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GNSS RTK provides precise positions in real time. This work presents a detailed performance analysis of five compact GNSS modules and four antennas used as GPS RTK Rovers over a medium baseline length. Better than 50 cm accuracy in 2- and 3-dimension is obtained within the hardware cost 200–400 USD, while sub-10 cm accuracy is achievable using dual frequency compact GNSS modules for around 1200 USD. This work also presents the comparable performance of the compact GNSS modules to their geodetic counterpart and strong antenna dependence on the solution quality. The results would be helpful for RTK popularisation. [ABSTRACT FROM AUTHOR]

AbstractPlatelet-derived growth factor (PDGF)-induced signalling via PDGF receptor β (PDGFRβ) leads to activation of downstream signalling pathways which regulate multiple cellular responses. It is unclear how PDGFRβ is degraded; both lysosomal and proteasomal degradation have been suggested. In this study, we have characterised the proteolytic cleavage of ligand-activated PDGFRβ, which results in two fragments: a larger fragment containing the extracellular domain, the transmembrane segment, and a part of the intracellular juxtamembrane region with a molecular mass of ∼130 kDa, and an intracellular ∼70 kDa fragment released into the cytoplasm. The proteolytic processing did not take place without internalisation of PDGFRβ. In addition, chelation of intracellular Ca2+ inhibited proteolytic processing. Inhibition of the proteasome affected signal transduction by increasing the phosphorylation of PDGFRβ, PLCγ, and STAT3 while reducing it on Erk1/2 and not affecting Akt. The proteolytic cleavage was observed in fibroblasts or cells that had undergone epithelial-mesenchymal transition. [ABSTRACT FROM AUTHOR]

Unmodeled errors materially affect the float solutions of both ambiguities and coordinates in global navigation satellite systems (GNSS), and thus also the fixed solution. Recently, extensive attempts have been made to guarantee the reliability of integer ambiguity or reject observation faults for improving the fixed solution in real-time kinematic positioning (RTK), while far too little studies have achieved this by processing the unmodeled errors in long baselines. This contribution is therefore set out to address the unmodeled errors in GNSS RTK long baseline fixed solution. At first, we establish an equation using the quadratic form of the float ambiguity to estimate the float ambiguity bias. Then, based on the estimated float ambiguity bias, a procedure for processing the unmodeled errors in the fixed solution is proposed. Finally, a simulation experiment and a real-measured experiment are conducted, respectively. By applying the proposed procedure, the improvements in the mean and RMSE of the fixed solution bias are found to be approximately 1.11–6.17 cm and 1.06–5.73 cm in three dimensions. [ABSTRACT FROM AUTHOR]

UAVs are nowadays used for several surveying activities, some of which imply flying close to tall walls, in and out of tunnels, under bridges, and so forth. In these applications, RTK GNSS positioning delivers results with very variable quality. It allows for centimetric-level kinematic navigation in real time in ideal conditions, but limitations in sky visibility or strong multipath effects negatively impact the positioning quality. This paper aims at assessing the RTK positioning limitations for lightweight and low-cost drones carrying cheap GNSS modules when used to fly in some meaningful critical operational conditions. Three demanding scenarios have been set up simulating the trajectories of drones in tasks such as infrastructure (i.e., building or bridges) inspection. Different outage durations, flight dynamics, and obstacle sizes have been considered in this work to have a complete overview of the positioning quality. The performed tests have allowed us to define practical recommendations to safely fly drones in potentially critical environments just by considering common software and standard GNSS parameters. [ABSTRACT FROM AUTHOR]

The paradigm "one drug fits all" or "one dose fits all" will soon be challenged by pharmacogenetics research and application. Drug response—efficacy or safety—depends on interindividual variability. The current clinical practice does not include genetic screening as a routine procedure and does not account for genetic variation. Patients with the same illness receive the same treatment, yielding different responses. Integrating pharmacogenomics in therapy would provide critical information about how a patient will respond to a certain drug. Worldwide, great efforts are being made to achieve a personalized therapy-based approach. Nevertheless, a global harmonized guideline is still needed. Plasma membrane proteins, like receptor tyrosine kinase (RTK) and G protein-coupled receptors (GPCRs), are ubiquitously expressed, being involved in a diverse array of physiopathological processes. Over 30% of drugs approved by the FDA target GPCRs, reflecting the importance of assessing the genetic variability among individuals who are treated with these drugs. Pharmacogenomics of transmembrane protein receptors is a dynamic field with profound implications for precision medicine. Understanding genetic variations in these receptors provides a framework for optimizing drug therapies, minimizing adverse reactions, and advancing the paradigm of personalized healthcare. [ABSTRACT FROM AUTHOR]

At mining enterprises, the use of modern geodetic devices is gaining more and more popularity. These technologies are easy to use, capable of performing complex mathematical calculations and significantly shorten the time of measurement work. Despite all their advantages, in some cases, modern devices can face certain difficulties, which can significantly affect the accuracy of measuring the coordinates of points, the time it takes to complete a job, and the efficiency of using a particular device in general. When using a GPS receiver, the most important thing is the stability of receiving data from satellites. As a rule, quarries do not always provide ideal conditions for using GPS receivers. The main problem is the complex relief of the area, which blocks the direct visibility of the satellites. Due to the formation of such a situation, the receiver is unable to function properly, causing delays in the performance of works. Such methods as D-GPS (Differential GPS), RTK (Real-Time Kinematic), PPP (Precise Point Positioning) can be used to solve this problem. The solution to improve the satellite signal can be the use of a controlled antenna, which, although complex in structure, is reasonably effective. The use of a virtual satellite, which serves as an additional satellite to correct the geometry of real satellites, is also considered. The article describes each of the methods used to improve the radio signal. Depending on the complexity of the local conditions, the requirements for accuracy and the financial capacity of the mining enterprise, any of the described methods may be used in reality.

