As we move towards 6G, the demand for high-precision, cost-effective positioning solutions becomes increasingly critical. Single-anchor positioning offers a promising alternative to traditional multi-anchor approaches, particularly in complex propagation environments where infrastructure costs and deployment constraints present significant challenges. This paper provides a comprehensive evaluation of key algorithmic choices in the development of a single-anchor 5G uplink positioning testbed. Our developed testbed uses angle of arrival (AoA) estimation combined with range measurements from an ultra-wideband pair, to derive the position. The simulations conducted assess the impact of the selected algorithms on channel order and AoA estimation, while the influence of antenna calibration errors on AoA estimation is also examined. Finally, we compare simulations and results obtained from our developed platform.
This paper presents a novel testbed designed for 5th-Generation (5G) positioning using Universal Software Radio Peripherals (USRPs). The testbed integrates multiple units: an Operation Unit for test management, a User Unit equipped with an Ettus E312 USRP, and a Station Unit featuring an Ettus N310 USRP equipped with a three-element Uniform Linear Array for Angle of Arrival estimation. Alongside ultra wide-band ranging, the testbed estimates the user’s position relative to the base station. Signal processing algorithms are executed in a dedicated processing unit. Key challenges addressed include phase misalignment between RX channel pairs due to different Local Oscillators in the Ettus N310, necessitating real-time calibration for precise signal alignment. High sampling rates (up to 61.44 MSps) result in large IQ sample files, managed efficiently using a snapshot technique to optimize storage without compromising testbed positioning capabilities. The testbed synchronizes angular measurements with ranging estimates allowing consistent performance evaluation for real-life cases of dynamic users (e.g. pedestrian). Experimental results demonstrate the testbed’s effectiveness in achieving accurate pedestrian user localization.
Future 5G and 6G non-terrestrial networks (NTNs) will incorporate a low earth orbit (LEO) satellite component, offering an opportunity to complement communication services with positioning. One of the available solutions for positioning with the New Radio NTN (NR-NTN) is the downlink time-of-arrival (TOA) technique in which the user equipment (UE) computes its position with code phase measurements estimated from downlink signals. In this work, the update of a publicly available real-time software receiver called STARE enabling estimation of code phase and Doppler frequency from 5G NR-NTN signals is presented and evaluated. The update includes a new snapshot processing mode, importable custom pilot patterns, and an extended carrier frequency offset (CFO) search algorithm covering large Doppler shifts experienced in NTN. STARE is evaluated with a 100 MHz wide 5G NR-NTN downlink signal transmitted live in Ka-band from Telesat LEO 3 demonstration satellite operating as a bent pipe. To allow the code phase estimation, the current definition of the positioning reference signal (PRS) is taken to facilitate the generation of three 5G NR-NTN waveforms with various numerologies and signal bandwidths. The waveforms are evaluated in terms of achievable code phase errors using Cramer-Rao lower bound (CRLB) and the most suitable waveform with 100 MHz signal bandwidth is used for transmission. To transmit and capture the signal, a setup based on a software-defined radio (SDR) running STARE is deployed at the European Space Agency (ESA) European Space Research and Technology Centre (ESTEC). To the best of the authors' knowledge, this is the first documented live transmission and reception of a 100 MHz wide 5G NR-NTN signal with PRS in the Ka-band.
Solid solutions based on (Eu,Gd)Sc3(BO3)4 , Gd)Sc 3 (BO 3 ) 4 (C2/c) and Gd 0.25 Sc 0.75 BO 3 (R R 3) in the EuSc3(BO3)4-GdSc3(BO3)4 3 (BO 3 ) 4-GdSc 3 (BO 3 ) 4 system were studied. Synthesis at 1250 degrees C provides wide homogeneity regions which are stable at room temperature. Melt-solution crystallization of both compounds from LiBO2-LiF 2-LiF flux was shown. All the obtained samples have luminescence characteristic of Eu3+ 3+ with a largest peak at 615 nm corresponding to the 5 D 0 -> 7 F 2 transition. In this series the luminescence intensity monotonically increases with an increase of Eu content. The largest quantum yield of luminescence (53 %) in the EuSc3(BO3)4-GdSc3(BO3)4 3 (BO 3 ) 4-GdSc 3 (BO 3 ) 4 system is demonstrated by EuSc3(BO3)4 3 (BO 3 ) 4 sample.
