The 2023 MDPI Annual Report has
been released!
 
19 pages, 11957 KiB  
Article
Modeling Melanoma Heterogeneity In Vitro: Redox, Resistance and Pigmentation Profiles
by Larissa Anastacio da Costa Carvalho, Isabella Harumi Yonehara Noma, Adriana Hiromi Uehara, Ádamo Davi Diógenes Siena, Luciana Harumi Osaki, Mateus Prates Mori, Nadja Cristhina de Souza Pinto, Vanessa Morais Freitas, Wilson Araújo Silva Junior, Keiran S. M. Smalley and Silvya Stuchi Maria-Engler
Antioxidants 2024, 13(5), 555; https://doi.org/10.3390/antiox13050555 (registering DOI) - 30 Apr 2024
Abstract
Microenvironment and transcriptional plasticity generate subpopulations within the tumor, and the use of BRAF inhibitors (BRAFis) contributes to the rise and selection of resistant clones. We stochastically isolated subpopulations (C1, C2, and C3) from naïve melanoma and found that the clones demonstrated distinct [...] Read more.
Microenvironment and transcriptional plasticity generate subpopulations within the tumor, and the use of BRAF inhibitors (BRAFis) contributes to the rise and selection of resistant clones. We stochastically isolated subpopulations (C1, C2, and C3) from naïve melanoma and found that the clones demonstrated distinct morphology, phenotypic, and functional profiles: C1 was less proliferative, more migratory and invasive, less sensitive to BRAFis, less dependent on OXPHOS, more sensitive to oxidative stress, and less pigmented; C2 was more proliferative, less migratory and invasive, more sensitive to BRAFis, less sensitive to oxidative stress, and more pigmented; and C3 was less proliferative, more migratory and invasive, less sensitive to BRAFis, more dependent on OXPHOS, more sensitive to oxidative stress, and more pigmented. Hydrogen peroxide plays a central role in oxidative stress and cell signaling, and PRDXs are one of its main consumers. The intrinsically resistant C1 and C3 clones had lower MITF, PGC-1α, and PRDX1 expression, while C1 had higher AXL and decreased pigmentation markers, linking PRDX1 to clonal heterogeneity and resistance. PRDX2 is depleted in acquired BRAFi-resistant cells and acts as a redox sensor. Our results illustrate that decreased pigmentation markers are related to therapy resistance and decreased antioxidant defense. Full article
(This article belongs to the Special Issue Antioxidants to Overcome Resistance in Cancer Therapy)
12 pages, 240 KiB  
Article
Tchaikovsky, Onegin, and the Art of Characterization
by Francis Maes
Arts 2024, 13(3), 82; https://doi.org/10.3390/arts13030082 (registering DOI) - 30 Apr 2024
Abstract
Tchaikovsky enjoyed composing Yevgeni Onegin. He expressed his fulfillment in a famous letter to Sergey Taneyev. What could his enthusiasm convey about the content of the project? Music criticism has taken Tchaikovsky’s words as proof for the thesis that the opera is [...] Read more.
Tchaikovsky enjoyed composing Yevgeni Onegin. He expressed his fulfillment in a famous letter to Sergey Taneyev. What could his enthusiasm convey about the content of the project? Music criticism has taken Tchaikovsky’s words as proof for the thesis that the opera is connected to autobiographical circumstances. In this mode of thinking, the quality of Tchaikovsky’s music is the result of the composer’s identification with the subject matter. Despite the objection of several Tchaikovsky scholars, the autobiographical paradigm remains very much alive in the reception of Tchaikovsky’s music. As an alternative, Tchaikovsky scholarship has explored a hermeneutical approach that would link his music to its context in Russian society and culture. In this paper, I present another possible reaction to Tchaikovsky’s statement: an exploration of the composer’s approach to musical characterization. Analysis of some key scenes reveals that the definition of characters and situations by musical means is more precise than standard interpretations of the opera would concede. This discovery may lead to a new assessment of characterization as a critical tool to refine the definition of Tchaikovsky’s position in European music history. The method may be applied to examples outside his operatic output, such as Serenade for Strings and the Fifth Symphony. Full article
17 pages, 1845 KiB  
Article
Numerical Modeling of Venous Outflow from the Cranial Cavity in the Supine Body Position
by Marian Simka, Joanna Czaja, Agata Kawalec, Paweł Latacz and Uliana Kovalko
Appl. Sci. 2024, 14(9), 3878; https://doi.org/10.3390/app14093878 (registering DOI) - 30 Apr 2024
Abstract
The hemodynamic relevance of differently located stenoses of the internal jugular veins remains undetermined. It particularly concerns nozzle-like strictures in the upper parts of these veins and stenotic jugular valves located at the end of these veins. This study was aimed at understanding [...] Read more.
The hemodynamic relevance of differently located stenoses of the internal jugular veins remains undetermined. It particularly concerns nozzle-like strictures in the upper parts of these veins and stenotic jugular valves located at the end of these veins. This study was aimed at understanding flow disturbances caused by such stenoses. The computational fluid dynamics software Flowsquare+ was used. We constructed 3-dimensional models of the venous outflow, comprising two alternative routes: the tube representing the internal jugular vein and an irregular network representing the vertebral veins. At the beginning of the tube representing the internal jugular vein, differently shaped and sized short strictures representing nozzle-like strictures were built in. At the end of this tube, differently shaped membranes representing the jugular valve were built in. With the use of computational fluid dynamics modeling, we studied how these two obstacles influenced the outflow. We found that the most relevant outflow disturbances were evoked by the nozzle-like strictures in the upper part of the internal jugular vein that were small, long, or asymmetrically positioned. Very tight stenotic valves and septum-like malformed valve were equally hemodynamically relevant. These findings suggest that both upper and lower strictures of the internal jugular vein can be of clinical significance. Full article
(This article belongs to the Special Issue Advances in Active and Passive Techniques for Fluid Flow Manipulation)
45 pages, 7562 KiB  
Review
Hamiltonian Computational Chemistry: Geometrical Structures in Chemical Dynamics and Kinetics
by Stavros C. Farantos
Entropy 2024, 26(5), 399; https://doi.org/10.3390/e26050399 (registering DOI) - 30 Apr 2024
Abstract
The common geometrical (symplectic) structures of classical mechanics, quantum mechanics, and classical thermodynamics are unveiled with three pictures. These cardinal theories, mainly at the non-relativistic approximation, are the cornerstones for studying chemical dynamics and chemical kinetics. Working in extended phase spaces, we show [...] Read more.
