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Search Results (462)

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11 pages, 231 KiB  
Article
Tempol Induces Oxidative Stress, ER Stress and Apoptosis via MAPK/Akt/mTOR Pathway Suppression in HT29 (Colon) and CRL-1739 (Gastric) Cancer Cell Lines
by Gorkem Ozdemir and Halil Mahir Kaplan
Curr. Issues Mol. Biol. 2025, 47(7), 574; https://doi.org/10.3390/cimb47070574 - 21 Jul 2025
Viewed by 194
Abstract
Tempol is a synthetic antioxidant that shows promise in preclinical cancer studies by inhibiting growth and inducing apoptosis. Given that the Mitogen-Activated Protein Kinase (MAPK) and Protein Kinase B/Mammalian Target of Rapamycin (Akt/mTOR) signaling pathways are frequently dysregulated in gastric and colon cancers [...] Read more.
Tempol is a synthetic antioxidant that shows promise in preclinical cancer studies by inhibiting growth and inducing apoptosis. Given that the Mitogen-Activated Protein Kinase (MAPK) and Protein Kinase B/Mammalian Target of Rapamycin (Akt/mTOR) signaling pathways are frequently dysregulated in gastric and colon cancers and contribute to their progression, we investigated Tempol’s anti-cancer potential in HT29 (colon) and CRL-1739 (gastric) cancer cells. Cells were treated with 2 mM Tempol for 48 h, with untreated cells as controls. We evaluated apoptosis (Bax, cleaved caspase-3, and Bcl-2), key signaling pathway activity (p-ERK, p-JNK, p-AKT, and p-mTOR), and levels of stress- and apoptosis-related proteins (WEE1, GADD153, GRP78, and AIF). Tempol significantly increased pro-apoptotic Bax and cleaved caspase-3 (p < 0.0001) and decreased anti-apoptotic Bcl-2 (p < 0.0001) in both cell lines. Furthermore, Tempol markedly reduced the activity of p-ERK, p-JNK, p-AKT, and p-mTOR (p < 0.0001) and significantly increased the protein levels of WEE1, GADD153, GRP78, and AIF (p < 0.0001). Tempol treatment also led to a significant increase in total oxidant status and a decrease in total antioxidant status. In conclusion, our findings suggest that Tempol exhibits its anti-cancer activity through multiple interconnected mechanisms, primarily inducing apoptosis and oxidative stress, while concurrently suppressing pro-survival signaling pathways. These results highlight Tempol’s potential as a therapeutic agent for gastric and colon cancers. Full article
(This article belongs to the Section Biochemistry, Molecular and Cellular Biology)
19 pages, 3397 KiB  
Article
Large-Scale Transmission Expansion Planning with Network Synthesis Methods for Renewable-Heavy Synthetic Grids
by Adam B. Birchfield, Jong-oh Baek and Joshua Xia
Energies 2025, 18(14), 3844; https://doi.org/10.3390/en18143844 - 19 Jul 2025
Viewed by 199
Abstract
With increasing electrification and the connection of more renewable resources at the transmission level, bulk interconnected electric grids need to plan network expansion with new transmission facilities. The transmission expansion planning (TEP) problem is particularly challenging because of the combinatorial, integer optimization nature [...] Read more.
