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Inoue, Bruna Hitomi. "Bases moleculares da microalbuminúria associada à hipertensão arterial essencial: papel da reabsorção tubular de albumina." Universidade de São Paulo, 2012. http://www.teses.usp.br/teses/disponiveis/5/5166/tde-13122012-161119/.
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Evidências epidemiológicas indicam que a presença de microalbuminúria prediz maior freqüência de eventos cardiovasculares e mortalidade em hipertensos essenciais. A microalbuminúria pode ser decorrente do aumento da permeabilidade glomerular e/ou da diminuição da reabsorção desta macromolécula no túbulo proximal. Todavia não é sabido se os mecanismos que regulam a reabsorção de albumina em túbulo proximal renal encontram-se alterados na hipertensão essencial. Este trabalho teve como objetivo investigar as bases moleculares da microalbuminúria associada à hipertensão arterial essencial, focando na reabsorção tubular de albumina. Para tanto, avaliamos a evolução temporal da excreção urinária de albumina em ratos espontaneamente hipertensos (SHR) com 6 semanas de idade (pressão arterial sistólica, PAS, = 105 ± 4 mmHg), 14 semanas de idade (PAS = 180 ± 2 mmHg) e 21 semanas de idade (PAS = 202 ± 2 mmHg). Ratos normotensos Wistar da mesma idade serviram de controle. Observou-se que a excreção urinária diária de albumina aumentou progressivamente com o aumento da pressão arterial em SHR (10,5 ± 1,9; 92 ± 7,0 e 154 ± 27 g/dia, em SHR com PAS média igual a 105, 180 e 202 mmHg respectivamente). Este aumento progressivo não foi observado em ratos normotensos com idade correspondente, indicando que este fenômeno é decorrente do aumento da pressão arterial e não pode ser atribuído ao aumento da idade dos animais durante o período estudado. A análise das proteínas urinárias por eletroforese em gel de poliacrilamida (SDS-PAGE) mostrou que SHR excretam proteínas do tamanho da albumina ou menores (< 70kDa), padrão típico de proteinúria tubular. Adicionalmente, verificou-se que os níveis de expressão dos receptores endocíticos megalina e cubilina, bem como do canal para cloreto ClC-5 diminuem progressivamente no córtex renal de SHR com o aumento da pressão arterial. Observou-se também uma diminuição significativa na expressão de uma outra macromolécula importante no processo de endocitose mediada por receptor em túbulo proximal renal, a v-H+-ATPase. Entretanto, a diminuição da expressão protéica da subunidade B2 desta ATPase foi estatisticamente significante apenas em SHR com 21 semanas comparado aos com 6 semanas de idade. Não foram encontradas alterações no padrão de expressão de componentes estruturais da barreira glomerular como a nefrina e podocina. Em suma, o nosso estudo demonstra que o aumento da excreção urinária de proteínas, especialmente de albumina, está associado com uma menor expressão de componentes essenciais do aparelho endocítico do túbulo proximal renal. É tentador especular que a disfunção da via endocítica no túbulo proximal renal possa ser o principal mecanismo subjacente ao desenvolvimento de microalbuminúria na hipertensãoEpidemiological evidences indicate that the presence of microalbuminuria predicts a higher frequency of cardiovascular events and mortality in essential hypertensive patients. Microalbuminuria may arise from increased glomerular permeability and/or reduced proximal tubular reabsorption of albumin. However, it remains to be determined whether the mechanisms that regulate the renal proximal tubular reabsorption of albumin are altered in essential hypertension. The purpose of this work was to investigate the molecular basis of microalbuminuria in essential hypertension, focusing on the renal tubular reabsorption of albumin. To this end, we evaluated the temporal evolution of urinary albumin excretion in spontaneously hypertensive rats (SHR) at 6 weeks of age (systolic arterial pressure, SAP, = 105 ± 4 mmHg), 14 weeks of age (SAP = 180 ± 2 mmHg) and 21 weeks of age (SAP = 202 ± 2 mmHg). Age-matched normotensive Wistar rats were used as controls. It was observed that the daily urinary excretion of albumin progressively increased with blood pressure in SHR from 6 to 21 weeks of age (10.5 ± 1.9, 92 ± 7.0 and 154 ± 27 g in SHR with 105, 180 and 202 mmHg of average SAP, respectively). This progressive increase in microalbuminuria has not been observed in age-matched normotensive Wistar rats, indicating that this phenomenon cannot be attributed to age progression over the studied period. SDS-PAGE analysis of urinary proteins showed that microalbuminuric SHR virtually excreted proteins of the size of albumin or smaller (< 70kDa), typical of tubular proteinuria. Additionally, it was verified that the protein expression levels of the endocytic receptors megalin and cubilin as well as of the chloride channel ClC-5 progressively decreased in the renal cortex of SHR from 6 to 21 weeks of age. Moreover, it was observed reduction of expression of another macromolecule that plays an important role in the process of receptor mediated endocytosis in the renal proximal tubule, the v-H+- ATPase, was reduced. However, reduced cortical expression of the B2 subunit of the v- H+-ATPase, was only statistically significant in 21-wk-old vs. 6-wk-old SHR. Expression levels of structural components of the glomerular barrier such as nephrin and podocin were unchanged. To sum up, our study demonstrates that the increase in urinary protein excretion, especially of albumin, is associated with lower expression of key components of the apical endocytic apparatus in the renal proximal tubule. It is tempting to speculate that dysfunction of the apical endocytic pathway in the renal proximal tubule may be the major mechanism underlying development of microalbuminuria in essential hypertension
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Larsson, Mårten. "Megalin, an Endocytotic Receptor with Signalling Potential." Doctoral thesis, Uppsala University, Department of Medical Biochemistry and Microbiology, 2006. http://urn.kb.se/resolve?urn=urn:nbn:se:uu:diva-6585.
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Megalin is an endocytotic receptor belonging to the low-density lipoprotein family. It has often been viewed only as merely a scavenger receptor of absorptive and secretory epithelia. Recent work has revealed that the megalin intracellular domain contains several motifs potentially binding proteins involved in signal transduction.
To find potential intracellular proteins binding to megalin, a yeast two-hybrid screening was initiated with the intracellular tail of megalin as the bait. A partial clone encoding the scaffolding protein postsynaptic protein 95 (PSD-95) was found to bind to megalin with its second PDZ-domain. Co-localization experiments in HEK-293 cells and kidney, placenta and parathyroid tissue confirmed this interaction. The PSD-95 related proteins PSD-93 and SAP102 were also confirmed to bind megalin with their PDZ2-domains, but the corresponding domain from SAP97 did not bind. Mutation analysis revealed that an amino acid residue change Ala to Thr was the cause of this.
Megalin has within the central nervous system (CNS) been shown to be expressed only in the ependymal cells and choroid plexus. Nothing has been known about megalin expression in the spinal cord. To study spatio-temporal expression of megalin in the spinal cord, extensive staining of prenatal and postnatal mouse spinal cord was undertaken. Megalin expression was found in the dorsal part of the embryonic spinal cord. Most of these cells also expressed vimentin, suggesting that megalin has a role in the normal development of astrocytes. In the postnatal mouse, megalin seems to be expressed in oligodendrocytes only in the spinal cord white matter, and co-incident with myelination. This suggests that megalin is involved in the formation and maintenance of myelin along long spinal pathways. Megalin staining was clearly seen in the nucleus of these cells, indicating that megalin works in a notch-like signalling pathway.
Uptake of retinol to the retina pigment epithelium (RPE) has long been thought to be a diffusion process. Staining for megalin in RPE revealed strong expression, and uptake experiments with 3H-retinol bound to retinol-binding protein and blocking with the LDL-receptor family specific antagonist receptor-associated protein (RAP) showed that megalin is a receptor for uptake of retinol to the RPE.
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Wicher, Grzegorz. "Clusterin and Megalin in The Spinal Cord." Doctoral thesis, Uppsala : Acta Universitatis Upsaliensis, 2006. http://urn.kb.se/resolve?urn=urn:nbn:se:uu:diva-7365.
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Borba, Susan Caroline Pinto. "Pesquisa de anticorpos anti-megalina em pacientes transplantados renais." Universidade de São Paulo, 2010. http://www.teses.usp.br/teses/disponiveis/5/5146/tde-13092010-161121/.
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Introdução: O papel do sistema HLA na evolução do transplante é indiscutível. Dados da literatura internacional e do nosso laboratório têm mostrado que este não é o único sistema envolvido nos processos de RMA (rejeição mediada por anticorpo) Esse fato é comprovado a partir da constatação de que transplantes realizados entre irmãos com total identidade HLA também são alvos da RMA. Entretanto, os alvos antigênicos desses anticorpos permanecem desconhecidos, dificultando assim o diagnostico e tratamento da RMA não-HLA. No transplante renal a presença desses anticorpos têm sido associada com anticorpos anti células endoteliais, células epiteliais tubulares, podocitos, células mesangiais e monócitos. Nosso objetivo neste estudo foi avaliar a presença e a relevância clínica de anticorpos contra a megalina, membro da família de receptores de LDL, expressa na membrana apical dos túbulos proximais, com importante papel na reabsorção de proteínas no rim. Métodos: Soros pré-transplante de 105 pacientes submetidos a transplante renal, realizado no Serviço de Transplante Renal do Hospital das Clínicas da Faculdade de Medicina da Universidade de São Paulo (UTR-HC-FMUSP) foram testados por ELISA contra 2 peptídeos da megalina estudados e sintetizados em nosso laboratório. (convencionalmente chamados 18 e 19) Resultado: Não foi detectada a presença de anticorpos do isotipo IgG nas amostras prétransplante dos pacientes estudados. Entretanto, foi detectada a presença de anticorpos do isotipo IgM anti-peptídeo 18 em 33 (31,4%) amostras de soro e anti-peptídeo 19 em 23 (21,9%). Para avaliar a significância clinica desses anticorpos dividimos os pacientes em 2 grupos: pacientes com pelo menos 1 episodio de rejeição aguda (Grupo I) e pacientes sem rejeição (Grupo II) e observamos a distribuição dos pacientes positivos nos 2 grupos. O numero de pacientes com anticorpos anti-peptídeo 18 foi igualmente distribuída nos dois grupos. (12/42, 28,5% no Grupo I e 21/63, 33,3% no Grupo II p=ns). A maioria dos pacientes com anticorpos anti-peptídeo 19 pertenciam ao grupo I (17/42, 40,5% ; 6/63, 9,5% p=0,0003). Esta analise demonstrou uma boa correlação entre presença de anticorpos anti-peptídeo 19 no soro pré-transplante e rejeição. Conclusão: Nossos dados sugerem que anticorpos IgM anti-megalina no pré-transplante podem ser um fator de risco na rejeição do aloenxerto renal. É importante salientar que a nosso conhecimento este é o primeiro estudo envolvendo megalina e rejeição no transplante clínico.Background. Preformed donor-specific human leukocyte antigen (HLA)- antibodies are accountable for the majority of antibody-mediated rejections (AMR). However, recipients of HLA identical kidneys can develop AMR implicating putative pathogenic antibodies that are directed against non-HLA antigens. Unknown immune targets and consecutive lack of detection methods make non-HLA AMR particularly difficult to diagnose and treat. In renal transplant rejection, the presence of antibodies to non-HLA has been associated with antibodies against endothelial cells, tubular epithelial cells, podocytes, mesangial cells and monocytes. The aim of this study was to evaluate the presence and clinical relevance of preformed antibodies against megalin, a member of the LDL receptor family, expressed on the apical membrane of proximal tubules. Megalin performs a central role in renal protein reabsorption. Methods. Pré-transplant sera of 105 recipients of kidney allograft transplanted at Serviço de Transplante Renal do Hospital das Clínicas da Faculdade de Medicina da Universidade de São Paulo (STRHCFMUSP) were tested by enzyme-linked immunosorbent assay (ELISA) against 2 megalin-peptides (conventionally named 18 and 19) studied and synthetized in our laboratory. Results. Antibodies were not detected in pretranplant sera when tested for IgG isotype. However, in 33 (31,4%) sera we detected the presence of IgM antibodies to megalin-peptide18 and in 23 (21,9%) to megalin-peptide 19. To evaluate the clinical significance of these antibodies we divided the patients in 2 groups: Group I - 42 patients with at least one rejection episode during the first post-transplant year and Group II - 63 patients without any rejection episode and observed the distribution of positive patients in each of the 2 groups. Patients with megalin-peptide18 antibodies had the same distribution in both groups. (12/42, 28, 5% Group I and 21/63, 33,3% no Group II p=ns). However, patients with megalinpeptide19 antibodies were more frequent in group I. (17/42, 40,5% group I and 6/63, 9,5% group II p=0,0003). This analysis demonstrated a good correlation between preformed anti-megalin-peptide19 antibodies and allograft rejection Conclusion. Our data suggest that presence of IgM megalin antibodies before transplantation might be a risk factor for kidney allograft rejection. To our knowledge, this is the first study involving megalin and rejection in clinical transplantation.
