bluuebunny/crossref_metadata_2025 huggingface dataset:
Research on Efficient Operation for Compound Interchange in China from an Auxiliary Lanes Configuration Aspect
Authors: Tian Xin , Shi Mengmeng , Yang Hang , Peng Junning , Pan Binghong
Published: September 2023

Interchanges are the key nodes of the freeway. Due to the existence of weaving behavior, the traffic flow situation is more complicated for small spacing interchanges. Continuous auxiliary lanes are usually used to connect the entrance and exit to form a compound interchange to reduce the interference of weaving behavior. However, when it comes to the design of auxiliary lane forms, China lacks relevant design specifications and research in this area. As a result, there often exists the phenomenon of mismatch between the design form and the traffic volume. In this paper, we took a compound interchange in Xi’an as the research object, proposing four auxiliary lane design schemes and using VISSIM (2022 student) software to establish the simulation model. Additionally, various traffic conditions were simulated through sensitivity analysis. Finally, using the factor analysis method and entropy method, we comprehensively assigned weights to the indexes. By obtaining the weighted scores for various schemes, it became possible to determine the applicability of each scheme under different traffic conditions. The results indicate that the gradient auxiliary lane can be applied to most traffic conditions and has a smaller land occupation than the traditional design, which is an optimization and improvement for the traditional design form.
Structure and Electrical Properties of AlFe Matrix Composites with Graphene
Authors: Petrova Anastasiia N. , Rasposienko Dmitry Y. , Brodova Irina G. , Yolshina Liudmila A. , Muradymov Roman V. , Markin Artem A. , Marchenkov Vyacheslav V. , Fominykh Bogdan M.
Published: September 2023

Composites based on Al-Fe alloys and reinforced with three-layer graphene sheets were synthesized “in situ” under a layer of molten salts. Composites containing 0.12 wt.% graphene were subjected to severe plastic deformation via high-pressure torsion. SEM and TEM were used to study the morphological and size characteristics of the composite structure in the as-cast and deformed states. Herein, it is shown that severe plastic deformation leads to the deformation-induced dissolution of iron-containing aluminides with the formation of a supersaturated Al solid solution with a submicrocrystalline structure. The hardness and electrical properties of the graphene composites were measured in different structural states and compared to the characteristics of the matrix alloy.
Analysis and Optimized Design of Rigid–Flexible Coupling Characteristics of Crab Apple Picking Machines and Crab Apple Trees
Authors: Zhao Hao , Su Lide , Zhang Yong , Cui Hongmei , Wang Jian , Ren Kailin
Published: September 2023

In recent years, with the gradual expansion of the planting area for Chinese crab apple trees, the traditional method of picking crab apples has become inadequate due to its large workload, low efficiency, and high cost. To address this issue, this paper presents the design of a trunk-type vibration picker specifically for crab apple picking. The design process began with a modal analysis and a harmonic response analysis of a crab apple tree using Ansys Workbench. Through these analyses, the optimal excitation frequency for the crab apple tree was determined to be 12.7 Hz. Subsequently, the picker was designed, and its key components underwent modal and stress analyses. A comparison revealed no resonance between the picker and the key components, ensuring the feasibility of the picker. To further evaluate the performance of the picker, a rigid–flexible coupling analysis was conducted using Adams. This analysis determined the acceleration response curves of the lateral branch points of the crab apple tree at various excitation frequencies: 9.7 Hz, 12.7 Hz, 15.7 Hz, and 18.7 Hz. Finally, field trials were carried out to validate the reliability of the data obtained from Adams. The results showed that the lateral branch point acceleration increased with higher excitation frequencies. However, when the optimal excitation frequency of 12.7 Hz was reached, the lateral branch point acceleration decreased. This indicated that the most effective vibration frequency for picking crab apples was 12.7 Hz.
DESTformer: A Transformer Based on Explicit Seasonal–Trend Decomposition for Long-Term Series Forecasting
Authors: Wang Yajun , Zhu Jianping , Kang Renke
Published: September 2023

Seasonal–trend-decomposed transformer has empowered long-term time series forecasting via capturing global temporal dependencies (e.g., period-based dependencies) in disentangled temporal patterns. However, existing methods design various auto-correlation or attention mechanisms in the seasonal view while ignoring the fine-grained temporal patterns in the trend view in the series decomposition component, which causes an information utilization bottleneck. To this end, a Transformer-based seasonal–trend decomposition methodology with a multi-scale attention mechanism in the trend view and a multi-view attention mechanism in the seasonal view is proposed, called DESTformer. Specifically, rather than utilizing the moving average operation in obtaining trend data, a frequency domain transform is first applied to extract seasonal (high-frequency) and trend (low-frequency) components, explicitly capturing different temporal patterns in both seasonal and trend views. For the trend component, a multi-scale attention mechanism is designed to capture fine-grained sub-trends under different receptive fields. For the seasonal component, instead of the frequency-only attention mechanism, a multi-view frequency domain (i.e., frequency, amplitude, and phase) attention mechanism is designed to enhance the ability to capture the complex periodic changes. Extensive experiments are conducted on six benchmark datasets covering five practical applications: energy, transportation, economics, weather, and disease. Compared to the state-of-the-art FEDformer, our model shows reduced MSE and MAE by averages of 6.5% and 3.7%, respectively. Such experimental results verify the effectiveness of our method and point out a new way towards handling trends and seasonal patterns in long-term time series forecasting tasks.
Interaction between Local Shielding Gas Supply and Laser Spot Size on Spatter Formation in Laser Beam Welding of AISI 304
Authors: Diegel Christian , Mattulat Thorsten , Schricker Klaus , Schmidt Leander , Seefeld Thomas , Bergmann Jean Pierre , Woizeschke Peer
Published: September 2023

