Model System Research Articles

Secondary Sphere Lewis Acid Activated Heme Superoxo Adducts Mimic Crucial Non‐Covalent Interactions in IDO/TDO Heme Dioxygenases

Heme enzymes play a central role in a medley of reactivities within a wide variety of crucial biological systems. Their active sites are highly decorated with pivotal evolutionarily optimized non‐covalent interactions that precisely choreograph their biological functionalities with specific regio‐, stereo‐, and chemo‐selectivities. Gaining a clear comprehension of how such weak interactions within the active sites control reactivity offers powerful information to be implemented into the design of future therapeutic agents that target these heme enzymes. To shed light on such critical details pertaining to tryptophan dioxygenating heme enzymes, this study investigates the indole dioxygenation reactivities of Lewis acid‐activated heme superoxo model systems, wherein an unprecedented kinetic behavior is revealed. In that, the activated heme superoxo adduct is observed to undergo indole dioxygenation with the intermediacy of a non‐covalently organized precursor complex, which forms prior to the rate‐limiting step of the overall reaction landscape. Spectroscopic and theoretical characterization of this precursor complex draws close parallels to the ternary complex of heme dioxygenases, which has been postulated to be of crucial importance for successful 2,3‐dioxygenative cleavage of indole moieties.

Proteomic Insights into Trichome Responses to Elevated Elemental Stress in Cation Exchanger (CAX) Mutants.

Research on elemental distribution in plants is crucial for understanding nutrient uptake, environmental adaptation, and optimizing agricultural practices for sustainable food production. Plant trichomes, with their self-contained structures and easy accessibility, offer a robust model system for investigating elemental repartitioning. Transport proteins, such as the four functional cation exchangers (CAXs) in Arabidopsis, are low-affinity, high-capacity transporters primarily located on the vacuole. Mutants in these transporters have been partially characterized, with one of the phenotypes of the CAX1 mutant being altered tolerance to low-oxygen conditions. A simple visual screen demonstrated trichome density and morphology in cax1 and quadruple CAX (cax1-4: qKO) mutants remained unaltered. Here we used SXRF (Synchrotron X-Ray Fluorescence) to show that trichomes in CAX-deficient lines accumulated high levels of chlorine, potassium, calcium, and manganese. Proteomic analysis on isolated Arabidopsis trichomes. showed changes in protein abundance in response to changes in element accumulation. The CAX mutants showed an increased abundance of plasma membrane ATPase and vacuolar H-pumping proteins, and proteins associated with water movement and endocytosis, while also showing changes in proteins associated with the regulation of plasmodesmata. These findings advance our understanding of the integration of CAX transport with elemental homeostasis within trichomes and shed light on how plants modulate protein abundance under conditions of altered elemental levels.

Seminar: Functional Exposomics and Mechanisms of Toxicity-Insights from Model Systems and NAMs.

Significant progress has been made over the past decade in measuring the chemical components of the exposome, providing transformative population-scale frameworks in probing the etiologic link between environmental factors and disease phenotypes. While the analytical technologies continue to evolve with reams of data being generated, there is an opportunity to complement exposome-wide association studies (ExWAS) with functional analyses to advance etiologic search at organismal, cellular, and molecular levels. Exposomics is a transdisciplinary field aimed at enabling discovery-based analysis of the nongenetic factors that contribute to disease, including numerous environmental chemical stressors. While advances in exposure assessment are enhancing population-based discovery of exposome-wide effects and chemical exposure agents, functional screening and elucidation of biological effects of exposures represent the next logical step toward precision environmental health and medicine. In this work, we focus on the use, strategies, and prospects of alternative approaches and model systems to enhance the current human exposomics framework in biomarker search and causal understanding, spanning from bench-based nonmammalian organisms and cell culture to computational new approach methods (NAMs). We visit the definition of the functional exposome and exposomics and discuss a need to leverage alternative models as opposed to mammalian animals for delineating exposome-wide health effects. Under the "three Rs" principle of reduction, replacement, and refinement, model systems such as roundworms, fruit flies, zebrafish, and induced pluripotent stem cells (iPSCs) are advantageous over mammals (e.g., rodents or higher vertebrates). These models are cost-effective, and cell-specific genetic manipulations in these models are easier and faster, compared to mammalian models. Meanwhile, in silico NAMs enhance hazard identification and risk assessment in humans by bridging the translational gaps between toxicology data and etiologic inference, as represented by in vitro to in vivo extrapolation (IVIVE) and integrated approaches to testing and assessment (IATA) under the adverse outcome pathway (AOP) framework. Together, these alternatives offer a strong toolbox to support functional exposomics to study toxicity and causal mediators underpinning exposure-disease links. https://doi.org/10.1289/EHP13120.

