The purpose of this study was to compare the positional accuracy in UAV measurements using three methods: RTK (Real-Time Kinematic), PPK (Post-Processed Kinematic) with base station data, and MakeItAccurate (MIA) with both web service and KlauPPK software. The measurements were conducted at Karlstad University and evaluated against HMK standard levels. The study investigated the positional accuracy in UAV measurements. Data were collected using RTK, PPK with base station data, and post-processing with base station data, MIA's web service, and the KlauPPK software. RTK and PPK with base station data achieved high positional accuracy in the horizontal plane, both meeting HMK standard level 3. RTK showed a Root Mean Square Error (RMSE) of 0.026 meters horizontally and 0.15 meters vertically, while PPK with base station data showed an RMSE of 0.038 meters horizontally and 0.20 meters vertically. MIA's web service exhibited significant discrepancies in the horizontal plane (0.55 and 0.68 meters, respectively) and varying vertical results, indicating unreliability. MIA in KlauPPK demonstrated consistent but inadequate results in the horizontal plane with an RMSE of approximately 0.81 meters, but good vertical accuracy (0.0438-0.0506 meters), meeting HMK standard level 3. The results indicate that RTK and PPK with base station data performed best in horizontal accuracy but had poorer vertical accuracy. MIA's web service was the least reliable method, while MIA in KlauPPK showed better vertical accuracy but poorer horizontal accuracy. In conclusion, no methods alone meet HMK standard level 3 in horizontal and vertical planes without ground support. For further assurance, more measurements and calculations under varying conditions and expanded testing in different environments are recommended. / Syftet med denna studie var att jämföra lägesnoggrannheten vid UAV-mätningar med tre metoder: RTK (Real-Time Kinematic), PPK (Post-Processed Kinematic) med basstationsdata, och MakeItAccurate (MIA) med både webbtjänst och programvaran KlauPPK. Mätningarna utfördes vid Karlstads universitet och utvärderades mot HMK standardnivåer. Under arbetet undersöktes lägesnoggrannheten vid UAV-mätningar. Data samlades in med RTK, PPK med basstationsdata, och efterberäkning med skedde med basstationsdata, MIA:s webbtjänst och KlauPPK-programvaran. RTK och PPK med basstationsdata uppnådde hög lägesnoggrannhet i plan, där båda uppfyllde HMK standardnivå 3. RTK visade en RMS på 0,026 meter i plan och 0,15 meter i höjd, medan PPK med basstationsdata visade en RMS på 0,038 meter i plan och 0,20 meter i höjd. MIA:s webbtjänst visade stora avvikelser i plan (0,55 respektive 0,68 meter) och varierande höjdresultat, vilket indikerar opålitlighet. MIA i KlauPPK visade konsekventa men otillräckliga resultat i plan med en RMS på cirka 0,81 meter, men god höjdnoggrannhet (0,0438–0,0506 meter), som uppfyllde HMK standardnivå 3. Resultaten visar att RTK och PPK med basstationsdata presterade bäst i plan noggrannhet, men har sämre höjdnoggrannhet. MIA:s webbtjänst var den mest opålitliga metoden, medan MIA i KlauPPK visar bättre höjdnoggrannhet men sämre noggrannhet i plan. Slutsatsen är att ingen av metoderna ensam uppfyller HMK standardnivå 3 i både plan och höjd utan markstöd. För ytterligare säkerhet rekommenderas fler mätningar och beräkningar under varierande förhållanden, samt utökad testning i olika miljöer.

