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Advances in Molecular Mechanisms and Therapies for Rett Syndrome: From MECP2 Dysfunction to Small-Molecule Interventions
No full textRett syndrome (RTT) is a rare and severe neurodevelopmental disorder primarily affecting females, caused by pathogenic mutations in the MECP2 gene, which disrupts neuronal transcriptional regulation and synaptic function. Understanding the molecular basis of MECP2dysfunction has catalyzed the development of targeted therapies aiming to restore neuronal homeostasis. This paper integrates current knowledge of MECP2 structure, function and mutation-driven pathology, highlighting how disruptions in its methyl-CpG-binding, transcriptional repression, and C-terminal domains lead to widespread neuronal deficits. This study summarizes emerging therapeutic strategies, focusing on small-molecule approaches including protein stabilization, readthrough compounds, synaptic and neurotrophic pathway modulation and epigenetic regulation. Notably, trofinetide, the first FDA-approved therapy, underscores the potential of translational progress while revealing limitations in delivery and efficacy. This paper further discusses cutting-edge drug discovery pipelines leveraging iPSC-derived neurons and organoids, and explores future solutions such as nanocarriers, PROTACs and precision medicine approaches. By bridging molecular mechanisms to therapeutic innovation, this review underscores the promise of rationally designed treatments to move beyond symptomatic management toward disease modification in RTT
Real-time evaluation of wear condition in aviation self-lubricating bearings based on acoustic emission
No full textWear of the self-lubricating liner in aviation spherical plain bearings leads to increased clearance between the inner and outer rings, causing precision degradation of the control mechanism, thereby seriously threatening flight safety. Acoustic emission (AE)-based condition monitoring possesses many advantages such as high sensitivity, early-warning capability, and strong anti-interference performance, which can effectively address the limitation of traditional inspection methods in their inability to real-time characterize bearing operational states. First, a wear test setup with multiaxial loading capability for self-lubricating bearings and a split-type bearing base integrated with embedded AE sensors were designed, ensuring the fidelity of AE signal acquisition. Then, the evolutionary laws of AE signals from self-lubricating bearings in both time and frequency domains were studied, revealing the dual dominant frequency characteristics of AE signals and their dynamic energy evolution mechanism. A method for constructing bearing wear index based on acoustic emission time-frequency features and the multi-criteria feature selection strategy was proposed, enabling real-time assessment of the wear condition of self-lubricating bearings via wear index curves. It was found that the dynamic equilibrium of the PTFE transfer film in the bearing liner influences the energy distribution of AE frequency components. The critical transition interval for the test bearings between the running-in phase and stable wear phase was identified as 9 747 to 10 773 revolutions; and it was determined that the test bearings ultimately remained in the stable wear phase. Finally, the accuracy of the proposed wear index-based condition prediction method was validated using torque data. Furthermore, the micro-wear characteristics of the bearings were characterized through scanning electron microscopy (SEM) and energy-dispersive spectroscopy (EDS). The migration behavior of the PTFE transfer film and the interfacial chemical composition under the final wear state demonstrated the consistency of the wear phase determination
Optimization of refueling docking trajectory for multi-UAV formation
No full textAiming at the optimization of autonomous docking trajectory of unmanned receiver in the in-flight refueling, a high-precision computational fluid dynamics method was used to calculate the dangerous area behind the refueling aircraft as the obstacle in the flight environment in the docking trajectory planning. An improved ant colony algorithm is proposed, which uses reverse learning to form a better initial population and greatly improves the convergence speed of the algorithm. Then the weight of the two cost functions of track safety and track distance is adaptively adjusted by using the fuzzy control, and the track distance is shortened on the premise of keeping the flight safety of the oil receiving aircraft. The simulated results show that the improved ant colony algorithm can realize the autonomous docking trajectory planning of single unmanned oil receiver and multi-aircraft formation refueling, and has higher track safety and faster convergence speed than the traditional ant colony algorithm