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Baines, Richard John. "Megalin cytoplasmic tail phosphorylation and function in kidney proximal tubular cells." Thesis, University of Leicester, 2011. http://hdl.handle.net/2381/9513.
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Kastner, Christian [Verfasser]. "Tubuläre Volumenregulation bei Glomerulonephritis in der Megalin-teildefizienten Maus / Christian Kastner." Berlin : Freie Universität Berlin, 2012. http://d-nb.info/1026695155/34.
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Burmeister, Regina. "Untersuchungen zur Rolle des Endozytoserezeptors Megalin in der zellulären Aufnahme von Steroidcarrierproteinen." [S.l.] : [s.n.], 2003. http://deposit.ddb.de/cgi-bin/dokserv?idn=967999014.
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Akour, Amal. "The role of megalin in the transport of aminoglycosides across human placenta." VCU Scholars Compass, 2012. http://scholarscompass.vcu.edu/etd/448.
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Background: Intra-amniotic infections (IAIs) are common complications of labor and delivery. If inadequately treated, these infections can lead to significant morbidity and mortality in the mother and the fetus. Intrapartum aminoglycoside (AG) administration is recommended for the management of IAIs. AGs are known to cross the placenta and achieve bactericidal concentrations in fetal serum. However, the highest and most persistent fetal levels are achieved in renal tissue. So, the fetus may be vulnerable to the nephrotoxic effects of AGs. Megalin, a 600 kDaendocytic receptor, is responsible for the uptake of AGs into renal proximal tubular epithelial cells. This receptor is also expressed in human term placenta and it is reasonable to speculate that it is similarly involved in the placental transport of AGs. However, the mechanisms responsible for placental AG uptake and transport have not yet been characterized. Objective: To evaluate the role of megalin in the transport of AGs across human placenta. Specific aims: (1) To assess and compare megalin expression in term and preterm placental villous tissue, and (2) assess the functional activity of megalin in in vitro placental models. Methods: (1) Following IRB approval, placental tissue samples were collected from pregnant women undergoing term or preterm deliveries. Placental villous tissueswere used to quantify megalin expression by western blotting and q-PCR (2) The human choriocarcinoma cell line (BeWo cells) were grown on Transwell plates, and then megalin expression and function were assessed. Results: Megalin protein and mRNA expression were confirmed in samples of human placental villous tissues. Megalin mRNA expression declined steeply with gestational age till week 31 of gestation then it plateaued thereafter. Also, the expression in the early preterm (n=2) was six fold higher than that of both late preterm (n=3) and term placenta (n=10) (p<0.05). The uptake of 3H-gentamicin by the BeWo cells was time-dependent, saturable (Vmax=42.9 ± 4.9 nmol/mg protein/min; Km=2.93±0.68mM) and partially inhibited by megalin inhibitors. Conclusion: Megalin is expressed in human placental villous tissues as well as the BeWo cells. When grown on Transwell® plates, the BeWo cells appear to be the most appropriate model to study the in vitro transport of AGs across the apical membrane. Time, temperature and concentration dependence of gentamicin uptake in the BeWo cells indicate protein-mediated transport. The inhibition data are consistent with megalin-mediated endocytosis of AGs.
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Burmeister, Regina. "Untersuchungen zur Rolle des Endozytoserezeptors Megalin in der zellulären Aufnahme von Steroidcarrierproteinen." Doctoral thesis, Humboldt-Universität zu Berlin, Mathematisch-Naturwissenschaftliche Fakultät I, 2003. http://dx.doi.org/10.18452/14867.
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Der Endozytoserezeptor Megalin gehört zu einer Gruppe von strukturell und funktionell verwandter Rezeptoren, der LDL R Gen Familie. Es sind zwei Arten von Lipidtransportpartikel beschrieben worden, die durch Megalin in Zellen aufgenommen werden. Zum einen werden Lipoproteine über ihre Apoproteine von Megalin erkannt und endozytiert. Zum anderen nimmt Megalin die hydrophoben Vitamine A und D über ihre Carrierproteine in ihre Zielzellen auf. Es handelt sich um Vitamin D bindendes Protein (DBP) und Retinol bindendes Protein (RBP). Zweck dieser Arbeit war es zu untersuchen, ob die Endozytose von Steroidcarriern durch Megalin ein genereller Mechanismus ist oder ob DBP und RBP Ausnahmen darstellen. Hierzu wurden exemplarisch drei Carrierproteine (24p3, Apo D und CCSP) für Steroide ausgesucht, die in Megalin-exprimierende Gewebe aufgenommen werden. Der (rekombinante) Retinolcarrier 23p3 zeigte bei surface plasmon resonance Analysen keine direkte Bindung an Megalin. Der Progesteron-Carrier Apo D hingegen bindet Megalin, ferner konnte in Zellkulturversuchen Endozytose und lysosomale Degradation von Apo D in Megalin-exprimierende Zellen nachgewiesen werden. Auch der Progesteron-Carrier CCSP wird durch Megalin in Zellen aufgenommen, allerdings ist zur Endozytose von CCSP ein Co-Rezeptor notwendig. Mit dieser Arbeit ist die erste in vivo-Beschreibung eines dualen Rezeptorsystems aus Megalin und einem peripheren Membranprotein namens Cubilin gelungen, welches u.a. im proximalen Tubulus der Niere existiert. Abschließend wurde exemplarisch für ein Steroidhormon-abhängiges Gewebe der murine Uterus hinsichtlich seiner Megalin-Expression untersucht. Es konnte ein bereits bekannter Ligand Megalins, das Glykoprotein Laktoferrin, aus der uterinen, luminalen Flüssigkeit aufgereinigt werden. Ferner konnte gezeigt werden, dass die Expression von Laktoferrin im Uterus strenger hormoneller Kontrolle unterliegt.The endozytic receptor Megalin belongs to a group of structurally and functionally related receptors called LDL R gene family. Two different types of lipid particles are taken up by Megalin into target cells. The first type, lipoproteins are recognized and internalized by Megalin via their apoproteins. In addition, Megalin mediates the endocytosis of the lipophilic vitamins A and D into target cells by means of their carrier proteins. These proteins are the vitamin D binding protein (DBP) and retinal binding protein (RBP). The aim of the investigations was to determine, if the endocytosis of steroid hormone carriers by Megalin is a common occurrence or restricted only to DBP and RBP. Therefore, three carrier proteins for steroids (24p3, Apo D and CCSP) were chosen as an example. All of them are known to be taken up in Megalin expressing tissues. In surface plasmon resonance analysis recombinant 24p3, a carrier of retinol, showed no affinity to Megalin. Whereas the progesterone carrier Apo D bound to Megalin. Furthermore, it was endozytosed and degraded in lysosomes by Megalin expressing cells. The cellular uptake of the progesterone carrier CCSP is mediated by Megalin as well, however a co-receptor is needed. This work demonstrates for the first time the existence of a dual receptor pathway consisting of Megalin and a peripheral membrane protein named Cubilin in vivo. This systems is functional in addition to other tissues in the proximal tubule of the kidney. Finally, the Megalin expression in the murine uterus as an example of a steroid dependent tissue was investigated. Lactoferrin a known Megalin ligand was purified from the luminal uterine fluid. Furthermore, Lactoferrin expression in the uterus was shown to be under tight hormonal control.
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Eimers, Meike [Verfasser]. "Die Rolle des Endozytoserezeptors Megalin (GP330) bei der Pathogenese progredienter Nephropathien / Meike Eimers." Berlin : Freie Universität Berlin, 2009. http://d-nb.info/1023623463/34.
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Anzenberger, Uwe. "A new role for LRP2 in forebrain development." Doctoral thesis, Humboldt-Universität zu Berlin, Mathematisch-Naturwissenschaftliche Fakultät I, 2006. http://dx.doi.org/10.18452/15565.
