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The navigation technology has developed rapidly and immensely over the past few decades. Among the multiple navigation technologies, the representative and promising techniques are Real-time Kinematic (RTK) technique and Simultaneous Localization and Mapping (SLAM). RTK can provide real-time positioning results with high accuracy, while SLAM can not only locate the user but also construct a map of the new ambient. The first smartphone, the Xiaomi MI 8, equipped with the dual-frequency Global Navigation Satellite System (GNSS), hit the market in May 2018, providing valid carrier-phase measurements for RTK owe to the developer option of ”Force full GNSS measurements.” Nevertheless, RTK underperforms in urban areas as the buildings and trees can block the satellite signals. RTK cannot even provide positioning results when the GNSS outage happens. However, SLAM can effectively make up the drawbacks of RTK as it utilizes no more information than the images. SLAM can also be combined with the Inertial Measurement Unit (IMU) called Visual-Inertial SLAM (VI-SLAM,) with the improvement of accuracy and robustness. Therefore, our study mainly aims to confirm the feasibility of continuous positioning based on RTK and VI-SLAM with the Xiaomi MI 8. An application is developed to execute the functions, including logging images, measurements of IMU, and GPS measurements in Receiver INdependent EXchange (RINEX) format with the Xiaomi MI 8. The performances of RTK with and without the assistance of VI-SLAM are assessed respectively in the urban area. The experimental results demonstrate that the combination of RTK and VI-SLAM based on smartphones can effectively provide continuous positioning results. We believe our application will facilitate research and development in relation to positioning algorithms. Readers have access to this application at https://github.com/Nronaldo/CIGRLogger.

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., Competing Interests: Conflict of interest The authors declare that they have no conflicts of interest with the contents of this article., (Copyright © 2024 The Authors. Published by Elsevier Inc. All rights reserved.)

Oncoprotein expression is controlled at the level of mRNA translation and is regulated by the eukaryotic translation initiation factor 4F (eIF4F) complex. eIF4A, a component of eIF4F, catalyzes the unwinding of secondary structure in the 5'-untranslated region (5'-UTR) of mRNA to facilitate ribosome scanning and translation initiation. Zotatifin (eFT226) is a selective eIF4A inhibitor that increases the affinity between eIF4A and specific polypurine sequence motifs and has been reported to inhibit translation of driver oncogenes in models of lymphoma. Here we report the identification of zotatifin binding motifs in the 5'-UTRs of HER2 and FGFR1/2 Receptor Tyrosine Kinases (RTKs). Dysregulation of HER2 or FGFR1/2 in human cancers leads to activation of the PI3K/AKT and RAS/ERK signaling pathways, thus enhancing eIF4A activity and promoting the translation of select oncogenes that are required for tumor cell growth and survival. In solid tumor models driven by alterations in HER2 or FGFR1/2, downregulation of oncoprotein expression by zotatifin induces sustained pathway-dependent anti-tumor activity resulting in potent inhibition of cell proliferation, induction of apoptosis, and significant in vivo tumor growth inhibition or regression. Sensitivity of RTK-driven tumor models to zotatifin correlated with high basal levels of mTOR activity and elevated translational capacity highlighting the unique circuitry generated by the RTK-driven signaling pathway. This dependency identifies the potential for rational combination strategies aimed at vertical inhibition of the PI3K/AKT/eIF4F pathway. Combination of zotatifin with PI3K or AKT inhibitors was beneficial across RTK-driven cancer models by blocking RTK-driven resistance mechanisms demonstrating the clinical potential of these combination strategies. [ABSTRACT FROM AUTHOR]

• Dopamine (DA) increased kainate-induced γ oscillations in the CA3 area of rat hippocampal slices. • DA-mediated increase in γ power is associated with dopamine receptor (DR) 1 and 2 activation. • Receptor tyrosine kinase (RTK) and ERK are the main intracellular kinases that mediate DA enhancement of γ. • DA-mediated enhancement of γ oscillation is involved in the activation of DR1/2-RTK-ERK signaling pathway. Network oscillations at γ frequency band (30–80 Hz), generated by the interaction between inhibitory interneurons and excitatory neurons, have been proposed to be associated with higher brain functions such as learning and memory. Dopamine (DA), one of the major CNS transmitters, modulates hippocampal γ oscillations but the intracellular mechanisms involved remain elusive. In this study, we recorded kainate-induced γ oscillations in the CA3 area of rat hippocampal slices, and found that DA strongly enhanced γ power, which was largely blocked by dopamine receptor 1 (DR1) antagonist SCH23390, receptor tyrosine kinase (RTK) inhibitor UNC569 and ERK inhibitor U0126, partially blocked by D2/3R antagonist raclopride, PKA inhibitor H89 and PI3K inhibitor wortmannin, but not affected by AKT inhibitor TCBN or NMDAR antagonist D-AP5. Our results indicate that DA-mediated γ enhancement is involved in the activation of signaling pathway of DR1/2-RTK-ERK. Our data demonstrate a strong, rapid modulation of DA on hippocampal γ oscillations and provide a new insight into cellular mechanisms of DA-mediated γ oscillations. [ABSTRACT FROM AUTHOR]

Aiming at the problems of scale uncertainty, traj ectory drift caused by accumulated errors in large scenes and relative pose in a local coordinate system when monocular vision SLAM was used for pose estimation of U AV aerial images, this paper proposed a real-time pose estimation scheme for U AV aerial images. Firstly, this scheme tracked the visual image in real time, then obtained the transformation relationship between the visual coordinate system and the world coordinate system by introducing RTK information, and solved the problems of scale uncertainty and trajectory drift. Finally, it obtained a pose in the world coordinate system. Considering that the video stream processed by visual SLAM would process redundant images and increase the pressure of image storage, shooting and calculation, this scheme used the processing of discontinuous low overlap images to calculate the pose to avoid these problems. In real scene experiments, the experimental results show that the accuracy of the scheme is higher than that of the current mainstream open source frameworks ORB-SLAM2, DSO and OpenMVG, and the average of the overall trajectory error is less than 10 cm. [ABSTRACT FROM AUTHOR]