With increasing electrification and the connection of more renewable resources at the transmission level, bulk interconnected electric grids need to plan network expansion with new transmission facilities. The transmission expansion planning (TEP) problem is particularly challenging because of the combinatorial, integer optimization nature of the problem and the complexity of engineering analysis for any one possible solution. Network synthesis methods, that is, heuristic-based techniques for building synthetic electric grid models based on complex network properties, have been developed in recent years and have the capability of balancing multiple aspects of power system design while efficiently considering large numbers of candidate lines to add. This paper presents a methodology toward scalability in addressing the large-scale TEP problem by applying network synthesis methods. The algorithm works using a novel heuristic method, inspired by simulated annealing, which alternates probabilistic removal and targeted addition, balancing the fixed cost of transmission investment with objectives of resilience via power flow contingency robustness. The methodology is demonstrated in a test case that expands a 2000-bus interconnected synthetic test case on the footprint of Texas with new transmission to support 2025-level load and generation. Full article
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17 pages, 3483 KiB  
Article
A Feasibility Study of a Virtual Power Line Device to Improve Hosting Capacity in Renewable Energy Sources
by Seong-Eun Rho, Sung-Moon Choi, Joong-Seon Lee, Hyun-Sang You, Seung-Ho Lee and Dae-Seok Rho
Energies 2025, 18(14), 3714; https://doi.org/10.3390/en18143714 - 14 Jul 2025
Viewed by 276
Abstract
As many renewable energy sources have been waiting to be interconnected with distribution systems due to the lack of power system infrastructure in Korea, studies to solve the delayed problem for renewable energy sources required. In order to overcome these problems, this paper [...] Read more.
As many renewable energy sources have been waiting to be interconnected with distribution systems due to the lack of power system infrastructure in Korea, studies to solve the delayed problem for renewable energy sources required. In order to overcome these problems, this paper presents an introduction model and optimal capacity algorithm of a VPL (virtual power line) device, which is a virtual power line operation technology to manage the power system by operating an ESS installed at the coupling point of renewable energy source without additionally expanding the power system infrastructure in a conventional way; this paper also proposes an economic evaluation method to assess the feasibility of the VPL device. The optimal capacity of the VPL device is determined by solving the over-voltage problem for the customer, and the economic evaluation method for the VPL device is considered by cost and benefit elements to evaluate the feasibility of introduction model for VPL device. From the simulation result of the proposed optimal capacity algorithm and economic evaluation method based on the introduction model in the VPL device, and it was confirmed that the optimal kW capacity of VPL device was selected as the maximum value in power control values, and the optimal kWh capacity was also determined by accumulating the power control values over the time intervals; also, the proper capacity of the VPL can be more economical than the investment cost of power system infrastructure expansion in the conventional method. Full article
(This article belongs to the Special Issue Stationary Energy Storage Systems for Renewable Energies)
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16 pages, 3070 KiB  
Article
Global Sensitivity Analysis of Tie-Line Power on Voltage Stability Margin in Renewable Energy-Integrated System
by Haifeng Zhang, Song Gao, Jiajun Zhang, Yunchang Dong, Han Gao and Deyou Yang
Electronics 2025, 14(14), 2757; https://doi.org/10.3390/electronics14142757 - 9 Jul 2025
Viewed by 204
Abstract
With the increasing load and renewable energy capacity in interconnected power grids, the system voltage stability faces significant challenges. Tie-line transmission power is a critical factor influencing the voltage stability margin. To address this, this paper proposes a fully data-driven global sensitivity calculation [...] Read more.
With the increasing load and renewable energy capacity in interconnected power grids, the system voltage stability faces significant challenges. Tie-line transmission power is a critical factor influencing the voltage stability margin. To address this, this paper proposes a fully data-driven global sensitivity calculation method for the tie-line power-voltage stability margin, aiming to quantify the impact of tie-line power on the voltage stability margin. The method first constructs an online estimation model of the voltage stability margin based on system measurement data under ambient excitation. To adapt to changes in system operating conditions, an online updating strategy for the parameters of the margin estimation model is further proposed, drawing on incremental learning principles. Subsequently, considering the source–load uncertainty of the system, a global sensitivity calculation method based on analysis of variance (ANOVA) is proposed, utilizing online acquired voltage stability margin and tie-line power data, to accurately quantify the impact of tie-lines on the voltage stability margin. The accuracy of the proposed method is verified through the Nordic test system and the China Electric Power Research Institute (CEPRI) standard test case; the results show that the error of the proposed method is less than 0.3%, and the computation time is within 1 s. Full article
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18 pages, 3954 KiB  
Article
Remolding Water Content Effect on the Behavior of Frozen Clay Soils Subjected to Monotonic Triaxial Loading
by Shuai Qi, Jinhui Liu, Wei Ma, Jing Wang, Houwang Bai and Shaojian Wang
Appl. Sci. 2025, 15(13), 7590; https://doi.org/10.3390/app15137590 - 7 Jul 2025
Viewed by 214
Abstract
Understanding the mechanical behavior of frozen clay subgrade soils was essential for ensuring the safe and stable operation of transportation lines. However, the influence of remolding water content w on this behavior remained unclear. To address this gap, this study examined the effect [...] Read more.