Background. Spatter formation at melt pool swellings at the keyhole rear wall is a major issue for laser deep penetration welding at speeds beyond 8 m/min. A gas nozzle directed towards the keyhole, that supplies shielding gas locally, is advantageous in reducing spatter formation due to its simple utilization. However, the relationship between local gas flow, laser spot size, and the resulting effects on spatter formation at high welding speeds up to 16 m/min are not yet fully understood. Methods. The high-alloy steel AISI 304 (1.4301/X5CrNi18-10) was welded with laser spot sizes of 300 μm and 600 μm while using a specially designed gas nozzle directed to the keyhole. Constant welding depth was ensured by Optical Coherence Tomography (OCT). Spatter formation was evaluated by precision weighing of samples. Subsequent processing of high-speed images was used to evaluate spatter quantity, size, and velocity. The keyhole oscillation was determined by Fast Fourier Transform (FFT) analysis. Tracking the formation of melt pool swellings at the keyhole rear wall provided information on the upward melt flow velocity. Results. The local gas flow enabled a significant reduction in the number of spatters and loss of mass for both laser spot sizes and indicated an effect on surface tension by shielding the processing zone from the ambient atmosphere. The laser spot size affected the upward melt flow velocity and spatter velocity.
Sorption Capacity of Carbon-Based Mandarin Orange Peels for Removing Methylene Blue and Ibuprofen from Water
Authors: Thabede Patience Mapule
Published: September 2023

Pharmaceutical pollutants in water pose a serious environmental challenge. This research compared the adsorption capacity of mandarin orange peels (MOP) and activated carbon mandarin orange peels (AC-MOP) to adsorb methylene blue (MB) and Ibuprofen (IBF) from an aqueous solution. This is the first study to report on the uptake of Ibuprofen using carbonized mandarin orange peels activated with hydrochloric acid. The biomaterials were characterized using FTIR and SEM. Batch experiments with operational parameters such as pH, contact time, concentration and temperature were investigated for the adsorption of MB and IBF. Isotherms, kinetic calculations and thermodynamic parameters were calculated for the adsorption of MB and IBF. A positive ΔH° suggested the reaction was endothermic, and ΔG° values showed that the sorption process was spontaneous. The isotherm models best fit the Langmuir model with maximum sorption capacities of 74.15 and 78.15 mg/g for MB and IBF, respectively. The adsorption rate for MB was fast and took place within the first 10 min, whilst the removal of IBF was observed at 40 min. The kinetic model evaluation showed that pseudo-second-order was a suitable fit for the mechanism. The re-usability data indicated that the recovery of MB was 70.13%, and IBF was 87.17%. The adsorption capacity of IBF with the carbon-based MOP was higher than that of MB. The results indicated that AC-MOP could be used as an adsorbent for MB and IBF from water. The major advantage of this method is its effectiveness in reducing the concentration of dyes and pharmaceutical pollutants using inexpensive adsorbents.
Estimation of Changes in Sediment Transport along the Free-Flowing Middle Danube River Reach
Authors: Đorđević Dejana , Tamás Enikő Anna , Mihajlović Ljubiša , Abonyi Csaba , Vujanović Aleksandar , Kalocsa Béla
Published: September 2023

The subject of this study is an approximately 300 km long Middle Danube River reach that spans from river kilometer (rkm) 1581 in Hungary to (rkm) 1255 in Serbia. The observed drying of floodplains in Hungary some thirty years ago initiated the hydrological studies. However, problems related to the navigation route maintenance of the Danube River and those in the water supply of irrigation and drainage canal networks are now present in the whole free-flowing middle Danube region. The study aims at investigating the correlation between the observed water level decrease and recorded incision of the river bed at gauging stations and the indirect estimation of the long-term sediment transport along the sand-bed reach based on the surveillance cross-sections’ data collected during regular monitoring surveys on the navigable Danube. It starts with hydrological analyses of the 70-year-long time series of water level and discharge yearly data and continues with morphological and correlation studies. It ends with the estimation of sediment transport. The decreasing trend in water levels and the increasing trend in cross-sectional areas are persistent. There is a linear correlation between the two. Longitudinal changes in sediment transport indicate the existence of both degrading and aggrading riverbed reaches.
Experimental Study on the Condensation Heat Transfer on a Wettability-Interval Grooved Surface
Authors: Ren Shaojun , Gao Shangwen , Xu Ze , Wu Suchen , Deng Zilong
Published: September 2023

