Дисертації: "NRT1"

1

Faure, Sandrine. "Étude de l'absorption du nitrate chez Brassica napus L. : évolution de l'activité des transporteurs et de la transcription des gènes NRT1 et NRT2 en réponse à une privation en NO 3, évaluation de leur rôle sur le cycle de culture." Caen, 2000. http://www.theses.fr/2000CAEN2007.

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Le colza, espece phylogenetiquement proche d'arabidopsis thaliana et presentant des capacites d'absorption elevees, a ete choisi pour etudier le metabolisme azote des especes cultivees. Les etudes cinetiques revelent un profil d'absorption du nitrate biphasique, suggerant qu'il existe au moins 2 systemes d'absorption : un systeme saturable a forte affinite agissant pour des faibles concentrations externes en no 3 (hats), et un systeme non saturable a faible affinite intervenant pour les fortes concentrations (lats). Ces deux systemes seraient constitues chacun d'une composante constitutive (chats et clats) et d'une composante inductible (ihats et ilats). Le suivi de la transcription des genes nrt1 et nrt2 au cours d'une privation partielle ou totale en azote conforte l'hypothese selon laquelle le gene nrt2 code un systeme ihats alors que le gene nrt1 code un systeme ilats. Si dans nos conditions experimentales, l'existence d'un mecanisme de de-induction et/ou de repression par les acides amines libres pourrait expliquer la chute de la transcription des genes nrt1 et nrt2 pendant les 48 premieres heures de privation. Par contre aucun mecanisme de de-repression n'a pu etre mis en evidence. L'expression des genes nrt1 et nrt2 est regulee au niveau transcriptionnel par le no 3 externe et probablement par la demande en azote des parties aeriennes, mais aussi au niveau post-transcriptionnel. Nos resultats montrent que chez le colza, les pools racinaires en no 3 et en acides amines libres n'interviennent pas au niveau transcriptionnel. Nous avons initier un modele mecaniste de l'absorption du nitrate au cous d'un cycle de culture uniquement base sur l'offre en nitrate du sol et sur le fonctionnement des transporteurs. Les simulations realisees montrent que le systeme hats intervient pour 94% en l'absence de fertilisation et pour 82% lors d'un apport azote a l'automne. Une fertilisation azotee augmente la capacite et la duree d'intervention du systeme lats.

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2

Caillaud, Kevin. "Etude de l'impact du vieillissement sur les effets métaboliques et musculaires de la Neureguline 1." Thesis, Clermont-Ferrand 2, 2015. http://www.theses.fr/2015CLF20065/document.

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3

Lampropoulou, Anastasia Syrmalenia. "NRP1 regulation of endothelial cell signalling." Thesis, University College London (University of London), 2017. http://discovery.ucl.ac.uk/1574397/.

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Neuropilin 1 (NRP1) is a transmembrane protein that is essential for blood vessel growth and the regulation of vascular barrier properties. Yet, at the time of starting my PhD research, it was poorly understood how NRP1 affects endothelial cell behaviour to enhance either blood vessel growth or modulate vascular permeability. In particular, it was controversial whether NRP1 mainly acts to promote VEGF signalling through the VEGF receptor tyrosine kinase VEGFR2, or if it has other roles that synergise with VEGFR2 pathways to promote effective tissue vascularisation or vascular permeability. The aims of this study were therefore to (a) investigate whether NRP1 modulates angiogenesis and vascular hyperpermeability together with or independently of VEGFR2, (b) determine whether NRP1 regulates gene transcription to modulate endothelial behaviour; (c) define the molecular mechanism by which NRP1 regulates angiogenesis and VEGF-induced vascular hyperpermeability. My experiments have revealed that NRP1 promotes blood vessel growth both independently of, and synergistically with, VEGFR2-driven pathways. In particular, I found that VEGFR2-independent signalling involves the intracellular signal transducers CDC42 and ABL1 kinase, which promote actin remodelling during cell migration. Instead, my experiments have revealed that NRP1 promotes VEGF-induced vascular permeability in a complex with VEGFR2. Specifically, I found that that both NRP1 and VEGFR2 are required for the VEGF induced activation of SRC family kinases (SFKs), which are known to be essential for VEGF-induced vascular permeability signalling. Moreover, I found that NRP1 is important, because it is required for ABL1 activation, which in turn is essential for SFK activation in this pathway. Finally, I observed that NRP1 regulates several transcription factors and the expression of their target genes in endothelial cells, particularly genes involved in actin remodelling and cell proliferation. Together, this knowledge increases our understanding of the mechanisms of blood vessel formation and function. By identifying molecular pathways in blood vessel growth and permeability, these findings may, in the long run, benefit translational research aimed at developing novel therapies for diseases with vascular dysfunction.

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4

Mirza, Nazzia Nosheen. "Neuregulin-1 (NRG1) in colorectal cancer." Thesis, University of Birmingham, 2009. http://etheses.bham.ac.uk//id/eprint/7892/.

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Previous studies identified a distinct region of interstital deletion at c8p12 locus in colorectal cancer. Deletions at c8p12 were more frequent in early than advanced colorectal tumours. Further studies defined more closely this interstitial deletion, implicating a cluster of genes close to marker D85259 in early colorectal tumours. Although interstitial deletions normally correspond to tumour suppressor genes, the above findings suggest that this region contains genes with tumour suppressive and oncogenic effects. We investigated NRG1, one of the genes in this region in colorectal tumourigenesis. To determine the expression profile of NRG1 , multiple approaches were utilised. Results from these studies identified deletion (loss of one allele) of \(NRG1\) in early colorectal tumours. Increased expression of NRG1 protein was identified in advanced tumours compared to early colorectal tumours and adenomas. A significant correlation between NRG1 protein expression and erb82 protein overexpression was identified. Although the range of NRG1 isoforms expressed was qualitatively similar throughout tumour progression, semi-quantitative real-time RT -PCR, showed overall decreased expression in early tumours compared with normal tissue. In advanced cancers, the results were more heterogeneous, but no consistent pattern emerged between the cases investigated. Although these studies did not demonstrate any functional relationship, the data strengthens the candidacy of a role for NRG1 in colorectal tumour progression.

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5

Wu, Suquin, and s3102813@student rmit edu au. "Performance of regional atmospheric error models for NRTK in GPSnet and the implementation of a NRTK system." RMIT University. Mathematical and Geospatial Sciences, 2009. http://adt.lib.rmit.edu.au/adt/public/adt-VIT20091014.144831.

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Many high-accuracy regional GPS continuously operating reference (CORS) networks have been established globally. These networks are used to facilitate better positioning services, such as high accuracy real-time positioning. GPSnet is the first state-wide CORS network in Australia. In order to maximize the benefits of the expensive CORS geospatial infrastructure, the state of Victoria in collaboration with three universities (RMIT University, the University of NSW and the University of Melbourne) embarked on research into regional atmospheric error modelling for Network-based RTK (NRTK) via an Australian Research Council project in early 2005. The core of the NRTK technique is the modelling of the spatially-correlated errors. The accuracy of the regional error model is a determining factor for the performance of NRTK positioning. In this research, a number of error models are examined and comprehensively analysed. Among them, the following three models are tested: 1) the Linear Interpolation Method (LIM); 2) the Distance-Based interpolation method (DIM); and 3) the Low-order surface model (LSM). The accuracy of the three models is evaluated using three different observation sessions and a variety of network configurations of GPSnet. Results show that the LIM and DIM can be used to significantly reduce the double-differenced (DD) residuals (up to 60% improvement), and the LIM is slightly better than the DIM (most at mm level). However the DD residuals with the LSM corrections are, in some cases, not only much worse than that of the LIM and DIM but also even must greater/worse than the DD residuals without any corrections applied at all. This indicates that there are no advantages by using the LSM for the error modelling for NRTK in GPSnet, even though it is the most commonly used method by researchers. The performance difference of the LIM for different GPSnet configurations is also tested. Results show that in most cases, the performance difference mainly caused by the number of reference stations used is not significant. This implies that more redundant reference stations may not contribute much to the accuracy improvement of the LIM. However, it may mitigate the station specific errors (if any). The magnitude of the temporal variations of both the tropospheric and ionospheric effects in GPSnet observations is also investigated. Test results suggest that the frequency of generating and transmitting the tropospheric corrections should not be significantly different from that for the ionospehric corrections. Thus 1Hz frequency (i.e. once every second) is recommended for the generation and transmission for both types of the atmospheric corrections for NRTK in GPSnet. The algorithms of the NRTK software package used are examined and extensive analyses are conducted. The performance and limitation of the NRTK system in terms of network ambiguity resolution are assessed. The methodology for generating virtual reference station (VRS) observations in the system is presented. The validation of the algorithms for the generated VRS observations is undertaken. It is expected that this research is significant for both the selection of regional error models and the implementation of the NRTK technique in GPSnet or in the Victorian region.

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6

Setiawan, Careza [Verfasser], and Moritz [Akademischer Betreuer] Rossner. "NRG1 cleavage assay and small molecule screen for modulators of NRG1 processing / Careza Setiawan ; Betreuer: Moritz Rossner." München : Universitätsbibliothek der Ludwig-Maximilians-Universität, 2018. http://d-nb.info/1168145848/34.

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7

Werling, Kristoffer, and Andreas Höglund. "Jämförelse av mätosäkerhet i höjd över tid med NRTK : Undersökning av tidsvariationer för GNSS-höjder inmätta med NRTK." Thesis, Karlstads universitet, Institutionen för miljö- och livsvetenskaper (from 2013), 2021. http://urn.kb.se/resolve?urn=urn:nbn:se:kau:diva-85239.

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Global Navigation Satellite Systems (GNSS) i kombination med Nätverks-RTK (NRTK) har idag blivit en vanlig metod för geodetiska inmätningar i plan och höjd. Inmätningar med NRTK har fördelen att de är relativt enkel att använda, ger koordinater i realtid och med låg mätosäkerhet (2–3 cm). Dock har användare rapporterat om att större avvikelser i höjd är vanligare än avvikelser i plan, vilka varierar över tid. Tidigare studier har inte funnit samband mellan avvikelser i höjd med NRTK och variationen över tid. Studiens syfte var att undersöka hur resultatet av inmätta höjder med NRTK varierar över tid och vad som påverkar avvikelsen i höjd samt om det går att finna ett samband för avvikelserna. I studien användes en GNSS-mottagare med NRTK för att på två stompunkter insamla mätdata en gång i minuten i tre timmar på varje punkt, under totalt två dagar. Mätdata som lagrades och analyserades var antal satelliter, PDOP, vertikal precision, och tidpunkt för inmätt höjd och höjdvärde. Under fältarbetet användes också två olika elevationsvinklar, 10 och 15 grader, för att se hur mätosäkerheten påverkades. Vidare utfördes en dubbelavvägning mellan stompunkterna som en kontroll av de angivna höjdkoordinaterna. Resultatet visar att variationen för enskild inmätt höjd är slumpmässig. En undersökning av PDOP, antal satelliter, horisontell och vertikal precision gav inga korrelationer till mätresultatet. Standardosäkerheten i höjd för mätserie på punkt 8316 med 10° elevationsvinkel beräknades till 1,2 cm och med en förändring till 15° elevationsvinkel 1,6 cm. På punkt 8318 med 10° elevationsvinkel beräknades 2,6 cm och med 15° elevationsvinkel 3,4 cm. Analysen av mätdata förtydligar att behov finns för att öka tillförlitligheten vid GNSS-mätning med NRTK. Standardosäkerheten överskrider angiven mätosäkerhet för metoden, vid mätning på 8318 med 15° elevationsvinkel. Med elevationsvinkel 10° uppnås inte 68 % av mätningarna inom sigmanivå 2, och drygt 13 % återfinns inom sigmanivå 2–3. Vid en beräkning av standardosäkerhet, med medeltals-bildning, erhölls markanta förbättringar på punkt 8316 för båda mätserierna upp till 20 min medan det följande ger avtagande förbättringar. På punkt 8318 erhölls ständiga förbättringar kontinuerligt till 60 min vilket var den högsta gränsen som undersöktes. Differens mellan högsta och lägsta avvikelse för inmätt höjd, jämfört med känd höjd, beräknades till 9,2 cm för punkt 8316 med 15° elevation och 6,9 cm med 10°. Motsvarande för punkt 8318 med 15° beräknades avvikelsen till 16,5 cm och 12,3 cm för 10°. För GNSS-användare behövs insikt i att enskilda mätningar, med lågt angivna värden i handenheten, inte säkerställer goda mätresultat. Flera mätningar under kort tid kan ge mycket låg standardosäkerhet, men en timme senare kan samma låga standard-osäkerhet för nya mätningar fortfarande representera en avvikande inmätt höjd. Medeltalsbildning, tidsseparation och en lämplig elevationsvinkel är sannolikt krav för att tillförlitligt kunna säkerställa att metoden uppnår 2–3 cm mätosäkerhet i höjd för 68 % av mätningarna.
The usage of GNSS is becoming increasingly more common due to its efficiency and time saving capacities. Network-RTK is a method that uses relative positioning and is supposed to deliver measurements with a positional accuracy of about 2-3 cm for plane and height. Previous research shows variety in measuring results using NRTK at different times or days, but the focus was on other aspects than time itself. This study focused on time and its impact on GNSS-derived heights, linked to used methods for practical use of GNSS, and these results were meant to create guidelines or routines for increased reliability in measuring data if it exceeded the positional accuracy. Measurment data were gathered at two vertical control points during three hours each, on two separate days, with data being collected at a one-minute interval. The findings of this study show that the variety over time is random, and that there are no standard settings or routines that guarantee reliability for the method to deliver commonly stated positional accuracies. Although, we found that certain steps for improving measurements are time-separating, averaged measurements for at least twenty minutes, and a good understanding of how to set an appropriate elevation mask.

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8

Brash, James Thomas. "VEGF isoforms and NRP1 in vascular hyperpermeability." Thesis, University College London (University of London), 2018. http://discovery.ucl.ac.uk/10058912/.

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The cardiovascular system serves to deliver oxygen and nutrients to the tissues of the body whilst simultaneously removing waste products. Blood vessels display a degree of basal permeability to achieve this function, which is regulated at the level of the endothelial monolayer. In response to certain stimuli, the integrity of the endothelial barrier is reduced, rendering blood vessels hyperpermeable. Best known as a potent inducer of angiogenesis, the vascular endothelial growth factor (VEGF) was originally identified as a vascular permeability factor. In certain diseases, such as those characterised by ischemia, VEGF upregulation causes vascular hyperpermeability and pathological oedema. VEGF exists in three major isoforms, termed VEGF120, VEGF164 and VEGF188, which variably engage one or more of several VEGF receptors, termed VEGFR1, VEGFR2 and NRP1. A better understanding of the how the different VEGF isoforms engage their receptors and downstream signalling pathways to promote vascular hyperpermeability may help refine current therapeutic strategies to target VEGF-induced oedema. In this volume of work, I have studied VEGF induced vascular hyperpermeability from several perspectives. Using an in vivo model of vascular hyperpermeability, I have compared VEGF isoform potency and investigated which receptors are required by different VEGF isoforms to promote vascular leakage. Using tissue culture models of vascular endothelium coupled with biochemical techniques, I have determined how VEGF isoforms and their receptors affect known hyperpermeability signal transduction pathways. Specifically, I have shown that NRP1 and its cytoplasmic domain (NCD) impact two VEGF hyperpermeability signalling axes, and that the NCD interacts with proteins previously linked to endothelial tight junctions and paracellular permeability. Finally, I have examined the expression of VEGF isoforms in several disease models that are characterised by vascular hyperpermeability.

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9

Huang, H. E. "Chromosome aberrations targeting the NRG1 gene in cancer." Thesis, University of Cambridge, 2004. http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.604700.

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Thirty-four breast and nine pancreatic cancer cell lines were surveyed for alterations of the NRG1 gene by fluorescence in situ hybridization (FISH). A recent chromosome translocation breakpoint that targets the NRG1 gene was found in five breast and two pancreatic lines. High-resolution mapping by two-colour FISH showed that the breakpoints were clustered in a 1.1 Mb interval within NRG1. RT-PCR showed an extensive complexity of NRG1 transcripts in the translocation-positive lines, suggesting that expression of the ligand is a consequence of these structural arrangements. This study was extended to primary tumour material to confirm the presence and prevalence of NRG1 translocation in uncultured cancer cells. I designed a FISH strategy (using a custom FISH probe-the Neuprobe), which was used in a high-throughput manner on archival paraffin embedded material in the form of tissue microarrays (TMAs).A survey of 339 primary breast carcinomas identified a disruption targeting NRG1 in approximately 6% of all cases examined. The common abnormality seen was a deletion in the 5’ end of the gene, often accompanied by amplification of the 3’ end. Genomic alteration of NRG1 was associated with ectopic expression of NRG1 α and β isoforms. Fine mapping confirmed that these breakpoints cluster within the same region seen in cell lines. These results were independently validated by array-based CGH, using a custom made array with overlapping BACS spanning 8p12. NRG1 translocation was associated with high-grade tumours, low HER2 expression, and high expression levels of FGFR1, TACC (both in close genomic proximity to NRG1). A further survey of 242 primary ovarian tumours identified the same abnormality in 10% of tumours.