Bioreactor on a chip: a microfluidic device for closed production of human dendritic cells

We have exploited the unique physics available in microfluidic devices to engineer a platform capable of integrating all critical elements of cell therapy into a microfluidic device. The platform can be used to isolate, count, identify and culture cells on a device in a closed Current Good Manufacturing Practice-compatible system. We have used the culture and isolation of human mature dendritic cells (DCs) as our model system, demonstrating each critical element in manufacturing a therapeutic product. We used the system to immunomagnetically isolate CD14+ cells from peripheral blood mononuclear cells, perform on-chip enumeration and surface marker characterization to confirm purity of isolation (mean, 98.6 ± 1.6%) and culture cells in the presence of cytokines to drive differentiation to CD83+ mature DCs. Successful DC maturation was confirmed using on-chip surface marker characterization (positive CD83 expression) with process yields comparable to conventional DC production. The technology presented is the first demonstration of a chip bioreactor capable of recapitulation of all critical elements of cell therapy manufacturing. Its closed nature, scalability and integration of both manufacturing and release testing show the potential for a new approach to industrialization and rapid distribution of cell therapies.

SUPERMAN genes: uncovering a new function in the development of complex inflorescences.

The Arabidopsis SUPERMAN (SUP) gene and its orthologs in eudicots are crucial in regulating the number of reproductive floral organs. In Medicago truncatula, in addition to this function, a novel role in controlling meristem activity during compound inflorescence development was assigned to the SUP-ortholog (MtSUP). These findings led us to investigate whether the role of SUP genes in inflorescence development was legume-specific or could be extended to other eudicots. To assess that, we used Solanum lycopersicum as a model system with a cymose complex inflorescence and Arabidopsis thaliana as the best-known example of simple inflorescence. We conducted a detailed comparative expression analysis of SlSUP and SUP from vegetative stages to flower transition. In addition, we performed an exhaustive phenotypic characterisation of two different slsup and sup mutants during the plant life cycle. Our findings reveal that SlSUP is required for precise regulation of the meristems that control shoot and inflorescence architecture in tomato. In contrast, in Arabidopsis, SUP performs no meristematic function, but we found a role of SUP in floral transition. Our findings suggest that the functional divergence of SUP-like genes contributed to the modification of inflorescence architecture during angiosperm evolution.

Solid phase epitaxy of SrRuO3 encapsulated by SrTiO3 membranes

Solid phase epitaxy (SPE) has been widely employed for various thin-film materials, making it valuable for industrial applications due to its scalability. In complex oxides, SPE has been limited to a few materials because of the challenges in maintaining stoichiometric control during growth, particularly when volatile phases are present at high temperatures. Here, we investigate the impact of encapsulation layers on the SPE of complex oxides, using SrRuO3 (SRO) as a model system. An amorphous SRO layer was deposited on a SrTiO3 (STO) substrate, followed by the transfer of a single-crystalline STO membrane as an encapsulation layer in order to suppress the evaporation of volatile species (RuO2) during the SPE process. Whereas both encapsulated and unencapsulated SRO layers were successfully crystallized, the unencapsulated films suffered a substantial loss of Ru ions—exceeding 20%—compared to their encapsulated counterparts. This loss of Ru ions led to a loss of metallicity in the unencapsulated SRO layers, whereas the encapsulated layers retained their metallic ferromagnetic properties. This study demonstrates that the encapsulation provided by oxide membranes effectively suppresses stoichiometric loss during SPE, presenting a new strategy in stabilizing a broader class of functional oxides as epitaxial thin films.

