Tesis sobre el tema "Human Development – physiology"
Siga este enlace para ver otros tipos de publicaciones sobre el tema: Human Development – physiology.
Crea una cita precisa en los estilos APA, MLA, Chicago, Harvard y otros
Consulte los 50 mejores tesis para su investigación sobre el tema "Human Development – physiology".
Junto a cada fuente en la lista de referencias hay un botón "Agregar a la bibliografía". Pulsa este botón, y generaremos automáticamente la referencia bibliográfica para la obra elegida en el estilo de cita que necesites: APA, MLA, Harvard, Vancouver, Chicago, etc.
También puede descargar el texto completo de la publicación académica en formato pdf y leer en línea su resumen siempre que esté disponible en los metadatos.
Explore tesis sobre una amplia variedad de disciplinas y organice su bibliografía correctamente.
1
McElroy, Mary Catherine. "The role of antioxidant enzymes in human lung development". Thesis, University of Southampton, 1991. http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.293725.
Texto completo
2
Parker, Dawn Fiona. "Factors controlling the development and strength of human skeletal muscle". Thesis, University College London (University of London), 1989. http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.244016.
Texto completo
3
Kuo, Hongqi. "Nuclear and chromosomal abnormalities in human preimplantation development in vitro". Thesis, King's College London (University of London), 2001. http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.251676.
Texto completo
4
Fryer, Anthony Alan. "Studies on the biochemical development of human lung and brain". Thesis, Keele University, 1991. http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.306225.
Texto completo
5
Bucklow, C. W. M. "English science and the development of plant physiology in the second half of the seventeenth century". Thesis, University of Oxford, 1986. http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.371615.
Texto completo
6
Zhu, Meidong. "Development and regression of the human hyaloid system". Thesis, Sydney Medical School, 1998. http://hdl.handle.net/2123/14472.
Texto completo
7
Xu, Li Jing. "Oxygen and lung development in newborn rats and chick embryos". Thesis, McGill University, 1988. http://digitool.Library.McGill.CA:80/R/?func=dbin-jump-full&object_id=61955.
Texto completo
8
Chandaria, Rehma. "Scaffold development to engineer human intestinal epithelial tissue grafts". Thesis, University of Nottingham, 2017. http://eprints.nottingham.ac.uk/41875/.
Texto completoResumen
Epithelial crypts isolated from normal colon mucosa have been cultured in vitro in the form of organoids. These organoids have been shown to have regenerative potential when implanted in mouse models of denuded colon mucosa. However, a major limitation in the translation of these studies to a clinical setting is the use of Matrigel, which is clinically unsuitable due to its undefined composition and potential for tumourigenicity. Additionally, enclosed organoids do not fully reproduce the structure and function of native tissue, and do not lead to full integration into the host. Therefore, the overall aim of this thesis was to investigate different scaffolds for their ability to support growth of primary colon epithelial cells in order to form an open monolayer structure that resembles native epithelium. It was anticipated that in vitro culture of primary colon cells would be more efficient with isolated stem cells than with an entire heterogeneous epithelial cell population. Therefore, the side population technique was explored using established cell lines as a method of isolating a population enriched in stem cells, based on their ability to efflux the Hoechst 33342 dye. This was found to be irreproducible and unreliable so was not pursued further. Various scaffolds were manufactured, characterised and seeded with colon epithelial cell lines to investigate how their morphological and biochemical characteristics influenced cell proliferation and differentiation. Electrospun nanofibre and microfibre scaffolds made from the synthetic material PET, and the natural polymer gelatin were fabricated. All electrospun scaffolds supported proliferation, and cells on gelatin nanofibre scaffolds differentiated to form tight junctions that are typical of epithelial cells, while also expressing increased levels of the stem cell marker ABCG2. Thereby, gelatin nanofibres demonstrated the ability to support appropriate cell differentiation while maintaining a pool of stem cells. Gelatin in the form of hydrogel scaffolds was also investigated for its ability to support cell proliferation and influence cell differentiation. Moreover, a novel method of rapidly 3D printing scaffolds using unmodified gelatin was presented. Both planar and 3D gelatin scaffolds were able to support proliferation and tight junction formation in Caco2 cells. Thus, it was concluded that gelatin hydrogels are a suitable substrate for proliferation and differentiation of colon carcinoma cell lines, and that the addition of the printed topography did not have any negative effects on cell growth and behaviour. Epithelial crypts were isolated from human colon mucosa and expanded in vitro in the form of organoids, as previously published. It was found that the precise nature and source of organoid media components are critical for successful primary cell culture. A method in which the Wnt signalling cascade is indirectly activated by GSK3β inhibition was found to be partially successful for growing organoids and may be a potential alternative culture method. Primary organoid cells were seeded onto gelatin nanofibre and hydrogel scaffolds, however the cells did not proliferate in these preliminary experiments. Overall, it was concluded that although the gelatin scaffolds demonstrated promising results with colon carcinoma cell lines, more research would be required in order to produce scaffolds that can support growth of primary colon epithelial cells.
9
Ahmad, Mehtab. "Interleukin-1α as a biomarker of human abdominal aortic aneurysm (AAA) development and progression". Thesis, University of Birmingham, 2017. http://etheses.bham.ac.uk//id/eprint/7712/.
Texto completoResumen
This Thesis presents an analysis of the role of interleukin (IL)-1α (IL-1α) as a potential future surrogate biomarker for AAA. It is the only research work to date to have looked into the role of IL-1α as a biomarker in AAA disease, correlating titres with different anatomical, morphological and patient-related factors. It is the first piece, in over 20 years of published literature, to have performed a robust methodology study on the measurement of IL-1a in serum samples using different techniques. A comparison study of commercially available immunoassays in the context of IL-1α has never been undertaken before, and we are the first to undertake one. Additionally the work on the natural history of AAA is one of the largest single-centre cohort studies to analyse AAA growth in surveillance. The work covers three main areas: identifying why current strategies for monitoring AAA are ineffective, analysis of different serum processing methodologies and commercially available immunoassays used to measure IL-1α, and linking IL-1α to different anatomical, morphological and patient-related AAA factors.
10
Cavilla, Jennifer Louise. "The effects of factors influencing human oocyte maturation upon fertilization and preimplantation embryo development". Thesis, University of Warwick, 2002. http://wrap.warwick.ac.uk/73509/.
Texto completoResumen
The competence of oocytes to mature and undergo fertilization and embryonic development is known to be influenced by the conditions under which their maturation occurs. Suboptimal maturation in vitro currently limits the use of immature oocytes for embryo creation. This project examines the relationship between the conditions of in vitro maturation of human oocytes and aspects of their subsequent developmental competence through the in vitro creation and analysis of research embryos. This work is essential in defining effective and safe conditions for the use of human immature oocytes in programmes of clinical treatment to alleviate infertility. Human immature oocytes were exposed in vitro to various concentrations of meiosis activating sterol (FF-MAS), an endogenous mediator of follicle and oocyte function, or epidermal growth factor (EOP), in the absence of other hormonal support. Their survival and further development relative to controls were measured by assessing the proportions maturing, fertilizing by sperm injection (ICSI), and cleaving in vitro. Image analysis was used to measure various dimensions of oocytes and embryos daily. A pilot study of chromosome and spindle configurations at meiotic metaphase was also conducted. The major findings of this project are that FF-MAS supplementation of maturation medium has different positive effects upon immature oocytes arising from patient groups having different endocrine profiles and yielding differing oocyte populations. FF-MAS at 30J.lg/ml promotes survival of oocytes from unstimulated patients with polycystic ovaries (p
11
Singh, Harsimrat. "Development of EEG based BCI approaches for detection of awareness in human disorders of consciousness". Thesis, University of Warwick, 2009. http://wrap.warwick.ac.uk/3790/.
Texto completoResumen
Electroencephalogram (EEG) based Brain Computer Interfaces (BCIs) have been successfully developed to help patients with motor disabilities but with retained cognitive abilities. In this thesis, the BCI techniques are developed for patients with severe brain injuries such as those in minimally conscious states (MCS) and vegetative states (VS). In 2006, neuroimaging based volitional imagery paradigms akin to the ones used for the development of motor imagery based BCIs revealed that a VS patient could produce neural responses indistinguishable from those produced by a healthy subject. The work presented in the thesis is inspired by this revelation and presents first attempts to develop electrophysiology based objective bedside methods to detect awareness in disorders of consciousness. The benefit of electrophysiology based methods is that they are able to register the response from the brain immediately and provide far better time resolution than imaging. As many patients either cannot undergo a fMRI scan or do not have access to it, it is believed that long term benefits to quality of life for this patient group can be better achieved at the bedside by an electrophysiological solution. In order to achieve the objectives, EEG data is collected using two BCI approaches: volitional imagery and event related potentials (ERPs) through rare/odd presentation of a target stimulus amongst a sequence of stimuli which produces high amplitude EEG wave after 300ms of its occurrence, this is called P300. Four different variants of volitional paradigms of 'imagine playing tennis' and 'spatial navigation' are used to collect data from 19 healthy subjects and the P300 speller is used to collect data from 5 healthy subjects, two MCS and two VS patients. In the case of imagery data, a channel selection scheme based on classifier performance, which also evaluates the contribution of each channel to the classification process, is used. This scheme is developed from the offline analysis of a benchmark dataset from the BCI competition III. The comparative results of algorithms for BCI imagery data analysis (time domain parameters (TDP), adaptive autoregressive (AAR) and bandpower (BP) for feature extraction and linear discriminant analysis (LDA), support vector machines (SVM) for classification) is presented to determine the feasibility of using these paradigms with patients. Consistent performance accuracy Figures for classification, in the range of 80-90%, are achieved showing that volitional tasks are distinguishable through EEG. A combination of AAR and LDA outperformed the other combinations of algorithms. The actively contributing channels, in achieving these classification results, are used to create EEG signatures for the volitional tasks. The EEG signatures indirectly signify the areas of brain activation for each of the volitional tasks and are found to be comparable to those obtained from neuroimaging. The validation of techniques is performed using a two class, 64-channel electrocorticogram (ECoG) dataset and initial data exploration was performed using principal component analysis (PCA). The derivative of the linear least fit polynomial was used as features and 64% classification was achieved on the unlabelled test data with multi layer perceptron (MLP) as the benchmark mechanism. Ten channels which actively contributed to the classification process were selected using genetic algorithms (GAs), thereby reducing the dimensionality, an important benefit when analysing multichannel, multi-trial datasets. Feature extraction techniques, which can combine spatial and temporal information such as common spatial patterns (CSP), were evaluated and 86% trials were classified correctly using MLP classification. The validation of classifier performance based channel selection produced six channels of interest, the bipolar combinations of which produced a best accuracy of 86% classification with AAR features and LDA classifier and also with TDP features and SVM classification. The P300 data recorded from the patients was investigated for a reproducible P300 response to the target letters. This is achieved by signal averaging and the analysis of square of Pearson‘s correlation coefficient (r-square). Clearly identifiable differential responses to the target letters were observed for three patients. It is believed that with auditory addition to the stimulus presentation in the stimulation procedure, training and consistency of responses, a tool for an objective method of diagnosis and assistive communication could be developed for this patient group. The BCI technology had not been used for the cognitively impaired patient groups such as MCS and VS, hence, the results of this work are new and contribute to bridging the gap between the core BCI research and its applications for patients. The objective measures of awareness developed through EEG based BCI methods will help to reduce the misdiagnosis rate, which is 43% for this patient group. The findings of the work presented in this thesis can be used to further develop an assistive communication tool for patients in this group.
