Search Results (16)

This paper addresses the challenge of cooperatively escorting a moving underwater target, such as a human-occupied vehicle (HOV), using a multi-AUV formation in complex ocean environments. We propose a comprehensive framework, RG-SAPF scheme, that integrates a rigidity graph (RG)-based reconfigurable formation control strategy with a safe artificial potential field (SAPF) motion planning method. The RG-based controller enables the AUVs to form and dynamically reconfigure a 3D escort formation around the target using only relative position information, ensuring the target remains within the formation’s convex hull. Meanwhile, the SAPF algorithm, enhanced with an adaptive Widrow–Hoff rule, enables real-time and collision-free path planning in obstacle-rich environments. Simulation and experimental results demonstrate that the proposed method effectively maintains formation integrity, supports flexible obstacle avoidance, and provides continuous target escort under dynamic conditions, validating its potential for practical underwater escort applications. Full article

This paper considers a target-defense game in an open area with one or two defenders as well as an intruder. The intruder endeavors to reach the boundary of the island, while the defenders strive to prevent that by capturing the intruder through contact. Islands, as closed areas, restrict the free movement of the defenders, since the defenders—represented by USVs—cannot traverse the target area directly. First, we are concerned with the barrier, which is the boundary of the winning zones, taking into account the impact of the target. For the initial states lying in the defenders’ winning zone, there exists a strategy for the defenders to intercept the intruder regardless of the intruder’s best effort, while for the initial states lying in the intruder’s winning zone, the intruder can always invade successfully. We propose a geometric method to construct the barrier analytically for two kinds of speed ratios. Then, by taking index functions into consideration, we present optimal strategies for the players after constructing the dominance regions when their initial states lie in different winning zones. Simulation results verify the effectiveness of the proposed method. This study can be extended to scenarios involving multiple defenders. Full article

Middle East Respiratory Syndrome (MERS-CoV) is a coronavirus-caused viral respiratory infection initially detected in Saudi Arabia in 2012. In UAE, high seroprevalence (97.1) of MERS-CoV in camels was reported in several Emirate of Abu Dhabi studies, including camels in zoos, public escorts, and slaughterhouses. The objectives of this research include simulation of MERS-CoV spread using a customized animal disease spread model (i.e., customized stochastic model for the UAE; analyzing the MERS-CoV spread and prevalence based on camels age groups and identifying the optimum control MERS-CoV strategy. This study found that controlling animal mobility is the best management technique for minimizing epidemic length and the number of affected farms. This study also found that disease dissemination differs amongst camels of three ages: camel kids under the age of one, young camels aged one to four, and adult camels aged four and up; because of their immunological state, kids, as well as adults, had greater infection rates. To save immunization costs, it is advised that certain age groups be targeted and that intense ad hoc unexpected vaccinations be avoided. According to the study, choosing the best technique must consider both efficacy and cost. Full article

The prevalence of metabolic dysfunction-associated steatotic liver disease (MASLD) is rapidly increasing worldwide at an alarming pace, due to an increase in obesity, sedentary and unhealthy lifestyles, and unbalanced dietary habits. MASLD is a unique, multi-factorial condition with several phases of progression including steatosis, steatohepatitis, fibrosis, cirrhosis, and hepatocellular carcinoma. Sterol element binding protein 1c (SREBP1c) is the main transcription factor involved in regulating hepatic de novo lipogenesis. This transcription factor is synthesized as an inactive precursor, and its proteolytic maturation is initiated in the membrane of the endoplasmic reticulum upon stimulation by insulin. SREBP cleavage activating protein (SCAP) is required as a chaperon protein to escort SREBP from the endoplasmic reticulum and to facilitate the proteolytic release of the N-terminal domain of SREBP into the Golgi. SCAP inhibition prevents activation of SREBP and inhibits the expression of genes involved in triglyceride and fatty acid synthesis, resulting in the inhibition of de novo lipogenesis. In line, previous studies have shown that SCAP inhibition can resolve hepatic steatosis in animal models and intensive research is going on to understand the effects of SCAP in the pathogenesis of human disease. This review focuses on the versatile roles of SCAP/SREBP regulation in de novo lipogenesis and the structure and molecular features of SCAP/SREBP in the progression of hepatic steatosis. In addition, recent studies that attempt to target the SCAP/SREBP axis as a therapeutic option to interfere with MASLD are discussed. Full article

