Search

A major limitation of current prostate cancer pharmacotherapy approaches is the inability of these compounds to target androgen receptor variants or mutants that develop during prostate cancer progression. The demand for novel therapeutics to prevent, slow, and treat prostate cancer is significant because FDA approved anti-androgens are associated with adverse events and can eventually drive drug-resistant prostate cancer. This study evaluated α-mangostin for its novel ability to degrade the androgen receptor and androgen receptor variants. α-Mangostin is one of more than 70 isoprenylated xanthones isolated from Garcinia mangostana that we have been evaluating for their anticancer potential. Prostate cancer cells treated with α-mangostin exhibited decreased levels of wild-type and mutated androgen receptors. Immunoblot, immunoprecipitation, and transfection experiments demonstrated that the androgen receptor was ubiquitinated and subsequently degraded via the proteasome, which we hypothesize occurs with the assistance of BiP, an ER chaperone protein that we have shown to associate with the androgen receptor. We also evaluated α-mangostin for its antitumor activity and promotion of androgen receptor degradation in vivo. In summary, our study demonstrates that androgen receptor degradation occurs through the novel activation of BiP and suggests a new therapeutic approach for prostate cancer.

This study addresses a signal processing technique in a search and rescue system. An international disaster rescue communications support programme such as COSPAS‐ search and rescue satellite‐aided tracking (SARSAT) estimates the position of a beacon based on time difference of arrival (TDOA) and frequency difference of arrival (FDOA) techniques. To backtrack signals from encrypted beacons without knowing the encryption codes, the cross ambiguity function (CAF) is proposed to estimate the TDOA and FDOA, in which high sampling rates are needed to increase the positioning accuracy of existing CAF algorithms, which entail high calculation loads. To overcome this, an interpolation method is proposed for peaks of Fourier transform capable of maintaining high accuracy at low calculation loads after a well‐performed initial acquisition. The numerical simulation shows an improved estimation accuracy of the proposed algorithm compared with existing peak detection methods.

An adaptive digital phase-locked loop (DPLL) continually adjusts the noise bandwidth of the loop filter in global navigation satellite system (GNSS) receivers to track signals by measuring the signal-to-noise ratio and/or dynamic stress. Such DPLLs have a relatively large amount of computational complexity compared with the conventional DPLL. A table-based adaptive DPLL is proposed that adjusts the noise bandwidth value by extracting it from the pre-generated table without additional calculations. The values of the noise bandwidth table are computed in an optimal manner in consideration of the thermal noise, oscillator phase noise, and dynamic stress error. The calculation method of the proper integration time to maintain the stability of the loop filter is presented. Additionally, the simulation is configured using the trajectory analysis results from the Moon exploration mission and shows that the proposed algorithm operates stably in harsh environments, while a conventional fixed bandwidth loop cannot. The proposed algorithm has a similar phase jitter performance to the existing adaptive DPLL algorithms and has an execution time that is approximately 2.4–5.4 times faster. It is verified that the proposed algorithm is computationally efficient while maintaining jitter performance.

A numerical analysis is conducted for assessing the feasibility on the use of Global Navigation Satellite System (GNSS) receivers for Korea Positioning System (KPS) satellites in space service volume (SSV). KPS is planned to provide a navigation and timing service by constructing seven satellites over the Korean Peninsula, which will orbit above the GNSS constellation in SSV. The major problems caused by such orbital characteristics include reduced satellite visibility due to poor geometric diversity and weak signals, causing an increase in the user range error (URE). To address these constraints, this study considers multi‐GNSS and 1‐st side‐lobe signal utilization scenarios. More specifically, the GNSS satellite visibility, geometric dilution of precision, carrier‐to‐noise ratio, URE, and navigation error for KPS satellites in SSV are analysed through a numerical simulation. A trade‐off between visibility and received signal power as well as their effects on positioning accuracy is analysed to describe the utility of side‐lobe signals. Finally, based on numerical analysis of the simulation results, this verifies the applicability of GNSS SSV for KPS satellites through multi‐GNSS and side‐lobe utilization scenarios.