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LRP2 wird waehrend der fruehen Embryonalentwicklung hauptsaechlich im Dottersack und im Neuroepithel exprimiert. Der funktionelle Verlust dieses 600 kDa grossen Proteins in Maeusen fuehrt zu Fehlbildungen bei der Vorderhirnentwicklung, die als Holoprosenzephalie bezeichnet werden. LRP2 kommt daher eine wichtige Funktion waehrend der Vorderhirnentwicklung zu. Fuer diese Arbeit wurden Maeuse verwendet, bei denen lrp2 im gesamten Tier oder nur in bestimmten Geweben inaktiviert war. Die Expression von LRP2 im Neuroepithel, nicht aber im Dottersack ist wichtig fuer die korrekte Vorderhirnentwicklung. Das Fehlen des Proteins fuehrte am Tag 9.5 der Embryonalentwicklung zu einer UEberaktivierung des Bmp4 Signalweges im rostralen Telencephalon. Am Tag 10.5 war ein Verlust der shh-Expression in der anterioren entopeduncularen Zone (AEP) zu sehen. Das Fehlen von Shh in der AEP fuehrte zum Verlust von ventralen Oligodendrozyten und Interneuronen. AEhnliche Defekte wurden ebenfalls in Maeusen beschrieben, bei denen der Bmp4 Signalweg verstaerkt ist. Bmp4 bindet in vitro an LRP2. Diese Ergebnisse deuten darauf hin, dass LRP2 an der Entwicklung des ventralen Telencephalons beteiligt ist - moeglicherweise indem es die verfuegbare Menge an Bmp4 durch Endozytose reguliert. Die Signalwege, in die LRP2 eingebunden ist, sollten im Zebrafisch weiter untersucht werden. Tiere, denen funktionelles LRP2 fehlte, wurden durch die Injektion von Morpholinos generiert. Injizierte Tiere zeigten Stoerungen bei Resorptionsvorgaengen im Pronephros, was darauf hin deutet, dass die Funktion von LRP2 im Zebrafisch Pronephros und in der Niere der Saeugetiere konserviert ist. Die Expressionsmuster von Markergenen fuer die Vorderhirnentwicklung waren allerdings normal.Vermutlich war die Stoerung der lrp2-mRNA Prozessierung nicht ausreichend, um hier einen Effekt hervorzurufen, da bereits im 1-Zell Stadium genuegend komplett prozessierte maternale lrp2-mRNA fuer die Translation von LRP2 vorhanden war.LRP2 is mainly expressed in the yolk sac and in the neuroepithelium of the early embryo. Deficiency for this 600 kDa protein in mice results in holoprosencephaly, indicating a role for LRP2 in forebrain development. Mice with a complete or a conditional loss of lrp2 function were used to elucidate the consequences of the lack of LRP2 expression. The presence of LRP2 in the neuroepithelium but not in the yolk sac is crucial for early forebrain development. Lack of the receptor resulted in an increase of Bmp4 signaling in the rostral telencephalon at E9.5. As a consequence, shh expression at E10.5 was lost completely in a ventral region of the telencephalon termed anterior entopeduncular area (AEP). The absence of Shh activity in this area led to the loss of ventrally induced oligodendroglial and interneuronal cell populations in lrp2-deficient mice. Similar dorsalizing effects have also been observed in mice with increased Bmp4 signaling. Taking into account that Bmp4 was found to bind to LRP2 in vitro and in vivo, these results suggest a role for LRP2 in patterning the rostral ventral neural tube, possibly by acting as a clearance receptor for Bmp4. The underlying molecular mechanisms were then further analyzed in the zebrafish. LRP2-deficient animals were generated by injecting Morpholinos that interfered with the splicing of the lrp2-pre-mRNA leading to a deletion of the transmembrane-exon. Injected animals suffered from impaired renal clearance processes, demonstrating the functional conservation of LRP2 in the larval zebrafish pronephros. Brain structures were not affected in these animals and the expression patterns of marker genes for early forebrain development that were changed in the mouse were not changed. Apparently, Morpholino mediated interfering with the splicing of the lrp2-pre-mRNA did not affect the early forebrain formation because properly processed lrp2-mRNA was supplied maternally and sufficient for proper brain formation.
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Van, Praet Oliver. "Co-expression and interaction of cubilin and megalin in the adult male rat reproductive system." Thesis, McGill University, 2002. http://digitool.Library.McGill.CA:80/R/?func=dbin-jump-full&object_id=29485.
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Cubilin is a peripheral membrane protein that co-operates with the endocytic receptor megalin to mediate the endocytosis of ligands in various polarized epithelia. Megalin is expressed in the male reproductive tract where is has been implicated in the process of sperm membrane remodeling. A potential role for cubilin in the male reproductive tract has not been explored. Using RT-PCR, we found that cubilin and megalin mRNAs are expressed in the efferent ducts, corpus and cauda epididymides, and proximal and distal vas deferens. Immunohistological analysis revealed that cubilin was expressed in non-ciliated cells of the efferent ducts, principal cells of the corpus and cauda epididymides and vas deferens. Electron microscopic immunogold labeling showed cubilin in endocytic pits, endocytic vesicles and endosomes of these cells. The expression profile of cubilin in the male reproductive tract was coincident with that of megalin except in principal cells of the caput epididymidis. Double immunogold labeling showed that cubilin and megalin co-localized with one another within the endocytic apparatus and recycling vesicles of efferent duct cells. Neither protein was found in lysosomes. Injection of RAP, an antagonist of megalin interaction with cubilin, reduced the level of intracellular cubilin in cells of the efferent ducts and vas deferens. In conclusion, cubilin and megalin are co-expressed in cells of the epididymis and vas deferens and the endocytosis of cubilin in these tissues is dependent on megalin. Together, these findings highlight the potential for a joint endocytic role for cubilin and megalin in the male reproductive tract.
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Mori, Keita. "Increase of Total Nephron Albumin Filtration and Reabsorption in Diabetic Nephropathy." 京都大学 (Kyoto University), 2017. http://hdl.handle.net/2433/225488.
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Fatah, Hiwa Ramadhan. "Reduced proximal tubular expression of megalin and neonatal Fc receptor in proteinuria : the role of matrix metalloproteinases." Thesis, University of Leicester, 2018. http://hdl.handle.net/2381/41079.
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Proteinuria is clearly associated with the progression of chronic kidney disease (CKD) but the mechanisms underlying this relationship remain unclear. Recent evidence suggests that altered proximal tubular (PT) handling of filtered proteins may significantly modulate urine protein excretion and progressive renal disease. Megalin and neonatal Fc receptor (FcRn) are endocytic receptors responsible for the PT reabsorption of glomerular ultrafiltered proteins by receptor-mediated endocytosis (RME) and transcytosis, and are expressed on the luminal surface of the PT. This study aimed to investigate the expression and turnover of megalin and FcRn in proteinuria, and the possible mechanisms underlying down-regulation of expression of these receptors. In protein overload proteinuria (POP), the PT expression of megalin and FcRn were both downregulated compared to control animals. In addition, significant amount of both receptor were detected in the urine of proteinuric animals. This reduction in megalin and FcRn protein expression was accompanied by a significant increase in the urinary excretion of plasma proteins including the most abundant albumin. Increased expression and activity of both matrix metalloproteinase (MMP) and gamma secretase (γ-secretase) was evident in proteinuric animals and was paralleled with the urinary excretion of both megalin and FcRn. Megalin was previously identified to undergo regulated intramembrane proteolysis (RIP). RIP includes the MMP-mediated cleavage of the extracellular domain of megalin which in turn excreted into the urine, and the subsequent cleavage of the intracellular domain by γ-secretase. A synthetic inhibitor of MMPs, batimastat (BB-94) significantly reduced urinary excretion and also preserved the PT expression of megalin. In addition, inhibition of MMPs appeared to be antiproteinuric by markedly reducing urinary excretion of albumin and plasma proteins. The urinary excretion of FcRn was also reduced in BB-94 treated animals but the mechanism of this reduction was not clear. Further, BB-94 treatment preserved PT expression of FcRn in proteinuric animals. The POP model was developed to investigate the degree of tubulointerstitial damage in experimental animals. Injury was detected in the interstitium of proteinuric animals with significant increases in inflammatory markers including tumour necrosis factor alpha (TNF-α), interleukin-6 (IL-6) and the transforming growth factor-beta (TGF-β) as well as interstitial collagen deposition and marked interstitial infiltration of macrophages (F4/80). Blockade of MMP in proteinuric animals significantly reduced the expression of these markers in the kidney and abrogated the progression of interstitial inflammation and fibrosis. In summary this is the first study to correlate the reduced expression of megalin and FcRn, and the urinary excretion of these receptors with the increased cellular activity of MMP and the possible occurrence of RIP in vivo. Inhibition of MMP could be of great importance in treating proteinuria and the progression of tubulointerstitial inflammation and fibrosis, the most characteristic features of CKD.
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Jerichow, Timo [Verfasser]. "Die Rolle der Proteinendozytose bei der Pathogenese der tubulointerstitiellen Nierenerkrankung in der Megalin-teildefizienten Maus / Timo Jerichow." Berlin : Medizinische Fakultät Charité - Universitätsmedizin Berlin, 2011. http://d-nb.info/1025239687/34.
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Rader, Katherine A. "Megalin is a clearance receptor for insulin in proximal tubules and interacts with a novel intracellular protein ANKRA /." Diss., Connect to a 24 p. preview or request complete full text in PDF format. Access restricted to UC campuses, 2000. http://wwwlib.umi.com/cr/ucsd/fullcit?p9970666.
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Buchäckert, Yasmin [Verfasser]. "Role of megalin in albumin transport across the alveolar epithelium and its dysregulation by transforming growth factor beta / Yasmin Buchäckert." Gießen : Universitätsbibliothek, 2012. http://d-nb.info/1064990622/34.
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Mazzocchi, Luciana Carla [Verfasser]. "TGF-beta impairs alveolar protein clearance through downregulation of the endocytic receptor megalin in alveolar epithelial cells / Luciana Carla Mazzocchi." Gießen : Universitätsbibliothek, 2017. http://d-nb.info/1136268766/34.
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Gallagher, Hugh. "Megalin, cubilin and the proximal tubular epithelial cell : extracellular and intracellular interactions and their relevance to the progression of chronic renal disease." Thesis, St George's, University of London, 2004. http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.416020.
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Gianesello, Lisa. "Protein Uptake at Glomerular Level: Possible Involvement of an Endocytic Machinery in Cell Culture and in Patients with Lupus Nephritis." Doctoral thesis, Università degli studi di Padova, 2017. http://hdl.handle.net/11577/3425702.
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ClC-5 with megalin (LRP2), cubilin, Disabled 2 (Dab2), and Amnionless (AMN), is part of the molecular complex involved at proximal tubular level in the endocytic re-uptake of low-molecular-weight proteins and albumin. ClC-5, megalin and cubilin expression in podocytes of human renal biopsies was already reported. Moreover, it was demonstrated that podocytes are able to internalize albumin through an endocytic process. It is reasonable to assume that there should be an involvement of this system in protein uptake mediated by podocytes. A disruption of this system can lead to proteinuria which is one of the first manifestation of kidney disease in Systemic Lupus Erythematous (SLE).
Aims of this study were to explore the presence of the tubular endocytic machinery components also in human podocytes in vitro and to evaluate whether albumin modulates this system. Moreover, we wanted to verify and quantify the expression of ClC-5, megalin and cubilin in both glomerular and tubular compartments in renal biopsies of patients presenting Lupus nephritis and observing the presence of a relationship with clinical data.