This study documented the contribution of precise positioning involving a global navigation satellite system (GNSS) and a real-time kinematic (RTK) system in unmanned aerial vehicle (UAV) photogrammetry, particularly for establishing the coordinate data of ground control points (GCPs). Without augmentation, GNSS positioning solutions are inaccurate and pose a high degree of uncertainty if such data are used in UAV data processing for mapping. The evaluation included a comparative assessment of sample coordinates involving RTK and an ordinary GPS device and the application of precise GCP data for UAV photogrammetry in field crop research, monitoring nitrogen deficiency stress in maize. This study confirmed the superior performance of the RTK system in providing positional data, with 4 cm bias as compared to 311 cm with the non-augmented GNSS technique, making it suitable for use in agronomic research involving row crops. Precise GCP data in this study allow the UAV-based Normalized Difference Red-Edge Index (NDRE) data to effectively characterize maize crop responses to N nutrition during the growing season, with detailed analyses revealing the causal relationship in that a compromised optimum canopy chlorophyll content under limiting nitrogen environment was the reason for reduced canopy cover under an N-deficiency environment. Without RTK-based GCPs, different and, to some degree, misleading results were evident, and therefore, this study warrants the requirement of precise GCP data for scientific research investigations attempting to use UAV photogrammetry for agronomic field crop study. [ABSTRACT FROM AUTHOR]

The development and growth of cancer is fundamentally dependent on pro-tumor changes in metabolism. Cancer cells generally shift away from oxidative phosphorylation as the primary source of energy and rely more heavily on glycolysis. Receptor tyrosine kinases (RTKs) are a type of receptor that is implicated in this shift to pro-tumor metabolism. RTKs are important drivers of cancer growth and metastasis. One such family of RTKs is the MET family, which consists of MET and RON (MST1R). The overexpression of either MET or RON has been associated with worse cancer patient prognosis in a variety of tumor types. Both MET and RON signaling promote increased glycolysis by upregulating the expression of key glycolytic enzymes via increased MYC transcription factor activity. Additionally, both MET and RON signaling promote increased cholesterol biosynthesis downstream of glycolysis by upregulating the expression of SREBP2-induced cholesterol biosynthesis enzymes via CTTNB1. These changes in metabolism, driven by RTK activity, provide potential targets in limiting tumor growth and metastasis via pharmacological inhibition or modifications in diet. This review summarizes pro-tumor changes in metabolism driven by the MET family of RTKs. In doing so, we will offer our unique perspective on metabolic pathways that drive worse patient prognosis and provide suggestions for future study. [ABSTRACT FROM AUTHOR]

Neuroendocrine tumors (NETs) represent a diverse group of neoplasms originating from neuroendocrine cells, presenting varied clinical behaviors and posing significant challenges in management. This review explores the emerging roles of receptor tyrosine kinases (RTKs) in the pathogenesis and progression of NETs, including vascular endothelial growth factor receptors (VEGFRs), insulin-like growth factor receptors (IGF-1R), RET, epidermal growth factor receptor (EGFR), and ALK. The dysregulation of RTK signaling pathways contributes to key cellular processes such as proliferation, survival, and invasion in NETs. We discuss the potential of targeting RTKs as therapeutic strategies in NETs, with a focus on recent developments in RET inhibitors and the therapeutic implications of RTK alterations. [ABSTRACT FROM AUTHOR]

We present surface and structural models of a swarm of dm-scale subparallel faults exposed in a ∼2000 m2 glaciated outcrop near Franz Josef Glacier, in the Southern Alps of New Zealand. These structures are inferred to have slipped at ∼20 km depth in the hanging-wall Alpine Schist of the Alpine Fault under conditions that were variably brittle to ductile as the Pacific Plate was tilted and uplifted. Using field mapping, real-time kinematic GPS and digital images from a remotely piloted aircraft system, we have created a digital surface model of the outcrop and orthophotographs at a ground resolution of ∼1 cm to map compositional layering in the metasediments and the array of brittle-ductile faults displacing them. In order of decreasing relative age (and average thickness), displaced markers in the schist include primary psammite and pelite beds, quartz veins, and a deformational foliation. The surface models have been used to create 2-D transects and a 3-D model where faults are projected down-dip, to determine the connectivity, topology and intersection types of the fault swarm. Lithological variations, particularly the interface between pelitic and psammitic schist, were a primary control on the topology of the fault network and the spacing between faults. [ABSTRACT FROM AUTHOR]

Abstract CSF1R is a receptor tyrosine kinase responsible for the growth/survival/polarization of macrophages and overexpressed in some AML patients. We hypothesized that a novel multi-kinase inhibitor (TKi), narazaciclib (HX301/ON123300), with high potency against CSF1R (IC50 ~ 0.285 nM), would have anti-AML effects. We tested this by confirming HX301’s high potency against CSF1R (IC50 ~ 0.285 nM), as well as other kinases, e.g. FLT3 (IC50 of ~ 19.77 nM) and CDK6 (0.53 nM). An in vitro proliferation assay showed that narazaciclib has a high growth inhibitory effect in cell cultures where CSF1R or mutant FLT3-ITD variants that may be proliferation drivers, including primary macrophages (IC50 of 72.5 nM) and a subset of AML lines (IC50