Understanding the mechanical behavior of frozen clay subgrade soils was essential for ensuring the safe and stable operation of transportation lines. However, the influence of remolding water content w on this behavior remained unclear. To address this gap, this study examined the effect of w through monotonic triaxial testing. Three typical remolding water contents (w = 19%, 27.5% and 35%) and three confining pressures (σ3 = 200 kPa, 700 kPa and 1200 kPa) were considered. Results showed that the mechanical behavior of frozen clay soils displayed a clear dependence on w, which was controlled by microstructural evolution. As w increased, the shear strength qmax, resilient modulus E0 and cohesion c increased, which resulted from the progressive development of ice bonding within the shear plane. A threshold w value was found at wopt = 27.5%, marking a structural transition and separating the variations of qmax, E0 and c into two regimes. When w ≤ 27.5%, the soil fabric was controlled by clay aggregates. As w increased, the growth in ice cementation was confined within these aggregates, leading to limited increase in qmax, E0 and c. However, as w exceeded 27.5%, the soil fabric transitioned into a homogeneous matrix of dispersed clay particles. In this case, increasing w greatly promoted the development of an interconnected ice cementation network, thus significantly facilitating the increase in qmax, E0 and c. The friction angle φ decreased with w increasing, primarily due to the lubrication effect caused by the growing ice. In addition, the enhanced lubrication effect in the clay particle-dominated fabric (w > 27.5%) resulted in a larger reduction rate of φ. Regarding Poisson’s ratio v and dilation angle ψ, the w increase led to growth in both parameters. This phenomenon could be explained by the increased involvement of solid ice into the soil structure. Full article
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16 pages, 5185 KiB  
Article
Analysis the Mechanical Response of Tunnels Under the Action of Vertical Jacking in Shield Construction and Research on Reinforcement
by Mingxun Hou, Chunshan Yang, Jiayi Yang, Yuefei Zeng and Zhigang Zhu
Buildings 2025, 15(13), 2321; https://doi.org/10.3390/buildings15132321 - 2 Jul 2025
Viewed by 243
Abstract
This research examines the effects of vertical jacking construction on the mechanical behavior of shield tunnels. Model tests simulating vertical jacking were performed utilizing a purpose-built apparatus to quantify the reaction forces generated by the diffusion block during the jacking operation. A systematic [...] Read more.
This research examines the effects of vertical jacking construction on the mechanical behavior of shield tunnels. Model tests simulating vertical jacking were performed utilizing a purpose-built apparatus to quantify the reaction forces generated by the diffusion block during the jacking operation. A systematic analysis was conducted on the mechanical responses of shield tunnel lining segments and their interconnecting joints. Utilizing Particle Flow Code (PFC) methodology, a deformation prediction model specifically tailored for vertical jacking conditions was formulated. Correlating simulation results with experimental measurements quantified the sensitivity of tunnel deformation to grouting reinforcement, enabling the identification of an optimal reinforcement zone. Key findings reveal that the jacking reaction force distribution exhibits pronounced nonlinearity: a substantial increase precedes failure, followed by rapid post-failure reduction and eventual stabilization in advanced jacking stages. Tunnel convergence deformation evolves through four distinct phases: significant growth, rapid attenuation, gradual diminution, and final stabilization. The primary zone of influence encompasses the opening ring and its two adjacent rings. Jacking induces longitudinal bending deformation, with maximum joint opening occurring at the opening ring. Abrupt longitudinal load fluctuations cause dislocation between the opening ring and neighboring rings. Internal segment stresses exhibit initial tensile and compressive increases followed by subsequent relaxation. Externally applied grouting reinforcement effectively attenuates jacking-induced tunnel deformation. An optimal reinforcement range was determined at the 60° position relative to the segment springline, substantially lowering resource consumption and construction risks compared to conventional reinforcement strategies. These outcomes furnish theoretical underpinnings and technical benchmarks for optimizing engineering design and facilitating the implementation of vertical jacking technology. Full article
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36 pages, 4430 KiB  
Article
Rethinking Masdar and The Line Megaprojects: The Interplay of Economic, Social, Political, and Spatial Dimensions
by Mohamad Kashef
Land 2025, 14(7), 1358; https://doi.org/10.3390/land14071358 - 26 Jun 2025
Viewed by 1442
Abstract
This study critically examines the rapid proliferation of megaprojects across the Arab region, with a focus on the Gulf Cooperation Council (GCC) countries, where large-scale developments are strategically deployed to reshape global economic influence and enhance geopolitical positioning. Megaprojects, characterized by their vast [...] Read more.