To verify the presence of an uptake mechanism in human podocytes in vitro, we performed time lapse experiments with a low dose of FITC albumin (10 µg/ml). We observed albumin internalization starting from 2 to 15 hours. To evaluate the uptake kinetic, we stimulated podocytes at different time (30 min and 2 hours) and doses (10 µg/ml, 100 µg/ml and 1 mg/ml) at 37°C and 4°C. We observed a significant dose dependent increase in fluorescence vs controls after 2 hours’ stimulation with a typical receptor-mediated kinetic since it is inhibited at 4 °C. Moreover, we disclosed the presence of ClC-5, Dab2 and AMN beyond megalin and cubilin, in this in vitro system using immunohistochemistry (IHC) and immunofluorescence (IF) techniques, highlighting a co-localization between albumin and both receptors. To analyze whether the proteinuric environment modulates CLCN5, LRP2, CUBN, DAB2 and AMN expression, we stimulated human podocytes with increasing concentrations of BSA (range 10 µg/ml - 30 mg/ml) and we evaluated the mRNA expression at different time points (2, 4, 8, 24, 48 and 72 hours). Using Real Time PCR we observed a significant time and dose dependent increase in CLCN5, CUBN and AMN expression and an up-regulation of DAB2 only at 24 hours.
We collected 23 SLE renal biopsies, 6 control biopsies and 1 case of Minimal Change Disease. As clinical parameters we considered proteinuria and pharmacological therapy. IHC and IF were used to analyze ClC-5, megalin and cubilin protein expression in serial sections. Morphometric quantification revealed a direct correlation between tubular and glomerular expression of all molecules in SLE patients, highlighting a relationship between glomerular and tubular compartments independently from proteinuria levels. Furthermore, preliminary data on patients without ACEi/ARB and immunosuppressive drugs disclosed a positive trend among these molecules at glomerular level.
Interestingly, we revealed megalin and cubilin expression in hypertrophic PECs of some SLE patients and characterization experiments identified a subpopulation with an intermediate phenotype between mature and progenitor cells.
In conclusion, for the first time we demonstrated that human podocytes are naturally committed to perform albumin endocytosis via a receptor-mediated mechanism. Moreover, protein overload upregulates CUBN, AMN and CLCN5 in these cells.
Functional studies regarding the role of cubilin in albumin uptake underlined its participation in this mechanism even if this is not the only pathway involved. Further studies will be necessary to analyze which may be the partner(s) of the CUBAM complex in this mechanism.
For the first time we demonstrated the presence of ClC-5, megalin and cubilin in glomeruli of patients with SLE and MCD in addition to controls confirming in vitro data. Furthermore, in SLE biopsies we highlighted a strong correlation between the two renal compartments in the expression of the protein uptake system, supporting the idea of a partnership between tubular and glomerular cells in albumin uptake via the same mechanism of internalization. In addition, preliminary data on patients without ACEi/ARB and immunosuppressive drugs lead us to suppose that the pharmacological therapy could affect the expression of this system, in particular at glomerular level.
The differences observed from in vivo and in vitro data, especially on megalin expression, underline the involvement of other glomerular cell types in addition to podocytes in protein uptake.
Finally, megalin and cubilin expression in PECs of SLE patients is a real interesting but complex data, since characterization experiments identified a subpopulation with an intermediate phenotype between mature and progenitor cells. Further studies will be performed to better characterize the role of these double-positive cells and their correlation with clinical data and/or disease progression.ClC-5, megalina (LRP2), cubilina, Disabled 2 (Dab2) ed Amnionless (AMN) fanno parte del complesso molecolare coinvolto a livello del tubulo prossimale nel recupero delle proteine a basso peso molecolare e dell’albumina mediante endocitosi. È già stata riportata la presenza di ClC-5, megalina e cubilina a livello dei podociti in biopsie renali umane. Inoltre è stato dimostrato che i podociti sono in grado di internalizzare l’albumina attraverso un meccanismo di endocitosi. Il mancato funzionamento di questo sistema può portare a proteinuria, che è una delle prime manifestazioni del coinvolgimento renale nel Lupus Eritematoso Sistemico (LES). È quindi ragionevole supporre che vi possa essere un coinvolgimento di questo sistema nel meccanismo di uptake delle proteine da parte dei podociti. Gli scopi di questo studio sono stati di esplorare la presenza dei componenti del sistema tubulare di endocitosi delle proteine in podociti umani in coltura e di valutare se e come l’albumina ne modulasse l’espressione. Inoltre, si è voluto indagare l’espressione di ClC-5, megalina e cubilina sia a livello glomerulare che tubulare in biopsie renali di pazienti con nefrite lupica, valutando una possibile relazione con i dati clinici. Abbiamo verificato la presenza di un meccanismo di uptake in podociti umani in coltura attraverso esperimenti di time-lapse con basse dosi di FITC-BSA (10 µg/ml) ed abbiamo osservato l’inizio del processo di internalizzazione in un periodo di tempo variabile dalle 2 alle 15 ore. Per caratterizzare il tipo di cinetica di uptake della FITC-BSA, i podociti sono stati stimolati a differenti tempi (30 min e 2 ore) e dosi (10 µg/ml, 100 µg/ml and 1 mg/ml) mantenendo la coltura a 37°C o 4°C. Si è osservato un aumento significativo della fluorescenza dose-dipendente rispetto al controllo dopo 2 ore dalla stimolazione con una tipica cinetica di internalizzazione recettore-mediata poiché veniva inibita a 4°C. Abbiamo osservato la presenza di ClC-5, Dab2 e AMN oltre a quella di megalina e cubilina in podociti umani in coltura in condizioni basali mediante tecniche di immunoistochimica (IHC) ed immunofluorescenza (IF) ed abbiamo dimostrato la co-localizzazione dei due recettori con l’albumina fluorescente. Per valutare se l’ambiente proteinurico fosse in grado di modulare l’espressione di CLCN5, LRP2, CUBN, DAB2 ed AMN, i podociti umani sono stati stimolati con concentrazioni crescenti di BSA (range 10 µg/ml - 30 mg/ml) e l’espressione dell’RNA messaggero è stata valutata a tempi diversi (2, 4, 8, 24, 48 and 72 hours). Mediante analisi in Real Time PCR, abbiamo osservato un aumento significativo tempo e dose-dipendente di CLCN5, CUBN ed AMN ed un aumento di DAB2 solamente alle 24 ore. Abbiamo raccolto 23 biopsie renali di pazienti con LES, 6 biopsie di controllo ed un caso di Minimal Change Disease. Come parametri clinici abbiamo considerato la proteinuria e la terapia farmacologica. Mediante IHC ed IF abbiamo analizzato l’espressione proteica di ClC-5, megalina e cubilina in sezioni seriali. La quantificazione eseguita mediante analisi morfometrica ha rivelato una correlazione diretta dell’espressione di tutte le molecole in analisi tra il compartimento tubulare e glomerulare, evidenziando una stretta relazione tra i due compartimenti indipendentemente dai livelli di proteinuria. Inoltre, dati preliminari su pazienti privi di terapia farmacologica (ACEi/ARB o immunosoppressivi) hanno mostrato un trend positivo tra l’espressione di queste molecole a livello glomerulare. Curiosamente, abbiamo evidenziato l’espressione di megalina e cubilina in cellule parietali della capsula (PECs) con morfologia ipertrofica in alcuni pazienti LES che, mediante esperimenti di caratterizzazione, abbiamo identificato come una nuova sottopopolazione con un fenotipo intermedio tra cellule mature e progenitrici. Concludendo, per la prima volta abbiamo dimostrato che i podociti umani sono naturalmente predisposti ad effettuare l’endocitosi dell’albumina attraverso un meccanismo recettore-mediato. Inoltre, l’overload proteico è in grado di aumentare l’espressione di CLCN5, CUBN ed AMN in queste cellule. Studi funzionali per dimostrare il ruolo di cubilina nel processo di uptake dell’albumina hanno sottolineato la sua partecipazione in questo meccanismo anche se, verosimilmente, non è l’unico pathway coinvolto. Ulteriori studi saranno necessari per analizzare quali altre molecole possano essere chiamate in causa in questo meccanismo. Per la prima volta abbiamo dimostrato la presenza di ClC-5, megalina e cubilina in glomeruli di pazienti con LES, MCD e controlli, confermando i dati in vitro. Inoltre, nelle biopsie dei pazienti LES abbiamo evidenziato una stretta relazione tra i due compartimenti renali nell’espressione dei componenti di questo sistema, supportando l’idea di una partnership tra cellule tubulari e glomerulari nell’uptake dell’albumina attraverso lo stesso meccanismo di internalizzazione. In aggiunta, dati preliminari ottenuti da pazienti privi di terapia con ACEi/ARB o immunosoppressivi ci ha fatto supporre che il trattamento farmacologico possa influire sull’espressione di questo sistema a livello glomerulare. Le differenze osservate tra lo studio in vivo e quello in vitro, in particolare riguardo l’espressione di megalina, suggeriscono il coinvolgimento di altre cellule del glomerulo oltre ai podociti. Infine, l’espressione di megalina e cubilina nelle PECs dei pazienti LES è un dato molto interessante ma complesso, poiché gli esperimenti di caratterizzazione hanno identificato una sottopopolazione con un fenotipo intermedio tra cellule mature e progenitrici. Ulteriori studi dovranno essere condotti per meglio caratterizzare il ruolo di queste cellule con doppia positività e la loro correlazione con i dati clinici o di progressione della malattia.
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Joseph, Antoine. "La mégaline/lrp2 exprimée dans le neuroépithélium antérieur est critique pour la croissance oculaire." Thesis, Paris 6, 2015. http://www.theses.fr/2015PA066144/document.
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La mégaline est un récepteur endocytique multiligand essentiellement connu comme récepteur clé pour la réabsorption protéique rénale. Au cours du développement embryonnaire murin la mégaline a été impliquée dans le développement du prosencéphale et de l’œil mais la mortalité périnatale des souris Meg-/- empêche sone étude à des stades ultérieurs. Pour analyser le rôle de la mégaline dans le système visuel nous avons généré dans le laboratoire des souris conditionnelles FoxG1-Cre MegL/L.L’analyse phénotypique des souris mutantes montre que l’absence de la mégaline dans le neuroépithélium antérieur conduit à une augmentation anormale et progressive de la taille de l’œil accompagnée par un amincissement de la rétine et la diminution, entre autres, des cellules ganglionnaires. Ces observations immunomorphologiques suggèrent que les souris mutantes présentent des signes de myopie forte et sont confirmées par l’analyse ophtalmologique. Les analyses biochimiques des souris mutantes montrent que l’absence de mégaline entraine des modification dans la structure et la fonction du corps ciliaire, à l’origine de cet élongation excessive du globe oculaire. Les résultats obtenus montent que les souris Foxg1-Cre MegL/L sont le premier modèle génétique murin qui reproduit les caractéristiques de la myopie forte. L’élucidation des mécanismes physiopathologiques sous-jacents au développement de la myopie est un préalable indispensable à l’élaboration d’en éventuel traitement préventif, espoir pour les 0,5% à 2% de la population touchés par la cécité liée aux complications de la myopie forteMegalin is a large multiligand endocytic receptor essentially known as the key receptor for protein reabsorption in the renal proximal tubule. Murin megalin appears to be essential for early forebrain and eye development but the perinatal lethality of Meg-/- mice precludes further analysis. To study the implication of megalin in the formation of the eye we generated (in the laboratory ) FoxG1-Cre MegL/L mice lacking megalin specifically in the anterior neuroepithelium.The phenotypic analysis of these mice show that they suffer from an excessive and progressive eye growth associated with retinal thinning and a strong decrease of some retinal cell types including the ganglion cells. The immunomorphological studies suggest that the mutant mice are highly myopic which is confirmed by the ophtalmological analysis data. The biochemical analysis of these mutant mice shows that the absence of megalin causes structural and functional modifications in the ciliary epithelium, leading to the excessive elongation of the eyeball. These results show that the FoxG1-Cre MegL/L mice are the first murine genetic model recapitulating the characteristics of high myopia. The elucidation of underlying physiopathological mechanisms of high myopia development is essential for the elaboration of a preventive treatment, hope for 0,5 to 2% of the population suffering from blindness caused by the complications of high myopia
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Alammari, Dalia Muhammed. "Comparative in vitro analyses of the effect of immunoglobulin λ light chain and fatty acid free albumin on proximal tubular epithelial cells-involvement of megalin phosphorylation." Thesis, University of Leicester, 2016. http://hdl.handle.net/2381/38821.
