Search Results (332)

This study addresses the motion and inertia parameter estimation problem of a torque-free, tumbling, non-cooperative space object (target) under long-term occlusions. To solve this problem, we employ a data-driven Gaussian process (GP) to simulate sensor measurements. In particular, we implement the multi-output GP to predict the projection measurements of a stereo-camera system onboard a chaser spacecraft. A product kernel, consisting of two periodic kernels, is used in the GP models to capture the periodic trends from non-periodic projection data. The initial guesses for the periodicity hyper-parameters of the GP models are intelligently derived from fast Fourier transform (FFT) analysis of the projection data. Additionally, we propose an unscented Kalman filter–Gaussian process (UKF-GP) fusion algorithm for target motion and inertia parameter estimation. The predicted projections from the GP models and their derivatives are used as the pseudo-measurements for UKF-GP during long-term occlusion. Results from Monte Carlo (MC) simulations demonstrate that, for varying tumbling frequencies, the UKF-GP can accurately estimate the target’s motion variables over hundreds of seconds, a capability the conventional UKF algorithm lacks. Full article

Gene II Protein (Gp2/P2) is a nicking enzyme of the M13 bacteriophage that plays a role in the DNA replication of the viral genome. P2 recognizes a specific sequence at the f1 replication origin and nicks one of the strands and starts replication. This study was conducted to address the limitations of previous experiments, improve methodologies, and precisely determine the biochemical activity conditions of the P2 enzyme in vitro. For these purposes, the gene encoding P2 was cloned in Escherichia coli and expressed as a hybrid protein together with a green fluorescent protein (P2-GFP). P2-GFP was purified via metal affinity chromatography, and its nicking activity was determined by conversion of supercoiled DNA to open circular or linear forms. We discovered that, among the two loops of the f1 origin defined previously, P2 can recognize just the A1 loop. When a supercoiled plasmid containing the f1 origin was treated with P2-GFP, the plasmid was present in an open circular form, indicating that a nick was created on only one of the strands. However, when the A1 loop sequence was inserted into the 3′ ends of both strands by cloning a PCR product obtained by primers with the A1 loop sequence, the plasmid was linearized by treatment with P2-GFP, indicating that nicks were created on both strands. Certain infectious diseases are caused by single-stranded DNA viruses, and some of them have specific nicking enzymes that enable strand displacement and free 3′ end of a single strand that works as a primer for their replication mechanisms like M13 bacteriophages, such as parvovirus B19. Despite there being different host viruses such as bacteria and humans, their DNA replication mechanisms are very similar in this concept. Investigating the features of the P2-nicking enzyme may deepen the understanding of human pathogenic single-stranded viruses and facilitate the development of drugs that inhibit viral replication. Full article

This paper presents a new approach for enhancing autonomous vehicle navigation and obstacle avoidance based on the integration of reinforcement learning with multiple sensors for navigation. The proposed system is designed to enable a reinforcement learning decision algorithm capable of making real-time decisions in aiding the adaptive capability of a vehicle. This method was tested on a prototype vehicle with navigation based on a Ublox Neo 6M GPS and a three-axis magnetometer, while for obstacle detection, this system uses three ultrasonic sensors. The use of a model-free reinforcement learning algorithm and use of an effective sensor for obstacle avoidance (instead of LiDAR and a camera) provides the proposed system advantage in terms of computational requirements, adaptability, and overall cost. Our experiments show that the proposed method improves navigation accuracy substantially and significantly advances the ability to avoid obstacles. The prototype vehicle adapts very well to the conditions of the testing track. Further, the data logs from the vehicle were analyzed to check the performance. It is this cost-effective and adaptable nature of the system that holds some promise toward a solution in situations where human intervention is not feasible, or even possible, due to either danger or remoteness. In general, this research showed how the application of reinforcement learning combined with sensor fusion enhances autonomous navigation and makes vehicles perform more reliably and intelligently in dynamic environments. Full article