CytoCellDB: a comprehensive resource for exploring extrachromosomal DNA in cancer cell lines.

Recently, the cancer community has gained a heightened awareness of the roles of extrachromosomal DNA (ecDNA) in cancer proliferation, drug resistance and epigenetic remodeling. However, a hindrance to studying ecDNA is the lack of available cancer model systems that express ecDNA. Increasing our awareness of which model systems express ecDNA will advance our understanding of fundamental ecDNA biology and unlock a wealth of potential targeting strategies for ecDNA-driven cancers. To bridge this gap, we created CytoCellDB, a resource that provides karyotype annotations for cell lines within the Cancer Dependency Map (DepMap) and the Cancer Cell Line Encyclopedia (CCLE). We identify 139 cell lines that express ecDNA, a 200% increase from what is currently known. We expanded the total number of cancer cell lines with ecDNA annotations to 577, which is a 400% increase, covering 31% of cell lines in CCLE/DepMap. We experimentally validate several cell lines that we predict express ecDNA or homogeneous staining regions (HSRs). We demonstrate that CytoCellDB can be used to characterize aneuploidy alongside other molecular phenotypes, (gene essentialities, drug sensitivities, gene expression). We anticipate that CytoCellDB will advance cytogenomics research as well as provide insights into strategies for developing therapeutics that overcome ecDNA-driven drug resistance.

A simple and accurate method for the determination of Rh, Pd, and Pt in e-waste and spent automotive catalysts using HR-CS FAAS for assessing the value of secondary raw materials

This work presents a simple and accurate method for the fast sequential determination of Rh, Pd, and Pt in spent automotive catalysts and e-wastes using high-resolution continuum source flame atomic absorption spectrometry (HR-CS FAAS). Extensive research was carried out in model systems on the impact of potential interfering substances on analyte’s signals measured in two types of flame (air-C2H2 and N2O-C2H2). Mutual analyte interactions were also taken into account. Different background corrections offered by the HR-CS AAS spectrometer were tested to obtain interference-free analyte signals and the best detectability. Using an air-C2H2 flame and 1 % La solution as a spectrochemical buffer provided good sensitivity and accurate determinations of Rh, Pd, and Pt using a simple calibration graph. Microwave-assisted leaching of PGE from waste samples with aqua regia at 240 °C for 60 min efficiently leached all target metals, which significantly simplified and shortened the sample preparation step. The detectability of the method (detection limit of 0.4, 0.6, and 5 mg kg-1 for Rh, Pd, and Pt, respectively) and precision (< 7 %) were satisfactory. The accuracy of the method was confirmed by analysis of certified reference materials (spent automotive catalyst (ERM-EB504), electronic scrap (BAM-M505a)), and calculated zetascore values. The recoveries for Rh, Pd, and Pt in ERM-EB504 were 93, 101, and 96 %, respectively, and for Pd in BAM-M505a, 97 %. The developed method can be used to assess the value of secondary raw materials, such as various types of spent catalysts and e-waste containing Rh, Pd, and Pt.