To provide further insight into humid air condensation on hybrid surfaces, an experiment was conducted to visually investigate the condensation process on wettability-interval grooved surfaces, which had hydrophobic ridges and hydrophilic grooves. The droplet dynamic behavior and heat transfer performance of condensation on a wettability-interval grooved surface were explored and compared with four other functional surfaces, including the plain hydrophilic surface, plain hydrophobic surface, hydrophilic grooved surface, and hydrophobic grooved surface. The presence of hydrophobic ridges perpendicular to the groove direction and hydrophilic grooves allowed for the exclusion and easy spreading of droplets, respectively. Compared with the other four functional surfaces, the coupling phenomena during condensation, i.e., the spontaneous suction and directional drainage via hydrophilic grooves, were only found on the wettability-interval grooved surface. These could not only remove condensate quickly but also suppress the formation of the flooded liquid film, which was beneficial to the enhancement of heat transfer performance. It was proven by the experimental results that at subcooling 12 K, the condensation heat flux on the wettability-interval grooved surface reached 1280 W/m2, which was 1.25 times that of the plain hydrophobic surface (1030 W/m2), and 15% higher than that of the hydrophobic grooved surface (1110 W/m2). This indicated that the wettability-interval microgrooves could effectively enhance humid air condensation heat transfer performance.
Research and Application of Steam Condensation Heat Transfer Model Containing Noncondensable Gas on a Wall Surface
Authors: Li He , Yang Xiaoming , Wang Chen , Shi Shang , Ma Rubing , Yuan Yidan
Published: September 2023

Steam condensation plays an important role in various engineering processes due to its excellent heat transfer performance. However, condensation in the presence of noncondensable gas has attracted great attention in recent years since noncondensable gas will have a negative effect on condensation heat transfer. The present study proposes a comprehensive model coupled with convective heat transfer, liquid film heat transfer and steam condensation for the heat transfer of condensation with noncondensable gas and uses it in the Program Integrated for Severe Accident Analysis (PISAA) for a nuclear power plant. The condensation heat transfer model has good universality, the calculation process is stable with less iteration and a fast convergence and it is verified and validated by comparing the simulation results of the PISAA and those from traditional containment analysis codes, as well the experiments from the Wisconsin condensation tests; then, a sensitivity analysis for the parameters of the heat transfer coefficient is performed. The validation results show that the average error of the condensation heat transfer coefficient is approximately 10%, and the maximum error does not exceed 30%. The deviation from the experimental data is limited in the acceptable range, which could fulfill the requirement for the analysis of containment accidents in nuclear power plants.
Chemical Characterization and Optical Properties of the Aerosol in São Paulo, Brazil
Authors: Vieira Erick Vinicius Ramos , do Rosario Nilton Evora , Yamasoe Marcia Akemi , Morais Fernando Gonçalves , Martinez Pedro José Perez , Landulfo Eduardo , Maura de Miranda Regina
Published: September 2023

Air pollution in the Metropolitan Area of São Paulo (MASP), Brazil, is a serious problem and is strongly affected by local sources. However, atmosphere column composition in MASP is also affected by biomass burning aerosol (BB). Understanding the impacts of aerosol particles, from both vehicles and BB, on the air quality and climate depends on in-depth research with knowledge of some parameters such as the optical properties of particles and their chemical composition. This study characterized fine particulate matter (PM2.5) from July 2019 to August 2020 in the eastern part of the MASP, relating the chemical composition data obtained at the surface and columnar optical parameters, such as aerosol optical depth (AOD), Ångström Exponent (AE), and single-scattering albedo (SSA). According to the analyzed data, the mean PM2.5 concentration was 18.0 ± 12.5 µg/m3; however, daily events exceeded 75 times the air quality standard of the World Health Organization (15 µg/m3). The mean black carbon concentration was 1.8 ± 1.5 µg/m3 in the sampling period. Positive matrix factorization (PMF) identified four main sources of aerosol: heavy vehicles (42%), followed by soil dust plus local sources (38.7%), light vehicles (9.9%), and local sources (8.6%). AOD and AE presented the highest values in the dry period, during which biomass burning events are more frequent, suggesting smaller particles in the atmosphere. SSA values at 440 nm were between 0.86 and 0.94, with lower values in the winter months, indicating the presence of more absorbing aerosol.
Simulation of Storm Surge Heights Based on Reconstructed Historical Typhoon Best Tracks Using Expanded Wind Field Information
Authors: Suh Seung-Won
Published: September 2023

A numerical model integrating tides, waves, and surges can accurately evaluate the surge height (SH) risks of tropical cyclones. Furthermore, incorporating the external forces exerted by the storm’s wind field can help to accurately reproduce the SH. However, the lack of long-term typhoon best track (BT) data degrades the SH evaluations of past events. Moreover, archived BT data (BTD) for older typhoons contain less information than recent typhoon BTD. Thus, herein, the wind field structure, specifically its relationship with the central air pressure, maximum wind speed, and wind radius, are augmented. Wind formulae are formulated with empirically adjusted radii and the maximum gradient wind speed is correlated with the central pressure. Furthermore, the process is expanded to four quadrants through regression analyses using historical asymmetric typhoon advisory data. The final old typhoon BTs are converted to a pseudo automated tropical cyclone forecasting format for consistency. Validation tests of the SH employing recent BT and reconstructed BT (rBT) indicate the importance of the nonlinear interactions of tides, waves, and surges for the macrotidal west and microtidal south coasts of Korea. The expanded wind fields—rBT—based on the historical old BT successfully assess the return periods of the SH. The proposed process effectively increases typhoon population data by incorporating actual storm tracks.
A Convolutional Neural Network for Steady-State Flow Approximation Trained on a Small Sample Size
Authors: Zhong Guodong , Xu Xuesong , Feng Jintao , Yuan Lei
Published: September 2023