Income Risk Analysis and Sustainability of Shallot Farming in Bantul Yogyakarta, Indonesia
No full textThis study examines three key aspects of shallot farming in Srigading Village: (1) farmers' income, the associated income risks, and their determining factors; (2) the overall sustainability performance of the farming system; and (3) the relationship between income and sustainability indicators. The research location was purposively selected, and 100 farmers were surveyed using proportional random sampling. Data were analyzed through descriptive quantitative methods, including risk analysis, sustainability index assessment, multiple linear regression, and Spearman rank correlation. Findings indicate that average farmer income reached IDR 9,589,576 per season. However, the income risk was high, with a coefficient of variation of 1.16 (116%), reflecting extreme seasonal volatility and substantial uncertainty for farmers. Income was significantly influenced by KCl fertilizer costs, organic fertilizer expenditure, and labor inputs, while income risk was affected by the costs of KCl fertilizer, labor, NPK fertilizer, and organic fertilizers. The sustainability index reached 52.80, indicating moderate sustainability. Although income showed no significant correlation with the overall sustainability score, it was positively associated with economic sustainability and negatively associated with ecological and social dimensions
The Impact of Crude Palm Oil Downstreaming Policies on the Indonesian Palm Oil Industry
No full textThe Indonesian palm oil industry plays a strategic role in the national economy, both as a source of foreign exchange, a major employer, and a driver of regional growth. However, the dominance of crude palm oil (CPO) exports raises concerns about the resilience of domestic value addition and vulnerability to global price fluctuations. To address this, the government is promoting downstreaming policies through mandatory biodiesel use as a means of strengthening the industry's structure. This study aims to analyze the performance of biodiesel policies in supporting CPO downstreaming, identify the factors influencing biodiesel development, and evaluate their impact on the Indonesian palm oil industry. This study employed a simultaneous equation model with nine structural equations estimated using the Two Stage Least Squares (2SLS) method, validated using RMSPE and U-Theil. Time series data from 2000 to 2024 were used to analyze key variables such as oil palm plantation area, domestic CPO prices, biodiesel production, and exports. The analysis results indicated that the B35 and B40 mandatory policies had driven increases in biodiesel prices and exports, but on the other hand, they had reduced CPO exports and crude palm oil production. This signified a shift in the industry's orientation from raw material exports to domestic value-added utilization. These policies had important implications for energy distribution, price stability, and the competitiveness of the national industry. Therefore, further policy support is needed in the form of incentives, infrastructure strengthening, and a balance between energy, food, and environmental needs to achieve sustainable palm oil downstreaming
Quantifying Indonesia's Coffee Stockout Risk: A Monte Carlo Simulation of Production-Consumption Gaps
No full textAs Indonesia's premier agricultural export commodity, coffee faces an emerging domestic supply crisis. This study examines Indonesia's coffee stock dynamics through Monte Carlo simulation, utilizing secondary data from FAO and IPCC (2010-2019) encompassing production, consumption, trade flows, stocks, and climate parameters. Four key metrics—Self-Sufficiency Ratio (SSR), Import Dependency Ratio (IDR), Export Intensity Ratio (EIR), and Food Security Index (FSI)—quantify sectoral vulnerabilities. Results indicate Indonesia's coffee exports exceed domestic production, creating supply deficits exacerbated by climate change impacts, particularly El Nino events. The analysis reveals critical thresholds where export-oriented policies compromise domestic availability. Three mitigation strategies emerge: a 20% export reduction to rebalance domestic supply, cultivation of climate-resilient coffee varieties to enhance production, and implementation of a buffer stock policy to stabilize domestic markets. These measures address the fundamental tension between maintaining export competitiveness and ensuring national coffee security amid changing climatic conditions
Seventy-five years later, the prisoner's dilemma narrative continues to impart new wisdom