This study critically examines the rapid proliferation of megaprojects across the Arab region, with a focus on the Gulf Cooperation Council (GCC) countries, where large-scale developments are strategically deployed to reshape global economic influence and enhance geopolitical positioning. Megaprojects, characterized by their vast scale, substantial financial investment, and long-term impact, remain a subject of intense academic debate. While much of the literature questions their economic viability, citing frequent cost overruns and misalignment with localized urban priorities, megaprojects continue to emerge worldwide. Governments and developers promote megaprojects as catalysts for foreign investment, tourism growth, and enhancing the global stature of host countries and regions. Beyond financial and economic imperatives, megaprojects are fundamentally shaped by socio-spatial, socio-political, and capital accumulation dynamics, each playing a critical role in their justification and implementation. These interconnected forces influence the prioritization of large-scale developments, often reinforcing their persistence as dominant urban and infrastructural strategies despite well-documented uncertainties and risks. The study employs a comparative case study approach to analyze two high-profile megaprojects: Masdar City in Abu Dhabi and The Line in NEOM, Saudi Arabia. By examining their underlying motivations, political, social, and economic dynamics, and projected success factors, the study aims to provide an evidence-based assessment of the forces driving these large-scale developments and their potential for completion and long-term viability. This study contributes to the ongoing discourse on megaproject development by offering a nuanced, evidence-based analysis of the socio-political and economic forces shaping large-scale urban initiatives in the Arab region. By critically evaluating the motivations and viability of Masdar City and The Line, this research provides valuable insights that can inform future scholarly inquiries into the governance, planning, and long-term sustainability of megaprojects. The Study offers a strategic framework for policymakers, urban planners, and investors to make more informed, balanced decisions that align large-scale developments with broader economic and social priorities, mitigating risks associated with cost overruns, feasibility challenges, and socio-spatial disparities. Full article
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26 pages, 9909 KiB  
Article
Three-Tiered Defensive System and Ethnic Fusion: A Study of Architectural Art in Guomari Fortress, Eastern Qinghai
by Liyue Wu, Qinchuan Zhan and Yanjun Li
Buildings 2025, 15(13), 2218; https://doi.org/10.3390/buildings15132218 - 24 Jun 2025
Viewed by 437
Abstract
Guomari fortress in eastern Qinghai Province exemplifies vernacular architecture shaped by multiethnic interaction, environmental adaptation, and localized defense strategies. Originally a Ming Dynasty military-agricultural outpost, it evolved into a Tu ethnic settlement. Fieldwork, including architectural surveys and spatial analysis, identified a three-tiered defensive [...] Read more.