The wind microclimate plays an important role in architectural design, and computational fluid dynamics is a method commonly used for analyzing the issue. However, due to its high technical difficulty and time-consuming nature, it limits the interaction and exploration between designers and environment performance analyses. To address the issue, scholars have proposed a series of approximation models based on machine learning that have partially improved computational efficiency. However, these methods face challenges in terms of balancing applicability, prediction accuracy, and sample size. In this paper, we propose a method based on the classic Vggnet deep convolutional neural network as the backbone to construct an approximate model for predicting steady-state flow fields in urban areas. The method is trained on a small amount of sample data and can be extended to calculate the wind environment performance. Furthermore, we investigated the differences between geometric representation methods, such as the Boolean network representation and signed distance function, as well as different structure models, such as Vgg-CFD-11, Vgg-CFD-13, Vgg-CFD-16, and Vgg-CFD-19. The results indicate that the model can be trained using a small amount of sample data, and all models generally possess the ability to predict the wind environment. The best performance on the validation set and test set was achieved with an RMSE (Root Mean Square Error) of 0.7966 m/s and 2.2345 m/s, respectively, and an R-Squared score of 0.9776 and 0.8455. Finally, we embedded the best-performing model into an architect-friendly urban comprehensive analysis platform, URBAN NEURAL-CFD.
Standardized Precipitation and Evapotranspiration Index Approach for Drought Assessment in Slovakia—Statistical Evaluation of Different Calculations
Authors: Slavková Jaroslava , Gera Martin , Nikolova Nina , Siman Cyril
Published: September 2023

In the conditions of rising air temperature and changing precipitation regimes in Central Europe and Slovakia over the last two decades, it is necessary to analyse drought, develop high-quality tools for drought detection, and understand its reactions to the emerging drought situation. One of the frequently used meteorological drought indices is the Standardized Precipitation and Evapotranspiration Index (SPEI). Several parameters can be modified in different steps of the calculation process of SPEI. In the article, we analyse the influence of selected adjustable parameters on the index results. Our research has shown that the choice of a statistical distribution (Log-logistic, Pearson III, or Generalized Extreme Value) for fitting water balance can affect the feasibility of calculating distribution parameters (and thus the index) from the provided input data, as well as lead to either underestimation or overestimation of the index. The normality test of SPEI can be used as a tool for the detection and elimination of highly skewed indices and cases when the indices were not well determined by the distribution function. This study demonstrated improved results when using the GEV distribution, despite the common use of the Log-logistic distribution. With the Pearson III distribution, unusually high or low SPEI values (|SPEI| > 6) were detected.
Concentration Gradients of Ammonia, Methane, and Carbon Dioxide at the Outlet of a Naturally Ventilated Dairy Building
Authors: Sahu Harsh , Hempel Sabrina , Amon Thomas , Zentek Jürgen , Römer Anke , Janke David
Published: September 2023

In natural ventilation system-enabled dairy buildings (NVDB), achieving accurate gas emission values is highly complicated. The external weather affects measurements of the gas concentration of pollutants (cP) and volume flow rate (Q) due to the open-sided design. Previous research shows that increasing the number of sensors at the side opening is not cost-effective. However, accurate measurements can be achieved with fewer sensors if an optimal sampling position is identified. Therefore, this study attempted to calibrate the outlet of an NVDB for the direct emission measurement method. Our objective was to investigate the cP gradients, in particular, for ammonia (cNH3), carbon dioxide (cCO2), and methane (cCH4) considering the wind speed (v) and their mixing ratios ([cCH4/cNH3¯]) at the outlet, and assess the effect of sampling height (H). The deviations in each cP at six vertical sampling points were recorded using a Fourier-transform infrared (FTIR) spectrometer. Additionally, wind direction and speed were recorded at the gable height (10 m) by an ultrasonic anemometer. The results indicated that, at varied heights, the average cNH3 (p < 0.001), cCO2 (p < 0.001), and (p < 0.001) were significantly different and mostly concentrated at the top (H = 2.7). Wind flow speed information revealed drastic deviations in cP, for example up to +105.1% higher cNH3 at the top (H = 2.7) compared to the baseline (H = 0.6), especially during low wind speed (v < 3 m s−1) events. Furthermore, [cCH4/cNH3¯] exhibited significant variation with height, demonstrating instability below 1.5 m, which aligns with the average height of a cow. In conclusion, the average cCO2, cCH4, and cNH3 measured at the barn’s outlet are spatially dispersed vertically which indicates a possibility of systematic error due to the sensor positioning effect. The outcomes of this study will be advantageous to locate a representative gas sampling position when measurements are limited to one constant height, for example using open-path lasers or low-cost devices.
Electro-Thermal Analysis of a Pouch–Type Lithium–Ion Battery with a High Discharge Rate for Urban Air Mobility
Authors: Lee Geesoo
Published: September 2023