12
Mold, Jeffrey Eron. "The development of the human adaptive immune system and its role in promoting immunological tolerance". Diss., Search in ProQuest Dissertations & Theses. UC Only, 2009. 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:3352466.
Texto completo
13
Al-Sho'ala, Afaf Sayed Ali. "Evaluation of wet bulb globe temperature index for a population adapted to work in the heat : and development of a heat stress limit for occupational accident prevention predicted from meteorological data and building design". Thesis, University of London, 1995. http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.339094.
Texto completo
14
Kanady, John. "Morphogenesis of lymphatic vascular networks| Insights from connexin and Foxc2 knockout mice". Thesis, The University of Arizona, 2015. http://pqdtopen.proquest.com/#viewpdf?dispub=3671779.
Texto completoResumen
To maintain human health, the lymphatic system requires a structurally and functionally sound network of lymph vessels to absorb lipid-based nutrients, preserve extracellular fluid homeostasis, and mediate immune responses. Aside from lymphedema, investigations in the past few decades have found that impairment of the lymphatic vasculature is also involved in processes such as inflammation, tumor metastasis, fat metabolism, and obesity. However, despite a long history of study and rekindled vigor in the field of lymphatic vascular research, our knowledge of lymph vessel development and physiology is still quite limited. Recently, mutations in a protein family known as connexins (Cxs) were identified as the cause of lymphatic dysfunction in some cases of inherited lymphedema. This dissertation explores the role of primarily two specific connexins, Cx37 and Cx43, and the transcription factor Foxc2 in the morphogenesis and function of the lymphatic vasculature in mice. To accomplish this, phenotypic characterization of mice with genetic deficiencies (knockout mice) in Cx37, Cx43, and/or Foxc2 was performed principally via necropsy, histological techniques (immuno-fluorescence microscopy and H&E staining), and Evans blue dye (EBD) injections. Developmental abnormalities were found in lymphatic vascular growth, patterning, and remodeling in mice lacking Cx37, Cx43, Foxc2 or a combined deficiency of these proteins. Reductions or complete loss of lymphatic valves were a common finding in mice lacking one or more of these proteins. These valve deficits underlay lymphatic insufficiencies that resulted in lymphedema and chylothorax in some genotypes. Foxc2 was found to be a regulator of Cx37 expression. Moreover, Foxc2 was also dependent on Cx37 function for proper morphogenesis of lymph vessels. These findings pertaining to the expression of connexins in the lymphatic vasculature, their role in lymphatic valvulogenesis, and the interdependence of Cx37 and Foxc2 during lymph-vascular development represent my original contributions to human knowledge.
15
Khalil, Omari S. "Effects on brain development of prenatal inhibition of Kynurenine-3-Monooxygenase". Thesis, University of Glasgow, 2014. http://theses.gla.ac.uk/5075/.
Texto completoResumen
Much is known about the disease pathology related to schizophrenia, however, little is known with regards to its aetiology. Recent evidences suggest a neurodevelopmental hypothesis for schizophrenia where environmental factors including: infection, stress and malnutrition, can adversely affect the pregnant mother thereby elevating the risk for schizophrenia developing in the offspring during adulthood (Meyer et al., 2008d; Meyer and Feldon, 2009; 2012; Forrest et al., 2012; Meyer, 2013). Since a variety of viral and bacterial infections in animal models have demonstrated to increase the risk in schizophrenia, it is proposed that factors common to the immune response may mediate this link. While many laboratories have reported several behavioural abnormalities following maternal immune activation, we sought to examine molecular changes following poly(I:C) exposure, a synthetic viral mimetic, in the pregnant mother and assessed a range of protein markers with known developmental roles, since an appreciable understanding of the molecular alterations taking place would permit suitable therapies to follow. Interestingly, poly(I:C) was able to induce a range of changes resembling those observed during schizophrenia, where the major NMDA receptor subunit GluN1 and α-Synuclein was reduced in postnatal day 21 animals born to mothers treated with poly(I:C) during gestation days 14, 16 and 18. Furthermore, these changes suggest a mechanism by which maternal immune activation may lead to the subsequent emergence of schizophrenia. Another aspect of this work examined the role of the kynurenine pathway on brain development. There is increasing evidence suggesting the involvement of the kynurenine pathway, a biochemical pathway responsible for the oxidative metabolism of tryptophan, in the disease pathology of schizophrenia, including neurodegenerative disorders such as Parkinson’s, Alzheimer’s and Huntington’s disease (Giorgini et al., 2005; Ting et al., 2009; Bonda et al., 2010). Since immune activation induces the activation of the kynurenine pathway, it was hypothesised that alterations in central kynurenine concentrations during development may be involved in mediating the subsequent increased risk for schizophrenia (Forrest et al., 2013, Khalil et al., 2013, 2014). As very little is known about the physiological activity of the kynurenine pathway during development, we sought to examine the potential consequence of disrupting this pathway and examining its effects upon brain development. Therefore, a kynurenine monooxygenase inhibitor, Ro61-8048, was administered to pregnant rats during gestation day 14, 16, and 18, that would inhibit the synthesis of the neurotoxic metabolite quinolinic acid, while redirecting the pathway to increase the neuroprotectant kynurenic acid. Brain development was assessed by examining changes in protein expression of markers intimately involved in synaptic transmitter release machinery, neurogenesis and many aspects of neuronal development. Interestingly, we found the kynurenine pathway is highly active during brain development, and induces a variety of changes in protein markers that may be involved in precipitating a range of neuronal and cognitive deficits. While Ro61-8048 induced no changes in the embryo brains at 5 and 24 h following treatment, delayed changes were seen in postnatal day 21 animals displaying a decrease in RhoB expression as examined in the western blots. Since the full blow symptoms of schizophrenia become apparent during early adulthood, we sought to examine any changes in protein expression in postnatal day 60 animals in regions of the cortex, hippocampus, midbrain and cerebellum. Interestingly, profound alterations were seen in doublecortin and the netrin receptors responsible for axonal guidance. Perhaps the most striking protein change in the postnatal day 60 animals is the significant alteration induced in the expression of disrupted in schizophrenia (DISC)-1, a protein strongly linked with schizophrenia. Glutamate function was assessed as indicated by the density of glutamate transporters, VGLUT-1 and VGLUT-2, in the CA1 region of the hippocampus of postnatal day 60 animals using immunocytochemistry. While the relative density of glutamate transporters were substantially increased, there were no changes in the GABA transporters, indicating that while GABA transmission remained the same, glutamate function may have increased in the absence of an increase in synaptic connections. Spine densities of pyramidal neurons in the hippocampus were also examined, using the golgi-impregnation method, to reveal a significant loss in spines of the apical and basal dendrites, consistent with reports in schizophrenia. To conclude, the kynurenine pathway is highly active during development, and alterations in central kynurenines during pregnancy, as induced by environmental factors such as stress and infection, may be involved in the subsequent emergence of neurodevelopmental disorders.
16
Scott, Ryan 1981. "Investigating the natural history of human islet-derived duct-like structures transplanted subcutaneously into nude mice". Thesis, McGill University, 2008. http://digitool.Library.McGill.CA:80/R/?func=dbin-jump-full&object_id=112362.
Texto completoResumen
Islet plasticity has proven to be an important platform for the engineering of alternative islet tissue for transplantation. In vitro studies have shown the ability of islets to transdifferentiate into duct-like epithelial structures (DLS) thought to possess progenitor cells capable of replenishing damaged tissue within the pancreas. The aim of this study was to investigate the natural history of human derived duct-like epithelial structures transplanted into nude mice.Human islet derived duct-like structures from three cadaver pancreases were subcutaneously transplanted into 6-8 week old male HSD athymic nude-Foxn1 mice. Six mice were sacrificed at day 3, 7, 14 and 21 from each time period. DLS were also placed in matrigel for in-vitro control samples. DLS were processed for immunohistochemistry for endocrine markers, epithelial markers, cell death and proliferation markers, islet maturation markers and angiogenic factors.
Our results show that as DLS are transplanted, there is an increase in cell death and proliferation. This increase in cell death and proliferation causes an increase in PDX-1 expression as well as VEGF, an angiogenic factor. But over time, transplanted DLS do not show an increase in cell death and show a small decrease in cell proliferation from pre-transplanted DLS. At day 3 of engraftment, DLS show a significant expression of PDX-1. We see a small increase in endocrine tissue after 3 days of transplantation, then an increase in endocrine cell death, which returns the percentage of endocrine cells back to pre-transplantation levels at day 21. DLS were shown to express VEGF, and once transplanted into an initial hypoxic environment there is a substantial increase in expression, followed by a recruitment of microvessels. Although there is a dynamic change in expression of cell markers throughout engraftment, there is no significant change in DLS size, nuclei per DLS or cell morphology over time.
DLS have been shown to survive subcutaneous transplantation and possess an initial increase in cell proliferation leading to increases in PDX-1 and VEGF expression. Transplanted DLS have shown to possess significant angiogenic properties with the recruitment of microvessels into subcutaneous DLS grafts. Subcutaneous DLS transplantation could be used in combination with islet transplantation to alleviate current problems with islet transplantation such as islet cell death and insufficient blood supply.
17
Byrd, Alyson. "Evidence for a receptor binding 24R, 25-dihydroxyvitamin D3 in developing bone". Thesis, McGill University, 1999. http://digitool.Library.McGill.CA:80/R/?func=dbin-jump-full&object_id=21519.
Texto completoResumen
Although 24R,25(OH)2D3 has been implicated in bone development, its biological role and mechanism of action remain controversial. In search for evidence of a receptor, nuclear and cytosol extracts were isolated from mandibles and calvaria of E17.5 mice. Competition and saturation analysis identified a saturable, specific and high affinity (Kd=1.1nM) 24R,25(OH) 2D3 binding-protein. The results of these and sucrose sedimentation studies indicate that this protein is not vitamin D receptor (VDR) or vitamin D binding protein (DBP). Tissue specificity experiments suggest that this putative receptor is also present in liver but not brain.pBDGal4-hRXRalpha bait was used to screen neonate and embryonal mandible/calvaria cDNA libraries using the yeast two-hybrid system. PCR screening was also performed using primers from the zinc-finger region of the VDR. To date no positive clones have been identified. Isolation of this putative receptor will provide valuable insight into the mechanism of this metabolite's role in bone development.
18
Willerton, Louise. "Gene expression in mouse testis during development". Thesis, Connect to electronic version, 2003. http://theses.gla.ac.uk:82/theses/available/etd-07042003-142909/.
Texto completoResumen
Thesis (Ph. D.)--University of Glasgow, 2003.Ph. D. thesis submitted to the Faculty of Veterinary Medicine, University of Glasgow, 2003. Includes bibliographical references. Electronic version also available via Glasgow University e-Theses service.
19
Middlebrook, Aaron J. "Nicotine and TNF alpha, modulators of T cell signaling-effects on T cell development in fetal thymus organ culture". Diss., The University of Arizona, 2004. http://hdl.handle.net/10150/280628.