Altered receptor tyrosine kinase (RTK) signaling contributes to tumorigenesis and suppression of immune-mediated destruction of cancer cells. Cabozantinib is an oral tyrosine kinase inhibitor that inhibits several RTKs involved in tumorigenesis, and is approved for the treatment of patients with progressive metastatic medullary thyroid cancer, advanced renal cell carcinoma, and hepatocellular carcinoma that has been previously treated with sorafenib. We present an up-to-date evaluation of preclinical evidence for RTK inhibition with cabozantinib, specifically VEGFR, MET, KIT, RET, AXL, FLT3, and associated antitumor effects. Preclinical investigations of cabozantinib in combination with other anticancer drugs are also reviewed. Preclinical evidence shows that cabozantinib has antitumor activity against various cancer cells and exhibits synergy with other anticancer agents, including immune checkpoint inhibitors and hormone receptor or metabolic pathway inhibitors. Further optimization of cabozantinib treatment requires the identification of biomarkers of response and resistance, and exploration of complementary drug targets. Investigation of mechanisms of adaptive resistance, such as epithelial to mesenchymal transition (cancer intrinsic) and immunomodulation by the tumor microenvironment (cancer extrinsic), as well as identification of novel drug targets based on characterization of cancer stem cell metabolomic phenotypes, appear to be promising approaches. [ABSTRACT FROM AUTHOR]

Centimetre accurate geolocation service is beneficial to a wide range of applications, ranging from sports engineering, civil infrastructure, autonomous vehicles, surveying to digitisation of historically significant structures. Previously, these features were confined to prohibitively expensive commercial hardware, requiring technical knowledge and experience to operate. Continued technological advancements have seen the miniaturisation of electronics and antennas, coupled with an increase in the number and performance of global navigation satellite systems (GNSS) by various nations and organisations, providing global signal coverage. This paper demonstrates a low-cost, mobile, real-time kinematic (RTK) geolocation service for engineering and research applications, fabricated from components readily available from commercial suppliers. This solution, consisting of a mobile RTK base station and RTK rover, provides centimetre-accuracy performance up to a distance of 15 km away from the base station. Correction data is transmitted over the internet using free and open software solutions. The small footprint of both the RTK base station and RTK rover, provides versatile applications even in remote locations. The performance of the geolocation service is validated using field experiments, comparing measurements against state-of-the-art photogrammetry, light detection and ranging (LiDAR) and digital level measurement technologies. The authors encourage the adoption of the RTK geolocation solution based on the calibrated results.

Unmanned Aircraft Systems (UAS) are used in a variety of applications with the aim of mapping detailed surfaces from the air. Despite the high level of map automation achieved today, there are still challenges in the accuracy of georeferencing that can limit both the speed and the efficiency in mapping urban areas. However, the integration of topographic grade Global Navigation Satellite System (GNSS) receivers on UAS has improved this phase, leading to a reach of up to a centimeter-level accuracy. It is therefore necessary to adopt direct georeferencing (DG), real-time kinematic positioning (RTK)/post-processed kinematic (PPK) approaches in order to largely automate the photogrammetric flow. This work analyses the positional accuracy using Ground Control Points (GCP) and the repeatability and reproducibility of photogrammetric products (Digital Surface Model and ortho-mosaic) of a commercial multi-rotor system equipped with a GNSS receiver in an urban environment with a DG approach. It was demonstrated that DG is a viable solution for mapping urban areas. Indeed, PPK with at least 1 GCP considerably improves the RMSE (x: 0.039 m, y: 0.012 m, and z: 0.034 m), allowing for a reliable 1:500 scale urban mapping in less time when compared to conventional topographic surveys.

Global Navigation Satellite Systems provide autonomous vehicles with precise position information through the process of position augmentation. This paper presents a series of performance tests aimed to compare the position accuracy of augmentation techniques such as classical Differential Global Navigation Satellite System, Real-time Kinematic and Real-time eXtended. The aim is to understand the limitations and choose the best position augmentation technique in order to obtain accurate, trustworthy position estimates of a vehicle in urban environments. The tests are performed in and around the German cities of Wuppertal and Duesseldorf, using a vehicle fitted with the navigation system POS-LV 220, developed by Applanix Corporation. In order to evaluate the real-time performance of position augmentation techniques in a highly challenging environment, a total of four test regions are selected. The four test regions are characterized mainly by uneven terrain with tall buildings around the University of Wuppertal, flat terrain with roads of varying width in the city centre of Wuppertal and Duesseldorf and flat terrain in a tunnel section located in the city of Wuppertal. The performances of the different position augmentation are compared using a Root Mean Square (RMS) error estimate obtained as an output from the Applanix system. Furthermore, a High-Definition map of the environment is used for the purpose of model validation, which justifies the use of RMS error estimate as an evaluation metric for the performance analysis tests. According to the performance tests carried out as per the conditions specified in this paper, the Real-time eXtended (RTX) position augmentation method enables to obtain a more robust position information of the vehicle than Real-time Kinematic (RTK) method, with a typical accuracy of a few centimeter in an urban environment.

The global navigation satellite system (GNSS) real-time kinematic (RTK) technique is used to achieve relative positioning centimeter levels among multiple agents on the move. A typical GNSS RTK estimates the relative positions of multiple rover receivers with respect to a single-base receiver. In a fleet of rover GNSS receivers, this approach is inefficient because each rover receiver only uses GNSS measurements of its own and those sent from a single-base receiver. In this study, we propose a novel GNSS RTK framework that facilitates the precise positioning of a swarm of moving vehicles through the GNSS measurements of multiple receivers and broadcasts fixed-integer ambiguities of GNSS carrier phases. The proposed framework not only provides efficient RTK positioning but also reliable performance with a limited number of GNSS satellites in view. Our experimental flight tests with six GNSS receivers showed that the systematic procedure of the proposed framework could maintain lower than 6 cm of 3D RMS positioning errors, whereas the conventional RTK failed to resolve the correct integer ambiguities of double difference carrier phase measurements more than 13% in five out of nine total baselines.