The common geometrical (symplectic) structures of classical mechanics, quantum mechanics, and classical thermodynamics are unveiled with three pictures. These cardinal theories, mainly at the non-relativistic approximation, are the cornerstones for studying chemical dynamics and chemical kinetics. Working in extended phase spaces, we show that the physical states of integrable dynamical systems are depicted by Lagrangian submanifolds embedded in phase space. Observable quantities are calculated by properly transforming the extended phase space onto a reduced space, and trajectories are integrated by solving Hamilton’s equations of motion. After defining a Riemannian metric, we can also estimate the length between two states. Local constants of motion are investigated by integrating Jacobi fields and solving the variational linear equations. Diagonalizing the symplectic fundamental matrix, eigenvalues equal to one reveal the number of constants of motion. For conservative systems, geometrical quantum mechanics has proved that solving the Schrödinger equation in extended Hilbert space, which incorporates the quantum phase, is equivalent to solving Hamilton’s equations in the projective Hilbert space. In classical thermodynamics, we take entropy and energy as canonical variables to construct the extended phase space and to represent the Lagrangian submanifold. Hamilton’s and variational equations are written and solved in the same fashion as in classical mechanics. Solvers based on high-order finite differences for numerically solving Hamilton’s, variational, and Schrödinger equations are described. Employing the Hénon–Heiles two-dimensional nonlinear model, representative results for time-dependent, quantum, and dissipative macroscopic systems are shown to illustrate concepts and methods. High-order finite-difference algorithms, despite their accuracy in low-dimensional systems, require substantial computer resources when they are applied to systems with many degrees of freedom, such as polyatomic molecules. We discuss recent research progress in employing Hamiltonian neural networks for solving Hamilton’s equations. It turns out that Hamiltonian geometry, shared with all physical theories, yields the necessary and sufficient conditions for the mutual assistance of humans and machines in deep-learning processes. Full article
(This article belongs to the Special Issue Kinetic Models of Chemical Reactions)
27 pages, 1778 KiB  
Article
Deep Learning-Based Classification and Semantic Segmentation of Lung Tuberculosis Lesions in Chest X-ray Images
by Chih-Ying Ou, I-Yen Chen, Hsuan-Ting Chang, Chuan-Yi Wei, Dian-Yu Li, Yen-Kai Chen and Chuan-Yu Chang
Diagnostics 2024, 14(9), 952; https://doi.org/10.3390/diagnostics14090952 (registering DOI) - 30 Apr 2024
Abstract
We present a deep learning (DL) network-based approach for detecting and semantically segmenting two specific types of tuberculosis (TB) lesions in chest X-ray (CXR) images. In the proposed method, we use a basic U-Net model and its enhanced versions to detect, classify, and [...] Read more.
We present a deep learning (DL) network-based approach for detecting and semantically segmenting two specific types of tuberculosis (TB) lesions in chest X-ray (CXR) images. In the proposed method, we use a basic U-Net model and its enhanced versions to detect, classify, and segment TB lesions in CXR images. The model architectures used in this study are U-Net, Attention U-Net, U-Net++, Attention U-Net++, and pyramid spatial pooling (PSP) Attention U-Net++, which are optimized and compared based on the test results of each model to find the best parameters. Finally, we use four ensemble approaches which combine the top five models to further improve lesion classification and segmentation results. In the training stage, we use data augmentation and preprocessing methods to increase the number and strength of lesion features in CXR images, respectively. Our dataset consists of 110 training, 14 validation, and 98 test images. The experimental results show that the proposed ensemble model achieves a maximum mean intersection-over-union (MIoU) of 0.70, a mean precision rate of 0.88, a mean recall rate of 0.75, a mean F1-score of 0.81, and an accuracy of 1.0, which are all better than those of only using a single-network model. The proposed method can be used by clinicians as a diagnostic tool assisting in the examination of TB lesions in CXR images. Full article
14 pages, 1307 KiB  
Article
Further Examination of the Pulsed- and Steady-Pedestal Paradigms under Hypothetical Parvocellular- and Magnocellular-Biased Conditions
by Jaeseon Song, Bruno G. Breitmeyer and James M. Brown
Vision 2024, 8(2), 28; https://doi.org/10.3390/vision8020028 (registering DOI) - 30 Apr 2024
Abstract
The pulsed- and steady-pedestal paradigms were designed to track increment thresholds (ΔC) as a function of pedestal contrast (C) for the parvocellular (P) and magnocellular (M) systems, respectively. These paradigms produce contrasting results: linear relationships between ΔC and C are observed in [...] Read more.