Rheumatoid arthritis (RA) is a multifactorial immune-mediated disease, the pathogenesis of which involves different cell types. T-cell activation plays an important role in RA. Therefore, inhibiting T-cell activation is one of the current therapeutic strategies. Cytotoxic T-lymphocyte antigen 4-immunoglobulin (CTLA4-Ig), also known as abatacept, reduces cytokine secretion by inhibiting T-cell activation. To achieve a homeostatic therapeutic effect, CTLA4-Ig has to be administered repeatedly over several weeks, which limits its applicability in RA treatment. To overcome this limitation, we increased the number of sialic acid-capped antennas by genetically engineering the CTLA4 region to increase the therapeutic effect of CTLA4-Ig. N-acetylglucosaminyltransferase (GnT) and α2,6-sialyltransferase (α2,6-ST) were co-overexpressed in Chinese hamster ovary (CHO) cells to generate a highly sialylated CTLA4-Ig fusion protein, named ST6. The therapeutic and immunogenic effects of ST6 and CTLA4-Ig were compared. ST6 dose-dependently decreased paw edema in a mouse model of collagen-induced arthritis and reduced cytokine levels in a co-culture cell assay in a similar manner to CTLA4-Ig. ST6- and CTLA4-Ig-induced T cell-derived cytokines were examined in CD4 T cells isolated from peripheral blood mononuclear cells after cell killing through irradiation followed by flow- and magnetic-bead-assisted separation. Interestingly, compared to CTLA4-Ig, ST6 was substantially less immunogenic and more stable and durable. Our data suggest that ST6 can serve as a novel, less immunogenic therapeutic strategy for patients with RA.

Low-cost signal jammers, which are illegal in many countries but continue to be traded in the black market, emit weak global navigation satellite system (GNSS) jamming signals. This study proposes a method to detect, identify, and localise these signals based on a cloud-data processing technique in which the jamming detection, identification, and localisation are performed sequentially after gathering received signals from low-cost GNSS receivers distributed in a monitoring network. This technique consists of two steps: two-dimensional image correlation in the time-frequency domain for detection and identification, and signal correlation in the time domain and relevant processing for localisation. For this, technical descriptions of the proposed cloud-data processing method are first presented with various jamming scenarios. Then, numerical simulations are performed to evaluate the proposed method by generating satellite and jamming signals. The authors are thus able to verify the feasibility of the technique and conclude that, in practical applications, it would allow efficient and extensive monitoring of low-cost signal jammers.

This paper presents the experimental results for the effect of Out-of-Band (OOB) interference on Radio-Navigation Satellite Service (RNSS) receivers in the S-band. In areas not included in NavIC's service area, there is a limit to analyzing the effect of S-band OOB interference on real RNSS signals. Therefore, we imitate the OOB interference environment in the S-band and then analyze the OOB interference effects on the L-band RNSS signals. The OOB interference signals, such as Long Term Evolution (LTE), WirelessFidelity (Wi-Fi), and the microwave oven signals, are recorded by the USRP, and re-radiated in the L-band. The experiment results show that the OOB interference may induce severe degradations on the performance of RNSS receivers.

Global Navigation Satellite System (GNSS) receivers suffer from low signal power and high dynamic stress when operating in the Space Service Volume (SSV). Therefore, the dedicated design of receivers for challenging environments is needed. In this paper, a Look-Up Table (LUT)-based adaptive Digital Phase Locked Loop (DPLL) is proposed. It continually adjusts the noise bandwidth of the DPLL properly by continuously measuring current C/N0 and jerk dynamic stress. Because it contains the LUT that has several pre-computed noise bandwidth values, an additional calculation process of the appropriate noise bandwidth value is not needed. Therefore, the receivers simply get the proper noise bandwidth value from LUT in a short time for stable operation. Numerical simulations configured using the moon exploration mission trajectory show that the proposed algorithm maintains tracking of the signal parameters successfully even in the harsh environment simulation scenarios such as the low signal power and/or high dynamics regions, while the conventional fixed noise bandwidth method may lose its lock.

This paper presents a high-level radio frequency (RF) compatibility analysis for Korea Positioning System (KPS) signal design. The employed methodology is a simulation-based sequential assessment method that includes analytical and numerical approaches, together. For this, a high-level RF compatibility assessment by using two kinds of simulation and hardware is presented. This method can overcome the limitations on the analytical approach where the ideal outcomes are different from actual results. The inclusion of the test by using the hardware components provides an opportunity to monitor the transmission and reception of the designed signals at the RF level, reflecting the actual RF front-end hardware impact.

This paper presents GNSS/INS integration Kalman filter for enhancement of positioning accuracy and robustness to surrounding environment. In the Kalman filter system, filter parameters such as process noise covariance and measurement noise covariance selected in the tuning process determine the characteristics of the overall system. Therefore, the empirical knowledge of the filter designer should be fully employed in the tuning process, and finding proper parameter values is still a challenging work. We adopt reinforcement learning to find the process noise covariance of the filter parameter. The experimental results show that the improvement of navigation performance is achieved by the efficient use of the learned process noise covariance matrix.