The dynamic behavior and thermal performance of a high-power, high-energy-density lithium-ion battery for urban air mobility (UAM) applications were analyzed by using an electro-thermal model. To simulate the behavior of pouch-type nickel-cobalt-manganese (NCM) lithium–ion batteries, a battery equivalent circuit with a second order of resistance–capacitance (RC) elements was employed. The values of the RC models were determined by using curve fitting based on experimental data for the lithium-ion battery. A three–dimensional model of the lithium-ion battery was created, and a thermal analysis was performed while considering the external temperature and flight time under a 20 min load condition. At an external temperature of 20 °C, the heat generation increased proportionally to the square of the current as the C–rate increased. For 3C, the reaction heat source was 45.5 W, and the average internal temperature of the cell was 36 °C. Even at the same 3C, as the external temperature decreased to 0 °C, the increase in internal resistance led to a greater reaction heat source of 58.27 W, which was 36.9% higher than that at 20 °C. At 5C, the maximum operating time was 685.6 s. At this point, the average internal temperature of the cell was 59.8 °C, which allowed for normal operation. When the C–rate of the battery cell reached 8, which was the momentary maximum high-discharge condition, the temperature sharply rose before the state of charge (SoC) reached 0. With an average internal cell temperature of 80 °C, the maximum operating time became 111.9 s. This met the design requirements for urban air mobility (UAM) in this study.
sEMG Spectral Analysis and Machine Learning Algorithms Are Able to Discriminate Biomechanical Risk Classes Associated with Manual Material Liftings
Authors: Donisi Leandro , Jacob Deborah , Guerrini Lorena , Prisco Giuseppe , Esposito Fabrizio , Cesarelli Mario , Amato Francesco , Gargiulo Paolo
Published: September 2023

Manual material handling and load lifting are activities that can cause work-related musculoskeletal disorders. For this reason, the National Institute for Occupational Safety and Health proposed an equation depending on the following parameters: intensity, duration, frequency, and geometric characteristics associated with the load lifting. In this paper, we explore the feasibility of several Machine Learning (ML) algorithms, fed with frequency-domain features extracted from electromyographic (EMG) signals of back muscles, to discriminate biomechanical risk classes defined by the Revised NIOSH Lifting Equation. The EMG signals of the multifidus and erector spinae muscles were acquired by means of a wearable device for surface EMG and then segmented to extract several frequency-domain features relating to the Total Power Spectrum of the EMG signal. These features were fed to several ML algorithms to assess their prediction power. The ML algorithms produced interesting results in the classification task, with the Support Vector Machine algorithm outperforming the others with accuracy and Area under the Receiver Operating Characteristic Curve values of up to 0.985. Moreover, a correlation between muscular fatigue and risky lifting activities was found. These results showed the feasibility of the proposed methodology—based on wearable sensors and artificial intelligence—to predict the biomechanical risk associated with load lifting. A future investigation on an enriched study population and additional lifting scenarios could confirm the potential of the proposed methodology and its applicability in the field of occupational ergonomics.
Matrix Metalloproteinases and the Pathogenesis of Recurrent Corneal Erosions and Epithelial Basement Membrane Dystrophy
Authors: Jadczyk-Sorek Katarzyna , Garczorz Wojciech , Bubała-Stachowicz Beata , Francuz Tomasz , Mrukwa-Kominek Ewa
Published: September 2023

Matrix metalloproteinases (MMPs) are a group of proteolytic enzymes which are members of the zinc endopeptidase family. They have the ability to degrade extracellular matrix elements, allowing for the release of binding molecules and cell migration. Although metalloproteinases regulate numerous physiological processes within the cornea, overexpression of metalloproteinase genes and an imbalance between the levels of metalloproteinases and their inhibitors can contribute to the inhibition of repair processes, the development of inflammation and excessive cellular proliferation. The involvement of MMPs in the pathogenesis of dystrophic corneal diseases needs clarification. Our analyses focus on the involvement of individual metalloproteinases in the pathogenesis of recurrent corneal erosions and highlight their impact on the development of corneal epithelial basement membrane dystrophy (EBMD). We hypothesize that abnormalities observed in patients with EBMD may result from the accumulation and activation of metalloproteinases in the basal layers of the corneal epithelium, leading to basement membrane degradation. A barrier formed from degradation materials inhibits the normal migration of epithelial cells to the superficial layers, which contributes to the development of the aforementioned lesions. This hypothesis seems to be lent support by the elevated concentrations of metalloproteinases in the corneal epithelium of these patients found in our previous studies on the relationships between MMPs and recurrent corneal erosions.
Selective Noradrenaline Depletion in the Neocortex and Hippocampus Induces Working Memory Deficits and Regional Occurrence of Pathological Proteins
Authors: Prinzi Chiara , Kostenko Anna , de Leo Gioacchino , Gulino Rosario , Leanza Giampiero , Caccamo Antonella
Published: September 2023