Texto completoResumen
T cell development is regulated by signals generated in the interactions between developing thymocytes and the thymic stroma. Using fetal thymus organ culture (FTOC) as a model of T cell development, we investigated the ability of two potent signal modulators to influence this process. These studies show that both nicotine and tumor necrosis factor-alpha have the ability to influence T cell receptor (TCR) signaling and the maturational capacity of treated cultures. FTOC treated with low concentrations of nicotine produced more immature T cells and fewer mature T cells. These expanded populations of cells also expressed CD69, CD95 (FAS) and elevated levels of recombinase activating genes (RAG). This phenotype reflects the fact that these cells have received a positive selection signal, are for apoptosis and are likely attempting secondary TCR rearrangements. Nicotine effects were partially blocked by the nicotinic antagonist, d-tubocurarine. Furthermore, d-tubocurarine alone blocked the development of T cells entirely, suggesting the presence of an endogenous ligand that may engage nicotinic acetylcholine receptors and regulate normal thymopoeisis. These observations underscore the linkage between the nervous and the immune systems, not only in terms of shared resources, but also in terms of direct interactions between these two systems. In another study we used FTOC and an associated in vitro Type 1 diabetes mellitus model to reconcile the role of TNF-alpha in thymopoiesis with its role in diabetes. Our data indicate that thymocytes from NOD FTOC express lower levels of TNF receptors and produce more TNF-alpha compared to non-diabetic C57BL/6 (B6) FTOC. Neutralization of endogenous TNF-alpha in NOD FTOC with a soluble TNF receptor (sTNF R1) rescued insulin production in our in vitro diabetes model. NOD FTOC treated with TNF-alpha produced greater numbers of mature T cells and a higher percentage of cells expressing CD95L (Fas ligand). Treatment with sTNF R1 had the opposite effect. TNF-alpha's known ability to attenuate TCR signaling coupled with these observations suggest that its overproduction in these animals may be driving T cells to maturity, altering the process of negative selection and ultimately enhancing the survival of potentially diabetogenic T cells resulting in disease susceptibility in these animals.
20
Liu, Yanhe. "Human oocytes and embryos viewed by time-lapse videography, and the development of an embryo deselection model". Thesis, Edith Cowan University, Research Online, Perth, Western Australia, 2016. https://ro.ecu.edu.au/theses/1787.
Texto completoResumen
Despite its wide application today, in vitro fertilization (IVF) treatment continues to have relatively low efficacy, largely due to inaccuracy in selecting the best quality embryo(s) from the cohort for transfer. Novel methodologies for improved selection are being developed, and time-lapse observation of human embryos is gaining increasing popularity due to the more detailed morphokinetic information obtained plus uninterrupted culture conditions. The morphokinetic information enables the use of quantitative timings in developmental milestones of embryos and qualitative measures of abnormal biological events, to assist embryo selection/deselection. This project aimed to identify current limitations in the use of such measures and to develop recommendations for improvement in clinical application.
In the current study, most data were collected retrospectively from infertile couples seeking IVF treatment at a fertility clinic, with consent to use time-lapse incubation (Embryoscope) for embryo culture. Comparisons of time-lapse measures were made between embryos with confirmed implantation and non-implantation outcomes following uterine transfers. Thereafter, an embryo deselection model was proposed based on the retrospective findings, followed by prospective validation.
It was found in the current study that the reference starting time point (t0) in certain existing time-lapse systems was inaccurate due to (i) the early biological variations between sibling oocytes, (ii) technical limitations in current equipment and protocols, and (iii) different insemination methods used (Papers 1&2). The above variations may be minimized by using pronuclear fading (PNF, a biological time point) as t0 rather than insemination (a procedural time point) (Paper 2). An example of such application was the comparison of embryo development between patients with high and low serum progesterone levels on the trigger-day (Paper 3). Furthermore, the growth rate of embryos reported in the literature is subject to multiple clinical or laboratory factors, and this was in agreement with the present study where a published time-lapse algorithm emphasizing quantitative timing parameters was shown to lose its discriminatory power in implantation prediction when applied in two different laboratories (Paper 4). Interestingly, the qualitative measures seemed to have better inter-laboratory transferability due to the embryo growth patterns appearing independent of clinical and technical factors (Paper 4). Two novel qualitative measures were reported in the present study, namely reverse cleavage and less than 6 intercellular contact points at the end of the 4-cell stage, showing negative correlations with embryo implantation outcomes (Papers 5&6). A qualitative embryo deselection model was therefore proposed, including several qualitative measures with implantation rates being potentially increased from 22.4% to 33.6% (Paper 6). Finally, an embryo deselection model combining both qualitative and quantitative measures was reported with the use of PNF as t0, showing significant prediction of implantation outcomes in embryos regardless of insemination method (Paper 7).
In conclusion, this thesis demonstrates the usefulness of time-lapse embryo selection during IVF treatment in one specific laboratory. However, any new time-lapse parameter or model for embryo selection requires external validation by properly designed large-scale studies. Future clinical research and the development of integrated engineering and computer technology may further improve the efficacy of time-lapse selection of human embryos.
21
Wright, Audrey F. "The influence of gender and sex hormones in the development of translational and experimental pulmonary arterial hypertension". Thesis, University of Glasgow, 2014. http://theses.gla.ac.uk/5209/.
Texto completoResumen
Pulmonary arterial hypertension (PAH) is a progressive and debilitating disease characterised by increases in pulmonary vasoconstriction and excessive remodelling of the pulmonary arteries. Together, these processes lead to sustained elevations in pulmonary arterial pressure, right heart failure and eventual death if left untreated. Despite the number and variety of treatment options available, the survival rate in incident and prevalent cases of PAH remains poor. Therefore, a better understanding of the pathobiology of PAH is required to generate novel therapeutic approaches with improved efficiency in patients. In PAH there is a well described gender bias. Women are consistently reported to represent up to 75% of the total PAH population; however, the reasons for this female predominance remain unclear. Recently, estrogen has been implicated as a major risk factor, for example, elevated estrogen levels and alterations in estrogen metabolism are closely correlated with PAH development in females. The role of testosterone in PAH is currently under investigated. Effects of estrogen are mediated through two classical estrogen receptors (ER)-α and –β, or the novel G-protein-coupled estrogen receptor (GPER). Expression of all of these receptors is identified in pulmonary vasculature, including in smooth muscle and endothelial cells. The role they play in PAH pathogenesis in females is largely undetermined. Given the diverse effects of estrogen described in the pulmonary vasculature during PAH, for example, proliferative effects in pulmonary artery smooth muscle cells (PASMCs), we hypothesised that estrogen receptors play an integral role in PAH in females. To examine this, we used both translational and experimental studies to characterise ERs in PAH. Chronic hypoxic male and female mice, and mice over-expressing the serotonin transporter (SERT+ mice), which demonstrate female susceptibility, were used to investigate the effects of an ERα antagonist in vivo. GPER knockout mice were also investigated in chronic hypoxia. In situ and in vitro studies in human PASMCs with ER agonists and antagonists added clinical relevance to our findings. In addition, testosterone manipulation was investigated in male mice by castration in vivo. Immunohistochemistry, immunoblotting and qRT-PCR analysis demonstrated that ERα was increased in PASMCs and pulmonary arteries from female PAH patients and chronic hypoxic mice, respectively. On the other hand, ERβ was decreased in PAH and hypoxia. It was also observed that females expressed higher levels of ERα in PAH compared to males whereas ERβ was lower in females. PAH was assessed by measuring right ventricular systolic pressure (RVSP), right ventricular hypertrophy (RVH) and pulmonary vascular remodelling and muscularisation. Chronic hypoxia induced-pulmonary hypertension (PH) was attenuated in female mice dosed with the ERα antagonist MPP, shown by marked reductions in RVSP and pulmonary vascular remodelling. Hypoxic male mice remained unaffected by MPP treatment. Spontaneous PH and chronic hypoxia induced-PH observed in female SERT+ mice were reversed by treatment with MPP. Immunoblotting and qRT-PCR analysis revealed that the possible mechanism involved in the beneficial effect of MPP in females in vivo involved restoring the dysfunctional bone morphogenetic protein receptor-2 (BMPR2) axis observed in PAH. This effect was only observed in female mice. In addition, chronic hypoxia induced- PH in male and female mice was unaffected by GPER deletion. Expression of GPER between female non-PAH controls and PAH patients was unchanged. In isolated human PASMCs estrogen induced proliferation was inhibited by MPP, but not PHTPP or G15, an ERβ and GPER antagonist, respectively. The ERα agonist, PPT stimulated proliferation of human PASMCs. Both estrogen and PPT induced proliferation was dependent on downstream PI3K/Akt and ERK MAPK activity. In males, testosterone deprivation by surgical castration had no effect on chronic-hypoxia induced PH. RVSP, RVH and pulmonary vascular remodelling were unchanged in hypoxic castrated mice relative to sham controls. Testosterone levels, assessed by enzyme linked immunosorbent assay (ELISA) demonstrated no effects of hypoxia on plasma testosterone levels. Testosterone levels were approximately halved by castration. qRT-PCR analysis showed that in mouse lung there were also no difference in expression of the androgen receptor (AR) and 5α-reducatse, the testosterone metabolising enzyme. Testosterone had no effect on proliferation of human PASMCs, although its primary metabolite, dihydrotestosterone (DHT), stimulated proliferation in a dose-dependent manner. In summary of these findings, we have identified an ERα-dependent mechanism of PAH in females, but not in males. ERα is noticeably increased in female human PASMCs from PAH patients compared to male PAH patients. Additionally, ERα activation in female human PASMCs leads to proliferation driven by PI3K/Akt and ERK MAPK activation. Treatment with an ERα antagonist attenuated the development of chronic hypoxia induced-PH in females but not males, and reversed PH in SERT+ female mice. We demonstrate that the mechanism attributed to the beneficial effect of MPP in vivo involved restoration of the dysfunctional BMPR2 signalling axis. Our results suggest that increased ERα expression may drive PAH development in females. Furthermore, we demonstrate that ERα does not play a key role in the development of hypoxia induced-PH in male mice. In addition we conclude that testosterone does not contribute to chronic hypoxic-PH observed in males. We suggest that altered local synthesis and metabolism in the lung and right ventricle may however, facilitate progression of established PAH in males and worsening survival rates. Overall, our results provide evidence for ERα in PAH development and implicate targeting ERs as a novel therapeutic target in PAH treatment.
22
Singh, Sally. "Development of a 10 metre shuttle walking test to access patients with chronic airways limitation". Thesis, Loughborough University, 1993. https://dspace.lboro.ac.uk/2134/6754.