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Kidney disease is a major challenge for health care systems, and the prevalence is increasing. Proteinuria is a hallmark of progressive renal dysfunction and describes the pathological excess of plasma proteins in urine, mainly albumin. Multiple Myeloma is a cancer of plasma cells that leads to excessive presence of free light chain protein (FLC) in blood. Renal failure due to overproduction of FLC and the associated light chain proteinuria occurs as a result of decreased renal function or as a direct toxic effect on the proximal tubular cells (PTCs) by excessive protein. Proteins are normally reabsorbed by endocytosis via megalin receptor that binds proteins and mediates their uptake. Exceeding the proximal tubular epithelial cells (PTECs) reabsorption capacity might trigger inflammation detrimental to the kidney. In proteinuric nephropathy the cytoplasmic tail of megalin (MegCT) is phosphorylated after interaction between proteins and megalin on the PTECs, which activates signalling cascades that regulate the phosphorylation. An in vitro proteinuric model was established using HK2 cells (a proximal tubular epithelial cell line derived from normal human kidney) treated with high concentrations of essentially fatty acid free human serum albumin (FAF-HSA) or lambda light chain (λ-LC) isolated and purified from the urine of a myeloma patient, to induce cellular damage. The potential pathogenic role for FAF-HSA and λ-LC on HK2 cells was examined. Also, renal toxicity that comes from the intracellular signalling through phosphorylation of MegCT was addressed by utilising antibodies directed against specific phosphorylation site (PPPSP) of the intracellular portion of megalin in HK2 cells stimulated with different concentrations of FAF-HSA and λ-LC, so-called pre-stimulated HK2. In vitro analyses showed (i) a detrimental effect of FAF-HSA and λ-LC on viability of HK2, (ii) phosphorylation of the cytoplasmic tail of megalin in pre-stimulated HK2 cells. (iii) Production of inflammatory cytokines and H2O2 generation, activation of autophagy process and increase in several kidney biomarkers/ injury mediators, which are involved in different pathways in response to protein overload. All these reasons are likely to contribute to direct PTECs injury and kidney failure in patients. Potentially these mechanisms may be attractive for drug development to benefit patients with kidney failure and help to inhibit the progression of proteinuric nephropathy and as such may save lives.
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Komuraiah, Myakala. "Proliferation Signal Inhibitor associated proteinuria in a renal transplant recipient: Dysfunction of proximal tubular epithelial cells is a result of decreased cubilinand/or megalin expression? : Proliferation Signal Inhibitor associated Proteinuria." Thesis, University of Skövde, School of Life Sciences, 2010. http://urn.kb.se/resolve?urn=urn:nbn:se:his:diva-3885.
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Background The proliferation signal inhibitors (PSIs) sirolimus (SRL) and everolimus (ERL) are the potent immunosuppressive drugs using in organ transplantation and has been used successfully in renal transplant recipients (RTX) as well. PSIs are the key factors to overcome the allograft rejections after successful organ transplantation since the immune system starts to react against the graft. SRL and ERL prevents the action of immune system b inhibits the proliferation of T- and B-cells by inhibiting the intracellular signaling of interleukin-2. The presence of excess amount of serum proteins including albumin in the urine is considered as proteinuria, which reflects the loss of kidney function. The occurrence of proteinuria can be the result of abnormal glomerular filtration and/or impaired tubular endocytic function of renal proximal tubular epithelial cells (PTECs). Megalin and cubulin are two scavenger receptors present on epical surface of PTECs and involved in reabsorption of proteins after glomerular ultrafiltration process in the kidney. Proteinuria appears too high in renal transplanted patients during ongoing treatment with PSIs.
Aim Our study aimed to investigate and correlate the expression level of megalin and cubilin and albumin uptake in PTEC of renal transplanted patients before and after conversion to PSI.
Methods To retrieve the maximal expression of our interest molecules in renal PTECs, we optimized antigen retrieval (AR) method and primary antibody dilution for each molecule separately. An optimization experiment was performed on 3 different normal patients renal biopsies were used. Later, human renal biopsy specimens originated from 4 different renal transplanted patients were used in this study. From all the 4 patients biopsy specimens were taken before and ongoing administration of PSIs (SRL, ERL). The expression of megalin, cubilin and albumin uptake in PTEC of renal transplant patients was determined by immunohistochemical staining.
Results Based on the optimization experiments, we selected the AR method and primary antibody dilution for the expression of megalin, cubilin and albumin uptake. In 4 renal transplanted patients following administration of PSIs results in patients 1, 2, 3 expression of megalin, cubilin and albumin uptake during ongoing PSI treatment was not comparable or even more intense than before PSIs introduction. The expression of megalin, cubilin and albumin uptake was reduced in patient 4 during ongoing PSI treatment.
Conclusion Our findings suggest that the renal transplant patient 4 developed proteinuria during PSI medication. The expression of megalin, cubilin and albumin uptake was markedly decreased during ongoing PSI treatment in patient 4. We concluded that there is a direct link between PSI medication and tubular dysfunction, which might cause proteinuria
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Sousa, Fátima Carina Gonçalves. "Utilização do modelo SCRUM na Megasis." Master's thesis, Instituto Superior de Economia e Gestão, 2018. http://hdl.handle.net/10400.5/20214.
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Mestrado em Gestão de Sistemas de InformaçãoO presente Trabalho Final de Mestrado tem como objetivo descrever todas as atividades desenvolvidas durante a realização do estágio curricular no Centro de Business Intelligence da Megasis/TAP IT, colocando em prática e consolidando conhecimentos adquiridos ao longo do mestrado. Aborda um conjunto de atividades que permitem a automatização de vários processos manuais associados ao modelo Agile de desenvolvimento de software e dá também a conhecer como é aplicada a metodologia Scrum num departamento de Business Intelligence. O relatório começa por dar conta da revisão da literatura explicando o que é o scrum, quem são os participantes e quais as coreografias. De seguida, são descritas as atividades desenvolvidas no estágio, desde o enriquecimento do modelo de dados de scrum com novos conceitos como também a criação de relatórios e dashboards, sendo estes o output final da solução de BI. É feita uma análise critica comparando a literatura existente e as atividades do estágio assim como uma apreciação pessoal sobre as mesmas. As atividades são descritas e acompanhadas com o anexo de imagens dos vários dashboards criados.
The purpose of this master's Report is to describe all the activities developed during the internship at the Megasis/TAP IT Business Intelligence Center, putting into practice and consolidating knowledge acquired through out the master's program. It addresses a set of activities that allow the automation of several manual processes associated with the Agile model of software development. It also shows how the Scrum model is applied in a Business Intelligence Department. The literature review describes topics such scrum, the participants and the events. What it comes next is the description of the activities of the internship, the enrichment of the model of scrum with new concepts and last the dashboards and reports that are the BI final solution output. A critical analysis, as well as a personal assessment, is made comparing the existing literature and the internship activities. The activities are described and accompanied by image attachments of the various dashboards created.
info:eu-repo/semantics/publishedVersion
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Egan, Emily Catherine. "Nestor's Megaron: Contextualizing a Mycenaean Institution at Pylos." University of Cincinnati / OhioLINK, 2015. http://rave.ohiolink.edu/etdc/view?acc_num=ucin1439295528.
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Jenkins, Mary A. "To megali idea - dead or alive?: the domestic determinants of Greek foreign policy." Thesis, Monterey, California. Naval Postgraduate School, 1994. http://hdl.handle.net/10945/42939.
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Approved for public release, distribution unlimitedThis thesis provides an algorithm based on marginal analysis to help CLF Supply Officers load ships with Provisions (food), High Usage Load List (HULL), and ship store stock. The algorithm is incorporated into an EXCEL spreadsheet and produces a prioritized list of items in their optimum stocking sequence. The algorithm is compared to both the Atlantic and Pacific Fleet current loading methods using a food item example and shows a 60-70% increase in expected supply effectiveness. Furthermore, the algorithm is generic and can be applied to and inventory problem where a demand distribution is known and space is the limiting factor in determining stocking levels.
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Araiza, Jesús. "Die aristotelischen Ethica megala eine philosophische Interpretation." Berlin Münster Lit, 2007. http://d-nb.info/996034005/04.
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Palanisamy, Megala [Verfasser]. "High moisture extrusion of plant proteins / Megala Palanisamy." Hannover : Gottfried Wilhelm Leibniz Universität Hannover, 2019. http://d-nb.info/1198398574/34.
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Sanders, Jeffrey R. "Sacral landscapes : narratives of the megalith in north western Europe." Thesis, University of Edinburgh, 2007. http://hdl.handle.net/1842/2671.
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The construction of archaeological narrative is influenced by a number of factors. Some come from within disciplinary boundaries, whilst others are traced from the wider influences of social, cultural or academic contexts. This thesis examines three areas identified as Neolithic ‘landscapes’, all of which have been the subject of archaeological investigation since the 19th century. The history of research of these areas allows an evaluation of how these disparate influences interact. In this way, the three landscapes act as an arena in which to explore aspects of the archaeological approach itself. This leads to a critical examination of the interpretative tools available to the archaeologist. How concepts such as ‘landscape’ are formed and affect discourse is explored. Wider themes of demarcation, typology and the underlying assumptions of research are investigated in relation to the interpretation of the Neolithic and Early Bronze Age of North Western Europe. The large span of time that these periods encompass allows exploration of change from the short to very long term, although this is not always utilised within archaeological accounts. The treatment of time is therefore considered in conjunction with explanations of change in prehistory. A powerful approach to time is suggested by combining aspects of the work of Pierre Bourdieu and Fernand Braudel and the potential for this is evaluated against the archaeological record of the three areas. How the assumptions of the archaeological approach are acted out within the historiography of each area highlights a number of recurring metaphors that are used to interpret the material record. These promote a portrayal of Neolithic life that combines with the range of influences from the history of archaeology itself to promote an idea of the prehistoric mentalité. A very durable and underlying type that constantly resurfaces in these accounts is the idea of the ‘sacral landscape’, which is the central topic of this thesis.