The cell-surface targeting of neo-synthesized G protein-coupled receptors (GPCRs) involves the recruitment of receptors into COPII vesicles budding at endoplasmic reticulum exit sites (ERESs). This process is regulated for some GPCRs by escort proteins, which facilitate their export, or by gatekeepers that retain the receptors in the ER. PRAF2, an ER-resident four trans- membrane domain protein with cytoplasmic extremities, operates as a gatekeeper for the GB1 protomer of the heterodimeric GABA_B receptor, interacting with a tandem di-leucine/RXR retention motif in the carboxyterminal tail of GB1. PRAF2 was also reported to interact in a two-hybrid screen with a peptide corresponding to the carboxyterminal tail of the chemokine receptor CCR5 despite the absence of RXR motifs in its sequence. Using a bioluminescence resonance energy transfer (BRET)-based subcellular localization system, we found that PRAF2 inhibits, in a concentration-dependent manner, the plasma membrane export of CCR5. BRET-based proximity assays and Co-IP experiments demonstrated that PRAF2/CCR5 interaction does not require the presence of a receptor carboxyterminal tail and involves instead the transmembrane domains of both proteins. The mutation of the potential di-leucine/RXR motif contained in the third intracellular loop of CCR5 does not affect PRAF2-mediated retention. It instead impairs the cell-surface export of CCR5 by inhibiting CCR5’s interaction with its private escort protein, CD4. PRAF2 and CD4 thus display opposite roles on the cell-surface export of CCR5, with PRAF2 inhibiting and CD4 promoting this process, likely operating at the level of CCR5 recruitment into COPII vesicles, which leave the ER. Full article

Choroideremia (CHM) is a rare X-linked chorioretinal dystrophy, affecting the photoreceptors, retinal pigment epithelium (RPE) and choroid, with no approved therapy. CHM is caused by mutations in the CHM gene, which encodes the ubiquitously expressed Rab escort protein 1 (REP1). REP1 is involved in prenylation, a post-translational modification of Rab proteins, and plays an essential role in intracellular trafficking. In this study, we examined oxidative and endoplasmic reticulum (ER) stress pathways in chm^ru848 zebrafish and CHM^Y42X patient fibroblasts, and screened a number of neuroprotectants for their ability to reduce stress. The expression of the oxidative stress markers txn, cat and sod3a, and the ER stress markers bip, atf4 and atf6, were dysregulated in chm^ru848 fish. The expression of SOD2 was also reduced in CHM^Y42X fibroblasts, along with reduced BIP and increased CHOP expression. The lack of REP1 is associated with defects in vesicular trafficking, photoreceptor outer segment phagocytosis and melanosome transport, leading to increased levels of stress within the retina and RPE. Drugs targeting oxidative and ER stress pathways represent novel therapeutic avenues. Full article

In order to achieve the goal of carbon peaking and carbon neutralization, we must vigorously develop renewable energy. As one of the important renewable energy sources, the development and utilization of biomass energy has a high cost, and it is difficult to compete with traditional fossil energy in the early stage of development. Therefore, it is necessary for the government to escort the development of the biomass energy industry through legal means. First of all, on the basis of fully analyzing the development prospects of China’s biomass energy, the article sorts out the laws and regulations related to biomass energy in China, and finds the shortcomings. Secondly, this paper draws on the institutional experience of the United States, Brazil, Sweden and other countries with relatively developed biomass energy industry, and provides suggestions for improvement from three aspects: law, policy and administrative system, with a view to supporting China’s development of biomass energy industry and realizing the “dual carbon target” theoretically. Full article

Gene delivery is the basis for developing gene therapies that, in the future, may be able to cure virtually any disease, including viral infections. The use of short interfering RNAs (siRNAs) targeting viral replication is a novel strategy for treating HIV-1 infection. In this study, we prepared chitosan particles containing siRNA tat/rev via ionotropic gelation. Chitosan-based particles were efficiently internalized by cells, as evidenced by fluorescence microscopy. The antiviral effect of chitosan-based particles was studied on the C8166 cell line infected with HIV-1 and compared with the use of commercial liposomes (ESCORT). A significant reduction in HIV replication was also observed in cells treated with empty chitosan particles, suggesting that chitosan may interfere with the early steps of the HIV life cycle and have a synergic effect with siRNA to reduce viral replication significantly. Full article