The pulsed- and steady-pedestal paradigms were designed to track increment thresholds (ΔC) as a function of pedestal contrast (C) for the parvocellular (P) and magnocellular (M) systems, respectively. These paradigms produce contrasting results: linear relationships between ΔC and C are observed in the pulsed-pedestal paradigm, indicative of the P system’s processing, while the steady-pedestal paradigm reveals nonlinear functions, characteristic of the M system’s response. However, we recently found the P model fits better than the M model for both paradigms, using Gabor stimuli biased towards the M or P systems based on their sensitivity to color and spatial frequency. Here, we used two-square pedestals under green vs. red light in the lower-left vs. upper-right visual fields to bias processing towards the M vs. P system, respectively. Based on our previous findings, we predicted the following: (1) steeper ΔC vs. C functions with the pulsed than the steady pedestal due to different task demands; (2) lower ΔCs in the upper-right vs. lower-left quadrant due to its bias towards P-system processing there; (3) no effect of color, since both paradigms track the P-system; and, most importantly (4) contrast gain should not be higher for the steady than for the pulsed pedestal. In general, our predictions were confirmed, replicating our previous findings and providing further evidence questioning the general validity of using the pulsed- and steady-pedestal paradigms to differentiate the P and M systems. Full article
16 pages, 2602 KiB  
Article
Design of High-Precision Driving Control System for Charge Management
by Yang Wang, Boyan Lv, Tao Yu, Longqi Wang and Zhi Wang
Sensors 2024, 24(9), 2883; https://doi.org/10.3390/s24092883 (registering DOI) - 30 Apr 2024
Abstract
Due to the interaction of accumulated charges on the surface of a test mass with the surrounding electric and magnetic fields, the performance of inertial sensors is affected, necessitating charge management for the test mass. Discharge technology based on Ultraviolet LEDs is internationally [...] Read more.
Due to the interaction of accumulated charges on the surface of a test mass with the surrounding electric and magnetic fields, the performance of inertial sensors is affected, necessitating charge management for the test mass. Discharge technology based on Ultraviolet LEDs is internationally recognized as the optimal solution for charge management. Precision driving of Ultraviolet LEDs is considered a key technology in charge management. This paper presents the driving control system used for Ultraviolet LEDs, achieving precision pulse-width-modulation-type current output with controllable pulse width and amplitude. The system generates the pulse-width-controllable pulse voltage signal via analog pulse-width modulation, and subsequently regulates the amplitude of the PWM signal through range switching. To convert the voltage into the pulse-width-modulation-type driving current, the improved Howland current source is employed. The test results demonstrate that the driving control system can output controllable current in the range of 0.01 mA to 10 mA, with a minimum step of 0.01 mA. The accuracy of the current reaches 1%, the stability within 1 h is better than 1%, and the load regulation is better than 2%. The driving control system provides an important reference for the integration of charge management system and the precision drive control method for LEDs. Full article
(This article belongs to the Section Electronic Sensors)
54 pages, 4100 KiB  
Article
A Tiny Viral Protein, SARS-CoV-2-ORF7b: Functional Molecular Mechanisms
by Gelsomina Mansueto, Giovanna Fusco and Giovanni Colonna
Biomolecules 2024, 14(5), 541; https://doi.org/10.3390/biom14050541 (registering DOI) - 30 Apr 2024
Abstract
This study presents the interaction with the human host metabolism of SARS-CoV-2 ORF7b protein (43 aa), using a protein–protein interaction network analysis. After pruning, we selected from BioGRID the 51 most significant proteins among 2753 proven interactions and 1708 interactors specific to ORF7b. [...] Read more.
This study presents the interaction with the human host metabolism of SARS-CoV-2 ORF7b protein (43 aa), using a protein–protein interaction network analysis. After pruning, we selected from BioGRID the 51 most significant proteins among 2753 proven interactions and 1708 interactors specific to ORF7b. We used these proteins as functional seeds, and we obtained a significant network of 551 nodes via STRING. We performed topological analysis and calculated topological distributions by Cytoscape. By following a hub-and-spoke network architectural model, we were able to identify seven proteins that ranked high as hubs and an additional seven as bottlenecks. Through this interaction model, we identified significant GO-processes (5057 terms in 15 categories) induced in human metabolism by ORF7b. We discovered high statistical significance processes of dysregulated molecular cell mechanisms caused by acting ORF7b. We detected disease-related human proteins and their involvement in metabolic roles, how they relate in a distorted way to signaling and/or functional systems, in particular intra- and inter-cellular signaling systems, and the molecular mechanisms that supervise programmed cell death, with mechanisms similar to that of cancer metastasis diffusion. A cluster analysis showed 10 compact and significant functional clusters, where two of them overlap in a Giant Connected Component core of 206 total nodes. These two clusters contain most of the high-rank nodes. ORF7b acts through these two clusters, inducing most of the metabolic dysregulation. We conducted a co-regulation and transcriptional analysis by hub and bottleneck proteins. This analysis allowed us to define the transcription factors and miRNAs that control the high-ranking proteins and the dysregulated processes within the limits of the poor knowledge that these sectors still impose. Full article
(This article belongs to the Section Biomacromolecules: Proteins)
13 pages, 5252 KiB  
Article
Effect of TiB2 Addition on the Microstructure and Mechanical Properties of Laser-Directed Energy Deposition TiAl Alloy
by Yancheng Yang, Yi Hu, Hongyan Chen, Yu Li, Jiawei Wang, Xu Cheng, Haibo Tang, Xianzhe Ran and Dong Liu
Metals 2024, 14(5), 533; https://doi.org/10.3390/met14050533 (registering DOI) - 30 Apr 2024
Abstract
The microstructure characteristics of TiAl alloy prepared by laser-directed energy deposition (L-DED) are coarse columnar grains parallel to the building direction, which results in serious mechanical properties and anisotropy and limits its application. In the present study, TiB2 can be used as [...] Read more.
