On assiste aujourd'hui à l'importation des NTIC (Nouvelles Technologies de l'Information et de la Télécommunication) dans la robotique. L'union de ces technologies donnera naissance, dans les années à venir, à la robotique de service grand-public.Cet avenir, s'il se réalise, sera le fruit d'un travail de recherche, amont, dans de nombreux domaines : la mécatronique, les télécommunications, l'automatique, le traitement du signal et des images, l'intelligence artificielle ... Un des aspects particulièrement intéressant en robotique mobile est alors le problème de la localisation et de la cartographie simultanée. En effet, dans de nombreux cas, un robot mobile, pour accéder à une intelligence, doit nécessairement se localiser dans son environnement. La question est alors : quelle précision pouvons-nous espérer en terme de localisation? Et à quel coût?Dans ce contexte, un des objectifs de tous les laboratoires de recherche en robotique, objectif dont les résultats sont particulièrement attendus dans les milieux industriels, est un positionnement et une cartographie de l'environnement, qui soient à la fois précis, tous-lieux, intègre, bas-coût et temps-réel. Les capteurs de prédilection sont les capteurs peu onéreux tels qu'un GPS standard (de précision métrique), et un ensemble de capteurs embarquables en charge utile (comme les caméras-vidéo). Ce type de capteurs constituera donc notre support privilégié, dans notre travail de recherche. Dans cette thèse, nous aborderons le problème de la localisation d'un robot mobile, et nous choisirons de traiter notre problème par l'approche probabiliste. La démarche est la suivante, nous définissons nos 'variables d'intérêt' : un ensemble de variables aléatoires. Nous décrivons ensuite leurs lois de distribution, et leur modèles d'évolution, enfin nous déterminons une fonction de coût, de manière à construire un observateur (une classe d'algorithme dont l'objectif est de déterminer le minimum de notre fonction de coût). Notre contribution consistera en l'utilisation de mesures GPS brutes GPS (les mesures brutes - ou raw-datas - sont les mesures issues des boucles de corrélation de code et de phase, respectivement appelées mesures de pseudo-distances de code et de phase) pour une navigation bas-coût précise en milieu extérieur suburbain. En utilisant la propriété dite 'entière' des ambiguïtés de phase GPS, nous étendrons notre navigation pour réaliser un système GPS-RTK (Real Time Kinematic) en mode différentiel local précise et bas-coût. Nos propositions sont validées par des expérimentations réalisées sur notre démonstrateur robotique. / We are witnessing nowadays the importation of ICT (Information and Communications Technology) in robotics. These technologies will give birth, in upcoming years, to the general public service robotics. This future, if realised, shall be the result of many research conducted in several domains: mechatronics, telecommunications, automatics, signal and image processing, artificial intelligence ... One particularly interesting aspect in mobile robotics is hence the simultaneous localisation and mapping problem. Consequently, to access certain informations, a mobile robot has, in many cases, to map/localise itself inside its environment. The following question is then posed: What precision can we aim for in terms of localisation? And at what cost?In this context, one of the objectives of many laboratories indulged in robotics research, and where results impact directly the industry, is the positioning and mapping of the environment. These latter tasks should be precise, adapted everywhere, integrated, low-cost and real-time. The prediction sensors are inexpensive ones, such as a standard GPS (of metric precision), and a set of embeddable payload sensors (e.g. video cameras). These type of sensors constitute the main support in our work.In this thesis, we shed light on the localisation problem of a mobile robot, which we choose to handle with a probabilistic approach. The procedure is as follows: we first define our "variables of interest" which are a set of random variables, and then we describe their distribution laws and their evolution models. Afterwards, we determine a cost function in such a manner to build up an observer (an algorithmic class where the objective is to minimize the cost function).Our contribution consists of using brute GPS measures (brute measures or raw datas are measures issued from code and phase correlation loops, called pseudo-distance measures of code and phase, respectively) for a low-cost navigation, which is precise in an external suburban environment. By implementing the so-called "whole" property of GPS phase ambiguities, we expand the navigation to achieve a GPS-RTK (Real-Time Kinematic) system in a precise and low-cost local differential mode.Our propositions has been validated through experimentations realized on our robotic demonstrator.

