that CaBP7 and CaBP8 form an evolutionarily distinct branch within the CaBPs (also known as the calneurons) a finding that is consistent with earlier observations characterising a putative C-terminal transmembrane (TM) spanning helix in each of these proteins which is essential for their sub-cellular targeting to the Golgi apparatus and constitutive secretory vesicles. The C-terminal position of the predicted TM-helix suggests that CaBP7 and CaBP8 could be processed in a manner analogous to tail-anchored integral membrane proteins which exhibit the ability to insert across membranes post-translationally. In this study we have investigated the topology of CaBP7 and CaBP8 within cellular membranes through a combination of trypsin protection and epitope accessibility analyses. Our results indicate that the TM-helices of CaBP7 and CaBP8 insert fully across membranes such that their extreme C-termini are luminal. The observed type-II membrane topology is consistent with processing of CaBP7 and CaBP8 as true tail-anchored proteins. This targeting mechanism is distinct from any other calmodulin related Ca2+-sensor and conceivably underpins unique physiological functions of these proteins

    Evolution and functional diversity of the Calcium Binding Proteins (CaBPs)

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    The mammalian central nervous system (CNS) exhibits a remarkable ability to process, store, and transfer information. Key to these activities is the use of highly regulated and unique patterns of calcium signals encoded by calcium channels and decoded by families of specific calcium-sensing proteins. The largest family of eukaryotic calcium sensors is those related to the small EF-hand containing protein calmodulin (CaM). In order to maximize the usefulness of calcium as a signaling species and to permit the evolution and fine tuning of the mammalian CNS, families of related proteins have arisen that exhibit characteristic calcium binding properties and tissue-, cellular-, and sub-cellular distribution profiles. The Calcium Binding Proteins (CaBPs) represent one such family of vertebrate specific CaM like proteins that have emerged in recent years as important regulators of essential neuronal target proteins. Bioinformatic analyses indicate that the CaBPs consist of two subfamilies and that the ancestral members of these are CaBP1 and CaBP8. The CaBPs have distinct intracellular localizations based on different targeting mechanisms including a novel type-II transmembrane domain in CaBPs 7 and 8 (otherwise known as calneuron II and calneuron I, respectively). Recent work has led to the identification of new target interactions and possible functions for the CaBPs suggesting that they have multiple physiological roles with relevance for the normal functioning of the CNS

    The Resilient Families Project @ Wayside’s Hotel Louisville: Strategies for Building Resilience, Mindfulness & Happiness in At-Risk Adults

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    The Resilient Families Project (RFP) provides educational experiences to strengthen evidence-based habits of resilience, mindfulness, and happiness in at-risk individuals. RFP holds programs for adults facing homelessness and women in drug/alcohol recovery who are housed by Wayside Christian Mission in their Emergency Shelter or Hotel Louisville. RFP programs work to promote healthy attachment relations, a sense of belonging/purpose, and interactive reading, and children’s storybooks serve as the foundation for designing programs. The book “The Boy, The Mole, The Fox, and The Horse\u27\u27 was reviewed through content analysis to emphasize diversity, equity, and inclusion, as well as RFP Core Ideas. Thanks to the Gheen’s Foundation Grant awarded by UofL’s Office of Community Engagement, we were able to provide this book, as well as program T-shirts and other materials for participants. This presentation will describe the partnership between our department, key Wayside staff, and our RFP team (composed of current UofL students, alumni, faculty, and community volunteers). Feedback received via participant surveys where we discuss the program, troubleshoot challenges/issues, and work to best meet the needs of participants will be included. Connections of our work to Little Free Libraries (LFL) will also be addressed, as RFP is steward to five LFL’s in Louisville. RFP established the first LFL on UofL’s campus and we are proud to be celebrating the grand opening of UofL’s first diversity, equity, and inclusion focused LFL, to be housed in our department. Finally, lessons learned, current project needs, recruitment efforts, and directions for the future will be described

    Modulation of phosphatidylinositol 4-phosphate levels by CaBP7 controls cytokinesis in mammalian cells

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    Calcium and phosphoinositide signaling regulate cell division in model systems, but their significance in mammalian cells is unclear. Calcium-binding protein-7 (CaBP7) is a phosphatidylinositol 4-kinaseIIIβ (PI4KIIIβ) inhibitor required during cytokinesis in mammalian cells, hinting at a link between these pathways. Here we characterize a novel association of CaBP7 with lysosomes that cluster at the intercellular bridge during cytokinesis in HeLa cells. We show that CaBP7 regulates lysosome clustering and that PI4KIIIβ is essential for normal cytokinesis. CaBP7 depletion induces lysosome mislocalization, extension of intercellular bridge lifetime, and cytokinesis failure. These data connect phosphoinositide and calcium pathways to lysosome localization and normal cytokinesis in mammalian cells