Noradrenaline (NA) depletion occurs in Alzheimer’s disease (AD); however, its relationship with the pathological expression of Tau and transactive response DNA-binding protein 43 (TDP-43), two major hallmarks of AD, remains elusive. Here, increasing doses of a selective noradrenergic immunotoxin were injected into developing rats to generate a model of mild or severe NA loss. At about 12 weeks post-lesion, dose-dependent working memory deficits were detected in these animals, associated with a marked increase in cortical and hippocampal levels of TDP-43 phosphorylated at Ser 409/410 and Tau phosphorylated at Thr 217. Notably, the total levels of both proteins were largely unaffected, suggesting a direct relationship between neocortical/hippocampal NA depletion and the phosphorylation of pathological Tau and TDP-43 proteins. As pTD43 is present in 23% of AD cases and pTau Thr217 has been detected in patients with mild cognitive impairment that eventually would develop into AD, improvement of noradrenergic function in AD might represent a viable therapeutic approach with disease-modifying potential.
Expanding the MAPPs Assay to Accommodate MHC-II Pan Receptors for Improved Predictability of Potential T Cell Epitopes
Authors: Hartman Katharina , Steiner Guido , Siegel Michel , Looney Cary M. , Hickling Timothy P. , Bray-French Katharine , Springer Sebastian , Marban-Doran Céline , Ducret Axel
Published: September 2023

A critical step in the immunogenicity cascade is attributed to human leukocyte antigen (HLA) II presentation triggering T cell immune responses. The liquid chromatography–tandem mass spectrometry (LC-MS/MS)-based major histocompatibility complex (MHC) II-associated peptide proteomics (MAPPs) assay is implemented during preclinical risk assessments to identify biotherapeutic-derived T cell epitopes. Although studies indicate that HLA-DP and HLA-DQ alleles are linked to immunogenicity, most MAPPs studies are restricted to using HLA-DR as the dominant HLA II genotype due to the lack of well-characterized immunoprecipitating antibodies. Here, we address this issue by testing various commercially available clones of MHC-II pan (CR3/43, WR18, and Tü39), HLA-DP (B7/21), and HLA-DQ (SPV-L3 and 1a3) antibodies in the MAPPs assay, and characterizing identified peptides according to binding specificity. Our results reveal that HLA II receptor-precipitating reagents with similar reported specificities differ based on clonality and that MHC-II pan antibodies do not entirely exhibit pan-specific tendencies. Since no individual antibody clone is able to recover the complete HLA II peptide repertoire, we recommend a mixed strategy of clones L243, WR18, and SPV-L3 in a single immunoprecipitation step for more robust compound-specific peptide detection. Ultimately, our optimized MAPPs strategy improves the predictability and additional identification of T cell epitopes in immunogenicity risk assessments.
Review of Non-Eosinophilic Esophagitis-Eosinophilic Gastrointestinal Disease (Non-EoE-EGID) and a Case Series of Twenty-Eight Affected Patients
Authors: Kinoshita Yoshikazu , Sanuki Tsuyoshi
Published: September 2023

Eosinophilic gastrointestinal disease (EGID) is divided into eosinophilic esophagitis (EoE) and non-eosinophilic esophagitis eosinophilic gastrointestinal disease (non-EoE-EGID) based on the involved gastrointestinal segments. Reports regarding non-EoE-EGID are limited, in part because of its rarity. The present study was performed to review non-EoE-EGID, including its pathogenesis, diagnosis, treatment, and prognosis. Additionally, details regarding 28 cases of non-EoE-EGID recently diagnosed at our Japanese tertial medical center are presented and compared with 20 EoE cases diagnosed during the same period at the same medical center. Comparisons of the two groups clarified differences regarding age- and gender-dependent prevalence between the two conditions, and also showed that systemic involvement and disease severity were greater in the non-EoE-EGID patients. Notably, diagnosis of non-EoE-EGID is difficult because of its lack of specific or characteristic symptoms and endoscopic findings. The clinical characteristics of EoE and non-EoE-EGID differ in many ways, while they also share several genetic, clinical, laboratory, and histopathological features.
Conservation of Glutathione Transferase mRNA and Protein Sequences Similar to Human and Horse Alpha Class GST A3-3 across Dog, Goat, and Opossum Species
Authors: Hubert Shawna M. , Samollow Paul B. , Lindström Helena , Mannervik Bengt , Ing Nancy H.
Published: September 2023

The glutathione transferase A3-3 (GST A3-3) homodimeric enzyme is the most efficient enzyme that catalyzes isomerization of the precursors of testosterone, estradiol, and progesterone in the gonads of humans and horses. However, the presence of GST A3-3 orthologs with equally high ketosteroid isomerase activity has not been verified in other mammalian species, even though pig and cattle homologs have been cloned and studied. Identifying GSTA3 genes is a challenge because of multiple GSTA gene duplications (e.g., 12 in the human genome); consequently, the GSTA3 gene is not annotated in most genomes. To improve our understanding of GSTA3 gene products and their functions across diverse mammalian species, we cloned homologs of the horse and human GSTA3 mRNAs from the testes of a dog, goat, and gray short-tailed opossum, the genomes of which all currently lack GSTA3 gene annotations. The resultant novel GSTA3 mRNA and inferred protein sequences had a high level of conservation with human GSTA3 mRNA and protein sequences (≥70% and ≥64% identities, respectively). Sequence conservation was also apparent for the 12 residues of the “H-site” in the 222 amino acid GSTA3 protein that is known to interact with the steroid substrates. Modeling predicted that the dog GSTA3-3 may be a more active ketosteroid isomerase than the corresponding goat or opossum enzymes. However, expression of the GSTA3 gene was higher in liver than in other dog tissue. Our results improve understanding of the active sites of mammalian GST A3-3 enzymes, inhibitors of which might be useful for reducing steroidogenesis for medical purposes, such as fertility control or treatment of steroid-dependent diseases.
An Overview of the Safety Profile and Clinical Impact of CDK4/6 Inhibitors in Breast Cancer—A Systematic Review of Randomized Phase II and III Clinical Trials
Authors: Stanciu Ioana-Miruna , Parosanu Andreea Ioana , Nitipir Cornelia
Published: September 2023