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Ett på marknaden nyligen introducerat GNSS-instrument är Leica GS18 T med inbyggd lutningskompensator, baserad på kombinerad GNSS- och tröghetsnavigeringsteknik (INS), som gör att mätstången med GNSS-instrumentet inte behöver centreras över den punkt som ska mätas in. Förutom att utföra snabbare mätningar möjliggör lutningskompensatortekniken inmätning av dolda punkter där konventionell GNSS-mätning normalt inte är möjlig utan mer tidskrävande indirekta metoder måste användas. Instrumentet har även avancerad GNSS-signalspårningsteknik som möjliggör mätning i svåra miljöer. På uppdrag av Lantmäteriet har som ett inledande test av Leica GS18 T lägesosäkerheten vid nätverks-RTK-mätning med lutande mätstång undersökts i tre situationer: vid mätning i olika lutningsgrader i både normal och svår mätmiljö, vid lutning mot olika väderstreck för att studera lutningsriktningens eventuella inverkan samt vid inmätning av hushörn som exempel på ett tillämpningsområde. I det senare fallet jämfördes resultatet med vad som erhålls med en indirekt metod, i detta fall dold punkt genom inbindning, som mätning med lutningskompensator möjligen skulle kunna ersätta. Analys av lägesosäkerheten baseras på beräkningar av standardosäkerhet, RMS (Root Mean Square) och medelavvikelse. Mätningarna med olika lutningsgrader på mätstången resulterade i en lägesosäkerhet på cm-nivå i plan för både normal och svår mätmiljö. Lägesosäkerheten i höjd hamnade på mm-nivå i normal mätmiljö och på cm-nivå i svår mätmiljö. Vidare pekar resultaten på att mätstångens lutningsriktning påverkar lägesosäkerheten. Orsaken till detta är dock inte klarlagd och kräver vidare undersökning. Inmätning av hushörn gav en medelavvikelse på ca 12 mm när mätstången lutades 30°. Metoden dold punkt genom inbindning gav generellt en lägre medelavvikelse, även om skillnaden är relativt liten (4 mm som lägst). En sammanfattande bedömning är att instrumentet fungerar bra vid detaljmätning, åtminstone vid positionsosäkerhetskrav på cm-nivå. / A recently introduced GNSS instrument on the market is Leica GS18 T with tilt compensation, based on GNSS/Inertial Navigation Systems (INS) integration, with no need to centre the survey pole with the GNSS instrument over the target point being measured. Besides making surveying faster, the tilt compensation technique enables measuring of hidden points where the use of conventional GNSS measuring normally is not possible without more time-consuming methods. The instrument also has advanced GNSS signal tracking which makes surveying in challenging environments possible. In this study, the Leica GS18 T has on behalf of Lantmäteriet been tested through studying the measurement uncertainty in network RTK measurement with tilted survey pole in three different situations: with the survey pole tilted in various degrees in both favourable and challenging survey environments; with tilt towards north, east, south and west to test if the tilt direction would affect the result; and for surveying of building corners as a possible field of application. In the latter case, the result was compared with what can be achieved with the conventional hidden point method using intersection of distances. The analysis of the measurement uncertainty was based on calculations of standard uncertainty, RMS (Root Mean Square) and mean deviation. The measurement uncertainty from the first part of the test was on cm-level horizontally, both in favourable and challenging survey environments, and in height on mm-level in favourable survey environment and on cm-level in challenging survey environment. Further, the results indicate that the tilt direction affects measurement uncertainty. The reason for this is not clarified and needs further investigation. The measurements of building corners resulted in a mean deviation of approximately 12 mm when the survey pole was tilted 30°. The hidden point method using intersection of distances generally resulted in lower mean deviation, even though the difference is relatively small (4 mm at best). To summarize, Leica GS18 T seems to be well suited for measuring with tilt in detailed surveying, at least if the requirements of position uncertainty is on cm-level.