Poor anti-metastasis effects and side-effects remain a challenge for the clinical application of camptothecin (CPT). Mitochondria can be a promising target for the treatment of metastatic tumors due to their vital roles in providing energy supply, upregulating pro-metastatic factors, and controlling cell-death signaling. Thus, selectively delivering CPT to mitochondria appears to be a feasible way of improving the anti-metastasis effect and reducing adverse effects. Here, we established a 2-(dimethylamino) ethyl methacrylate (DEA)-modified N-(2-hydroxypropyl) methacrylamide (HPMA) copolymer–CPT conjugate (P-DEA-CPT) to mediate the mitochondrial accumulation of CPT. The mitochondria-targeted P-DEA-CPT could overcome multiple barriers by quickly internalizing into 4T1 cells, then escaping from lysosome, and sufficiently accumulating in mitochondria. Subsequently, P-DEA-CPT greatly damaged mitochondrial function, leading to the reactive oxide species (ROS) elevation, energy depletion, apoptosis amplification, and tumor metastasis suppression. Consequently, P-DEA-CPT successfully inhibited both primary tumor growth and distant metastasis in vivo. Furthermore, our studies revealed that the mechanism underlying the anti-metastasis capacity of P-DEA-CPT was partially via downregulation of various pro-metastatic proteins, such as hypoxia induction factor-1α (HIF-1α), matrix metalloproteinases-2 (MMP-2), and vascular endothelial growth factor (VEGF). This study provided the proof of concept that escorting CPT to mitochondria via a mitochondrial targeting strategy could be a promising approach for anti-metastasis treatment. Full article

Pregnant women usually turn to natural products to relieve pregnancy-related ailments which might pose health risks. Mentha pulegium L. (MP, Lamiaceae) is a common insect repellent, and the present work validates its abortifacient capacity, targeting morphological anomalies, biological, and behavioral consequences, compared to misoprostol. The study also includes untargeted metabolite profiling of MP extract and fractions thereof viz. methylene chloride (MecH), ethyl acetate (EtOAc), butanol (But), and the remaining liquor (Rem. Aq.) by UPLC-ESI-MS-TOF, to unravel the constituents provoking abortion. Administration of MP extract/fractions, for three days starting from day 15th of gestation, affected fetal development by disrupting the uterine and placental tissues, or even caused pregnancy termination. These effects also entailed biochemical changes where they decreased progesterone and increased estradiol serum levels, modulated placental gene expressions of both MiR-(146a and 520), decreased uterine MMP-9, and up-regulated TIMP-1 protein expression, and empathized inflammatory responses (TNF-α, IL-1β). In addition, these alterations affected the brain's GFAP, BDNF, and 5-HT content and some of the behavioral parameters escorted by the open field test. All these incidences were also perceived in the misoprostol-treated group. A total of 128 metabolites were identified in the alcoholic extract of MP, including hydroxycinnamates, flavonoid conjugates, quinones, iridoids, and terpenes. MP extract was successful in terminating the pregnancy with minimal behavioral abnormalities and low toxicity margins. Full article

The translation of RNA into protein is a dynamic process which is heavily regulated during normal cell physiology and can be dysregulated in human malignancies. Its dysregulation can impact selected groups of RNAs, modifying protein levels independently of transcription. Integral to their suitability for translation, RNAs undergo a series of maturation steps including the addition of the m⁷G cap on the 5′ end of RNAs, splicing, as well as cleavage and polyadenylation (CPA). Importantly, each of these steps can be coopted to modify the transcript signal. Factors that bind the m⁷G cap escort these RNAs through different steps of maturation and thus govern the physical nature of the final transcript product presented to the translation machinery. Here, we describe these steps and how the major m⁷G cap-binding factors in mammalian cells, the cap binding complex (CBC) and the eukaryotic translation initiation factor eIF4E, are positioned to chaperone transcripts through RNA maturation, nuclear export, and translation in a transcript-specific manner. To conceptualize a framework for the flow and integration of this genetic information, we discuss RNA maturation models and how these integrate with translation. Finally, we discuss how these processes can be coopted by cancer cells and means to target these in malignancy. Full article