Autonomous vehicles are equipped with multiple heterogeneous sensors and drive while processing data from each sensor in real time. Among the sensors, the global navigation satellite system (GNSS) is essential to the localization of the vehicle itself. However, if a GNSS-denied situation occurs while driving, the accident risk may be high due to the degradation of the vehicle positioning performance. This paper presents a cooperative positioning technique based on the lidar sensor and vehicle-to-everything (V2X) communication. The ego-vehicle continuously tracks surrounding vehicles and objects, and localizes itself using tracking information from the surroundings, especially in GNSS-denied situations. We present the effectiveness of the cooperative positioning technique by constructing a GNSS-denied case during autonomous driving. A numerical simulation using a driving simulator is included in the paper to evaluate and verify the proposed method in various scenarios.

This paper verifies the applicability of multiple Global Navigation Satellite Systems (GNSSs) and side lobe signal utilization in Space Service Volume (SSV), especially for Geostationary Earth Orbit (GEO) missions over the Korean region. Unlike the ground or terrestrial systems, various constraints of space exploration in SSV cause a problem when estimating position using GNSS. This is mainly due to the limit of GNSS signal availability where its dominant variables include altitude, side lobe issues, as well as longitude because of different constellations of several GNSS. The numerical simulation shows the effectiveness of additional side lobe signals from multi-GNSS. In addition, the effect of non-MEO satellites’ signals in SSV for different longitudes is presented.

sWnt/ Wingless (Wg) is essential for embryonic development and adult homeostasis in all metazoans, but the mechanisms by which secreted Wnt/Wg is processed remain largely unknown. A Drosophila Sol narae (Sona) is a member of ADisintegrin And Metalloprotease with ThromboSpondin motif (ADAMTS) family, and positively regulates Wg signaling by promoting Wg secretion. Here we report that Sona and Wg are secreted by both conventional Golgi and exosomal transports, and Sona cleaves extracellular Wg at the two specific sites, leading to the generation of N-terminal domain (NTD) and C-terminal domain (CTD) fragments. The cleaved forms of extracellular Wg were detected in the extracellular region of fly wing discs, and its level was substantially reduced in sona mutants. Transient overexpression of Wg-CTD increased wing size while prolonged overexpression caused lethality and developmental defects. In contrast, Wg-NTD did not induce any phenotype. Moreover, the wing defects and lethality induced by sona RNAi were considerably rescued by Wg-CTD, indicating that a main function of extracellular Sona is the generation of Wg-CTD. Wg-CTD stabilized cytoplasmic Armadillo (Arm) and had genetic interactions with components of canonical Wg signaling. Wg-CTD also induced Wg downstream targets such as Distal-less (Dll) and Vestigial (Vg). Most importantly, Cyclin D (Cyc D) was induced by Wg-CTD but not by full-length Wg. Because Sona also induces Cyc D in a cell non-autonomous manner, Wg-CTD generated by Sona in the extracellular region activates a subset of Wg signaling whose major function is the regulation of cell proliferation.

To minimise the problems associated with the development of navigation satellite systems, the authors need to verify the suitability of the system and operation technology by constructing a ground test-bed in advance. When operating a ground test-bed, they must take extra care to prevent the ground transmission signal from interfering with very-low-power satellite signals received within the service area. Therefore, in this study, they first explain the concepts necessary to analyse the interference level between ground transmission signals and satellite signals, and then discuss the simulation results of the analysis of the interrelation between the ground transmitter power output and the interference range for Global Positioning System (GPS) L1 signals in the ground test-bed environment. The results confirmed that, as the ground transmitter power output increases, the maximum interference range for GPS L1 signals increases. Moreover, considering a ground test-bed environment where six transmitters with the same transmit power were arranged at equal distances, they conclude that, as the altitudes and distances of the transmitters increase, the service area becomes wider under certain conditions.

Cell survival is essential for all living organisms to cope against multiple environmental insults. Intercellular signaling between dying and surviving cells plays an important role to ensure compensatory proliferation, preventing tissue loss after environmental stresses. Here, we show that Sol narae (Sona), a Disintegrin and metalloproteinase with thrombospondin motifs (ADAMTS) in Drosophila is required for cell survival. sona exhibited a positive genetic interaction with Death-associated inhibitor of apoptosis 1 (Diap1), and a negative genetic interaction with reaper (rpr). Transcription patterns of sona, Diap1, and rpr genes in the pouch region of wing discs were coordinately changed after irradiation. Interestingly, there was a negative correlation in the expression levels of Sona and DIAP1, and both cell types, one with high Sona level and the other with high Diap1 level, were resistant to irradiation-induced cell death. The sona-expressing cells rarely entered into cell cycle themselves but promoted the nearby cells to proliferate in irradiation conditions. We found that these sona-expressing cells are able to upregulate Cyclin D (Cyc D) and increase tissue size. Furthermore, transient Sona overexpression increased survival rate and promoted development of flies in irradiation conditions. We propose that the two types of radiation-resistant cells, one with high Sona level and the other with high Diap1 level, communicate with dying cells and between each other for cell survival and proliferation in response to irradiation.