Guomari fortress in eastern Qinghai Province exemplifies vernacular architecture shaped by multiethnic interaction, environmental adaptation, and localized defense strategies. Originally a Ming Dynasty military-agricultural outpost, it evolved into a Tu ethnic settlement. Fieldwork, including architectural surveys and spatial analysis, identified a three-tiered defensive system: (1) strategic use of terrain and rammed-earth walls; (2) labyrinthine alleys with L-, T-, and cross-shaped intersections; and (3) interconnected rooftops forming elevated circulation routes. Courtyards are categorized into single-line, L-shaped, U-shaped, and fully enclosed layouts, reflecting adaptations to terrain, ritual functions, and thermal needs. Architectural features such as thick loam-coated walls and flat roofs demonstrate climatic adaptation, while the integration of Han timber frameworks, Tibetan prayer halls, and Tu decorative elements reveals cultural convergence. Traditional craftsmanship, including carved wooden scripture blocks and tsampa-based murals, is embedded within domestic and ritual spaces. The fortress’s circulation patterns mirror Tibetan Buddhist cosmology, with mandala-like alleys and rooftop circumambulation routes. These findings offer insights into vernacular resilience and inform conservation strategies for multiethnic fortified settlements. Full article
(This article belongs to the Section Building Materials, and Repair & Renovation)
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22 pages, 3776 KiB  
Article
Passenger-Centric Integrated Timetable Rescheduling for High-Speed Railways Under Multiple Disruptions
by Letian Fan, Ke Qiao, Yongsheng Chen, Meiling Hui, Tiqiang Shen and Pengcheng Wen
Sustainability 2025, 17(12), 5624; https://doi.org/10.3390/su17125624 - 18 Jun 2025
Viewed by 285
Abstract
In high-speed railway networks, multiple spatiotemporal correlated disruptions often cause passenger trip failures and delay propagation. Conventional single-disruption rescheduling strategies struggle to resolve such cross-line conflicts, necessitating an integrated, passenger-centric rescheduling framework for multiple correlated disruptions. This paper proposes a mixed-integer linear programming [...] Read more.
In high-speed railway networks, multiple spatiotemporal correlated disruptions often cause passenger trip failures and delay propagation. Conventional single-disruption rescheduling strategies struggle to resolve such cross-line conflicts, necessitating an integrated, passenger-centric rescheduling framework for multiple correlated disruptions. This paper proposes a mixed-integer linear programming (MILP) model to minimize total passenger delay time and trip failures under scenarios involving disruptions that are geographically dispersed but operationally interconnected. Two rescheduling mechanisms are introduced: a stepwise rescheduling method, which iteratively applies single-disruption models to optimize local problems, and an integrated rescheduling method, which simultaneously considers the global impact of all disruptions. Case studies on a real-world China’s high-speed railway network (29 stations, 42 trains, and 36,193 passenger trips) demonstrate that the proposed integrated rescheduling method reduces total passenger delays by 13% and trip failures by 67% within a 300 s computational threshold. By systematically coordinating spatiotemporal interdependencies among disruptions, this approach enhances network accessibility and service quality while ensuring operational safety, providing theoretical foundations for intelligent railway rescheduling. Full article
(This article belongs to the Special Issue Innovative Strategies for Sustainable Urban Rail Transit)
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14 pages, 263 KiB  
Article
On the Laplace Transforms of Derivatives of Special Functions with Respect to Parameters
by Sergei Rogosin, Filippo Giraldi and Francesco Mainardi
Mathematics 2025, 13(12), 1980; https://doi.org/10.3390/math13121980 - 16 Jun 2025
Viewed by 392
Abstract
This article is devoted to the derivation of the Laplace transforms of the derivatives with respect to parameters of certain special functions, namely, the Mittag–Leffler-type, Wright, and Le Roy-type functions. These formulas show the interconnection of these functions and lead to a better [...] Read more.