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10

Zhao, Zhe. "Transcription regulation of Nrp1 during endothelial cell differentiation." Thesis, University of Oxford, 2014. http://ora.ox.ac.uk/objects/uuid:a76152dd-72f0-450c-aad2-d0db732f2e6d.

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Various diseases, including cancer, stroke and heart attack, are associated with disruption of the vascular system. However, lack of a profound understanding of the transcription regulation during vascular development hinders the formation of effective molecular intervention strategies targeting angiogenesis. Here we describe an enhancer of Neuropilin1 (Nrp1) from the second intron of the gene that directs arterial and coronary endothelial cell-specific expression. Mice transgenic for either human or mouse sequences of the Nrp1in2 enhancers drove expression of the LacZ reporter gene specifically in the endothelial cells within the arterial compartment from early in development, while no expression was detected in veins. In addition, the hNrp1in2 enhancer directed expression to the endothelial cells in the developing coronary vasculature, with the initial expansion from around the sinus venosus at E11.5, and eventually contributed to the capillary, venous and arterial compartments of the coronary vessels but not the endocardium. This expression pattern is consistent with that reported in the Apelin-nlacZ line (Red-Horse et al., 2010), making the Nrp1 enhancer the first identified mammalian regulating enhancer of the coronary endothelial cell. Phylogenetic footprinting, and a tissue culture reporter assay suggested that this enhancer contains a 184bp minimal core region hNrp1in2peakA2 that recapitulates the expression profile of the full length enhancer. hNrp1in2peakA2 has conserved and in vitro validated recognition sites for Gata, Ets, and Fox. The validated Fox and Ets sites form a functional FOX:ETS motif, and the FOX:ETS motif is responsible for synergistic activation ofthe enhancer by FoxC2 and Etv2 in reporter assays. Mutation introduction to the functional Ets sites or compound ablation of the Gata and Fox site in hNrp1in2peakA2 result in total loss of vascular expression, in terms of both arterial and coronary expression. The Fox, Ets and Gata recognition sites may be sufficient to achieve arterial- and coronary- specific expression of the hNrp1in2peakA2.

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11

Svensson, Mikael, and Daniel Lidbom. "En kvalitetsjämförelse av NRTK-mätningar med olika GNSS-instrument." Thesis, Karlstads universitet, 2018. http://urn.kb.se/resolve?urn=urn:nbn:se:kau:diva-70289.

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12

Argimón, Silvia. "Regulation of Als3 and Nrg1 during morphogenesis in Candida albicans." Thesis, University of Aberdeen, 2006. http://digitool.abdn.ac.uk/R?func=search-advanced-go&find_code1=WSN&request1=AAIU602322.

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Candida albicans is an opportunistic human pathogen. Several factors contribute to the virulence of this fungus. These include phenotypic switching, biofilm formation, the secretion of hydrolytic enzymes, the production of adhesion molecules, and the ability to undergo reversible morphological changes from yeast to (pseudo)hyphae in response to the host physiological conditions. Multiple signalling pathways link the relevant environmental signals to hyphal growth, and several downstream transcription factors promote or repress genes involved in the yeast-to-hypha transition. A number of genes are induced specifically during hyphal development. ALS3 encodes a hypha-specific cell wall protein of the Agglutinin-Like Sequence family of adhesins. The first aim of this project was to study the transcriptional regulation of ALS3. Previous work in our laboratory identified two sequences that bind the transcriptional repressor Nrgl (NREs), and that are required for repression under yeast inducing conditions. Moreover, a region of 150 bp between -471 and -321 was defined as being important for ALS3 activation (A1 region). However, no short sequence or known response element within this activation region, in isolation, was sufficient for hypha- specific activation of ALS3. In this study we identified an additional activation region (A2) located between -1438 and -1050. Furthermore, we found that the transcription factors Efgl, Bcrl and Teel are required for the activation of ALS3 under serum- inducing conditions. Also, Cphl contributes to the hypha-specific activation of ALS3, but it is not essential for expression. Teel does not act directly through the five putative Teel binding sites present in the ALS3 promoter, which are not functional, but mediates activation of ALS3 indirectly via Bcrl. Under conditions that promote yeast growth, ALS3 expression is repressed by Nrgl, Tupl and Rfgl, but not by Ssn6 or the mating factor al. The morphogenetic repressor Nrgl targets the global repressor Tupl to the promoters of hypha-specific genes and other genes to inhibit the yeast-to-hypha transition. The second aim of our project was to study the regulation of Nrgl. Previous work in our laboratory showed that, as expected, NRG1 mRNA levels decrease during hyphal development. However, the down-regulation of NRG1 was too slow to account for the rapid induction of hyphal growth. In this study we found that Nrgl is a phosphoprotein that is found phosphorylated in yeast cells and becomes rapidly and transiently dephosphorylated in serum-induced cells. In addition, Efgl is required for Nrgl- mediated repression via the NRE under non-inducing conditions, whereas the release of Nrgl-mediated repression under inducing conditions is dependent on components of the cAMP-PKA pathway. Furthermore, we found that the Nrgl-mediated repression of an NRE-containing reporter construct in yeast cells requires both Tupl and Ssn6, although this might not always be the case for native promoters. Altogether, the results of this project show that several signalling pathways converge at the promoter of the hypha-specific gene ALS3 to regulate its expression. The activity of one of the negative regulators of ALS3, the morphogenetic repressor Nrgl, appears to be modulated both at the transcriptional and post-translational level. Furthermore, the cAMP-PKA pathway seems to link positive and negative regulation of morphogenesis in C. albicans.

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13

Hérou, Mathias, and Ragnar Boll. "Bestämning av vattenytor med hjälp av Nätverks-RTK och totalstation : Inmätning av Karlbergsån i Grums kommun." Thesis, Karlstads universitet, Fakulteten för samhälls- och livsvetenskaper, 2010. http://urn.kb.se/resolve?urn=urn:nbn:se:kau:diva-6118.

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This report is presenting an approach that can be used to measure water surfaces in difficult conditions caused by dense vegetation and lack of nearby known points. The objective was to make a contribution to necessary measures for adaptation against floods in Grums Municipality along the stream Karlbergsån, which may occur when persistent rain raises the level of the stream. Along the river there are low-lying areas prone to flooding. According to Grums Municipality, the stream may widen where the water level differences are large, to create a better flow path and to counteract flooding. Grums Municipality was also interested in survey stormwater discharges which may affect the water level in the stream. The requirement for measurement accuracy must be reached is less than 0.1 m in height with the maximum of 10 m between the measured points in plane. The question we asked ourselves was: "How can an area be measured when there is a lack of nearby known fixpoints and when the visibility to satellites is poor due to dense vegetation?" To be able to measure the area, we established a net of temporary fixpoints with NRTK , which later was used for the measuring of water surfaces and stormwater discharges by using total station. For measuring, both prism and reflectorless measurement have been used. Coordinates for the net of temporary fixpoints, input water levels and storm water discharges are presented and the report files and coordinates for station establishment. Graphic elevation profiles of water levels are registered. Visualization was created by using aerial photographs and measured data showing the entire surveyed area, including free station establishment with directions to the reference points together with the measured fixpoints and stormwater discharges. We believe we have come below the accuracy requirement of 0.1 m and sought a distance between points at less than 10 m but in some places where the measurements were limited the distance is greater than 10 m.

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14

Fleck, Daniel. "Regulated intramembrane proteolysis of NRG1 type III dediates postnatal peripheral myelination." Diss., Ludwig-Maximilians-Universität München, 2015. http://nbn-resolving.de/urn:nbn:de:bvb:19-183725.

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Neuregulin-1 (NRG1) type III is a growth factor on the surface of neurons in the peripheral nervous system (PNS). It is required for initial myelination of nerves by Schwann cells after birth and for remyelination after injury. Neuregulin-1 type III is activated by cleavage (shedding) in its extracellular juxtamembrane region generating a membrane-bound N-terminal fragment (NTF) that contains a bioactive epidermal growth factor (EGF)-like domain. This domain signals to neighboring Schwann cells in a contact-dependent manner prompting the cells to initiate myelination. The β-site APP cleaving enzyme 1 (BACE1) was identified as the enzyme that cleaves NRG1 type III and promotes myelination. Consequently, loss of BACE1 cleavage results in dramatically reduced myelin sheaths around nerves in the PNS of BACE1 knockout mice. Besides its role in myelination, BACE1, better known as β-secretase, is also involved in the generation of the neurotoxic amyloid β-peptide (Aβ) which is the main component of amyloid plaques in the brain of patients suffering from Alzheimer’s disease (AD). The Aβ peptide is derived through sequential cleavage of the amyloid precursor protein APP, first by BACE1 in the extracellular domain and subsequently by the γ-secretase in the transmembrane domain (TMD). Inhibition of BACE1 and γ-secretase is therefore considered a promising therapeutic strategy for AD. However, this approach harbors the risk of mechanism-based side effects due to impaired processing of substrates beside APP such as NRG1 type III which is not only a substrate for BACE1 but like APP is also cleaved in its TMD by the γ-secretase. Adding another layer of complexity, ADAM10 and ADAM17, the so-called α-secretases of AD, also cleave NRG1 type III. In the first part of this study, the proteolytic processing of NRG1 type III in its ectodomain was investigated in detail. The precise juxtamembrane shedding sites of BACE1, ADAM10 and ADAM17 were determined by mass spectrometry and two novel cleavage sites of BACE1 and ADAM17 N-terminal of the EGF-like domain were discovered. Cleavage at these novel sites by ADAM17 and BACE1 results in the secretion of the EGF-like domain from NRG1 type III as α-sEGF and β-sEGF, respectively. Using novel monoclonal antibodies generated against the identified cleavage sites the processing of NRG1 type III could also be confirmed in primary neurons. The soluble EGF-like domains were found to be functionally active and induced signaling pathways required for myelination in cultured Schwann cells. Furthermore, β-sEGF rescued the myelination deficit in the PNS of a zebrafish model lacking BACE1, thereby demonstrating its activity in vivo. Using cell culture and the zebrafish model the effects of BACE1- and ADAM17-mediated shedding on the activity of the soluble EGF-like domains were carefully dissected. In contrast to published evidence, however, both the BACE1- as well as the ADAM17-shed sEGF were found to be equally active and to promote myelination in vivo. Together this suggests that NRG1 type III dependent myelination is not only controlled by membrane-retained NRG1 type III but also in a contact-independent manner via proteolytic liberation of the EGF-like domain. The second part of this study investigates the processing of the C-terminal fragment (CTF) which remains after shedding of NRG1 type III. Intramembranous cleavage of the CTF by the γ-secretase was previously shown to release the NRG1 intracellular domain, which acts as transcriptional regulator of proteins involved in neuronal maturation and brain plasticity. Interestingly, a mutation within the TMD of NRG1 type III is associated with an increased risk of schizophrenia linking γ-secretase processing of NRG1 type III to this neurological disorder. Using a novel antibody against the N-terminus of the NRG1 CTF it was possible to detect a NRG1 β-peptide that is secreted during γ-secretase cleavage and could potentially serve as marker for this processing. Moreover, by means of mass spectrometry, the precise cleavage sites within the TMD of NRG1 could be identified. Strikingly, the ɛ-like cleavage site was found to be located exactly at the position of the schizophrenia-associated mutation providing a possible mechanism for the reported interference of this mutation with γ-secretase cleavage. The evidence presented unambiguously establishes NRG1 type III as a γ-secretase substrate and provides a basis for further investigation of the mechanisms which link its processing to the development of schizophrenia. In summary and with regard to BACE1 and γ-secretase being prime targets for a potential AD therapy, the results of this work call for further careful investigation of the consequences of altered NRG1 type III signaling due to chronic treatment with inhibitors.
Als Wachstumsfaktor auf der Oberfläche von Neuronen des peripheren Nervensystems (PNS) ist Neuregulin-1 (NRG1) Typ III nach der Geburt essentiell für die Ausbildung der die Nerven umgebenden Myelinscheiden durch Schwann-Zellen sowie zur Re-myelinisierung nach einer Verletzung. Hierfür wird NRG1 Typ III durch proteolytische Spaltung seiner extrazellulären Domäne (so genanntes Shedding) durch die Protease BACE1 (engl. β-site APP cleaving enzyme 1) aktiviert. Dabei entsteht ein membranständiges N-terminales Fragment (NTF), das in kontaktabhängiger Weise durch seine bioaktive, dem Epidermalen Wachstumsfaktor ähnliche (engl. epidermal growth factor, EGF) Domäne die Myelinisierung durch benachbarte Schwann-Zellen einleitet. Folglich führt der Verlust der BACE1-vermittelten Spaltung von NRG1 Type III in BACE1 Knockout-Mäusen zu stark reduzierten Myelinscheiden der peripheren Nerven. Neben seiner Rolle bei der Myelinisierung ist BACE1, besser bekannt als β-Sekretase, auch an der Bildung des neurotoxischen Amyloid β Peptides (Aβ), Haupt¬bestandteil der Amyloidplaques im Gehirn von Alzheimer-Patienten, beteiligt. Das Aβ Peptid entsteht durch die aufeinanderfolgende Spaltung des Amyloid-Vorläufer-Proteins APP (engl. amyloid precursor protein) erst durch BACE1 innerhalb der extra¬zellulären Domäne und anschließend durch die γ-Sekretase in der Transmembrandomäne (TMD). Die Hemmung von BACE1 und der γ-Sekretase gilt deshalb als vielversprechender Ansatz für die Therapie von Alzheimer. Allerdings könnte dies zu starken Nebenwirkungen führen, weil beispiels¬weise NRG1 Typ III wie APP auch von BACE1, der γ-Sekretase sowie von ADAM10 und ADAM17, den α-Sekretasen der Alzheimer Krankheit, prozessiert wird. Im ersten Teil dieser Studie wurde die proteolytische Prozessierung der Ektodomäne von NRG1 genauer untersucht. Mithilfe massenspektrometrischer Untersuchungen wurden die genauen Schnittstellen von BACE1, ADAM10 und ADAM17 in der extrazellulären membrannahen Region von NRG1 Typ III bestimmt und zusätzlich zwei neue Schnittstellen auf der N-terminalen Seite der EGF-ähnlichen Domäne identifiziert. Die proteolytische Spaltung von NRG1 Typ III durch ADAM17 und BACE1 an diesen zuvor unbekannten Stellen setzt die EGF-ähnliche Domäne von NRG1 Typ III als α-sEGF und β-sEGF frei. Mit neuen gegen die Schnittstellen gerichteter monoklonaler Antikörpern gelang es zudem, die Prozessierung von NRG1 Typ III auch in primären Nervenzellen nachzuweisen. Es wurde gezeigt, dass die löslichen EGF-ähnlichen Domänen funktional sind und die zur Ausbildung von Myelinscheiden notwendigen Signalkaskaden in Schwann-Zellen auslösen. Außerdem war β-sEGF in der Lage, den Myelinisierungsdefekt im PNS eines BACE1-defizienten Zebrafish-Modells zu beheben, was die Aktivität von β-sEGF in vivo bestätigt. Der Einfluss, den das Shedding durch BACE1 und ADAM17 auf die Aktivität der löslichen EGF-ähnlichen Domäne hat, wurde in Zellkultur und im Zebrafish-Modell ausführlich untersucht. Im Widerspruch zu bisher veröffentlichten Daten wurde festgestellt, dass sowohl das von BACE1 als auch das von ADAM17 geschnittene sEGF gleichermaßen aktiv ist und die Ausbildung von Myelinscheiden fördert. Zusammengenommen deutet dies darauf hin, dass die von NRG1 Typ III abhängige Myelinisierung nicht nur von membrangebundenem NRG1 Typ III gesteuert wird, sondern auch auf eine kontaktunabhängige Weise von der durch Proteolyse freigesetzten löslichen EGF-ähnlichen Domäne. Der zweite Teil dieser Studie befasst sich mit der Prozessierung des durch das Shedding von NRG1 Typ III entstandenen C-terminalen Fragments (CTF). Wie bereits früher gezeigt wurde, führt die Intramembranproteolyse des CTFs durch die γ-Sekretase zur Freisetzung der intrazellulären Domäne von NRG1, die an der Regulierung der neuronalen Reifung und der Plastizität des Gehirns beteiligt ist. Interessanterweise ist eine Mutation innerhalb der TMD von NRG1 Typ III mit einem erhöhten Risiko an Schizophrenie zu erkranken verbunden und stellt damit einen Zusammenhang zwischen der Prozessierung von NRG1 Typ III durch die γ-Sekretase und dieser neurologischen Erkrankung dar. Die Verwendung eines neuen Antikörpers gegen den N-Terminus des NRG1 CTFs ermöglichte es, ein NRG1 β Peptid zu detektieren, das während der Spaltung durch die γ-Sekretase freigesetzt wird und möglicherweise als Biomarker für diese Prozessierung dienen könnte. Des Weiteren konnten massen¬spektrometrisch die genauen Schnittstellen innerhalb der TMD von NRG1 identifiziert werden. Bemerkenswerterweise liegt die ɛ-ähnliche Schnittstelle genau an der Position der mit Schizophrenie assoziierten Mutation, was möglicherweise die von dieser Mutation ausgehende Beeinträchtigung der γ-Sekretase-bedingten Spaltung, über die früher schon berichtet wurde, erklären könnte. Die hier vorgelegten Daten zeigen eindeutig, dass NRG1 Typ III ein Substrat der γ-Sekretase ist und bereiten die Grundlage für weiterführende Untersuchungen des Zusammenhangs zwischen der Prozessierung von NRG1 Typ III und der Entwicklung von Schizophrenie. Vor dem Hintergrund, dass die Hemmung bzw. Modulation von BACE1 und der γ-Sekretase als vielversprechende Strategie zur Behandlung der Alzheimer Krankheit gilt, machen die Ergebnisse dieser Arbeit deutlich, dass es weiterer Untersuchungen der Auswirkungen bedarf, die eine veränderte Signalübertragung von NRG1 Typ III aufgrund der Hemmung dieser beiden Enzyme zur Folge hätte.