Background/Objectives: Pinocembrin is a promising drug candidate for treating ischemic stroke. The interaction of pinocembrin with drug transporters and drug-metabolizing enzymes is not fully revealed. The present study aims to evaluate the interaction potential of pinocembrin with cytochrome P450 (CYP450: CYP2B6, CYP2C9, and CYP2C19) and drug transporters including organic anion transporters (OAT1 and OAT3), organic cation transporters (OCT1 and OCT2), multidrug and toxin extrusion (MATE1 and MATE2, P-glycoprotein (P-gp), and breast cancer resistance protein (BCRP). Methods: The interactions of pinocembrin on drug transporters were determined in the Madin–Darby canine kidney (MDCK) cells overexpressing human (h)OAT1 or hOAT3 and in the Chinese hamster ovary (CHO-K1) cells overexpressing hOCT1, hOCT2, hMATE1, or hMATE2. The interactions of pinocembrin with BCRP and P-glycoprotein were determined in Caco-2 cells. The CYP450 enzyme inhibitory activity was assessed by a cell-free CYP450 screening assay. Results: Pinocembrin effectively inhibited the function of OAT1 and OAT3 with a half-inhibitory concentration (IC₅₀) and inhibitory constant (Ki) of ∼2 μM. In addition, it attenuated the toxicity of tenofovir, a substrate of hOAT1, in cells overexpressing hOAT1. Based on the kinetic study and molecular docking, pinocembrin inhibited OAT1 and OAT3 via a competitive inhibition. In contrast to hOAT1 and hOAT3, pinocembrin did not significantly inhibit the function of OCT1, OCT2, MATE1, MATE2, BCRP, and P-glycoprotein. In addition, pinocembrin potently inhibited the activity of CYP2C19, whereas it exhibited low inhibitory potency on CYP2B6 and CYP2C9. Conclusions: The present study reveals the potential drug interaction of pinocembrin on OAT1, OAT3, and CYP2C19. Co-administration with pinocembrin might affect OAT1-, OAT3-, and CYP2C19-mediated drug pharmacokinetic profiles. Full article

It is well stablished that docosahexaenoic (DHA) and arachidonic (ARA) acids fulfill relevant biological activities, especially in newborns. However, oils containing these fatty acids are not always optimally digestible. To address this, various formulation strategies and lipid delivery systems have been developed. This study compares the following three formulations in an in vitro digestion model to assess bioaccessibility: Enfamil^® DHA & ARA (Mead Johnson & Company), an emulsion of Formulaid^TM, AquaCelle^®, and pasteurized donated human milk, and a previously characterized enzymatic glycerolysis product (GP) of ARA oil and microalgae oil in a 2:1 (w:w) ratio. To evaluate digestibility, parameters such as the percentage of oily phase (OP), micellar phase (MP), free fatty acids, and monoacylglycerols in the digestion product (DP) were considered. Additionally, diacylglycerol content in the MP can be used as an indirect marker of the emulsification capacity of the DP, and consequently, as an indicator of bioaccessibility. The GP demonstrated the highest bioaccessibility, with a DP containing more than 80% MP (<14% OP), rich in free fatty acids (60%) and monoacylglycerols (17%). Furthermore, more than 40% of total diacylglycerols were present in MP, highlighting GPs’ potential as a superior delivery system for DHA and ARA in preterm infant formulations. Full article

Objectives: In this paper, we investigate the association of glycoprotein 96 (GP96) and androgen receptor (AR) expression with clinicopathological factors, additional axillary lymph node burden, and their potential role in predicting 5-year overall survival (OS) and disease-free survival (DFS) in breast cancer (BC) patients with sentinel lymph node (SLN) involvement. We also explore the prognostic value of the presence of extranodal extension (ENE) in SLN. Methods: We retrospectively enrolled 107 female patients with cT1-T2 invasive BC and positive SLN biopsy. GP96 and AR expression were immunohistochemically evaluated on tissue microarrays constructed from two 2 mm diameter cores of formalin-fixed paraffin-embedded tumor tissues from each patient. ENE in SLN was measured in the highest (HD-ENE) and widest diameter (WD-ENE). Relative GP96 gene expression was determined using real-time quantitative PCR. Results: The analysis revealed ENE in SLN as the strongest predictive factor for non-SLN metastases. Patients with WD-ENE > HD-ENE had a higher risk of non-SLN metastases and worse DFS compared to those with WD-ENE ≤ HD-ENE. High GP96 expression was associated with a greater relative risk for locoregional recurrence but showed no significant impact on OS or DFS. Histological grade 3, extensive intraductal component (EIC), higher lymph node ratio (LNR), and negative AR were associated with worse DFS, while age, histological grade 3, EIC, and higher LNR were independent predictors of OS. GP96 mRNA levels were elevated in BC tissue compared to normal breast tissue. Conclusions: ENE in SLN is the strongest predictor of non-SLN involvement and could also have prognostic significance. While GP96 expression does not influence survival outcomes, AR expression could be used as a valuable biomarker in the follow-up of BC patients. Full article