Outliers can significantly impact the accuracy and reliability of Global Navigation Satellite System (GNSS) real-time kinematic (RTK) positioning. To enhance the robustness of RTK in GNSS-challenged environments, we propose an enhanced random sample consensus RTK (RANSAC-RTK) algorithm capable of effectively handling multiple and continuous outliers. The enhancements to the RANSAC algorithm include threshold setting, pre-screening samples and sample verification tailored to the characteristics of GNSS data. The experimental results indicate that the standard RTK algorithm is vulnerable to outliers. By contrast, the enhanced RANSAC-RTK algorithm can effectively handle multiple and continuous outliers, resulting in 33% increase in the ambiguity fixing rate and 15% improvement in positioning accuracy. [ABSTRACT FROM AUTHOR]

Real-Time Kinematic Global Navigation Satellite System (RTK-GNSS) is currently the premier technique for achieving centimeter-level accuracy quickly and easily. However, the robustness of RTK-GNSS diminishes in challenging environments due to severe multipath effects and a limited number of available GNSS signals. This is a pressing issue, especially for GNSS users in the navigation industry. This paper proposes and evaluates several methodologies designed to overcome these issues by enhancing the availability and reliability of RTK-GNSS solutions in urban environments. Our novel approach involves the integration of conventional methods with a new technique that leverages surplus satellites—those not initially used for positioning—to more reliably detect incorrect fix solutions. We conducted three tests in densely built-up areas within the Tokyo region. The results demonstrate that our approach not only surpasses the fix rate of the latest commercial receivers and a popular open-source RTK-GNSS program but also improves positional reliability to levels comparable to or exceeding those of the aforementioned commercial technology. [ABSTRACT FROM AUTHOR]

The techniques and tools developed for geodetic determinations have made it possible, over the past half century, to carry out measurements using global navigation satellite systems. As the accuracy and precision of positioning solutions, such as Fast Static and RTK, improve through technological advances, more applications will become available that can provide users with positioning information over time, autonomously verify the integrity of transmitted data, and ensure sufficient accuracy for their intended purposes. In our study for the interpretation, analysis, and visualization of raw and/or processed RINEX GNSS data recorded over time at a geodetic point using the information available from the Fast Static technique, we used the GeoRinex library from the Python programming language. This library converts data to xarray.data set, for easy use in processing parameter sets, from Rinex files: of ROMPOS reference stations and of the new B10 point resulting from measurements using the Fast Static technique: pseudorange (C1, C2, P1, P2....), carrier phase (L1, L2,...), doppler (D1, D2....) and signal strength (S1, S2....). All this information will help us to analyse and interpret the degradation of the parameters associated with Rinex version 2.11 epoch positioning files 12.02.2023, time interval 12:00-14:00 (fast static) and to understand their accuracy and behavior in different environments. Based on this study, our aim was to evaluate the error in determining the positioning accuracy of the B10 point located in a crowded and heavily trafficked area, which allows sufficient coverage of the GNSS satellites. [ABSTRACT FROM AUTHOR]

CSF1R is a receptor tyrosine kinase responsible for the growth/survival/polarization of macrophages and overexpressed in some AML patients. We hypothesized that a novel multi-kinase inhibitor (TKi), narazaciclib (HX301/ON123300), with high potency against CSF1R (IC50 ~ 0.285 nM), would have anti-AML effects. We tested this by confirming HX301's high potency against CSF1R (IC50 ~ 0.285 nM), as well as other kinases, e.g. FLT3 (IC50 of ~ 19.77 nM) and CDK6 (0.53 nM). An in vitro proliferation assay showed that narazaciclib has a high growth inhibitory effect in cell cultures where CSF1R or mutant FLT3-ITD variants that may be proliferation drivers, including primary macrophages (IC50 of 72.5 nM) and a subset of AML lines (IC50 < 1.5 μM). In vivo pharmacology modeling of narazaciclib using five AML xenografts resulted in: inhibition of MV4-11 (FLT3-ITD) subcutaneous tumor growth and complete suppression of AM7577-PDX (FLT3-ITD/CSF1Rmed) systemic growth, likely due to the suppression of FLT3-ITD activity; complete suppression of AM8096-PDX (CSF1Rhi/wild-type FLT3) growth, likely due to the inhibition of CSF1R ("a putative driver"); and nonresponse of both AM5512-PDX and AM7407-PDX (wild-type FLT3/CSF1Rlo). Significant leukemia load reductions in bone marrow, where disease originated, were also achieved in both responders (AM7577/AM8096), implicating that HX301 might be a potentially more effective therapy than those only affecting peripheral leukemic cells. Altogether, narazaciclib can potentially be a candidate treatment for a subset of AML with CSF1Rhi and/or mutant FLT3-ITD variants, particularly second generation FLT3 inhibitor resistant variants. [ABSTRACT FROM AUTHOR]