This article is devoted to the derivation of the Laplace transforms of the derivatives with respect to parameters of certain special functions, namely, the Mittag–Leffler-type, Wright, and Le Roy-type functions. These formulas show the interconnection of these functions and lead to a better understanding of their behavior on the real line. These formulas are represented in a convoluted form and reconstructed in a more suitable form by using the Efros theorem. Full article
(This article belongs to the Special Issue Fractional Differential Equations: Theory and Application)
32 pages, 8500 KiB  
Article
Risks, Obstacles and Challenges of the Electrical Energy Transition in Europe: Greece as a Case Study
by Georgios Fotis, Theodoros I. Maris and Valeri Mladenov
Sustainability 2025, 17(12), 5325; https://doi.org/10.3390/su17125325 - 9 Jun 2025
Cited by 1 | Viewed by 643
Abstract
The European Union’s 2030 target of decreasing net greenhouse gas emissions by at least 55% has resulted in a significant uptake of renewable energy sources (RESs) in the European power system, primarily wind and solar power, as well as the closure of conventional [...] Read more.
The European Union’s 2030 target of decreasing net greenhouse gas emissions by at least 55% has resulted in a significant uptake of renewable energy sources (RESs) in the European power system, primarily wind and solar power, as well as the closure of conventional power plants that mostly used fossil fuels. The European Union’s members have accelerated the process of energy transition driven by climate change, and public authorities’ involvement in this process is impressive. The goal of this study is to present a broad overview of the existing challenges for the energy transition in Europe and how they can affect the reliability and stability of the interconnected power system in Europe and future investments, focusing especially on Greece. Unfortunately, this environmentally friendly transition is taking place without the required amount of investment in electrical energy storage technology, which raises the risk of a blackout due to the high predicted variability of RES. The gradual abandonment of conventional energy production units such as natural gas in the coming decades will intensify the problem of frequency regulation, which will become even more acute due to the particularly increased installed capacity in RESs across Europe and Greece. The European Power System, being partially unprepared for the energy transition, frequently faces a paradox: it rejects green power originating from high-RES production because of low demand, a lack of transmission line interconnections, or extremely low energy storage capacity. This paper examines all the prerequisites, including how the European electrical transmission system will be developed in the future and how new energy storage technologies will be used. Lastly, Greece’s energy future and potential risks associated with realizing the environmental goals of the European Green Deal is studied using a PESTEL analysis. Full article
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15 pages, 2714 KiB  
Article
A Low-Loss and High-Bandwidth Horizontally Polarized Transition Between Rectangular Polymer Dielectric Waveguide and Microstrip Line for Array Application
by Haibing Zhan, Xiaochun Li, Changsheng Sun and Ken Ning
Electronics 2025, 14(12), 2345; https://doi.org/10.3390/electronics14122345 - 8 Jun 2025
Viewed by 389
Abstract
To achieve interconnects of rectangular polymer dielectric waveguides (PDWs) at the W-band, this paper presents a novel low-loss and high-bandwidth horizontally polarized transition between a rectangular PDW and a microstrip line (ML), which can achieve a rectangular PDW array. The proposed structure consists [...] Read more.
To achieve interconnects of rectangular polymer dielectric waveguides (PDWs) at the W-band, this paper presents a novel low-loss and high-bandwidth horizontally polarized transition between a rectangular PDW and a microstrip line (ML), which can achieve a rectangular PDW array. The proposed structure consists of a patch, a bent ridge waveguide, a tapered ridge waveguide, a dielectric-filled waveguide, and a tapered horn. An equivalent circuit model is established for synthesis design, and the transition is manufactured utilizing printed circuit board (PCB) and computerized numerical control (CNC) technologies. A rectangular PDW interconnect with two designed transitions is constructed and experiments are conducted. The measured results indicate that the rectangular PDW interconnect with two transitions operates within a frequency range (|S11| < −10 dB) of 81.9–108.2 GHz, and the insertion loss of the transition is 0.51–2.01 dB in this frequency range. Then, the designed transition is used to achieve a rectangular PDW array with two rectangular PDWs and two transitions, which has a far-end crosstalk (FEXT) of −55.4 to −21.7 dB in the frequency range of 78.1–110 GHz. Full article
(This article belongs to the Section Circuit and Signal Processing)
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35 pages, 24700 KiB  
Article
Optimizing Load Frequency Control of Multi-Area Power Renewable and Thermal Systems Using Advanced Proportional–Integral–Derivative Controllers and Catch Fish Algorithm
by Saleh A. Alnefaie, Abdulaziz Alkuhayli and Abdullah M. Al-Shaalan
Fractal Fract. 2025, 9(6), 355; https://doi.org/10.3390/fractalfract9060355 - 29 May 2025
Viewed by 638
Abstract
Renewable energy sources (RESs) are increasingly combined into the power system due to market liberalization and environmental and economic benefits, but their weather-dependent variability causes power production and demand mismatches, leading to issues like frequency and regional power transmission fluctuations. To maintain synchronization [...] Read more.