Att tidigt kunna detektera samt åtgärda sättningar och deformationer är viktigt inom exempelvis bygg-, anläggnings- och gruvindustrin för att kontrollera att verksamheten inte påverkar närliggande områden och strukturer. UAV (Unmanned Aerial Vehicle) fotogrammetri är en lämplig metod för att utföra upprepade mätningar i svårtillgänglig miljö där sättningar kan uppkomma. Syftet med denna studie har varit att undersöka möjligheten till att detektera sättningar med UAV fotogrammetri samt att jämföra direkt och indirekt georeferering. Detta har undersökts genom att ett antal objekt har använts till att simulera sättningar med förändringar på centimeternivå. Området som studien utfördes på flögs över med en fotogrammetrisk UAV i två epoker varav den första epoken var innan sättning och den andra epoken var efter en simulerad sättning av objekten. Punkter markerades på objekten vilka mättes in med totalstation för båda epokerna och dessa mätningar användes som referensvärden (hädanefter kallat True Value). Bearbetning skedde därefter i två programvaror: Agisoft Metashape och Leica Infinity. I Metashape skapades punktmoln för båda epokerna indirekt georefererade med markstödpunkter. I Infinity skapades punktmoln för båda epokerna direkt georefererade med Nätverks-RTK (N-RTK). Punktmolnens avvikelser mot kontrollpunkter kontrollerades. Koordinater för markeringarna på objekten extraherades och jämfördes med koordinater inmätta med totalstation. Resultatet av bearbetningen blev fyra olika punktmoln. I de indirekt georefererade punktmolnen var det möjligt att detektera deformeringar på centimeternivå. Det var däremot inte möjligt i de direkt georefererade punktmolnen då de var påverkade av ett systematiskt fel i höjd. De två programvarornas arbetsgång och resultat jämfördes även mot varandra och där kan det konstateras att om de två programvarorna båda har höga systemkrav så var Leica Infinity betydligt mer krävande både vad gäller hårdvara och tidsåtgång än Agisoft Metashape. De slutsatser vi kan dra utifrån denna studie är att N-RTK ännu inte är en tillräckligt bra georefereringsmetod när låga osäkerheter efterfrågas. I detta fall är indirekt georeferering eller registrering av punktmolnen med hjälp av ICP (Iterative Closest Point) algoritmer att föredra. Det är också viktigt att generera punktmoln med en så hög punkttäthet som möjligt för att kunna göra noggranna mätningar i molnen. / The early detection and measure of subsidence and deformations is important within construction-, civil engineering and the mining industry to control whether the operations affect nearby areas and structures. UAV (Unmanned Aerial Vehicle) photogrammetry is a suitable method to conduct repeated measurements in environments which is hard to access where subsidence can occur. The purpose of this study has been to investigate the possibility of detecting subsidence with UAV photogrammetry and compare direct and indirect georeferencing. This has been investigated by using several objects to simulate subsidence at centimeter level. The area where the study was conducted was flown over with a photogrammetric UAV in two epochs of which the first epoch was before subsidence and the second epoch was after a simulated subsidence of the objects. Points was marked on the objects who were measured with a total station for both epochs and these measurements was used as reference values (hereafter called True Value). Processing was thereafter done in two different software: Agisoft Metashape and Leica Infinity. In Metashape point clouds was created for both epochs indirectly georeferenced with ground control points. In Infinity point clouds was created for both epochs directly georeferenced with Network-RTK (N-RTK). The deviations of the point clouds towards checkpoints were verified. Coordinates of the markings on the objects was extracted and compared against coordinates measured with total station. The photogrammetric processing resulted in four different point clouds. In the indirectly georeferenced pointclouds it was possible to detect deformations at centimeterlevel. This was however not possible using the directly georeferenced pointclouds as they were affected by a systematic error in heigth. The workflow and the resulting point clouds from the two different software was also compared to each other and by that it was established that even though they both have high system requirements the Leica Infinity software was much more demanding and additionally time consuming. The conclusion from this study is that N-RTK is not yet a satisfactory method for georeferencing when low uncertainties are required. In this case, indirect georeferencing or registration of the point clouds with ICP (Iterative Closest Point) algorithms is to be preferred. It is also important to create point clouds with the highest density possible to be able to make exact measurements.

Gastric cancer ranks the fifth most common and third leading cause of cancer‐related deaths worldwide. Alterations in the RTK/MAPK, WNT, cell adhesion, TP53, TGFβ, NOTCH, and NFκB signaling pathways could be identified as main oncogenic drivers. A combination of altered pathways can be associated with molecular subtypes of gastric cancer. In order to generate model systems to study the impact of different pathway alterations in a defined genetic background, we generated three murine organoid models: a RAS‐activated (KrasG12D, Tp53R172H), a WNT‐activated (Apcfl/fl, Tp53R172H), and a diffuse (Cdh1fl/fl, Apcfl/fl) model. These organoid models were morphologically and phenotypically diverse, differed in proteome expression signatures and possessed individual drug sensitivities. A differential vulnerability to RTK/MAPK pathway interference based on the different mitogenic drivers and according to the level of dependence on the pathway could be uncovered. Furthermore, an association between RTK/MAPK pathway activity and susceptibility to HDAC inhibition was observed. This finding was further validated in patient‐derived organoids from gastric adenocarcinoma, thus identifying a novel treatment approach for RTK/MAPK pathway altered gastric cancer patients.