Global Navigation Satellite Systems (GNSS)-based technologies have become an indispensable part of current structural health monitoring (SHM) systems because of the unique capability of the GNSS technologies to provide accurate real-time displacement information. GNSS equipment with a data sampling rate of up to about 20 Hz has been widely used for this purpose. High-rate GNSS systems (typically up to about 100 Hz) offer additional advantages in structural health monitoring as some highly dynamic civil structures, such as some bridges, require high-rate monitoring data to capture the dynamic behaviors. However, the performance of high-rate GNSS positioning in the context of structural health monitoring is not entirely known, as studies on structural monitoring with high-rate GNSS positioning are very limited, especially considering that some of the satellite systems just reached their full constellations very recently. We carried out a series of experiments with the help of a shaking table to assess the SHM performance of a set of 100 Hz GNSS equipment and three commonly used GNSS positioning techniques, PPP (precise point positioning), PPP-AR (precise point positioning with ambiguity resolution), and RTK (real-time kinematic). We found that the standard deviations of the 100 Hz GNSS displacement solutions derived from PPP, PPP-AR, and RTK techniques were 5.5 mm, 3.6 mm, and 0.8 mm, respectively, when the antenna was in quasi-static motion, and about 9.2 mm, 6.2 mm, and 3.5 mm, respectively, when the antenna was in vibration (up to about 0.7 Hz), under typical urban observational conditions in Hong Kong. We also found that the higher a sampling rate is, the lower the accuracy of a measured displacement series is. On average, the 10 Hz and 100 Hz results are 5.5% and 10.3%, respectively, noisier than the 1 Hz results.

In this study, sowing was carried out with 3 different tractor guidance methods: operator-controled, GPS-controled and automatic-controled. The optimum nutrient areas required for each plant were evaluated using voronoi polygons. Voronoi polygons were used to obtain nutrient areas. Voronoi polygons were used to obtain living spaces. The plant coordinates taken with CORS-RTK GPS were loaded into the CBS program and the voronoi polygon for each plant was obtained. Comparison of nutrient areas was made with shape coefficients calculated using polygon area and perimeter values. Shape coefficient was 0.731 in operator-controlled application, 0.746 in GPS-controlled application and 0.715 in automatic-controled application. Compared to operator-controlled application, shape coefficients were found to be 2 % more in GPS-controlled application and 2 % less in automatic-controlled application. Although the shape coefficients are relatively less in the automatic-controlled system, it can be seen that better results can be obtained in terms of field success due to the advantages such as low workload on the operator, ease of application at night and improvements in time utilization coefficient. As a result of the statistical analysis, it has been found that there is no difference between the applications and can be used interchangeably. As a result, when the systems are compared with each other, it is seen that the automatic-controlled application is more successful. [ABSTRACT FROM AUTHOR]

[Display omitted] • Receptor tyrosine kinases (RTKs) regulate pivotal cellular processes and are dysregulated in cancer. • RTKs are extensively glycosylated and this modification affects cellular functions of these receptors. • Galectins are carbohydrate binding proteins implicated in developmental processes and cancers. Galectins directly and indirectly affect RTKs, modulating RTKs activation, their cross-talk with other cell surface proteins and their cellular trafficking. • Galectins are responsible for oncogenic activation of RTKs. • RTK-galectin interplay constitutes an attractive target for development of anti-cancer therapies. Receptor tyrosine kinases (RTKs) constitute a large group of cell surface proteins that mediate communication of cells with extracellular environment. RTKs recognize external signals and transfer information to the cell interior, modulating key cellular activities, like metabolism, proliferation, motility, or death. To ensure balanced stream of signals the activity of RTKs is tightly regulated by numerous mechanisms, including receptor expression and degradation, ligand specificity and availability, engagement of co-receptors, cellular trafficking of the receptors or their post-translational modifications. One of the most widespread post-translational modifications of RTKs is glycosylation of their extracellular domains. The sugar chains attached to RTKs form a new layer of information, so called glyco-code that is read by galectins, carbohydrate binding proteins. Galectins are family of fifteen lectins implicated in immune response, inflammation, cell division, motility and death. The versatility of cellular activities attributed to galectins is a result of their high abundance and diversity of their cellular targets. A various sugar specificity of galectins and the differential ability of galectin family members to form oligomers affect the spatial distribution and the function of their cellular targets. Importantly, galectins and RTKs are tightly linked to the development, progression and metastasis of various cancers. A growing number of studies points on the close cooperation between RTKs and galectins in eliciting specific cellular responses. This review focuses on the identified complexes between galectins and RTK members and discusses their relevance for the cell physiology both in healthy tissues and in cancer. [ABSTRACT FROM AUTHOR]

Rutting is one of the severe pavement distresses. It is defined as longitudinal depression under wheel path, caused by repeated traffic load, and it is an indicator of the structural failure as well as having effect on road user's safety and riding quality. The objectives of this study are to use geomatics techniques such as terrestrial laser scanner, precise positioning system (RTK) and cellular phone for rutting measurements in minor roads in northern part of Jordan, in addition to develop rutting and lateral displacement models using different parameters such as annual average daily traffic (AADT), truck percent, lane width, pavement age and pavement thickness. Manual measurement of rutting was used as reference method for verifying the results obtained from laser scanning, RTK and cellular phone. The study showed that the used methods produced accurate and reliable results compared with the manual method based on root-mean-square (RMSE) which was 0.557 cm for the RTK measurements, 0.577 cm for cellular phone measurements and 0.592 cm of the laser scanner system, respectively. On the other hand, the consistency of accuracy of measurements was slightly better for the cellular phone measurements with a mean average error (MAE) of 0.415 cm, while it was 0.422 cm for the RTK system and 0.442 cm for the laser scanner measurements. The finding of this research will support the development of using geomatics techniques for the measurement of pavement rutting which facilitate the processes and give reliable surface measurement in short time. [ABSTRACT FROM AUTHOR]