This paper presents a comprehensive exploration of Angle of Arrival (AoA) estimation techniques in 5G environments, using the Sounding Reference Signal (SRS) in Uplink scenarios both in simulations and with actual measurements. Leveraging 5G capabilities, we investigate AoA algorithms for single-base station positioning. The study includes simulations and practical tests on a developed dedicated testbed featuring a base station equipped with a three-element Uniform Linear Array (ULA), considering Line of Sight conditions in an open environment. The testbed, employing Ettus E312 as the transmitter and Ettus N310 as the receiver, details waveform structures and reception processes. Additionally, our study examines the performance of Angle of Arrival (AoA) estimation algorithms, such as Multiple Signal Classification (MUSIC), Estimation of Signal Parameters via Rotational Invariant Techniques (ESPRIT), and Joint Angle and Delay Estimation (JADE) ESPRIT. A MATLAB ray tracing propagation model of the environment where the measurements are conducted, has been constructed. Simulation results using this model are presented, along with the actual measurements. The obtained results affirm the effectiveness of our implementation.
The integration of positioning capabilities within upcoming Fifth Generation (5G) and Sixth Generation (6G) satellite networks is envisaged as a key feature for network access and complementary navigation purposes. Nowadays, the use of Global Navigation Satellite Systems (GNSS) is widely adopted as the backbone technology for absolute outdoor positioning, including the exploitation of the user equipment (UE) location for connectivity access to non-terrestrial networks (NTN). Thus, the native use of 5G and 6G satellite networks for positioning is expected to be very relevant to complement GNSS, in case of degradation or outages. This paper describes the most relevant groups of use cases with positioning needs and highlights the opportunities for 5G and 6G satellite positioning, in terms of scenarios with respect to the coverage of terrestrial networks. Then, the key enabling technologies for 5G and 6G satellite positioning are discussed, concluding on the need to prioritize the study of the signals improving the depth of coverage, the user positioning, navigation and timing (PNT) algorithm, the high-accuracy algorithms and the user antenna.
Background: Oncological diseases are a major focus in medicine, with millions diagnosed each year, leading researchers to seek new diagnostic and treatment methods. One promising avenue is the development of targeted therapies and rapid diagnostic tests using recognition molecules. The pharmaceutical industry is increasingly exploring nucleic acid-based therapeutics. However, producing long oligonucleotides, especially aptamers, poses significant production challenges. Objectives: This study aims to demonstrate the efficacy of using molecular modeling, supported by experimental procedures, for altering aptamer nucleotide sequences while maintaining their binding capabilities. The focus is on reducing production costs and enhancing binding dynamics by removing nonfunctional regions and minimizing nonspecific binding. Methods: A molecular modeling approach was employed to elucidate the structure of a DNA aptamer, Gli-55, facilitating the truncation of nonessential regions in the Gli-55 aptamer, which selectively binds to glioblastoma (GBM). This process aimed to produce a truncated aptamer, Gli-35, capable of forming similar structural elements to the original sequence with reduced nonspecific binding. The efficiency of the truncation was proved by flow cytometry, fluorescence polarization (FP), and confocal microscopy. Results: The molecular design indicated that the new truncated Gli-35 aptamer retained the structural integrity of Gli-55. In vitro studies showed that Gli-35 had a binding affinity comparable to the initial long aptamer while the selectivity increased. Gli-35 internalized inside the cell faster than Gli-55 and crossed the blood-brain barrier (BBB), as demonstrated in an in vitro model. Conclusions: The success of this truncation approach suggests its potential applicability in scenarios where molecular target information is limited. The study highlights a strategic and resource-efficient methodology for aptamer development. By employing molecular modeling and truncation, researchers can reduce production costs and avoid trial and error in sequence selection. This approach is promising for enhancing the efficiency of therapeutic agent development, particularly in cases lacking detailed molecular target insights.