Influence of phospholipid structures on volatile organic compounds generation in model systems

To investigate the regularities and differences in oxidation products of phosphatidylcholine (PC) and phosphatidylethanolamine (PE) by gas chromatography-mass spectrometry (GC–MS), and examine the influence of variations in fatty acid compositions and head groups on the kinds and contents of volatile organic compounds (VOCs) generated. A total of 42 VOCs were identified from PE (16:0–18:2), PC (16:0–18:2), and PC (16:0–18:1), with aldehydes and ketones being the main VOCs in three phospholipids (PLs). The content of most VOCs produced by PE (16:0–18:2), PC (16:0–18:2), and PC (16:0–18:1) increases with the increase of oxidation temperature and time. Reached peak at 175 ℃ for 60 min. The total VOCs contents generated by PE (16:0–18:2) and PC (16:0–18:2) were higher than those produced by PC (16:0–18:1), with PC (16:0–18:2) showing the highest total VOCs contents. PLs exhibited three mass loss processes with increasing temperature, namely stability, reduction, and stabilization. PC (16:0–18:2) experienced the highest mass loss, followed by PE (16:0–18:2), while PC (16:0–18:1) showed the least mass loss. These findings showed that polyunsaturated fatty acids were more susceptible to oxidation and degradation during oxidation, and the presence of choline groups in the form of PE may enhance the oxidative stability of fatty acyl groups compared to PC.

P01-81 Exploring Gold/PLGA nanoparticles as potential drug-delivery system in a co-culture blood-brain barrier model

P01-81 Exploring Gold/PLGA nanoparticles as potential drug-delivery system in a co-culture blood-brain barrier model

Development and functional testing of battery management system algorithm for an electric bicycle using hardware in the loop testbench

An embedded Battery Management System (BMS) ensures the effective functionality and longevity of the vehicle battery systems. Testing the BMS using the Hardware in Loop (HIL) approach effectively increases safety and reduces product development time in the manufacturing sector. This research aims to develop an efficient battery management system with two-level protection for electric bicycles and test its functionality in the HIL configuration. The bicycle traction model and battery management system were first developed using a model-based design. Further, the model is tested and validated using battery emulators in the HIL methodology. The battery management system receives input data, such as current, voltage, and temperature, and monitors these parameters. The first level of protection involves the vehicle user receiving the warning when the monitoring parameters values exceed the given first safety threshold. As per the second safety threshold values, the BMS trips off the charging or discharging process when the voltage is 51V, the charge current is 5A, the discharge current is -5A and the IC temperature is 80 degrees. Also, BMS balances the cells in 3.84 min using passive balancing. Additionally, the BMS delivers a controlled current of 2.5A for safe battery charging. This methodology increases safety by reducing the potential risks of testing the BMS algorithms in the actual electric bicycle.

Modification of regulatory tyrosine residues biases human Hsp90α in its interactions with cochaperones and clients

The highly conserved Hsp90 chaperones control stability and activity of many essential signaling and regulatory proteins including many protein kinases, E3 ligases and transcription factors. Thereby, Hsp90s couple cellular homeostasis of the proteome to cell fate decisions. High-throughput mass spectrometry revealed 178 and 169 posttranslational modifications (PTMs) for human cytosolic Hsp90α and Hsp90β, but for only a few of the modifications the physiological consequences are investigated in some detail. In this study, we explored the suitability of the yeast model system for the identification of key regulatory residues in human Hsp90α. Replacement of three tyrosine residues known to be phosphorylated by phosphomimetic glutamate and by non-phosphorylatable phenylalanine individually and in combination influenced yeast growth and the maturation of 7 different Hsp90 clients in distinct ways. Furthermore, wild-type and mutant Hsp90 differed in their ability to stabilize known clients when expressed in HepG2 HSP90AA1-/- cells. The purified mutant proteins differed in their interaction with the cochaperones Aha1, Cdc37, Hop and p23 and in their support of the maturation of glucocorticoid receptor ligand binding domain in vitro. In vivo and in vitro data correspond well to each other confirming that the yeast system is suitable for the identification of key regulatory sites in human Hsp90s. Our findings indicate that even closely related clients are affected differently by the amino acid replacements in the investigated positions, suggesting that PTMs could bias Hsp90’s client specificity.