    Collaborative individualisms in the autobiographical writings of H.D., Djuna Barnes, Gertrude Stein and Emily Coleman

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    In this thesis I investigate how far ‘collaboration’ can be used an aesthetic interpretative category to examine the subjectivities narrated in the autobiographical writing of H.D., Gertrude Stein, Djuna Barnes and Emily Coleman. These writers were living and working in the collaborative literary networks of the modernist period, which provided aesthetic stimulus, models of exchange and reciprocity, and creative influence. I argue that, beyond being a social context, collaboration was also a central narrative tool used by these writers to achieve autobiographical self-definition by presenting the self relationally through the prism of an other. I engage directly with relevant theoretical frameworks that examine relationality, including crowd theorists who were writing about the impact of the multitude and proposing methodologies for navigating the boundaries of individualism and collectivism, and contemporary autobiographical theory that examines the plurality of the autobiographical subject and how it is constituted by its relations with others. In chapter one I look at the autobiographical novels of H.D. that include the depiction of a collaborative union with Bryher that manifested in the self-creation of multiple relational subjectivities. In chapter two I examine the journalism of Barnes from 1913 to 1931, as well as her novel Nightwood (1936), and find her navigating varying levels of connection to explore how subjects are constituted in and by their relations to an other or several others. In chapter three I turn to Stein’s Everybody’s Autobiography (1938), in which she is developing a narrative and stylistic conception of the inescapable effect of the multitude on a subject’s self-perception, while also trying to carve a space for the subject to exist outside this context in order to preserve their individuality. In chapter four I find that Coleman’s diaries are an account of an ultimately futile search for a creative other with whom she could collaborate to fully realise her autobiographical selfhoods. The notion of collaboration enables an interrogation of the specific textual strategies that these writers use for autobiographical self-representation, which reveals distinctive methodologies for writing in a way that takes account of the context of the multitude in the shaping of and insistence on the individual

    Characterisation of the Interaction of the C-Terminus of the Dopamine D2 Receptor with Neuronal Calcium Sensor-1

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    NCS-1 is a member of the neuronal calcium sensor (NCS) family of EF-hand Ca2+ binding proteins which has been implicated in several physiological functions including regulation of neurotransmitter release, membrane traffic, voltage gated Ca2+ channels, neuronal development, synaptic plasticity, and learning. NCS-1 binds to the dopamine D2 receptor, potentially affecting its internalisation and controlling dopamine D2 receptor surface expression. The D2 receptor binds NCS-1via a short 16-residue cytoplasmic C-terminal tail. We have used NMR and fluorescence spectroscopy to characterise the interactions between the NCS-1/Ca2+ and D2 peptide. The data show that NCS-1 binds D2 peptide with a Kd of ∼14.3 µM and stoichiometry of peptide binding to NCS-1 of 2∶1. NMR chemical shift mapping confirms that D2 peptide binds to the large, solvent-exposed hydrophobic groove, on one face of the NCS-1 molecule, with residues affected by the presence of the peptide spanning both the N and C-terminal portions of the protein. The NMR and mutagenesis data further show that movement of the C-terminal helix 11 of NCS-1 to fully expose the hydrophobic groove is important for D2 peptide binding. Molecular docking using restraints derived from the NMR chemical shift data, together with the experimentally-derived stoichiometry, produced a model of the complex between NCS-1 and the dopamine receptor, in which two molecules of the receptor are able to simultaneously bind to the NCS-1 monomer

    Current Understanding of Circulating Tumor Cells - Potential Value in Malignancies of the Central Nervous System

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    Detection of circulating tumor cells (CTCs) in the blood via so-called 'liquid biopsies' carries enormous clinical potential in malignancies of the central nervous system (CNS) because of the potential to follow disease evolution with a blood test, without the need for repeat neurosurgical procedures with their inherent risk of patient morbidity. To date studies in non-CNS malignancies, particularly in breast cancer, show increasing reproducibility of detection methods for these rare tumor cells in the circulation. However, no method has yet received full recommendation to use in clinical practice, in part because of lack of a sufficient evidence base regarding clinical utility. In CNS malignancies one of the main challenges is finding a suitable biomarker for identification of these cells, because automated systems such as the widely used Cell Search system are reliant on markers such as the epithelial cell adhesion molecule (EpCAM) which are not present in CNS tumors. This review examines methods for CTC enrichment and detection, and reviews the progress in non-CNS tumors and the potential for using this technique in human brain tumors
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