Gliomas remain challenging brain tumors to treat due to their infiltrative nature. Accurately identifying tumor boundaries during surgery is crucial for successful resection. This study introduces an innovative intraoperative visualization method utilizing surgical fluorescence microscopy to precisely locate tumor cell dissemination. Here, the focus is on the development of a novel contrasting agent (IR-Glint) for intraoperative visualization of human glial tumors comprising infrared-labeled Glint aptamers. The specificity of IR-Glint is assessed using flow cytometry and microscopy on primary cell cultures. In vivo effectiveness is studied on mouse and rabbit models, employing orthotopic xenotransplantation of human brain gliomas with various imaging techniques, including PET/CT, in vivo fluorescence visualization, confocal laser scanning, and surgical microscopy. The experiments validate the potential of IR-Glint for the intraoperative visualization of gliomas using infrared imaging. IR-Glint penetrates the blood-brain barrier and can be used for both intravenous and surface applications, allowing clear visualization of the tumor. The surface application directly to the brain reduces the dosage required and mitigates potential toxic effects on the patient. The research shows the potential of infrared dye-labeled aptamers for accurately visualizing glial tumors during brain surgery. This novel aptamer-assisted fluorescence-guided surgery (AptaFGS) may pave the way for future advancements in the field of neurosurgery.
Background: Oncological diseases are a major focus in medicine, with millions diagnosed each year, leading researchers to seek new diagnostic and treatment methods. One promising avenue is the development of targeted therapies and rapid diagnostic tests using recognition molecules. The pharmaceutical industry is increasingly exploring nucleic acid-based therapeutics. However, producing long oligonucleotides, especially aptamers, poses significant production challenges. Objectives: This study aims to demonstrate the efficacy of using molecular modeling, supported by experimental procedures, for altering aptamer nucleotide sequences while maintaining their binding capabilities. The focus is on reducing production costs and enhancing binding dynamics by removing nonfunctional regions and minimizing nonspecific binding. Methods: A molecular modeling approach was employed to elucidate the structure of a DNA aptamer, Gli-55, facilitating the truncation of nonessential regions in the Gli-55 aptamer, which selectively binds to glioblastoma (GBM). This process aimed to produce a truncated aptamer, Gli-35, capable of forming similar structural elements to the original sequence with reduced nonspecific binding. The efficiency of the truncation was proved by flow cytometry, fluorescence polarization (FP), and confocal microscopy. Results: The molecular design indicated that the new truncated Gli-35 aptamer retained the structural integrity of Gli-55. In vitro studies showed that Gli-35 had a binding affinity comparable to the initial long aptamer while the selectivity increased. Gli-35 internalized inside the cell faster than Gli-55 and crossed the blood–brain barrier (BBB), as demonstrated in an in vitro model. Conclusions: The success of this truncation approach suggests its potential applicability in scenarios where molecular target information is limited. The study highlights a strategic and resource-efficient methodology for aptamer development. By employing molecular modeling and truncation, researchers can reduce production costs and avoid trial and error in sequence selection. This approach is promising for enhancing the efficiency of therapeutic agent development, particularly in cases lacking detailed molecular target insights.