The demand for high-precision positioning has risen substantially in modern urban settings. In that regard, Global Navigation Satellite Systems (GNSS) offer several advantages such as global coverage, real-time capability, high accuracy, ease of use, and cost-effectiveness. The accuracy of GNSS-based positioning, however, suffers in urban environments due to signal blockage, reflection, and diffraction, which makes it difficult to fix ambiguities correctly within a real-time kinematic (RTK). To address this issue, this paper applies random sample consensus (RANSAC) to develop a novel single-epoch triple-frequency RTK positioning method. In our proposed method, the ambiguities of the extra-wide-lane, wide-lane, and original frequencies are resolved sequentially. RANSAC then detects and excludes incorrectly fixed ambiguities. To validate the effectiveness of the proposed method, two static experiments (cases 1 and 2) and one dynamic experiment (case 3) were conducted in representative urban areas. The findings demonstrate that the proposed method outperforms all comparative methods in positional availability, with comparable positional accuracy in terms of root-mean-square errors (RMSEs). In cases 1, 2, and 3, the proposed method achieves 3D RMSEs of 2.74, 4.29, and 20.35 cm, and the positional availabilities of 100%, 75.0%, and 73.1%, using a 10-degree mask angle (and a carrier-to-noise ratio (C/N0) threshold 35 dB-Hz). The corresponding RMSEs (positional availabilities) of comparative methods are from 1.51 to 4.04 cm (75.7 to 96.3%) in case 1, 4.19 to 7.78 cm (34.5 to 49.9%) in case 2, and 23.52 to 37.54 cm (15.4 to 33.9%) in case 3, respectively. Compared to these methods, the proposed method shows improvements of positional availabilities between 3.7 and 24.3 percentage points in case 1, between 25.1 and 40.5 percentage points in case 2, and between 39.2 and 57.7 percentage points in case 3. [ABSTRACT FROM AUTHOR]

Cancer remains a leading cause of mortality worldwide and calls for novel therapeutic targets. Membrane proteins are key players in various cancer types but present unique challenges compared to soluble proteins. The advent of computational drug discovery tools offers a promising approach to address these challenges, allowing for the prioritization of "wet-lab" experiments. In this review, we explore the applications of computational approaches in membrane protein oncological characterization, particularly focusing on three prominent membrane protein families: receptor tyrosine kinases (RTKs), G protein-coupled receptors (GPCRs), and solute carrier proteins (SLCs). We chose these families due to their varying levels of understanding and research data availability, which leads to distinct challenges and opportunities for computational analysis. We discuss the utilization of multi-omics data, machine learning, and structure-based methods to investigate aberrant protein functionalities associated with cancer progression within each family. Moreover, we highlight the importance of considering the broader cellular context and, in particular, cross-talk between proteins. Despite existing challenges, computational tools hold promise in dissecting membrane protein dysregulation in cancer. With advancing computational capabilities and data resources, these tools are poised to play a pivotal role in identifying and prioritizing membrane proteins as personalized anticancer targets. [ABSTRACT FROM AUTHOR]

The performance of low-cost smart terminals is limited by the performance of their low-cost Global Navigation Satellite System (GNSS) hardware and chips, as well as by the impact of complex urban environments, which affect the positioning accuracy and stability of GNSS services. To this end, this paper proposes a robust adaptive Kalman filter for different environments that can be applied after data preprocessing. Based on the Kalman filter algorithm, a robust estimation approach is introduced into real-time kinematic (RTK) positioning to make judgments on the abnormal observation values of low-cost smart terminals, which amplifies the variance and covariance of the outlier observation equation, and reduces the impact of outliers on positioning performance. The Institute of Geodesy and Geophysics III (IGG III) function is used for regulation purposes, where prior information is modified and refreshed using the equivalent weight matrix and adaptive factors, thus reducing the impact of system model errors on system state estimation results. In addition, a robust factor is defined to adjust positioning deviation weighting between the pre- and post-test robust estimates. The experimental results show that after robust RTK positioning in the static experiments, the overall improvement in positioning accuracies of the Xiaomi 8, Huawei P40, Huawei mate40, and low-cost M8 receiver reached 29.6%, 31.3%, 32.1%, and 30.7%, respectively. Similarly, after applying the proposed robust method in the dynamic experiments, the overall positioning accuracies of the Xiaomi 8, Huawei P40, Huawei mate40, and the low-cost M8 receiver improved by 28.3%, 32.9%, 35.4%, and 26.2%, respectively. The experimental results reveal that an excellent positioning effect of a smartphone is positively correlated with robust RTK positioning performance. However, it is worth noting that when the positioning accuracy reaches a high level, such as the positioning results achieved using low-cost receivers, the robustness performance shows a relatively decreasing trend. This finding suggests that under the condition of high positioning accuracy, the sensitivity of specific positioning equipment to interference sources may increase, resulting in a decline in the effect of robust RTK positioning. [ABSTRACT FROM AUTHOR]

For GNSS Real-Time Kinematic (RTK), the reference Base receiver operating at a precise location together with the wirelessly connected Rover receiver(s) provide(s) high-quality real-time position solutions. This work shows the potential of compact, low-cost, single-frequency (CLS) GNSS modules as the RTK Rover up to large baseline distances. A combination of the uBLOX M8T CLS module and the Tallysman TW2710 patch antenna is used in single and hybrid GNSS combinations for short-to-long single-baseline lengths with the open-source RTKLib as the processing software. The results show that, for up to 288 km baseline distance, GPS, GLONASS and Galileo standalone operation provides below 1, 3 and 2 m precisions, respectively and sub-0.5 m precision is achieved for GPS+GLONASS+Galileo and GPS+Galileo+QZSS operations. The work shows the advantages of CLS modules as Rover those exploits the multi-constellation signal availability from India using open-source RTK processing software for reduction of the overall RTK infrastructure cost. [ABSTRACT FROM AUTHOR]

Despite all efforts to enhance safety, construction sites remain a major location for traffic accidents. Short-term construction sites, in particular, face limitations in implementing extensive safety measures due to their condensed timelines. This paper seeks to enhance safety in short-term construction sites by alerting maintenance personnel and approaching vehicles to potentially dangerous scenarios. Focusing on defining the exact dimensions of static construction sites, this method employs high-precision Real-Time-Kinematics-GNSS for localizing traffic cones and deriving the construction site geometry through respective algorithms. By analyzing the geometry, we can identify situations where maintenance personnel are in close proximity to the active lane or when vehicles enter the construction site. To increase awareness of hazardous situations, we present methods for distributing information to maintenance personnel and vehicles, along with technical solutions for warning those involved. Additionally, we discuss the distribution of the construction site’s geometry among approaching vehicles, which can provide future automated vehicles with crucial information on the site’s exact start and end points.

