Search Results (17)

Background: Human African trypanosomiasis (HAT), caused by Trypanosoma brucei, is a neglected tropical disease with limited treatments, highlighting the pressing need for new drugs. Cell division cycle-2-related kinase 12 (CRK12), a pivotal protein involved in the cell cycle regulation of T. brucei, has emerged as a promising therapeutic target for HAT, yet effective CRK12 inhibitors remain lacking. Methods: An integrated strategy combining computational modeling, virtual screening, molecular dynamics (MD) simulations, and experimental validation was adopted to discover potential inhibitors against CRK12. By using the predicted and refined 3D structure of CRK12 from AlphaFold2 and MD simulation, over 1.5 million compounds were screened based on multiple-scale molecular docking, and 26 compounds were selected for evaluation of biological activity based on anti-T. brucei bioassays. Dose–response curves were generated for the most potent inhibitors, and the interaction mechanism between the top four compounds and CRK12 was explored by MD simulations and MM/GBSA binding free energy analysis. Results: Of the 26 compounds, six compounds demonstrated sub-micromolar to low-micromolar IC₅₀ values (0.85–3.50 µM). The top four hits, F733-0072, F733-0407, L368-0556, and L439-0038, exhibited IC₅₀ values of 1.11, 1.97, 0.85, and 1.66 µM, respectively. Binding free energy and energy decomposition analyses identified ILE335, VAL343, PHE430, ALA433, and LEU482 as hotspot residues for compound binding. Hydrogen bonding analysis demonstrated that these compounds can form stable hydrogen bonds with the hinge residue ALA433, ensuring their stable binding within the active site. Conclusions: This study establishes a robust and cost-effective pipeline for CRK12 inhibitor discovery, identifying several novel inhibitors demonstrating promising anti-HAT activity. The newly discovered scaffolds exhibit structural diversity distinct from known CRK12 inhibitors, providing valuable lead compounds for anti-trypanosomal drug development. Full article

Drugs are prescribed worldwide to treat diseases but with the risk of idiosyncratic drug-induced liver injury (iDILI). The most important difficulty is how best to establish causality. Based on strong evidence and principles of artificial intelligence (AI) to solve complex processes through quantitative algorithms using scored elements, progress was achieved with the Roussel Uclaf Causality Assessment Method (RUCAM) in its original and updated versions, often viewed now as the gold standard. As a highly appreciated diagnostic algorithm, the RUCAM is in global use with around 100,000 iDILI cases published worldwide using RUCAM to assess causality, largely outperforming any other specific causality assessment tool in terms of case numbers. Consequently, the RUCAM helps to establish a list of top-ranking drugs worldwide implicated in iDILI and to describe clinical and mechanistic features of iDILI caused by various drugs. In addition, the RUCAM was recently applied in iDILI cases of patients treated for coronavirus disease 2019 (COVID-19) infections or cancer patients treated with immune checkpoint inhibitors (ICIs), as well as in the search for new treatment options with conventional drugs in iDILI. Analyses of RUCAM-based iDILI cases are helpful to support pathogenetic steps like immune reactions, genetic predisposition as evidenced by human leucocyte antigens (HLA) genotypes for selected drugs, and the role of the gut microbiome. To achieve consistency in data collection, analysis, and specific clinical and pathogenetic presentation, researchers, regulatory agencies, and pharmaceutical firms should place iDILI and the updated RUCAM as the causality tool under one and the same hat in review articles and clinical guidelines for the diagnosis and treatment of iDILI. Full article

Space environment surveillance is very important for space security, which is easy to be disturbed by stray light and hot pixels, and the image background presents a certain degree of nonuniformity. The existing methods can not achieve the accurate segmentation of weak targets while correcting the nonuniform background. To solve this problem, this paper presents an accurate and robust correction method for the wide-field surveillance camera, called the enhanced new top-hat transform (ENTHT). Firstly, we analyze the formation mechanism and influence of the nonuniformity background from multiple dimensions. Secondly, because of the dependence and limitations of the background suppression effect of the new top-hat transform on the selection of structural elements, we improve the new top-hat transform by designing a noise structure element (NSE). Finally, we analyze the performance and advantages of the ENTHT method. In the field experiment, the method can accurately correct the complex space nonuniform background, eliminate the stray light and hot pixels, and realize the accurate segmentation of weak targets. In the complex space environment, it brings great help to space-moving target recognition and tracking. Full article