The plasma membrane in eukaryotic cells contains microdomains that are enriched in certain glycosphingolipids, gangliosides, and sterols (such as cholesterol) to form membrane/lipid rafts (MLR). These regions exist as caveolae, morphologically observable flask-like invaginations, or as a less easily detectable planar form. MLR are scaffolds for many molecular entities, including signaling receptors and ion channels that communicate extracellular stimuli to the intracellular milieu. Much evidence indicates that this organization and/or the clustering of MLR into more active signaling platforms depends upon interactions with and dynamic rearrangement of the cytoskeleton. Several cytoskeletal components and binding partners, as well as enzymes that regulate the cytoskeleton, localize to MLR and help regulate lateral diffusion of membrane proteins and lipids in response to extracellular events (e.g., receptor activation, shear stress, electrical conductance, and nutrient demand). MLR regulate cellular polarity, adherence to the extracellular matrix, signaling events (including ones that affect growth and migration), and are sites of cellular entry of certain pathogens, toxins and nanoparticles. The dynamic interaction between MLR and the underlying cytoskeleton thus regulates many facets of the function of eukaryotic cells and their adaptation to changing environments. Here, we review general features of MLR and caveolae and their role in several aspects of cellular function, including polarity of endothelial and epithelial cells, cell migration, mechanotransduction, lymphocyte activation, neuronal growth and signaling, and a variety of disease settings. This article is part of a Special Issue entitled: Reciprocal influences between cell cytoskeleton and membrane channels, receptors and transporters. Guest Editor: Jean Claude Hervé.

Changes in cytoprotective signaling may influence cardiac aging, and underpin sensitization to ischemic insult and desensitization to 'anti-ischemic' therapies. We tested whether age-dependent shifts in ischemia-reperfusion (I-R) tolerance in murine and human myocardium are associated with reduced efficacies and coupling of membrane, cytoplasmic and mitochondrial survival-signaling. Hormesis (exemplified in ischemic preconditioning; IPC) and expression of proteins influencing signaling/stress-resistance were also assessed in mice. Mouse hearts (18 vs. 2-4 mo) and human atrial tissue (75±2 vs. 55±2 yrs) exhibited profound age-dependent reductions in I-R tolerance. In mice aging negated cardioprotection via IPC, G-protein coupled receptor (GPCR) agonism (opioid, A1 and A3 adenosine receptors) and distal protein kinase c (PKC) activation (4 nM phorbol 12-myristate 13-acetate; PMA). In contrast, p38-mitogen activated protein kinase (p38-MAPK) activation (1 μM anisomycin), mitochondrial ATP-sensitive K(+) channel (mKATP) opening (50 μM diazoxide) and permeability transition pore (mPTP) inhibition (0.2 μM cyclosporin A) retained protective efficacies in older hearts (though failed to eliminate I-R tolerance differences). A similar pattern of change in protective efficacies was observed in human tissue. Murine hearts exhibited molecular changes consistent with altered membrane control (reduced caveolin-3, cholesterol and caveolae), kinase signaling (reduced p70 ribosomal s6 kinase; p70s6K) and stress-resistance (increased G-protein receptor kinase 2, GRK2; glycogen synthase kinase 3β, GSK3β; and cytosolic cytochrome c). In summary, myocardial I-R tolerance declines with age in association with dysfunctional hormesis and transduction of survival signals from GPCRs/PKC to mitochondrial effectors. Differential changes in proteins governing caveolar and mitochondrial function may contribute to signal dysfunction and stress-intolerance.

Nowadays, the need for a more precise positioning is a very high, therefore very demanding one, and this is one of the reasons why very large research funding is allocated in satellite technology, the second reason being global geopolitics situation. New satellite constellations are being developed existing satellites that have completed their mission are being replaced with satellites that incorporate technology far superior to their predecessors. Currently we have four constellations with global coverage, NAVSTAR-GPS and Glonass, Galileo and Compass. With the development of these global satellite systems, it is also necessary to develop the user segment, so this requires terrestrial reference stations to be updated to recognize the new signals from them. The article presents the situation of the global satellite systems and the situation of the permanent reference networks in Romania, which are developed by state or private companies.

Abstract Background Overexpression of AXL receptor tyrosine kinase (AXL) in various human cancers correlates with reduced patients overall survival and resistance to first line therapies. Therefore, several AXL tyrosine kinase inhibitors (TKIs) are currently under clinical evaluation. Results AXL TKI BMS777607 treatment increased AXL protein levels after 24 h as observed by Western blot and flow cytometry analysis. Mechanistically, this inhibition-induced AXL cell surface accumulation was neither associated with epigenetic modifications, nor altered transcriptional and translational regulation. Further, we saw no impact on glycosylation and receptor shedding by α-secretases. However, we observed that BMS777607 increased the glycosylated 140 kDa AXL protein abundance, which was impaired in the kinase dead mutant AXL (K567R). We demonstrated that AXL kinase activity and subsequent kinase phosphorylation is necessary for GAS6-dependent receptor internalization and degradation. Blocking of kinase function by BMS777607 resulted in ubiquitination prohibition, impaired internalization and subsequent cell surface accumulation. Subsequently, AXL cell surface accumulation was accompanied by increased proliferation of 3D-Speroids induced by low μM levels of BMS777607 treatment. Conclusion Our data suggest a re-evaluation of anti-AXL clinical protocols due to possible feedback loops and resistance formation to targeted AXL therapy. An alternative strategy to circumvent feedback loops for AXL targeting therapies may exist in linkage of AXL TKIs to a degradation machinery recruiting unit, as already demonstrated with PROTACs for EGFR, HER2, and c-Met. This might result in a sustained inhibition and depletion of the AXL from tumor cell surface and enhance the efficacy of targeted anti-AXL therapies in the clinic.

En las últimas décadas la comunidad robótica ha adoptado cada vez más el uso de sensores GPS-RTK para estimar de forma precisa la localización de robots móviles en ambientes exteriores. En este trabajo se presenta la caracterización de un sistema GPS-RTK de bajo costo. A partir del montaje de las unidades base y móvil se adquirieron datos de posición corregidos en tiempo real por el mismo sistema RTK bajo diferentes disposiciones físicas, velocidades de actualización y condiciones ambientales presentándose posteriormente un estudio estadístico de los resultados obtenidos.