Network Real Time Kinematic (NRTK) measurements are currently the most popular surveying method in geodesy. In most countries, there are networks of Continuously Operating Reference Stations (CORS), which form the core of the terrestrial infrastructure that allows for NRTK measurements. In many countries, including Poland, several CORS networks operate in parallel and independently. The paper presents the characteristics of the CORS network in Poland. The results of several day NRTK and Real Time Kinematic (RTK) test measurements performed tied to five CORS networks operating in Poland: ASG-EUPOS, NadowskiNET, SmartNet, TPINETpro, VRSNet.pl, were subjected to a comparative analysis. VRS, FKP, MAC and POJ streams were used in the test measurements. The research mainly concerned the possibility of the occurrence of systematic errors when NRTK and RTK measurements were tied to different CORS networks for the survey of the same points. Conclusions from the comparative analysis of the accuracy and precision of the NRTK and RTK measurement results for each coordinate were also included.

UAVs are nowadays used for several surveying activities, some of which imply flying close to tall walls, in and out of tunnels, under bridges, and so forth. In these applications, RTK GNSS positioning delivers results with very variable quality. It allows for centimetric-level kinematic navigation in real time in ideal conditions, but limitations in sky visibility or strong multipath effects negatively impact the positioning quality. This paper aims at assessing the RTK positioning limitations for lightweight and low-cost drones carrying cheap GNSS modules when used to fly in some meaningful critical operational conditions. Three demanding scenarios have been set up simulating the trajectories of drones in tasks such as infrastructure (i.e., building or bridges) inspection. Different outage durations, flight dynamics, and obstacle sizes have been considered in this work to have a complete overview of the positioning quality. The performed tests have allowed us to define practical recommendations to safely fly drones in potentially critical environments just by considering common software and standard GNSS parameters.

The development and growth of the eye depends on normal lens morphogenesis and its growth. This growth, in turn, is dependent on coordinated proliferation of the lens epithelial cells and their subsequent differentiation into fiber cells. These cellular processes are tightly regulated to maintain the precise cellular structure and size of the lens, critical for its transparency and refractive properties. Growth factor-mediated MAPK signaling driven by ERK1/2 has been reported as essential for regulating cellular processes of the lens, with ERK1/2 signaling tightly regulated by endogenous antagonists, including members of the Sprouty and related Spred families. Our previous studies have demonstrated the importance of both these inhibitory molecules in lens and eye development. In this study, we build on these findings to highlight the importance of Spreds in regulating early lens morphogenesis by modulating ERK1/2-mediated lens epithelial cell proliferation and fiber differentiation. Conditional loss of both Spred1 and Spred2 in early lens morphogenesis results in elevated ERK1/2 phosphorylation, hyperproliferation of lens epithelia, and an associated increase in the rate of fiber differentiation. This results in transient microphakia and microphthalmia, which disappears, owing potentially to compensatory Sprouty expression. Our data support an important temporal role for Spreds in the early stages of lens morphogenesis and highlight how negative regulation of ERK1/2 signaling is critical for maintaining lens proliferation and fiber differentiation in situ throughout life. [ABSTRACT FROM AUTHOR]

Background: Erythropoietin-producing hepatocellular (EPH) receptors are the largest known family of receptor tyrosine kinases characterized in humans. These proteins are involved in tissue organization, synaptic plasticity, vascular development and the progression of various diseases including cancer. The Erythropoietin-producing hepatocellular receptor tyrosine kinase member EphB6 is a pseudokinase which has not attracted an equivalent amount of interest as its enzymatically-active counterparts. The aim of this study was to assess the expression of EphB6 in pituitary tumors. Methods and Results: Human normal pituitaries and pituitary tumors were examined for EphB6 mRNA expression using real-time PCR and for EphB6 protein by immunohistochemistry and Western blotting. EphB6 was highly expressed in non-functioning pituitary neuroendocrine tumors (NF-PitNETs) versus the normal pituitary and GH-secreting PitNETs. EphB6 mRNA expression was correlated with tumor size. Conclusions: Our results suggest EphB6 aberrant expression in NF-PitNETs. Future studies are warranted to determine the role and significance of EphB6 in NF-PitNETs tumorigenesis. [ABSTRACT FROM AUTHOR]

Unmanned Aircraft Systems (UASs) have become increasingly important assets for naval and maritime law enforcement operations. In response to the ever-increasing demand for autonomous systems, this paper presents a design, development, integration, and flight testing of an unmanned rotorcraft system capable of operating with a moving ship. The system was developed initially by playing back ship motion data in a simulation environment. Ship motion prediction, relative guidance, operator control interface, and landing flight management system were developed and tested against simulated sea state motion. The system was then flight tested using a 15-kg electric helicopter operating off a US Naval Academy’s yard patrol craft. The craft was instrumented with IMU and GPS for the craft’s own state estimation. The craft was also used as a moving-base station for Real-time Kinematic (RTK) relative positioning. The flight operation was done in the Chesapeake Bay. Autonomous capabilities including takeoff, landing, station-keeping, and maneuvering relative to a moving ship were successfully demonstrated. [ABSTRACT FROM AUTHOR]