Robots have become an essential part of modern industries in welding departments to increase the accuracy and rate of production. The intelligent detection of welding line edges to start the weld in a proper position is very important. This work introduces a new approach using image processing to detect welding lines by tracking the edges of plates according to the required speed by three degrees of a freedom robotic arm. The two different algorithms achieved in the developed approach are the edge detection and top-hat transformation. An adaptive neuro-fuzzy inference system ANFIS was used to choose the best forward and inverse kinematics of the robot. MIG welding at the end-effector was applied as a tool in this system, and the weld was completed according to the required working conditions and performance. The parts of the system work with compatible and consistent performances, with acceptable accuracy for tracking the line of the welding path. Full article

In infrared small target detection, the infrared patch image (IPI)-model-based methods produce better results than other popular approaches (such as max-mean, top-hat, and human visual system) but in some extreme cases it suffers from long processing times and inconsistent performance. In order to overcome these issues, we propose a novel approach of dividing the traditional target detection process into two steps: suppression of background noise and elimination of clutter. The workflow consists of four steps: after importing the images, the second step applies the alternating direction multiplier method to preliminarily remove the background. Comparatively to the IPI model, this step does not require sliding patches, resulting in a significant reduction in processing time. To eliminate residual noise and clutter, the interim results from morphological filtering are then processed in step 3 through an improved new top-hat transformation, using a threefold structuring element. The final step is thresholding segmentation, which uses an adaptive threshold algorithm. Compared with IPI and the new top-hat methods, as well as some other widely used methods, our approach was able to detect infrared targets more efficiently (90% less computational time) and consistently (no sudden performance drop). Full article

This paper investigates the structural performance of a new two-way profiled steel decking system for steel-concrete composite slabs. Several studies have investigated steel decking for steel-concrete composite slabs and focused on utilising the conventional deck as a one-way floor system. The newly developed deck consists of top-hat sections formed by bending corrugated sheets at 90°, which are attached to a corrugated base sheet. The deck is designed for improved composite and two-way action contributed by its unique geometry due to corrugations in the transverse and longitudinal directions. This paper experimentally tested a novel steel decking geometry under construction stage loading. It was in the absence of concrete to establish the deck’s suitability for construction and contribution towards loading capacity and performance for future use as a two-way composite slab. Ultimate load, two-way action, and failure modes were identified. A finite element model was also developed, and parameters assessed that could influence the performance when the deck is potentially used in the composite stage. It was concluded that, while increasing the thickness of the corrugated base sheet significantly affects the load-carrying capacity, the thickness of the top hats has no significant impact. Improved load transfer with two-way behaviour is observed when the bottom flanges of the top hats are continuously connected to the bottom flanges of the adjacent top hats to form a deck. This contrasts with the concept deck, where individual top hats are attached to a corrugated base sheet. In this case, decks with a corrugated base sheet perform 54% better in ultimate load capacity than decks without a corrugated base sheet. Full article

We present a new subgrid stress model for the large eddy simulation of turbulent flows based on the solution of transport equations for stress tensor components. The model was a priori term-by-term calibrated against an open DNS database on forced isotropic turbulence (Johns Hopkins University database). After that, it was applied in a large eddy simulation of non-premixed turbulent combustion. To demonstrate the impact of the new subgrid stress model on scalar fields, we excluded the backward effect of heat release on the subgrid stresses, considering an isothermal reaction (i.e., diluted mixture; the density variations associated with chemical heat release can be neglected) and a Burke–Schumann reaction sheet approximation. A periodic box filled with a homogeneous turbulent velocity field and a three-layer top-hat mixture fraction field was studied. Four simulations were performed in which a fixed model for mixture fraction and its variance was combined with either the proposed subgrid stress model or one of the standard models, including Smagorinsky, dynamic Smagorinsky and WALE. Qualitatively correct backscatter was observed in a simulation with the new model. The differences in the statistics of the mixture fraction and reactive component fields caused by the new subgrid stress model were analyzed and discussed. The importance of using an advanced subgrid stress model was highlighted. Full article

In healthcare, a multitude of data is collected from medical sensors and devices, such as X-ray machines, magnetic resonance imaging, computed tomography (CT), and so on, that can be analyzed by artificial intelligence methods for early diagnosis of diseases. Recently, the outbreak of the COVID-19 disease caused many deaths. Computer vision researchers support medical doctors by employing deep learning techniques on medical images to diagnose COVID-19 patients. Various methods were proposed for COVID-19 case classification. A new automated technique is proposed using parallel fusion and optimization of deep learning models. The proposed technique starts with a contrast enhancement using a combination of top-hat and Wiener filters. Two pre-trained deep learning models (AlexNet and VGG16) are employed and fine-tuned according to target classes (COVID-19 and healthy). Features are extracted and fused using a parallel fusion approach—parallel positive correlation. Optimal features are selected using the entropy-controlled firefly optimization method. The selected features are classified using machine learning classifiers such as multiclass support vector machine (MC-SVM). Experiments were carried out using the Radiopaedia database and achieved an accuracy of 98%. Moreover, a detailed analysis is conducted and shows the improved performance of the proposed scheme. Full article