Cyclin-dependent kinase 4 and 6 inhibitors (CDK4/6is) have transformed the treatment of hormone receptor-positive (HR+) and human epidermal growth factor receptor 2-negative (HER2−) breast cancer over the last decade. These inhibitors are currently established as first- and second-line systemic treatment choices for both endocrine-sensitive and -resistant breast cancer populations alongside endocrine therapy (ET) or monotherapy. Data on targeted therapy continue to mature, and the number of publications has been constantly rising. Although these drugs have been demonstrated to prolong overall survival (as well as progression-free survival (PFS) in breast cancer patients), changing the paradigm of all current knowledge, they also cause important adverse events (AEs). This review provides the latest summary and update on the safety profile of the three CDK4/6 inhibitors, as it appears from all major phase II and III randomized clinical trials regarding palbociclib, ribociclib, and abemaciclib, including the most relevant 15 clinical trials.
Metabolomics Analysis and Biochemical Profiling of Arsenic-Induced Metabolic Impairment and Disease Susceptibility
Authors: Shoaib Syed Muhammad , Afzal Samina , Feezan Ali , Akash Muhammad Sajid Hamid , Nadeem Ahmed , Mir Tahir Maqbool
Published: September 2023

Our study aimed to conduct a comprehensive biochemical profiling and metabolomics analysis to investigate the effects of arsenic-induced metabolic disorders, with a specific focus on disruptions in lipid metabolism, amino acid metabolism, and carbohydrate metabolism. Additionally, we sought to assess the therapeutic potential of resveratrol (RSV) as a remedy for arsenic-induced diabetes, using metformin (MF) as a standard drug for comparison. We measured the total arsenic content in mouse serum by employing inductively coupled plasma mass spectrometry (ICP-MS) after administering a 50-ppm solution of sodium arsenate (50 mg/L) in purified water. Our findings revealed a substantial increase in total arsenic content in the exposed group, with a mean value of 166.80 ± 8.52 ppb (p < 0.05). Furthermore, we investigated the impact of arsenic exposure on various biomarkers using enzyme-linked immunosorbent assay (ELISA) methods. Arsenic exposed mice exhibited significant hyperglycemia (p < 0.001) and elevated levels of homeostatic model assessment of insulin resistance (HOMA-IR), hemoglobin A1c (Hb1Ac), Inflammatory biomarkers as well as liver and kidney function biomarkers (p < 0.05). Additionally, the levels of crucial enzymes linked to carbohydrate metabolism, including α-glucosidase, hexokinase, and glucose-6-phosphatase (G6PS), and oxidative stress biomarkers, such as levels of glutathione (GSH), glutathione reductase (GR), glutathione peroxidase (GPx), catalase, and superoxide dismutase (SOD), were significantly reduced in the arsenic-exposed group compared to the control group (p < 0.05). However, the level of MDA was significantly increased. Molecular analysis of gene expression indicated significant upregulation of key enzymes involved in lipid metabolism, such as carnitine palmitoyl-transferase-I (CPT-I), carnitine palmitoyl-transferase-II (CPT-II), lecithin–cholesterol acyltransferase (LCAT), and others. Additionally, alterations in gene expression related to glucose transporter-2 (GLUT-2), glucose-6-phosphatase (G6PC), and glucokinase (GK), associated with carbohydrate metabolism, were observed. Amino acid analysis revealed significant decreases in nine amino acids in arsenic-exposed mice. Metabolomics analysis identified disruptions in lipid metabolomes, amino acids, and arsenic metabolites, highlighting their involvement in essential metabolic pathways. Histopathological observations revealed significant changes in liver architecture, hepatocyte degeneration, and increased Kupffer cells in the livers of arsenic-exposed mice. In conclusion, these findings enhance our comprehension of the impact of environmental toxins on metabolic health and offer potential avenues for remedies against such disruptions.
Plasma Brain-Derived Neurotrophic Factor Levels in First-Episode and Recurrent Major Depression and before and after Bright Light Therapy in Treatment-Resistant Depression
Authors: Kosanovic Rajacic Biljana , Sagud Marina , Begic Drazen , Nikolac Perkovic Matea , Dvojkovic Anja , Ganoci Lana , Pivac Nela
Published: September 2023

Brain-derived neurotrophic factor (BDNF) is implicated in the etiology and treatment response in major depressive disorder (MDD). However, peripheral BDNF concentrations have not been compared across different MDD stages. Bright light therapy (BLT) offers some potential in treatment-resistant depression (TRD), but its effects on BDNF levels are unknown. This study included a cross-sectional analysis of plasma BDNF concentration in females with TRD, unmedicated MDD patients, and healthy controls (HC), and measurements of longitudinal BLT effects on plasma BDNF levels in TRD patients. The present study included 55 drug-naïve, first-episode patients, 25 drug-free recurrent-episode MDD patients, 71 HC participants, and 54 TRD patients. Patients were rated by Hamilton Depression Rating Scale (HAMD)-17 and the Montgomery–Åsberg Depression Rating Scale (MADRS). Patients with TRD received BLT during 4 weeks. The total HAMD-17 and MADRS scores decreased following BLT. All patient groups had lower plasma BDNF than HC, but BDNF levels did not differ between first- and recurrent-episode BDNF patients and TRD patients before or after BLT. However, responders and remitters to BLT had higher post-treatment plasma BDNF concentrations than patients who did not achieve response or remission. The changes in plasma BDNF levels may be candidates for biomarkers of treatment response to BLT in TRD patients.
Advances in Histological and Molecular Classification of Hepatocellular Carcinoma
Authors: Choi Joon Hyuk , Thung Swan N.
Published: September 2023