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Wille, Michael [Verfasser], and Jörn [Gutachter] Wilms. "NRTA - A Live View of Astronomy / Michael Wille ; Gutachter: Jörn Wilms." Erlangen : Friedrich-Alexander-Universität Erlangen-Nürnberg (FAU), 2017. http://d-nb.info/1139171518/34.

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Wille, Michael Verfasser], and Jörn [Gutachter] [Wilms. "NRTA - A Live View of Astronomy / Michael Wille ; Gutachter: Jörn Wilms." Erlangen : Friedrich-Alexander-Universität Erlangen-Nürnberg (FAU), 2017. http://d-nb.info/1139171518/34.

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Machado, Alex Barreto. "Caracterização de sistemas envolvidos nos processos de purificação de biodiesel." [s.n.], 2010. http://repositorio.unicamp.br/jspui/handle/REPOSIP/266930.

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Orientadores: Maria Regina Wolf Maciel, Martín Aznar
Tese (doutorado) - Universidade Estadual de Campinas, Faculdade de Engenharia Química
Made available in DSpace on 2018-08-17T10:23:34Z (GMT). No. of bitstreams: 1 Machado_AlexBarreto_D.pdf: 10485061 bytes, checksum: 1bbe757a7cc410835bff5b7be09c251b (MD5) Previous issue date: 2010
Resumo: Vários são os interesses que têm impulsionado o investimento em novos processos de produção de fontes alternativas de energia: preocupação com o esgotamento de fontes limitadas de petróleo; dependência do mercado brasileiro de recursos estrangeiros, apelo a fontes renováveis de matéria prima e preocupações ambientais (Protocolo de Kyoto). Dentre as alternativas aos combustíveis fósseis, o biodiesel aparece como uma alternativa promissora. O biodiesel pode ser definido como sendo um mono-alquil éster de ácidos graxos derivado de fontes renováveis, como óleos e gorduras, obtido através de processo de transesterificação, no qual ocorre a transformação de triacilgliceróis em moléculas menores de ésteres de ácidos graxos, rendendo como subproduto o glicerol (ou glicerina). O biodiesel encontra-se registrado na Environmental Protection Agency (EPA-USA) como combustível e como aditivo para combustíveis e pode ser usado puro a 100% (B100), em mistura com o diesel de petróleo, por exemplo de 20% (B20), ou em uma proporção baixa (1 a 5%) como aditivo, sendo o seu uso possível sem nenhuma modificação nos motores convencionais. Inúmeros trabalhos vêm sendo desenvolvidos testando diferentes óleos, processos e misturas finais, mas para a correta avaliação destes trabalhos torna-se necessário caracterizar o produto obtido e reconhecer as diferenças presentes nas matérias primas capazes de alterar positivamente o resultado final. Além disso, torna-se necessário entender os equilíbrios líquido-líquido formados com as misturas e estudar os equilíbrios líquido-vapor envolvidos nas destilações necessárias para a purificação do biodiesel. Tais dados não são encontrados na literatura atualmente e inviabilizam a construção de plantas virtuais e a realização de simulações computacionais. Assim, o presente projeto visa apresentar uma caracterização de sistemas envolvidos na purificação do biodiesel, permitindo obter dados de equilíbrios líquido-líquido e líquido-vapor em sistemas contendo etanol, glicerol, biodiesel de óleo de soja (Bio-OS), biodiesel de óleo de mamona ( Bio-OM ), água e catalisador
Abstract: There are several concerns that have driven investment in new production processes for alternative energy sources: concern over the depletion of limited supplies of oil, dependence on the Brazilian market of foreign funds, call for renewable raw materials and environmental concerns (Protocol Kyoto). Among the alternatives to fossil fuels, biodiesel appears as a promising alternative. Biodiesel can be defined as a mono-alkyl ester of fatty acids derived from renewable sources such as vegetable oils and animal fats obtained through transesterification process, which occurs in the transformation of triacylglycerols into smaller molecules of fatty acid esters, yielding as a byproduct glycerol (or glycerin). Biodiesel is registered with the Environmental Protection Agency (EPA-USA) as fuel and fuel additive and can be used at 100% (B100), mixed with petroleum diesel, for example, 20% (B20) or in a low proportion (1-5%) as an additive, which makes their use possible without any modification in conventional engines. Numerous studies have been developed by testing different oils, processes and final mixtures, but for proper assessment of this work, it is necessary to characterize the product and recognize the differences present in the raw materials that can positively change the outcome. Moreover, it is necessary to understand the liquid-liquid equilibria formed with the mixtures and to study the vapor-liquid equilibria involved in distillation required for the purification of biodiesel. Such data are not found in the open literature and currently hinder the construction of virtual plants and conducting computer simulations. Thus, this project aims to present a characterization of systems involved in the purification of biodiesel, allowing to get data from liquid-liquid equilibria and vapor-liquid systems containing ethanol, glycerol, biodiesel from soybean oil ( Bio-SO) and biodiesel from castor oil ( Bio-CO), water and catalyst (NaOH)
Doutorado
Desenvolvimento de Processos Químicos
Doutor em Engenharia Química

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Thierfelder, Katrin. "Der Einfluss genetischer Variationen in NRG1, G72, DAO und PPP3CC auf Schizophrenie." Diss., lmu, 2011. http://nbn-resolving.de/urn:nbn:de:bvb:19-131429.

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Liang, Xiaoting, and 梁小婷. "Activation of NRG1-ERBB4 signaling potentiates mesenchymal stem cell-mediated myocardial repairs." Thesis, The University of Hong Kong (Pokfulam, Hong Kong), 2015. http://hdl.handle.net/10722/208584.

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Mesenchymal stem cell (MSC) transplantation has achieved only modest success in the treatment of ischemic heart disease due to poor cell viability in the diseased microenvironment. Genetic manipulation on the MSCs holds promising prospects in enhancing cell tolerance against adverse environmental conditions. Recent studies demonstrate that the activation of the NRG1 (neuregulin 1) - ERBB4 (v-erb-b2 avian erythroblastic leukemia viral oncogene homolog 4) pathway can enhance pro-survival signaling, stimulate mature cardiomyocyte cell cycle re-entry and cell division. In this study, I aimed to determine whether activating NRG1-ERBB4 in MSCs can enhance their cardioprotective effects following myocardial infarction. In chapter 3, I determined that MSC endogenously expresses NRG1, but not ERBB4. Considering the absence of ERBB4 in the MSCs might lead to mute response to its ligand NRG1, I exogenously manipulated ERBB4 into MSCs. In chapter 4, MSCs, with or without ERBB4 overexpression were transplanted into mice following myocardial infarction. The transplantation of MSCs with ERBB4 expression considerably improved left ventricular ejection fraction and reduced infarctsize, compared to unmodified MSCs and direct NRG1 injection. ERBB4 overexpression induced greater MSC survival following infarction. The transduction of ERBB4 in MSCs increased cell mobility and apoptotic resistance via a PI3K/Akt pathway under hypoxic conditions in the presence of NRG1. The transplantation of MSCs with ERBB4 expression induced cardiomyocyte division and protected them against apoptosis during early phase of infarction. In chapter 5, a novel autocrine loop regarding to NRG1-ERBB4-NRG1 signaling was identified. MSCs with ERBB4 overexpression in turn increased NRG1 synthesis and secretion. Conditioned medium of ERBB4-expressing MSCs containing elevated NRG1, promoted cardiomyocyte growth, division and anti-senescence, whereas neutralization of NRG1 blunted these effects. Injecting ERBB4-expressing MSCs restored NRG1 in the infarcted myocardium to a level comparable with that of the normal myocardium. These findings collectively suggest overexpressing ERBB4 in MSCs enhances the effectiveness of MSCtherapy following myocardial in farction through potentiating MSC survival and revitalizing endogenous repair and regeneration. The combination of ERBB4 and MSC is more efficient than naïve MSC or solely recombinant NRG1 injection, emerging as potential target for developing novel strategy in treating myocardial diseases.
published_or_final_version
Medicine
Doctoral
Doctor of Philosophy

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Tyle, Robert. "Metoder för att etablera fri station : En jämförelsestudie av GNSS-etableringar och traditionell etablering." Thesis, Karlstads universitet, Institutionen för miljö- och livsvetenskaper, 2017. http://urn.kb.se/resolve?urn=urn:nbn:se:kau:diva-55235.

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Syftet med detta examensarbete är att jämföra kvaliteten som erhålls vid olika typer av fri stationsetablering. Tre olika metoder har jämförts vilka är etablering mot kända stompunkter (traditionell metod), etablering mot GNSS-bestämda punkter med snabb metod och etablering mot GNSS-bestämda punkter med långsam metod. Den snabba metoden går ut på att mäta in en punkt med fem (5) positionsbestämmelser med GNSS samtidigt som totalstationen mäter in punkten som ett bakåtobjekt. Varje punkt behöver då besökas endast en gång. Den långsamma metoden går ut på att mäta in alla punkter som ska användas som bakåtobjekt med tjugo (20) positionsbestämmelser med GNSS, för att därefter mäta in dem med totalstation. Varje bakåtobjekt måste då besökas två gånger. Arbetet utfördes i Arvika kommun. Tre stompunkter användes som huvudsakliga bakåtobjekt. Dessa punkter användes som bakåtobjekt för att jämföra kvaliteten på GNSS-mätningarna relativt de sanna koordinaterna på stompunkterna vilka hämtas från respektive punktbeskrivning. Olika antal bakåtobjekt mättes in med GNSS för att undersöka hur kvaliteten förändrades i takt med att fler bakåtobjekt tillkom. Fri stationsetablering genomfördes i varje metod med tre, fem och sju bakåtobjekt. Det gjordes tre mätomgångar för att kunna jämföra mätningarna med varandra. Slutsatser som dras är att vid uppdatering av primärkartan räcker det med att använda den snabba GNSS-metoden tillsammans med tre bakåtobjekt för att uppnå tillfredsställande kvalitet. Vid finutsättning bör den långsamma metoden med fem bakåtobjekt användas istället. Arbetet beskriver även teorin bakom GNSS-tekniken och fri station.
The purpose of this degree project is to compare the quality obtained from different types of free station establishment. Three different methods have been compared. The methods are establishing towards control points (traditional method), establishing towards GNSSdetermined points with a fast method and establishing towards GNSS-determined points with a slow method. The fast method is to measure a point with five (5) positions with GNSS while the total station measures the point as backsights simultaneously. Using this method each point needs to be visited only once. The slow method is to first measure all points to be used as backsights with 20 positions with GNSS, then return to each point and measure them with the total station. Each point must then be visited twice. Three control points in the city of Arvika were used as backsights. It was also those points that were measured with GNSS to compare the quality of GNSS measurements relative to their "true" coordinates extracted from the point description. Different number of backsights were used to investigate how the quality changed as more backsights were added. Free station establishment was performed with each method using three, five and seven backward objects. Three measuring rounds were made to compare the measurements in each round with each other. Conclusions drawn are that, when updating the primary chart, it is sufficient to use the fast GNSS method along with three backsights to achieve satisfactory quality, but in construction measuring where the quality needs to be very high the slow method with five backsights should be used instead. The work also describes the theory behind GNSS technology and free station.

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Håkansson, Linn, and Elenore Herrström. "Transformerade koordinater i referenssystemet SWEREF 99." Thesis, Högskolan Väst, Avdelningen för data-, elektro- och lantmäteriteknik, 2015. http://urn.kb.se/resolve?urn=urn:nbn:se:hv:diva-8923.

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Sverige är uppbyggt av fastigheter och en fastighet avgränsas med hjälp av punkter, exempelvis dubb i berg eller rör i mark. Fastighetsgränsers fysiska läge stämmer inte alltid överens med koordinaterna i referenssystemet, vilket resulterar i avvikelser. Genom åren har flera referenssystem använts och vid varje byte genomförs en transformation mellan till- och frånsystemet. Idag är SWEREF 99 det mest tillämpade referenssystemet i Sverige vid mätning i plan. Syftet med studien var att utreda gränspunkter och stompunkter i del av området Ammenäs, Uddevalla kommun. Frågor som besvaras är: Hur väl stämmer de angivna, transformerade, koordinaterna i referenssystemet SWEREF 99 med gränspunkters och stompunkters fysiska läge? Vad kan vara orsaken till eventuella avvikelser? Påverkar eventuella avvikelser detpraktiska arbetet och vad kan de ge för effekter samt går det att komma till rätta med dem? Genom studien har både kvalitativ och kvantitativ metod tillämpats. Den kvalitativa metoden har används för faktainsamling, både via litteratur och genom intervjuer samt mailkontakt med personal på Uddevalla kommun. Den kvantitativa metoden användes för inmätning av fastighetsgränser och stompunkter. Insamlad mätdata jämfördes med de angivna koordinaterna i referenssystemet SWEREF 99. Resultatet har visat att avvikelser finns mellan de fysiska gränspunkterna och de angivnakoordinaterna i referenssystemet SWEREF 99. Stompunkterna i området stämmer dock väl överens med referenssystemet och därför kan det uteslutas att stompunkterna i systemet gett upphov till gränsernas avvikelser. Under studien har det framkommit att spänningar existerade redan under 1940-talet och de har sedan följt med i de olika referenssystemsbyten som gjorts genom åren. Spänningar kan uppkomma vid sammankoppling av olika stomnät och ge upphov till avvikelser vid mätning. Stomnätet i området är etablerat efter att de första fastigheterna bildades. Inför transformationen till SWEREF 99 utfördes stödmätning endast på stompunkterna, sålunda har alla gränspunkter transformerats tillsammans med punkterna. För att komma tillrätta med gränsernas avvikelser krävs en ny transformation där stödmätning görs även på gränspunkter. Då avvikelserna inte påverkar det praktiska arbetet i Ammenäs finns dock inga planer på att en sådan process ska genomföras för området.
Sweden is made up of properties and a property is bounded by means of markings, such as stud in rock or pipes in the ground. The physical location of a property's bounds does not always correspond with the coordinates in the reference system, resulting in discrepancies. Through the years, several reference systems has been used, and with each change implemented, a transformation between the old and the new system is done. Today SWEREF 99 is the most applied reference system in Sweden when measuring in the plane.The purpose of this study was to investigate the boundary markers and reference points in part of the area of Ammenäs in Uddevalla municipality. Questions to be answered is: How well does the physical boundary markers and the reference points correspond with the transformed coordinates in the reference system SWEREF 99? What can be the cause ofdifferences? How do deviations affect the practical work with ordinances in the area and how can these be overcome? Through the study, both qualitative and quantitative methodology were applied. The qualitative method has been used for fact collection, both through literature and through interviews and e-mail contact with staff at Uddevalla municipality. The quantitative method was used for the measurement of property boundaries and reference points. Collected data were compared with the coordinates in the reference system SWEREF 99. The results have shown discrepancies between the physical boundary markers and the transformed coordinates in the reference system SWEREF 99. Reference points in the area are consistent with the reference system. The gist of the result is that reference points in part of the area has not given rise to the boundary deviations. The study has revealed that discrepancies existed already in the 1940s, the deviations have since followed in the different reference system changes made over the years. Discrepancies can occur at the interconnection of different core networks and can cause differences in the measurement. The reference network was established in the area after the first properties were formed. Before the SWEREF transition only support measurement on the reference points was performed. To deal with the discrepancies, a new transformation which also supports measurements at boundary markings are needed. Since the deviations do not affect the practical work in Ammenäs, such a process will not take place.

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Wheeler, Joel. "USING SOUTHERN BLOTTING AND NON-RADIOACTIVE PROBE HYBRIDIZATION AS A TOOL TO MEASURE 2’,3’-DIDEOXYCYTIDINE INDUCED MITOCHONDRIAL DNA DEPLETION IN HUMAN CELL LINES." OpenSIUC, 2019. https://opensiuc.lib.siu.edu/theses/2637.

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Mitochondria are membrane bound organelles important for energy production in respiring cells through the process of oxidative phosphorylation. They have their own multi-copied mitochondrial DNA (mtDNA) genome separate from that in the nucleus that is needed for mitochondria to function properly and can exist in both wild type and mutant forms in the same cell. The integrity of the mtDNA is therefore of vital importance for the survival of the organism and as such understanding the mechanisms of mtDNA maintenance is relevant to human health and disease. This study employs a Southern blotting and non-radioactive probe method to examine various aspects of mtDNA maintenance. Restriction endonuclease mapping utilizing mtDNA-specific and nuclear DNA-specific digoxigenin (DIG)-labeled probes was performed to show that the synthesized probes are indeed specific for their target sequences. The DIG-labeled probes were used to quantitate mtDNA content from different DNA isolation methods. Whole-cell DNA extraction was found to yield higher levels of mtDNA compared to a commercially available spin-column kit. Next, Southern blots were used to analyze mtDNA copy number as well as mtDNA depletion in the hepatocarcinoma-derived cell line HepaRG following exposure to the nucleoside reverse transcriptase inhibitor 2’,3’-dideoxycytidine (ddC), a known mitochondrial toxicant. In comparison to proliferative HepaRG differentiated HepaRG contained about 2-fold more mtDNA. Relative to untreated control cells, proliferating HepaRG exposed to ddC had greater than a 96% reduction in mtDNA and had decreased cellular viability. Differentiated HepaRG cell viability was not affected after 13 days of ddC treatment; however, significant mtDNA depletion was observed. We estimate that differentiated HepaRG mtDNA depletion occurs quickly at about 20 molecules per hour.