Positioning with cellular networks can serve as a backup or as a complement to the Global Navigation Satellite System (GNSS), making it relevant for autonomous vehicle navigation with integrity monitoring. The position is computed using code phase and carrier phase measurements that are obtained by tracking the downlink cellular signals in the receiver. Integrity monitoring requires rigorous characterization of cellular measurements and modeling errors. An important component of the downlink code phase and carrier phase measurements is the base station (BS) clock offset, which represents the deviation of the BS clock from a reference clock. Leaving the BS clock offset uncorrected or using a clock prediction model that does not fit the clock dynamics properly when computing the position can result in an unacceptable degradation of the positioning performance. The BS clock offset is studied using cellular measurements collected by tracking the cell-specific reference signal (CRS) of two commercially operated long-term evolution (LTE) BS uninterruptedly for eleven days. To avoid cycle slips or losses of the signal lock during high clock dynamics, the optimal bandwidths of the receiver tracking loop filters are first determined via simulations. The analysis of the carrier phase measurements shows that the main contributor to the BS clock offset are regular oscillator frequency jumps. The oscillator frequency jump is a sudden change of the clock oscillator frequency that might occur when the BS steers the clocks toward the primary reference clock. The results of the code-minus-carrier (CMC) analysis show that both monitored stations adjust the code phase and carrier phase clocks coherently. The impact of the BS clock offset on positioning performance is evaluated in a terrestrial cellular scenario, in which the cellular measurements are used to coast during GNSS unavailability. The results show that a clock prediction model can significantly reduce the horizontal position error (HPE) when compared to an uncorrected BS clock offset.
Dental implant therapy is a well-accepted treatment modality. Despite good predictability and success in the early stages, the risk of postplacement inflammation in the long-term periods remains an urgent problem. Surgical access and decontamination with chemical and mechanical methods are more effective than antibiotic therapy. The search for the optimal and predictable way for peri-implantitis treatment remains relevant. Here, we evaluated four cleaning methods for their ability to preserve the implant's surface for adequate mesenchymal stem cell adhesion and differentiation. Implants isolated after peri-implantitis were subjected to cleaning with diamond bur; Ti-Ni alloy brush, air-flow, or Er,Cr:YSGG laser and cocultured with mice MSC for five weeks. Dental bur and titanium brushes destroyed the implants' surfaces and prevented MSC attachment. Air-flow and laser minimally affected the dental implant surface microroughness, which was initially designed for good cell adhesion and bone remodeling and to provide full microbial decontamination. Anodized with titanium dioxide and sandblasted with aluminum oxide, acid-etched implants appeared to be better for laser treatment. In implants sandblasted with aluminum oxide, an acid-etched surface better preserves its topology when treated with the air-flow. These cleaning methods minimally affect the implant's surface, so it maintains the capability to absorb osteogenic cells for further division and differentiation.
Here, we present DNA aptamers capable of specific binding to glial tumor cells in vitro, ex vivo, and in vivo for visualization diagnostics of central nervous system tumors. We selected the aptamers binding specifically to the postoperative human glial primary tumors and not to the healthy brain cells and meningioma, using a modified process of systematic evolution of ligands by exponential enrichment to cells; sequenced and analyzed ssDNA pools using bioinformatic tools and identified the best aptamers by their binding abilities; determined three-dimensional structures of lead aptamers (Gli-55 and Gli-233) with small-angle X-ray scattering and molecular modeling; isolated and identified molecular target proteins of the aptamers by mass spectrometry; the potential binding sites of Gli-233 to the target protein and the role of post-translational modifications were verified by molecular dynamics simulations. The anti-glioma aptamers Gli-233 and Gli-55 were used to detect circulating tumor cells in liquid biopsies. These aptamers were used for in situ, ex vivo tissue staining, histopathological analyses, and fluorescence-guided tumor and PET/CT tumor visualization in mice with xenotransplanted human astrocytoma. The aptamers did not show in vivo toxicity in the preclinical animal study. This study demonstrates the potential applications of aptamers for precise diagnostics and fluorescence-guided surgery of brain tumors.