The machair is a coastal grassland system found only in parts of northern and western Scotland and Ireland. Despite its limited geographic distribution, machair landscapes have high ecological, geomorphological, and cultural significance, as recognised by numerous conservation designations and legislation. In January 2005 a severe storm caused extensive damage in the Outer Hebrides, drawing attention to the sensitivity of the machair coast to erosion. The aim of this research was to investigate variations and trends in the sensitivity of three field sites within the South Uist machair to soil and coastal erosion, and to interpret measured change alongside analysis of historic climate data. Two of the sites selected, Cille Pheadair and Staoinebrig, experienced some of the most dramatic geomorphological changes associated with the 2005 storm, while the third site, Milton, appeared to be more resistant to change. A combination of fieldwork, laboratory tests, and archive work was used to obtain and analyse information about sediment budgets, shoreline indicator change, and sediment erodibility, along with contextual climatic information. A key result of this work is the provision of a detailed framework of short-medium term cyclical changes and fluctuations in the coastal change, which provides a context for interpreting and responding to longer term trends in erosion and/or accretion. Results indicated high spatial and temporal variability in the erodibility of machair soils and landforms, with no clear relationship between climatic factors and rates of erosion. Considerable short-term variations in beach volume and the position of dynamic shoreline indicators caution against the relaibility of using ‘snap-shot’ historic datasets to infer long-term rates of change. It is proposed that the machair landscape currently functions in a state of highly dynamic equilibrium, which has been maintained over the last ~130 years. While storm events such as the January 2005 storm have locally dramatic consequences, they do not appear to have disrupted the overally physical and ecological functions of the system. This contribution is particularly timely given current concerns for the future of the machair landscape under predicted sea-level and climate change scenarios, and the potential for inappropriate hard-engineering responses to the perceived risk.

Unmanned aerial vehicle (UAV) technology was used to determine tidal extent in Kimages Creek, a restored tidal wetland located in Charles City County, Virginia. A Sensefly eBee Real-Time Kinematic UAV equipped with the Sensor Optimized for Drone Applications (SODA) camera (20-megapixel RGB sensor) was flown during a single high and low tide event in Summer 2017. Collectively, over 1,300 images were captured and processed using Pix4D. Horizontal and vertical accuracy of models created using ground control points (GCP) ranged from 0.176 m to 0.363 m. The high tide elevation model was subtracted from the low tide using the ArcMap 10.5.1 raster calculator. The positive difference was displayed to show the portion of high tide that was above the low tide. These results show that UAVs offer numerous spatial and temporal advantages, but further research is needed to determine the best method of GCP placement in areas of similar forest structure.

<p>Fledermaus is software where different kind of analysis with spatial data can be done. The main area where to use Fledermaus is related to hydrographical surveys. This study is aimed to test and analyse the way Swedish Maritime Administration (Sjöfartsverket) uses Fledermaus. Through step by step explaining how to do when measuring sea bed conditions from a vessel, this text is possible to use as a manual for the applications that are mentioned in this report.</p><p>Another thing that is treated is the squat effect that belongs to vessel dynamic motions. Test of visualization that concerning squat in Fledermaus is done, but with a negative result when squat in a perspective to show motions in height that can be up to about a metre is very hard in a terrain model of thousands of metres. By further tests by arranging the input data, several interesting diagrams have been created through Microsoft Excel where graphs show that the depths are affecting the squat effect. This is showed in same diagram but with two different scales to show the relationship between how a point at the vessel moves in height compared to the depth under the vessel when the vessel is navigating in the sea.</p> / <p>Fledermaus är en programvara där olika analyser med rumsliga data kan genomföras. Största användningsområdet är att använda Fledermaus till mätningar som är relaterade till sjömätning. Den här studien är inriktad till att testa och analysera applikationer som Sjöfartsverket använder sig av i Fledermaus. Genom att steg för steg förklara hur Fledermaus ska användas när bottenförhållanden ska mätas sett från ett fartyg, så blir texten även möjlig att använda som en manual till de applikationer i Fledermaus som är nämnda i denna rapport.</p><p>Det andra som behandlas är squateffekten som tillhör ett fartygs dynamiska rörelser. Test av visualisering som behandlar squat i Fledermaus är genomförd, dock med negativt resultat då squat i ett perspektiv med att visa rörelser i höjd som kan uppgå till runt en meter är väldigt svårt i en terrängmodell som sträcker sig tusentals meter. Dock genom vidare tester genom behandling av indata, har flertalet intressanta diagram skapats genom Microsoft Excel där kurvor visar att djupet inverkar på squateffekten. Detta visas genom att i samma diagram fast med två olika skalor visa förhållandet mellan hur en punkt på båten rör sig i höjd jämfört med att djupet under fartyget ändras då fartyget gör fart genom vattnet.</p>

