The emerging GNSSs make single-frequency (SF) RTK positioning possible. In this contribution two different types of low-cost (few hundred USDs) RTK receivers are analyzed, which can track L1 GPS, B1 ...BDS, E1 Galileo and L1 QZSS, or any combinations thereof, for a location in Dunedin, New Zealand. These SF RTK receivers can potentially give competitive ambiguity resolution and positioning performance to that of more expensive (thousands USDs) dual-frequency (DF) GPS receivers. A smartphone implementation of one of these SF receiver types is also evaluated. The least-squares variance component estimation (LS-VCE) procedure is first used to formulate a realistic stochastic model, which assures that our receivers at hand can achieve the best possible ambiguity resolution and RTK positioning performance. The best performing low-cost SF RTK receiver types are then assessed against DF GPS receivers and survey-grade antennas. Real data with ionospheric disturbances at low, medium and high levels are analyzed, while making use of the ionosphere-weighted model. It will be demonstrated that when the presence of the residual ionospheric delays increases, instantaneous RTK positioning is not possible for any of the receivers, and a multi-epoch model is necessary to use. It is finally shown that the low-cost SF RTK performance can remain competitive to that of more expensive DF GPS receivers even when the ionospheric disturbance level reaches a Kp-index of 7−, i.e. for a strong geomagnetic storm, for the baseline at hand.
PPP-RTK combines the advantages of both precise point positioning (PPP) and real-time kinematic (RTK) techniques. While constructing PPP-RTK models based on undifferenced and uncombined observations ...offers apparent benefits, these observation equations suffer from a rank deficiency issue. To address this problem, the Singularity-system (S-system) theory can be utilized. This theory imposes constraints on a minimal subset of parameters, known as the S-basis, by setting them to arbitrary values, typically zeros. Despite the existence of multiple options for the S-basis, prevailing research conventionally selects the parameters of one receiver—the pivot—as the S-basis. In this study, we depart from this practice by selecting the mean of receiver-related parameters as the S-basis. This departure prompts an exploration into how the S-basis choices influence PPP-RTK outcomes regarding network product precision and user positioning performance. Our comparative analysis of the mean receiver (MR) and pivot receiver (PR) models unveils distinctions in the combined product precision. These products include satellite clocks, satellite phase biases, and ionospheric delays (excluding tropospheric delays). The distinction emerges because the estimable satellite clocks in the PR model incorporate atmospheric delays specific to the pivot receiver, in contrast to the MR model, which integrates mean atmospheric delays from all receivers. Despite the distinction in the analytical form of combined product and its precision, both model results in similar positioning performance. This is because variations in product precision levels caused by selecting different atmospheric parameters as the S-basis can be nullified by the parameterized atmospheric delays on the user side. With the inclusion of tropospheric delays, the PR and MR models also demonstrate similar performance and yield more accurate user positioning when located near the pivot receiver compared to positions farther from the pivot receiver when employing ambiguity-float network products. This dependence on the pivot receiver stems from both models selecting the pivot receiver ambiguities as the S-basis, while opting for mean ambiguities across all receivers negates the integer nature of ambiguities. Our conclusion underscores that identical positioning outcomes in PR and MR PPP-RTK models rely on both models selecting the same ambiguities as the S-basis. This highlights the potential variability in PPP-RTK performance when different ambiguity parameters are selected as the S-basis, particularly in the absence of network integer ambiguity resolution.
Galileo is Europe’s Global Navigation Satellite System (GNSS), which provides improved positioning and timing data with significant benefits for many European services and users. Galileo enables ...users to know their exact location with greater precision than other available systems. Access to the Galileo signal in the obstructed and unobstructed environment provides benefits and opportunities for work, thanks to the improved performance and accuracy. The use of a Galileo-enabled receiver increases the number of satellites in view significantly. When compared to the performance of single-constellation receivers, this significantly reduces the time required to obtain a position with centimetre-level accuracy. The results indicate the current Galileo constellation’s suitability for high-precision RTK applications, as well as improved availability, accuracy, reliability, and time-to-fix in the obstructed and unobstructed environments. The results of RTK GPS and RTK GPS/Galileo obtained at different times of the same day by using two reference points were compared. The results of this study illustrate that integrating RTK GPS system with Galileo is favorable for surveying applications (cm accuracy). This study shows that in surveying applications requiring centimetre accuracy, the RTK GPS/Galileo method can replace other survey methods (Total Station).