Unmanned Aerial Vehicles (UAVs) equipped with Real-Time Kinematic (RTK) Global Navigation Satellite System (GNSS) technology have gained prominence in geospatial applications, particularly in urban environments. This study focuses on assessing the mapping accuracy of UAV RTK photogrammetry in urban areas without the traditional use of Ground Control Points (GCPs). The exclusion of GCPs is motivated by the desire to streamline data acquisition processes and reduce the time and cost associated with fieldwork. The study employs a comprehensive evaluation framework to analyze the accuracy of UAV RTK photogrammetry outputs, considering factors such as point cloud density, positional accuracy, and 3D model precision. Data acquisition is carried out using a state-of-the-art UAV platform equipped with high-resolution cameras and RTK-enabled GNSS receivers. Preliminary results indicate promising mapping accuracy without the need for GCPs, demonstrating the potential efficiency of UAV RTK photogrammetry in urban contexts. However, challenges related to GNSS signal obstructions and urban canyon effects are also explored, highlighting the need for further refinement in data processing algorithms. The findings of this study contribute valuable insights into the feasibility and limitations of UAV RTK photogrammetry for urban mapping applications, paving the way for optimized workflows in the rapidly evolving field of geospatial technology. The results show that the horizontal accuracy is ± 0.025m and vertical accuracy is ± 0.035m. [ABSTRACT FROM AUTHOR]

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We compare the performance of dual-band (GPS L1/L2 and Galileo E1/E5a) real-time kinematic (RTK) positioning in an open sky and urban scenarios in southern Finland using two different authentication schemes: one using only satellites authenticated by Galileo's open service navigation message authentication (OSNMA) service (which at the moment of our tests led to using only authenticated Galileo satellites) and the other with no authentication. The results show the actual trade-off between accuracy and availability vs. authenticity associated with using only OSNMA-authenticated satellites, while the authentication of only Galileo satellites is possible (e.g., a drop of RTK positioning availability from 96.67 to 86.01% in our open sky and from 73.55 to 18.65% in our urban scenarios, respectively), and an upper bound of the potential performance that could be reached in similar experimental conditions had the authentication of GPS satellites been supported (e.g., an overall 14 cm and 10.20   m 95% horizontal accuracy in our open sky and urban scenarios, with below 30, 20 and 10 c m during 97.39, 96.03 and 92.43% of the time in the open sky and 49.12, 45.96 and 39.63% in the urban scenarios, respectively). [ABSTRACT FROM AUTHOR]

Simple Summary: Receptor tyrosine kinases (RTKs) are a family of transmembrane proteins that play crucial roles in regulating various cellular processes. The introduction of ImmunoPET targeting RTKs by specific monoclonal antibodies (mAbs) or antibody fragments is regarded as a promising tool for imaging treatment efficacy and developing anticancer drugs. Herein, we review the current clinical research on ImmunoPET targeting RTKs, with particular interest in the epidermal growth factor family, or HER family, and vascular endothelial-derived growth factor/receptor. Receptor tyrosine kinases, or RTKs, are one large family of cell surface receptors involved in signal transduction, which represent an integral part of the signaling pathways. They play a crucial role in most important cellular processes, starting with the cell cycle, proliferation and differentiation, as well as cell migration, metabolism and survival. The introduction of ImmunoPET evaluating the expression of RTKs by specific monoclonal antibodies (mAbs) or antibody fragments is regarded as a promising tool for imaging treatment efficacy and developing anticancer therapeutics. Our review focuses mainly on the current clinical research regarding ImmunoPET targeting RTKs, with particular interest in the epidermal growth factor family, or HER family, and vascular endothelial-derived growth factor/receptor. [ABSTRACT FROM AUTHOR]

Transactivation of receptor tyrosine kinases (RTK) is a crosstalk mechanism exhibited by G-protein–coupled receptors (GPCR) to activate signaling pathways classically associated with growth factors. The discovery of RTK transactivation was a breakthrough in signal transduction that contributed to developing current concepts in intracellular signaling. RTK transactivation links GPCR signaling to important cellular processes, such as cell proliferation and differentiation, and explains the functional diversity of these receptors. Purinergic (P2Y and adenosine) receptors belong to class A of GPCR; in the present work, we systematically review the experimental evidence showing that purinergic receptors have the ability to transactivate RTK in multiple tissues and physiopathological conditions resulting in the modulation of cellular physiology. Of particular relevance, the crosstalk between purinergic receptors and epidermal growth factor receptor is a redundant pathway that participates in multiple pathophysiological processes. Specific and detailed knowledge of purinergic receptor-regulated pathways advances our understanding of the complexity of GPCR signal transduction and opens the way for pharmacologic intervention in the pathological context. [ABSTRACT FROM AUTHOR]

This study documented the contribution of precise positioning involving a global navigation satellite system (GNSS) and a real-time kinematic (RTK) system in unmanned aerial vehicle (UAV) photogrammetry, particularly for establishing the coordinate data of ground control points (GCPs). Without augmentation, GNSS positioning solutions are inaccurate and pose a high degree of uncertainty if such data are used in UAV data processing for mapping. The evaluation included a comparative assessment of sample coordinates involving RTK and an ordinary GPS device and the application of precise GCP data for UAV photogrammetry in field crop research, monitoring nitrogen deficiency stress in maize. This study confirmed the superior performance of the RTK system in providing positional data, with 4 cm bias as compared to 311 cm with the non-augmented GNSS technique, making it suitable for use in agronomic research involving row crops. Precise GCP data in this study allow the UAV-based Normalized Difference Red-Edge Index (NDRE) data to effectively characterize maize crop responses to N nutrition during the growing season, with detailed analyses revealing the causal relationship in that a compromised optimum canopy chlorophyll content under limiting nitrogen environment was the reason for reduced canopy cover under an N-deficiency environment. Without RTK-based GCPs, different and, to some degree, misleading results were evident, and therefore, this study warrants the requirement of precise GCP data for scientific research investigations attempting to use UAV photogrammetry for agronomic field crop study.