A probabilistic hazard assessment for cyanobacterial toxins accounting for regional geography and water body trophic status

Under climate change scenarios freshwater eutrophication is expected to increase, and with it the occurrence of cyanobacterial toxin-producing harmful algal blooms. In the current study, microcystin toxin occurrence data from literature sources and a long-term provincial monitoring program were used to conduct a probabilistic hazard assessment for Alberta, Canada. The large temporal and spatial range of data makes Alberta a model system for identifying regional geography and water body trophic status factors driving toxin concentrations. Environmental exposure distributions of microcystin concentrations were plotted and used to identify the likelihood of a given sample exceeding water guideline values as a function of regional geography, total phosphorus and chlorophyll-a concentration. This process identified regions with intensive cultivation and those most prone to water deficits associated with climate change to be most associated with exceedances of regulatory guideline values. Elevated phosphorus and chlorophyll-a concentrations were also drivers of toxin occurrence. This assessment can be used to identify water bodies of greatest risk to human and animal populations from cyanotoxins and thereby inform regulators as to most effective monitoring strategies.

Density functional theory study of physisorption of ionic liquid pairs on hydroxylated and oxygen terminated α-SiO2 (001) surfaces

In this work, we investigate the ion pair tetramethylphosphonium cation, [P1,1,1,1]+, and bis(oxalato)borate anion, [BOB]−, as a model system for the study of ionic liquids interacting with both hydroxylated and oxygen terminated α-SiO2 (001) surfaces, using first-principles electronic structure theory. We use a single ionic pair and clusters of ion pairs, in order to have exclusively neutral supercell slab models. We use dispersion-corrected density functional theory (DFT) to ascertain that both the strong physical binding between the ions, dominated by ionic binding, and the weaker physical binding of ions to the different surfaces are correctly described. We have found that the binding of ion pairs is stronger to the hydroxylated α-SiO2 (001) surface compared to the oxygen terminated surface, which is attributed to the formation of H-binding with the oxygen atom(s) of the [BOB]− anion. Through rotation of ionic pair(s), we estimate the surface-ions energy barrier for translational movement and, thus, the strength of H-binding of the ions. At the surface of hydroxylated α-SiO2 (001), we have studied how water molecules form a network of H-binding with the OH groups of the surface and the [BOB]− anion, which offers an explanation for the reduction in the friction of ionic liquids on the inclusion of water. We suggest modeling protocols for simulation of ion pairs on surfaces, which can open up the possibility to use DFT to aid in designing and understanding the physicochemical mechanism of interactions of ionic materials (including ionic liquids) in various technological applications.

Towards electrochemical regeneration of redox photocatalysts? The example of the tris(2,2′-bipyridine)ruthenium(II)/methylviologen system

The regeneration of redox photocatalysts usually requires the use of sacrificial reagents that are added to the medium in stoichiometric amounts, either as an electron donor or as an electron acceptor, to act as an electron relay to the photocatalyst to ensure its effective regeneration. In the present work, we consider the possibility of direct electrochemical regeneration of the catalyst using a model system made of tris(2,2′-bipyridine)ruthenium(II) ([Ru(bpy)3]2+) as photosensitizer and methylviologen (MV2+) as quenching substrate. Based on hydrodynamic amperometry experiments, we demonstrate that this can indeed be possible provided that appropriate potential values are applied to ensure the electrochemical reduction of [Ru(bpy)3]3+ back to [Ru(bpy)3]2+ while avoiding interfering processes arising from electron transfer reactions involving the quencher and/or the products/intermediates generated in the course of the photocatalytic event. Furthermore, using EDTA as a sacrificial electron donor, we show that photocurrents can also be exploited for regenerating the quenching substrate by reduction of the reaction product MV+ (back into MV2+).