Texto completoResumen
The purpose of this study was to develop an incremental field exercise test of disability to use in the assessment of functional capacity in patients with chronic airways limitation (CAL). The test was modified from the 20m shuttle running test, employed to predict the maximal oxygen uptake of sporting individuals. The protocol devised for the patients was adapted from the running speeds proposed by Leger and Lambert (1982). The shuttle walking test requires patients to walk up and down a 10m course at speeds dictated by a series of audio signals played from a tape cassette, increasing each minute to a symptom limited maximum performance. Examination of the reproducibility of the test revealed strong test/retest reliability, after just one practice walk. The mean between trial difference (test 2 vs test 3) was -2m,(n=10), (95% CI -21.9 to 17.9m). The shuttle walking test was validated against the traditional measurement of peak oxygen uptake (Vo2pmk) measured conventionally during an incremental maximal treadmill test with Douglas bags (n=19). The results from this exercise test were compared against the patients' performance (distance achieved) on the shuttle walking test (after one practice walk) and revealed a strong relationship between the two variables (r=0.88). The validity and the resistance to breathing, of a portable oxygen consumption meter was examined. Validation, again in comparison to Douglas bag measurements, involved four cohorts (two healthy and two patient groups). After some modifications to the equipment, measurements of lib2 by the two different methods were not significantly different. The patients' response to the shuttle walking test was examined (n=10). The heart rate, ventilation and 7Orck2 increased gradually in response to the increasing intensity of the shuttle walking test. Again Vo 2wa measurements related strongly to the patients performance (r=0.81). A further study employing a treadmill test and shuttle walking test confirmed that the latter provided a comparable metabolic and physiological challenge to the patients as the conventional treadmill test. Comparison with the 6 minute walking test (6MWT), one of the most commonly employed field exercise tests in this patient population) revealed that the heart rate response was significantly higher in the shuttle walking test than the 6 MWT and graded, a response not observed in the 6MWT. The shuttle test reflected the true extent of the patients disability more accurately than the 6MWT. The shuttle walking test provides a simple, reproducible exercise test of disability in patients with CAL that relates well to Vb2puk . The external pacing of the test allows more valid intra- and inter- subject comparison than has previously been possible with field tests alone.
23
Pelland, Lucie. "Strategies for motor control analysis in children". Thesis, McGill University, 2000. http://digitool.Library.McGill.CA:80/R/?func=dbin-jump-full&object_id=37808.
Texto completoResumen
The goal of the research described in this thesis is to further our understanding of the motor control strategies that are available to the child when learning to produce meaningful interactions with environmental surfaces. The principal aim is to explore the analytical techniques that could be used to evaluate the range of neuromechanical responses for the lower limb that would provide stability at the limb/environment interface during growth and development. Five studies are presented that provide both experimental data and theoretical perspectives that were coalesced in the formulation of a general model for the control of stability at the limb/environment interface. The first study presents an analytical technique that was devised to classify the spatial-temporal organization of the surface myoelectric activity into one of three distinct patterns: Burst, Tonic, and Tonic Burst. This classification permits the matching between the pattern of muscle activity and the kinematic and kinetic control of the ground contact phase of landing. In the second, and companion paper, different distributions of the Burst, Tonic, and Tonic Burst patterns across the muscles of the lower limb were associated with three mechanical responses of the limb to ground contact. Mechanically, the three limb responses show a progression toward an effective control of stability at the limb/environment interface and it was therefore proposed that the distribution of activity patterns could reflect the priorities of system at different stages of growth and development. The results support our hypothesis that more complex movements can be executed when the limits of stability are maximized. Study three presents a formal model for the control of stability at the limb/environment interface. The model was further applied to propose new theoretical approaches that could be used in the clinical milieu, shifting the focus of the evaluation to the range of feasible movements that would be available
24
Negrey, John Patrick. "The effect of dietary methylmercury on Na+,K+-ATPase activity and growth in fall-run chinook salmon (O. tshawytscha) from California's Central Valley". Thesis, San Jose State University, 2014. http://pqdtopen.proquest.com/#viewpdf?dispub=1552274.
Texto completoResumen
Hatchery reared Chinook salmon from California’s Central Valley were fed for 67 days (Apr-Jun, 2008) on fish pellets mixed with either 0, 1, 3, or 5 µg·g−1 methylmercury hydroxide. Weight, fork length, condition factor, and Na+,K+-ATPase measurements were determined every two weeks and a 96-h seawater challenge was conducted at the conclusion of the experiment.
Results from two-way ANOVA, with treatment and date as independent variables, indicated no significant differences for weight (F3,32 = 1.38; P = 0.280), length (F3,32 = 0.986; P = 0.412) and condition factor (F3,32 = 0.239; P = 0.869). Post-hoc analysis following two-way ANOVA indicated mean ATPase activity in the high (x¯ = 3.08, S.E. = 0.19; P = 0.008) and medium treatments (x¯ = 2.86, S.E. = 0.57; P = 0.017) was significantly increased in early May compared with the control group (x¯ = 1.47, S.E. = 0.34). The results from the 96 h seawater challenge were consistent with those of other studies indicating weight has the greatest influence for survival in the transition from freshwater to seawater. Overall, results from this study indicated methylmercury, a known neurotoxin, altered ATPase activity in fall-run Chinook but did not significantly affect mortality in the transition from freshwater to seawater.
25
Valls, Margarit Maria. "Development of an advanced 3D culture system for human cardiac tissue engineering". Doctoral thesis, Universitat de Barcelona, 2017. http://hdl.handle.net/10803/458734.
Texto completoResumen
Ischemic heart disease is a major cause of human death worldwide owing to the heart minimal ability to repair following injury. Other than heart transplantation, there are currently no effective or long-lasting therapies for end-stage heart failure. Therefore, it is crucial to develop not only alternative therapies that potentiate heart regeneration or repair, but also new tools to study human cardiac physiology and pathophysiology in vitro. In this context, cardiac tissue engineering arises a promising strategy, as it is aimed at generating cardiac tissue analogues that would act as in vitro models of human cardiac tissue or as surrogates for heart repair. Thus, having 3D human cardiac tissue constructs resembling human myocardium could revolutionize drug discovery and toxicity testing, cardiac disease modelling and regenerative medicine.
An strategy to obtain reliable cardiac tissue constructs is to mimic the native cardiac environment. The classical approach is based on seeding cardiomyocytes in biocompatible 3D scaffolds, and then culturing the construct in a biomimetic signaling system, usually a bioreactor. Although major advances have been made, the generation of thick and mature tissue constructs from human induced pluripotent stem cells-derived cardiomyocytes (hiPSC-CM) is still a challenge. Therefore, the hypothesis of our study is that the combination of hiPSC-CM with 3D scaffolds and appropriate regulatory signals may lead to the generation of mature human cardiac tissue constructs resembling human myocardium, both functionally and structurally. To address this, we have characterized a collagen-based 3D scaffold and established an efficient method for cell seeding into the scaffold. We have also developed a parallelized perfusion bioreactor system, which ensures an effective mass transport between cells and culture medium and allows culturing multiple replicas of tissue constructs. In addition, we have designed and fabricated a perfusion chamber including electrodes to electrically stimulate cells during culture, as well as to monitor tissue function. With this advanced 3D culture system, we have been able to generate thick 3D human cardiac constructs with tissue-like functionality. Our results indicate that perfusion of culture medium combined with electrical stimulation and collagen-based scaffold improve the structural and functional maturation of hiPSC-CM. In general terms, electrical stimulation has improved the structural organization, alignment and coupling of cardiomyocytes in our cardiac tissue constructs. Moreover, electrical stimulation has promoted the formation of synchronous contractile constructs at the macroscale with improved electrophysiological functions. Through the development of a new electrophysiological recording system, we report for the first time to our knowledge a technique that provides information about the electrical activity of intact cardiac tissue constructs in real time. Specifically, the combination of action potentials generated by hiPSC-CM composing cardiac constructs produces ECG-like signals, which could be monitored online. Finally, we have demonstrated the ability of stimulated human cardiac tissue constructs to detect drug-induced cardiotoxicity, as typical features of arrhythmias (e.g. prolongation of RR intervals and regular blockades) could be observed upon treatment with sotalol.
Taken together, results indicate that macroscopic human cardiac tissue constructs with tissue-like functionality can be obtained through the use of our advanced 3D culture system. We have studied the effects of electrical stimulation on cardiomyocytes at multiple levels: molecular (presence, distribution and expression of cardiac proteins), ultrastructural (sarcomere width and presence of specialized cellular junctions), cellular (morphology and alignment), and functional (amplitude, directionality and strain of contractions, and electrophysiological recordings). Findings validate our in vitro approach as a valuable system to obtain 3D cardiac patches with an improved maturity and functionality. Importantly, the online monitoring system developed in this study can provide essential electrophysiological information of intact cardiac tissue constructs, which opens up myriad possibilities in the field of cardiovascular research.La cardiopatia isquèmica és una de les principals causes de mort a nivell mundial. Exceptuant el trasplantament de cor, les teràpies actuals són insuficients per restablir la funció cardíaca. Per tant, cal desenvolupar teràpies alternatives que fomentin la regeneració i/o reparació del cor, així com també noves eines per estudiar la fisiologia i fisiopatologia cardíaca in vitro. Una de les estratègies més prometedores és l’enginyeria tissular cardíaca, ja que té com a finalitat generar constructes de teixit cardíac que mimetitzin el teixit real. Aquests constructes podrien utilitzar-se com a models in vitro del miocardi humà i també com a empelts per reparar el cor malmès. Per obtenir constructes de teixit cardíac humà cal reproduir l’entorn cardíac real. Una de les estratègies més habituals consisteix en sembrar cardiomiòcits en una estructura 3D (bastida), i després cultivar el constructe en un sistema de senyalització biomimètic, normalment un bioreactor. Tanmateix, generar constructes grans i semblants al miocardi humà adult a partir de cardiomiòcits humans derivats de cèl·lules mare de pluripotència induïda (hiPSC-CM) segueix sent un repte. Així doncs, la hipòtesi d’estudi és que combinant hiPSC-CM amb una bastida 3D i estímuls biofísics adequats, es podrien generar constructes de teixit cardíac semblants al miocardi humà tant a nivell estructural com funcional. Per abordar la hipòtesi, en aquest treball s’ha caracteritzat una bastida 3D constituïda principalment per col·lagen i s’ha definit un mètode eficient per sembrar cardiomiòcits dins l’estructura. A més a més, s’ha desenvolupat un bioreactor de perfusió de sistema en paral·lel que assegura un transport de massa efectiu entre les cèl·lules i el medi de cultiu. També s’ha dissenyat una càmera de perfusió que inclou elèctrodes per estimular elèctricament les cèl·lules durant el cultiu, així com també per monitorar la funció del teixit artificial. Amb aquest avançat sistema de cultiu, s’han generat constructes de teixit cardíac humà 3D amb una funcionalitat semblant a la del teixit real. A més a més, el sistema ha permès monitorar l’electrofisiologia del teixit artificial en temps real, així com també demostrar el paper crucial de l’estimulació elèctrica per obtenir constructes amb una funcionalitat òptima.
26
Araghi-Niknam, Moshen 1960. "Effects of dehydroepiandrosterone supplementation in aged humans and C57BL/6 mice". Diss., The University of Arizona, 1997. http://hdl.handle.net/10150/282417.