Rab5 (Ras-related in brain) and Rab4 are small monomeric GTPases that mediate the intracellular trafficking of endocytosed growth factor receptors. Active Rab5-GTP has low intrinsic GTP hydrolysis activity that is stimulated by GTPase activating proteins (GAPs) to make inactive Rab5-GDP. GAPs provide both a catalytic arginine and switch region stabilization functions. The p85 regulatory subunit of phosphatidylinositol 3′-kinase (PI3K) has GAP activity towards Rab5 and Rab4, which is not seen in other PI3Ks. The arginine “finger” residue within p85 is R274. It is unlikely that p85 stabilizes the switch regions of Rab5, which undergo large conformational changes between activation states, because it interacts with both Rab5-GTP and Rab5-GDP. In contrast, the PI3K catalytic subunit p110β binds only Rab5-GTP, suggesting it interacts with the switch regions. Thus, the GAP functions may be provided to Rab5 by the subunits of PI3K acting together, where p85 provides the arginine finger and p110β stabilizes the switch regions. The binding interface of Rab5:p85 was sought using mutations of Rab5 residues not present in the switch regions which were conserved in p85-binding Rab proteins (S84, E106, N113, F145, E172, M175, K179, K180) in GST pull-down experiments with FLAG-p85. The p85 binding site was not resolved with these experiments, suggesting that p85 interaction may involve the contribution of multiple residues of the Rab5 protein. The p110β interaction site on Rab5 was investigated using Rab5 switch region mutants. Pull-down experiments using a stabilized p110 protein construct, where the p85-iSH2 domain was fused to p110 (alpha or beta), were performed. Rab5 mutants I53A, F57A, W74A, Q79L, E80R, Y82A, H83E, L85A, M88A, Y89A and R91E showed reduced p110β binding. All of these residues except E80 and H83 are involved in binding other Rab5 effectors. The Rab5 binding site on p110β was also resolved through mutation of p110β in its Ras binding domain, and includes residues I234, E238 and Y244. This generation of non-binding mutants of both Rab5 and p110β will be invaluable in the characterization of the importance of the p110β:Rab5-GTP interaction for receptor trafficking to endosomes in mammalian cells.

This thesis examines the current implementations for the distribution of real-time GNSS data over IP networks such as the public Internet, focusing on two essential components of the system, data format and transport protocol. The provision of a suitable data format will allow users to take full advantage of the real-time GNSS data distribution system. Types of GNSS supported, message sizes, data rates, data precision levels, hardware and software support and possible future developments are investigated. An analysis is carried out on commonly known GNSS data formats, highlighting the most suitable standard for each evaluation criterion. A similar investigation is carried out on the transport protocols. An analysis is conducted on various design aspects of NTRIP and RT-IGS protocols, covering factors such as data latency, integrity, firewalls and proxy server compatibility and scalability. The analysis also covers the design aspects of the new draft Version 2 of NTRIP. The latter parts of this thesis report on the experiment results aimed at providing assessment of the current level of implementation of NTRIP. Data latency and integrity using NTRIP over the Internet are examined. Their impacts on users applications as the quality of real-time kinematic positioning is assessed. The results show that the performance of the system satisfies the rigorous requirement of the end-user application. The draft version of the new NTRIP indicates that UDP will be also supported. A similar investigation is carried out, providing the first experiment results on the new option. Tests using similar metrics, data latency and integrity, were carried out to verify the inherent differences between TCP and UDP. It was ascertained that, in most cases, UDP does offer improvement in terms of reduced latency over TCP. However this improvement is not significant enough to affect the performance of users applications tested. Compatibility tests were also carried out and the test results show that the new option experiences some compatibility issues with firewalls and wireless networks.

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No description available.