Autonomous unmanned aerial vehicles work seamlessly within the GPS signal range, but their performance deteriorates in GPS-denied regions. This paper presents a unique collaborative computer vision-based approach for target tracking as per the image’s specific location of interest. The proposed method tracks any object without considering its properties like shape, color, size, or pattern. It is required to keep the target visible and line of sight during the tracking. The method gives freedom of selection to a user to track any target from the image and form a formation around it. We calculate the parameters like distance and angle from the image center to the object for the individual drones. Among all the drones, the one with a significant GPS signal strength or nearer to the target is chosen as the master drone to calculate the relative angle and distance between an object and other drones considering approximate Geo-location. Compared to actual measurements, the results of tests done on a quadrotor UAV frame achieve $99\%$ location accuracy in a robust environment inside the exact GPS longitude and latitude block as GPS-only navigation methods. The individual drones communicate to the ground station through a telemetry link. The master drone calculates the parameters using data collected at ground stations. Various formation flying methods help escort other drones to meet the desired objective with a single high-resolution first-person view (FPV) camera. The proposed method is tested for Airborne Object Target Tracking (AOT) aerial vehicle model and achieves higher tracking accuracy. Full article

The 26S proteasome is a 2.5-MDa protease complex responsible for the selective and ATP-dependent degradation of ubiquitylated proteins in eukaryotic cells. Proteasome-mediated protein degradation accounts for ~70% of all cellular proteolysis under basal conditions, and thereby any dysfunction can lead to drastic changes in cell homeostasis. A major function of ubiquitylation is to target proteins for proteasomal degradation. Accompanied by deciphering the structural diversity of ubiquitin chains with eight linkages and chain lengths, the ubiquitin code for proteasomal degradation has been expanding beyond the best-characterized Lys48-linked ubiquitin chains. Whereas polyubiquitylated proteins can be directly recognized by the proteasome, in several cases, these proteins need to be extracted or segregated by the conserved ATPases associated with diverse cellular activities (AAA)-family ATPase p97/valosin-containing protein (VCP) complex and escorted to the proteasome by ubiquitin-like (UBL)–ubiquitin associated (UBA) proteins; these are called substrate-shuttling factors. Furthermore, proteasomes are highly mobile and are appropriately spatiotemporally regulated in response to different cellular environments and stresses. In this review, we highlight an emerging key link between p97, shuttling factors, and proteasome for efficient proteasomal degradation. We also present evidence that proteasome-containing nuclear foci form by liquid–liquid phase separation under acute hyperosmotic stress. Full article

This study investigates the coordinated control problem of Euler–Lagrange systems with model uncertainties in environments containing obstacles when escorting a target. Using an outer–inner loop control structure, a null-space-based behavioral (NSB) control architecture was proposed in the outer loop considering obstacles. This architecture generates the desired velocity for the inner loop. The adaptive proportional derivative sliding mode control (APD-SMC) law was applied to the inner loop to ensure fast convergence and robustness. All the robots were distributed around the target evenly and escorted the target at a specified distance while avoiding obstacles in a $p-$ dimensional space (where $p\ge 2$ is a positive integer). Stability and convergence analyses were conducted rigorously using a Lyapunov-based approach. The simulation results of three scenarios verified the effectiveness and high-precision performance of the proposed control algorithm compared to that of the adaptive sliding mode control (ASMC) in both two-dimensional and three-dimensional space. It is shown that all the robots can move into appropriate positions on the surface of a sphere/circle during an escort mission and reconfigure the formation automatically when an obstacle avoidance mission is active. Full article

Currently, RNAi based approaches for cancer treatment involving short double stranded RNA molecules (siRNA) are under vigorous scrutinization. Due to numerous biological obstacles, siRNA delivery into target cells requires protective escort. On the other hand, combining of siRNA-mediated gene silencing and action of conventional chemotherapeutics can propose additional enhancement of anticancer activity. In the present study, we investigated a siRNA cocktail able to downregulate anti-apoptotic genes (BCL-xL, BCL-2, MCL-1) and the chemotherapeutic agent 5-fluorouracil (5-FU) to evaluate multi-target cytotoxic effect on human cervical carcinoma cells (HeLa cell line). Novel phosphorus containing dendrimers of 3rd and 4th generations (namely AE2G3 and AE2G4) with voluminous piperidine terminal cationic groups were designed and tested as siRNA carriers. Dendrimers of both generations showed remarkable ability to bind pro-apoptotic siRNAs and provided 80–100% siRNA uptake by HeLa cells in the serum containing medium, while the widespread transfection agent Lipofectamine showed only ~40% uptake. SiRNA cocktail (in low concentrations 50 and 100 nM) delivered by AE2G3 dendrimer caused almost complete elimination of cancer cells. We have discovered considerable increase of 5-FU cytotoxic effect by addition of AE2G3/siRNA cocktail complexes in low doses. Thus, we demonstrated the effectiveness of combined multi-target siRNA anticancer approach and described new highly effective serum stable nanomaterial vehicle for gene-based drugs. Full article