Texto completoResumen
DHEA (dehydroepiandrosterone) is a major adrenal hormone, with known accepted function. In both animals and humans low DHEA and DHEA-sulfate levels are associated with a number of problems in the aging: immunosenescence, increased mortality, increased incidence of several cancers, loss of sleep, decreased feelings of well-being, osteoporosis, atherosclerosis and premature death. DHEA hormone replacement in aged mice significantly normalized immunosenescence suggesting that this hormone plays a key role in aging and stimulating immune regulation in mice. Similarly osteoclasts and lymphoid cells, were stimulated by DHEA replacement which should delay osteoporosis. Recent studies do not support the original suggestion that low serum DHEA levels were associated with Alzheimer's and other losses of mental function in aged people. As DHEA modulates energy metabolism low levels should affect lipogenesis and gluconeogenesis, increasing the risk of diabetes and heart disease. Most of the actions of DHEA restoration are hypothesized from epidemiological or animal model studies and need to be tested in human trials. Those conducted in humans show essentially no toxicity of DHEA treatment at levels restoring serum DHEAS levels without evidence of altering some aging physiological systems. Thus DHEA is a steroid whose deficiency could facilitate development of some diseases common to the aged. Dehydroepiandrosterone (DHEA) and DHEA-sulfate (DHEAS) are steroids, synthesized from cholesterol (Fig. 1.1). While DHEA is secreted primarily by the adrenal gland in larger quantities than any other adrenal steroid including cortisol, the precise functions of DHEA and DHEAS in humans are not known (1-5). The decline of DHEAS levels during aging is parallel to development of immunosensecence, an inability to conserve protein, a physical frailty, decreased muscle mass, an increased fat mass, decreased ability to cope, disrupted sleep patterns and increased incidence of disease. Thus DHEAS serves as a marker of aging in humans. While the precise biological functions of DHEA and DHEAS are not known, both animal and human studies suggest some hypotheses while dispelling others. Therefore key physiological dysfunctions are investigated here to determine biological relationships which participate in the declining blood levels of DHEA with age.
27
Schrader, Lauran N. "Does ANA-positive SLE human serum promote development of Libman-Sacks endocarditis in the NP-SLE Lewis rat model?" Muncie, IN : Ball State University, 2009. http://cardinalscholar.bsu.edu/675.
Texto completo
28
Detton, Alan James. "The Creation of a 3D Interactive Human Neural Development Resource and Its Evaluation Through a Video Analytic Usability Study". The Ohio State University, 2012. http://rave.ohiolink.edu/etdc/view?acc_num=osu1337966847.
Texto completo
29
Milliken, Laura Ann 1970. "Bone mineral density, bone remodeling, insulin-like growth factors, hormone replacement therapy, and exercise training in postmenopausal women". Diss., The University of Arizona, 1998. http://hdl.handle.net/10150/282746.
Texto completoResumen
Osteoporosis is a condition of reduced bone mineral density (BMD) resulting in an increased susceptibility to bone fractures. The purpose of this study was to determine the effects of 12 months of weight bearing and resistance exercise on BMD, bone formation, measured by serum osteocalcin (OC) and bone resorption, measured by urinary excretion of deoxypyridinoline crosslinks (Dpd), in 2 groups of postmenopausal women who were either taking or not taking hormone replacement therapy (HRT). Secondary aims were to characterize the changes in insulin-like growth factors-l and -2 (IGF-l and -2) and IGF binding protein 3 (IGFBP3) in response to exercise training, and to determine the contribution of these growth factors in predicting changes in bone mineral density in the 2 populations of postmenopausal women. Women who were three to ten years postmenopausal and aged 40-65 years were included in the study. Women in HRT and no HRT groups were randomized into the exercise intervention resulting in four groups: (1) women not taking HRT, not exercising; (2) women taking HRT, not exercising; (3) women exercising, not taking HRT; and (4) women exercising, taking HRT. The number of subjects per group after one year was 27, 21, 25, and 16, respectively. Exercise training and HRT increase BMD similarly at most BMD sites whereas the combination of exercise and HRT produced increases in BMD greater than either treatment alone. Bone remodeling was surpressed in the groups taking HRT regardless of exercise status. The bone remodeling response to exercise training in women not taking HRT was not significantly different from those not exercising but the direction of change suggests an elevation in bone remodeling in response to exercise training. Exercise training does not stimulate a change in IGF-1, IGF-2, IGF-1:IGF-2, and IGFBP3. Markers of bone remodeling and IGF-1 are significant predictors of BMD changes but the overall amount of variation in BMD changes accounted for is low. Exercise and HRT status were significant predictors of changes in BMD even after accounting for variation due to bone remodeling indicating that bone changes are regulated by factors not addressed in this study.
30
Kolatorowicz, Adam. "Patterns of Morphological Integration in Modern Human Crania: Evaluating Hypotheses of Modularity using Geometric Morphometrics". The Ohio State University, 2015. http://rave.ohiolink.edu/etdc/view?acc_num=osu1429881785.
Texto completo
31
Goliath, Jesse Roberto. "A 3D Morphological Analysis of the Ontogenetic Patterning of Human Subchondral Bone Microarchitecture in the Proximal Tibia". The Ohio State University, 2017. http://rave.ohiolink.edu/etdc/view?acc_num=osu1494273830449469.
Texto completo
32
Ryan, Helen Joanne. "The development of a reliable and valid netball intermittent activity test : a thesis presented in partial fulfilment of the requirements for the degree of Master of Science in Sport and Exercise Science at Massey University, Auckland, New Zealand". Massey University, 2009. http://hdl.handle.net/10179/1130.
Texto completoResumen
The purpose of the present investigation was to identify the exercise intensity of netball match play in order to assist in the development of a Netball Intermittent Activity Test (NIAT). A further aim was to assess the criterion validity and the test-retest reliability of the NIAT. Eleven female netball players (21.4 ± 3.1 years, 1.73 ± 0.06 m, 69.3 ± 5.3 kg and 48.4 ± 4.9 ml•kg-1•min–1 mean ± SD, age, height, body mass and VO2max, respectively) volunteered to participate in the study. Heart rate data was recorded for all participants from at least two full 60 minute games during Premier Club competition. Individual maximum heart rate values were acquired for all subjects from the performance of the Multistage Fitness Test, and used to transform heart rate recordings into percent maximum heart rate (%HRmax). Patterns in %HRmax were used to indicate positional grouping when developing the NIAT from time motion analysis data. Subjects performed two trials of the NIAT separated by at least seven days. Physiological and performance markers were measured systematically throughout the NIAT. Exercise intensity as denoted by %HRmax significantly decreased from the first half of match play to the second half (90.4 ± 2.7% v 88.3 ± 2.8%; p<0.05). Significant differences (p<0.05) were observed between positional groups and led to the grouping of Defence (D), Centre Court (CC), and Attack (A) players for NIAT performance. Comparisons of %HRmax between match play and NIAT performance indicated that the NIAT had good criterion validity for D (match Mdn = 92.52% vs. NIAT Mdn = 86.27%, p>0.05) and A (match Mdn = 86.95% vs. NIAT Mdn = 82.93%, p>0.05) players, but that %HRmax during the NIAT (Mdn = 79.70%) was significantly lower than match play (Mdn = 89.70%) for CC group (p<0.05). Measures of 5 m sprint performance (1.27 ± 0.06 s v 1.25 ± 0.06 s; p>0.05; r=0.66, p<0.001), vertical jump height (29.12 ± 4.17 cm v 28.82 ± 3.60 cm; p>0.05; r=0.91, p<0.001), circuit time (107.49 ± 3.22 s v 107.89 ± 4.27 s; p>0.05; r=0.72, p>0.001) and %HRmax (82.56 ± 4.66% v 81.03 ± 4.13%; p>0.05; r=0.82, p<0.001) for NIAT1 vs. NIAT2 indicated good test-retest reliability. These data suggest that netball players experience a reduction in exercise intensity over the duration of a game, with exercise intensity being related to on-court position. Whilst the NIAT appears to be a repeatable activity pattern, it is not a good simulation of physiological strain for all positional groups. More work is required in order to create a netball simulation that is both reliable and valid for all players.
33
Bernabeu, Llinares Miguel Oscar. "An open source HPC-enabled model of cardiac defibrillation of the human heart". Thesis, University of Oxford, 2011. http://ora.ox.ac.uk/objects/uuid:9ca44896-8873-4c91-9358-96744e28d187.
Texto completoResumen
Sudden cardiac death following cardiac arrest is a major killer in the industrialised world. The leading cause of sudden cardiac death are disturbances in the normal electrical activation of cardiac tissue, known as cardiac arrhythmia, which severely compromise the ability of the heart to fulfill the body's demand of oxygen. Ventricular fibrillation (VF) is the most deadly form of cardiac arrhythmia. Furthermore, electrical defibrillation through the application of strong electric shocks to the heart is the only effective therapy against VF. Over the past decades, a large body of research has dealt with the study of the mechanisms underpinning the success or failure of defibrillation shocks. The main mechanism of shock failure involves shocks terminating VF but leaving the appropriate electrical substrate for new VF episodes to rapidly follow (i.e. shock-induced arrhythmogenesis). A large number of models have been developed for the in silico study of shock-induced arrhythmogenesis, ranging from single cell models to three-dimensional ventricular models of small mammalian species. However, no extrapolation of the results obtained in the aforementioned studies has been done in human models of ventricular electrophysiology. The main reason is the large computational requirements associated with the solution of the bidomain equations of cardiac electrophysiology over large anatomically-accurate geometrical models including representation of fibre orientation and transmembrane kinetics. In this Thesis we develop simulation technology for the study of cardiac defibrillation in the human heart in the framework of the open source simulation environment Chaste. The advances include the development of novel computational and numerical techniques for the solution of the bidomain equations in large-scale high performance computing resources. More specifically, we have considered the implementation of effective domain decomposition, the development of new numerical techniques for the reduction of communication in Chaste's finite element method (FEM) solver, and the development of mesh-independent preconditioners for the solution of the linear system arising from the FEM discretisation of the bidomain equations. The developments presented in this Thesis have brought Chaste to the level of performance and functionality required to perform bidomain simulations with large three-dimensional cardiac geometries made of tens of millions of nodes and including accurate representation of fibre orientation and membrane kinetics. This advances have enabled the in silico study of shock-induced arrhythmogenesis for the first time in the human heart, therefore bridging an important gap in the field of cardiac defibrillation research.
34
Rahim, Mir Munir Ahmed 1975. "Pathogenesis of HIV-1 nef in adult mice". Thesis, McGill University, 2008. http://digitool.Library.McGill.CA:80/R/?func=dbin-jump-full&object_id=115698.
Texto completoResumen
Development of a suitable animal model of AIDS is much needed in AIDS research to study infection and pathogenesis as well as to evaluate methods of prevention and treatment of HIV infection. Small animals such as rodents are attractive candidates for AIDS research due to the availability of various inbred and genetically engineered strains, extensive knowledge or their immune system, especially in mice, and the relative ease of breeding and maintaining animal colonies. Transgenic small animal models carrying entire HIV genome or selected genes have been instrumental to understand functions of HIV genes in vivo and their role in HIV pathogenesis. The type of cells in which HIV genes are expressed seems to be an import prerequisite for the study of HIV gene functions in transgenic mice. Mice constitutively expressing the entire HIV-1 genome or HIV-1 nef gene in CD4 + T cells and in the cells of macrophage/dendritic lineage develop an AIDS-like disease very similar to AIDS disease in humans. Similarly, expression of Nef in adult mice, using inducible system, results in the AIDS-like disease. This disease is characterized by thymic atrophy, impaired thymocyte maturation, loss of CD4+ T cells, increased activation and turnover of T cells, which can occur in the absence of lymphypenia, and non-lymphoid organ disease involving the lungs and kidneys. Susceptibility of adult mice to the pathological effects of Nef suggests that the AIDS-like disease in the constitutively expressing Nef Tg mice is not due to developmental defects caused by early expression of Nef. This model highlights the important role of Nef in HIV-1 pathogenesis. The high similarity in the disease in these Tg mice with human AIDS strongly suggest that these mice are a relevant model to study AIDS. This study further evidence that mouse cells can support functions of Nef and these Tg mice represent a unique model to study Nef functions in vivo in the context of the primary immune system. Moreover, the inducible Nef Tg model has given us the ability to control the level and time of expression of Nef which was impossible to do in the previously reported constitutive Nef Tg mouse models. These mice will be useful to study immune reconstitution since Nef expression can be turned off after withdrawal from dox.
