bluuebunny/crossref_metadata_2025_split huggingface dataset:
TNBC response to paclitaxel phenocopies interferon response which reveals cell cycle-associated resistance mechanisms
Authors: Calistri Nicholas L. , Liby Tiera A. , Hu Zhi , Zhang Hongmei , Dane Mark A. , Gross Sean M. , Heiser Laura M. 
Published: February 2025

Abstract
Paclitaxel is a standard of care neoadjuvant therapy for patients with triple negative breast cancer (TNBC); however, it shows limited benefit for locally advanced or metastatic disease. Here we used a coordinated experimental-computational approach to explore the influence of paclitaxel on the cellular and molecular responses of TNBC cells. We found that escalating doses of paclitaxel resulted in multinucleation, promotion of senescence, and initiation of DNA damage induced apoptosis. Single-cell RNA sequencing (scRNA-seq) of TNBC cells after paclitaxel treatment revealed upregulation of innate immune programs canonically associated with interferon response and downregulation of cell cycle progression programs. Systematic exploration of transcriptional responses to paclitaxel and cancer-associated microenvironmental factors revealed common gene programs induced by paclitaxel, IFNB, and IFNG. Transcription factor (TF) enrichment analysis identified 13 TFs that were both enriched based on activity of downstream targets and also significantly upregulated after paclitaxel treatment. Functional assessment with siRNA knockdown confirmed that the TFs FOSL1, NFE2L2 and ELF3 mediate cellular proliferation and also regulate nuclear structure. We further explored the influence of these TFs on paclitaxel-induced cell cycle behavior via live cell imaging, which revealed altered progression rates through G1, S/G2 and M phases. We found that ELF3 knockdown synergized with paclitaxel treatment to lock cells in a G1 state and prevent cell cycle progression. Analysis of publicly available breast cancer patient data showed that high ELF3 expression was associated with poor prognosis and enrichment in programs associated with cell cycle progression. Together these analyses disentangle the diverse aspects of paclitaxel response and identify ELF3 upregulation as a putative biomarker of paclitaxel resistance in TNBC.
Development of an mPBPK machine learning framework for early target pharmacology assessment of biotherapeutics
Authors: Patidar Krutika , Pillai Nikhil , Dhakal Saroj , Avery Lindsay B. , Mavroudis Panteleimon D. 
Published: February 2025

Abstract
Development of antibodies often begins with the assessment and optimization of their physicochemical properties, and their efficient engagement with the target of interest. Decisions at the early optimization stage are critical for the success of the drug candidate but are constrained due to the limited knowledge of the antibody and target pharmacology. In the present work, we propose a machine learning-based target pharmacology assessment framework that utilizes minimal physiologically based pharmacokinetic (mPBPK) modeling and machine learning (ML) to infer optimal physicochemical properties of antibodies and their targets. We use a mPBPK model previously developed by our group that incorporates a multivariate quantitative relationship between antibodies’ physicochemical properties such as molecular weight (MW), size, charge, and in silico + in vitro derived descriptors with their PK properties. In this study, we perform a high-throughput exploration of virtual antibody drug candidates with varying physicochemical properties (binding affinity, charge, etc.), and virtual target candidates with varying characteristics (baseline expression, half-life, etc.) to unravel rules for antibody drug candidate selection that achieve favorable drug-target interaction, which is defined by target occupancy (TO) percentage. We identified that variations in the antibody dose and dosing scheme, target form (soluble or membrane-bound), antibody charge, and site of action had a significant effect on the TO and selection criteria for antibody drug candidates. By unraveling new design rules for antibody drug properties that are dependent on ML-based TO assessment, we deliver a first-in-class ML-based target pharmacology assessment framework toward better understanding of the biology-specific PK and ADME processes of antibody drug candidate proteins and reduce the overall time for drug development.
Production of novel theranostic nano-vector based on superparamagnetic iron oxide nanoparticles/miR-497 targeting colorectal cancer
Authors: Elfiky Asmaa M. , Eid May M. , El-Manawaty May , Elshahid Zeinab A. , Youssef Elham Mohamed , Mahmoud Khaled 
Published: February 2025

