2D, 3D-QSAR study and docking of vascular endothelial growth factor receptor 3 (VEGFR3) inhibitors for potential treatment of retinoblastoma

Background: Retinoblastoma is currently the most common malignant tumor seen in newborns and children’s eyes worldwide, posing a life-threatening hazard. Chemotherapy is an integral part of retinoblastoma treatment. However, the chemotherapeutic agents used in clinics often lead to drug resistance. Thus there is a need to investigate new chemotherapy-targeted agents. VEGFR3 inhibitors are anti-tumour-growth and could be used to develop novel retinoblastoma-targeted agents.Objective: To predict drug activity, discover influencing factors and design new drugs by building 2D, 3D-QSAR models.Method: First, linear and non-linear QSAR models were built using heuristic methods and gene expression programming (GEP). The comparative molecular similarity indices analysis (COMISA) was then used to construct 3D-QSAR models through the SYBYL software. New drugs were designed by changing drug activity factors in both models, and molecular docking experiments were performed.Result: The best linear model created using HM had an R2, S2, and R2cv of 0.82, 0.02, and 0.77, respectively. For the training and test sets, the best non-linear model created using GEP had correlation coefficients of 0.83 and 0.72 with mean errors of 0.02 and 0.04. The 3D model designed using SYBYL passed external validation due to its high Q2 (0.503), R2 (0.805), and F-value (76.52), as well as its low standard error of SEE value (0.172). This demonstrates the model’s reliability and excellent predictive ability. Based on the molecular descriptors of the 2D model and the contour plots of the 3D model, we designed 100 new compounds using the best active compound 14 as a template. We performed activity prediction and molecular docking experiments on them, in which compound 14.d performed best regarding combined drug activity and docking ability.Conclusion: The non-linear model created using GEP was more stable and had a more substantial predictive power than the linear model built using the heuristic technique (HM). The compound 14.d designed in this experiment has the potential for anti-retinoblastoma treatment, which provides new design ideas and directions for retinoblastoma-targeted drugs

Incorporating causal factors into reinforcement learning for dynamic treatment regimes in HIV

Abstract Background Reinforcement learning (RL) provides a promising technique to solve complex sequential decision making problems in health care domains. However, existing studies simply apply naive RL algorithms in discovering optimal treatment strategies for a targeted problem. This kind of direct applications ignores the abundant causal relationships between treatment options and the associated outcomes that are inherent in medical domains. Methods This paper investigates how to integrate causal factors into an RL process in order to facilitate the final learning performance and increase explanations of learned strategies. A causal policy gradient algorithm is proposed and evaluated in dynamic treatment regimes (DTRs) for HIV based on a simulated computational model. Results Simulations prove the effectiveness of the proposed algorithm for designing more efficient treatment protocols in HIV, and different definitions of the causal factors could have significant influence on the final learning performance, indicating the necessity of human prior knowledge on defining a suitable causal relationships for a given problem. Conclusions More efficient and robust DTRs for HIV can be derived through incorporation of causal factors between options of anti-HIV drugs and the associated treatment outcomes

Tropical Cyclone Wind Field Reconstruction and Validation Using Measurements from SFMR and SMAP Radiometer

Accurate information on tropical cyclone position, intensity, and structure is critical for storm surge prediction. Atmospheric reanalysis datasets can provide gridded, full coverage, long-term and multi-parameter atmospheric fields for the research on the impact of tropical cyclones on the upper ocean, which effectively makes up for the uneven temporal and spatial distribution of satellite remote sensing and in situ data. However, the reanalysis data cannot accurately describe characteristic parameters of tropical cyclones, especially in high wind conditions. In this paper, the performance of the tropical cyclone representation in ERA5 (European Centre for Medium-Range Weather Forecasts Reanalysis 5th Generation) is investigated and analyzed with respect to IBTrACS (International Best Track Archive for Climate Stewardship) during the period 2018–2020. Comparisons demonstrate that ERA5 winds significantly underestimate the maximum wind speed during the tropical cyclones (>30 m/s) compared to those provided by IBTrACS. An effective wind reconstruction method is examined to enhance tropical cyclone intensity representation in reanalysis data in 94 cases of 31 tropical cyclones 2018–2020. The reconstructed wind speeds are in good agreement with the SFMR (Stepped Frequency Microwave Radiometer) measured data and SMAP (Soil Moisture Active Passive) L-band radiometer remotely sensed measurements. The proposed wind reconstruction method can effectively improve the accuracy of the tropical cyclone representation in ERA5, and will benefit from the establishment of remote sensing satellite retrieval model and the forcing fields of the ocean model

Geometry and Kinematics of the Central Fault Zone, Fula Sag, Central Africa Shear Zone

The Central Africa Shear Zone (CASZ) harbors abundant hydrocarbon resources within its Central Fault Zones (CFZs). The studies of CASZ have dominantly focused on the evolution and superimposition processes of prototype basins in CASZ. Meanwhile, research on the geometry and segmental growth of main faults in CFZs remains poorly understudied, which limits hydrocarbon exploration. In this paper, we focus on the CFZ of the Fula sag as an example of CASZ and utilize the 3-D throw mapping technique along with the maximum throw subtraction method to investigate its geometric and growth processes. Results show faults in the northern and central parts of the CFZ form multiple Y-shaped combinations, and a system of sub-parallel faults in the south forms the bookshelf faults. Meanwhile, the divergent overlapping transfer zone is identified in the CFZ. Our investigation found abrupt changes in throw-distance diagrams of main faults in the CFZ, which indicate that the main faults, F1, F3 and F2, are laterally segmented into 4, 4, and 3 segments, respectively. As an intracontinental passive rift basin, the Fula sag has undergone three major rifting cycles since the Early Cretaceous, triggered by the segmental expansion of the Atlantic Ocean, the rapid opening of the Indian Ocean, and the separation of the Red Sea. Our analysis also reveals that the main faults in the CFZ were primarily active during the second rifting, with the fault segments undergoing isolated growth, soft linkage, and eventually forming fully grown faults during the third rifting. We observe a significant decrease in activity intensity during the transition between the second and third rifting cycles. Our findings provide insights into the growth and activity of the CFZ faults, which are applicable to other CFZs of similar origin in rift basins, and provide suggestions for hydrocarbon exploration and production