Hepatocellular carcinoma (HCC) is a primary liver cancer characterized by hepatocellular differentiation. HCC is molecularly heterogeneous with a wide spectrum of histopathology. The prognosis of patients with HCC is generally poor, especially in those with advanced stages. HCC remains a diagnostic challenge for pathologists because of its morphological and phenotypic diversity. However, recent advances have enhanced our understanding of the molecular genetics and histological subtypes of HCC. Accurate diagnosis of HCC is important for patient management and prognosis. This review provides an update on HCC pathology, focusing on molecular genetics, histological subtypes, and diagnostic approaches.
Using Footpad Sculpturing to Enhance the Maneuverability and Speed of a Robotic Marangoni Surfer
Authors: Bechard Samuel , Timm Mitchel L. , Masoud Hassan , Rothstein Jonathan P.
Published: September 2023

From insects to arachnids to bacteria, the surfaces of lakes and ponds are teaming with life. Many modes of locomotion are employed by these organisms to navigate along the air–water interface, including the use of lipid-laden excretions that can locally change the surface tension of the water and induce a Marangoni flow. In this paper, we improved the speed and maneuverability of a miniature remote-controlled robot that mimics insect locomotion using an onboard tank of isopropyl alcohol and a series of servomotors to control both the rate and location of alcohol release to both propel and steer the robot across the water. Here, we studied the effect of a series of design changes to the foam rubber footpads, which float the robot and are integral in efficiently converting the alcohol-induced surface tension gradients into propulsive forces and effective maneuvering. Two designs were studied: a two-footpad design and a single-footpad design. In the case of two footpads, the gap between the two footpads was varied to investigate its impact on straight-line speed, propulsion efficiency, and maneuverability. An optimal design was found with a small but finite gap between the two pads of 7.5 mm. In the second design, a single footpad without a central gap was studied. This footpad had a rectangular cut-out in the rear to capture the alcohol. Footpads with wider and shallower cut-outs were found to optimize efficiency. This observation was reinforced by the predictions of a simple theoretical mechanical model. Overall, the optimized single-footpad robot outperformed the two-footpad robot, producing a 30% improvement in speed and a 400% improvement in maneuverability.
The Crosstalk between the EGFR and IFN-γ Pathways and Synergistic Roles in Survival Prediction and Immune Escape in Gliomas
Authors: Zhou Xingang , Liang Tingyu , Ge Yulu , Wang Yu , Ma Wenbin
Published: September 2023

Glioma is the most common primary malignant brain tumor. The poor prognosis of gliomas, especially glioblastoma (GBM), is associated with their unique molecular landscape and tumor microenvironment (TME) features. The epidermal growth factor receptor (EGFR) gene is one of the frequently altered loci in gliomas, leading to the activation of the EGFR signaling pathway and thus, promoting the genesis of gliomas. Whether there exist factors within the TME that can lead to EGFR activation in the context of gliomas is currently unexplored. In total, 702 samples from The Cancer Genome Atlas (TCGA) and 325 samples from The Chinese Glioma Genome Atlas (CGGA) were enrolled in this study. Gene signatures related to EGFR signaling and interferon-γ (IFN-γ) response were established via the LASSO-COX algorithm. Gene Set Enrichment Analysis (GSEA) and Gene Ontology (GO) analysis were applied for function exploration. Kaplan–Meier (KM) curves and single sample GSEA (ssGSEA) of immune cell subpopulations were performed to analyze the prognosis and TME characteristics of different subgroups. Moreover, Western blotting (WB) and flow cytometry (FCM) demonstrated the correlation between IFN-γ and EGFR signaling activation and the subsequent induction of programmed death ligand 1 (PD-L1) expression. An EGFR signaling-related risk score was established, and a higher score was correlated with poorer prognosis and a more malignant phenotype in gliomas. Biological function analysis revealed that a higher EGFR-related score was significantly associated with various cytokine response pathways, especially IFN-γ. Long-term (7 days) exposure to IFN-γ (400 ng/mL) induced the activation of EGFR signaling in the u87 cell line. Next, an IFN-γ response-related risk score was established; the combination of these two scores could be used to further reclassify gliomas into subtypes with different clinical features and TME features. Double high-risk samples tended to have a poorer prognosis and more immunosuppressive TME. Additionally, FCM discovered that the activation of EGFR signaling via EGF (100 ng/mL) could trigger PD-L1 protein expression. This research indicates that IFN-γ, an inflammatory cytokine, can activate the EGFR pathway. The combination of EGFR signaling and IFN-γ response pathway can establish a more precise classification of gliomas.