Abstract
Colorectal cancer (CRC) is a serious public health concern worldwide. Immune checkpoint inhibition medication is likely to remain a crucial part of CRC clinical management. This study aims to create new super paramagnetic iron oxide nano-carrier (SPION) that can effectively transport miRNA to specific CRC cell lines. In addition, evaluate the efficiency of this nano-formulation as a therapeutic candidate for CRC. Bioinformatics tools were used to select a promising tumor suppressor miRNA (mir-497-5p). Green route, using Fusarium oxyporium fungal species, manipulated for the synthesis of SPION@Ag@Cs nanocomposite as a carrier of miR-497-5p. That specifically targets the suppression of PD1/PDL1 and CTLA4pathways for colorectal therapy. UV/visible and FTIR spectroscopy, Zeta potential and MTT were used to confirm the allocation of the miR-497 on SPION@Ag@Cs and its cytotoxicity against CRC cell lines. Immunofluorescence was employed to confirm transfection of cells with miR-497@NPs, and the down- regulation of CTLA4 in HT29, and Caco2 cell lines. On the other hand, PDL1 showed a significant increase in colorectal cell lines (HT-29 and Caco-2) in response to mir497-5p@Nano treatment. The data suggest that the mir-497 -loaded SPION@Ag@Cs nano-formulation could be a good candidate for the suppression of CTLA4in CRC human cell lines. Consequently, the targeting miR-497/CTLA4 axis is a potential immunotherapy treatment strategy for CRC.
Cultural diversity shaped neolithic subsistence in the Carpathian Basin
Authors: Depaermentier M. L. C. , Kempf M. , Bánffy E. , Alt K. W. 
Published: February 2025

Abstract
Stable carbon and nitrogen isotope analysis from archaeological human and animal bone collagen is a powerful tool to enlighten past socio-agricultural systems and their close links to environmental conditions. To assess whether isotopic patterns are a function of cultural behavior or rather determined by environmental diversity, we test the spatio-temporal effects of conditional and multivariate exploratory and environmental models on stable isotope variability in the Neolithic and Chalcolithic Carpathian Basin (6000–2800 BCE). Our results stress that variation in environmental settings influence both the isotope baselines and the subsistence strategies of early agricultural societies. Major shifts in isotopic patterns are, however, culturally-driven, which is particularly visible with the development and intensification of adapted agropastoral practices from 5500 − 5350 BCE and among the diet between different cultural groups. We conclude that socio-cultural diversity was the main driver of dietary habits and isotopic variability in early agropastoral societies of Neolithic Hungary.
Three-dimensional ultrastructural analysis of human skin with the arrector pili muscle interacting with the hair follicle epithelium
Authors: Ezure Tomonobu , Matsuzaki Kyoichi , Urakubo Hidetoshi , Ohno Nobuhiko 
Published: February 2025

Abstract
This study developed a three-dimensional ultrastructural analysis application using serial block-face scanning electron microscopy (SBF-SEM) to investigate surgically acquired human skin tissues containing the arrector pili muscle. We utilized the en bloc staining, including reduced osmium, thiocarbohydrazide, and lead aspartate, as well as the embedding using a carbon-based conductive resin. Next, we obtained serial images with SBF-SEM. The results revealed dense nerve fiber networks branching from nearby nerve fiber bundles outside the muscle and running among muscle fibers. Additionally, the dense nerve network running through and along arrector pili muscle fibers rarely penetrates the connective tissues between smooth muscle fibers and epithelial cells. Furthermore, in the observation area, no individual smooth muscle fibers formed adhesion structures with the epithelial cells of the hair follicle, ending in the dermal extracellular matrix near the epithelial cells. These results indicate the usefulness of this approach for three-dimensional ultrastructural analyses of human skin tissues comprising follicular units and revealing structural changes in skin tissues, especially the arrector pili muscle and nerve fibers with hair follicular epithelium, in aging and diseased conditions.
Decision-making model for production and operation of underground gold mines considering low-carbon condition
Authors: Hou Jie , Gu Yingyu , Li Guoqing , Guo Guangjun , Yu Qianqian 
Published: February 2025

