Epithelial-mesenchymal transition (EMT) is a key process associated with the progression of epithelial cancers to metastatic disease. In melanoma, a similar process of phenotype switching has been ...reported and EMT-related genes have been implicated in promotion to a metastatic state. This review examines recent research on the role of signaling pathways and transcription factors regulating EMT-like processes in melanoma and their association with response to therapy in patients, especially response to BRAF inhibition, which is initially effective but limited by development of resistance and subsequent progression. We highlight studies implicating specific roles of various receptor tyrosine kinases (RTKs) in advancing melanoma progression by conferring a proliferative advantage and through promoting invasive phenotypes and metastasis. We also review the current knowledge of the mechanisms underlying resistance to BRAF inhibition and the potential role of melanoma phenotype switching in this process. In particular, we discuss how these important new insights may significantly enhance our ability to predict patterns of melanoma progression during treatment, and may facilitate rational development of combination therapies in the future.
Breast cancer is a multifactorial disease and driven by aberrant regulation of cell signaling pathways due to the acquisition of genetic and epigenetic changes. An array of growth factors and their ...receptors is involved in cancer development and metastasis. Receptor Tyrosine Kinases (RTKs) constitute a class of receptors that play important role in cancer progression. RTKs are cell surface receptors with specialized structural and biological features which respond to environmental cues by initiating appropriate signaling cascades in tumor cells. RTKs are known to regulate various downstream signaling pathways such as MAPK, PI3K/Akt and JAK/STAT. These pathways have a pivotal role in the regulation of cancer stemness, angiogenesis and metastasis. These pathways are also imperative for a reciprocal interaction of tumor and stromal cells. Multi-faceted role of RTKs renders them amenable to therapy in breast cancer. However, structural mutations, gene amplification and alternate pathway activation pose challenges to anti-RTK therapy.
With the increasing complexity of electromagnetic environment and the continuous progress of electronic interference technology, Global Navigation Satellite System (GNSS) spoofing attacks have become ...a practical threat. As a result, the focus of GNSS improvement has shifted from improving accuracy to improving reliability. Combining an inertial navigation system (INS) is effective for spoofing detection and mitigation since INS can independently provide high frequency, high accuracy, multi-category navigation information within a period of time. This article focuses on analyzing the impact of spoofing attacks on GNSS/INS integration and explores potential anti-spoofing methods. A Beidou Navigation Satellite System (BDS) real-time kinematic (RTK)/INS tightly coupled model that involves spoofing measurements is established. The article describes an adaptively robust Kalman filter (ARKF)-based spoofing detection and mitigation method. The impact of spoofing attacks on the adaptively robust estimation is theoretically assessed. A combined spoofing-resistant strategy of ARKF and partial ambiguity resolution (PAR) is proposed to improve the ability of state estimation under GNSS spoofing. Semi-physical and semi-simulation experiments are carried out to verify our analysis and approach, which shows that compared with using extended Kalman filter (EKF), the BDS RTK/INS tightly coupled integration using ARKF can suppress the effect of spoofing attacks. However, its performance is degraded under ramp spoofing attacks and long-term step spoofing attacks. Additionally, employing a partial ambiguity resolution can reduce the effect of outliers on ambiguity resolution, improve the accuracy of state estimation under spoofing attacks, and further enhance the system's robustness under GNSS spoofing.
UAV Photogrammetry today already enjoys a largely automated and efficient data processing pipeline. However, the goal of dispensing with Ground Control Points looks closer, as dual-frequency GNSS ...receivers are put on board. This paper reports on the accuracy in object space obtained by GNSS-supported orientation of four photogrammetric blocks, acquired by a senseFly eBee RTK and all flown according to the same flight plan at 80 m above ground over a test field. Differential corrections were sent to the eBee from a nearby ground station. Block orientation has been performed with three software packages: PhotoScan, Pix4D and MicMac. The influence on the checkpoint errors of the precision given to the projection centers has been studied: in most cases, values in Z are critical. Without GCP, the RTK solution consistently achieves a RMSE of about 2–3 cm on the horizontal coordinates of checkpoints. In elevation, the RMSE varies from flight to flight, from 2 to 10 cm. Using at least one GCP, with all packages and all test flights, the geocoding accuracy of GNSS-supported orientation is almost as good as that of a traditional GCP orientation in XY and only slightly worse in Z.