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Tiralongo, Emilia. "Complesso macromolecolare responsabile dell'endocitosi dell'albumina: un ruolo a livello glomerulare? Studio di espressione genica di CLCN5 e megalina in biopsie microdissezionate di nefropatie proteinuriche." Doctoral thesis, Università degli studi di Padova, 2009. http://hdl.handle.net/11577/3426054.
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ClC-5 and Megalin are part of the same macromolecular complex involved in the re-uptake of albumin in the proximal tubuli. To understand the relationship between this mechanism and proteinuric kidney diseases, we have performed gene expression study of CLCN5 and Megalin genes in glomerular (gl) and tubular interstitial (ti) compartments of patients with type 2 diabetes (NIDDM) and IgA nephropathy (IgAN).
Gene expression of CLCN5 and Megalin was investigated by Real-Time PCR in microdissected biopsies (mpb) (under a stereomicroscope) from patients with IgAN (n 10) and with NIDDM (n 9). Both groups had similar level of proteinuria. As controls, we used cortical tissues obtained from sites remote from tumor bearing renal tissue (n 9). Moreover, we analyzed human mesangial cells (HMC), endothelial cells (HuVEC), tubular cells (HK-2) and podocytes (HP) in basal conditions. HMC and HK-2 were also examined in high glucose and albumin conditions respectively.
We found that: 1) CLCN5 and Megalin were expressed in all mbp both at gl and ti levels, and their expression did not differ between gl and ti of NIDDM and IgAN; 2) CLCN5 and Megalin expression levels were significantly higher in proteinuric nephropathies than in controls both at gl and ti compartment. In order to exclude ti contamination in microdissected glomeruli, we performed gene expression analysis of CLCN5 and Megalin also on laser microdissected glomeruli from 28 NIDDM patients and 14 controls that confirmed our previous results. In these mbp a direct correlation between CLCN5 and Megalin was evidenced (r=0,50 p=0,0039); 3) CLCN5 transcript was evidenced in all cells analyzed, on the contrary, very low levels of Megalin were detected; 4) HK-2 treated with albumin showed the same level of CLCN5 expression as untreated cells; 5) HMC treated with high glucose for 24 and 48 hours showed the same level of CLCN5 expression as untreated cells.
Our study reveals, for the first time, that CLCN5 and Megalin genes are expressed in human glomeruli, and that all the cell types constituting the glomerulus express in vitro CLCN5. The overexpression of CLCN5 and Megalin in diabetic and IgA nephropathy biopsies suggests that proteinuria might regulate their expression. The in vitro experiments on HMC exclude the role of glucose in the up-regulation of ClC-5 expression in diabetic glomerulopathy. A role might be hypothesized for podocytes since podocyte endocytosis of proteins does occur in proteinuric patients.ClC-5 e Megalina sono due delle proteine che compongono il complesso macromolecolare coinvolto nel riassorbimento dellâalbumina a livello del tubulo prossimale. Per comprendere meglio se ci fosse una relazione tra questo meccanismo e le patologie proteinuriche abbiamo effettuato uno studio di espressione per i geni CLCN5 e Megalina nei compartimenti glomerulare e tubulo interstiziale di pazienti con diabete di tipo II (NIDDM) e nefropatia a depositi di IgA (IgAN). Lâespressione di CLCN5 e Megalina è stata investigata mediante Real-Time PCR in biopsie microdissezionate manualmente grazie allâausilio di uno stereomicroscopio. Queste sono stete ottenute da pazienti con diabete di tipo II (n°9) e nefropatia a depositi di IgA (n°9). Come controllo è stato utilizzato tessuto corticale ottenuto da polo renale indenne in corso di nefrectomia per tumore. Entrambi i gruppi di pazienti analizzati presentavano livelli simili di proteinuria. Abbiamo inoltre analizzato cellule mesangiali umane (HMC), cellule endoteliali umane (HuVEC) cellule tubulari umane (HK-2) e podociti umani (HP) in condizioni basali. HMC e HK-2 sono state anche analizzate rispettivamente in presenza di alte concentrazioni di glucosio e a diverse concentrazioni di albumina. Abbiamo trovato che: 1) CLCN5 e Megalina sono entrambi espressi in tutte le biopsie microdissezionate sia a livello glomerulare che a livello tubulo interstiziale e i loro livelli di espressione erano simili nei due compartimenti in entrambe le patologie; 2) i livelli di espressione sono risultati maggiori nelle nefropatie proteinuriche rispetto ai controlli sia a livello tubulo interstiziale che a livello glomerulare. Per escludere unâeventuale contaminazione del compartimento glomerulare da parte del tubulo prossimale abbiamo chiesto la collaborazione del Dott. J.J.Baelde del Leiden University Medical Center che ha effettuato lâanalisi di espressione di CLCN5 e Megalina su glomeruli microdissezionati mediante laser ottenuti da biopsie di pazienti NIDDM (n°28) e su glomeruli sani di controllo (n°14), confermando i nostri precedenti risultati. In queste biopsie microdissezionate è inoltre emersa una correlazione diretta tra CLCN5 e Megalina (r=0,5, p=0,0039); 3) la presenza di CLCN5 è stata evidenziata e quantificata in tutte le cellule analizzate, mentre per Megalina sono stati rilevati livelli molto bassi di espressione; 4) le cellule HK-2 stimolate con albumina hanno mostrato gli stessi livelli di espressione di CLCN5 delle cellule non trattate; 5) le cellule HMC stimolate con glucosio hanno mostrato gli stessi livelli di espressione di CLCN5 delle cellule non trattate. Il nostro studio evidenzia per la prima volta la presenza di CLCN5 e Megalina a livello del compartimento glomerulare nellâuomo ed inoltre che tutti i tipi cellulari costituenti il glomerulo esprimono in vitro CLCN5. La sovrespressione di CLCN5 e Megalina nelle biopsie dei pazienti diabetici e con nefropatia da IgA suggerisce un loro ruolo nella fisiopatologia della proteinuria e la loro correlazione diretta, emersa tra lâespressione genica delle due proteine nel glomerulo, fa ipotizzare un loro meccanismo dâazione coordinato simile a quello presente nel tubulo prossimale. Gli esperimenti in vitro sulle HMC escludono un ruolo del glucosio nella modulazione dellâespressione di CLCN5 nella patologia diabetica. Un ruolo in questo processo potrebbe essere ipotizzato per i podociti in quanto i risultati da noi ottenuti bene si affiancano ai dati in letteratura che mostrano che i podociti, nei pazienti proteinurici, sono in grado di endocitare proteine.
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Zelepos, Ioannis. "Die Ethnisierung griechischer Identität 1870-1912 : Staat und private Akteure vor dem Hintergrund der "Megali Idea /." München : R. Oldenbourg, 2002. http://catalogue.bnf.fr/ark:/12148/cb39910376f.
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Hannula, A. (Anu). "En studie om hur funktionell inlärning beaktas i lågstadieläroboken Megafon 1." Bachelor's thesis, University of Oulu, 2019. http://jultika.oulu.fi/Record/nbnfioulu-201904251536.
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Goswami, Swagata. "Geomorphology, hydrology and human-environment interactions in the Kosi megafan, India." Thesis, University of Oregon, 2019. http://hdl.handle.net/1794/24549.
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The continuing channel modification and change in the course of the River Kosi have got a greater implication on the geomorphic evolution processes within its megafan surface. A considerable portion of the land in Kosi megafan remains flooded and later waterlogged every year, a phenomenon that has been exacerbated by the rapid development of roads and railroads. Crop yields are also lowest in parts of the megafan where waterlogging is a bigger problem. This research applies GIS and remote sensing techniques to examine the Kosi channel change from 1975-2015 and map waterlogging and transport network driven ‘disconnectivity’ of the Kosi megafan located in the Indo-Gangetic Plains, India from 2005-2015. This study also used semi-structured interviews of 960 farm-households from four case studies to analyze farm-related changes, especially due to waterlogging and identify factors responsible for a farmer’s adaptation to waterlogging stress from 2014-2015. The findings reveal that there have been substantial changes in the main Kosi channel. The massive development in the road-rail transport network along with the increase in the minor channels within the megafan have led to staggering increase in transport-river intersections and foster both seasonal and permanent waterlogging. The case studies suggest that 90% of the farmers have made changes to their farms due to waterlogging and other factors associated with that. The study also shows that there are limits to adaptation, which are caused by barriers of available technology, knowledge and institutional frameworks. These barriers undermine the effectiveness of the initiatives promoted both at the national as well as local level.
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Lo, Edward Limin. "FLUVIAL-LACUSTRINE PROCESSES SHAPING THE LANDFORMS OF THE DISTAL PARAGUAY FLUVIAL MEGAFAN." UKnowledge, 2017. http://uknowledge.uky.edu/ees_etds/54.
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Tropical wetlands such as the Pantanal help regulate global biogeochemical cycles, but climate change is modifying these environments. Controls on environmental changes can potentially be assessed from ancient, well-dated lacustrine sedimentary records. An integrated field and laboratory approach was undertaken to study the limnogeology of Lake Uberaba in the northern Pantanal, and test whether the lake has preserved a reliable record of environmental change in its strata. This study was designed to understand how the basin accumulates sediment and to assess its sensitivity to hydroclimatic variability. The data showed that modern Lake Uberaba is a highly dynamic, freshwater fluvial-lacustrine basin. Modern lake floor sediments are largely siliciclastic silts, with limited organic matter content and abundant sponge spicules. This sedimentary composition reflects the lake’s open hydrology and well-mixed water column. Limited data from sediment cores indicates that Lake Uberaba may have formed ~1760 CE, following an abrupt transgression over an oxidized floodplain depositional environment. The stratal contact between lacustrine and floodplain deposits suggests the presence of an erosional unconformity, the timing and duration of which remains unknown. The environmental change favoring lake formation appears to be linked to increased effective precipitation provided by the Intertropical Convergence Zone (ITCZ) in the northern Pantanal.
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Vaske, Kristofer. "Megalith Grave Escape : Using escape room game mechanics for cultural heritage sites." Thesis, Högskolan i Skövde, Institutionen för informationsteknologi, 2019. http://urn.kb.se/resolve?urn=urn:nbn:se:his:diva-17025.
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This report documents the development of a concept and prototype for a mobile application with the purpose of making the megalith graves surrounding the town of Falköping more engaging and interactive for visitors. Because of the limitations of working with heritage sites that cannot be altered to support a gaming experience, the usage of escape room game mechanics is explored. Because escape room games depend on the user's observation and exploration of their environment, they serve as a usable inspiration for applications with the purpose of making visitors experience a location in a similar way. The prototype developed for the project contains puzzles designed for four different megalith grave sites which were then tested with groups of children and parents playing together.