Abstract
Within the framework of a low-carbon transition and integrated mineral resource exploitation, this study presents an innovative system dynamics (SD) model designed to optimize decision-making and enhance profitability in underground gold mining operations. The novel approach seamlessly integrates critical subsystems, including reserves, mining, ore dressing, smelting, financial, and carbon reduction, offering a comprehensive framework for the analysis of efficiency and sustainability. Utilizing causal loop and system flow diagrams, the model elucidates the synergistic impacts of index variations on mine operational efficiency. The model is applied to a case study involving three mining areas within a specific gold mine in China, where sensitivity analysis identifies key indicators affecting profitability. Furthermore, it examines dynamic trends under varying carbon tax scenarios. The findings reveal that mining strategic adjustments can significantly enhance profitability, extend the operational lifespan of mines, and reduce emissions.
Multimodal mechanisms of human centriole engagement and disengagement
Authors: Ito Kei K , Takumi Kasuga , Matsuhashi Kyohei , Sakamoto Hirokazu , Nagai Kaho , Fukuyama Masamitsu , Yamamoto Shohei , Chinen Takumi , Hata Shoji , Kitagawa Daiju 
Published: February 2025

Abstract
Centrioles are unique cellular structures that replicate to produce identical copies, ensuring accurate chromosome segregation during mitosis. A new centriole, the “daughter”, is assembled adjacent to an existing “mother” centriole. Only after the daughter centriole is fully developed as a complete replica, does it disengage and become the core of a new functional centrosome. The mechanisms preventing precocious disengagement of the immature daughter centriole have remained unclear. Here, we identify three key mechanisms maintaining mother–daughter centriole engagement: the cartwheel, the torus, and the pericentriolar material (PCM). Among these, the torus critically establishes the characteristic orthogonal engagement. We also demonstrate that engagement mediated by the cartwheel and torus is progressively released during centriole maturation. This release involves structural changes in the daughter, known as centriole blooming and distancing, respectively. Disrupting these structural transitions blocks subsequent steps, preventing centriole disengagement and centrosome conversion in the G1 phase. This study provides a comprehensive understanding of how the maturing daughter centriole progressively disengages from its mother through multiple steps, ensuring its complete structure and conversion into an independent centrosome.
Microwave-assisted synthesis of mesoporous high-entropy alloy and core–shell nanoparticles
Authors: Ni Chuyi , Guo Suni , Butler Cole , Veinot Jonathan G. C. 
Published: February 2025

Mesoporous high-entropy alloy core-shell nanoparticles (Au-RhAgCuPdPt) can be synthesized via microwave-assisted heating. Their thermal conversion to high-entropy alloy nanoparticles (AuRhAgCuPdPt) were further invesitgated by in situ heating TEM.
Field analysis of directionality measurement with inverter based resources in India
Authors: Shyamaprasad Ashoka , Vittal K. P. , AN Praveen , Naidu O. D. 
Published: February 2025

AbstractRenewable energy sources are getting integrated into the electrical power network since many years. The characteristics of these sources are completely different from traditional synchronous generators. This is posing challenges for power engineers from system protection and control perspective. Cases of maloperations of protective relays have been a focus of research across industries and universities. India has been growing in deploying distributed energy resources. Most of the maloperations reported relate to transmission line protection. Studies on maloperation of directional element are not duly addressed from Indian grid perspective. Few cases from India have been chosen for research. Fault data from Type‐4 and Type‐3 wind plant and solar park has been analysed and compared with literature reports. The objective of this paper is to document the behaviour of directional elements for a distributed energy resource connected system in India. In addition, aim is to understand the gaps from existing research to the behaviours of the current directional protections. This would help in identifying mechanisms to ascertain directionality for similar systems in the future. The conclusion from the paper is that the detection of fault direction must be completed before the time inverter control kicks in to operation in any algorithm.
Radial dependence of solar energetic particle peak fluxes and fluences
Authors: Cao Yihang , Wang Yubao , Guo Jingnan 
Published: February 2025

