Search Results (8,459)

Interference gating (iGate) has emerged as a groundbreaking technique for ultrafast time-resolved electron holography in transmission electron microscopy, delivering nanometer spatial and nanosecond temporal resolution with minimal technological overhead. This study employs iGate to dynamically observe the local projected electric potential within the space-charge region of a contacted transmission electron microscopy (TEM) lamella manufactured from a silicon diode during switching between unbiased and reverse-biased conditions, achieving a temporal resolution of 25 ns at a repetition rate of 3 MHz. By synchronizing the holographic acquisition with the applied voltage, this approach enables the direct visualization of time-dependent potential distributions with high precision. Complementary static and dynamic experiments reveal a remarkable correspondence between modeled and measured projected potentials, validating the method’s robustness. The observed dynamic phase progressions resolve and allow one to differentiate between localized switching dynamics and preparation-induced effects, such as charge recombination near the sample edges. These results establish iGate as a transformative tool for operando investigations of semiconductor devices, paving the way for advancing the nanoscale imaging of high-speed electronic processes. Full article

Fourier ptychographic microscopy (FPM) has recently emerged as an important non-invasive imaging technique which is capable of simultaneously achieving high resolution, wide field of view, and quantitative phase imaging. However, FPM still faces challenges in the image reconstruction due to factors such as noise, optical aberration, and phase wrapping. In this work, we propose a semi-supervised Fourier ptychographic transformer network (SFPT) for improved image reconstruction, which employs a two-stage training approach to enhance the image quality. First, self-supervised learning guided by low-resolution amplitudes and Zernike modes is utilized to recover pupil function. Second, a supervised learning framework with augmented training datasets is applied to further refine reconstruction quality. Moreover, the unwrapped phase is recovered by adjusting the phase distribution range in the augmented training datasets. The effectiveness of the proposed method is validated by using both the simulation and experimental data. This deep-learning-based method has potential applications for imaging thicker biology samples. Full article

Menin (MEN1) is a well-recognized powerful tumor promoter in acute leukemias (AL) with KMT2A rearrangements (KMT2Ar, also known as MLL) and mutant nucleophosmin 1 (NPM1m) acute myeloid leukemia (AML). MEN1 is essential for sustaining leukemic transformation due to its interaction with wild-type KMT2A and KMT2A fusion proteins, leading to the dysregulation of KMT2A target genes. MEN1 inhibitors (MIs), such as revumenib, ziftomenib, and other active small molecules, represent a promising new class of therapies currently under clinical development. By disrupting the MEN1-KMT2Ar complex, a group of proteins involved in chromatin remodeling, MIs induce apoptosis and differentiation AL expressing KMT2Ar or NPM1m AML. Phase I and II clinical trials have evaluated MIs as standalone treatments and combined them with other synergistic drugs, yielding promising results. These trials have demonstrated notable response rates with manageable toxicities. Among MIs, ziftomenib received orphan drug and breakthrough therapy designations from the European Medicines Agency in January 2024 and the Food and Drug Administration (FDA) in April 2024, respectively, for treating R/R patients with NPM1m AML. Additionally, in November 2024, the FDA approved revumenib for treating R/R patients with KMT2Ar-AL. This review focuses on the pathophysiology of MI-sensitive AL, primarily AML. It illustrates data from clinical trials and discusses the emergence of resistance mechanisms. In addition, we outline future directions for the use of MIs and emphasize the need for further research to fully realize the potential of these novel compounds, especially in the context of specific genetic subtypes of challenging AL. Full article

This paper explores the feasibility of floating urban development in Italy, given its extensive coastline and inland hydrographic network. The key drivers for floating urban development, as an adaptive approach in low-lying waterfront areas, include the increasing threats posed by rising sea levels and flooding and the shortage of land for urban expansion. However, as not all waterfront areas are suitable for floating urban development, a geographical analysis based on a thorough evaluation of multiple factors, including urban–economic parameters and climate-related variables, led to the identification of a specific area of the Lazio coast, the river Tiber Delta. A comprehensive urban mapping process provided a multifaceted geo-referenced information layer, including several climatic, urban, anthropic, and environmental parameters. Within the GIS environment, it is possible to extract and perform statistical analyses crucial for assessing the impact of flood and sea-level rise hazards, particularly regarding buildings and land cover. This process provides a robust framework for understanding the spatial dimensions of flood and sea-level rise impacts and supporting informed design-making. A research-by-design phase follows the simulation research and mapping process. Several design scenarios are developed aimed at regenerating this vulnerable area. These scenarios seek to transform its susceptibility to flooding into a resilient, adaptive, urban identity, offering climate-resilient housing solutions for a population currently residing in unauthorized, substandard housing within high flood-risk zones. This paper proposes a comprehensive analytical methodology for supporting the design process of floating urban development, given the highly determinant role of site-specificity in such a challenging and new urban development approach. Full article