35
Quirk, Calvin. "Development of a Method to Assess the Impact of Saline Infusion on Venous Physiology and Injury in Humans". Thesis, Griffith University, 2021. http://hdl.handle.net/10072/405192.
Texto completoResumen
Background and Aims: Peripherally inserted catheters (PIVCs) are one of the most commonly utilised invasive device globally [1-3]. However, despite the frequent usage of PIVCs, up to 69% [4-8] of these devices fail (unplanned removal) before the completion of therapy. Failure of PIVCs can delay treatment, cause discomfort (due to the requirement for new cannula insertion) as well as increase the risk of infection [9]. Reducing the failure rate of PIVCs by 10% (assuming a 69% failure rate and a $70 replacement fee) would also save AUD 210 million per annum, given that approximately 30 million PIVC's are used annually [2] in Australia. Considering the impact of PIVC failure on clinical practice and patient outcomes, there is a significant need to improve our understanding of the determinants of PIVC failure. The current thesis aimed to develop a method that measures the velocity of saline infusion by measuring the pressure within the infusion line. Secondly, this thesis sought to determine whether high, yet clinically relevant infusion rates (i.e. 1.5 mL/s), result in vascular damage.
Methods: The current thesis was comprised of three main parts; part 1, 2 and 3. Part 1 developed a software application using LabVIEW to assess real-time infusion flow rates from a pressure transducer. Part 2 identified the relationship between pressure and flow rate in an in vitro and in vivo system. Part 3 investigated the impact of high (1.5 mL/s) and low (0.1 mL/s) infusion flow rates on platelet activation, haemolysis, and plasma concentrations of single-stranded deoxyribonucleic acid (ssDNA).
Results: A second-order polynomial relationship existed between pressure and flow rate; with the pressure increase being proportional to the flow rate squared. The pressure values within the 22G PIVC were significantly greater than that of the 18G PIVC at the same flow rate, in both the in vitro and in vivo experiments. No significant increase was observed in blood platelet activation, haemolysis and plasma ssDNA concentration at the highest flow rate tested (1.5mL/s) when compared to the lowest flow rate tested in vivo (0.1mL/s) or between either catheter gauge (18/22G).
Conclusion: This study aimed to develop a software application that could measure real-time infusion flow rates and assess the implication of clinically relevant flow rates on the vasculature. There was a significant relationship between pressure and flow rate, and as a result, the Infusion Pressure-Rate (IPR) application was able to determine the infusion flow rate accurately. Unfortunately, due to COVID-19, the study was prematurely ended with a small number of participants for the in vivo section. As a result, no significance was observed in the platelet activation, haemolysis and plasma ssDNA concentrations between catheter gauge (18 and 22G) and flow rate (0.1 and 1.5 mL/s); however, this study was successful as several methods were developed and refined. Future studies will be able to use the application to monitor the flow rate at which clinicians flush.Thesis (Masters)
Master of Medical Research (MMedRes)
School of Pharmacy & Med Sci
Griffith Health
Full Text
36
Alhaj, Hussen Kutaiba. "Developmental architecture of human lymphopoiesis". Thesis, Sorbonne Paris Cité, 2016. http://www.theses.fr/2016USPCC308.
Texto completoResumen
Selon le modèle standard de l'hématopoïèse, la différenciation des cellules souches hématopoïétiques est un processus graduel de type arborescent. La première séparation a lieu au niveau de cellules multipotentes qui se scindent en progéniteurs lymphoïdes et myéloïdes communs. Bien que l'architecture de l'hématopoïèse humaine reste encore mal connue, de nombreux travaux suggèrent qu'elle ne suit pas le modèle standard. À ce jour encore, la question de l'existence d'un équivalent humain du CLP murin, n'a pas été tranchée. L'étude de l'hématopoïèse humaine soulève des problèmes méthodologiques. Ceci est lié au difficile accès au; prélèvements de moelle primaire et les études sur le sang placentaire ne reflètent pas complétement le développement médullaire. Dans ce travail, nous avons utilisé un modèle in vivo d'hématopoïèse foetale humaine chez la souris NSG par xénogreffe de progéniteurs du sang placentaire. La caractérisation faite sur les populations générées dans la moelle osseuse de souris a révélé que ce modèle reproduit l'hématopoïèse foetale humaine. Nous montrons que la lymphopoïèse foetale humaine présente une organisation originale caractérisée par une duplication des axes développementaux. Nos travaux mettent en évidence l'émergence indépendante de deux type de progéniteurs lymphoïdes à partir d'un intermédiaire multipotent: une population ancestrale CD127+générant principalement des lymphocytes B folliculaires, ainsi que des cellules ILC3 ; une population CD127- générant des lymphocytes T, des lymphocytes B de la zone marginale, et des cellules NK/ILC1. Ces résultats montrent que l'hématopoïèse humaine ne suit pas le modèle standard établi chez la sourisThe standard model of hematopoiesis proposes that hematopoietic differentiation is a stepwise bifurcation process. The first separation downstream of hematopoietic stem cells will segregate mutipotent progenitors into common lymphoid and myeloid progenitors. In human many evidences support the idea that human hematopoietic organization doesn't follow the classical model, but the question was not concluded and need for further investigation. Due to limited access to primary bone marrow samples and lack of appropriate in vivo model human studies face many difficulties. In this work, we used a xenogeneic model of human fetal hematopoiesis in immune-deficient mice to dissect the early stages of lymphoid development. This model relies on the injection of UCB CD34+ cells into NSG mice. Flow cytometry analysis and gene expression profiling of humanized mice BM populations revealed that this model faithfully reproduces human fetal hematopoiesis. Combining in vitro differentiation assays to molecular studies and genetic approaches, we show that fetal human lymphopoiesis displays a dual organization, split into an ancestral CD127+ CLP-like population devoid o myeloid potential that differentiate preferentially into follicular B cells and ILC3s, and into a previously undescribed CD127- population mainly dedicated to the generation of T, marginal zone B, NK, and ILC1s We also provide evidence that Early Lymphoid Progenitors emerge independently from multipotent developmental intermediates referred to as lympho-mono'dendritic progenitors. These results confirm that human hematopoiesis doesn't follow the standard model of hematopoietic differentiation established in the mouse
37
Gonzalez, Laurie Jackson. "The Influence of Membrane Lipid Order on Cell Shape and Microvesiculation in Human Erythrocytes". BYU ScholarsArchive, 2006. https://scholarsarchive.byu.edu/etd/1058.
Texto completoResumen
Exposure of human erythrocytes to elevated intracellular calcium causes alterations in cell shape and stimulates shedding of the cell membrane in the form of microvesicles. We hypothesized that both the shape transition and microvesiculation are influenced by microscopic membrane physical properties such as lipid order. To test this hypothesis, membrane properties were manipulated by varying the experimental temperature, membrane cholesterol content, and the internal ionic environment. Changes in membrane order were assessed using steady-state fluorescence spectroscopy with an environment-sensitive probe, laurdan. Our observations led us to the following conclusions: 1) the modest temperature dependence of membrane structure observed with laurdan is shifted to lower temperatures and becomes more cooperative upon removal of membrane cholesterol, 2) the calcium-induced shape change observed in erythrocytes requires a decrease in membrane order, 3) the influence of membrane order is not limited to shape transitions induced only by calcium, and 4) decreased order is also a permissive factor for microvesicle shedding. Our data suggest that while the mechansims that regulate the shape transition and the release of microvesicles are different, they both require a state of membrane disorder.
38
Mason, Nena Lundgreen. "The Anatomy of Porcine and Human Larynges: Structural Analysis and High Resolution Magnetic Resonance Imaging of the Recurrent Laryngeal Nerve". BYU ScholarsArchive, 2015. https://scholarsarchive.byu.edu/etd/5783.
Texto completoResumen
The recurrent laryngeal nerve (RLN) innervates all the intrinsic muscles of the larynx that are responsible for human vocalization and language. The RLN runs along the tracheoesophageal groove bilaterally and is often accidentally damaged or transected during head and neck surgical procedures. RLN palsy and vocal cord paralysis are the most common and serious post op complications of thyroid surgeries. Patients who suffer from RLN injury can develop unilateral or bilateral vocal fold paralysis (BVFP). Theoretically, selective reinnervation of the posterior cricoarytenoid muscle would be the best treatment for BVFP. The phrenic nerve has been shown in several studies to be the best candidate to anastomose to the distal end of a severed RLN to restore glottal abduction. Successful PCA reinnervation has been sporadically achieved in both human patients and in animal models. Another notable ramification of recurrent laryngeal nerve injury is vocal instability caused by the alteration of mechanical properties within the larynx. In phonosurgery, alterations to the position and framework of the laryngeal apparatus are made to improve voice quality. Accurate and realistic synthetic models are greatly needed to predict the outcome of various adjustments to vocal cord tension and position that could be made surgically. Despite the sporadically successful attempts at PCA reinnervation, thus far, there are still several deficits in our anatomical familiarity and technological capability, which hinder the regularity of successful PCA reinnervation surgeries and our capacity to generate synthetic models of the human larynx that are both realistic and functional. We will address three of these deficits in this project using the porcine larynx as a model. Firstly, we will identify the anatomical variations of the porcine recurrent laryngeal nerve branches. A microscribe digitizer will be used to create three-dimensional mapping of the recurrent laryngeal nerve branches that are relevant to the posterior cricoarytenoid muscle and the abduction of the vocal folds. Secondly, we will develop a magnetic resonance imaging technique to correlate recurrent laryngeal nerve branching patterns with high-resolution MR images that can be used to determine the branching patterns present in a given specimen without surgery. Lastly, we will determine the distribution and composition of different tissue types found within human vocal folds. High resolution MRI, and Mallory's trichrome and H&E histological staining will be used to distinguish and identify the tissue composition of the vocal folds and surrounding laryngeal structures. Detailed information regarding vocal fold tissue composition and histological geometry will enable laryngeal modelers to select more sophisticated and life-like materials with which to construct synthetic vocal fold models.
39
Hubbell, Zachariah Randall. "Developmental Mechanobiology of the Metaphyseal Cortical-Trabecular Interface in the Human Proximal Tibia and Proximal Humerus". The Ohio State University, 2016. http://rave.ohiolink.edu/etdc/view?acc_num=osu1452264587.
Texto completo
40
Spaw, Alexandra J. "Fetal Developmental Anatomy of the Human Cardiovascular and Central Nervous Systems Using Lugol’s Iodine Staining and Micro-Computed Tomography". Ohio University Honors Tutorial College / OhioLINK, 2014. http://rave.ohiolink.edu/etdc/view?acc_num=ouhonors1398950897.