With the increasing demand for wind energy, the vertical axis wind turbine (VAWT) is attracting more and more attention. In order to design the VAWT array for better performance, the VAWT wake model needs to reflect the wake characteristics well. Based on the asymmetric wake characteristic, a new VAWT wake model is proposed in this paper, which is a combination of two semi Gaussian functions with different deviations, and can be called the “double semi Gaussian functions wake model”. The model is simple and has only four parameters (mean, amplitude, left deviation and right deviation). Compared with the traditional Gaussian and Top-hat model, this model can better reflect the asymmetric characteristic of the VAWT wake. In particular, it can describe the behavior of wake merging in the case of counter-rotating twin turbines. Based on this wake model, the velocity field of VAWT array can be reproduced accurately. The goal function is mainly based on the performance of a basic array unit, and it can ensure the rapidity of the optimization process. The optimal arrangements under two different criteria are analyzed. Moreover, the truncation ratio is introduced to ensure that the downstream turbine works at the rated condition, and the optimal arrangements under different truncation ratios are analyzed. In this paper, the proposed wake model provides a good choice for the preliminary design of the VAWT array, and some relevant suggestions on the array arrangement have been put forward. Full article

Vehicle crashworthiness is an important aspect to consider when designing a vehicle to ensure the safety of the occupants. Besides this, vehicles are also designed to reduce weight for better fuel economics. One possible approach to reducing weight without compromising vehicle safety is by looking at new designs and usage of composite materials, along with the usage of computational models to reduce time and cost. Hence, this paper displays the experimental results of a carbon fiber reinforced closed top-hat section subjected to both quasi-static and dynamic crushing loading. The results were used to validate the computational model developed in the study. The specimens were made of carbon composite prepregs MTM-44 sheets stacked at the alternative orientation of ±45° and 0°/90°, where 0° direction coincides with the axis of the member. The samples were prepared by using a mold and carbon prepregs under vacuum bagging followed by curing in an autoclave. Trigger initiation was applied to ensure the specimens demonstrated a stable crushing mode of failure during the test. Experimental investigations were carried out under the ambient conditions with different loading conditions, and different kinetic energy ranges (2, 3 and 6 kJ). Experimental data was used to validate the finite element analysis (FEA). The maximum errors obtained between experimental and FEA for mean load, mean energy absorption, and crushing displacement were 13%, 13% and 7%, respectively. The numerically obtained results were in strong agreement with the experimental data and showed that they were able to predict the failure of the specimens. The work also showed the novelty of using such structures for energy absorption applications. Full article

Panoramic dental radiography is one of the most used images of the different dental specialties. This radiography provides information about the anatomical structures of the teeth. The correct evaluation of these radiographs is associated with a good quality of the image obtained. In this study, 598 patients were consecutively selected to undergo dental panoramic radiography at the Department of Radiology of the Faculty of Dentistry, Universidad Nacional de Asunción. Contrast enhancement techniques are used to enhance the visual quality of panoramic dental radiographs. Specifically, this article presents a new algorithm for contrast, detail and edge enhancement of panoramic dental radiographs. The proposed algorithm is called Multi-Scale Top-Hat transform powered by Geodesic Reconstruction for panoramic dental radiography enhancement (MSTHGR). This algorithm is based on multi-scale mathematical morphology techniques. The proposal extracts multiple features of brightness and darkness, through the reconstruction of the marker (obtained by the Top-Hat transformation by reconstruction) starting from the mask (obtained by the classic Top-Hat transformation). The maximum characteristics of brightness and darkness are added to the dental panoramic radiography. In this way, the contrast, details and edges of the panoramic radiographs of teeth are improved. For the tests, MSTHGR was compared with the following algorithms: Geodesic Reconstruction Multiscale Morphology Contrast Enhancement (GRMMCE), Histogram Equalization (HE), Brightness Preserving Bi-Histogram Equalization (BBHE), Dual Sub-Image Histogram Equalization (DSIHE), Minimum Mean Brightness Error Bi-Histogram Equalization (MMBEBHE), Quadri-Histogram Equalization with Limited Contrast (QHELC), Contrast-Limited Adaptive Histogram Equalization (CLAHE) and Gamma Correction (GC). Experimentally, the numerical results show that the MSTHGR obtained the best results with respect to the Contrast Improvement Ratio (CIR), Entropy (E) and Spatial Frequency (SF) metrics. This indicates that the algorithm performs better local enhancements on panoramic radiographs, improving their details and edges. Full article