In satellite navigation receivers, the hardware delays of code and carrier are different because of their different tracking processes, which is called as the code-carrier hardware delay difference. This difference depends on the condition of receivers and varies from one to another. Therefore, in the carrier phase RTK (real-time kinematic) position process, the bias of code-carrier hardware delay difference between the base receiver and the moving receiver will cause the baseline resolution error. In this article, we analyze the code-carrier hardware delay difference, and the theoretical derivation shows that the baseline resolution error increases with the bias as well as the signal Doppler frequency. For a static RTK user on the ground, a microsecond level bias leads to a baseline resolution error in millimeter level, compared to a centimeter level error caused by the LEO satellite whose speed can reach several kilometers per second. In that case, the bias needs to be calibrated for those high precision RTK applications. However, there are few researches to calibrate the receiver carrier hardware delay because the carrier phase measurement integral ambiguity is difficult to be measured. In this article, we propose a method to measure and calibrate the bias of code-carrier hardware delay difference between different receivers. Real data test results show that the proposed method can effectively eliminate the RTK baseline resolution error caused by the bias of code-carrier hardware delay differences between the base receiver and the moving receiver.

Recently, FGFR inhibitors have been highlighted as promising targeted drugs due to the high prevalence of FGFR1 amplification in cancer patients. Although various potential biomarkers for FGFR inhibitors have been suggested, their functional effects have been shown to be limited due to the complexity of the cancer signaling network and the heterogenous genomic conditions of patients. To overcome such limitations, we have reconstructed a lung cancer network model by integrating a cell line genomic database and analyzing the model in order to understand the underlying mechanism of heterogeneous drug responses. Here, we identify novel genomic context-specific candidates that can increase the efficacy of FGFR inhibitors. Furthermore, we suggest optimal targets that can induce more effective therapeutic responses than that of FGFR inhibitors in each of the FGFR-resistant lung cancer cells through computational simulations at a system level. Our findings provide new insights into the regulatory mechanism of differential responses to FGFR inhibitors for optimal therapeutic strategies in lung cancer.

To improve the positioning accuracy and reliability of autonomous navigation agricultural machinery and reduce the cost of high-precision positioning, an integrated navigation system based on Real-Time Dynamic Kinematic BeiDou Navigation Satellite System (RTK-BDS) and Inertial Navigation System (INS) is designed in this study. On the one hand, an autonomous navigation control board is designed and made in the system, which integrates BDS high-precision analysis module, Inertial Measurement Unit (IMU) module, and radio module, and realizes the integrated navigation algorithm on the control board. On the other hand, low-cost RTK technology is realized by building differential reference stations and vehicle-mounted mobile stations. Experiments are carried out on actual farm machinery under different road conditions including open road, signal-shielded road, and urban congested road. According to the angular velocity and acceleration information from INS and the position and velocity information from the BDS high-precision analysis module, the system uses Kalman filter algorithm for data fusion to calculate the precise position, velocity, and attitude information of agricultural machinery in real time. The experimental results show that the position error of the integrated navigation system on the open road is within 3 cm, the azimuth error is within 0.6°, and the inclination error is within 1°, all of which converge rapidly when encountering bad road conditions. It can be known from the experimental results that the RTK-BDS/INS integrated navigation system has high positioning accuracy, strong adaptive anti-interference ability, and low implementation cost of RTK technology, which provides a reliable way for automatic navigation control of agricultural machinery.

The BeiDou Navigation Satellite System (BDS) is fully operational and provides positioning, navigation, and timing services to users worldwide. To comprehensively evaluate the BeiDou-3 Navigation Satellite System (BDS-3) global real-time kinematic (RTK) positioning performance, five sets of IGS/MEGX stations with different baseline lengths are selected in this research, and the visibility of current BDS-3, BDS-2+BDS-3, and Global Positioning System (GPS) system satellites are analyzed. The single frequency, dual-frequency, and triple-frequency positioning accuracy as well as ambiguity fixing rate under short baseline and long baseline are also analyzed. The experimental results show that the positioning accuracies of B1C, BII, L1, and B3I single-frequency bands were about the same, while for band B2a it was lower. For the short baseline dual-frequency RTK positioning mode, the accuracy of BDS-3 (B1C/B2a), BDS-3 (B1I/B3I), triple-frequency BDS-3 (B1C/B2a/B3I), and GPS (L1L2) is comparable and slightly better than that of BDS-3 (B1I/B3I). With the increase in baseline length, the advantages of dual-frequency BDS-3 (B1C/B2a) and triple frequency BDS (B1C/B2a/B3I) are more obvious, with triple-frequency BDS-3 (B1C/B2a/B3I) having the best positioning accuracy. In terms of ambiguity fixing performance, dual-frequency BDS-2+BDS-3 (B1I/B3I) and dual-frequency GPS (L1L2) have the highest ambiguity fixing rate. The ambiguity fixing rate of dual-frequency BDS-3 (B1C/B2a) and triple-frequency BDS-3 (B1C/B2a/B3I) can be higher than 90% within 100 km. In the case of positioning using only the BDS-3 system, the triple-frequency BDS-3 (B1C/B2a/B3I) is superior to both the dual-frequency BDS-3 (B1I/B3I) and dual-frequency BDS-3 (B1C/B2a) in terms of both positioning accuracy and ambiguity fixing rate. The BDS-2+BDS-3 (B1I/B3I) dual-frequency RTK, which has reached a level comparable to GPS, can provide global users with real-time centimeter-level differential positioning services.