Renewable energy sources (RESs) are increasingly combined into the power system due to market liberalization and environmental and economic benefits, but their weather-dependent variability causes power production and demand mismatches, leading to issues like frequency and regional power transmission fluctuations. To maintain synchronization in power systems, frequency must remain constant; disruptions in the proper balance of production and load might produce frequency variations, risking serious issues. Therefore, a mechanism known as load frequency control (LFC) or automated generation control (AGC) is needed to keep the frequency and tie-line power within predefined stable limits. In this study, advanced proportional–integral–derivative PID controllers such as fractional-order PID (FOPID), cascaded PI(PDN), and PI(1+DD) for LFC in a two-area power system integrated with RES are optimized using the catch fish optimization algorithm (CFA). The controllers’ optimal gains are attained through using the integral absolute error (IAE) and ITAE objective functions. The performance of LFC with CFA-tuned PID, PI, cascaded PI(PDN), and FOPID, PI(1+DD) controllers is compared to other optimization techniques, including sine cosine algorithm (SCA), particle swarm optimization (PSO), brown bear algorithm (BBA), and grey wolf optimization (GWO), in a two-area power system combined with RESs under various conditions. Additionally, by contrasting the performance of the PID, PI, cascaded PI(PDN), and FOPID, PI(1+DD) controllers, the efficiency of the CFA is confirmed. Additionally, a sensitivity analysis that considers simultaneous modifications of the frequency bias coefficient (B) and speed regulation (R) within a range of ±25% validates the efficacy and dependability of the suggested CFA-tuned PI(1+DD). In the complex dynamics of a two-area interconnected power system, the results show how robust the suggested CFA-tuned PI(1+DD) control strategy is and how well it can stabilize variations in load frequency and tie-line power with a noticeably shorter settling time. Finally, the results of the simulation show that CFA performs better than the GWO, BBA, SCA, and PSO strategies. Full article
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24 pages, 2742 KiB  
Article
Mono-CYP CHO Model: A Recombinant Chinese Hamster Ovary Cell Platform for Investigating CYP-Specific Tamoxifen Metabolism
by Christian Schulz, Sarah Stegen, Friedrich Jung and Jan-Heiner Küpper
Int. J. Mol. Sci. 2025, 26(9), 3992; https://doi.org/10.3390/ijms26093992 - 23 Apr 2025
Viewed by 663
Abstract
The metabolism of drugs and foreign substances in humans typically involves multiple enzymatic steps, particularly in phase-1 biotransformation in the liver, where various cytochrome P450 monooxygenases (CYPs) play crucial roles. This complexity can lead to a wide range of metabolites. Understanding the contributions [...] Read more.