Trapezoidal-shaped thin-walled metallic profiled sheets are used in composite floor construction to enable rapid construction and reduce reinforcement and formwork requirements in concrete casting. However, relevant literature reported the early failure of steel sections due to the buckling and shear of existing trapezoidal and re-entrant decking profiles. There are also limitations regarding design rules for composite flooring systems. Current work aims to develop a new type of composite top-hat section for possible use in composite slim-floor construction. Sinusoidal metallic corrugated sheets that are widely used in building construction were utilized and a new bending technique was used to produce deck components, in which transverse corrugations were introduced along the main direction of the corrugated profile. This paper investigates the structural response of these new sections for several loading and support conditions using a pilot experimental scheme. The developed top-hat sections demonstrated considerable resistance to bending as well as buckling through effective stress re-distributions under considered construction stage loading for single span and continuous span conditions. Currently available design equations recommended by Australian Standards for a similar type of corrugated decks were used to predict the design strength and to compare it with those obtained experimentally. It was concluded that the expressions proposed by the code were inadequate for single span loading cases and would require modifications before being applied to the new profile. Full article

Breast cancer is the leading cause of cancer death in women, and early detection can reduce mortality. Architectural distortion (AD) is a feature of clinical manifestations for breast cancer, however, due to its complex structure and low detection accuracy, which cause a high mortality of breast cancer. In order to improve the accuracy of AD detection and reduce the mortality of breast cancer, this paper proposes a new method by combining the non-subsampled contourlet transform (NSCT) with the improved pulse coupled neural network (PCNN). Firstly, the top–bottom hat transformation and the exponential transformation are employed to enhance the image. Secondly, the NSCT is employed to expand the overall contrast of the mammograms and filter out the noise. Finally, the improved PCNN by the maximum inter-class variance threshold selection method is employed to complete the AD detection. This proposed approach is tested on the public and authoritative database—Digital Database for Screening Mammography (DDSM). The specificity of the method is 98.73%, the accuracy is 93.16%, and the F1-score is 79.80%, and the area under curve (AUC) of the receiver operating characteristic (ROC) curve is 0.93, these results clearly demonstrate that the proposed method is comparable with those methods in recent literatures. This proposed method is simple, furthermore it can achieve high accuracy and help doctors to perform computer-aided detection of AD effectively. Full article

Period detection technology for weak characteristic signals is very important in the fields of speech signal processing, mechanical engineering, etc. Average magnitude difference function (AMDF) is a widely used method to extract the period of periodic signal for its low computational complexity and high accuracy. However, this method has low detection accuracy when the background noise is strong. In order to improve this method, this paper proposes a new method of period detection of the signal with single period based on the morphological self-complementary Top-Hat (STH) transform and AMDF. Firstly, the signal is de-noised by the morphological self-complementary Top-Hat transform. Secondly, the average magnitude difference function of the noise reduction sequence is calculated, and the falling trend is suppressed. Finally, a calculating adaptive threshold is used to extract the peaks at the position equal to the period of periodic signal. The experimental results show that the accuracy of periodic extraction of AMDF after Top-Hat filtering is better than that of AMDF directly. In summary, the proposed method is reliable and stable for detecting the periodic signal with weak characteristics. Full article

Wind Farm Layout Optimization (WFLO) can be useful to minimize power losses associated with turbine wakes in wind farms. This work presents a new evolutionary WFLO methodology integrated with a recently developed and successfully validated Gaussian wake model (Bastankhah and Porté-Agel model). Two different parametrizations of the evolutionary methodology are implemented, depending on if a baseline layout is considered or not. The proposed scheme is applied to two real wind farms, Horns Rev I (Denmark) and Princess Amalia (the Netherlands), and two different turbine models, V80-2MW and NREL-5MW. For comparison purposes, these four study cases are also optimized under the traditionally used top-hat wake model (Jensen model). A systematic overestimation of the wake losses by the Jensen model is confirmed herein. This allows it to attain bigger power output increases with respect to the baseline layouts (between 0.72% and 1.91%) compared to the solutions attained through the more realistic Gaussian model (0.24–0.95%). The proposed methodology is shown to outperform other recently developed layout optimization methods. Moreover, the electricity cable length needed to interconnect the turbines decreases up to 28.6% compared to the baseline layouts. Full article