Road safety applications for automotive scenarios rely on the ability to estimate vehicle positions with high precision. Global navigation satellite systems (GNSS) and, in particular, the global positioning system (GPS), are commonly used for self localization. But, especially in urban vehicular scenarios, due to obstructions, they may not provide the requirements for crucial position-based applications. In this paper, we investigate the potential of GPS-free positioning schemes and, in particular, we compute the ultimate performance, i.e., Cramér–Rao lower bounds (CRLB), of localization schemes in which each vehicle estimates its position exploiting range and/or angle measurements of an assigned set of landmarks with a known position. Full article

Background: Previously, we proposed that the immune-modified Glasgow Prognostic Score (imGPS), which adds the lymphocyte count to the mGPS, is helpful as a prognostic marker for patients with head and neck squamous cell carcinoma. In this study, we investigated the imGPS as a marker for the therapeutic effect of pembrolizumab in treating recurrent and metastatic head and neck cancer (RMHNC). Methods: This study included RMHNC patients who were treated with pembrolizumab from December 2019 to April 2024. ALB, CRP, lymphocyte counts, neutrophil-to-lymphocyte ratios (NLRs), mGPSs, and imGPSs were extracted as biomarkers, and the response rate and prognosis were analyzed for each. Results: A total of 54 patients were enrolled. Lymphocyte counts were correlated with the overall response rates (ORRs) (p = 0.0082). Although the mGPS did not show significant differences in ORRs, imGPSs revealed a significant difference (p = 0.013). CRP, ALB, and lymphocyte counts were correlated with overall survival (OS) and/or progression-free survival (PFS). NLRs, mGPSs, and imGPSs were also correlated with OS and/or PFS, with imGPSs showing the greatest area under the curve (OS; AUC = 0.795, PFS; AUC = 0.754). Conclusions: This study demonstrates that the imGPS is an excellent predictive marker for the therapeutic effect and prognosis of pembrolizumab for RMHNC. The imGPS can be employed with daily blood tests, highlighting the potential to forecast the impact of the ICI with high reliability. Full article

Crop rotation is widely recognized as a key strategy to mitigate the adverse effects associated with continuous cropping. Recent studies have demonstrated that biochar has a significant potential for preventing and controlling these challenges. However, the ameliorative effects of green manure rotation and biochar application on continuous pepper cultivation in the karst mountainous regions of Southwest China remain largely unexplored. To address this gap, a field experiment was conducted from 2020 to 2023 to investigate the effects of green manure rotation and biochar application on the continuous cropping of peppers. The experiment consisted of five treatments: CK (no green manure and no biochar), WP (winter fallow and conventional pepper production with chemical fertilization), GP (green manure and pepper rotation, the amount of fresh green manure returned to the field was about 15 t·ha⁻¹), WP + B (winter fallow and pepper rotation with 1500 kg·ha⁻¹ of biochar applied during the pepper season), and GP + B (green manure and pepper rotation with 1500 kg·ha⁻¹ of biochar applied during the pepper season, the amount of fresh green manure returned to the field was about 15 t·ha⁻¹). The results showed that all the improved measures (GP, WP + B, GP + B) increased the yield of fresh pepper and dry pepper by 26.97–72.98% and 20.96–65.70%, respectively, and the yield of dry pod pepper increased by 14.69–40.63% and 21.44–73.29% in 2021 to 2023, respectively, and significantly improved the yield stability and sustainability of continuous cropping of peppers compared with WP treatments. In addition, green manure rotation or biochar application alone or in combination enhanced the nutritional quality of pepper fruits by increasing the content of free amino acids (8.62–19.42%), reducing sugars (15.30–34.62%) and vitamin C (26.19–43.52), and decreasing the nitrate content (26.93–40.17%). Furthermore, the application of green manure rotation or biochar alone or in combination significantly improved the absorption of nitrogen (23.73–60.23%), phosphorus (18.12–61.71%), and potassium (20.57–61.48%) nutrients in the continuous cropping of peppers, which contributed to the improvement of fertilizer use efficiency. Notably, GP + B treatment not only improved the yield and quality of continuous cropping peppers but also resulted in higher production value and net income compared to the GP and WP + B treatments. In conclusion, the combination of green manure rotation and biochar application represents an effective strategy for mitigating the challenges of continuous cropping in pepper cultivation within the karst mountainous regions of Southwest China. Full article