The microstructure characteristics of TiAl alloy prepared by laser-directed energy deposition (L-DED) are coarse columnar grains parallel to the building direction, which results in serious mechanical properties and anisotropy and limits its application. In the present study, TiB2 can be used as an effective grain refiner due to the extremely high Q value (growth inhibition factor; the larger the Q value of an alloying element, the stronger its grain refinement effect.) of B. With TiB2 addition, TiAl alloys prepared by laser-directed energy deposition with the microstructure of full equiaxed grains were obtained, and the grain size was significantly reduced by about 30% with 0.45 wt.% TiB2. This value has been further increased to 45% when adding 0.9 wt.% TiB2. Moreover, the γm phase was nearly eliminated and the width of (α2 + γ) lamellar was significantly decreased, which has positive effects on mechanical properties. Meanwhile, TiB2 precipitates uniformly distribute in the matrix, as a reinforced particle to increase the hardness and compressive strength of the alloys. The microhardness of the TiAl alloy increased with the increasing content of TiB2. The addition of TiB2 improved the room and high-temperature compressive properties of TiAl alloy while slightly increasing its ductility. These findings have important guiding significance for expanding the application of TiAl alloys. Full article
(This article belongs to the Special Issue Advances in Laser Metal Deposition Processes)
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23 pages, 2943 KiB  
Article
Simulation and Attribution Analysis of Spatial–Temporal Variation in Carbon Storage in the Northern Slope Economic Belt of Tianshan Mountains, China
by Kun Zhang, Yu Wang, Ali Mamtimin, Yongqiang Liu, Lifang Zhang, Jiacheng Gao, Ailiyaer Aihaiti, Cong Wen, Meiqi Song, Fan Yang, Chenglong Zhou and Wen Huo
Land 2024, 13(5), 608; https://doi.org/10.3390/land13050608 (registering DOI) - 30 Apr 2024
Abstract
Intensive economic and human activities present challenges to the carbon storage capacity of terrestrial ecosystems, particularly in arid regions that are sensitive to climate change and ecologically fragile. Therefore, accurately estimating and simulating future changes in carbon stocks on the northern slope economic [...] Read more.
Intensive economic and human activities present challenges to the carbon storage capacity of terrestrial ecosystems, particularly in arid regions that are sensitive to climate change and ecologically fragile. Therefore, accurately estimating and simulating future changes in carbon stocks on the northern slope economic belt of Tianshan Mountains (NSEBTM) holds great significance for maintaining ecosystem stability, achieving high-quality development of the economic belt, and realizing the goal of “carbon neutrality” by 2050. This study examines the spatiotemporal evolution characteristics of the NSEBTM carbon stocks in arid regions from 1990 to 2050, utilizing a combination of multi-source data and integrating the Patch-generating Land use Simulation (PLUS) and Integrated Valuation of Ecosystem Services and Trade-offs (InVEST) models. Additionally, an attribution analysis of carbon stock changes is conducted by leveraging land use data. The findings demonstrate that (1) the NSEBTM predominantly consists of underutilized land, accounting for more than 60% of the total land area in the NSEBTM. Unused land, grassland, and water bodies exhibit a declining trend over time, while other forms of land use demonstrate an increasing trend. (2) Grassland serves as the primary reservoir for carbon storage in the NSEBTM, with grassland degradation being the leading cause of carbon loss amounting to 102.35 t over the past three decades. (3) Under the ecological conservation scenario for 2050 compared to the natural development scenario, there was a net increase in carbon storage by 12.34 t; however, under the economic development scenario compared to the natural development scenario, there was a decrease in carbon storage by 25.88 t. By quantitatively evaluating the land use change in the NSEBTM and its impact on carbon storage in the past and projected for the next 30 years, this paper provides scientific references and precise data support for the territorial and spatial decision making of the NSEBTM, thereby facilitating the achievement of “carbon neutrality” goals. Full article
(This article belongs to the Special Issue Land-Based Greenhouse Gas Mitigation for Carbon Neutrality)
20 pages, 2175 KiB  
Article
New Methods of Series Expansions between Three Anomalies
by Dongfang Zhao, Houpu Li, Shaofeng Bian, Yongbing Chen and Wenkui Li
Appl. Sci. 2024, 14(9), 3873; https://doi.org/10.3390/app14093873 (registering DOI) - 30 Apr 2024
Abstract
The calculation of satellite orbit involves some very complex formula derivations and expansions, which are very difficult to manually derive and prone to errors. And the efficiency of manual derivation is not high. We can use computer algebra systems to derive complex formulas [...] Read more.
The calculation of satellite orbit involves some very complex formula derivations and expansions, which are very difficult to manually derive and prone to errors. And the efficiency of manual derivation is not high. We can use computer algebra systems to derive complex formulas related to satellite orbits. This can avoid some of the drawbacks of manual derivation and significantly improve computational efficiency and accuracy. In the past, the relationship among three anomalies was generally represented in the form of a trigonometric series with the first eccentricity e as the parameter. In this paper, the trigonometric series with the parameter m=11e2e is used, as determined by the Lagrange conjugate series. We can use the formula of the Lagrange conjugate series to derive the relationship between the true anomaly and elliptic anomaly. And the relationship between the elliptic anomaly and the mean anomaly is derived by using the symbolic iteration method. In this research paper, we calculated the accuracy of the trigonometric series expansion among three types of anomalies at the first eccentricity e equal to values of 0.01, 0.1, and 0.2. The calculation results indicate that the accuracy of the trigonometric series expansion with m as the parameter is better than 10−5. Moreover, in some cases, the trigonometric series expansion among the three anomalies with m as a parameter is simpler in form than the expansion expressed with parameter e. This paper also derived and calculated the symbolic expressions and extreme values of the difference among three anomalies and expressed the extreme values of the difference in the form of a power series of e. It can be seen that the extreme value increases with the increase in eccentricity e. And the absolute values of the extreme value of the difference between the elliptic anomaly and the mean anomaly, the true anomaly and the elliptic anomaly, and the true anomaly and the mean anomaly increase in this order. When the eccentricity is small, the absolute value of the extreme value of the difference between the true anomaly and the mean anomaly is about twice as large as the elliptic anomaly and the mean anomaly and the true anomaly and the mean anomaly. Full article
21 pages, 749 KiB  
Article
Optimised Congestion Management Using Curative Measures in Combined AC/DC Systems with Flexible AC Transmission Systems
by Denis Mende and Lutz Hofmann
Energies 2024, 17(9), 2157; https://doi.org/10.3390/en17092157 (registering DOI) - 30 Apr 2024
Abstract
Due to the increasing demand for transport of electrical energy, measures for power flow control, congestion management, and higher utilisation of the existing grid play a decisive role in the transformation of the power system. Hence, enormous efforts must be undertaken using measures [...] Read more.