Wingless (Wg)/Wnt family proteins are essential for animal development and adult homeostasis. Drosophila Wg secreted from the dorsal-ventral (DV) midline in wing discs forms a concentration gradient that is shaped by diffusion rate and stability of Wg. To understand how the gradient of extracellular Wg is generated, we compared the secretion route of NRT-Wg, an artificial membrane-tethered form of Wg that is supposedly not secreted but still supports fly development, to that of wild-type Wg. We found that wild-type Wg is secreted by both conventional Golgi transport and via extracellular vesicles (EVs), and NRT-Wg can be also secreted via EVs. Furthermore, wild-type Wg secreted by Golgi transport diffused and formed Wg gradient but Wg-containing EVs did not diffuse at all. In case of Wg stability, Sol narae (Sona), a metalloprotease that cleaves Wg, contributes to generate a steep Wg gradient. Interestingly, Wg was also produced in the presumptive wing blade region, which indicates that NRT-Wg on EVs expressed in the blade allows the blade cells to proliferate and differentiate without Wg diffused from the DV midline. We propose that EV-associated Wg induces Wg signaling in autocrine and juxtaposed manners whereas Wg secreted by Golgi transport forms gradient and acts in the long-range signaling, and different organs differentially utilize these two types of Wg signaling for their own development.

Armadillo (Arm) is crucial for transducing Wingless (Wg) signaling. Previously, we have shown that Klp64D, a motor subunit of Drosophila kinesin-II, interacts with Arm for Wg signaling. Molecular basis for this interaction has remained unknown. Here we identify a critical Arm repeat (AR) required for binding Klp64D and Wg signaling. Arm/$${\varvec{\beta}}$$ β -catenin family proteins contain a conserved domain of 12 Arm repeats (ARs). Five of these ARs can interact with Klp64D, but only the second AR (AR2) binds to the cargo/tail domain of Klp64D. Overexpression of AR2 in wing imaginal disc is sufficient to cause notched wing margin. This phenotype by AR2 is enhanced or suppressed by reducing or increasing Klp64D expression, respectively. AR2 overexpression inhibits Wg signaling activity in TopFlash assay, consistent with its dominant-negative effects on Klp64D-dependent Wg signaling. Overexpression of the Klp64D cargo domain also results in dominant-negative wing notching. Genetic rescue data indicate that both AR2 and Klp64D cargo regions are required for the function of Arm and Klp64D, respectively. AR2 overexpression leads to an accumulation of Arm with GM130 Golgi marker in Klp64D knockdown. This study suggests that Wg signaling for wing development is regulated by specific interaction between AR2 and the cargo domain of Klp64D.

Localization using GNSS alone may cause relatively large errors due to problems such as multipath and satellite visibility especially in urban areas compared to open areas. Many techniques for improving position accuracy using ADAS sensors such as cameras and Lidar were studied. In case of camera, performance decreases due to external environment such as illuminance is problematic, whereas the algorithm using Lidar is relatively robust to external factors, having less performance degradation than camera. V2X is ideally suited to obtain the navigation information of the surrounding objects. In this paper, we propose a localization method using the information of the surrounding objects acquired with V2X which can know the position in the navigation coordinate system and the Lidar which can know the relative position in the coordinate system of the center of the user's vehicle. Simulation results obtain by using a real-time driving simulator are included in the paper to show the performance of the proposed methods.

Geometry-free linear combination of dual-frequency signal code and carrier phase observations have been used for multiple purpose such as to remove ionosphere-delays, improve the success rate in integer ambiguity resolution and accuracy in position solution. Out of three civil signals in GPS L1/L2C/L5 and Galileo E1/E5/E6, a user has many ways to form geometry-free linear combinations to solve integer ambiguity in carrier phase observations. In precise carrier phase positioning, probability of fixing integer ambiguities using code-carrier and carrier-carrier difference models rely on the ionosphere bias and code phase observation noise. When three frequency signals are available, the code phase observation noise can be reduced using ionosphere delay matched linear combination of carrier phase observations. Furthermore, the low noise smoothed code phase observations can be used to form a code-carrier difference model to fix ionosphere-free integer ambiguity. In this study, analyzed the propagation of observation noise and ionosphere bias in a geometry-free linear combination of GPS L1/L2/L5 code and carrier phase observations, i.e. ionosphere-free, wide-lane, extra wide-lane, medium-lane, and narrow-lane. Further, the feasibility and success-rate of using smoothed code phase observations in a wide-lane integer ambiguity solution is analyzed in precise positioning applications. Experimental validation is provided.