Evaluation of distributed and semi-distributed hydrological models in complex River Basin system, Nepal

Hydrological information is essential for planning water resource projects and for simulating hydrological models to calibrate and generate streamflow data. This study evaluates the performance of distributed and semi-distributed hydrological models in the Tamakoshi River Basin (TRB), Nepal. The models assessed include the Spatial Process in Hydrology (SPHY), Hydrologiska Byråns Vattenbalansavdelning (HBV), and Hydrologic Engineering Centre Hydrologic Modeling System (HEC-HMS). The models were evaluated using metrics such as Nash-Sutcliffe Efficiency (NSE) ranging from 0.62 to 0.77, Coefficient of Determination (R2) from 0.76 to 0.77, and Percentage Bias (P Bias) from 26.16 % to −3.54 % during daily calibration. All three models were successfully calibrated and validated on a daily and monthly basis using observed discharge data at the Busti station in the TRB. The SPHY model performed better during the calibration period compared to the validation period, while the HBV and HEC-HMS models showed better performance during validation than calibration. Among the statistical indicators, the coefficient of determination closely matched, but NSE and P Bias showed some deviations. This comparative analysis of calibrated and validated models is valuable for filling gaps in hydrological data records and for selecting appropriate hydrological models for planning, managing, and developing water resource projects in the TRB.

Abnormal inter-hemispheric effective connectivity from left to right auditory regions during Mismatch Negativity (MMN) tasks in psychosis

Anomalous Mismatch Negativity (MMN) in psychosis could be a consequence of disturbed neural oscillatory activity at sensory/perceptual stages of stimulus processing. This study investigated effective connectivity within and between the auditory regions during auditory odd-ball deviance tasks. The analyses were performed on two magnetoencephalography (MEG) datasets: one on duration MMN in a cohort with various diagnoses within the psychosis spectrum and neurotypical controls and one on duration and pitch MMN in first-episode psychosis patients and matched neurotypical controls. We applied spectral Granger causality to MEG source-reconstructed signals to compute effective connectivity within and between the left and right auditory regions. Both experiments showed that duration-deviance detection was associated with early increases of effective connectivity in the beta band followed by increases in the alpha and theta bands, with the connectivity strength linked to the laterality of the MMN amplitude. Compared to controls, people with psychosis had overall smaller effective connectivity, particularly from left to right auditory regions, in the pathway where bilateral information converges toward lateralized processing, often rightward. Blunted MMN in psychosis might reflect a deficit in inter-hemispheric communication between auditory regions, highlighting a “dysconnection” already at preattentive stages of stimulus processing as a model system of widespread pathophysiology.

Development of Two Layer Fibrous Scaffolds for 3D In Vitro Modelling: Effects of Morphology and Surface Properties on Cell Proliferation, Adhesion and Drug Sensitivity

Three-dimensional (3D) in vitro cell models are gaining popularity in cancer research compared to two-dimensional (2D) cell culture models because of their ability to more accurately represent the tissue microenvironment. This study introduces a novel approach for the fabrication of 3D cell culture models by combining modified melt-electrospinning technology and solution electrospinning to create 3D two-layer fibrous scaffolds. By manipulating electrospinning parameters (voltage 11-12kV and feed rate 0.85-1.55 mg/min), we engineered poly(ε-caprolactone) (PCL) scaffolds with varying fiber diameters (8.9±2.2 to 23.1±3.4 μm) and pore sizes (32.7±12.8 to 122.5±21.1 μm). Non-thermal plasma (NTP) treatment at energy density of 0.23 J/cm2 enhanced surface hydrophilicity, evident in a significant reduction in water contact angles from 113±0 ° to 64±0 °. A comprehensive set of characterization techniques, including X-ray diffraction (XRD), differential scanning calorimetry (DSC), and thermogravimetric analysis (TGA) confirmed that plasma treatment altered the surface wettability without compromising the scaffold’s chemical stability or crystalline structure. Biological assays involving human breast cancer MDA-MB-231 cells and human glioblastoma U-87 MG cells demonstrated high cell viability, indicating biocompatibility of the scaffolds. A pronounced difference in proliferation patterns was noted between MDA-MB-231 and U-87 MG, with the latter fully utilizing voids for the formation of cell aggregates, especially in the “fine” scaffold, indicating the dependence of cell behavior on scaffold architecture, which must be adjusted according to the modelled system and duration. Furthermore, investigation of the therapeutic efficacy of doxorubicin revealed a distinct drug response in 3D cultures, EC50 values of doxorubicin in 3D culture was approximately twice higher compared to 2D. These findings underscore the potential of tailored PCL scaffolds to create more physiologically relevant models for cancer research, tissue engineering, and drug screening applications, highlighting the necessity for careful consideration of scaffold design to achieve the desired in vitro model.