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Jansson, Wilma. "Utvärdering av noggrannhet i digitala terrängmodeller framtagna med totalstation, NRTK, UAV och NH." Thesis, Karlstads universitet, Fakulteten för hälsa, natur- och teknikvetenskap (from 2013), 2020. http://urn.kb.se/resolve?urn=urn:nbn:se:kau:diva-78798.

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Det finns flertal användningsområden för digitala höjdmodeller där det krävs hög noggrannhet för att problematik och ekonomiska konsekvenser inte ska uppstå. Digitala höjdmodeller kan användas till volymberäkning, projektering och geografiska analyser. Digitala höjdmodeller kan kategoriseras som antingen digital ytmodell eller digital terräng-modell. Då hög noggrannhet eftersträvas i digitala terrängmodeller har SIS framställt en standard benämnd SIS-TS 21144:2016 som beskriver hur inmätning och kontroll av data till digitala terrängmodeller ska hanteras. För insamling av höjdinformation till en digital terrängmodell finns olika terrestra och flygburna mätmetoder. Vanliga terrestra mätmetoder är totalstation, GNSS och terrester laserskanning medan flygburna mätmetoder är flygburen laserskanning eller olika metoder med digital fotogrammetri. Syftet med studien är att undersöka noggrannheten hos höjdmodeller kategoriserade som digitala terräng-modeller. Insamling av höjdinformation skedde med totalstation, GNSS-metoden NRTK och UAV samt inhämtning av LAS-data från NH för tre olika karaktäristiska grönområden inom Karlstad med omnejd. SIS-TS 21144:2016 har klassificerat terrängmodeller beroende på användningsområde och terräng. Klassificeringen går mellan klass 1–10 och varje klass har en maximal tolerans i höjd. För studien har tre studieområden som går under klassificeringarna klass 2, klass 3 och klass 5 valts ut för undersökning. Samtliga studieområden är avgränsade till 40 x 40 meter. Innan insamling av data markerades och mättes bakåtobjekt och avvägning genomfördes. Samtlig insamlad data bearbetades i programvaran SBG Geo och UAV data bearbetades även i programvaran Agisoft PhotoScan Professional. För kontroll av samtliga terrängmodeller genomfördes inmätning av tre kontrollprofiler med totalstation enligt SIS-TS 21144:2016. Resultatet visade att UAV är inom tolerans för samtliga studieområden medan NH-data resulterade i enstaka kontrollpunkter utanför klassningens tolerans för samtliga studie-områden. De två terrestra mätmetoderna är båda inom tolerans för klass 2 och varsin kontrollpunkt utanför tolerans för klass 5. Vid studieområde klass 3 är fem kontrollpunkter för totalstation utanför tolerans respektive åtta för NRTK. Vid analys av vilken mätmetod som resulterar i noggrannast terrängmodell inom samtliga studieområden krävs beaktning av antal inmätningspunkter och trianglar som terrängmodellen är uppbyggd av. För klass 2 ger de flygburna mätmetoderna flest antal inmätningspunkter och trianglar medan UAV resulterar i betydligt högre värden för de två resterande studieområdena. Antal inmätnings-punkter för de terrestra mätmetoderna har operatör beslutat om under mätning, vilket har kunnat ökas för att generera terrängmodeller som består av fler trianglar. Resultatet från studien visar att UAV resulterar i terrängmodeller som klarar toleranser inom undersökta studieområden och SIS-TS 21144:2016 klassificeringar.
There are previous research about digital terrain models and how different methods of producing digital terrain models varies in accuracy and there are several different methods to produce a digital terrain models. In this study the following methods, tools and data are used to produce digital terrain models over three different characteristic study areas: total station, GNSS, UAV and NH. Previous work has failed to address the accuracy given by these four methods over the same three characteristic study areas thus preventing the understanding of most suitable methods for different areas. In this study three different green areas have been studied and the different digital terrain models has been produced and controlled with SIS standard SIS-TS 21144:2016. Data in form of height information were collected by the aforementioned methods and processed to generate results over the accuracy of each methods. The results shows that UAV provide most accurately digital terrains models in least time spent in field but also total station and GNSS generate digital terrain models that are accurate.

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Robie, Taylor A. "Improved Electrolyte-NRTL Parameter Estimation Using a Combined Chemical and Phase Equilibrium Algorithm." University of Cincinnati / OhioLINK, 2013. http://rave.ohiolink.edu/etdc/view?acc_num=ucin1368027260.

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Murad, Abdul Munir Abdul. "The role of NRG1 in the control of cellular morphogenesis in Candida albicans." Thesis, University of Aberdeen, 2001. http://digitool.abdn.ac.uk/R?func=search-advanced-go&find_code1=WSN&request1=AAIU602288.

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This thesis describes the isolation and characterisation of the C. albicans NRG1 gene, which encodes a repressor of filamentous growth in this pathogenic fiingus. A C. albicans SBP1 cDNA was previously isolated in a screen for transacting factors that bind to a STRE-like element (consensus sequence: CCCCT) (Leng, 1999). In S. cerevisiae, STRE is a stress-responsive element that is required for the regulation of many stress-responsive genes (Marchler et al., 1993). In C. albicans, this element had been identified in the promoters of two hypha-specific genes, ALS8 and HYR1. Since many conditions that induce yeast-hypha morphogenesis in C. albicans impose a stress, it was proposed that the STRE- binding protein (Sbpl) might influence yeast-hypha morphogenesis and/or stress responses in this human pathogen. The cDNA was then used to isolate the complete C. albicans SBP1 locus by colony hybridisation. Both the cDNA and gene were sequenced, revealing an ORF capable of encoding a protein of 310 amino acids containing a C2H2-zinc finger motifs near its C-terminus. The zinc finger region of this protein displayed the highest sequence similarity to S. cerevisiae NRG1 (67 % identity), and hence the gene was renamed CaNRGl. To examine the role of CaNrgl, a C. albicans nrgl/nrgl null mutant and a mutant over-expressing the NRG1 gene were created. Overexpression of NRG1 did not reveal any obvious phenotypes, but inactivation of NRG1 caused constitutive filamentous and invasive growth, as well as increased sensitivity to some stresses. Also, the expression of the hypha-specific genes, ALS8, ECE1, HWP1 and HYR1, was derepressed in the nrgl/nrgl mutants. Similar phenotypes were observed for a C. albicans tupl/tupl null mutant. These observations suggest that Nrgl represses filamentous growth in C. albicans, possibly by recruiting Tupl to specific promoters. Unlike the tupl/tupl mutant, nrgl/nrgl cells formed normal hyphae following pH and serum stimulation, they generated chlamydospores at normal rates, and they grew at 42 C. Transcript profiling of 2002 C. albicans genes revealed that Nrgl regulates a subset of Tupl-repressed genes, which includes known hypha- specific genes and some virulence factors. The data also showed that Tupl regulates other genes, which are not regulated by Nrgl, including glucose sensitive genes, amino acid and sterol biosynthesis genes, and genes encoding other virulence determinants. Taken together, this study demonstrates that Nrgl is a transcriptional repressor that regulates a set of functions required for yeast-hypha morphogenesis and virulence in C. albicans.

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Serezino, Luís Henrique Damasceno. "Caracterização fisiológica e transcricional dos processos de aquisição e remobilização de nitrato em cana-de-açúcar (Saccharum spp.)." Universidade de São Paulo, 2015. http://www.teses.usp.br/teses/disponiveis/64/64133/tde-02022016-141558/.

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A expansão da área de cultivo da cana-de-açúcar (Saccharum spp.) para solos marginais e a necessidade de manutenção da alta produtividade tem levado a maior aplicação de fertilizantes nitrogenados na cultura. Esta prática, porém, incorre em altos custos financeiros e ambientais. Comparado a outras culturas, cana-de-açúcar possui baixa resposta a aplicação de fertilizantes nitrogenados, mas as causas desta baixa eficiência no uso de N (NUE) permanecem desconhecidas. Na tentativa de compreender os mecanismos envolvidos no NUE em cana-de-açúcar, este trabalho realizou a caracterização fisiológica dos processos de absorção de nitrato e remobilização de N por estudos de cinética de absorção e experimentos de translocação de 15N. Além disso, analisou-se o perfil de expressão de genes codificadores de transportadores de nitrato (NRTs - NITRATE TRANSPORTERS). Plantas da cultivar \'SP80-3280\' foram expostas à condições distintas de suplemento de N para investigar a regulação do processo de aquisição. Além de comprovar a menor eficiência da cana-de-açúcar na aquisição de nitrato quando comparada com amônio, foi demonstrada a presença de sistema de transporte de alta afinidade (HATS, High Affinity Transport System) para ambas as fontes de N presentes em raízes, induzido sob baixas concentrações externas de N e/ou sob baixo status de N na planta. Observou-se que amônio regula negativamente a absorção de nitrato, modulando a expressão dos genes envolvidos neste processo. Em plantas sob condições de deficiência de N (-N) foi verificada a regulação tardia do HATS responsável pela aquisição de nitrato. A ausência de correlação entre o influxo de 15N e acúmulo de transcritos de transportadores de nitrato sugere a existência de uma regulação pós-transcricional dos transportadores do HATS em raízes submetidas a provisão de nitrato. Para caracterizar o processo de remobilização, plantas foram submetidas a condições contrastantes de disponibilidade de N na tentativa de identificar o mecanismo pelo qual nitrato pode ser regulado durante este processo. Apesar da reduzida eficiência na aquisição e estoque de nitrato, cana-de-açúcar possui a capacidade de utilizar nitrato como fonte de N, e em condições suficientes de suplemento de N, nitrato e amônio são utilizados como fonte de N. Sob restrição de N, porém, nitrato apresenta maior fluxo em raízes e colmos, enquanto que amônio ainda permanece como fonte de N em folhas jovens devido a alteração no carregamento de nitrato no xilema. Todavia, o suplemento de nitrato a ser reduzido e assimilado em folhas parece ter origem no colmo. Portanto, a modulação da expressão dos transportadores NRT assegura a alocação de nitrato em cana-de-açúcar quando N é limitante em solos
The expansion of sugarcane (Saccharum spp.) cultivated area to marginal lands and the need to maintain high yield have led to increasing application of nitrogen fertilizers. However, this practice represents high economic and environmental costs. Compared to other crops, sugarcane displays a low response to N fertilization, but the causation of the low nitrogen use efficiency (NUE) remains unknown. To understand the mechanism involved in NUE, this study was carried out to conduct the physiological characterization of nitrate uptake and N remobilization in sugarcane by uptake kinetic analysis and translocation experiments using 15N. Further, the expression profile of genes encoding nitrate transporters (NRTs - NITRATE TRANSPORTERS) involved in both processes was determined. Plantlets of cultivar \'SP80-3280\' were exposed to various N supplement conditions to investigate the regulation of the uptake process. The lower efficiency in nitrate acquisition compared to ammonium was corroborated and extended for low N conditions. The occurrence in sugarcane roots of high affinity uptake systems (HATS, High Affinity Transport System) for both N sources,, induced at low external concentrations of N and/or low N status in the plant was confirmed. Ammonium negatively regulates nitrate uptake by modulating the expression of genes involved in this process. Plants under N deficiency (-N) exhibited a late regulation of HATS responsible for nitrate uptake. The lack of correlation between 15N influx and transcript accumulation of nitrate transporter genes suggests the existence of a post-transcriptional regulation of HATS in roots subjected to nitrate resupply. To characterize the remobilization process, plants were submitted to contrasting conditions of N availability to identify the mechanisms by which nitrate may be affected during this process. Despite the low efficiency of nitrate uptake and storage, sugarcane demonstrates the ability to use nitrate as N source. In N sufficient conditions (+N), ammonium and nitrate are used as N source. Under restriction of N, however, nitrate has increased flow in roots and stems, while ammonium remains as N source to young leaves by change in nitrate loading into the xylem. However, the source of the nitrate to be reduced and assimilated in leaves appears to be originated from the culm. Therefore, modulation of NRT transporters expression ensures nitrate allocation in sugarcane when N is limited in soils

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Silva, Camila de Souza. "Equil?brio l?quido-vapor do sistema tern?rio etanol + ?gua + 1-etil-3-metil imidaz?lio cloreto: experimental e modelagem termodin?mica." Universidade Federal Rural do Rio de Janeiro, 2016. https://tede.ufrrj.br/jspui/handle/jspui/1784.

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Coordena??o de Aperfei?oamento de Pessoal de N?vel Superior - CAPES
Equilibrium data at low and high pressures are important to correct establish conditions of temperature and pressure for separation processes, and to supply the capacity of the solvent, the compositions of the phases and the selectivity of the solvent. The separation of ethanol-water system is of great importance for the industry due to numerous applications of anhydrous ethanol. In all of these applications, ethanol must be free of water and it is necessary to add a third component in the distillation to break the azeotrope. It can be add different solvents, as benzene, hexane, ethyleneglycol, salts, and, in the last years, many studies have been done with ionic liquids. So, the purpose of this work is to use an ionic liquid (1-ethyl-3-methylimidazolium chloride) as the third component, looking for the ethanol dehydration. Because of that, it was done a study to evaluate the effect of this ionic liquid in the liquid-vapor equilibrium behavior between water and ethanol. Experimental data were measured, in triplicate, under normal pressure, in an Othmer-type ebulliometer (300 mL of volume), with two condensers, and made of borosilicate glass. The sample analysis was done in a digital densimeter. The ionic liquid used was recovered from one solution to another, just by adding the required amount to complete each mass fraction. Experimental data was measured with ethanol-water solutions varying the molar concentrations from 0.2 to 0.99, and ionic liquid weight fraction masses from 5 to 60%, to evaluate the behavior of the equilibrium data of the ethanol+water+[emim][Cl] system. The experiments showed that [emim][Cl] with a minimum mass fraction of 20% is a promising solvent because it could ?break? the azeotrope between water and ethanol, and higher mass fraction of ionic liquid were better to enrich the vapor phase in ethanol. NRTL model was used to correlate experimental vapor-liquid equilibrium of the ternary system, estimating the binary parameters, applying the bubble point methodology. The deviations of temperature and vapor phase composition were 0.147 ?C and 0.049, respectively. The relative volatility was greater than 1 for the mass fractions from 20%. The activity coefficients decrease with the increase in the molar concentration of ethanol. Values of the excess Gibbs free energy show a positive deviation for all mass fractions worked, and the experimental data were consistent thermodynamically
Os dados de equil?brio a press?es baixas e elevadas s?o importantes para estabelecer as condi??es corretas de press?o e temperatura para os processos de separa??o e para fornecer a capacidade do solvente, as composi??es das fases e a seletividade do solvente. A separa??o do sistema etanol-?gua ? de grande import?ncia para a ind?stria devido a numerosas aplica??es do etanol anidro. Em todas essas aplica??es, o etanol deve ser livre de ?gua e, para isso, ? necess?rio adicionar um terceiro componente na destila??o para quebrar o aze?tropo. Podem ser adicionados diferentes solventes como o benzeno, hexano, etilenoglicol, sais e, nos ?ltimos anos, tem-se visto muitos estudos com l?quidos i?nicos. Com isso, o objetivo deste trabalho ? a utiliza??o de um l?quido i?nico (1-etil-3-metil imidaz?lio cloreto) como terceiro componente, visando a desidrata??o do etanol, al?m da avalia??o do efeito deste l?quido i?nico no comportamento do equil?brio l?quido-vapor entre a ?gua e o etanol. Os dados experimentais foram medidos, em triplicata, sob press?o normal, em um ebuli?metro tipo Othmer (300 mL de volume), com dois condensadores, feitos de vidro de borosilicato. As determina??es das amostras foram feitas em um dens?metro digital. Os dados foram medidos com solu??es de etanol-?gua em diferentes concentra??es molares (0,2 a 0,95), variando a fra??o m?ssica de l?quido i?nico de 0,05 a 0,60, para avaliar o comportamento dos dados de equil?brio do sistema etanol-?gua-[emim][Cl].Os resultados mostraram que o [emim][Cl] ? um solvente promissor, pois "quebra" o aze?tropo entre a ?gua e etanol a partir de 20% de l?quido i?nico, e a concentra??o de etanol na fase vapor foi maior com o aumento da fra??o m?ssica de LI.O modelo NRTL foi utilizado para correlacionar os dados experimentais de equil?brio, estimando-se os par?metros bin?rios, aplicando-se a metodologia do ponto de bolha. Os desvios em rela??o ? temperatura e a composi??o molar da fase vapor foram 0,147 ?C e 0,049, respectivamente. O l?quido i?nico, recuperado de uma solu??o para outra, passou por uma an?lise de RMN para avaliar se n?o houve altera??o na sua estrutura e, constatou-se que, ap?s ser recuperado, e novamente reutilizado, o solvente n?o perdeu as caracter?sticas originais. As volatilidades relativas foram superiores a 1 para as fra??es m?ssicas a partir de 20%, confirmando a quebra do aze?tropo. A energia livre de Gibbs em excesso apresentou valores que mostram um desvio positivo para todas as fra??es m?ssicas trabalhadas e os dados experimentais foram consistentes termodinamicamente

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Symington, Vicki Frances. "Structure and function of nitrate and nitrite transporters, NrtA and NitA, from Aspergillus nidulans /." St Andrews, 2009. http://hdl.handle.net/10023/748.