Normal receptor tyrosine kinases (RTKs) need to reach the plasma membrane (PM) for ligand-induced activation, whereas its cancer-causing mutants can be activated before reaching the PM in organelles, ...such as the Golgi/trans-Golgi network (TGN). Inhibitors of protein export from the endoplasmic reticulum (ER), such as brefeldin A (BFA) and 2-methylcoprophilinamide (M-COPA), can suppress the activation of mutant RTKs in cancer cells, suggesting that RTK mutants cannot initiate signaling in the ER. BFA and M-COPA block the function of ADP-ribosylation factors (ARFs) that play a crucial role in ER–Golgi protein trafficking. However, among ARF family proteins, the specific ARFs inhibited by BFA or M-COPA, that is, the ARFs involved in RTKs transport from the ER, remain unclear. In this study, we showed that M-COPA blocked the export of not only KIT but also PDGFRA/EGFR/MET RTKs from the ER. ER-retained RTKs could not fully transduce anti-apoptotic signals, thereby leading to cancer cell apoptosis. Moreover, a single knockdown of ARF1, ARF3, ARF4, ARF5, or ARF6 could not block ER export of RTKs, indicating that BFA/M-COPA treatment cannot be mimicked by the knockdown of only one ARF member. Interestingly, simultaneous transfection of ARF1, ARF4, and ARF5 siRNAs mirrored the effect of BFA/M-COPA treatment. Consistent with these results, in vitro pulldown assays showed that BFA/M-COPA blocked the function of ARF1, ARF4, and ARF5. Taken together, these results suggest that BFA/M-COPA targets at least ARF1, ARF4, and ARF5; in other words, RTKs require the simultaneous activation of ARF1, ARF4, and ARF5 for their ER export.
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•A series of thiourea derivatives were designed and synthesized as antitumor and antiangiogenic agents.•Excellent anti-proliferative effects against HUVECs and multiple cancer cell ...lines.•The inhibition of cancer cell malignant transformation and angiogenesis.•Excellent antiangiogenic activities.
A series of novel thiourea derivatives were synthesized and evaluated by biological activities. Among them, compound 10e containing 3,5-bis(trifluoromethyl)phenyl moiety (R1) at the terminal thiourea and phenylamino (R2) at the terminal acyl position showed the best cytotoxic activities against seven cancer cell lines (NCI-H460, Colo-205, HCT116, MDA-MB-231, MCF-7, HepG2, PLC/PRF/5) and HUVECs. Moreover, compound 10e moderately inhibited various RTKs such as VEGFR2, VEGFR3, and PDGFRβ. Notably, 10e exhibited much better inhibitory effect of tumor formation and antiangiogenic activities than Sorafenib and Regorafenib at the same concentration. Further docking studies suggested that 10e could serve as potential candidate for cancer therapy.
Recent advances in Next Generation Sequencing (NGS) have provided remarkable insights into the genomic characteristics of human cancers that have spurred a revolution in the field of oncology. The ...mitogen-activated protein kinase pathway (MAPK) and its activating cell receptor, the receptor tyrosine kinases (RTKs), which together encompass the (RTK)-RAS-RAF-MEK-ERK axis, are central to oncogenesis. A pan-cancer genomics analysis presented in this review is made possible by large collaborative projects, including The Cancer Genome Atlas (TCGA), the International Cancer Genome Consortium (ICGC), and others. Landmark studies contributing to these projects have revealed alterations in cell signaling cascades that vary between cancer types and within tumors themselves. We review several of these studies in major tumor types to highlight recent advances in our understanding of the role of (RTK)-RAS-RAF alterations in cancer. Further studies are needed to increase the statistical power to detect clinically relevant low-frequency mutations, in addition to the known (RTK)-RAS-RAF pathway alterations, and to refine the resolution of the genomic landscape that defines these cancer mutations. The (RTK)-RAS-RAF-MEK-ERK mutation status, and their prognostic value, are also examined and correlated with clinical phenotypes. Treatments targeting various components of this pathway are ongoing, and are often effective initially in defined subgroups of patients. However, resistance to these agents can develop through adaptive mechanisms. With our steady increase in understanding the molecular biology of cancer, ongoing evaluation and monitoring through genomic analysis will continue to provide important information to the clinician in the context of treatment selection, response, resistance and outcomes.