This paper presents the results of studying the characteristics of hydrogen sensors based on thin In2O3 films modified with tin and dysprosium with dispersed double Pt/Pd catalysts deposited on the surface. To control the content of Sn and Dy in the films, an original technology was developed, and ceramic targets were fabricated from powders of the In–Dy–O, Dy–Sn–O, and In–Dy–Sn–O systems synthesized by the sol–gel method. Films of complex composition were obtained by RF magnetron sputtering of the corresponding targets. Structural features of the obtained thin films were studied by Raman spectroscopy. It is shown that various combinations of tin and dysprosium concentrations, as well as the presence of Pt/Pd catalysts on the surface, have a significant effect on the defectiveness of the films and the density of oxygen adsorption centers. As a result, the resistance of sensors in pure air (R0), the activation energies of the temperature dependences of R0, the bending of the energy bands at the grain boundaries of the semiconductor, and the responses to the action of hydrogen in the concentration range of 20–25,000 ppm change. A unique feature of Pt/Pd/ In2O3: Sn (0.5 at%), Dy (4.95 at%) films is their high sensitivity at 20–100 ppm and the absence of signal saturation in the region of high hydrogen concentrations of 5000–25,000 ppm, allowing them to be used to detect H2 in a wide range of concentrations.
This paper sheds lights onto the challenging problem of achieving coherent phase reception between the RF channels of existing multi-channel software-defined radios (SDR). This is a key problem that must be solved, for instance, in applications dealing with 5G positioning and integrated sensing and communications (ISAC) when direction of arrival estimation is needed. Despite being a fundamental problem, it is far from being straightforward to implement in practice with existing SDR devices. In this regard, the present paper provides a set of golden guidelines in order to succeed in this endeavor, and thus to leverage the full potential that multi-channel SDR devices have to offer. Apart from phase coherence, practical recommendations are provided as well to achieve the highest possible data throughput between the SDR and the controlling computer. Finally, a comparison among the most relevant features of different models of Universal Software Radio Peripheral (USRP) SDR devices is discussed, including an analysis of their performance in terms of phase differences between RF channels.
One of the promising novel methods for radical tumor resection at a single-cell level is magneto-mechanical microsurgery (MMM) with magnetic nano- or microdisks modified with cancer-recognizing molecules. A low-frequency alternating magnetic field (AMF) remotely drives and controls the procedure. Here, we present characterization and application of magnetic nanodisks (MNDs) as a surgical instrument ("smart nanoscalpel") at a single-cell level. MNDs with a quasi-dipole three-layer structure (Au/Ni/Au) and DNA aptamer AS42 (AS42-MNDs) on the surface converted magnetic moment into mechanical and destroyed tumor cells. The effectiveness of MMM was analyzed on Ehrlich ascites carcinoma (EAC) cells in vitro and in vivo using sine and square-shaped AMF with frequencies from 1 to 50 Hz with 0.1 to 1 duty-cycle parameters. MMM with the "Nanoscalpel" in a sine-shaped 20 Hz AMF, a rectangular-shaped 10 Hz AMF, and a 0.5 duty cycle was the most effective. A sine-shaped field caused apoptosis, whereas a rectangular-shaped field caused necrosis. Four sessions of MMM with AS42-MNDs significantly reduced the number of cells in the tumor. In contrast, ascites tumors continued to grow in groups of mice and mice treated with MNDs with nonspecific oligonucleotide NO-MND. Thus, applying a "smart nanoscalpel" is practical for the microsurgery of malignant neoplasms.