Texto completo
41
Beck, Cameron McKell. "Construction of a COL11A1 Transgene Vector". Diss., CLICK HERE for online access, 2006. http://contentdm.lib.byu.edu/ETD/image/etd1545.pdf.
Texto completo
42
Ahmad, Faizzan Syed. "A novel human stem cell platform for probing adrenoceptor signaling in iPSC derived cardiomyocytes including those with an adult atrial phenotype". Thesis, University of Oxford, 2017. http://ora.ox.ac.uk/objects/uuid:17972018-6750-4e5c-8cc9-42e9c381f531.
Texto completoResumen
Scientific research is propelled by two objectives: Understanding and recognizing the essential biology of life, and deciphering this to uncover possible therapeutics in order to improve quality of life as well as relieve pain from disease. The aim of the work described in this thesis was to dissect the fundamental requirements of induced pluripotent stem cells both in pluripotency and differentiation with a particular focus on atrial specificity. Drug targeting of atrial-specific ion channels has been difficult because of lack of availability of appropriate cardiac cells, and preclinical testing studies have been carried out in non-cardiac cell lines, heterogeneous cardiac populations or animal models that have been unable to accurately represent human cardiomyocyte physiology. Therefore, we sought out to develop a preparation of cardiomyocytes showing an atrial phenotype with adult characteristics from human induced-pluripotent stem cells. A culture programme involving the use of Gremlin 2 allowed differentiation of cardiomyocytes with an atrial phenotype from human induced-pluripotent stem cells. When these differentiated cultures were dissociated into single myocytes a substantial fraction of cells showed a rod-shaped morphology with a single central nucleus that was broadly similar to that observed in cells isolated from atrial chambers of the heart. Immunolabelling of these myocytes for cardiac proteins (including RyR2 receptors, actinin-2, F-actin) showed striations with a sarcomere spacing of slightly less than 2um. The isolated rod-shaped cells were electrically quiescent unless stimulated to fire action potentials with an amplitude of 100 mV from a resting potential of approximately -70 mV. Proteins expressed included those for IK1, IKur channels. Ca2+ Transients recorded from spontaneously beating cultures showed increases in amplitude in response to stimulation of adrenoceptors (both alpha and beta). With the aim of identifying key signaling mechanisms in directing cell fate, our new protocol allowed differentiation of human myocytes with an atrial phenotype and adult characteristics that show functional adrenoceptor signaling pathways and are suitable for investigation of drug effects.
43
Poier, Paloma Hohmann. "Avaliação da oscilação corporal e marcha de idosos com a utilização de um andador com suporte de tronco desenvolvido na UTFPR". Universidade Tecnológica Federal do Paraná, 2013. http://repositorio.utfpr.edu.br/jspui/handle/1/744.
Texto completoResumen
Introdução: A instabilidade postural é uma das causas de incapacidade no individuo idoso e o uso de andadores é uma das estratégias para gerar maior estabilidade e segurança na manutenção da postura ortostática e na realização da marcha. Existem atualmente andadores considerados especiais por utilizarem coletes e sistemas de sustentação ou suporte parcial do corpo. Apesar dos benefícios da utilização destes andadores, estes apresentam alto custo. Com o intuito de se apresentar uma alternativa de qualidade e baixo custo, desenvolveu-se um andador com suporte de tronco confeccionado com PVC na UTFPR. O suporte de tronco acoplado ao andador tem o objetivo de suportar o peso do usuário no caso de uma queda. Objetivo: Avaliar a influência da utilização do andador desenvolvido com suporte de tronco, na oscilação corporal e marcha de idosos com instabilidade postural. Método: Foram realizados testes visando analisar a resistência mecânica do material utilizado e ensaios com o andador já construído. O PVC mostrou ser um material com alta resistência nos testes de flexão e impacto. A massa máxima suportada pelo andador no teste realizado foi de aproximadamente 226 kg. Após a avaliação do equipamento, 9 idosos com instabilidade postural foram submetidos à avaliação da oscilação corporal ou estabilometria e, 3 idosos à análise de marcha, sem e com a utilização do andador desenvolvido. Resultados: Com a utilização do andador desenvolvido houve diminuição da oscilação corporal em todos os idosos participantes. Sem a utilização do equipamento o valor médio da estabilometria foi de 10,297 cm² e com o andador foi de 3,264 cm². Na avaliação da análise de marcha com sensores acelerômetros localizados na articulação do quadril, sem o andador desenvolvido, os idosos tiveram uma maior extensão e menor flexão e, com o andador estes valores inverteram-se. Com o andador, a média da flexão direita passou de 15,33° para 20,67° e a extensão de 10° para 7,33°. O tempo necessário para realização de um percurso de 12 metros foi maior com a utilização do andador desenvolvido. Os resultados apontam para uma melhora na estabilidade e equilíbrio do idoso com a utilização do andador. A análise da marcha demonstrou uma reorganização da amplitude da passada, mas sem uma alteração significativa.Introduction: Postural instability is one of the causes of disability in the elderly and the use of walkers is one of the strategies to generate greater stability and safety in the maintenance of orthostatic posture and gait. There are currently walkers considered to be specials because they have braces and support systems or offer partial support of the body. Despite the benefits of using these walkers, they are very expensive. In order to present an alternative of quality and low cost, a walker with trunk support was developed, made of PVC. The trunk support attached to the walker is intended to support the weight of the user in the event of a fall. Objective: To evaluate the influence of the use of the walker with trunk support on body sway and gait of the elderly with postural instability. Method: Tests were carried out to analyze the mechanical resistance of the material used as well as the structure of the walker. PVC has proven to be a material with high resistance when submitted to flexion and impact tests. The maximum mass supported by the walker in the test was approximately 226 kg. After testing the equipment, 9 elderly with postural instability were submitted to evaluation of the body sway or stabilometry, and 3 elderly to gait analysis, with and without the use of the walker developed. Results: Using the walker there was a decrease of body sway in all elderly participants. Without the use of the equipment the stabilometry average value was 10,297 cm² and when using the walker it was 3.264 cm². In the evaluation of gait analysis with accelerometer sensors located at the hip joint, without the walker the elderly had greater hip extension and lower hip flexion and, with the walker the results had inverted values. For that, the average flexion on the right hip rose from 15.33° to 20.67° and the extension decreased from 10° to 7.33°. The time needed to finish a course of 12 meters was higher using the walker. The results point to an improvement in stability and balance for the elderly using the walker. The gait analysis demonstrated a reorganization of the length of the stride but without a significant change.
44
Huyard, Fanny. "Impact du stress hyperoxique en période néonatale sur la structure vasculaire : implication des phénomènes de sénescence et rôle possible dans la programmation développementale de l'hypertension artérielle". Thèse, Université de Lorraine, 2013. http://hdl.handle.net/1866/12773.
Texto completoResumen
Réalisé en cotutelle avec l'Université de Lorraine (France)Ce projet traite de la programmation développementale de l’hypertension artérielle (HTA) à travers des influences néonatales précoces pouvant moduler le développement vasculaire. Les bébés prématurés présentent des défenses antioxydantes diminuées comparés aux nouveau-nés à terme et sont exposés à la naissance à des concentrations élevées en oxygène (O2) engendrant la production d’espèces réactives de l’O2 (ERO). Les conséquences vasculaires à long terme de dommages liés aux ERO en période néonatale et les mécanismes impliqués sont très partiellement compris. Les précédents résultats du laboratoire ont montré qu’un stress hyperoxique néonatal conduit chez le rat adulte à de l’HTA, une dysfonction endothéliale et une rigidité artérielle, éléments de vieillissement vasculaire. Nous émettons l'hypothèse qu'un stress hyperoxique néonatale conduit à long terme à l'altération de la structure vasculaire et à un vieillissement vasculaire précoce. Nous avons démontré une diminution de la prolifération cellulaire, une capacité angiogénique altérée, des dommages à l’ADN et une augmentation de l’expression de protéines de sénescences (des indices de sénescence cellulaire) au-delà de la période néonatale suite à une exposition brève à l’O2 au niveau vasculaire dans un modèle animal (ratons Sprague-Dawley exposés à 80 % d’O2 du 3ème au 10ème jour de vie comparés à des ratons restés à l’air ambiant) et cellulaire (cellules musculaires lisses d'aortes thoraciques d'embryon de rat exposées à 40% O2 pendant 24h ou 48h, puis remises en normoxie pendant 96h). De plus, des altérations des composants de la structure vasculaire indiquant un remodelage vasculaire aortique ont été mises en évidence. Ces changements précèdent tous l’HTA et la dysfonction vasculaire observées dans le modèle animal à l’âge adulte et pourraient y contribuer. L’étude de jeunes adultes nés < 29 semaines comparés à des jeunes adultes nés à terme indique une augmentation de marqueurs de rigidité artérielle (indices d’un vieillissement vasculaire précoce) chez la population prématurée. L’ensemble des résultats démontre un vieillissement vasculaire précoce après une exposition néonatale transitoire à un stress hyperoxique permettant une meilleure compréhension des mécanismes physiopathologiques impliqués dans la survenue des troubles vasculaires retrouvés chez l’adulte et contribue à la mise en place de moyens de prévention chez des patients prématurés.
The scope of this thesis is developmental programming of arterial high blood pressure (HBP) hypertension through early neonatal stimuli that may alter vascular development. Premature newborns have decreased antioxidant defenses compared to term babies and are exposed upon birth to high oxygen (O2) concentration, causing reactive oxygen species (ROS) production. Long term vascular consequences of ROS related damage during the neonatal period and the mechanisms involved remain unknown. Recent data from the laboratory show that neonatal hyperoxic stress leads in adult rat to HBP, endothelial dysfunction and arterial rigidity, characteristic features of vascular aging. We hypothesize that a neonatal hyperoxic stress leads to long term vascular structure alteration explained by an early aging of the vascular system. We showed a decreased proliferation rate, an altered angiogenic capacity, as well as long term DNA damage and increased expression of senescence proteins at a vascular level following O2 exposure in the animal (male Sprague-Dawley pups kept at 80% O2 from postnatal days 3 to 10 vs. rats remained in room air) and cellular models (embryonic vascular smooth muscle cells from rat thoracic aorta exposed to 40% O2 for 24h or 48h followed by 96h recovery in control conditions). In addition, alterations of vascular structure components indicating vascular remodeling was shown before the onset of the HBP at adult age. Those changes precede the HBP and vascular dysfunction observed in our animal model at adult age and could contribute to them. Study of young adults born before 29 weeks vs. young adults born at term showed that young adults born preterm present indices of arterial stiffness vs. term controls. Results of the present thesis demonstrate a major role of premature vascular aging in the surge of vascular diseases in adulthood and contribute to a better understanding of the patho-physiological mechanisms involved and could put into practice new prevention strategies among preterm patients.
45
Goel, Vritti R. "A Proposal to Test the Effects of Factor ECAT1 on Pluripotency, from Reprogramming to Differentiation of Human Somatic Cells". Scholarship @ Claremont, 2012. http://scholarship.claremont.edu/cmc_theses/470.