Ruins, marked by decay and abandonment, present challenges for digital documentation due to their varied conditions and remote locations. Surveying inaccessible ruins demands innovative approaches for safety and accuracy. Drones with high-resolution cameras enable the detailed aerial inspection and imaging of these inaccessible areas. This study investigated how surveying technologies, particularly Unmanned Aerial Vehicles (UAVs), are used to document inaccessible ruins. Integration with Real-Time Kinematic (RTK) technologies allows direct georeferencing in photogrammetric processing. A case study of the Castle of Terracorpo in Italy was used to demonstrate UAV-only surveying feasibility in inaccessible environments, testing two different scenarios. The first scenario involved the use of a DJI Matrice 300 RTK coupled with the D-RTK2 base station to survey the Castle; both direct and indirect georeferencing were exploited and compared through the photogrammetric process. This first scenario confirmed that this approach can lead to a centimetre-level accuracy (about three times the GSD value for indirect georeferencing and seven times the GSD value for direct georeferencing exploting RTK). The second scenario testing the integration of data from drones at varying resolutions enabled the comprehensive coverage of ruinous structures. In this case, the photogrammetric survey performed with the dji Mavic 3 Cine drone (indirect georeferencing) was integrated with the photogrammetric survey performed with the dji Matrice 300 RTK drone (direct georeferencing). This scenario showed that GCPs extracted from a direct georeferencing photogrammetric survey could be successfully used to georeference and integrate other drone data. However, challenges persist in surveying underground or enclosed spaces that are inaccessible to UAVs. Future research will explore integrating robotic LiDAR survey systems and advanced data fusion techniques to enhance documentation.

Recently published work provide the first known evidence of a malignancy associated regulatory mechanism, functionally connecting a phospho-regulated degron domain embedded in a receptor tyrosine kinase (RTK), with its ectopic expression in cancer, conditional to a specific autocrine growth factor signal. Mechanistically, the growth factor-triggered phosphorylation inhibits the degron domain present in the regulated RTK, blocking access to a specific degradation complex. This ultimately rescues the RTK from rapid ubiquitin-proteasome-system-mediated degradation and, most importantly, causes its cellular overexpression. This mechanism, which has been here assigned the new functional name "Over-Expression by Degradation Rescue" (OEDR), provides an additional layer and potentially preferential tool for the control of RTKs expression in cancer, in addition to other mechanisms acting at the transcriptional and messenger transcript stabilization levels. We propose this newly defined phosphorylation/ubiquitination switch-dependent signal to bear wider unexploited relevance in cell biology and human pathophysiology. The recently identified mechanism underlying an OEDR-regulated RTK is discussed herein in the context of physiological endocrine circuits and cancer. [ABSTRACT FROM AUTHOR]

A drone was used to map an area of 18.99 hectares with millimeter accuracy. The mapping process involved creating eight targets on the ground that were visible to the drone at a height of 60 meters. The coordinates of the targets were determined using GPS methods. Classical topographic methods have also been used to calibrate the drone's GPS for further correction and accuracy. A flight plan was created using DJI software, which determined the flight area, height, time, frame rate, camera tilt, battery level, direction of flight, wind speed, latitude, longitude, and flight speed. The flight plan was uploaded to the drone's memory, and the drone was flown according to the established parameters. This technology allows to make high-resolution digital maps (orthophotoplans), as well as 3D models of some objectives - historical monuments, buildings, land. A drone can be defined as an unmanned aircraft capable of autonomous navigation without external control using autopilot or that can be controlled by a remote control device. This technology allows the creation of high-resolution digital maps. With the help of UAV technology it is possible to provide topographic support for the revision of General Urban Plans (GUP), elaboration of Zonal Urban Plans (PUZ), feasibility studies for investment works, such as road infrastructure, railways, electrical networks. etc. [ABSTRACT FROM AUTHOR]

This study presents an investigation of the positioning performance of the Real-Time Precise Point Positioning (RT-PPP) technique based on low-cost Global Navigation Satellite Systems (GNSS) observations and the contribution of multi-GNSS observations to the method. In the study, two different experiments were performed in static and kinematic modes employing two low-cost u-blox ZED-F9P receivers and ANN-MB-00 antennas. In both experiments, RT-PPP solutions were performed using the products obtained from the real-time precise orbit and clock corrections from the IGS03 stream based on Global Positioning System (GPS) and GPS+Galileo observations, and these results were compared with the Real-Time Kinematic (RTK) data based on GPS+Galileo observations. The findings of the experiment realized in static mode clearly demonstrated that the multi-GNSS observations converge about 30 minutes earlier than GPS-only observations and provide approximately ±3, ±11, and ±6 cm more precise position accuracy for the east, north, and up components, respectively. The kinematic test results indicated that the multi-GNSS observations improved the position accuracy obtained compared to a single system by 33% and 25% for horizontal and vertical components, respectively. However, considering that the results obtained from both experiments are in the order of dm, it is clear that the RT-PPP technique based on low-cost GNSS observations will not be sufficient in geodetic applications that require high accuracy, whereas it provides sufficient accuracy for navigation applications. [ABSTRACT FROM AUTHOR]