Signal distortion bias (SDB) in Global Navigation Satellite System (GNSS) data processing, defined as the time difference between the distorted chip and the ideal rectangular chip, leads to systematic biases in pseudoranges, affecting satellite and receiver differential code biases (DCBs). The stability of SDBs, allowing them to be treated as constant values, highlights the importance of investigating both their stability and estimation accuracy. Two different methods are used to estimate SDBs: (1) the hybrid method and (2) the geometry-free method. Data from approximately 430 stations, spanning the entire year of 2021, were analyzed to evaluate the estimation accuracy and the short-term and long-term stability of GPS SDBs. The analysis focused on two code signals: C1C (L1 Coarse/Acquisition) and C2W (L2 P(Y)). The results show that the short-term and long-term stability of GPS C1C and C2W SDBs is comparable for both methods, with only minor variations between them. Additionally, one month of data were used to validate the accuracy of estimated SDBs across different receiver groups. The results demonstrate that geometry-free SDBs provide stable satellite DCB estimates with an average bias below 0.15 ns and minimal residual biases, while hybrid SDBs provide satellite DCB estimates with an average bias below 0.20 ns. Overall, the comparison underscores the superior performance of geometry-free SDBs in achieving consistent satellite DCB estimates. Full article

FOLFIRI (5-FU, leucovorin, irinotecan) is the first-line chemotherapy for metastatic colorectal cancer (mCRC), but response rates are under 50%. This study aimed to develop a predictive signature for FOLFIRI response in mCRC patients. Firstly, Spearman’s rank correlation and Wilcoxon rank-sum test were used to select chemotherapy response genes and gene pairs, respectively. Then, an optimization procedure was used to determine the final signature. A predictive signature consisting of three gene pairs (3-GPS) was identified. In the training set, 3-GPS achieved an accuracy of 0.94. In a validation set of 60 samples, predicted responders had significantly better progression-free survival than the predicted non-responders (HR = 0.47, p = 0.01). A comparable result was observed in an additional validation set of 27 samples (HR = 0.06, p = 0.02). The co-expressed genes of the signature were enriched in pathways associated with the immunotherapy response, and they interacted extensively with FOLFIRI-related genes. Notably, the expression of signature genes significantly correlated with various immune cell types, including plasma cells and memory-resting CD4+ T cells. In conclusion, the REO-based signature effectively identifies mCRC patients likely to benefit from FOLFIRI. Furthermore, these signature genes may play a crucial role in the chemotherapy. Full article

Activating tumor necrosis factor receptor 1 (TNFR1) with tumor necrosis factor alpha (TNFα) is one of the key pathological mechanisms resulting in the exacerbation of rheumatoid arthritis (RA) immune response. Despite various types of drugs being available for the treatment of RA, a series of shortcomings still limits their application. Therefore, developing novel peptide drugs that target TNFα-TNFR1 interaction is expected to expand therapeutic drug options. In this study, the detailed interaction mechanism between TNFα and TNFR1 was elucidated, based on which, a series of linear peptides were initially designed. To overcome its large conformational flexibility, two different head-to-tail cyclization strategies were adopted by adding a proline-glycine (GP) or cysteine-cysteine (CC) to form an amide or disulfide bond between the N-C terminal. The results indicate that two cyclic peptides, R1_CC4 and α_CC8, exhibit the strongest binding free energies. α_CC8 was selected for further optimization using virtual mutations through in vitro activity and toxicity experiments due to its optimal biological activity. The L16R mutant was screened, and its binding affinity to TNFR1 was validated using ELISA assays. This study designed a novel cyclic peptide structure with potential anti-inflammatory properties, possibly bringing an additional choice for the treatment of RA in the future. Full article