<p>Proteins belonging to the Cbl family are multidomain scaffolds that participate in numerous processes, assembling signaling complexes and mediating attachment of ubiquitin to receptor and non-receptor tyrosine kinases.</p><p>We characterized a novel role for Cbl and Cbl-b in ligand-dependent internalization of growth factor receptors. Upon stimulation with epidermal growth factor (EGF), Cbl proteins associate with EGF receptor, become phosphorylated, and bind to the three SH3 domains of CIN85, which brings endophilins to the complex with active receptors. Endophilins can induce internalization of the plasma membrane, contributing to formation of clathrin-coated pits. We identified a minimal binding domain for CIN85 in the carboxyl termini of Cbl/Cbl-b and observed constitutive association between CIN85, Cbl/Cbl-b and oncogenically stimulated receptor tyrosine kinases. In addition to functioning as a ubiquitin ligase, Cbl forms a complex with CIN85 and endophilin, which is required for efficient endocytosis and downregulation of membrane receptors.</p><p>In EGF stimulated cells, we observed inducible modification of CIN85 and related CMS proteins by attachment of a single ubiquitin molecule. Monoubiquitination of CIN85 was mediated by the RING finger and dependent on the carboxyl terminal part of Cbl/Cbl-b, and demanded an intact carboxyl terminus of CIN85. Prolonged stimulation with EGF induced concomitant degradation of EGF receptors, Cbl, and monoubiquitinated forms of CIN85 in lysosomes.</p><p>Cbl regulates cytoskeletal processes in a variety of cell systems. We identified SH3P2, a protein with SH3 domain and ankyrin repeats, as a Cbl partner and described its phosphorylation by Src and its distribution in fibroblasts and osteoclasts. SH3P2 formed inducible complexes with Cbl and actin in spread cells and colocalized with dynamic actin structures.</p><p>Our data contribute to better understanding of the role of Cbl in downregulation of receptor tyrosine kinases as well as in controlling actin rearrangement.</p>

The receptor tyrosine kinase (RTK) c-Kit is expressed in hematopoietic stem and progenitor cells, mast cells and in several non-hematopoietic tissues. In the hematopoietic system c-Kit and its ligand Steel Factor (SF, aka Stem Cell Factor) are critical for proliferation, survival and differentiation. Mutations in either receptor or ligand lead to lethal anaemia, hematopoietic stem cell defects, mast cell deficiency and a series of non-hematological defects. The aims of the studies included in this thesis are to describe the signalling pathways downstream c-Kit in hematopoietic stem/progenitor cells and to further analyse the role of c-Kit signalling in fundamental biological functions. To study c-Kit signalling in the hematopoietic system we have employed hematopoietic stem cell-like cell lines which share many properties with primary hematopoietic stem cells in vitro and in vivo, including surface markers, multipotentiality, capacity for self-renewal and long term repopulation. In paper I we demonstrate that upon SF activation the RTK c-Kit is autophosphorylated and downstream signalling mediators are transiently activated. Surprisingly we find that the c-Kit mediated activation of the MAPK pathway is dependent on the activation of phosphoinositide 3-kinase (PI3K) in hematopoietic progenitor cells and that differentiation of these progenitors to mast cells results in a signalling switch where Raf activation changes from PI3K dependent to PI3K independent. We here establish that PI3K activity is required for viability and proliferation of hematopoietic progenitor cells. In paper II we studied the conventional protein kinase C (cPKC) involvement in c-Kit signalling. We observe that the cPKCs can phosphorylate c-Kit on serine 746 and that this phosphorylation negatively regulates the activation of the receptor. We demonstrate that inhibition of this negative phosphorylation results in dramatically increased protein kinase B (PKB) activation and as a consequence inhibition of cPKCs rescues cells from starvation induced apoptosis. Moreover we exhibit that the cPKCs are necessary for full activation of extracellular signal-regulated kinase (Erk) and that impaired PKC activity leads to hampered proliferation. In paper III we demonstrate that in addition to the cPKCs also the novel PKC is required for Erk activation and proliferation. Furthermore we present results indicating that PKC negatively regulates differentiation of bone marrow. In conclusion, with the studies in this thesis we display details in the signalling pathways induced upon RTK c-Kit activation and we demonstrate that c-Kit has significant effects on hematopoietic cell-physiology.