Photometric and Colorimetric Assessment of LED Chip Scale Packages by Using a Step-Stress Accelerated Degradation Test (SSADT) Method

By solving the problem of very long test time on reliability qualification for Light-emitting Diode (LED) products, the accelerated degradation test with a thermal overstress at a proper range is regarded as a promising and effective approach. For a comprehensive survey of the application of step-stress accelerated degradation test (SSADT) in LEDs, the thermal, photometric, and colorimetric properties of two types of LED chip scale packages (CSPs), i.e., 4000 °K and 5000 °K samples each of which was driven by two different levels of currents (i.e., 120 mA and 350 mA, respectively), were investigated under an increasing temperature from 55 °C to 150 °C and a systemic study of driving current effect on the SSADT results were also reported in this paper. During SSADT, junction temperatures of the test samples have a positive relationship with their driving currents. However, the temperature-voltage curve, which represents the thermal resistance property of the test samples, does not show significant variance as long as the driving current is no more than the sample’s rated current. But when the test sample is tested under an overdrive current, its temperature-voltage curve is observed as obviously shifted to the left when compared to that before SSADT. Similar overdrive current affected the degradation scenario is also found in the attenuation of Spectral Power Distributions (SPDs) of the test samples. As used in the reliability qualification, SSADT provides explicit scenes on color shift and correlated color temperature (CCT) depreciation of the test samples, but not on lumen maintenance depreciation. It is also proved that the varying rates of the color shift and CCT depreciation failures can be effectively accelerated with an increase of the driving current, for instance, from 120 mA to 350 mA. For these reasons, SSADT is considered as a suitable accelerated test method for qualifying these two failure modes of LED CSPs

All-in-One Deposition to Synergistically Manipulate Perovskite Growth for High-Performance Solar Cell

Nonradiative recombination losses originating from crystallographic distortions and issues occurring upon interface formation are detrimental for the photovoltaic performance of perovskite solar cells. Herein, we incorporated a series of carbamide molecules (urea, biuret, or triuret) consisting of both Lewis base (–NH2) and Lewis acid (–C=O) groups into the perovskite precursor to simultaneously eliminate the bulk and interface defects. Depending on the different coordination ability with perovskite component, the incorporated molecules can either modify crystallization dynamics allowing for large crystal growth at low temperature (60°C), associate with antisite or undercoordinated ions for defect passivation, or accumulate at the surface as an energy cascade layer to enhance charge transfer, respectively. Synergistic benefits of the above functions can be obtained by rationally optimizing additive combinations in an all-in-one deposition method. As a result, a champion efficiency of 21.6% with prolonged operational stability was achieved in an inverted MAPbI3 perovskite solar cell by combining biuret and triuret additives. The simplified all-in-one fabrication procedure, adaptable to different types of perovskites in terms of pure MAPbI3, mixed perovskite, and all-inorganic perovskite, provides a cost-efficient and reproducible way to obtain high-performance inverted perovskite solar cells

Low-Temperature Atomic Layer Deposition of Metal Oxide Layers for Perovskite Solar Cells with High Efficiency and Stability under Harsh Environmental Conditions

Rapid progress achieved on perovskite solar cells raises the expectation for their further development toward practical applications. Moisture sensitivity of perovskite materials is one of the major obstacles which limits the long-term durability of the perovskite solar cells, especially in outdoor operation where rainfall and water accumulation on the solar panels often occur. Micro/nanopinholes within the functional layers of the devices usually lead to water vapor penetration, thus subsequent decomposition of perovskites, and finally poor device performance and shortened operational lifetime. In this work, low-temperature atomic layer deposition (ALD) technique was utilized to incorporate pinhole-free metal oxide layers (TiO₂ and Al₂O₃) into an inverted perovskite solar cell consisting of indium tin oxide/NiO/perovskite/PC₆₁BM/TiO₂/Ag. The interface properties between the inserted TiO₂ layer and the perovskite layer were investigated by X-ray photoelectron spectroscopy. The results showed that TiO₂ ALD fabrication process had made negligible degradation to the perovskite layer. The TiO₂ layer can significantly reduce interfacial charge recombination loss, improve interfacial contact, and enhance water resistance. A maximum power conversion efficiency (PCE) of 18.3% was achieved for devices with TiO₂ interface layers. A stacked Al₂O₃ encapsulation layer was designed and deposited on top of the devices to further improve device stability under harsh environmental conditions. The encapsulated devices with the best performance retained 97% of the initial PCE after being stored in ambient condition for a thousand hours. They also showed great water resistance, and no significant degradation in terms of PCE and photocurrent of the devices was observed after they were immersed in deionized water for as long as 2 h. Our approach offers a promising way of developing highly efficient and stable perovskite solar cells under real-world operational conditions