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Symington, Vicki F. "Structure and function of nitrate and nitrite transporters, NrtA and NitA, from Aspergillus nidulans." Thesis, University of St Andrews, 2009. http://hdl.handle.net/10023/748.

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Membrane proteins play an integral role in the control of ion transport across the cell membrane in biological systems. However, due to experimental constraints, structural and functional data available for these proteins is limited, especially considering their importance. In this study, two membrane proteins which transport nitrate and nitrate into the model filamentous ascomycete Aspergillus nidulans were investigated. Work on the twelve trans-membrane domain nitrate transport protein NrtA is well established. As a member of the major facilitator super family (MFS) the role of signature sequences characteristic of this family have previously been studied. Here, a series of point mutations were made to facilitate an understanding of key residues in the nitrate binding domain, the first nitrate signature motif and residues of the unique fungal central-loop domain. Using an expanded alignment package, the proposed secondary structure of NrtA was enhanced and used as a starting point for mutagenesis. Alanine scanning mutagenesis showed that glycine residues in the conserved nitrate nitrite porter (NNP) motif were critical for NrtA function. Two asparagines in the NNP were investigated; N160 and N168. N168 was found to be critical for NrtA function as all mutants were devoid of growth on nitrate solid agar medium though they expressed in the membrane to varying degrees. The nitrate binding site has been studied previously, revealing the interaction of conserved arginine residues with the anion as it traverses the bilayer. Though it was thought that mutations of residue T83 to a small, charge neutral, amino acid would substitute for no alteration to enzyme kinetics in mutant T83S was found when using ¹³NO₃⁻. Another major part of this thesis examined NitA which is part of a distinct nitrite transport family to NrtA (the Formate Nitrite Transporters, FNT). A mutagenesis approach targeted NitA residues conserved amongst homologous proteins. Residues in position D88 in an alignment of homologues were conserved in terms of charge. Mutagenesis of D88 revealed that maintaining charge at this position was essential for NitA function, likely due to a role in salt-bridge formation during conformational changes. Mutations to asparagine, glutamine, serine and valine showed reduced growth on agar though the protein was expressed to approximately wild-type levels. Nitrite uptake assays using a ¹³NO₂⁻ tracer were performed on D88N, D88E and D88Q and all showed wild-type Km and Vmax. Finally, the role of conserved asparagine residues found throughout NitA was investigated by mutagenesis. Expression studies revealed that mutants created in N122 and N246, changed to aspartic acid, lysine, glutamine and serine were generally not present in the membrane and thus did not grow on nitrite agar. However, mutations in N173 (in Tm 4) and N214 (in Tm 5), which are conserved in > 95 % of NitA homologues, showed varying degrees of growth and expression. Both of these residues are located in FNT signature motifs, so it is likely that they are involved with conformational changes or protein dynamics.

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Ekman, Filip, and Malin Molander. "Utvärdering av GNSS-baserade fri stationsetableringsmetoder : En jämförelse av realtidsuppdaterad fri station och 180-sekundersmetoden." Thesis, Karlstads universitet, Fakulteten för hälsa, natur- och teknikvetenskap (from 2013), 2021. http://urn.kb.se/resolve?urn=urn:nbn:se:kau:diva-84934.

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Behovet av mätning med totalstation har inom många områden minskat till förmån för mätning med GNSS-baserad teknik som ett resultat av dess större flexibilitet och ofta acceptabla osäkerhet. GNSS-baserad mätning kan dock begränsas av olika faktorer, vilket skapar ett behov av mätning med totalstation. Etablering av totalstation sker traditionellt genom kända punkter, men när dessa inte finns tillgängliga behövs andra metoder för etablering som ger en låg osäkerhet. Syftet med denna studie är att undersöka två GNSS-baserade fri stationsetablerings-metoder. Realtidsuppdaterad fri station (RUFRIS) bygger på kombinerad mätning, där koordinaterna för minst 15 bakåtobjekt mäts in med NRTK samtidigt som totalstationen mäter längd och riktning mellan station och bakåtobjekt. 180-sekundersmetoden bygger på kontinuerlig mätning i tre minuter på minst tre punkter, för att sedan använda dessa punkter som bakåtobjekt under fri stationsetablering. Under tre dagar insamlades mätdata från totalt 60 etableringar i Skålsjön i Ovanåkers kommun. Totalt 30 etableringar per metod utfördes växlande med varandra för att få samma tidspåverkan för mätningarna. Platsen valdes till följd av en närliggande stompunkt av hög kvalitet samt en realistisk mätningsmiljö. Insamlade data bearbetades och beräknades med avseende på spridning och mätosäkerhet. Dessutom utfördes en tidsanalys av erhållna mätdata. Den enskilda standardosäkerheten för RUFRIS beräknades vara 6,7 mm i plan och 15 mm i höjd. För 180-sekundersmetoden beräknades standardsosäkerheten till 10 mm i plan och 7,2 mm i höjd. Enligt den lägeskontroll som utfördes i studien var det endast RUFRIS som klarade den beräknade toleransen i plan. I höjd var det enbart 180-sekundersmetoden som befann sig inom toleransen. RUFRIS klarade dock toleransen när samtliga grova fel uteslöts från beräkningen. Slutsatsen som drogs i denna studie var att RUFRIS lämpar sig väl för mätnings-situationer med fokus på plan i områden med god sikt. 180-sekundersmetoden lämpar sig däremot bättre till höjdmätning och kan potentiellt vara ett alternativ till avvägning när toleransen i höjd är inom 10 mm. Mätningarna utfördes under goda förhållanden med avseende på jonosfären, därav antogs upplevda störningar gällande erhållandet av fixlösning och mätvärden inte härstamma från denna felkälla. Mätosäkerheten ökade i samband med kraftigt snöfall, vilket tyder på att vädret påverkade resultatet. Sammanfattningsvis har båda metoderna sina styrkor och svagheter, men ingen av metoderna visade sig vara mer lämplig än den andra när etableringen avser mätning i både plan och höjd.
The purpose of this study is to investigate two GNSS-based methods of establishing a free total station. Due to technological advances made within GNSS-based measuring, the total station is seeing less use by surveyors in the field. Despite this, there are situations where GNSS-receivers might struggle and the need to use a total station arises. In these situations, there needs to be a reliable method of establishing the total station without known points and with a low uncertainty. This can be accomplished by utilizing real time updated free station (RUFRIS) and the 180-seconds method. Both RUFRIS and the 180-seconds method is frequently used by municipalities and companies, which raises the question about which of these methods performs better. To answer this, a comparison is made between these two methods regarding their uncertainty, their user friendliness, which situations they are best suited for and how different time aspects might affect them. A total of 60 establishments have been made over the course of three days while comparing the results to a known reference point. The results showed that RUFRIS is better suited for horizontal measurements, is quick to use and needs a larger area, while the 180-seconds method is better suited for vertical measurements, takes a bit longer and requires less space.

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Cederström, Tony, and Henrik Lysén. "Undersökning av förhållanden mellan positionsvariationer och säsong respektive montering/placering av monument : i Swepos® B-klassade fasta referensstationer." Thesis, Högskolan i Gävle, Avdelningen för Industriell utveckling, IT och Samhällsbyggnad, 2015. http://urn.kb.se/resolve?urn=urn:nbn:se:hig:diva-19987.

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En förtätning av Sveriges fasta referensnät SWEPOS® pågår för närvarande. De fasta referensstationerna i SWEPOS-nätet delas in i klass A och B med huvudsaklig skillnad i montering/placering av antenner och fästen. Under installationerna förankras klass Astationerna i berggrund medan klass B-stationerna monteras direkt på allmänna byggnader och anläggningar. Förtätningen sker primärt med B-stationer vilket innebär att SWEPOS-nätet består av dessa till ca 90 %. Förtätningen görs för att minska mätosäkerheten vid relativa mätningsmetoder som exempelvis NRTK (Network Real Time Kinematic). NRTK är den mest efterfrågade metoden idag och det finns ett behov från SWEPOS-användare att minska mätosäkerheten med NRTK. Eftersom förtätningen beräknas vara färdig under 2016 undersöks nu alternativa sätt att minska mätosäkerheten ytterligare med NRTK. Det här examensarbetet fungerar som en del i dessa undersökningar. Av den anledningen har det undersökts om positionsvariationer i B-klassade SWEPOS-stationer går att koppla till säsong (tid på året) eller montering/placering av antenn och fäste (monument). Med Fourier-analys av stationsobservationsdata (tidsserier) identifierades amplitudvärden hos periodiska funktioner som hade ett års våglängd. Värdena omberäknades i Excel vilket gav positionsvariationer i form av radiella amplituder (totala amplituder). Lantmäteriet förväntade att mellan 10-20 % av stationerna skulle ha höga totala amplituder, över 2 σ från stationsmedelvärden, i höjd eller plan. Därmed var en målsättning att undersöka denna förväntning. Ytterligare en målsättning var att undersöka om det fanns en tydlig “vintereffekt” inom SWEPOS. Det vill säga om perioder med snö påverkar stationernas mätningar negativt eller inte. Denna målsättning testades genom nollhypotesen: ”Det är högre total amplitud under snöperioden än under den snöfria perioden.”. Den tredje och sista målsättningen var att hitta ett förhållande mellan höga totala amplituder (höjd respektive plan) och monumentets montering/placering. Tidsserieanalys utfördes i programmet Tsview och dagliga koordinatobservationer från 217 B-klassade stationer analyserades. Efter bearbetning i Excel av utdatat från Tsview erhölls resultat. Totalt hade ca 18 % av stationerna höga positionsvariationer, i antingen höjd eller plan, vilket motsvarade förväntningen. Hypotesprövningen visade att det finns en signifikant “vintereffekt” men att den är begränsad till individuella stationer och vanligare i norra Sverige. Gällande positionsvariationer och montering/placering av antenn och fäste var det endast en klass som avvek nämnvärt. Denna var ”Taknock” och innebar att stationer som hade antennen och fästet placerade vid taknocken på en byggnad, hade högre positionsvariation (plan) i form av total amplitud.

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Chen, Yuxing. "Structure et fonction de la nucléoside diphosphate kinase : rôle dans l'activation des analogues de nucléotides à activité antivirale." Paris 11, 2003. http://www.theses.fr/2003PA112130.

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La nucléoside diphosphate kinase (NDP kinase) catalyse la phosphorylation réversible du NDP aux dépens du nucléoside triphosphate (NTP) par l'intermédiaire d'une phosphohistidine selon un mécanisme de ping-pong. La NDP kinase est impliquée dans la lutte contre le SIDA par son rôle dans l'activation des NRTI (nucleoside analog reverse transcriptase inhibitors), qui sont des médicaments qui ciblent la transcriptase inverse du VIH. Le groupe le 3'-OH du sucre des NRTI utilisées actuellement est absent ou substitué pour la terminaison de la polymérisation. Malheureusement ce groupe est important pour la catalyse de la NDP kinase par les études structurelles et cinétiques. Pour la recherche de nouvelle NRTI, nous avons résolu une structure du complexe de la NDPK-Dd avec la ribavirine triphoaphate (RTP). La structure a montrée que le RTP lie à la NDP kinase comme un nucléotide naturel. Le RTP n'à pas montré de capacité à inhiber l'ARN polymérase du phage T7 malgré un bon substrat de la NDP kinase. Un autre effort a porté sur le changement de la spécificité des kinases impliquées dans leur activation. Nous avons résolu la structure d'un complexe entre l'α-borano-AZT triphosphate (RB-AZTTP) et un variant de la NDP kinase portant la mutation N115S. Le RB-AZTTP se fixe à l'enzyme comme un substrat naturel, car le groupe carboxamide de S115 laisse de la place pour le groupe azido de AZT. Ceci explique l'amélioration de activation de l'enzyme mutant pour les dérivés de l'AZT. Nous avons déterminé la structure d'un complexe de la NDPK-A avec l'ADP et fait une comparaison du mode de fixation du nucléotide dans 19 structures différentes de NDP kinases et 27 structures des protéine kinases. La comparaison a montrée que la conformation différente se trouve dans la partie du phosphate β et γ. De plus, la chiralité de fixation du métal est opposée pour les deux types de kinases
Nucleoside diphosphate kinase (NDP kinase) catalyses the reversible phosphorylation of NDP dependent on nucleoside triphosphate (NTP) via a covalent phosphohistidine intermediate according to the ping-pong mechanism. NDP kinase was implied to be related to the AIDS control due to its activation of the nucleoside analogs which are potential inhibitors to reverse transcriptase of human immunodeficiency virus (HIV). The 3'-OH of currently used NRTIs are substituted or removed. Unfortunately, this group is very important for the catalysis of NDP kinase according to the structural and kinetic research. To verify the novel NRTI, we solved the structure of NDPK-Dd in complex with ribavirin triphosphate (RTP). It showed RTP fixes to NDP kinase in a similar manner to that of the natural nucleotides. RTP is a nice substrate of NDP kinase, but has no capaçity to inhibit RNA polymerase of phage T7. Another effort was made is to change the substrate specificity of NDP kinase. For this purpose, we solved the structure of a variant NDPK-A (N115S) complexed with α-borano-AZT triphosphate (RB-AZTTP). RB-AZTTP was fixed to NDP kinase as a natural substrate because the carboxamide group of S115 provided a space for the azido group of AZT, indicating the improvement of the activation of AZT derivates by the mutant NDP kinases. Finally, we solved the structure of NDPK-A in complex with ADP and compared this structure against 19 different NDP kinase structures and 27 protein kinase structures, from the viewpoint of fixation mode. The comparison indicated the different conformations of the moiety of phosphates β and γ. In addition, fixation chirality of the metal is opposite for the two types of kinases

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Tozlikian, Shant, and Erik Falk. "Marketing of Nicotine Replacement Therapy Products in a Deregulated Swedish Pharmacy Market." Thesis, Mälardalen University, School of Sustainable Development of Society and Technology, 2009. http://urn.kb.se/resolve?urn=urn:nbn:se:mdh:diva-5675.

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The thesis will provide a description of the previous Swedish NRT marketing mix, a description of the present plans of Swedish NRT marketers for the marketing mix of their products, and the present marketing mix of the previously deregulated pharmacy markets in Finland and Norway. The purpose is to develop conclusions on how marketers of NRT products could change their marketing mix in response to the deregulation of the Swedish pharmacy market.

This thesis relies on a descriptive method. Interviews are used as the source of primary data. This is because some of the information sought after is not readily available and cannot be found through secondary data.

Markets are mature only in the minds of the actors on the market. Due to the deregulation the market seems to be a window of opportunity for any innovative, aggressive marketing entrepreneur who wants to radically change his or her position in the market. NRT marketers could attempt to design a new, more aggressive strategy and work with the remaining Ps to unhinge what seems to be regarded a mature market. NRT marketers should work more actively to create an effective market feedback loop. NRT marketers should consider using the Internet to sell their products to consumers, thus opening a new channel.

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Björklund, Stefan. "Microtubule associated proteins 1B and 1S : interactions with NR1 and NR3A." Thesis, Mälardalen University, School of Sustainable Development of Society and Technology, 2008. http://urn.kb.se/resolve?urn=urn:nbn:se:mdh:diva-1197.

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In previous studies the carboxyl-terminus of microtubule-associated protein 1S was shown to interact with the N-methyl-D-aspartate receptor subunit NR3A (Eriksson et. al.)¹. In this study, interactions between three truncations of the microtubule-associated proteins 1B and one truncation of the microtubule-associated protein 1S carboxyl-terminus and the N-methyl-D-aspartate receptor subunits NR1 and NR3A were examined. The study showed that an interaction occurred between amino acids 2167 to 2365 of the microtubule-associated protein 1B and NR3A. That region of microtubule associated protein 1B corresponds to a microtubule-binding region in the light chain. It has been shown in earlier studies (Reviewed in Halpain S. et a1², Riederer, BM. et.al³.) that the light chain is a active part of the protein that have been post translational cleaved. The MAP 1 proteins are present in all tissue but has higher concentrations in the Post Synaptic Density of neurons in the central nervous system. The N-methyl-D-aspartate receptors are present in glial cells and in the dendritic shafts of the central nervous system neurons (Eriksson et. al.)¹. The diseases were these proteins may play a part is mainly memory destructive diseases such as Alzheimers disease and in muscular dystrophy, but these assumptions are still being speculated.

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Tagliaferro, André Luiz. "Estudo da variação genética natural em tomateiro (Solanum lycopersicum) para o processo de absorção de nitrogênio." Universidade de São Paulo, 2015. http://www.teses.usp.br/teses/disponiveis/64/64133/tde-05102015-143002/.