Introduction: Breast cancer (BC) diagnostics lack noninvasive methods and procedures for screening and monitoring disease dynamics. Admitted CellSearch® is used for fluid biopsy and capture of circulating tumor cells of only epithelial origin. Here we describe an RNA aptamer (MDA231) for detecting BC cells in clinical samples, including blood. The MDA231 aptamer was originally selected against triple-negative breast cancer cell line MDA-MB-231 using cell-SELEX.Methods: The aptamer structure in solution was predicted using mFold program and molecular dynamic simulations. The affinity and specificity of the evolved aptamers were evaluated by flow cytometry and laser scanning microscopy on clinical tissues from breast cancer patients. CTCs were isolated form the patients’ blood using the developed method of aptamer-based magnetic separation. Breast cancer origin of CTCs was confirmed by cytological, RT-qPCR and Immunocytochemical analyses.Results: MDA231 can specifically recognize breast cancer cells in surgically resected tissues from patients with different molecular subtypes: triple-negative, Luminal A, and Luminal B, but not in benign tumors, lung cancer, glial tumor and healthy epithelial from lungs and breast. This RNA aptamer can identify cancer cells in complex cellular environments, including tumor biopsies (e.g., tumor tissues vs. margins) and clinical blood samples (e.g., circulating tumor cells). Breast cancer origin of the aptamer-based magnetically separated CTCs has been proved by immunocytochemistry and mammaglobin mRNA expression.Discussion: We suggest a simple, minimally-invasive breast cancer diagnostic method based on non-epithelial MDA231 aptamer-specific magnetic isolation of circulating tumor cells. Isolated cells are intact and can be utilized for molecular diagnostics purposes.
This work presents field results of a dedicated fifth generation (5G) network with ground and aerial base stations (BSs) deployed at Airbus premises for positioning purposes. This field campaign is part of a first-of-a-kind testbed for hybrid Global Navigation Satellite Systems (GNSS), 5G new radio (NR) and sensor positioning, called Hybrid Overlay Positioning with 5G and GNSS (HOP5G) testbed. The dedicated 5G network exploits the standard positioning reference signal (PRS) to support positioning capabilities within the 5G NR downlink transmissions. The goal of this dedicated 5G network is to enhance the accuracy and reliability of hybrid positioning services based on the fusion of GNSS, 5G NR and sensors. This hybridization is especially relevant in the case of a service interruption by any of those technologies, being GNSS the most reliable but not exempt of vulnerabilities. To the best of authors’ knowledge, this paper presents the first field results of a 5G network with mixed setup of BSs deployed on ground and at unmanned aerial vehicle (UAV) payloads dedicated for positioning purposes. This field campaign is performed at a heliport within Airbus premises in Ottobrunn (Germany), as representative use case. The paper assesses the pseudorange noise of the real-time 5G NR measurements from three ground and one aerial BSs. These first field trials results achieve a pseudorange noise below 80cm in the 95% of cases, thanks to the 80-MHz PRS bandwidth, demonstrating the feasibility to deploy a dedicated 5G network of ground and flying BSs for high-accuracy positioning. Future work focuses on the assessment of sub-meter hybrid positioning accuracies.
Laboratory tests using a GNSS simulator and multiple GNSS receivers have demonstrated that a code step may lead to an overshoot in the output of the code tracking loop due to the employed loop filters. Although these tests have been performed using non-aviation receivers, the occurrence of overshoots in aviation receivers cannot be excluded, as current aviation standards are not imposing any restrictions on the use of higher-order code tracking loops. From an integrity perspective, an unbounded overshoot would be a concern, as a Satellite-Based Augmentation System (SBAS) or a Ground-Based Augmentation System (GBAS) has to protect the worst user being compliant with the applicable standard. The standards for aviation GNSS receivers are imposing smoothing of code measurements by using the Hatch filter. One could expect that smoothing should mitigate overshoots, at least partly. Simulations presented in this paper show that the problem of overshoot is not negligible during smoothing for particular implementations of code tracking loops. Based on the results of the simulations, new requirements have been added to the Dual-Frequency Multi-Constellation (DFMC) SBAS Minimum Operational Performance Standards (MOPS), to bound overshoots after smoothing. In order to offer flexibility to the receiver manufacturer, the use of higher-order code tracking loops is not forbidden, yet the receiver manufacturer shall demonstrate that the maximum overshoot after smoothing is limited to 5 cm.