Multi-agent cooperative positioning (CP) is widely applied in many applications of unmanned ground vehicles and unmanned aerial vehicles. Global Navigation Satellite System (GNSS) is an effective ...tool to conduct CP on a large scale. However, the performance of traditional GNSS-based CP algorithms is limited by the accuracy of single-agent self-positioning. In this paper, we propose a robust GNSS-based cooperative algorithm to achieve instantaneous precise positioning of multiple agents. In the proposed algorithm, precise point positioning-real-time kinematic (PPP-RTK) is utilized to conduct single-agent self-positioning, which is capable of achieving centimeter-level positioning rapidly with precise atmospheric corrections. Moreover, inter-agent associations derived from double-differenced carrier-phase observations and inter-epoch associations obtained via time-differenced carrier-phase observations are integrated with single-agent self-positioning by a factor graph-based optimizer. To evaluate the proposed scheme, real-world experiments with four agents in different scenarios were carried out. Based on the 30-minute field experimental results, the proposed scheme showed superior positioning performance with minimum and maximum three-dimension root mean square errors (3D-RMSEs) of 5.9 cm and 10.3 cm, respectively. It turned out that benefiting from PPP-RTK's characteristic of achieving precise positioning, the proposed method can converge to centimeter-level accuracy instantaneously.
Precise point positioning–real-time kinematic (PPP-RTK) achieves fast convergence in global navigation satellite system (GNSS) positioning and navigation. Correcting slant ionospheric delays is ...crucial for this purpose. One way to obtain the slant ionospheric corrections is by interpolating from nearby reference stations. However, the interpolation performance depends on many factors, such as time, elevation, and distance. This article aims to study the performance of three interpolation algorithms, i.e., inverse-distance weighting (IDW), radial basis function (RBF), and Kriging, under different ionospheric conditions. For inhomogeneously distributed ionospheric density, the performance of IDW is unsatisfying compared with the other two methods. In addition, we represent uncertainties on a 2-D map and find that the uncertainties increase on average linearly with distance. Elevation also plays an important role in interpolation uncertainty. Comprehensively, we build a mathematical model between the uncertainties of different interpolation methods as a function of time, elevation, and distance. They all degrade significantly with a large rate of change in the total electron content index (ROTI). Finally, we validate the proposed uncertainties by applying them to PPP-RTK processing. A convergence time within 2 min and positioning accuracy within 3.5 cm in horizontal and 6 cm in vertical directions are achieved.
Dengan berkembangnya teknologi dalam survei pemetaan seperti halnya penggunaan GPS Geodetik, maka penerapan dari teknologi untuk kebutuhan survei perlu memperhatikan faktor-faktor tertentu seperti ...ketersediaan alat, sumber daya manusia hingga kondisi lapangan. GPS atau biasa dikenal dengan Global Positioning System merupakan teknologi/alat atau sistem yang memberikan informasi berupa posisi kepada pengguna secara global dan real-time di permukaan bumi yang berbasis data satelit. Dengan teknologi tersebut diperoleh ketelitian yang tinggi dengan waktu yang singkat dalam penentuan sebuah posisi. Penelitian ini bertujuan untuk mengetahui ketelitian hasil pengukuran luas bidang tanah menggunakan teknologi GPS RTK-Radio dan GPS RTK NTRIP sebagai sikap pengambilan keputusan. Penelitian dilakukan terhadap daerah dengan obstruksi dan tanpa obstruksi fisik. Nantinya, dari penelitian ini diperoleh nilai-nilai koordinat (X,Y) dari GPS RTK-NTRIP maupun RTK-Radio, yang kemudian dihitung luasnya dan dibandingkan dari hasil pengukuran menggunakan ETS (Electronic Total Station) terhadap standar ketelitian luas dari BPN. Hasil perhitungan selisih luas lahan baik dengan obstruksi secara fisik maupun tidak, masih masuk dalam toleransi ketelitian BPN, walaupun untuk lahan yang terdapat obstruksi fisik memiliki selisih antara pengukuran menggunakan GPS dan ETS yang cukup besar yaitu hampir mencapai 5 m2.
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