Due to the increasing demand for transport of electrical energy, measures for power flow control, congestion management, and higher utilisation of the existing grid play a decisive role in the transformation of the power system. Hence, enormous efforts must be undertaken using measures of congestion management. Modelling and integration of corresponding measures in optimisation tools to support grid and system operation and therewith reduce the resulting efforts become more important. This is especially true because of the high intermittency and decentralisation of renewable generation leading to increased complexity of the power system, higher loading of assets, and a growing need for control over flexible alternating current transmission systems (FACTS) and high-voltage direct current (HVDC) converters. This work therefore describes the implementation of optimised congestion management in an A Mathematical Programming Language (AMPL)-based nonlinear optimisation problem. AMPL is an effective tool to deal with highly complex problems of optimisation and scheduling. Therefore, the modelling of assets and flexibilities for power flow control in AC/DC systems in combination with an innovative grid operation strategy using predefined curative measures for the optimised use of the existing grid is introduced. The nonlinear mathematical optimisation aims at the optimal cost selection of flexibility measures. The application of the optimisation technique in a combined AC/DC system shows the optimal preventive and curative use of measures in operational congestion management. Simulation results prove that, by using predefined curative measures, the volume of cost-intensive preventive measures can significantly be reduced, especially in association with power flow control. Full article
(This article belongs to the Section F1: Electrical Power System)
15 pages, 4551 KiB  
Article
QUBO Problem Formulation of Fragment-Based Protein–Ligand Flexible Docking
by Keisuke Yanagisawa, Takuya Fujie, Kazuki Takabatake and Yutaka Akiyama
Entropy 2024, 26(5), 397; https://doi.org/10.3390/e26050397 (registering DOI) - 30 Apr 2024
Abstract
Protein–ligand docking plays a significant role in structure-based drug discovery. This methodology aims to estimate the binding mode and binding free energy between the drug-targeted protein and candidate chemical compounds, utilizing protein tertiary structure information. Reformulation of this docking as a quadratic unconstrained [...] Read more.
Protein–ligand docking plays a significant role in structure-based drug discovery. This methodology aims to estimate the binding mode and binding free energy between the drug-targeted protein and candidate chemical compounds, utilizing protein tertiary structure information. Reformulation of this docking as a quadratic unconstrained binary optimization (QUBO) problem to obtain solutions via quantum annealing has been attempted. However, previous studies did not consider the internal degrees of freedom of the compound that is mandatory and essential. In this study, we formulated fragment-based protein–ligand flexible docking, considering the internal degrees of freedom of the compound by focusing on fragments (rigid chemical substructures of compounds) as a QUBO problem. We introduced four factors essential for fragment–based docking in the Hamiltonian: (1) interaction energy between the target protein and each fragment, (2) clashes between fragments, (3) covalent bonds between fragments, and (4) the constraint that each fragment of the compound is selected for a single placement. We also implemented a proof-of-concept system and conducted redocking for the protein–compound complex structure of Aldose reductase (a drug target protein) using SQBM+, which is a simulated quantum annealer. The predicted binding pose reconstructed from the best solution was near-native (RMSD=1.26 Å), which can be further improved (RMSD=0.27 Å) using conventional energy minimization. The results indicate the validity of our QUBO problem formulation. Full article
(This article belongs to the Special Issue Ising Model: Recent Developments and Exotic Applications II)
14 pages, 473 KiB  
Article
Speaker Anonymization: Disentangling Speaker Features from Pre-Trained Speech Embeddings for Voice Conversion
by Marco Matassoni, Seraphina Fong and Alessio Brutti
Appl. Sci. 2024, 14(9), 3876; https://doi.org/10.3390/app14093876 (registering DOI) - 30 Apr 2024
Abstract
Speech is a crucial source of personal information, and the risk of attackers using such information increases day by day. Speaker privacy protection is crucial, and various approaches have been proposed to hide the speaker’s identity. One approach is voice anonymization, which aims [...] Read more.
Speech is a crucial source of personal information, and the risk of attackers using such information increases day by day. Speaker privacy protection is crucial, and various approaches have been proposed to hide the speaker’s identity. One approach is voice anonymization, which aims to safeguard speaker identity while maintaining speech content through techniques such as voice conversion or spectral feature alteration. The significance of voice anonymization has grown due to the necessity to protect personal information in applications such as voice assistants, authentication, and customer support. Building upon the S3PRL-VC toolkit and on pre-trained speech and speaker representation models, this paper introduces a feature disentanglement approach to improve the de-identification performance of the state-of-the-art anonymization approaches based on voice conversion. The proposed approach achieves state-of-the-art speaker de-identification and causes minimal impact on the intelligibility of the signal after conversion. Full article
12 pages, 590 KiB  
Article
Decision Process for Identifying Appropriate Devices for Power Transfer between Voltage Levels in Distribution Grids
by Nassipkul Dyussembekova, Reiner Schütt, Ingmar Leiße and Bente Ralfs
Energies 2024, 17(9), 2158; https://doi.org/10.3390/en17092158 (registering DOI) - 30 Apr 2024
Abstract
During the energy transition, new types of electrical equipment, especially power electronic devices, are proposed to increase the flexibility of electricity distribution grids. One type is the solid-state transformer (SST), which offers excellent possibilities to improve the voltage quality in electricity distribution grids [...] Read more.