Melanoma manifests itself from the malignant transformation of melanocytes and represents the deadliest form of skin cancer, being responsible for the disproportionate majority of all skin cancer deaths. The 2002 discovery that 50% of all melanoma patients possess activating BRAF mutations ignited a significant paradigm shift in the way the melanoma field approached research and how patients were treated [1]. The era of targeted therapy had begun and with it came successful targeted BRAF inhibitor therapy regimens, which have accomplished improved clinical benefit (response rate, progression free survival, and overall survival) compared with treatment with chemotherapy in three phase III clinical trials [2]. Although there has been much success in the subgroup of patients whose melanomas harbor activating BRAF mutations, approximately 50% of all melanoma patients do not harbor BRAF mutations. This subgroup of melanoma is composed of ~15-20% of all patients with NRAS mutations and another ~25-30% of patients with neither BRAF nor NRAS mutations. Successful targeted treatment strategies are currently lacking for this subgroup of BRAF-wild type melanomas and therefore novel targeted therapeutic modalities are urgently needed. The work described in this dissertation sheds light on potential approaches for the treatment of BRAF wild type melanoma and will be split into three separate strategies. The first will focus upon the treatment of melanomas without BRAF or NRAS mutations (BRAF/NRAS wild type melanoma) and will expand upon a clinical observation where two melanoma patients were treated with an experimental combination of carboplatin and paclitaxel, with the addition of the AKT inhibitor MK-2206. We demonstrate that the inhibition of AKT significantly enhances the efficacy of chemotherapy in a reactive oxygen species (ROS) mediated fashion, and an induction of autophagy plays a cyto-protective role. The second story focuses upon the treatment of NRAS mutant melanomas by investigating resistance mechanisms to MEK inhibitor treatment. We discovered a MEKi-mediated induction of receptor tyrosine kinase (RTK) signaling to serve as a significant mechanism of escape for NRAS mutant melanomas treated chronically with the MEK inhibitor AZD6244, as well as the recently U.S. Food and Drug Administration (FDA) approved MEK inhibitor trametinib. Novel targeted therapy combinations were then added to overcome the escape from MEK inhibitor therapy. Co-targeting of the receptor tyrosine kinases AXL, PDGFR-β and c-MET with a pan-RTK inhibitor, as well as the mitogen-activated protein kinase (MAPK) pathway with a MEK inhibitor greatly enhanced treatment-induced apoptosis and inhibition of proliferation. The final strategy builds upon the observation that single agent MEK-inhibition is largely ineffective in the treatment of NRAS mutant melanomas. A recovery of MAPK pathway activity in response to MEK inhibition was established to play a significant role in escape of NRAS mutant cells from cell cycle arrest and apoptosis. The combination of a MEK inhibitor with the novel ERK inhibitor VTX-11e prevents the onset of resistant clones and enhances cytotoxicity of the NRAS mutant melanoma cells. This body of work establishes original targeted therapy combinations for the treatment of both NRAS mutant melanomas and BRAF/NRAS wild type melanomas. We propose future clinical investigation with these strategies in the treatment of BRAF wild type melanoma patients in hopes to further extend overall survival.

The speed and accuracy of conservation planning could be improved if maps indicating areas where grassed waterways should be placed to reduce erosion could be easily created. For five central Kentucky fields, elevation data were obtained with real time kinematic (RTK) global positioning system (GPS) and from US Geological Survey (USGS) digital elevation models (DEMs). Terrain attributes were calculated from these datasets which were used as predictor variables for neural network and logistic regression analyses. Grassed waterway prediction models were developed with these analyses. The type of activation function, type of standardization procedure, number of neurons, number of preliminary runs, and number of hidden layers had little impact on the results of the neural network analysis. Logistic regression and neural network analyses produced similar erosion prediction maps. The type of flow direction algorithm used to calculate terrain attributes did not change prediction maps substantially. Grassed waterways could be predicted in most cases with the RTK data but only in some cases with the USGS data. This modeling approach was robust and could aid conservation planners in identifying suitable areas for waterways more efficiently if accurate elevation data can be acquired.

This thesis examines the current implementations for the distribution of real-time GNSS data over IP networks such as the public Internet, focusing on two essential components of the system, data format and transport protocol. The provision of a suitable data format will allow users to take full advantage of the real-time GNSS data distribution system. Types of GNSS supported, message sizes, data rates, data precision levels, hardware and software support and possible future developments are investigated. An analysis is carried out on commonly known GNSS data formats, highlighting the most suitable standard for each evaluation criterion. A similar investigation is carried out on the transport protocols. An analysis is conducted on various design aspects of NTRIP and RT-IGS protocols, covering factors such as data latency, integrity, firewalls and proxy server compatibility and scalability. The analysis also covers the design aspects of the new draft Version 2 of NTRIP. The latter parts of this thesis report on the experiment results aimed at providing assessment of the current level of implementation of NTRIP. Data latency and integrity using NTRIP over the Internet are examined. Their impacts on users applications as the quality of real-time kinematic positioning is assessed. The results show that the performance of the system satisfies the rigorous requirement of the end-user application. The draft version of the new NTRIP indicates that UDP will be also supported. A similar investigation is carried out, providing the first experiment results on the new option. Tests using similar metrics, data latency and integrity, were carried out to verify the inherent differences between TCP and UDP. It was ascertained that, in most cases, UDP does offer improvement in terms of reduced latency over TCP. However this improvement is not significant enough to affect the performance of users applications tested. Compatibility tests were also carried out and the test results show that the new option experiences some compatibility issues with firewalls and wireless networks.