The metabolism of drugs and foreign substances in humans typically involves multiple enzymatic steps, particularly in phase-1 biotransformation in the liver, where various cytochrome P450 monooxygenases (CYPs) play crucial roles. This complexity can lead to a wide range of metabolites. Understanding the contributions of individual CYPs and their interactions within these intricate enzyme cascades can be challenging. We recently developed an in vitro biotransformation platform employing various Chinese Hamster Ovarian (CHO) cell clones. These clones express human cytochrome P450 oxidoreductase (CPR), and each is defined by a specific human CYP enzyme expression, thus exhibiting no detectable endogenous CYP enzyme activity (mono-CYP CHO platform). In this study, we investigated whether the mono-CYP CHO platform is a suitable tool for modeling complex drug metabolization reactions in vitro. Tamoxifen (TAM) was selected as a model substance due to its role as a prodrug widely used in breast cancer therapy, where its main active metabolite, endoxifen, arises from a two-step metabolism primarily involving the CYP system. Specifically, the combined activity of CYP3A4 and CYP2D6 is believed to be essential for efficient endoxifen production. However, the physiological metabolization pathway of TAM is more complex and interconnected, and the reasons for TAM’s therapeutic success and variability among patients are not yet fully understood. Analogous to our recently introduced mono-CYP3A4 CHO cells, we generated a CHO cell line expressing human CPR and CYP2D6, including analysis of CYP2D6 expression and specific activity. Comparative studies on the metabolization of TAM were performed with both mono-CYP CHO models individually and in co-culture with intact cells as well as with isolated microsomes. Supernatants were analyzed by HPLC to calculate individual CYP activity for each metabolite. All the picked mono-CYP2D6 clones expressed similar CYP2D6 protein amounts but showed different enzyme activities. Mono-CYP2D6 clone 18 was selected as the most suitable for TAM metabolization based on microsomal activity assays. TAM conversion with mono-CYP2D6 and -3A4 clones, as well as the combination of both, resulted in the formation of the expected main metabolites. Mono-CYP2D6 cells and microsomes produced the highest detected amounts of 4-hydroxytamoxifen and endoxifen, along with N-desmethyltamoxifen and small amounts of N,N-didesmethyltamoxifen. N-desmethyltamoxifen was the only TAM metabolite detected in notable quantities in mono-CYP3A4, while 4-hydroxytamoxifen and endoxifen were present only in trace amounts. In CYP2D6/3A4 co-culture and equal mixtures of both CYP microsomes, all metabolites were detected at concentrations around 50% of those in individual clones, indicating no significant synergistic effects. In conclusion, our mono-CYP CHO model confirmed the essential role of CYP2D6 in synthesizing the active TAM metabolite endoxifen and indicated that CYP2D6 is also involved in producing the by-metabolite N,N-didesmethyltamoxifen. The differences in metabolite spectra between the two mono-CYP models highlight the CYP specificity and sensitivity of our in vitro system. Full article
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23 pages, 5167 KiB  
Article
Optimal and Sustainable Operation of Energy Communities Organized in Interconnected Microgrids
by Epameinondas K. Koumaniotis, Dimitra G. Kyriakou and Fotios D. Kanellos
Energies 2025, 18(8), 2087; https://doi.org/10.3390/en18082087 - 18 Apr 2025
Cited by 1 | Viewed by 517
Abstract
Full dependence on the main electrical grid carries risks, including high electricity costs and increased power losses due to the distance between power plants and consumers. An energy community consists of distributed generation resources and consumers within a localized area, aiming to produce [...] Read more.
Full dependence on the main electrical grid carries risks, including high electricity costs and increased power losses due to the distance between power plants and consumers. An energy community consists of distributed generation resources and consumers within a localized area, aiming to produce electricity economically and sustainably while minimizing long-distance power transfers and promoting renewable energy integration. In this paper, a method for the optimal and sustainable operation of energy communities organized in interconnected microgrids is developed. The microgrids examined in this work consist of residential buildings, plug-in electric vehicles (PEVs), renewable energy sources (RESs), and local generators. The primary objective of this study is to minimize the operational costs of the energy community resulting from the electricity exchange with the main grid and the power production of local generators. To achieve this, microgrids efficiently share electric power, regulate local generator production, and leverage energy storage in PEVs for power management, reducing the need for traditional energy storage installation. Additionally, this work aims to achieve net-zero energy exchange with the main grid, reduce greenhouse gas (GHG) emissions, and decrease power losses in the distribution lines connecting microgrids, while adhering to numerous technical and operational constraints. Detailed simulations were conducted to prove the effectiveness of the proposed approach. Full article
(This article belongs to the Special Issue Advances in Sustainable Power and Energy Systems)
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