During the energy transition, new types of electrical equipment, especially power electronic devices, are proposed to increase the flexibility of electricity distribution grids. One type is the solid-state transformer (SST), which offers excellent possibilities to improve the voltage quality in electricity distribution grids and integrate hybrid AC/DC grids. This paper compares SST to conventional copper-based power transformers (CPT) with and without an on-load tap changer (OLTC) and with additional downstream converters. For this purpose, a corresponding electricity distribution grid is set up in the power system analysis tool DIgSILENT PowerFactory 2022. A DC generator like a photovoltaic system, a DC load like an electric vehicle fast charging station, and an AC load are connected. Based on load flow simulations, the four power transformers are compared concerning voltage stability during a generator-based and a load-based scenario. The results of load flow simulations show that SSTs are most valuable when additional generators and loads are to be connected to the infrastructure, which would overload the existing grid equipment. The efficiency of using SSTs also depends on the parameters of the electrical grid, especially the lengths of the low-voltage (LV) lines. In addition, a flowchart-based decision process is proposed to support the decision-making process for the appropriate power transformer from an electrical perspective. Beyond these electrical properties, an evaluation matrix lists other relevant criteria like characteristics of the installation site, noise level, expected lifetime, and economic criteria that must be considered. Full article
25 pages, 1456 KiB  
Article
Skin Tone Estimation under Diverse Lighting Conditions
by Success K. Mbatha, Marthinus J. Booysen and Rensu P. Theart
J. Imaging 2024, 10(5), 109; https://doi.org/10.3390/jimaging10050109 (registering DOI) - 30 Apr 2024
Abstract
Knowledge of a person’s level of skin pigmentation, or so-called “skin tone”, has proven to be an important building block in improving the performance and fairness of various applications that rely on computer vision. These include medical diagnosis of skin conditions, cosmetic and [...] Read more.
Knowledge of a person’s level of skin pigmentation, or so-called “skin tone”, has proven to be an important building block in improving the performance and fairness of various applications that rely on computer vision. These include medical diagnosis of skin conditions, cosmetic and skincare support, and face recognition, especially for darker skin tones. However, the perception of skin tone, whether by the human eye or by an optoelectronic sensor, uses the reflection of light from the skin. The source of this light, or illumination, affects the skin tone that is perceived. This study aims to refine and assess a convolutional neural network-based skin tone estimation model that provides consistent accuracy across different skin tones under various lighting conditions. The 10-point Monk Skin Tone Scale was used to represent the skin tone spectrum. A dataset of 21,375 images was captured from volunteers across the pigmentation spectrum. Experimental results show that a regression model outperforms other models, with an estimated-to-target distance of 0.5. Using a threshold estimated-to-target skin tone distance of 2 for all lights results in average accuracy values of 85.45% and 97.16%. With the Monk Skin Tone Scale segmented into three groups, the lighter exhibits strong accuracy, the middle displays lower accuracy, and the dark falls between the two. The overall skin tone estimation achieves average error distances in the LAB space of 16.40±20.62. Full article
(This article belongs to the Section Image and Video Processing)
23 pages, 1215 KiB  
Article
Phytostabilization of Heavy Metals and Fungal Community Response in Manganese Slag under the Mediation of Soil Amendments and Plants
by Hao Wang, Hui Liu, Rongkui Su and Yonghua Chen
Toxics 2024, 12(5), 333; https://doi.org/10.3390/toxics12050333 (registering DOI) - 30 Apr 2024
Abstract
The addition of soil amendments and plants in heavy metal-contaminated soil can result in a significant impact on physicochemical properties, microbial communities and heavy metal distribution, but the specific mechanisms remain to be explored. In this study, Koelreuteria paniculata was used as a [...] Read more.
The addition of soil amendments and plants in heavy metal-contaminated soil can result in a significant impact on physicochemical properties, microbial communities and heavy metal distribution, but the specific mechanisms remain to be explored. In this study, Koelreuteria paniculata was used as a test plant, spent mushroom compost (SMC) and attapulgite (ATP) were used as amendments, and manganese slag was used as a substrate. CK (100% slag), M0 (90% slag + 5% SMC + 5% ATP) and M1 (90% slag + 5% SMC + 5% ATP, planting K. paniculata) groups were assessed in a pilot-scale experiment to explore their different impacts on phytoremediation. The results indicated that adding the amendments significantly improved the pH of the manganese slag, enhancing and maintaining its fertility and water retention. Adding the amendments and planting K. paniculata (M1) significantly reduced the bioavailability and migration of heavy metals (HMs). The loss of Mn, Pb and Zn via runoff decreased by 15.7%, 8.4% and 10.2%, respectively, compared to CK. K. paniculata recruited and enriched beneficial fungi, inhibited pathogenic fungi, and a more stable fungal community was built. This significantly improved the soil quality, promoted plant growth and mitigated heavy metal toxicity. In conclusion, this study demonstrated that the addition of SMC-ATP and planting K. paniculata showed a good phytostabilization effect in the manganese slag and further revealed the response process of the fungal community in phytoremediation. Full article
13 pages, 716 KiB  
Systematic Review
Expanding the Phenotype of the CACNA1C-Associated Neurological Disorders in Children: Systematic Literature Review and Description of a Novel Mutation
by Lorenzo Cipriano, Raffaele Piscopo, Chiara Aiello, Antonio Novelli, Achille Iolascon and Carmelo Piscopo
Children 2024, 11(5), 541; https://doi.org/10.3390/children11050541 (registering DOI) - 30 Apr 2024
Abstract
CACNA1C gene encodes the alpha 1 subunit of the CaV1.2 L-type Ca2+ channel. Pathogenic variants in this gene have been associated with cardiac rhythm disorders such as long QT syndrome, Brugada syndrome and Timothy syndrome. Recent evidence has suggested the possible association between [...] Read more.