The Real-Time Kinematic (RTK) positioning algorithm is a promising positioning technique that can provide real-time centimeter-level positioning precision in GNSS-friendly areas. However, the performance of RTK can degrade in GNSS-hostile areas like urban canyons. The surrounding buildings and trees can reflect and block the Global Navigation Satellite System (GNSS) signals, obstructing GNSS receivers’ ability to maintain signal tracking and exacerbating the multipath effect. A common method to assist RTK is to couple RTK with the Inertial Navigation System (INS). INS can provide accurate short-term relative positioning results. The Extended Kalman Filter (EKF) is usually used to couple RTK with INS, whereas the GNSS outlying observations significantly influence the performance. The Robust Kalman Filter (RKF) is developed to offer resilience against outliers. In this study, we design an algorithm to improve the traditional RKF. We begin by implementing the tightly coupled RTK/INS algorithm and the conventional RKF in C++. We also introduce our specific implementation in detail. Then, we test and analyze the performance of our codes on public datasets. Finally, we propose a novel algorithm to improve RKF and test the improvement. We introduce the Carrier-to-Noise Ratio (CNR) to help detect outliers that should be discarded. The results of the tests show that our new algorithm’s accuracy is improved when compared to the traditional RKF. We also open source the majority of our code, as we find there are few open-source projects for coupled RTK/INS in C++. Researchers can access the codes at our GitHub.

In emergency response and disaster rescue, unmanned aerial vehicles (UAVs) onboard thermal infrared (TIR) sensors are an essential means of acquiring ground information in the nighttime working environment. To enable field personnel to make better decisions based on TIR video streams returned from a UAV, the geographic information enhancement of TIR video streams is required. At present, it is difficult for low-cost UAVs to carry high-precision attitude sensors and thus obtain high-precision camera attitude information to meet the enhanced processing requirements of UAV TIR video streams. To this end, this paper proposes an improved Kalman filter algorithm to improve the geographic registration (geo-registration) accuracy by fusing the positioning and heading data from the dual-antenna real-time kinematic global positioning system (RTK-GPS) with onboard internal measurement unit (IMU) data. This method can yield high-precision position and attitude data in real time based on low-cost UAV hardware, based on which high-precision geo-registration results can be obtained. The computational complexity can be reduced compared with video stream feature tracking algorithms. Furthermore, the problem of unstable matching due to the low resolution and texture level of TIR video streams can be avoided. The experimental results prove that the proposed method can reduce the registration error by 66.15%, and significantly improve the geo-registration accuracy of UAV TIR video streams. Thus, it can strongly support the popularization and practicality of the application of augmented reality (AR) technology to low-cost UAV platforms.

The Google Smartphone Decimeter Challenge (GSDC) was a competition held in 2021, where data from a variety of instruments useful for determining a phone’s position (signals from GPS satellites, accelerometer readings, gyroscope readings, etc.) using Android smartphones were provided to be processed/assessed in regard to the most accurate determination of the longitude and latitude of user positions. One of the tools that can be utilized to process the GNSS measurements is RTKLIB. RTKLIB is an open-source GNSS processing software tool that can be used with the GNSS measurements, including code, carrier, and doppler measurements, to provide real-time kinematic (RTK), precise point positioning (PPP), and post-processed kinematic (PPK) solutions. In the GSDC, we focused on the PPK capabilities of RTKLIB, as the challenge only required post-processing of past data. Although PPK positioning is expected to provide sub-meter level accuracies, the lower quality of the Android measurements compared to geodetic receivers makes this performance difficult to achieve consistently. Another latent issue is that the original RTKLIB created by Tomoji Takasu is aimed at commercial GNSS receivers rather than smartphones. Therefore, the performance of the original RTKLIB for the GSDC is limited. Consequently, adjustments to both the code-base and the default settings are suggested. When implemented, these changes allowed RTKLIB processing to score 5th place, based on the performance submissions of the prior GSDC competition. Detailed information on what was changed, and the steps to replicate the final results, are presented in the paper. Moreover, the updated code-base, with all the implemented changes, is provided in the public repository. This paper outlines a procedure to optimize the use of RTKLIB for Android smartphone measurements, highlighting the changes needed given the low-quality measurements from the mobile phone platform (relative to the survey grade GNSS receiver), which can be used as a basis point for further optimization for future GSDC competitions.

Extracranial rhabdoid tumours are rare, highly aggressive malignancies primarily affecting young children. The EU-RHAB registry was initiated in 2009 to prospectively collect data of rhabdoid tumour patients treated according to the EU-RHAB therapeutic framework. We evaluated 100 patients recruited within EU-RHAB (2009–2018). Tumours and matching blood samples were examined for SMARCB1 mutations by sequencing and cytogenetics. A total of 70 patients presented with extracranial, extrarenal tumours (eMRT) and 30 with renal rhabdoid tumours (RTK). Nine patients demonstrated synchronous tumours. Distant metastases at diagnosis (M+) were present in 35% (35/100), localised disease (M0) with (LN+) and without (LN−) loco-regional lymph node involvement in 65% (65/100). SMARCB1 germline mutations (GLM) were detected in 21% (17/81 evaluable) of patients. The 5-year overall survival (OS) and event-free survival (EFS) rates were 45.8 ± 5.4% and 35.2 ± 5.1%, respectively. On univariate analyses, age at diagnosis (≥12 months), M0-stage, absence of synchronous tumours, absence of a GLM, gross total resection (GTR), radiotherapy and achieving a CR were significantly associated with favourable outcomes. In an adjusted multivariate model presence of a GLM, M+ and lack of a GTR were the strongest significant negative predictors of outcome. We suggest to stratify patients with localised disease (M0), GTR+ and without proof of a GLM (5-year OS 72.2 ± 9.9%) as 'standard risk'. Patients presenting with one of the features M+ and/or GTR− and/or GLM+ belong to a high risk group (5-year, OS 32.5 ± 6.2%). These patients need novel therapeutic strategies such as combinations of targeted agents with conventional chemotherapy or novel experimental approaches ideally within international phase I/II trials. • Presence of GLM, M+ and lack of GTR are significant negative prognostic factors. • A Standard risk' (SR) group contains patients with M0 and GTR+ and without GLM. • A 'High risk' (HR) group presents patients with M+ and/or lack of GTR and/or GLM. • The SR group demonstrated significantly superior 5-year OS rates (72.2%). • SR patients benefit from standard conventional chemotherapy, HR patients need novel therapeutic strategies. [ABSTRACT FROM AUTHOR]