Context. We present a list of solar energetic particle (SEP) events detected by instruments on board the Solar and Heliospheric Observatory (SOHO), Parker Solar Probe (PSP), and Solar Orbiter between 2021 and 2023. The investigation focuses on identifying the peak flux and the fluence of SEP events in four energy ranges from 10.5 to 40 MeV, as observed by PSP or Solar Orbiter at heliospheric distances shorter than 1 AU and by SOHO at the Sun-Earth L1 Lagrangian point.
Aims. Based on the data from these events, we conduct a statistical analysis to study the radial dependence of the SEP proton peak flux and fluence at different energies.
Methods. We identified 42 SEP events with enhanced proton flux that were observed simultaneously by at least two out of three spacecraft (SOHO, PSP, and Solar Orbiter). These events were further selected based on a criterion of a difference smaller than a 30° difference in longitudinal separation between the magnetic footpoints of the two spacecraft. For the selected events, we used a linear interpolation method to compute the proton peak flux and fluence in four energy ranges and quantified their radial dependence as a function of Rα, where R is the radial distance of the observer from the Sun.
Results. The peak flux and fluence of the SEP events display the following radial dependence: The average values of α across all energies range between about −3.7 and −2 for the peak fluxes and between −2.7 and −1.4 for the fluences. We also obtained the energy dependence of |α|, which decreases with increasing energy. Additionally, based on theoretical functions, we find that the SEP source and transport parameters may have a significant impact on α(E), and the measurement-derived |α(E)| values and their distribution fall within the range of theoretical predictions.
Conclusions. (1) Despite the uncertainties arising from the low statistics and the longitudinal influence, the radial dependence of the peak flux agrees with the upper limit R−3 predicted by previous studies. (2) The radial dependence on the fluence R−2 tends to be weaker than the radial decay of the peak flux. (3) As the proton energy increases, the proton mean free path increases, and the adiabatic cooling effect modifies the proton energy. As a result, the peak flux and fluence decay more significantly with increasing radial distance for lower-energy particles.
Micromagnetic simulation of Nd–Fe–B grain with a dysprosium-containing shell
Authors: Li Kai , Dai Yingying , Dai Zhiming , Wang Zhenhua , Li Da , Liu Wei , Zhang Zhidong 
Published: February 2025

The effects of Dy-doped shell thickness on the magnetic properties and magnetization reversal behavior of a Nd–Fe–B grain have been systematically investigated using micromagnetic simulations based on a core–shell model. The Dy-containing shell can significantly enhance the coercivity of the model. Notably, when the shell thickness reaches 12 nm, the coercivity reaches its maximum value, and the nucleation sites shift from the core–shell interface to the grain corners. Ferromagnetic resonance spectra indicate that the low-frequency modes are associated with the nucleation sites, and the increased coercivity is related to the shift of the core–shell simultaneous resonance mode to higher frequency. In addition, we propose a multi-shell model to further enhance the coercivity by shifting the nucleation points. This approach of adjusting the nucleation sites can also be applied to improve the magnetic properties of other magnets.
Defect-induced modification of electronic and optical properties of CeO2 unveiled by many-body Green’s function theory
Authors: Zhang Mengyu , Song Yiting , Jiang Ya-nan , Ma Yuchen 
Published: February 2025

We explore the impact of point defects, including oxygen vacancies (Ov), cerium interstitials (Ce-int), and hydroxyl groups (Hy), on the electronic and optical properties of bulk CeO2 using many-body Green’s function theory (GW method and Bethe–Salpeter equation). Although these three defects all produce occupied electronic levels near the conduction band minimum, they impose quite different effects. Ov and Ce-int induce strong peaks in the low-energy region of the imaginary part of the microscopic dielectric function, indicating stronger electronic screening compared to the pristine CeO2. This causes pronounced narrowing of the bandgap, e.g., by 0.8 eV in G0W0 and 1.6 eV in the eigenvalue self-consistent GW for Ov. Comparatively, Hy affects little electronic screening and bandgap at different levels of GW calculations. For the lowest several 4f orbitals, the exchange part of the self-energy (|Σx| &gt; 9 eV) in GW is much stronger than the correlation part (|Σc| &lt; 5 eV) for Ov and Ce-int, while |Σc| is much stronger than |Σx| instead for the pristine CeO2 and Hy. Quasiparticle weights in Ov and Ce-int decrease by a large quantity compared to the pristine CeO2. Consideration of Ov and Ce-int might to some extent relieve the discrepancy between the GW bandgap of the pristine CeO2 and the experimental gap. Ov and Ce-int could reduce the excitonic binding energy several times and result in optical absorption, which corresponds to the experiments.
Low-voltage operation mode of ASCENT-propelled pulsed plasma thruster
Authors: Organski Lee , Jeffers Brian , Gresham Patrick , Kucharewicz Artur , Shashurin Alexey 
Published: February 2025