CACNA1C gene encodes the alpha 1 subunit of the CaV1.2 L-type Ca2+ channel. Pathogenic variants in this gene have been associated with cardiac rhythm disorders such as long QT syndrome, Brugada syndrome and Timothy syndrome. Recent evidence has suggested the possible association between CACNA1C mutations and neurologically-isolated (in absence of cardiac involvement) phenotypes in children, giving birth to a wider spectrum of CACNA1C-related clinical presentations. However, to date, little is known about the variety of both neurological and non-neurological signs/symptoms in the neurologically-predominant phenotypes. Methods and results: We conducted a systematic review of neurologically-predominant presentations without cardiac conduction defects, associated with CACNA1C mutations. We also reported a novel de novo missense pathogenic variant in the CACNA1C gene of a children patient presenting with constructional, dressing and oro-buccal apraxia associated with behavioral abnormalities, mild intellectual disability, dental anomalies, gingival hyperplasia and mild musculoskeletal defects, without cardiac conduction defects. Conclusions: The present study highlights the importance of considering the investigation of the CACNA1C gene in children’s neurological isolated syndromes, and expands the phenotype of the CACNA1C related conditions. In addition, the present study highlights that, even in absence of cardiac conduction defects, nuanced clinical manifestations of the Timothy syndrome (e.g., dental and gingival defects) could be found. These findings suggest the high variable expressivity of the CACNA1C gene and remark that the absence of cardiac involvement should not mislead the diagnosis of a CACNA1C related disorder. Full article
18 pages, 2887 KiB  
Article
Integrating Computational Fluid Dynamics for Maneuverability Prediction in Dual Full Rotary Propulsion Ships: A 4-DOF Mathematical Model Approach
by Qiaochan Yu, Yuan Yang, Xiongfei Geng, Yuhan Jiang, Yabin Li and Yougang Tang
J. Mar. Sci. Eng. 2024, 12(5), 762; https://doi.org/10.3390/jmse12050762 (registering DOI) - 30 Apr 2024
Abstract
To predict the maneuverability of a dual full rotary propulsion ship quickly and accurately, the integrated computational fluid dynamics (CFD) and mathematical model approach is performed to simulate the ship turning and zigzag tests, which are then compared and validated against a full-scale [...] Read more.
To predict the maneuverability of a dual full rotary propulsion ship quickly and accurately, the integrated computational fluid dynamics (CFD) and mathematical model approach is performed to simulate the ship turning and zigzag tests, which are then compared and validated against a full-scale trial carried out under actual sea conditions. Initially, the RANS equations are solved, employing the Volume of Fluid (VOF) method to capture the free water surface, while a numerical simulation of the captive model test is conducted using the rigid body motion module. Secondly, hydrodynamic derivatives for the MMG model are obtained from the CFD simulations and empirical formula. Lastly, a four-degree-of-freedom mathematical model group (MMG) maneuvering model is proposed for the dual full rotary propulsion ship, incorporating full-scale simulations of turning and zigzag tests followed by a full-scale trial for comparative validation. The results indicate that the proposed method has a high accuracy in predicting the maneuverability of dual full-rotary propulsion ships, with an average error of less than 10% from the full-scale trial data (and within 5% for the tactical diameters in particular) in spite of the influence of environmental factors such as wind and waves. It provides experience in predicting the maneuverability of a full-scale ship during the ship design stage. Full article
15 pages, 1378 KiB  
Article
Wide and Deep Learning Model for Satellite-Based Real-Time Aerosol Retrievals in China
by Nana Luo, Junxiao Zou, Zhou Zang, Tianyi Chen and Xing Yan
Atmosphere 2024, 15(5), 564; https://doi.org/10.3390/atmos15050564 (registering DOI) - 30 Apr 2024
Abstract
Machine learning methods have been recognized as rapid methods for satellite-based aerosol retrievals but have not been widely applied in geostationary satellites. In this study, we developed a wide and deep learning model to retrieve the aerosol optical depth (AOD) using Himawari-8. Compared [...] Read more.