Orientador: João Francisco Galera Monico / Banca: Leonardo Castro de Oliveira / Banca: Mauro Issamu Ishikawa / Resumo: Os avanços tecnológicos nos métodos de posicionamento têm possibilitado o desenvolvimento de metodologias que viabilizam a sua utilização pelo usuário numa diversidade de aplicações. Um dos métodos de posicionamento GNSS (Global Navigation Satellite System) de grande destaque é o RTK (Real Time Kinematic) utilizando o conceito de rede de estações. Esse método utiliza a infra-estrutura de uma rede de estações de referência, para disponibilizar correções ao usuário. O conceito clássico do RTK tem como princípio básico a alta correlação dos erros provocados pela ionosfera, troposfera e órbita dos satélites na estação de referência e em uma estação próxima de interesse. No entanto, com o afastamento entre o usuário e a estação base, a eficiência do método é degradada, pois a correlação dos erros é reduzida. Mas, quando se utiliza uma rede de estações de referência, pode-se realizar a modelagem dos erros na área de abrangência da rede. Esta concepção é denominada de RTK em Rede. No que concerne a rede de estações de referência GNSS, utilizou-se a rede estabelecida no oeste do estado de São Paulo (rede GNSS-SP). O software adotado para realizar o processamento em rede foi o GPSNet na versão 2.73. Outra questão levantada foi com relação aos padrões disponíveis para a transmissão dos dados ao usuário, tais como o RTCM e CMR, mostrando as evoluções e aplicações. A questão do enlace de comunicação (link) também foi abordada, mostrando os principais tipos disponíveis, mas com ênfase na telefonia móvel que foi utilizada para transmitir os dados via internet. Foram conduzidos vários experimentos... (Resumo completo, clicar acesso eletrônico abaixo) / Abstract: Technological advances in positioning methods have enabled the development of methodologies that allow its use in a great variety of applications. One method of GNSS (Global Navigation Satellite System) positioning of high performance is the RTK (Real Time Kinematic) network. This method uses the infrastructure of a network of reference stations. The original concept of RTK is the high correlation of the errors caused by ionosphere, troposphere and satellite orbit at a reference station and at a nearby station of interest. However, increasing the distance between the user and the base station, the efficiency of the method is degraded, because the error correlation is reduced. But when using a network of reference stations, a better error modeling in the area of the network is possible. This concept is the so called Network RTK. Regarding the network of GNSS reference stations, in this work the established network in the western state of São Paulo (GNSS network-SP) was used. The software adopted to perform the tests in the network was that GPSNet, version 2.73. Another issue raised during the investigation was related to the available standards for transmitting data to the user, such as CMR and RTCM. The developments and applications were presented. The issue of communication link (link) has been addressed, showing the main available types, but with emphasis on mobile phone that was the technology used to transmit data via the Internet. Several experiments were conducted in different locations to examine the integrity, availability and accuracy for RTK positioning and RTK network. The experiments performed with RTK and RTK network (using the concept of VRS (Virtual Reference Station)) showed some problems, probably related to the density of the network. Among them the accuracy, the initialization time span more than expected or even... (Complete abstract click electronic access below) / Mestre

The diploma thesis deals with a testing of the real coordinates accuracy measured in favorable and unfavorable conditions, which are determined by method GNSS RTK. The work explores the real accuracy and reliability of heights measurement with the signal noise and multipath interference occurring, caused by surrounding vegetation, buildings, power lines, and also the accuracy under optimal conditions while measuring in a meadow. Influence of day time, observation length, correction provider to internal and external precision is watched. It also examines the issues of initialization in these conditions. For this purpose was collected set of statistics containing 960 measurements on 30 points. During survey was used apparatus Trimble R4. GNSS measurements were statistically processed and evaluated and finally the results were compared with the results of Bc. Klára Kordasová, who measured the same tested points with identical methodology using apparatus from Leica company. Results of the thesis can be used in praxis.