The use of the GLONASS legacy signals for real-time kinematic positioning is considered. Due to the FDMA multiplexing scheme, the conventional CDMA observation model has to be modified to restore the integer estimability of the ambiguities. This modification has a strong impact on positioning capabilities. In particular, the ambiguity resolution performance of this model is clearly weaker than for CDMA systems, so that fast and reliable full ambiguity resolution is usually not feasible for standalone GLONASS, and adding GLONASS data in a multi-GNSS approach can reduce the ambiguity resolution performance of the combined model. Partial ambiguity resolution was demonstrated to be a suitable tool to overcome this weakness (Teunissen in GPS Solut 23(4):100, 2019). We provide an exhaustive formal analysis of the positioning precision and ambiguity resolution capabilities for short, medium, and long baselines in a multi-GNSS environment with GPS, Galileo, BeiDou, QZSS, and GLONASS. Simulations are used to show that with a difference test-based partial ambiguity resolution method, adding GLONASS data improves the positioning performance in all considered cases. Real data from different baselines are used to verify these findings. When using all five available systems, instantaneous centimeter-level positioning is possible on an 88.5 km baseline with the ionosphere weighted model, and on average, only 3.27 epochs are required for a long baseline with the ionosphere float model, thereby enabling near instantaneous solutions. [ABSTRACT FROM AUTHOR]

Heterotrimeric G proteins (Gαβγ) are molecular switches that relay signals from 7-transmembrane receptors located at the cell surface to the cytoplasm. The function of these receptors is so intimately linked to heterotrimeric G proteins that they are named G protein-coupled receptors (GPCRs), showcasing the interdependent nature of this archetypical receptor-transducer axis of transmembrane signaling in eukaryotes. It is generally assumed that activation of heterotrimeric G protein signaling occurs exclusively by the action of GPCRs, but this idea has been challenged by the discovery of alternative mechanisms by which G proteins can propagate signals in the cell. This review will focus on a general principle of G protein signaling that operates without the direct involvement of GPCRs. The mechanism of G protein signaling reviewed here is mediated by a class of G protein regulators defined by containing an evolutionarily conserved sequence named the Gα-binding-and-activating (GBA) motif. Using the best characterized proteins with a GBA motif as examples, Gα-interacting vesicle-associated protein (GIV)/Girdin and dishevelled-associating protein with a high frequency of leucine residues (DAPLE), this review will cover (i) the mechanisms by which extracellular cues not relayed by GPCRs promote the coupling of GBA motif-containing regulators with G proteins, (ii) the structural and molecular basis for how GBA motifs interact with Gα subunits to facilitate signaling, (iii) the relevance of this mechanism in different cellular and pathological processes, including cancer and birth defects, and (iv) strategies to manipulate GBA-G protein coupling for experimental therapeutics purposes, including the development of rationally engineered proteins and chemical probes., Competing Interests: Conflict of interest The authors declare that they have no conflicts of interest with the contents of this article., (Copyright © 2024 The Author. Published by Elsevier Inc. All rights reserved.)

Inactivation of the von Hippel Lindau tumor suppressor protein (pVHL) is a hallmark of clear cell Renal Cell Carcinoma (ccRCC), which is the most common form of kidney cancer in adults. In complex with Elongin B/C, pVHL functions as the substrate recognition subunit of a ubiquitin ligase, perhaps best known to target the hypoxia inducible factor (HIF) transcription factor for ubiquitin-dependent proteolysis. Beyond kidney cancer, the pseudo-hypoxic state caused due to chronic HIF activation in pVHL-deficient cells has become a biological model to study hypoxia's profound effects on tumor angiogenesis, metabolism, and epigenetics. However, a number of HIF-independent substrates of pVHL, which function in a broad range of biological pathways, have also been discovered. Independently, the development of high-throughput chemical and genetic screening strategies have enabled the identification of novel, HIF-independent, targetable dependencies in ccRCC. In this review we summarize the history of pVHL and HIF mediated oxygen sensing, discuss the current status of this field, and identify critical challenges that need to be overcome. The confluence of historical discovery, development of unbiased screening strategies, and the evolution of medicinal chemistry has allowed us to begin therapeutically targeting vulnerabilities that emerge due to pVHL loss in ccRCC. Ongoing mechanistic studies on the biological consequences of pVHL loss, therefore, are likely to become the cornerstones of modern therapeutics in renal cancer. [ABSTRACT FROM AUTHOR]

ABSTRACT: The adaptation of the Global Navigation Satellite Systems (GNSS) technology to fit the needs of farmers requires knowledge of the accuracy level delivered by a GNSS receiver in working conditions. To date, no methodology indicates the minimum number of replications to perform a statistical comparison. This study aims to advance knowledge on the methodological approach for evaluating the static and dynamic performance of GNSS receivers commonly used in agricultural operations. For the static test, a supporting frame in the ground carried all the receivers with coordinates properly transported. In the dynamic test, a circular rail with a 9.55 m radius was installed at ground level with a platform driven by an electric motor to carry the receivers at a constant speed. The transversal error of the receiver to the circular reference line was measured. The error with 95 % probability (E95) to receivers without differential correction ranged between 4.22 m and 0.85 m in the static test, and 2.25 m and 0.98 m in the dynamic test. Receivers with differential correction had E95 values below 0.10 m in the static test and 0.16 m in the dynamic test. Receivers with C/A code require five replications at minimum and 13 replications are needed for L1/L2 with differential correction signals in the dynamic test. The static test needs nine replications for C/A and five for L1/L2 with differential correction signals.