Drone target tracking, which involves instructing drone movement to follow a moving target, encounters several challenges: (1) traditional methods need accurate state estimation of both the drone and target; (2) conventional Proportional–Derivative (PD) controllers require tedious parameter tuning and struggle with nonlinear properties; and (3) reinforcement learning methods, though promising, rely on the drone’s self-state estimation, adding complexity and computational load and reducing reliability. To address these challenges, this study proposes an innovative model-free end-to-end reinforcement learning framework, the VTD3 (Vision-Based Twin Delayed Deep Deterministic Policy Gradient), for drone target tracking tasks. This framework focuses on controlling the drone to follow a moving target while maintaining a specific distance. VTD3 is a pure vision-based tracking algorithm which integrates the YOLOv8 detector, the BoT-SORT tracking algorithm, and the Twin Delayed Deep Deterministic Policy Gradient (TD3) algorithm. It diminishes reliance on GPS and other sensors while simultaneously enhancing the tracking capability for complex target motion trajectories. In a simulated environment, we assess the tracking performance of VTD3 across four complex target motion trajectories (triangular, square, sawtooth, and square wave, including scenarios with occlusions). The experimental results indicate that our proposed VTD3 reinforcement learning algorithm substantially outperforms conventional PD controllers in drone target tracking applications. Across various target trajectories, the VTD3 algorithm demonstrates a significant reduction in average tracking errors along the X-axis and Y-axis of up to $34.35\%$ and $45.36\%$, respectively. Additionally, it achieves a notable improvement of up to $66.10\%$ in altitude control precision. In terms of motion smoothness, the VTD3 algorithm markedly enhances performance metrics, with improvements of up to $37.70\%$ in jitter and $60.64\%$ in Jerk RMS. Empirical results verify the superiority and feasibility of our proposed VTD3 framework for drone target tracking. Full article

(a) Introduction: Zambia’s poultry industry comprises commercial chickens and small-scale producers of indigenous chickens (Gallus domesticus) (ICs). Large, integrated entities run the commercial chicken sector, while the indigenous chicken sector (IC sector) is predominantly run by small-scale farmers (SSFs). Increased costs and low access to formal markets for commercial chickens have motivated SSFs to enter the IC sector under the free-range system (FRS) and semi-intensive system (SIS). (b) Objective: This study aimed to highlight the price changes in poultry inputs and outputs and demonstrate that the IC sector has more potential to contribute to farm income than commercial chickens under family poultry production systems. (c) Method: We analysed the prices for inputs and outputs for Zambia’s poultry industry for the first quarter of 2016 to 2023 using data from the Poultry Association of Zambia (PAZ). We also analysed data from the 2021 Qualtrics survey to investigate the crops grown and crops used as feed and feed ingredients, the sources of feed, and the use of minerals and vitamins by SSFs for chickens. The gross profit (GP) and benefit–cost ratio (BCR) were analysed to compare the viability and profitability of ICs and broilers under SSFs. (d) Results: Our study shows that prices for day-old chicks (DOCs) and point-of-lay (POL) pullets increased by 57–125%, broiler and layer feeds increased by 67–96%, and soybean meal (SBM) and fishmeal rose by 143–229%. Prices for live ICs, commercial broilers, and ex-layers increased by 150%, 79%, and 71%, respectively. Egg prices rose by 100–124%. Farmers tried to look for local feed sources. Over 21% of the crops grown was maize, and nearly 43% was used for feed. (e) Conclusion: Our analysis and comparison between the ICs and broilers demonstrated that SSFs could achieve more farm income by producing ICs than commercial broilers. Full article

This study aimed to investigate the feasibility of using geopolymer paste (GP) as an adhesive agent for (i) anchoring steel bars in concrete substrates, (ii) repairing concrete, and (iii) repairing limestone and granite masonry blocks commonly found in historic buildings. In this investigation, seven cement-free GP mixes were developed with different combinations of binder materials (slag, silica fume, and metakaolin). The mechanical properties, adhesive performance, and production cost of the developed GP mixes were compared to those of a commercially epoxy adhesive mortar (EAM). The results obtained from this study indicated that the use of GPs enhanced the bonding between steel bars and concrete substrates, achieving bonding strengths that were 19.7% to 49.2% higher than those of control specimens with steel bars directly installed during casting. In concrete repairs, the GPs were able to restore about 60.6% to 87.9% of the original capacity of the control beams. Furthermore, GPs exhibited a promising performance in repairing limestone and granite masonry blocks, highlighting their potential suitability for masonry structures. The best adhesive performance was observed when a ternary binder material system consisting of 70% slag, 20% metakaolin and 10% silica fume was used. This combination, compared to the investigated EAM, showed comparable adhesive properties at a significantly low cost, indicating the viability of GPs as a cost-effective, eco-friendly adhesive agent. Full article