This study demonstrates the feasibility of operating a liquid-fed pulsed plasma thruster (PPT) at low voltages, in the magnetoplasmadynamic (MPD) arc range below 100 V, in contrast to conventional PPTs operating in the kV range. The system uses ASCENT (Advanced Spacecraft Energetic Nontoxic Propellant) as a propellant. Low voltage operation was achieved by eliminating long discharge electrodes and associated voltage drops. The designed thruster demonstrated consistent operation at discharge voltages of 50–150 V for discharge currents varying in the range of 2–8 kA. The measured V–I characteristics of the thruster’s discharge were consistent with self-field MPD arcs, and, correspondingly, the designed system can be classified as a pulsed-MPD thruster. We further confirmed the action of the accelerating Lorentz force on the propellant by measuring fast exhaust ion velocities in the range of 10–30 km/s. Photographic observations confirmed the formation of a plasma jet sourced from the ASCENT propellant, with minimal cathode spot formation, supporting that reduced cathode erosion and the system’s long operational lifetime can be expected. The designed ASCENT-propelled PPT can be utilized as an electric propulsion mode in a dual-mode propulsion system combining chemical and electric propulsion modes.
Tuning the magnetic properties by partial substitution of Cr in D022-Mn3Ga: A potential material for spin transfer torque applications
Authors: Perween Sonam , Gahtori Bhasker , Mohapatra Niharika 
Published: February 2025

This report presents the effect of partial substitution of the Cr atom at the itinerant octahedral site (Y2b site) of D022-type Mn3Ga. The Cr introduces a reduction of magnetization due to the antiparallel alignment of Cr atoms at the itinerant site to Mn atoms at the localized site (X4d) with variation in mixed valence states (Mn4+ and Mn3+) from that of the pristine as revealed from the deconvolution of the Mn2p peak. The alloy possesses irreversible magneto-structural phase transformation during heating and cooling modes of temperature-dependent magnetization study. During heating, the magnetic interaction between Mn and Cr atoms possesses an abrupt change in magnetization over temperature, leading to Hopkinson’s like effect with magneto-structural transition temperature (Tc) ∼ 780 K, notably higher than the parent alloy. The thermal variation of uniaxial magnetocrystalline anisotropy ≈1.20-0.2 Merg/cc in addition to high coercivity (∼1.2–2.85 kOe) can be utilized as potential material for spin transfer torque-based memory applications.
Numerical study of the effect of stenosis on the hemodynamics of a popliteal artery
Authors: Shi Liuliu , Xiang Xinru , Liu Jinlong , Zhu Wei 
Published: February 2025

The investigation of flow characteristics within the popliteal artery is fundamental to understanding the progression of lower limb arterial disease, given its high susceptibility to atherosclerosis and its frequent manifestation of stenosis. Research on the hemodynamics associated with popliteal artery stenosis remains limited, particularly in cardiovascular diseases. This study comprehensively examines how Newtonian and non-Newtonian fluid models influence the hemodynamic simulations of popliteal artery stenosis. Key hemodynamic parameters, such as velocity, time-averaged wall shear stress (TAWSS), oscillatory shear index (OSI), and relative residence time (RRT), were systematically examined through numerical simulations to assess their influence and variability in arteries exhibiting different degrees of stenosis compared to healthy arteries. The findings indicate that both models’ velocity and wall shear stress (WSS) distributions are largely comparable during the systolic phase (0.04–0.07 s), characterized by elevated velocities. However, during the countercurrent diastolic phase (0.21–0.40 s), the viscosity of the non-Newtonian fluid model experiences an increase, leading to reduced velocity distributions relative to the Newtonian fluid model. In particular, a 12% disparity in velocities is observed between the two models, indicating that the non-Newtonian model is better suited for comprehensive hemodynamic analysis in simulations involving stenotic popliteal arteries. Furthermore, a distinct flow separation occurs at the stenosis site, with blood flow velocity and WSS exhibiting significant increases as the stenosis severity escalates. For instances where hemodynamic parameters demonstrate minimal variations at stenosis levels below 60%, OSI and RRT are elevated. In contrast, TAWSS remains low, potentially fostering plaque formation. In contrast, when hemodynamic parameters undergo substantial changes at stenosis levels exceeding 60%, TAWSS rises, which may facilitate plaque rupture. This simulation provides a comprehensive analysis of hemodynamic parameter variations across different degrees of stenosis, offering clinicians a valuable instrument for enhancing their understanding of the pathogenic mechanisms associated with popliteal artery atherosclerosis and stenosis.