Ionospheric irregularities impair Global Navigation Satellite System (GNSS) signals and, in turn, affect the performance of GNSS positioning. Such effects are especially evident at low and high latitudes, which are currently gaining the attention of research and industry sectors. This study evaluates the impact of ionospheric irregularities on GNSS positioning in Greenland. We assess the performance of positioning methods that meet the demands of a wide range of users. In particular, we address the needs of the users of mass-market single-frequency receivers and those who require a solution of high precision provided by geodetic dual-frequency receivers. We take advantage of the datasets collected during three ionospheric storms: the St. Patrick’s Day storm of March 17, 2015, the storm on June 22, 2015, and another on August 25–26, 2018. We discover a significant impact of the ionospheric disturbances on the ambiguity resolution performance and the accuracy of the float solution in Real Time Kinematics (RTK) positioning. Next, assessing the single-frequency ionosphere-free Precise Point Positioning (PPP), we demonstrate that the model is generally unaffected by ionospheric disturbances. Hence, the model is predestined for the application by the users of single-frequency receivers in the areas of frequent ionospheric disturbances. Finally, based on the observation analyses, we reveal that phase signals on the L2 frequency band are more prone to cycle slips induced by ionospheric irregularities than those transmitted on the L1. Such signal properties explain a noticeable decline in the dual-frequency RTK performance during the ionospherically disturbed period and merely no effect for the single-frequency ionosphere-free PPP model.

Steep rock slopes present key opportunities and challenges within Earth science applications. Due to partial or complete inaccessibility, high-precision surveys of these high-relief landscapes remain a challenge. Direct georeferencing (DG) of unoccupied aerial vehicles (UAVs) with advanced onboard GNSS receivers presents opportunities to generate high-resolution 3D datasets without ground-based access to the study area. However, recent research has revealed large vertical errors using DG that may prove problematic in near-vertical terrain. To address these concerns, we examined more than 75 photogrammetric UAV-datasets with various imaging angles (nadir, oblique, and combinations) and ground control scenarios, including DG, along a steep slope exposure. Results demonstrate that mean errors in DG scenarios are up to 0.12 m higher than datasets using integrated georeferencing with well-distributed GCPs. Inclusion of GCPs greatly reduced mean error values but had limited influence on precision (

Multipath is a dominant error source in Real-Time Kinematic (RTK) applications that reduces the position, time and velocity accuracy. Mitigation of such errors can be achieved by better signal processing and antenna design. This paper attempts to examine the different height of RTK system antenna with regards to the multipath error. The results obtained in this work show height significantly change of multipath in pseudo range (MP1) and multipath in the carrier phase (MP2). Different antenna height does not give the same multipath error result in the tests that we have conducted in this work. The optimal height of the antenna was achieved as two meters in order to obtain a minimum multipath error for MP1 and MP2. At the end of this work, we experimentally proved that there is an inverse relationship between the height of the antenna and multipath with RTK algorithm.

The objective of this work is to determine the positional quality of the solutions offered by the Andalusia Positioning Network (RAP), an active geodetic network located in the autonomous community of Andalusia in southern Spain. Different tests are performed on the services offered by this active network, especially those that use real-time-Kinematic positioning techniques (RTK). Different parameters are analysed, including precision, accuracy and time of resolution of ambiguities. The system is then analysed from the perspective of the topographic survey; several small-scale topographic surveys are carried out, used for mining and civil engineering projects, with the aim of seeing if an active geodetic network can be used with performance similar to that for conventional RTK.

Matthew T Cook Department of Biology, Washburn University, Topeka, KS, USA Abstract: Metastatic breast cancer is typically an extremely aggressive cancer with poor prognosis. Metastasis requires the orchestration of homeostatic factors and cellular programs, many of which are potential therapeutic targets. Luteolin (2-[3,4-dihydroxyphenyl]-5,7-dihydroxy-4-chromenone), is a naturally occurring flavonoid found in fruits and vegetables that exhibits many anticancer properties. Luteolin obstructs metastasis through both direct and indirect mechanisms. For instance, luteolin may suppress breast cancer invasion by acting as an antiangiogenic therapeutic inhibiting VEGF production and its receptor’s activity. Furthermore, luteolin decreases epithelial–mesenchymal transition markers and metastatic proclivity. Luteolin also acts as an antiproliferative by suppressing receptor tyrosine-kinase activity and apoptosis, both of which could prevent incipient colonization of breast cancer. Many of these antimetastatic characteristics accredited to luteolin are likely functionally related. For instance, the PI3K/Akt pathway, which is impeded by luteolin, has several downstream programs involved in increased proliferation, survival, and metastatic potential in breast cancer. In this review, luteolin’s ability to ameliorate breast cancer is summarized. The paper also offers insight into the molecular mechanisms by which luteolin may suppress breast cancer metastasis. Keywords: angiogenesis, MMP, NOTCH, β-catenin, RTK, Akt

Emerging applications, such as improved all-weather safety for self-driving vehicles, require public positioning precision and reliability beyond the capability of open global navigation satellite system (GNSS) services. To meet these requirements, next-generation public positioning, navigation, and time (PNT) services should: 1) deliver ubiquitously available differential corrections and assistance information for massive numbers of concurrent users with fixed delay, indoor penetration and stable bit rate signals and 2) have navigation signals that are extremely enriched against challenging scenarios. The dilemma is that the free-of-charge public PNT service makes it a formidable challenge to build a dedicated information infrastructure. In this context, a natural question arises: where should we seek next-generation public PNT services in the age of Internet of Things? In this paper, we propose GNSS augmentation by FM radio symbiosis. Specifically, we propose GNSS augmentation-optimized digital data broadcasting for which the signal symbiotically co-exists with the analog FM radio in band and in channel without sensibly affecting the existing FM service. With this symbiotic digital data broadcasting, we then propose a GNSS augmentation system that can: 1) broadcast real-time kinematics correction to massive numbers of concurrent GNSS receivers to achieve outdoor precision at the centimeter-level; 2) deliver fine time GNSS assistance for significantly improved receiver sensitivity; and 3) provide common-view timing to enable GNSS independent ground positioning beacon signals. A prime challenge therein is to separate the symbiotic digital signal from the much stronger, spectrum-overlapping co-channel FM signal; this challenge represents a non-orthogonal de-multiplexing problem that is solved by a novel modulation structure. A prototype was designed, and field tests by authorized third parties were conducted with excellent results.