Impacts of different vehicle emissions on ozone levels in Beijing: Insights into source contributions and formation processes

Beijing, with the highest number of motor vehicles in China, significantly contributes to O3 pollution through substantial NOx and VOC emissions in the on-road transportation sector. Understanding the unique impact of emissions from different vehicle types on O3 levels is crucial for developing targeted strategies for O3 pollution. This study applied the Community Multiscale Air Quality Modeling System (CMAQ) to comprehensively investigate the impacts of emissions from different vehicle types on O3 levels in various regions of Beijing and to provide valuable insights into source contributions and formation processes. The results revealed that various vehicle types exhibited different spatial-temporal emission patterns, with medium-heavy duty trucks (HDT) and mini-light passenger vehicles (LDPV) identified as the primary contributors to NOx (36.1 %) and VOC (57.6 %) emissions. Using the Integrated Source Apportionment Method (ISAM) coupled in CMAQ, we found the total vehicle emissions contributed to over 20 % of daily maximum 8–h average O3 (MDA8 O3) concentration, ranked as the second largest contributor after regional transport. Contributions to O3 formation from LDPV and medium-large passenger vehicles (MDPV) were 2.6–4.0 and 4.2–6.8 ppb and mainly concentrated in urban areas, while the contributions from mini-light duty trucks (LDT) and HDT were 3.5–4.8 and 3.7–6.2 ppb and mainly concentrated in suburban areas. Through scenario analysis that removed emissions from specific types of vehicles, we found removing LDPV emissions led to decreases in daytime O3 concentration by 0.3–3.8 ppb. In contrast, removing MDPV emissions led to notable O3 increases by 4.0–11.8 ppb at rush hours. Removing LDT and HDT emissions resulted in 0.6–8.0 ppb increases in nocturnal O3 concentrations while 0.8–2.0 ppb decreases during the afternoon. This research highlights the necessity of tailoring control strategies for different vehicle types to effectively reduce O3 levels in Beijing and provides useful information for decision-makers to formulate effective measures of vehicle management in the future.

Artificial intelligence-based learning model to improve the talents of higher education students towards the digitalization era

Artificial intelligence (AI) technology is a hallmark of the 4.0 revolution. The two main issues in Indonesia are infrastructure that needs to be equipped with technology and intelligence-based curriculum integrated with business and industry programs, and lecturers as educators who do not want to use and develop AI technology in applying guided learning models. This research aims to create a learning model based on AI that will help college students develop their talents while maintaining the Pancasila principles in the age of digitization. This study contains four stages: data collection, data analysis, research analysis outcomes, and validation of research analysis results. This research developed an AI-based learning model for use in higher education consisting of four dimensions: input, process, output, and outcome. The input dimension includes components such as students, lecturers, organizations, and infrastructure ready to adopt AI-based learning models. The process dimension consists of the elements that influence the operation of the AI-based learning model system and the functionality provided by the learning model. The output dimension includes characteristics that may be directly measured and process feedback. Finally, the outcome comprises the predicted outputs from the AI-based learning model.