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O uso excessivo de fertilizantes nitrogenados com o intuito de aumentar a produtividade de culturas de tomateiro (Solanum lycopersicum) é decorrente da expansão da demanda mundial. No entanto, o acúmulo/excesso de formas orgânicas ou inorgânicas de nitrogênio no solo está associado a diversos problemas ambientais. Uma alternativa para contornar esses problemas é a identificação de variabilidade genética para aquisição de N, garantindo uma alta produtividade e uma possível melhoria na eficiência do uso de N (NUE). Para tanto, os genótipos S. lycopersicum cv \'Santa Clara\', S. pimpinellifolium e S. habrochaites, previamente identificadas com capacidade de contrastante de absorção de N, foram utilizados em ensaios de cinética de absorção e provisão utilizando traçadores com 15N. Além disso, foi realizada a quantificação da expressão gênica relativa via amplificação de transcritos reversos (RT-qPCR) de genes relacionados ao transporte de amônio (AMTs - AMMONIUM TRANSPORTER - AMT1.1, AMT1.2 e AMT2.1) e nitrato (NRTs - NITRATE TRANSPORTERS - NRT1.1, NRT2.1, NRT2.2 e NAR2) para correlacionar a capacidade de absorção de N com expressão desses genes.. Solanum pimpinellifolium possui maior capacidade de absorção de amônio por suas raízes quando comparado aos genótipos S. lycopersicum cv \'Santa Clara\' e S. habrochaites sob condições contrastantes de disponibilidade de N. Esse fenótipo está relacionado à maior indução da expressão do gene SlAMT1.1 em raízes S. pimpinellifolium. Durante a provisão de amônio, o genótipo S. habrochaites apresentou menor inibição do processo de aquisição de 15N-amônio quando comparado a S. lycopersicum cv \'Santa Clara\' e S. pimpinellifolium. A correlação com os níveis de expressão dos principais transportadores de amônio sugere uma regulação alostérica diferenciada da proteína SlAMT1.1 nesse genótipo. A clonagem e sequenciamento da região codificadora do gene SlAMT1.1 entre os genótipos indicou a existência de diferença na sequência de aminoácidos, principalmente de S. habrochaites. Em particular o resíduo Ser240Gly na alça citosólica, a qual é fundamental durante a regulação alostérica, o que pode estar relacionado à menor inibição do influxo de amônio sob provisão de N. A clonagem e sequenciamento da região promotora do gene SlAMT1.1 dos três genótipos indicaram a presença de motivos regulatórios distintos na região promotora de SlAMT1.1 de S. pimpinellifolium quando comparado a mesma região do genótipos S. lycopersicum cv \'Santa Clara\' e S. habrochaites, o que implicar numa correlação com a maior capacidade de aquisição de amônio em raízes de S. pimpinellifolium. Os resultados de cinética de aquisição de nitrato sugerem que S. pimpinellifolium apresenta maior capacidade quando comparado a S. lycopersicum cv \'Santa Clara\' e S. habrochaites, devido a maior indução dos principais genes de transportadores SlNRT2.1 e SlNRT2.2. A correlação dos estudos de influxo de nitrato e expressão de genes relacionados ao transporte dessa forma de N identificaram que SlNRT2.1 é o principal transportador a ser regulado em raízes dos três genótipos avaliados quando submetidos a condições de provisão de nitrato. Contudo, o genótipo S. habrochaites apresentou maior capacidade de induzir SlNRT2.1 quando comparado a S. lycopersicum cv \'Santa Clara\' e S. pimpinellifolium sob provisão de nitrato
High nitrogen fertilizer input is required to increase the yield of tomato (Solanum lycopersicum) to attend to the rising world demand. N fertilization might result in a detrimental impact on the environment, such as contributing to greenhouse gases and groundwater pollution. One approach to reducing the excessive use of N fertilizers is the evaluation of natural genetic variability for N use efficiency (NUE) of crop plants. Therefore, the genotypes S. pimpinellifolium, S. lycopersicum cv \'Santa Clara\', and S. habrochaites, previously identified with contrasting capacity of N absorption, were used in kinetic and provision assays using short-term 15N-labeled. Furthermore, the relative quantification of gene expression via quantitative reverse transcription PCR (RT-qPCR) of genes related to the ammonium transport (AMTs - AMMONIUM TRANSPORTER - AMT1.1, AMT1.2 and AMT2.1) and nitrate (NRTs - NITRATE TRANSPORTERS - NRT1.1, NRT2.1, NRT2.2 and NAR2) was performed to correlate the N absorption capacity with the expression of these genes. Solanum pimpinellifolium has greater ammonium absorption in its roots when compared to genotypes S. lycopersicum cv \'Santa Clara\' and S. habrochaites under contrasting conditions of N availability. This phenotype is associated with the greater induction of SlAMT1.1 expression in S. pimpinellifolium roots. During ammonium provision, genotype S. habrochaites showed lower inhibition of the 15N-ammonium acquisition compared to S. lycopersicum cv \'Santa Clara\' and S. pimpinellifolium. The correlation with the expression levels of the main ammonium transporter suggests a different allosteric regulation of SlAMT1.1 protein in S. habrochaites. The comparison of the SlAMT1.1 coding region in the three genotypes indicated the existence of differences in amino acid sequence, particularly in S. habrochaites. The change of Ser240Gly in the cytosolic loop of S. habrochaites, which is critical during the allosteric regulation, may be related to the inhibition of ammonium influx. The cloning and sequencing of the promoter region of the gene SlAMT1.1 indicates the presence of different regulatory motifs in the promoter of SlAMT1.1 in S. pimpinellifolium when compared to S. lycopersicum cv Santa Clara and S. habrochaites. This can be correlated with the highest ammonium acquisition capacity of S pimpinellifolium roots. Therefore, nitrate kinetic studies showed that S. pimpinellifolium has greater acquisition of nitrate in their roots when compared to S. lycopersicum cv Santa Clara and S. habrochaites, due to increased induction of SlNRT2.1 and SlNRT2.2 genes. The correlation among nitrate influx studies and expression of genes related to the transport of this N form suggest that SlNRT2.1 is the main transporter regulated in roots of the three genotypes under nitrate supply. In addition, the genotype S. habrochaites showed greater ability to induce SlNRT2.1 when compared to S. lycopersicum cv \'Santa Clara\' and S. pimpinellifolium in nitrate supply

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Alaalm, Leenah M. "Phospho-regulation of the Candida albicans hyphal repressor Nrg1 by the action of multiple kinases." Thesis, University of Sheffield, 2012. http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.604558.

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The ability of C. albicans to reversibly switch between different morphological forms contributes to its virulence as a fungal pathogen. In this research, the molecular mechanisms that control hyphal development in C. albicans were of particular interest because this phenomenon plays an essential role in this pathogen's virulence and pathogenicity. The morphological switching in C. albicans is triggered by various environmental cues. Signal transduction pathways are the primary mechanisms by which cells sense changes in their environment and initiate an adaptive response. In C. albicans, hyphal development is subjected to both positive and negative regulation. The negative regulation of hyphal development is mediated by a repression pathway that involves the recruitment of the repressor Tup1 to the DNA. This study examined the negative regulation of hyphal induction by a particular DNA-binding protein, namely, the negative regulator of filamentous growth (Nrg1). In particular, this study focused on the role of C. albicans Nrg1 in regulating hypha I growth. In C. albicans, cells that lack Nrg1 are characterised by a constitutive filamentous phenotype in both liquid and solid media. The inactivation of Nrg1 causes filamentous growth because the expression of hypha I-specific genes (HSGs) is de-repressed if Nrg1 fails to bind to the promotes of these HSGs. In this study, the mechanisms by which the repression of Nrg1 is relieved during the morphological transition from yeast to hyphae were investigated. In particular, this study assessed the possible phospho-regulation of Nrg1 by three kinases: the cyclin-dependent kinase Cdc28, the cell wall biosynthesis kinase Cbk1 and its upstream activating kinase Kic1. Three Cbk1 consensus target sites in Nrg1, namely, S200, T251 and T281, were identified in this study. Two of these Cbk1 phosphorylation sites, T251 and H 8t, are located in the DNA-binding domain of Nrg1 , specifically at the end of each zinc finger of this protein.

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Grégoire, Élodie. "Implication des gènes Nrg1 et Mmd2 dans le développement de la gonade chez la souris." Thesis, Paris, EPHE, 2015. http://www.theses.fr/2015EPHE3075.

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Chez les mammifères, la détermination du sexe permet à un organe bipotentiel, la gonade, de se différencier en ovaire ou en testicule. Nrg1 (Neuregulin 1) est un facteur de croissance qui agit par phosphorylation de protéines cibles. Chez la souris, Nrg1 est nécessaire à la fertilité des adultes. Les mutants perte de fonction présente une hypoplasie testiculaire. Cependant, Nrg1 est exprimé dans la gonade embryonnaire, ce qui suggère son rôle précoce dans le développement de cet organe. Son rôle durant la gonadogenèse restait encore à établir. Mes travaux ont montré que Nrg1 est impliqué dans la prolifération des précurseurs des cellules de Sertoli chez le mâle, dans l’établissement de la vascularisation et par conséquent l’organisation des cordons testiculaires. Ce phénotype est aggravé en l’absence d’expression du gène Rspo1, un facteur qui stimule également la prolifération des précurseurs des cellules de Sertoli. Cela suggère une fonction additive entre les voies de signalisation contrôlées par Nrg1 et Rspo1 au cours du développement testiculaire. Chez les femelles, les mutants Nrg1 présentent une hypoplasie ovarienne et une réduction de la fertilité. Cela est associé à des cellules germinales atypiques. L’impact de ce phénotype sur la fertilité reste à déterminer. Mmd2 est spécifiquement exprimé dans le testicule mais son rôle est encore inconnu. Pour le déterminer durant la gonadogenèse, j’ai généré des modèles murins de perte de fonction par le système CRISPR-Cas9. Les premiers résultats montrent des cellules somatiques apoptotiques dans les testicules de ce modèle murin. Ces études restent cependant préliminaires et les causes de ce phénotype à élucider
In mammals, sex determination allows a bipotential organ, the gonad, to differentiate into either an ovary or a testis. NRG1 (Neuregulin 1) is a growth factor that promotes phosphorylation of target proteins. In mice, Nrg1 is required for adult fertility. Loss-of-function mutants exhibit testicular hypoplasia. Nrg1 is expressed in embryonic gonads, suggesting an early role in the formation of this organ. However this role remained to be analysed. Here I show that Nrg1 is involved in the proliferation of precursors of Sertoli cells in male. It is also involved in the establishment of the vasculature and in turn partitioning of testis cords. This phenotype is more severe in the absence of Rspo1 expression. RSPO1 signalling also enhances proliferation of precursors of Sertoli cells. This suggests an additive function between the signalling pathways controlled by Nrg1 and Rspo1 during testicular development. In female, Nrg1 mutant ovaries exhibit hypoplasia and reduced fertility. This is associated with atypical germ cells. The relevance of this phenotype on fertility remains to be determined. Mmd2 is specifically expressed in testis but its role is still unknown. To investigate Mmd2 function, I have generated loss-of-function mouse models using the CRISPR-cas9 system. Preliminary results show apoptotic somatic cells in the testes of these mice. However, the causes of this phenotype remain to be clarified

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Ibrahim, Hussein [Verfasser], and Rolf [Gutachter] Marschalek. "The crosstalk between Nrf1 activity, lipids and hepatitis C virus / Hussein Ibrahim ; Gutachter: Rolf Marschalek." Frankfurt am Main : Universitätsbibliothek Johann Christian Senckenberg, 2020. http://d-nb.info/1222588897/34.

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39

Castenvall, Anna, and Elin Petersson. "Utvärdering av två digitala terrängmodeller på öppna ytor : Framställda med NRTK-GNSS och Laserdata NH." Thesis, Högskolan i Gävle, Samhällsbyggnad, 2020. http://urn.kb.se/resolve?urn=urn:nbn:se:hig:diva-32663.

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En digital terrängmodell (DTM) representerar endast markytans form och har en bred användning inom t.ex. samhällsplanering. Det finns olika framställningsmetoder för att skapa en DTM, där de mest använda metoderna är mark- eller flygburen laserskanning samt terrester- eller satellitbaserad mätning. Flygburen laserskanning (FLS) använder sig av tekniken LiDAR (Light Detection And Ranging) där avstånd mäts med laser. Lantmäteriet påbörjade ett projekt 2009, vilket gick ut på att laserskanna hela Sverige med FLS och projektet blev klart 2019. Resultatet blev Laserdata NH (Nationella Höjdmodellen) med en lägesnoggrannhet i höjd på 0,1 m. Syftet med studien är att kontrollera mätosäkerheten för Laserdata NH samt undersöka om den kan ersätta terrestra mätningar, t.ex. GNSS vid skapande av DTM:er. Studieområdet är ca 0,85 ha och består av en gräsyta omgiven av grusvägar. Området är beläget i Teknikparken, Gävle. För att se ifall Laserdata NH kan ersätta GNSS-mätningar skapades en DTM från Laserdata NH samt en DTM från mätningar med NRTK-GNSS. Alla inmätningar följde de krav och toleranser vilka specificeras i SIS-TS 21144:2016. För att kunna kontrollera mätosäkerheten för Laserdata NH mättes kontrollprofiler in, vilka agerade som referens. Kontrollprofilerna användes även som referens när de båda DTM:erna jämfördes mot varandra. Max- och min avvikelse, medelavvikelse, standardosäkerhet samt RMS räknades ut på varje enskild profil, per markyta och för de två modellerna. Beräkningarna utfördes för att se ifall värdena låg för högt eller för lågt i någon del av ett område samt för att kunna se sannolikheten för systematiska avvikelser. En statistisk analys utfördes för att se ifall det finns någon skillnad mellan DTM och kontrollprofilernas medelavvikelse. Resultatet visade att det fanns en statistisk signifikant avvikelse på medelavvikelsen mellan DTM skapad av Laserdata NH och kontrollprofiler för både grus- och gräsytorna. Detta innebär att Laserdata NH inte kan ersätta NRTK-GNSS på öppna, jämna gräsytor eller plana grusytor. Kontrollerna av de två DTM:erna klarar toleranserna enligt SIS-TS 21144:2016 och anses vara tillförlitliga. Studien kom till slutsatsen att Laserdata NH kan användas utan komplettering till översiktliga planeringar. Detaljerade analyser med Laserdata NH behöver dock kompletteras med ytterligare mätningar eller ortofoto för att erhålla mer trovärdiga resultat.
A Digital Terrain Model (DTM) only represent the surface and has a broad application within, for example, community planning. There are different ways of producing a DTM, with the most common methods being ground- or airborne laser scanning and terrestrial- or satellite based measurement. Airborne laser scanning (ALS) uses the technique LiDAR (Light Detection and Ranging) which measures distances with laser. Lantmäteriet, the Swedish cadastral mapping and surveying authority, began in 2009 with a project to scan entire Sweden with ALS and was finished in 2019. The outcome of the project was a new national height model that is called Laserdata NH with a positional accuracy of 0,1 m in height. The purpose of this bachelor thesis is to study the uncertainty of Laserdata NH and to investigate if it can replace terrestrial measurements, for example replacing Laserdata NH with GNSS mapping. The study area is approximately 0,85 hectares and consists of a grassland area surrounded by gravel paths. The area is located in Teknikparken, Gävle. To see if Laserdata NH can replace GNSS-measurements a DTM was created from Laserdata NH as well as a DTM created from measurements with NRTK-GNSS. All measurements followed the requirements and tolerances according to SIS-TS 21144:2016. To control the uncertainty for Laserdata NH, control profiles were measured, which acted as a reference. The control profiles were also used as a reference when comparing the two DTMs. Max and min deviation, mean deviation, standard deviation and RMS were calculated for each profile, per ground area and using two models. The calculations were performed to see if the values were too high or too low in any part of an area and to be able to see the probability of systematic deviations. A statistical analysis was performed to see if there were any difference between the DTM and the mean deviation of the control profiles. The result showed that there was a statistic significant deviation on the mean deviation between the DTM created by Laserdata NH and the control profile for both the gravel and the grass surface. This means that Laserdata NH cannot replace NRTK-GNSS on open, plain grass or gravel surfaces. The controls of the two DTMs are within the tolerances according to SIS-TS 21144:2016 and are considered reliable. The study concluded that Laserdata NH can be used without supplement to do general plans. However, for detailed analysis Laserdata NH needs to be supplemented with additional measurements or orthophoto.

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Koshima, Cristina Chiyoda. "Desterpenação de óleos essenciais de bergamota e limão: determinação de dados de equilíbrio líquido-líquido e modelagem termodinâmica de sistemas modelo, a 25ºC." Universidade de São Paulo, 2011. http://www.teses.usp.br/teses/disponiveis/74/74132/tde-11082011-092748/.