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Megatif, Lena [Verfasser]. "Development of new reactors for the photocatalytic treatment of polluted aquifers / Lena Megatif." Hannover : Gottfried Wilhelm Leibniz Universität Hannover, 2019. http://d-nb.info/1198398671/34.
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Hirschberger, Martina. "Gynaikon katalogos und megalai ehoiai : Ein Kommentar zu den Fragmenten zweier hesiodeischer Epen /." München : K. G. Saur, 2004. http://catalogue.bnf.fr/ark:/12148/cb392334817.
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Leier, Andrew. "The Cretaceous Evolution of the Lhasa Terrane, Southern Tibet." Diss., Tucson, Ariz. : University of Arizona, 2005. http://etd.library.arizona.edu/etd/GetFileServlet?file=file:///data1/pdf/etd/azu%5Fetd%5F1340%5F1%5Fm.pdf&type=application/pdf.
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Campbell, Bruce A. "A digital recording system for space-based applications utilizing four-megabit magnetic bubble memories." Thesis, Monterey, California. Naval Postgraduate School, 1985. http://hdl.handle.net/10945/21279.
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Andersson, Emelie. "Trattbägarkeramiken och dess ritualer : En studie av keramikhanteringen vid megalitgravar i Sydskandinavien under neolitikum." Thesis, University of Kalmar, University of Kalmar, University of Kalmar, University of Kalmar, School of Human Sciences, 2009. http://urn.kb.se/resolve?urn=urn:nbn:se:hik:diva-1019.
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This essay studies the funnel-beaker ceramic in connection with the megalith graves in South Scandinavia. In my work I have described the nature of ceramics and looked on the crockery types and ornamentation and then discussed the use of the material in a ritual perspective. In the first part I have focused on the critical aspects you have to think about when you do a study like this one. In the second part of this essay I have done a case study, with the ceramic material, in three passages graves in the area of Falbygden, Western Sweden and studied the ceramic material and the nature of it in South Scandinavia as well. Then in the third I discussed the potential use, there is two, of the ceramic material in general of South Scandinavia and looked at it in a ritual perspective.
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Kuerten, Sidney [UNESP]. "Evolução geomorfológica e mudanças ambientais no megaleque do Nabileque, quaternário do Pantanal mato-grossense." Universidade Estadual Paulista (UNESP), 2010. http://hdl.handle.net/11449/102880.
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O megaleque fluvial do Nabileque é um sistema deposicional que vem sendo construído pelo rio Paraguai na borda sudoeste do Pantanal Mato-Grossense desde tempos pleistocênicos. É um sistema aluvial peculiar, pois não está associado a rios oriundos de relevos altos situados nos planaltos adjacentes à planície. Trata-se de um megaleque fluvial construído pelo rio Paraguai, rio-tronco coletor das águas do todo sistema hidrográfico do Pantanal, na saída do rio para a planície do Chaco, onde coalesce com o megaleque do Pilcomayo. Com base em dados de sensores remotos e verificação de campo, foi realizada compartimentação e caracterização geomorfológica do megaleque, que ocupa área de aproximadamente 9100 km². Descrição e datação dos depósitos dos compartimentos identificados permitiram elaborar modelo evolutivo para a área, cuja maior parte é ocupada por vasta planície aluvial pleistocênica (idades LOE entre 57,8 e 12,8 Ka AP), marcada pela presença de intrincada rede de paleocanais distributários de baixa sinuosidade a meandrantes. Feições fluviais erosivas e redes de canais tributários superimpostos evidenciam que as áreas de ocorrência dos depósitos pleistocênicos se encontram em degradação, embora sujeitas a frequentes inundações, responsáveis pela deposição de delgadas e irregulares coberturas de sedimentos mais recentes. Um aspecto notável é a existência de dois cinturões de meandros formados no Holoceno, em vales incisos na planície de depósitos pleistocênicos. O rio Paraguai corre hoje em um destes vales, que corta longitudinalmente o megaleque, ajustado a padrões de fratura NE associados ao lineamento Transbrasiliano, com deflexão para SSE ao se encontrar com o rio Negro (Bolívia), com o qual compõe a drenagem periférica do leque. No cinturão de meandros abandonado...
The Nabileque fluvial megafan is depositional system that has been built by the Paraguay River at the southwestern border of the Pantanal wetland since Pleistocene times. With an area of approximately 9100 km², it is a peculiar fan system because it is not associated with rivers flowing from adjacent plateaus. The Nabileque megafan has been forming by Paraguay River at the exit of the Pantanal wetland, in lateral coalescence with the Pilcomayo megafan of the Chaco basin. It is important to emphasize that, although the name is also used to name a small river within the wetland, the name Nabileque was adopted to designate the megafan because the whole area is known as the Pantanal of Nabileque. The establishement of its geomorphologic evolution was based on remote sensing data interpretation with field ground truthing, sediment vibrocore-sampling and optical luminescence dating (OSL). Most of the area is covered by alluvial deposits, which dating has revealed ages spanning from 57.8 to 12.8 ka BP, but probably older deposits are present that were not reached by vibrocoring. Distributary, low-sinuosity to meandering paleochannels are visible as ancient depositional geoforms, but the Pleistocene alluvial surface is degradational and the alluvial deposits have being affected by pedogenesis and dissected by tributary small channels. Despite its degradational nature, the area is inundated during exceptional flooding events; this process is responsible for reworking and depositing of thin and irregular layer of Holocene sediments capping the oldest deposits. Two Holocene meander belts, confined in broad and shallow incised-valleys, are conspicuous features and record paleo-hydrologic changes. One of them is an abandoned N-S meander belt, in which runs the Nabileque River that has a channel much smaller... (Complete abstract click electronic access below)
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Araujo, Davi Brito de. "Effects of Megalac-R supplementation on measures of inflammation and performance in transport-stressed beef calves." [Gainesville, Fla.] : University of Florida, 2009. http://purl.fcla.edu/fcla/etd/UFE0024681.
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Shellberg, Jeffrey Gray. "Alluvial Gully Erosion Rates and Processes Across the Mitchell River Fluvial Megafan in Northern Queensland, Australia." Thesis, Griffith University, 2011. http://hdl.handle.net/10072/366569.
Full textAbstract:
Gully erosion is the process by which running water cuts new unstable channels into erodible
regolith. It causes severe land degradation, is a major component of contemporary sediment
budgets, and is a major source of sediment pollution to aquatic ecosystems. In northern
Australia, there is widespread gully erosion into unconfined alluvial deposits on active and
abandoned floodplains – here defined as alluvial gully erosion. In catchments draining to the
Gulf of Carpentaria, alluvial gullies can cover 0.2% to 1.0 % of the total catchment area and
locally >10% of the floodplain area. Alluvial gully erosion has been poorly documented and
differs substantially from colluvial or hillslope gullying in south-eastern or northern Australia.
The objectives of this research were to investigate and quantify alluvial gully erosion processes
and rates at a variety of spatial and temporal scales across a pilot study area, which encompasses
the Mitchell River fluvial megafan on the Cape York Peninsula in northern Queensland.
Along the Mitchell megafan, alluvial gullies are concentrated along main drainage channels.
Their scarp heights and potential energy are highly correlated to the local relief between the
floodplain and river thalweg, which is a result of river incision into the megafan since the
Pleistocene. Other factors such as floodplain hydrology, soil texture and chemistry, vegetation
cover, and land-use disturbance also influence the distribution and propagation of gullies, via
changes in the driving and resisting forces. The frequency of river flood inundation of alluvial
gullies on the floodplain changes longitudinally according to river incision and confinement.
Near the top of the megafan, flood water is contained in the macro-channel up to the 100-yr
recurrence interval (RI) but still backwaters adjacent alluvial gullies. In downstream Holocene
floodplains, complete inundation of alluvial gullies occurs beyond the 3- to 5-yr RI and can
contribute significantly to total annual erosion. However, a majority of gully scarp retreat is still
driven by direct rainfall and infiltration-excess runoff, with the 24-hr rainfall total being the
most predictive variable. This direct erosion is enhanced by inherent soil dispersibility and the
lack of vegetative cover, with the later if present having the potential to dissipate the effective
kinetic energy of rainfall and promote infiltration.Thesis (PhD Doctorate)
Doctor of Philosophy (PhD)
Griffith School of Environment
Science, Environment, Engineering and Technology
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Wingren, Andreas, and Jonas Olsson. "Från torgmöten med megafon till Twitter och relationer : en studie om Nya Moderaternas arbete med Public Relations." Thesis, Mittuniversitetet, Institutionen för informationsteknologi och medier, 2012. http://urn.kb.se/resolve?urn=urn:nbn:se:miun:diva-15811.
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Studien har sin grund i de nya utmaningar som politiska partier idag står inför. De politiska värderingarna i samhället har under de senaste 20 åren förändrats, vilket tvingar de politiska partierna att i större grad lyssna på sin omvärld för att kunna föra en relevant politik. Intresset för studien väcktes då vi ville ta reda på hur, och om, politiska partier arbetar med att etablera relationer med sina väljare, för att hantera dessa utmaningar. Studien har sin grund i en relationsskapande syn på public relations där teorier inom området har används för att svara på studiens syfte. Syftet är att undersöka hur Nya Moderaterna anser sig arbeta med Public Relations, med fokus på att etablera relationer, och hur detta återspeglas i deras kommunikation på Twitter. Studiens frågeställningar har besvarats med hjälp av en kvalitativ metod. Inledningsvis genomförde vi samtalsintervjuer med anställda på Nya Moderaternas kommunikationsavdelning för att därefter genomföra ytterligare samtalsintervjuer med utvalda, centrala, representanter ute i organisationen. Slutligen har en kvalitativ innehållsanalys genomförts av samtliga intervjupersoners, samt organisationens, twitterinlägg. Resultatet visar att Nya Moderaterna är väl medvetna om att deras omvärld har ett stort inflytande över huruvida partiet skall nå framgång eller ej. Det har också framkommit att samtliga intervjupersoner inom Nya Moderaterna är bra på att lyssna på sin omgivning och att de via Twitter bedriver en del dialog. Resultatet visar att det finns en klyfta i sättet att se på kommunikation mellan de på kommunikationsavdelningen och representanterna. Representanterna är mer personliga i sin kommunikation och i större omfattning för dialog än respondenterna på kommunikationsavdelningen. Partiets syfte är dock inte att bygga ömsesidiga relationer, utan att utforma passande budskap. Studien kan konstatera att Nya Moderaterna inte har några strategier för hur de skall bygga relationer med sin omvärld, men att det ändå sker ett omedvetet arbete kring att etablera relationer med omvärlden, dock inte av ömsesidig karaktär.
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Kuerten, Sidney. "Evolução geomorfológica e mudanças ambientais no megaleque do Nabileque, quaternário do Pantanal mato-grossense /." Rio Claro : [s.n.], 2010. http://hdl.handle.net/11449/102880.