SummaryA primary goal of the US National Cancer Institute's Ras initiative at the Frederick National Laboratory for Cancer Research is to develop methods to quantify RAS signaling to facilitate development of novel cancer therapeutics. We use targeted proteomics technologies to develop a community resource consisting of 256 validated multiple reaction monitoring (MRM)-based, multiplexed assays for quantifying protein expression and phosphorylation through the receptor tyrosine kinase, MAPK, and AKT signaling networks. As proof of concept, we quantify the response of melanoma (A375 and SK-MEL-2) and colorectal cancer (HCT-116 and HT-29) cell lines to BRAF inhibition by PLX-4720. These assays replace over 60 Western blots with quantitative mass spectrometry-based assays of high molecular specificity and quantitative precision, showing the value of these methods for pharmacodynamic measurements and mechanism of action studies. Methods, fit-for-purpose validation, and results are publicly available as a resource for the community at assays.cancer.gov.MotivationA lack of quantitative, multiplexable assays for phosphosignaling limits comprehensive investigation of aberrant signaling in cancer and evaluation of novel treatments. To alleviate this limitation, we sought to develop assays using targeted mass spectrometry for quantifying protein expression and phosphorylation through the receptor tyrosine kinase, MAPK, and AKT signaling networks. The resulting assays provide a resource for replacing over 60 Western blots in examining cancer signaling and tumor biology with high molecular specificity and quantitative rigor.

The MET receptor tyrosine kinase (RTK) and its cognate ligand hepatocyte growth factor (HGF) comprise a signaling axis essential for development, wound healing and tissue homeostasis. Aberrant HGF/MET signaling is a driver of many cancers and contributes to drug resistance to several approved therapeutics targeting other RTKs, making MET itself an important drug target. In RTKs, homeostatic receptor signaling is dependent on autoinhibition in the absence of ligand binding and orchestrated set of conformational changes induced by ligand-mediated receptor dimerization that result in activation of the intracellular kinase domains. A fundamental understanding of these mechanisms in the MET receptor remains incomplete, despite decades of research. This is due in part to the complex structure of the HGF ligand, which remains unknown in its full-length form, and a lack of high-resolution structures of the complete MET extracellular portion in an apo or ligand-bound state. A current view of HGF-dependent MET activation has evolved from biochemical and structural studies of HGF and MET fragments and here we review what these findings have thus far revealed.

Pulmonary arterial hypertension (PAH) is a progressive and fatal disease without a cure. The exact pathogenic mechanisms of PAH are complex and poorly understood, yet a number of abnormally expressed genes and regulatory pathways contribute to sustained vasoconstriction and vascular remodeling of the distal pulmonary arteries. Mammalian target of rapamycin (mTOR) is one of the major signaling pathways implicated in regulating cell proliferation, migration, differentiation, and protein synthesis. Here we will describe the canonical mTOR pathway, structural and functional differences between mTOR complexes 1 and 2, as well as the crosstalk with other important signaling cascades in the development of PAH. The pathogenic role of mTOR in pulmonary vascular remodeling and sustained vasoconstriction due to its contribution to proliferation, migration, phenotypic transition, and gene regulation in pulmonary artery smooth muscle and endothelial cells will be discussed. Despite the progress in our elucidation of the etiology and pathogenesis of PAH over the two last decades, there is a lack of effective therapeutic agents to treat PAH patients representing a significant unmet clinical need. In this review, we will explore the possibility and therapeutic potential to use inhibitors of mTOR signaling cascade to treat PAH.

Real-Time Kinematic Global Navigation Satellite System (RTK-GNSS) is currently the premier technique for achieving centimeter-level accuracy quickly and easily. However, the robustness of RTK-GNSS diminishes in challenging environments due to severe multipath effects and a limited number of available GNSS signals. This is a pressing issue, especially for GNSS users in the navigation industry. This paper proposes and evaluates several methodologies designed to overcome these issues by enhancing the availability and reliability of RTK-GNSS solutions in urban environments. Our novel approach involves the integration of conventional methods with a new technique that leverages surplus satellites—those not initially used for positioning—to more reliably detect incorrect fix solutions. We conducted three tests in densely built-up areas within the Tokyo region. The results demonstrate that our approach not only surpasses the fix rate of the latest commercial receivers and a popular open-source RTK-GNSS program but also improves positional reliability to levels comparable to or exceeding those of the aforementioned commercial technology.

Today, ground control points (GCPs) represent indispensable tools for products’ georeferencing in all the techniques concerning remote sensing (RS), particularly in monitoring activities from unmanned aircraft system (UAS) platforms. This work introduces an innovative tool, smart GCPs, which combines different georeferencing procedures, offering a range of advantages. It can serve three fundamental purposes concurrently: (1) as a drone takeoff platform; (2) as a base station, allowing the acquisition of raw global navigation satellite system (GNSS) data for post-processed kinematic (PPK) surveys or by providing real-time GNSS corrections for precision positioning; (3) as a rover in the network real-time kinematic (NRTK) mode, establishing its position in real time with centimetric precision. The prototype has undergone testing in a dedicated study area, yielding good results for all three geodetic correction techniques: PPK, RTK, and GCP, achieving centimeter-level accuracy. Nowadays, this versatile prototype represents a unique external instrument, which is also easily transportable and able to connect to the GNSS RING network, obtaining real-time positioning corrections for a wide range of applications that require precise positioning. This capability is essential for environmental applications that require a multitemporal UAS-based study. When the real-time RING data are accessible to the scientific community operating in RS surveying, this work could be a helpful guide for researchers approaching such investigations.