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Uma possível perda de qualidade dos óleos essenciais pode estar associada à decomposição dos compostos terpênicos, quando submetidos ao aquecimento ou contato com o ar, produzindo odores desagradáveis. A redução do teor dos compostos terpênicos, processo conhecido como desterpenação, pode ser realizada por meio de diversas técnicas. Dentre as inúmeras possibilidades, a extração líquido-líquido tem apresentado resultados bastante promissores. Neste contexto, a presente dissertação de mestrado teve como objetivo a determinação experimental e modelagem do equilíbrio líquido-líquido, a (25,0 ± 0,1) °C, dos sistemas modelo de óleo essencial de bergamota e limão compostos, respectivamente, por: limoneno/ acetato de linalila/ linalol/ etanol/ água e limoneno/ γ- terpineno/ β- pineno/ citral/ etanol/ água. Adicionalmente, as propriedades físicas (viscosidade e densidade) dos sistemas supracitados, bem como dos compostos puros, foram também determinadas. Observou-se que o aumento do teor de água no solvente promoveu uma diminuição da extração do linalol (óleo de bergamota) e citral (óleo de limão), entretanto o maior nível de hidratação do etanol acarretou em aumento da região bifásica e da seletividade do solvente em ambos os sistemas estudados. Os dados experimentais obtidos foram correlacionados utilizando-se os modelos termodinâmicos NRTL e UNIQUAC. Para o sistema de óleo essencial de bergamota, o desvio global obtido foi de 0,43% para o modelo UNIQUAC e 0,52% para o NRTL. No que se refere ao sistema de óleo de limão, a equação NRTL foi a que proporcionou a melhor descrição, apresentando um desvio global de 0,29%, em relação ao modelo UNIQUAC, para o qual o desvio obtido foi de 0,32%. Quanto às propriedades físicas, notou-se que a água não exerce muita influência sobre as propriedades da fase terpênica (fase rica em componentes do óleo essencial); entretanto, na fase solvente observou-se que os valores de densidade e a viscosidade foram aumentados com o aumento do nível de água no etanol.
A possible oil quality loss may be associated to the terpenes compounds decomposition, when heated or exposed to air, producing off -flavors. Terpene partial removal, process known as deterpenation, can be performed using many different techniques. Among these various possibilities, the liquid-liquid extraction has shown successful results. The aim of this work was to determine and correlate the liquid-liquid equilibrium experimental data, using thermodynamic models at (25.0 ± 0.1) ºC for bergamot and lemon essential oils model systems composed respectively of limonene/ linalyl acetate/ linalool/ ethanol/ water and limonene/ γ- terpinene/ β- pinene/ citral/ ethanol/ water. Additionally, physical properties (viscosity and density) of the aforementioned systems and pure compounds were determined. It was observed that the higher water content in the solvent led to a lower linalool (bergamot oil) and citral (lemon oil) extraction. However, the highest level of ethanol hydration enlarged the biphasic region and solvent selectivity for both systems. The experimental data were correlated using the NRTL and UNIQUAC thermodynamic models. For bergamot essential oil system, the global deviation was 0.43% for UNIQUAC and 0.52% for NRTL. The NRTL equation provided a better representation of the lemon oil system, with a global deviation value of 0.29%, compared to the UNIQUAC model with a deviation of 0.32%. It was observed that water does not have a significant effect on the terpene phase (essential oil components rich phase) properties. On the other hand, in the solvent phase, it was observed that a higher water content in the ethanol led to higher density and viscosity values.

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41

Walker, Rosie May. "Investigation of putative regulatory loci relevant to the pathogenesis of psychiatric illness." Thesis, University of Edinburgh, 2013. http://hdl.handle.net/1842/8072.

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The genetic contribution to the aetiology of psychiatric illness is well-established; however, few variants that alter the encoded protein have been irrefutably identified as causative, leading to the hypothesis that variants affecting gene regulation may play a pathogenic role. This thesis focuses on two genes, Neuregulin 1 (NRG1) and Disrupted in Schizophrenia 1 (DISC1), for which there is strong genetic evidence for involvement in psychiatric illness, as well as evidence for altered expression in patients. Association analysis was carried out to assess the involvement of six intronic NRG1 single nucleotide polymorphisms (SNPs) in schizophrenia and bipolar disorder in two independent samples from the Scottish (Scottish 2; n = 307 control subjects, 303 schizophrenic patients, and 239 bipolar disorder patients and German populations (n = 397 control subjects, 396 schizophrenic patients, and 400 bipolar disorder patients). These SNPs form two haplotypes, one encompassing the 5’ and promoter region of the gene and the other located at the 3’ end of the gene, that were previously associated with schizophrenia and bipolar disorder in a Scottish sample (Scottish 1). The location of these haplotypes, together with the prior evidence for altered NRG1 expression in schizophrenia, suggested the potential involvement of regulatory variants. On combining the Scottish 1 and Scottish 2 samples (combined n = 765 control subjects, 682 schizophrenic patients and 601 bipolar disorder patients), a two- SNP haplotype spanning both coding and non-coding regions in the 3’ region was associated with schizophrenia (p = 0.0037, OR=1.3, 95% CI: 1.1-1.6) and the combined schizophrenia and bipolar disorder case group (p = 0.0080, OR=1.2, 95% CI: 1.1-1.5), with both these associations remaining significant after permutation analysis (p = 0.022 and p = 0.044, respectively). To further understanding of how DISC1, a leading candidate gene for schizophrenia that has also been implicated in other psychiatric disorders, is regulated the previously uncharacterised promoter region was assessed both bioinformatically and in vitro using the dual luciferase reporter assay. The region was found to lack canonical promoter motifs but to contain a CpG island, consistent with DISC1’s ubiquitous pattern of expression. A region located 300bp to -177bp relative to the transcription start site (TSS) was identified as contributing positively to DISC1 promoter activity, whilst a region -982bp to -301bp relative to the TSS was found to confer a repressive effect. FOXP2, a transcription factor which is mutated in a rare speech and language disorder and implicated in autism pathogenesis, was found to repress transcription from the DISC1 promoter. Two pathogenic FOXP2 point mutations reduced this transcriptional repression. Preliminary evidence for a bi-directional regulatory relationship between DISC1 and FOXP2 was observed: a mouse model of schizophrenia that carries a Disc1 L100P amino acid substitution and shows altered developmental Disc1 expression was also found to show altered developmental expression of Foxp2. These results further understanding of two genes whose altered expression might contribute to the pathogenesis of psychiatric illness.

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42

Testini, Chiara. "Regulation of VEGFR2 signaling in angiogenesis and vascular permeability." Doctoral thesis, Uppsala universitet, Institutionen för immunologi, genetik och patologi, 2016. http://urn.kb.se/resolve?urn=urn:nbn:se:uu:diva-300084.

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Angiogenesis and vascular permeability occur in physiological and pathological conditions. Angiogenesis denotes the process of blood vessel formation from preexisting quiescent vessels. Angiogenesis is initiated by proangiogenic factors, inducing endothelial cell sprouting, migration and anastomosis, followed by regression of the new vessels or maturation into a quiescent status. Vascular permeability is the process where blood vessels exchange nutrients, solutes and inflammatory cells with the surrounding tissue. Small molecules freely cross the endothelial wall, however macromolecules and cells leak out from the vasculature only after stimulation by certain factors, including VEGF. Angiogenesis and vascular permeability are tightly regulated physiological processes, but uncontrolled angiogenesis and excessive leakage lead to pathological conditions and the progression of several diseases. VEGF and its receptor VEGFR2 are critical players in angiogenesis and in vascular permeability. The binding of the ligand to the receptor is not the only event involved in the activation and regulation of the signaling cascade. Coreceptors, kinases, phosphatases, and other proteins involved in the trafficking of the complex modulate the signal amplitude and duration. VEGF/VEGFR2 complex combined with the coreceptor NRP1 has a strong pro-angiogenic action and a critical role in angiogenesis. Both VEGFR2 and NRP1 bind VEGF and can present VEGF in cis, when both VEGFR2 and NRP1 are expressed on the same endothelial cell or in trans, when NRP1 is expressed on an adjacent endothelial cell or another type of cell. Y949 and Y1212 are two of the main phosphorylation sites of VEGFR2 induced by VEGFA. The binding of phosphorylated Y949 to the SH2 domain of TSAd regulates vascular permeability leading to Src activation and adherens junction opening in vitro. Phospho-Y1212 is implicated in actin stress fiber remodeling via the adapter Nck, affecting the actin cytoskeleton and endothelial cell migration in vitro. Paladin is a vascular-enriched phosphatase-domain containing protein without reported phosphatase activity and is a negative regulator of insulin receptor and Toll-like receptor 9 signaling. In this thesis work, I have investigated the spatial dynamics of NRP1/VEGFR2 complex formation (in cis and in trans) for coordinating VEGF-mediated angiogenesis in physiological and in pathological conditions (Paper I). I have studied, in vivo, the role of VEGFR2 Y949 in vascular permeability and metastatic spread (Paper II) and the role of VEGFR2 Y1212 in angiogenic remodeling and vessel stability (Paper III). Furthermore, I have examined paladin’s role in regulating VEGF/VEGFR2 signaling and VE-cadherin junction stability, in angiogenic sprouting and vascular permeability (Paper IV). In conclusion, VEGF/VEGFR2 signaling is regulated by a multifactor system and each individual regulatory mechanism leads to a specific outcome in angiogenesis, vascular permeability and vessel stability.

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43

Günther, Victor, and Marcus Löfman. "Kvalitetsutredning av angiven lägesosäkerhet för gränspunkter." Thesis, Karlstads universitet, Fakulteten för hälsa, natur- och teknikvetenskap (from 2013), 2021. http://urn.kb.se/resolve?urn=urn:nbn:se:kau:diva-85116.

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Alla fastigheter inklusive fastighetsgränser i Sverige redovisas i ett nationellt, digitaltfastighetsregister. Fastighetsregistret redovisar fastighetsindelningen i Sverige samtinnehåller viktig information om varje fastighet. I studien undersöktes lägesosäkerheten påfastighetsgränspunkter för att se hur väl lägesosäkerheten stämmer överens med denangivna i det digitala fastighetsregistret. Områden för undersökning valdes utefter olikaårtionden för förrättning, varierande terräng och med olika lägesosäkerheter. De områdensom valdes var Rudsberg Strandvik, Arnäs samt Körsvik. Dessa har en variation mellanstugområde och skogsfastigheter. Rudsberg Strandvik tillkom på 1970-talet medan deandra är från 2000-talet. För att undersöka den specificerade lägesosäkerheten används GNSS-baserad NRTKmätning på varje enskild punkt. Med efterföljande bearbetning gavs koordinater som sedanjämfördes med de koordinater som fanns angivna i DRK. NRTK som mätmetod har visatsvara lämplig för två av tre områden. I det tredje skulle det vara lämpligt med kombineradNRTK och totalstation. Resultatet är varierande från de olika områdena. Vid Rudsberg Strandvik, Kristinehamnskommun, är 18 av 26 punkter inom den angivna lägesosäkerheten medan vid Arnäs, Grumskommun, visar lägesosäkerheten på att 11 av 23 punkter är inom angivna lägesosäkerheten.Resultatet av lägesosäkerheten vid skogsfastigheterna i Körsvik, Grums kommun, visar påatt alla de inmätta gränspunkterna hamnar inom den angivna lägesosäkerheten.Sammanfattningsvis visar mätningarna att 32 procent av punkterna inte når upp till denangivna lägesosäkerheten medan 68 procent gör det.

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44

Nassar, Mohammed Abdul Karim Deyab. "Reversible external control of gene expression in an NR1 knock-in mouse." Thesis, University College London (University of London), 1998. http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.298624.

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45

Fleck, Daniel [Verfasser], and Christian [Akademischer Betreuer] Haass. "Regulated intramembrane proteolysis of NRG1 type III dediates postnatal peripheral myelination / Daniel Fleck. Betreuer: Christian Haass." München : Universitätsbibliothek der Ludwig-Maximilians-Universität, 2015. http://d-nb.info/1074825357/34.

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46

Briand, Jean-Baptiste. "Etude du contrôle de la transcription envahissante par la terminaison de la transcription." Thesis, Paris 11, 2015. http://www.theses.fr/2015PA112079/document.

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La terminaison de la transcription est essentielle, aussi bien pour assurer la formation de l’extrémité 3’ de transcrits fonctionnels que pour éviter les phénomènes d’interférence transcriptionnelle entre des régions transcrites adjacentes. Ceci est particulièrement important dans un génome compact comme celui de S. cerevisiae. La terminaison est aussi l’une des stratégies principales que la cellule emploie pour contrôler et limiter la transcription dite envahissante ou cachée. Chez S. cerevisiae, l’ARN polymérase II est responsable de la transcription des ARNm et de nombreuses classes d’ARN non codants tels que les sn(o)ARN et les CUT (Cryptic Unstable Transcripts). Ces derniers représentent une fraction importante des transcrits issus de la transcription cachée. Il existe deux voies canoniques de terminaison de la transcription par cette polymérase. Elles font intervenir le complexe de clivage et de polyadénylation, CPF-CF, notamment pour la terminaison des ARNm ou le complexe NNS pour la terminaison des sn(o)ARN et des CUT. Au cours de ma thèse j’ai étudié deux aspects de la terminaison de la transcription : 1) l’étude des motifs de recrutement du complexe NNS et 2) l’identification et la caractérisation d’une nouvelle voie de terminaison par le facteur Rap1. Les complexes CPF-CF et NNS agissent tous les deux en liant le transcrit naissant et l’ARN pol II. Le complexe NNS lie l’ARN naissant grâce à ses sous-unités Nrd1 et Nab3 qui reconnaissent des motifs spécifiques. Cependant, bien que la séquence de ces motifs soit maintenant connue, leur présence ne permet pas de définir de façon certaine un terminateur. En effet, le nombre de ces motifs varie beaucoup d’un terminateur à l’autre. Afin de mieux comprendre la structure des terminateurs ciblés par le complexe NNS et l’organisation des motifs liés par Nrd1 et Nab3, j’ai recherché les séquences impliquées dans la terminaison d’un CUT modèle en réalisant une mutagenèse aléatoire et j’ai identifié par SELEX des motifs de fixation optimale du dimère Nrd1-Nab3. Un second volet de ma thèse porte sur la caractérisation d’une nouvelle voie de terminaison de la transcription dépendante du facteur Rap1. Rap1 est important pour la structure des télomères et c’est aussi un facteur de transcription ciblant des centaines de promoteurs. Il active ou réprime l’initiation de la transcription notamment en recrutant des complexes de remodelage de la chromatine sur les promoteurs ciblés. De façon surprenante, le motif de fixation de ce facteur a été identifié dans des séquences capables de terminer la transcription isolées au laboratoire. Mes travaux ont permis de caractériser le mécanisme de terminaison par Rap1 et de distinguer cette voie des voies de terminaison canoniques. Ce facteur, lié à l’ADN, agit comme une barrière en bloquant la progression de l’ARN polymérase II par un mécanisme de « road-block ». Les polymérases ainsi arrêtées sont ciblées par une voie qui permet leur élimination lorsqu’elles sont bloquées par des dégâts sur l’ADN, impliquant leur ubiquitination et vraisemblablement leur dégradation par le protéasome. Les ARN libérés sont polyadénylés par la poly(A)-polymérase Trf4 et dégradés par l’exosome nucléaire. Ce mécanisme de terminaison est utilisé dans un contexte naturel puisque j’ai identifié des transcrits endogènes de S. cerevisiae terminés par cette voie. Nous proposons que la terminaison par Rap1 contribue au contrôle de la transcription envahissante. Ce facteur assurerait ainsi au niveau des promoteurs qu’il lie une double fonction de facteur de transcription et de protection de ces promoteurs contre l’interférence transcriptionnelle
Transcription termination is essential, both for the 3’ end formation of functional transcripts and to avoid transcriptional interference between adjacent transcription units. This is particularly important in a compact genome such as S. cerevisiae. Termination is also one of the main strategies used by the cell to control and limit the “pervasive” or “hidden” transcription. In S. cerevisiae, RNA pol II is responsible for the transcription of the mRNAs and numerous non-coding RNA families such as the sn(o)RNAs and the CUTs (Cryptic Unstable Transcripts). CUTs represent a large fraction of the “pervasive” or “hidden” transcription. There are two canonical transcription termination pathways for this RNA polymerase. They involve the cleavage and polyadenylation complex (CPF-CF), in particular for the mRNAs termination, or the NNS complex for sn(o)RNAs and CUTs termination. During my thesis I studied two aspects or the transcription termination: 1) the motifs involved in the NNS complex recruitment on RNA and 2) the identification and the characterization of a new termination pathway by Rap1. CPF-CF and NNS complex are both recruited on the nascent transcript and on the RNA pol II. The NNS complex binds the RNA through its subunits Nrd1 and Nab3 which recognize specific motifs. Nonetheless, even if these motif sequences are now known, their presence does not elicit the certain identification of NNS dependent terminators. To clarify the NNS dependent terminator structure and the organization of the motifs bound by Nrd1 and Nab3 I looked for the sequences involved in a specific CUT termination doing a random mutagenesis experiment and I identified by SELEX the Nrd1-Nab3 dimer optimal binding motifs. A second part of my thesis concerns the characterization of a new transcription termination pathway dependent on the Rap1 factor. Rap1 is important for the telomere structure and it is also a transcription factor that targets hundred of promoters. It activates or represses transcription initiation recruiting chromatin remodeling complexes on the targeted promoters. Surprisingly, the Rap1 binding motifs have been identified among sequences eliciting termination isolated in the laboratory. My work has led to the characterization of the termination mechanism by Rap1 and distinguished this pathway from the two canonical pathways. This factor, bound to DNA, acts as a barrier blocking the RNA pol II progression by a road-block mechanism. These arrested polymerases are targeted by a pathway responsible for the elimination of RNA pol II blocked by DNA damages, implying their ubiquitination and probably their degradation by the proteasome. The released RNAs are polyadenylated by the poly(A) polymerase Trf4 and degraded by the nuclear exosome. This termination mechanism is used in a natural context since I identified S. cerevisiae endogenous transcripts terminated by this pathway. We propose that the Rap1 termination contributes to the pervasive transcription control. This factor could elicit, on its bound promoters, a double function of both transcription factor and protection of these promoters against transcriptional interference

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47

Salvany, Sara. "Organització molecular dels aferents sinàptics de tipus C i la seva implicació en la patologia degenerativa de la neurona motora." Doctoral thesis, Universitat de Lleida, 2022. http://hdl.handle.net/10803/674022.