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Orientador: Mario Luis AssineCoorientador: Edna Maria Facincani
Banca: Sandra Baptista da Cunha
Banca: Mauro Parolin
Banca: Edvard Elias de Souza Filho
Banca: José Cândido Stevaux
Resumo: O megaleque fluvial do Nabileque é um sistema deposicional que vem sendo construído pelo rio Paraguai na borda sudoeste do Pantanal Mato-Grossense desde tempos pleistocênicos. É um sistema aluvial peculiar, pois não está associado a rios oriundos de relevos altos situados nos planaltos adjacentes à planície. Trata-se de um megaleque fluvial construído pelo rio Paraguai, rio-tronco coletor das águas do todo sistema hidrográfico do Pantanal, na saída do rio para a planície do Chaco, onde coalesce com o megaleque do Pilcomayo. Com base em dados de sensores remotos e verificação de campo, foi realizada compartimentação e caracterização geomorfológica do megaleque, que ocupa área de aproximadamente 9100 km². Descrição e datação dos depósitos dos compartimentos identificados permitiram elaborar modelo evolutivo para a área, cuja maior parte é ocupada por vasta planície aluvial pleistocênica (idades LOE entre 57,8 e 12,8 Ka AP), marcada pela presença de intrincada rede de paleocanais distributários de baixa sinuosidade a meandrantes. Feições fluviais erosivas e redes de canais tributários superimpostos evidenciam que as áreas de ocorrência dos depósitos pleistocênicos se encontram em degradação, embora sujeitas a frequentes inundações, responsáveis pela deposição de delgadas e irregulares coberturas de sedimentos mais recentes. Um aspecto notável é a existência de dois cinturões de meandros formados no Holoceno, em vales incisos na planície de depósitos pleistocênicos. O rio Paraguai corre hoje em um destes vales, que corta longitudinalmente o megaleque, ajustado a padrões de fratura NE associados ao lineamento Transbrasiliano, com deflexão para SSE ao se encontrar com o rio Negro (Bolívia), com o qual compõe a drenagem periférica do leque. No cinturão de meandros abandonado... (Resumo completo, clicar acesso eletrônico abaixo)
Abstract: The Nabileque fluvial megafan is depositional system that has been built by the Paraguay River at the southwestern border of the Pantanal wetland since Pleistocene times. With an area of approximately 9100 km², it is a peculiar fan system because it is not associated with rivers flowing from adjacent plateaus. The Nabileque megafan has been forming by Paraguay River at the exit of the Pantanal wetland, in lateral coalescence with the Pilcomayo megafan of the Chaco basin. It is important to emphasize that, although the name is also used to name a small river within the wetland, the name Nabileque was adopted to designate the megafan because the whole area is known as the Pantanal of Nabileque. The establishement of its geomorphologic evolution was based on remote sensing data interpretation with field ground truthing, sediment vibrocore-sampling and optical luminescence dating (OSL). Most of the area is covered by alluvial deposits, which dating has revealed ages spanning from 57.8 to 12.8 ka BP, but probably older deposits are present that were not reached by vibrocoring. Distributary, low-sinuosity to meandering paleochannels are visible as ancient depositional geoforms, but the Pleistocene alluvial surface is degradational and the alluvial deposits have being affected by pedogenesis and dissected by tributary small channels. Despite its degradational nature, the area is inundated during exceptional flooding events; this process is responsible for reworking and depositing of thin and irregular layer of Holocene sediments capping the oldest deposits. Two Holocene meander belts, confined in broad and shallow incised-valleys, are conspicuous features and record paleo-hydrologic changes. One of them is an abandoned N-S meander belt, in which runs the Nabileque River that has a channel much smaller... (Complete abstract click electronic access below)
Doutor
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Zani, Hiran. "Mudanças morfológicas na evolução do megaleque do Taquari : uma análise com base em dados orbitais /." Rio Claro : [s.n.], 2008. http://hdl.handle.net/11449/92779.
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Orientador: Maria Luis AssineBanca: Márcio de Morisson Valeriano
Banca: Archimedes Perez Filho
Resumo: Esta dissertação visa caracterizar mudanças morfológicas recentes no megaleque do Taquari, através de dados de Sensoriamento Remoto. As baixas declividades do terreno e pequenas amplitudes das formas deposicionais, que predominam nesta paisagem, demandaram o desenvolvimento de métodos específicos para a extração das informações. Dados SRTM e imagens multiespectrais foram utilizados no mapeamento dos paleocanais e confecção de modelos digitais de elevação. A drenagem relicta foi mapeada através de desenho digital, sobre mosaicos georreferenciados dos sensores ASTER, MODIS e CBERS2. Nos vetores dos paleocanais identificados foi realizado cálculo de densidade areal e criados histogramas direcionais (rosetas), que ressaltaram relações topológicas e permitiram a interpretação de seis lobos deposicionais. Modelos digitais de elevação foram gerados através da subtração dos dados SRTM originais com uma superfície topográfica simplificada pelo método de regressão polinomial cúbica. Este processamento ressaltou zonas deprimidas no megaleque, espaços potenciais para acúmulo de sedimentos, e zonas de sobrelevadas, devido à processos agradacionais contínuos em determinadas áreas. A identificação e caracterização destas formas é passo inicial para a reconstituição dos eventos geomórficos e antevisão de futuras mudanças no curso do rio Taquari. A dinâmica de construção e abandono dos lobos mostrou-se mais complexa do que o apresentado em trabalhos anteriores, sendo de aspecto fragmentado e de natureza fractal.
Abstract: This work aims characterize morphological changes in Taquari megafan, by remote sensing techniques. Gentle slopes of landscape and low amplitudes of geoforms demands the development of specific methods to extract valuable topographic information. SRTM data and multispectral images were used to map paleochannels and to build digital elevation models (DEM). Relict streams were mapped by computer-aided design in GIS environment, using georeferenced mosaics of ASTER, CBERS and MODIS sensors. These vectors were used to calculate drainage density and directional histograms, revealing topological aspects and lead to interpret 6 depositional lobes. DEM was obtained by subtracting the original SRTM data from a simplified surface generated by cubic polynomial regression. This product revealed depressed areas in the Taquari megafan, potential accommodation spaces for deposition, and geoforms with a higher amplitude than their neighbor, probably because of continuous gradational processes in these specifics sites. The recognition of these landforms is the initial step for figure out the evolution of geomorphic events and to support a well done planning in land occupation. The dynamics of Taquari megafan showed to be more complex than previous studies proposed.
Mestre
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Hinders, Johan. "Dödsrikets livshistorier : Benkemiska isotopanalyser på artikulerade och disartikulerade individer i Frälsegårdens gånggrift." Thesis, Stockholms universitet, Arkeologiska forskningslaboratoriet, 2011. http://urn.kb.se/resolve?urn=urn:nbn:se:su:diva-62099.
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The aim in this thesis is to use carbon, nitrogen and sulfur isotope analysis on teeth and bone to track diet and mobility of the population as well as the individual level from the articulated and disarticulated individuals from the passage grave Frälsegården, situated in Gökhem parish in the region of Falbygden, western Sweden. 50 human samples were analyzed from tooth, mandibula and femur, together with 11 faunal samples from different bone elements of local wild and domestic animals. The results fall well in line with earlier stable isotope work done on passage grave individuals from Falbygden in stable isotopes: A homogenous group with a diet which was clearly terrestrial and lived on a pretty high trophic level. It also seems that the analyzed individuals deliberately focused their food intake to the cultural and natural, megalith and limestone landscape of Falbygden, and not to its surroundings, even if the passage grave is situated in the outermost areas of the region. A small study compares the sulfur results to with earlier work done on strontium isotopes. The results show that the different methods might provide a deeper understanding in the interpretation of the methods, and therefore suggesting that further work should be done to compare the methods.
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Werner, Kjell. "The Megaron during the Aegean and Anatolian Bronze Age : a study of occurrence, shape, architectural adaptation, and function /." Göteborg : P. Aströms Förlag, 1993. http://catalogue.bnf.fr/ark:/12148/cb37160168n.
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Zani, Hiran [UNESP]. "Mudanças morfológicas na evolução do megaleque do Taquari: uma análise com base em dados orbitais." Universidade Estadual Paulista (UNESP), 2008. http://hdl.handle.net/11449/92779.
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zani_h_me_rcla.pdf: 8429664 bytes, checksum: 62c5b99b684e6da2a2faa22d20ae412e (MD5)Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP)
Esta dissertação visa caracterizar mudanças morfológicas recentes no megaleque do Taquari, através de dados de Sensoriamento Remoto. As baixas declividades do terreno e pequenas amplitudes das formas deposicionais, que predominam nesta paisagem, demandaram o desenvolvimento de métodos específicos para a extração das informações. Dados SRTM e imagens multiespectrais foram utilizados no mapeamento dos paleocanais e confecção de modelos digitais de elevação. A drenagem relicta foi mapeada através de desenho digital, sobre mosaicos georreferenciados dos sensores ASTER, MODIS e CBERS2. Nos vetores dos paleocanais identificados foi realizado cálculo de densidade areal e criados histogramas direcionais (rosetas), que ressaltaram relações topológicas e permitiram a interpretação de seis lobos deposicionais. Modelos digitais de elevação foram gerados através da subtração dos dados SRTM originais com uma superfície topográfica simplificada pelo método de regressão polinomial cúbica. Este processamento ressaltou zonas deprimidas no megaleque, espaços potenciais para acúmulo de sedimentos, e zonas de sobrelevadas, devido à processos agradacionais contínuos em determinadas áreas. A identificação e caracterização destas formas é passo inicial para a reconstituição dos eventos geomórficos e antevisão de futuras mudanças no curso do rio Taquari. A dinâmica de construção e abandono dos lobos mostrou-se mais complexa do que o apresentado em trabalhos anteriores, sendo de aspecto fragmentado e de natureza fractal.
This work aims characterize morphological changes in Taquari megafan, by remote sensing techniques. Gentle slopes of landscape and low amplitudes of geoforms demands the development of specific methods to extract valuable topographic information. SRTM data and multispectral images were used to map paleochannels and to build digital elevation models (DEM). Relict streams were mapped by computer-aided design in GIS environment, using georeferenced mosaics of ASTER, CBERS and MODIS sensors. These vectors were used to calculate drainage density and directional histograms, revealing topological aspects and lead to interpret 6 depositional lobes. DEM was obtained by subtracting the original SRTM data from a simplified surface generated by cubic polynomial regression. This product revealed depressed areas in the Taquari megafan, potential accommodation spaces for deposition, and geoforms with a higher amplitude than their neighbor, probably because of continuous gradational processes in these specifics sites. The recognition of these landforms is the initial step for figure out the evolution of geomorphic events and to support a well done planning in land occupation. The dynamics of Taquari megafan showed to be more complex than previous studies proposed.
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McCool, Megan Elizabeth [Verfasser], and Christian [Akademischer Betreuer] Apfelbacher. "Epidemiology and care of female sexual dysfunction / Megan Elizabeth McCool ; Betreuer: Christian Apfelbacher." Regensburg : Universitätsbibliothek Regensburg, 2017. http://d-nb.info/1126724602/34.
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