Machine learning methods have been recognized as rapid methods for satellite-based aerosol retrievals but have not been widely applied in geostationary satellites. In this study, we developed a wide and deep learning model to retrieve the aerosol optical depth (AOD) using Himawari-8. Compared to traditional deep learning methods, we embedded a “wide” modeling component and tested the proposed model across China using independent training (2016–2018) and test (2019) datasets. The results showed that the “wide” model improves the accuracy and enhances model interpretability. The estimates exhibited better accuracy (R2 = 0.81, root-mean-square errors (RMSEs) = 0.19, and within the estimated error (EE) = 63%) than those of the deep-only models (R2 = 0.78, RMSE = 0.21, within the EE = 58%). In comparison with extreme gradient boosting (XGBoost) and Himawari-8 V2.1 AOD products, there were also significant improvements. In addition to higher accuracy, the interpretability of the proposed model was superior to that of the deep-only model. Compared with other seasons, higher contributions of spring to the AOD concentrations were interpreted. Based on the application of the wide and deep learning model, the near-real-time variation of the AOD over China could be captured with an ultrafine temporal resolution. Full article
(This article belongs to the Special Issue Natural Sources Aerosol Remote Monitoring (2nd Edition))
18 pages, 1191 KiB  
Article
Adaptive Scale and Correlative Attention PointPillars: An Efficient Real-Time 3D Point Cloud Object Detection Algorithm
by Xinchao Zhai, Yang Gao, Shiwei Chen and Jingshuai Yang
Appl. Sci. 2024, 14(9), 3877; https://doi.org/10.3390/app14093877 (registering DOI) - 30 Apr 2024
Abstract
Recognizing 3D objects from point clouds is a crucial technology for autonomous vehicles. Nevertheless, LiDAR (Light Detection and Ranging) point clouds are generally sparse, and they provide limited contextual information, resulting in unsatisfactory recognition performance for distant or small objects. Consequently, this article [...] Read more.
Recognizing 3D objects from point clouds is a crucial technology for autonomous vehicles. Nevertheless, LiDAR (Light Detection and Ranging) point clouds are generally sparse, and they provide limited contextual information, resulting in unsatisfactory recognition performance for distant or small objects. Consequently, this article proposes an object recognition algorithm named Adaptive Scale and Correlative Attention PointPillars (ASCA-PointPillars) to address this problem. Firstly, an innovative adaptive scale pillars (ASP) encoding method is proposed, which encodes point clouds using pillars of varying sizes. Secondly, ASCA-PointPillars introduces a feature enhancement mechanism called correlative point attention (CPA) to enhance the feature associations within each pillar. Additionally, a data augmentation algorithm called random sampling data augmentation (RS-Aug) is proposed to solve the class imbalance problem. The experimental results on the KITTI 3D object dataset demonstrate that the proposed ASCA-PointPillars algorithm significantly boosts the recognition performance and RS-Aug effectively enhances the training effects on an imbalanced dataset. Full article
(This article belongs to the Special Issue Deep Learning in Object Detection)
23 pages, 729 KiB  
Review
Tumor-Derived Antigenic Peptides as Potential Cancer Vaccines
by Stanislav Sotirov and Ivan Dimitrov
Int. J. Mol. Sci. 2024, 25(9), 4934; https://doi.org/10.3390/ijms25094934 (registering DOI) - 30 Apr 2024
Abstract
Peptide antigens derived from tumors have been observed to elicit protective immune responses, categorized as either tumor-associated antigens (TAAs) or tumor-specific antigens (TSAs). Subunit cancer vaccines incorporating these antigens have shown promise in inducing protective immune responses, leading to cancer prevention or eradication. [...] Read more.
Peptide antigens derived from tumors have been observed to elicit protective immune responses, categorized as either tumor-associated antigens (TAAs) or tumor-specific antigens (TSAs). Subunit cancer vaccines incorporating these antigens have shown promise in inducing protective immune responses, leading to cancer prevention or eradication. Over recent years, peptide-based cancer vaccines have gained popularity as a treatment modality and are often combined with other forms of cancer therapy. Several clinical trials have explored the safety and efficacy of peptide-based cancer vaccines, with promising outcomes. Advancements in techniques such as whole-exome sequencing, next-generation sequencing, and in silico methods have facilitated the identification of antigens, making it increasingly feasible. Furthermore, the development of novel delivery methods and a deeper understanding of tumor immune evasion mechanisms have heightened the interest in these vaccines among researchers. This article provides an overview of novel insights regarding advancements in the field of peptide-based vaccines as a promising therapeutic avenue for cancer treatment. It summarizes existing computational methods for tumor neoantigen prediction, ongoing clinical trials involving peptide-based cancer vaccines, and recent studies on human vaccination experiments. Full article
16 pages, 833 KiB  
Review
Development and Clinical Application of Left Ventricular–Arterial Coupling Non-Invasive Assessment Methods
by Alvaro Gamarra, Pablo Díez-Villanueva, Jorge Salamanca, Rio Aguilar, Patricia Mahía and Fernando Alfonso
J. Cardiovasc. Dev. Dis. 2024, 11(5), 141; https://doi.org/10.3390/jcdd11050141 (registering DOI) - 30 Apr 2024
Abstract
The constant and dynamic interaction between ventricular function and arterial afterload, known as ventricular-arterial coupling, is key to understanding cardiovascular pathophysiology. Ventricular–arterial coupling has traditionally been assessed invasively as the ratio of effective arterial elastance over end-systolic elastance (Ea/Ees), [...] Read more.
The constant and dynamic interaction between ventricular function and arterial afterload, known as ventricular-arterial coupling, is key to understanding cardiovascular pathophysiology. Ventricular–arterial coupling has traditionally been assessed invasively as the ratio of effective arterial elastance over end-systolic elastance (Ea/Ees), calculated from information derived from pressure–volume loops. Over the past few decades, numerous invasive and non-invasive simplified methods to estimate the elastance ratio have been developed and applied in clinical investigation and practice. The echocardiographic assessment of left ventricular Ea/Ees, as proposed by Chen and colleagues, is the most widely used method, but novel echocardiographic approaches for ventricular–arterial evaluation such as left ventricle outflow acceleration, pulse-wave velocity, and the global longitudinal strain or global work index have arisen since the former was first published. Moreover, multimodal imaging or artificial intelligence also seems to be useful in this matter. This review depicts the progressive development of these methods along with their academic and clinical application. The left ventricular–arterial coupling assessment may help both identify patients at risk and tailor specific pharmacological or interventional treatments. Full article
(This article belongs to the Section Imaging)
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