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L’esclerosi lateral amiotròfica (ELA) és una malaltia que cursa amb degeneració i pèrdua de les motoneurones (MNs), determinant una paràlisi muscular progressiva i de pronòstic fatal. L’acumulació de la proteïna superòxid dismutasa 1 mal plegada (mfSOD1) en les MNs és el factor intrínsec distintiu de la patologia en el model murí per l’estudi de l’ELA SOD1G93A que reprodueix una forma familiar de la ELA humana. No obstant, factors extrínsecs a les MNs tals com l’activitat elèctrica mitjançada per les aferències sinàptiques, així com l’entorn cel•lular determinat per les cèl•lules glials, també són molt rellevants en la fisiopatologia de l’ELA. Entre les aferències, els botons C (BC) són uns importants reguladors colinèrgics de l’excitabilitat de les MNs. Aquests es caracteritzen per tenir una cisterna subsinàptica (SSC) adjacent a la membrana postsinàptica, on s’hi ha descrit un complex macromolecular específic format per diferents proteïnes, entre elles, la neuregulina-1 (NRG1). Tot i que s’han descrit alteracions en els BC en l’ELA, la funció de la NRG1 en la fisiologia i la patologia de la MN es completament desconeguda. L’objectiu del present treball ha estat caracteritzar millor l’arquitectura molecular del BC i analitzar les seves alteracions així com la implicació en la regulació de la resposta microglial al voltant de les MNs danyades. Per a aquesta finalitat, hem analitzat la localització i distribució de diverses proteïnes dins dels subcompartiments sinàptics del BC i la seva relació amb la glia mitjançant microscòpia confocal i electrònica en diferents models animals. Els resultats demostren que, en la SSC, la NRG1 està situada en microdominis molt específics i no solapats amb altres proteïnes, mentre que el seu receptor, els ErbB2/4, estan presents en el compartiment presinàptic adjacent. D’altra banda, també s’ha evidenciat que les diferents isoformes de NRG1 regulen funcions diferents en el BC específicament a nivell pre- o postsinàptic. Les aferències de tipus C es desorganitzen en presència d’estressos aguts, tals com la lesió del nervi perifèric, on aquesta pèrdua de BCs es produeix en conjunció a un augment del reclutament de cèl•lules microglials. A més, la micròglia, està involucrada en l’eliminació del detritus de terminals sinàptics prèviament desintegrats per la via necroptòtica activada després de l’axotomia. En el model murí SOD1G93A, hem definit 3 fenotips de MNs d’acord a l’expressió de mfSOD1 i a la degeneració vacuolar. Hem caracteritzat aquesta vacuolització utilitzant marcadors mitocondrials i de vesícules extracel•lulars així com la seva relació amb els canvis en les aferències sinàptiques i l’activació microglial. En conjunt, els nostres resultats aporten noves dades sobre l’organització dels BC i dels canvis que tenen lloc tant en lesions agudes en les MNs com en l’ELA. També aportem noves dades sobre la citopatologia relacionada amb l’expressió de mfSOD1 durant les fases inicials de la degeneració de les MNs en l’ELA.
La esclerosis lateral amiotròfica (ELA) es una enfermedad que cursa con degeneración y pérdida de las motoneurones (MNs), determinando una parálisis muscular progresiva y de pronóstico fatal. La acumulación de la proteína superóxido dismutasa 1 mal plegada (mfSOD1) en las MNs es el factor intrínseco distintivo de la patología en el modelo murino para el estudio de la ELA SOD1G93A, el cual reproduce una forma familiar de la ELA humana. No obstante, factores extrínsecos a las MNs como la actividad eléctrica mediada por las aferencias sinápticas, así como el entorno celular determinado por las células gliales, también son muy relevantes en la fisiopatología de la ELA. Entre las aferencias, los botones C (BC) son unos importantes reguladores colinérgicos de la excitabilidad de las MNs. Estos se caracterizan por tener una cisterna subsináptica (SSC) adyacente a la membrana postsináptica, dónde se ha descrito un complejo macromolecular específico formado por distintas proteínas, entre ellas, la neuregulina-1 (NRG1). Aunque se han descrito alteraciones en los BC en la ELA, la función de la NRG1 en la fisiología y la patología de la MN es completamente desconocida. El objetivo del presente trabajo ha sido caracterizar mejor la arquitectura molecular del BC y analizar sus alteraciones, así como su implicación en la regulación de la respuesta microglial alrededor de las MNs dañadas. Para esta finalidad, hemos analizado la localización y distribución de varias proteínas de los subcompartimentos sinápticos de los BC y su relación con la glía mediante microscopía confocal y electrónica en distintos modelos animales. Los resultados demuestran que, en la SSC, la NRG1 está ubicada en microdominios muy específicos y no solapados con otras proteínas, mientras que su receptor, los ErbB2/4, están presentes en el compartimento presináptico adyacente. Por otro lado, también se ha evidenciado que las distintas isoformas de NRG1 regulan funciones diferentes en los BC específicamente a nivel pre- o postsináptico. Las aferencias de tipo C se desorganizan en presencia de un estrés agudo como es la lesión del nervio periférico, dónde ésta pérdida de BCs se produce junto a un aumento del reclutamiento de células microgliales. Además, la microglía, está involucrada en la eliminación de los detritus de los terminales sinápticos previamente desintegrados por la vía necroptótica activada después de la axotomía. En el modelo murino SOD1G93A, hemos definido 3 fenotipos de MNs de acuerdo a la expresión de mfSOD1 y a la degeneración vacuolar. Hemos caracterizado la vacuolización mediante marcadores mitocondriales y de vesículas extracelulares, así como su relación con los cambios con las aferencias sinápticas y la activación microglial. En conjunto, nuestros resultados aportan nuevos datos sobre la organización de los BC y de los cambios que tienen lugar tan en lesiones agudas en las MNs como en la ELA. También aportamos nuevos datos sobre la citopatologia relacionada con la expresión de mfSOD1 durante las fases iniciales de la degeneración de las MNs en la ELA.
Amyotrophic lateral sclerosis (ALS) is a fatal disease characterised by the degeneration and loss of motor neurons (MNs) determining a progressive muscle paralysis. A distinctive intrinsic factor in the ALS mice model SOD1G93A is the accumulation of superoxide dismutase protein in a misfolded form (mfSOD1), reproducing a familiar form of human ALS. However, extrinsic factors such as electric activity mediated by synaptic afferents, along with glial cellular environment, are crucial in ALS physiopathology. Among the afferents, C-boutons (BC) are very important cholinergic regulators of MN excitability. A distinctive feature of BC is the presence of an endoplasmic reticulum-related subsynaptic cistern (SSC) close to the postsynaptic membrane. At this site, a specific macromolecular complex formed by a variety of proteins, including neuregulin-1 (NRG1), has been described. Although some alterations in BC have been described in ALS, the role of NRG1 in BC signalling in normal or altered MNs is not known. The main objective of the present work is to characterise the molecular architecture of BC and to investigate how is altered in injured MNs; also the BC-derived signalling in the regulation of the neuroinflammatory response that takes place at the vicinity of damaged MNs was analysed. To this aim, we applied confocal and electron microscopy in different animal models, and the we have determined the localisation of a variety of proteins in relation to the distinct BC synaptic subcompartments and its relation with glial cells. Our results showed that NRG1 is specifically concentrated at the SSC forming non-overlapping microdomains with other SSC proteins. By contrast, its receptors ErbB2/4 are identified in the adjacent presynaptic compartment. Furthermore, we have also found that different NRG1 isoforms are involved in the regulation of BC morphogenesis acting differentially on its pre- or postsynaptic components. BCs is disorganised in response to acute stressors, such as a peripheral nerve injury. In this situation, the loss of BCs is produced in conjunction of local recruitment of microglial cells. We also described how microglia is involved in the elimination of degenerating synaptic terminal, which were previously disrupted by a mechanism involving necroptotic pathway that was activated after axotomy. In SOD1G93A mice model, we have defined 3 MN phenotypes according to the expression of mfSOD1 and vacuolar degeneration at the early presymptomatic stages of the disease. Vacuolar degeneration was characterised using mitochondrial and extracellular vesicle markers and its relationship with changes in afferent synapses and microglial cell activation. As a whole, our results provide new data on molecular organisation of the BC and the changes that takes place both, in acutely injured MNs and also during ALS. Furthermore, we provide new data regarding the cytopathology of mfSOD1 expression during early phases of MN degeneration in ALS.

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48

Nicolas, Christophe. "Contribution à l'étude des propriétés thermodynamiques des solutions très concentrées d'acétate de potassium en solvant aqueux et mixte : extension aux carboxylates de potassium." Vandoeuvre-les-Nancy, INPL, 2002. http://docnum.univ-lorraine.fr/public/INPL_T_2002_NICOLAS_C.pdf.

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Les électrolytes sont rencontrés aussi bien en sciences naturelles, en sciences du génie chimique qu'en sciences de l'environnement où ils interviennent en tant qu'agents polluants ou comme constituants de la biosphère. La description des propriétés thermodynamiques des solutions d'électrolyte en solvant aqueux ou mixte est d'une importance capitale dans de nombreux procédés de séparation, notamment les procédés de cristallisation ou de distillation. On comprend dès lors l'intérêt à la fois théorique et industriel que représente l'étude de ces systèmes. Panni les électrolytes, l'acétate de potassium connaît de nombreux développements techniques mais l'absence de données expérimentales limite son exploitation en milieu industriel. Ce travail constitue une contribution à la détermination expérimentale des propriétés thermodynamiques des solutions aqueuses et mixtes d'acétate de potassium et à leur représentation. Nous avons mesuré les équilibres liquide/solide à l'aide d'un dispositif mis au point au laboratoire. Nous avons utilisé un calorimètre C80 (SET ARAM) atm de déterminer les enthalpies de dissolution dans l'eau et dans les mélanges eau/éthanol à plusieurs températures. Enfin nous avons mesuré les volumes molaires des solutions à l'aide d'un densimètre DMA 60 (ANTON P AAR). La représentation de ces propriétés thermodynamiques a été obtenue à l'aide du modèle de Pitzer et de Chen (NR TL) en considérant dans un premier temps la dissociation complète de l'acétate de potassium sur tout le domaine de inola1ité. Dans un second temps, l'étude du modèle de Pitzer et des propriétés thermodynamiques ont permis de rendre compte de la dissociation partielle du sel. Ce travail établit une méthodologie pour l'étude des sels très solubles et souligne l'importance des données calorimétriques pour l'ajustement des paramètres des modèles thermodynamiques
Electrolytes can be found in biology, as weil as chemical engineering and environmental science in the form of polluting meters or as biosphere components. The description of thermodynamic properties of electrolyte solutions in aqueous or mixed solvents is critical in various separation processes, including crystallization or distillation. Therefore, the study of such systems is of great interest form a theoretical and industrial point of view. Due to a lack of experimental data, very few researches on potassium acetate lead to actual industrial applications. This work is a contribution to the experimental determination of thermodynamic properties of potassium acetate solutions in aqueous or mixed solvent and to their representation. We have measured liquidlsolid equilibrium thanks to an experimental deviee designed in the laboratory. We have used a C80 calorimeter (SETARAM) for the determination of dissolution enthalpies in water and in water/ethanol mixed solvents at several temperatures. Eventually, we have measured the molar volumes of solutions with a DMA 601 densitometer (ANTON PAAR) This thermodynamic properties representation was obtained with Pitzer and Chen models. This work provides a methodological approachfor study of highly soluble salts, and shows the importance of calorimetrie data for parame ter fitting of thermodynamic models

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Stukes, James Bernard. "Evidence for the association of NR1 plasmid DNA with inner membrane of proteus mirabilis." DigitalCommons@Robert W. Woodruff Library, Atlanta University Center, 1986. http://digitalcommons.auctr.edu/dissertations/1539.

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The examination of exponent i ally grown Proteus mirabilis, in the absence and presence of chloramphenicol revealed NR1 plasmid DNA-membrane complexes when isolated on 10-30% neutral sucrose (CLOS) gradients. Subsequent analysis of CLOS generated pl asmid DNA-membrane fract ions on 30- 50% isopycnic step neutral slJcrose gradients indicated preferential association of the plasmid DNA with the inner cytoplasmic membrane. In addition, plasmid DNA-membrane complexes isolated by the Clewell-Helinski "cleared lysate" procedure indicated preferential association with the inner cytoplasmic membrane, as well. Agarose gel analysis of covalently closed circular (CCC) NR1, isolated from exponentially grown cultures of P. mirabilis in the presence of chloramphenicol revealed that the plasmid molecules maintained their composite structure of 60 Mdaltons, and did not undergo transitioning. Further, EcoR! restriction digest of these molecules confirmed the existence of NR1 plasmid DNA.

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Noël, Jean-François. "Étude du rôle du complexe Smc5/6 dans le maintien des télomères, de la terminaison de la transcription de l'ARN de la télomérase, et de la taille des télomères dans la polyarthrite rhumatoïde." Thèse, Université de Sherbrooke, 2013. http://hdl.handle.net/11143/6654.

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Les télomères sont des structures nucléoprotéiques formées de séquences d’ADN répétées associées à des protéines spécialisées assurant la protection des extrémités des chromosomes eucaryotes et leur réplication complète. La télomérase est une ribonucléoprotéine catalysant l’ajout de répétitions télomérique pour contrer la perte de séquences inhérente à la réplication des extrémités des chromosomes linéaires. Plusieurs facteurs jouent des rôles importants dans le maintien de l’intégrité des télomères. Le champ d’étude de la biologie des télomères est toujours en expansion, étant donné les liens étroits entre les télomères, le cancer et le vieillissement. Les travaux présentés dans cette Thèse se divisent en trois parties. Les deux premières utilisent la levure Saccharomyces cerevisiae pour explorer les liens entre le complexe Smc5/6 et le maintien des télomères, ainsi que les mécanismes de terminaison de transcription de la composante ARN de la télomérase (T1c1). La troisième partie est une étude épidémiologique préliminaire examinant la taille des télomères de patients atteints de polyarthrite rhumatoïde (PR). Premièrement, les protéines SMC (structural maintenance of chromosomes) forment 3 complexes conservés requis pour la transmission des chromosomes lors des divisions cellulaires. Le complexe Smc5/6 a été impliqué dans la réparation de l’ADN et le maintien des télomères. Les rôles des complexes SMC, en particulier Smc5/6, dans la biologie des télomères ont donc été investigués. Les résultats montrent que les complexes SMC sont importants pour la survie pendant la sénescence en absence de télomérase. Les données obtenues pour Smc5/6 supportent un modèle dans lequel le complexe est requis pour la réplication complète et la réparation adéquate des chromosomes. De fréquentes cassures d’ADN au niveau des répétitions télomériques sont observées en absence du complexe, illustrant l’importance particulière de Smc5/6 pour la séparation des régions télomériques. Deuxièmement, il est établi que l’abondance de la télomérase est critique pour l’homéostasie des télomères. Mais le contrôle de l’expression de l’ARN T1c1 est encore obscur. L’analyse des séquences en 3' du gène TLC1 révèle des signaux reconnus par les 2 voies de terminaison de transcription par l’ARN polymérase II. Les résultats indiquent que la formation de T1c1 est contrôlée par la voie de terminaison des petits ARNs noncodants Nrd1/Nab3. T1c1 existe sous 2 formes, une majeure, non polyadénylée, présente dans la télomérase active, et une mineure, polyadénylée, dont le rôle est inconnu. Les données montrent que la synThèse et la fonction de l’ARN T1c1 mature ne nécessitent pas la forme polyA+ comme précurseur. La terminaison dépendante de la polyadénylation pourrait être un mécanisme de sûreté pour arrêter la transcription. Troisièmement, plusieurs maladies sont associées à des défauts dans le maintien des télomères. La PR est une maladie auto-immune causant une inflammation chronique et une destruction graduelle des articulations. Des études suggèrent que les lymphocytes de patients atteints de PR auraient des télomères anormalement courts. Ensuite, des marqueurs pronostiques fiables identifiant les patients qui développeront une arthrite persistante et sévère font actuellement défaut, mais seraient utiles afin d’élaborer des traitements plus efficaces. Une étude épidémiologique a donc été amorcée pour analyser l’érosion des télomères des lymphocytes dans une cohorte de patients avec arthrite débutante et évaluer de potentielles corrélations avec la progression et la sévérité de la maladie. Les résultats préliminaires obtenus par 3 techniques de mesure de la taille des télomères (TRF, STELA et qPCR) sont incomplets, mais semblent indiquer un défaut dans le maintien des télomères chez les patients. Les observations illustrent aussi les limites des études épidémiologiques longitudinales analysant la taille des télomères.

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