No full textThe prisoner's dilemma (PD) portrays the fundamental challenge of social interaction and ranks among the most-important models in the social sciences. Over the past two decades, the study of the PD has experienced a resurgence due to the introduction of concepts and techniques from statistical physics. In this Perspective, we recount the history of the substantive narrative underlying the PD to physicists who may not have encountered it yet and we show —on the narrative's 75th anniversary— that the original PD narrative hinted at a solution to the very problem of cooperation that it sought to describe. These hints at a solution to the PD foreshadowed a fascinating stream of contemporary research, thus further establishing the richness of the PD's narrative: 75 years after its inaugural articulation, the PD's substantive narrative continues to impart new wisdom
Influence of hybrid fibers on the fresh and hardened properties of silica fume blended concrete
No full textThis research explores impact of hybrid steel (ST) and polypropylene (PP) fibers on both fresh and hardened behavior of 10% silica fume (SF) blended M30 concrete. Hybrid fibers are introduced at dosages of 0%, 0.5%, 1.0%, 1.5%, and 2.0% total volume (equal proportions of ST and PP). As the fiber dosage increased, the slump declined from 132 mm (control) to 34 mm (2.0% hybrid fiber), reflecting decreased workability. The initial and final setting times increased from 3 h 15 min and 5 h 20 min (control) to 5 h 30 min and 7 h 50 min (2.0% hybrid fiber). The 28-day compressive strength augmented to a maximum of 49.5 MPa at 1.0% hybrid fiber compared to 39 MPa for the control sample. However, the flexural strength increased from 4.3 MPa to a highest of 6.5 MPa at 1.0% hybrid fiber. Increasing the fiber dosage increased fiber balling, contributing to less strength due to poor packing. Therefore, the optimal hybrid fiber dosage is determined to be 1.0% by volume (0.5% ST + 0.5% PP) because this dosage provides the best mechanical performance, crack resistance, and acceptable fresh properties. This configuration provides good post-crack performance as well as acceptable workability and setting times for structural applications
Performance of TiO
No full textThis study examines the performance of TiO2 nanolubricant at concentrations of 0, 0.2, and 0.4 g/L in a slightly modified refrigeration system, tested with door openings of 30, 60, 120, 180, 240, and 300 seconds. The system was charged with 30 g of either LPG or R600a refrigerant, combined with the specified TiO2 concentrations. Monitoring involved a digital pressure gauge, K-type thermocouples, and a wattmeter to assess energy behaviour under closed and open-door conditions. Key performance metrics included closed-door pull-down time, open-door air infiltration heat rate and load, power consumption, compressor power, and recovery rate. All tests complied with ISO 8187, achieving a minimum evaporator air temperature of -3°C within one hour of continuous operation. For both R600a and LPG refrigerants, air infiltration heat rate and load decreased from 0.02162 m3/s and 2.4365 kW at 30 seconds to 0.02085 m3/s and 0.602 kW for door openings of 60 to 300 seconds. Conversely, recovery rate, energy consumption, and compressor power increased with longer door openings. Adding TiO2 nanolubricant reduced recovery rate by 1.08%65.8% for R600a and 2.12% - 85% for LPG, compressor power by 4.14%43.01% for R600a and 5.92% -30.92% for LPG, and energy consumption by 13.33% - 66.67% for R600a and 5.88% - 80% for LPG. Overall, TiO2 nanolubricants substantially mitigated the impact of air infiltration into the evaporator cabinet
Sustainable water pumping using hybrid renewable energy sources
No full textThe water-energy nexus indicates today's intricate interdependence of water and energy and holds the key to human well-being and national development. It is particularly significant in countries with arid climatic conditions, such as is the case with Namibia, where water scarcity is coupled with a huge gap between electricity supply and demand. In this paper, we assessed the viability of using Hybrid Renewable Energy Systems (HRES) to sustainably power borehole schemes in Namibia. As a case study, grid-connected photovoltaic (PV), onshore wind, and battery storage technologies were used to meet the electric energy demands at the Berg Aukas borehole scheme, which consumes an average of 7,820 kWh/day with a peak demand of 1,162.5 kW. HOMER Grid software was used to model the utility grid tariff and net metering structures and determine optimal system configurations. For the sensitivity analysis, the discount rate (interest rate) was used as a sensitivity variable. The results show that at Namibia's average discount rate of 6.7%, the proposed optimal HRES had a levelized cost of energy (LCOE) and payback period of USD 0.0929 /kWh and 4.17 years, respectively. At a discount rate of 10%, the optimal HRES had an LCOE of USD 0.105 /kWh with a projected payback period of 3.77 years. At a discount rate of 13%, the LCOE was USD 0.115 /kWh with a payback period of 3.43 years. For all the modelled instances, the proposed systems for the borehole scheme were found to be economically feasible as each had a LCOE that was lower than that of the utility company (CENORED), i.e., USD 0.283 /kWh