Using a GNSS RTK (Global Navigation Satellite System Real Time Kinematic) -equipped unmanned aerial vehicle (UAV) could greatly simplify the construction of highly accurate digital models through SfM ...(Structure from Motion) photogrammetry, possibly even avoiding the need for ground control points (GCPs). As previous studies on this topic were mostly performed using fixed-wing UAVs, this study aimed to investigate the results achievable by a quadrocopter (DJI Phantom 4 RTK). Three image acquisition flights were performed for two sites of a different character (urban and rural) along with three calculation variants for each flight: georeferencing using ground-surveyed GCPs only, onboard GNSS RTK only, and a combination thereof. The combined and GNSS RTK methods provided the best results (at the expected level of accuracy of 1-2 GSD (Ground Sample Distance)) for both the vertical and horizontal components. The horizontal positioning was also accurate when georeferencing directly based on the onboard GNSS RTK; the vertical component, however, can be (especially where the terrain is difficult for SfM evaluation) burdened with relatively high systematic errors. This problem was caused by the incorrect identification of the interior orientation parameters calculated, as is customary for non-metric cameras, together with bundle adjustment. This problem could be resolved by using a small number of GCPs (at least one) or quality camera pre-calibration.
•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.
Georeferencing using ground control points (GCPs) is the most common strategy in photogrammetry modeling using unmanned aerial vehicle (UAV)-acquired imagery. With the increased availability of UAVs ...with onboard global navigation satellite system–real-time kinematic (GNSS RTK), georeferencing without GCPs is becoming a promising alternative. However, systematic elevation error remains a problem with this technique. We aimed to analyze the reasons for this systematic error and propose strategies for its elimination. Multiple flights differing in the flight altitude and image acquisition axis were performed at two real-world sites. A flight height of 100 m with a vertical (nadiral) image acquisition axis was considered primary, supplemented with flight altitudes of 75 m and 125 m with a vertical image acquisition axis and two flights at 100 m with oblique image acquisition axes (30° and 15°). Each of these flights was performed twice to produce a full double grid. Models were reconstructed from individual flights and their combinations. The elevation error from individual flights or even combinations yielded systematic elevation errors of up to several decimeters. This error was linearly dependent on the deviation of the focal length from the reference value. A combination of two flights at the same altitude (with nadiral and oblique image acquisition) was capable of reducing the systematic elevation error to less than 0.03 m. This study is the first to demonstrate the linear dependence between the systematic elevation error of the models based only on the onboard GNSS RTK data and the deviation in the determined internal orientation parameters (focal length). In addition, we have shown that a combination of two flights with different image acquisition axes can eliminate this systematic error even in real-world conditions and that georeferencing without GCPs is, therefore, a feasible alternative to the use of GCPs.
PPP-RTK is integer ambiguity resolution-enabled precise point positioning. In this contribution, we present the principles of PPP-RTK, together with a review of different mechanizations that have ...been proposed in the literature. By application of
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-system theory, the estimable parameters of the different methods are identified and compared. Their interpretation is essential for gaining a proper insight into PPP-RTK in general, and into the role of the PPP-RTK corrections in particular. We show that PPP-RTK is a relative technique for which the ‘single-receiver user’ integer ambiguities are in fact double-differenced ambiguities. We determine the transformational links between the different methods and their PPP-RTK corrections, thereby showing how different PPP-RTK methods can be mixed between network and users. We also present and discuss four different estimators of the PPP-RTK corrections. It is shown how they apply to the different PPP-RTK models, as well as why some of the proposed estimation methods cannot be accepted as PPP-RTK proper. We determine analytical expressions for the variance matrices of the ambiguity-fixed and ambiguity-float PPP-RTK corrections. This gives important insight into their precision, as well as allows us to discuss which parts of the PPP-RTK correction variance matrix are essential for the user and which are not.
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