Texto completoResumen
The field of stem cell research has been growing more because of the interest in using stem cells to cure diseases and heal injuries. Human embryonic stem cells, because of the controversy surrounding them—and subsequently the difficulties in acquiring samples of the existing aging cell lines—can only be used in limited capacities. While the development of induced pluripotent stem cells in the last decade has allowed the field to progress closer to medical treatments, the low efficiency of reprogramming a somatic cell to a pluripotent state, and the vast molecular and genomic differences between human embryonic stem cells and human induced pluripotent stem cells is still an issue. Therefore, the goal is to discover methods, chemicals, and factors that can reduce these differences and increase the efficiency of inducing pluripotency.
This proposal aims to look at the effects of the protein ECAT1 in inducing pluripotency in human somatic cells. Little is known about ECAT1, otherwise known as Embryonic Stem Cell-Associated Transcript 1, beyond its presence in human embryonic stem cells and oocytes and its absence in differentiated cells. While originally considered by scientists during the development of the reprogramming technique, ECAT1's effects have not been tested in humans. Therefore, a series of experiments will be performed in which ECAT1 will be used in conjunction with OSKM to induce pluripotency in adult human dermal fibroblasts, which will then be differentiated into spinal motor neurons. The three stages of this proposal--inducing pluripotency, comparing pluripotencies in the reprogrammed cells and embryonic stem cells, and differentiating the stem cells--should answer questions about ECAT1 and the reprogramming process. It is predicted that ECAT1 should reduce the genomic and molecular differences between embryonic stem cells and induced pluripotent stem cells. ECAT1's presence should also increase the efficiency of reprogramming as well as successful differentiation to other cell types.
46
Martel, Marie. "Body representations in action : development and plasticity in the sensory guidance of prehension". Thesis, Lyon, 2016. http://www.theses.fr/2016LYSE1288.
Texto completoResumen
Planifier, exécuter un mouvement fait appel à des représentations mentales de l'action. Ces dernières ont été formalisées par les sciences computationnelles sous le terme de modèles internes du contrôle moteur. Outre l'environnement, les informations concernant la posture, les dimensions de l'effecteur sont également cruciales et doivent être mises à jour fréquemment. Etonnamment, les modèles actuels de l‘action n'attribuent pas aux représentations du corps un rôle majeur. La mise à jour de ces représentations de l'action et du corps doit intervenir dès l'enfance, néanmoins leur développement reste méconnu. En premier lieu, je me suis attachée au développement des représentations de l'action chez les enfants de 5 à 10 ans, au développement typique d'une part et lors de Troubles des Acquisitions et de la Coordination (TAC) d'autre part. A travers la cinématique, j'ai cherché à comprendre comment les enfants développent leur capacité à anticiper et adapter leurs mouvements. Dans un deuxième temps, l'utilisation d'un outil qui allonge fonctionnellement le bras m'a permis d'examiner les inputs sensoriels (vision, proprioception) nécessaires à la plasticité des représentations du corps chez l'adulte. Enfin, j'ai interrogé ces mécanismes de plasticité des représentations de l'effecteur au cours de la croissance de l'individu alors que les dimensions corporelles changent progressivement. Dans ce but, j'ai étudié la plasticité induite par l'outil chez des enfants et adolescents au développement typique. Finalement, je discuterai des liens entre représentations du corps et contrôle moteur, deux notions indispensables à la cognition motriceTo prepare and perform movements efficiently, accurate action representations are necessary, formalized by computational science as “internal models”. Actions representations do not require exclusively the representation of object properties, information about the body and particularly the effector such as its posture and dimension are also crucial. Thus, effector representations need to be updated to account for postural changes, yet, they do not play a prominent role in the actual models of motor control. In addition, updates settings of both action and body representation are presumably established ontogenetically, but little is known on their developmental path. First, I investigated the maturation of action representation in children from 5 to 10 years of age, as well as the potential differences in children with Developmental Coordination Disorder (DCD). Through kinematics analyses, I sought to understand how children develop their ability to control their movements. Second, using a tool functionally extending arm length, I questioned the sensory inputs for body representation plasticity in adults, such as proprioception and vision. Third, I probed rapid body representations plasticity during the slowly changing dimensions of the body during growth. To this aim I investigated in typically developing children and adolescents tool-induced plasticity of the upper-limb representation. Finally, I discuss the relationship between body representations and motor control in adults and children, as despite being both related they have often times walked parallel ways
47
Puard, Vincent. "Marqueurs non-invasifs de la compétence ovocytaire au développement dans les cellules de cumulus chez l'humain". Thesis, Tours, 2013. http://www.theses.fr/2013TOUR3310/document.
Texto completoResumen
Prédire la capacité de développement et d'implantation des embryons reste un enjeu majeur pour l’Assistance Médicale à la Procréation (AMP). L’AMP doit répondre au désir du couple d’avoir un enfant en limitant les risques encourus par la mère et l’enfant en cas de grossesse multiple. Tous les laboratoires d’AMP utilisent des critères morphologiques pour évaluer la compétence au développement des embryons en dépit de la faible valeur prédictive de cette analyse. L'interaction ovocyte-cumulus participe à l’acquisition par l'ovocyte de sa compétence au développement. Cette interaction met en jeu l’expression de gènes spécifiques dans les cellules de cumulus (CCs). Notre objectif était d'identifier des marqueurs non invasifs de la compétence ovocytaire au développement. Ainsi nous avons recherché au niveau des CCs des gènes et des protéines exprimés en fonction de l’aptitude de l’ovocyte fécondé à atteindre le stade de blastocyste. L'expression des gènes des CCs a été étudiée par puce à ADN et qPCR haut débit. Après avoir tenu compte de la variabilité des patientes, nous avons identifié les gènes RGS2, POLR3K et CUL4B comme biomarqueurs. L'expression des protéines des CCs a été étudiée par puce à protéines et après validation des anticorps ciblant les protéines d'intérêt, les protéines RGS2, POLR3K et MERTK ont été identifiées comme biomarqueurs de la compétence au développement de l'ovocyte. Ces résultats permettent d’envisager la création d’un modèle prédictif multicritère incluant la morphologie de l’embryon à J2, les gènes et protéines marqueursThe ability to predict the developmental and implantation ability of embryos remains a major goal in human assisted reproductive technology (ART).ART should allow couple to become parents while limiting the risks to the mother and the child in case of multiple pregnancy. ART laboratories use morphological criteria to evaluate the oocyte competence despite the poor predictive value of this analysis. The oocyte-cumulus interaction helps the oocyte to acquire its developmental competence partly through the expression of specific genes at the cumulus level. Therefore our aim was to identify at the level of cumulus cells (CCs) genes and proteins related to oocyte developmental competence as non-invasive marker. Gene expression of CCs was studied using microarray and high throughput qPCR according to the developmental competence of the oocyte (ability to reach the blastocyst stage after fertilization). While taking into account the patient variability we identified RGS2, POLR3K and CUL4B as biomarkers at RNA level. Then protein expression of CCs was studied using Reverse Phase Protein Array. After validation of the antibodies targeting the proteins of interests, RGS2, POLR3K and MERTK were identified as protein biomarkers of the developmental competence of the oocyte. These results lead us to consider a multi variables predictive model including the morphology of the embryo at J2, genes and protein markers
48
Osama, Mohammad. "Function of Vascular Endothelial Cells in Aging and Hypothermia: Clinical Implications". Ohio University / OhioLINK, 2018. http://rave.ohiolink.edu/etdc/view?acc_num=ohiou1534939514503588.
Texto completo
49
Le, Bourgot Cindy. "La supplémentation périnatale en fibres prébiotiques (fructo-oligosaccharides à courte chaîne, scFOS) modifie le microbiote intestinal et programme le phénotype métabolique et immunitaire du porc, pris comme modèle de l’Homme". Thesis, Rennes, Agrocampus Ouest, 2016. http://www.theses.fr/2016NSARB285/document.
Texto completoResumen
La nutrition périnatale conditionne durablement les fonctions physiologiques, avec des conséquences sur la susceptibilité à développer des maladies métaboliques à l’âge adulte. Le microbiote représente un des acteurs de cette empreinte nutritionnelle. L’objectif est de déterminer chez le porc l’impact d’une supplémentation périnatale en fructo-oligosaccharides à courte chaîne (scFOS) sur le développement des fonctions immunitaires et endocrines intestinales et les conséquences sur la santé métabolique de l’adulte en situation de déséquilibre nutritionnel.La supplémentation maternelle en scFOS, en modifiant le microbiote de la mère et de la descendance et la qualité du lait, accélère la maturation du système immunitaire intestinal des porcelets allaités.La fenêtre d’exposition (maternelle vs post-sevrage) conditionne la nature des modifications immunes induites par les scFOS. La supplémentation périnatale en scFOS modifie la réponse métabolique de l’adulte à un régime déséquilibré en stimulant la fonction endocrine intestinale et la sensibilité du pancréas au glucose, en réduisant les risques d’inflammation, et en modifiant l’homéostasie métabolique, associé à des modulations du microbiote.En résumé, la consommation périnatale de prébiotiques programme le phénotype métabolique et immunitaire de l’adulte via des modulations persistantes du microbiote. L'approche intégrée des données a permis d’identifier des acteurs moléculaires impliqués dans l’adaptation différentielle des individus à un régime déséquilibré en fonction de leur alimentation périnatalePerinatal scFOS supplementation modifies metabolic response to an unbalanced diet in adults by stimulating intestinal endocrine function and pancreas sensitivity to glucose, by reducing risks of inflammation, and in fine by changing metabolic homeostasis in association with modifications of microbiota.In summary, prebiotic consumption during perinatal life programs the immune and metabolic phenotype of adults through persistent modulations of intestinal microbiota. The integrated approach of data enables us to identify molecular actors involved in the differential adaptation of individuals to an unbalanced diet according to their perinatal nutrition
50
Gosling, Cameron McRae. "Development of an incremental step test that accounts for lower limb length for people undergoing rehabilitation". Thesis, 1996. https://vuir.vu.edu.au/17883/.
Texto completoResumen
This study developed a multi-stage step test for the prediction of VO2peak in people with low tolerance to exercise. The aim was to develop a simple and safe protocol, that accounted for differences in statute height and is suitable for use in exercise rehabilitation. The step height (Hstep) was determined as 0.125 x the subject's height (Hsubject. People undergoing physical and psychological rehabilitation (n=23) were compared to a normal group (n=28), not undergoing rehabilitation. The symptom-limited step test began at a low cadence (14 cycles per minute, c.min-1) and increased by 4 c.min-1 to VO2peak. Peak values for rehabilitation subjects for VO2 and heart rate were 27.8 ± 6.2 ml.kg-1.min-1 and 168 ± 21 b.min-1, respectively. The corresponding peak values for normal subjects were 36.5 ± 6.8 ml.kg-1 .min-1 and 180 ± 15 b.min-1,
respectively. Five variables were entered into multiple quadratic regressions, to generate algorithms for the prediction of submaximal and peak VO2: age, sex, weight,
time and heart rate. Three algorithms were produced "All", "Normal" and "Rehabilitation". They explained 90%, 91% and 94% of the variation in results (r2 =0.90, 0.91, 0.94), with standard errors of 2.86, 2.72 and 2.04 ml.kg-1.min-1, respectively. It is envisaged that the test will be used to predict functional capacity in people undergoing exercise rehabilitation.