The particle size-dependent processes of structural relaxation and crystal growth in amorphous nifedipine were studied by means of non-isothermal differential scanning calorimetry (DSC) and Raman microscopy. The enthalpy relaxation was described in terms of the Tool–Narayanaswamy–Moynihan model, with the relaxation motions exhibiting the activation energy of 279 kJ·mol⁻¹ for the temperature shift, but with a significantly higher value of ~500 kJ·mol⁻¹ being obtained for the rapid transition from the glassy to the undercooled liquid state (the latter is in agreement with the activation energy of the viscous flow). This may suggest different types of relaxation kinetics manifesting during slow and rapid heating, with only a certain portion of the relaxation motions occurring that are dependent on the parameters of a given temperature range and time frame. The DSC-recorded crystallization was found to be complex, consisting of four sub-processes: primary crystal growth of α_p and β_p polymorphs, enantiotropic β_p → β_p′ transformation, and β_p/β_p′ → α_p recrystallization. Overall, nifedipine was found to be prone to the rapid glass-crystal growth that occurs below the glass transition temperature; a tendency of low-temperature degradation of the amorphous phase markedly increased with decreasing particle size (the main reason being the increased number of surface and bulk micro-cracks and mechanically induced defects). The activation energies of the DSC-monitored crystallization processes varied in the 100–125 kJ·mol⁻¹ range, which is in agreement with the microscopically measured activation energies of crystal growth. Considering the potential correlations between the structural relaxation and crystal growth processes interpreted within the Transition Zone Theory, a certain threshold in the complexity and magnitude of the cooperating regions (as determined from the structural relaxation) may exist, which can lead to a slow-down of the crystal growth if exceeded. Full article

The transformation of biomass into renewable fuels and chemicals has gained remarkable attention as a sustainable alternative to fossil-based resources. Metal-based catalysts, encompassing transition and noble metals, are crucial in these transformations as they drive critical reactions, such as hydrodeoxygenation, hydrogenation, and reforming. Transition metals, including nickel, cobalt, and iron, provide cost-effective solutions for large-scale processes, while noble metals, such as platinum and palladium, exhibit superior activity and selectivity for specific reactions. Catalytic advancements, including the development of hybrid and bimetallic systems, have further improved the efficiency, stability, and scalability of biomass transformation processes. This review highlights the catalytic upgrading of lignocellulosic, algal, and waste biomass into high-value platform chemicals, biofuels, and biopolymers, with a focus on processes, such as Fischer–Tropsch synthesis, aqueous-phase reforming, and catalytic cracking. Key challenges, including catalyst deactivation, economic feasibility, and environmental sustainability, are examined alongside emerging solutions, like AI-driven catalyst design and lifecycle analysis. By addressing these challenges and leveraging innovative technologies, metal-based catalysis can accelerate the transition to a circular bioeconomy, supporting global efforts to combat climate change and reduce fossil fuel dependence. Full article

Magnesium-based materials have been considered to be potential hydrogen storage materials due to their high hydrogen storage capacity and abundance in natural resources. In order to improve the hydrogen storage performance of magnesium-based materials, a Mg₉₅Ce₅ alloy was prepared by using the vacuum induction melting method. Moreover, TiS₂ was used as a catalyst, and a series of Mg₉₅Ce₅ + x wt% TiS₂ (x = 0, 3, 5 and 10) composites with different TiS₂ contents were prepared by the mechanical ball-milling method. The addition of TiS₂ as a catalyst broke the inherent symmetry of the Mg₉₅Ce₅ alloy at both the atomic and defect levels, potentially improving hydrogen storage by modifying hydrogen diffusion pathways and interaction sites. The structural analysis results indicate that the Mg₉₅Ce₅ alloy is composed of Mg and CeMg₁₂ phases. After the hydrogenation process, the Mg and CeMg₁₂ phases in the Mg₉₅Ce₅–TiS₂ composites transformed into CeH_2.73 and MgH₂. In addition, CeS₂ and TiH_1.5 could be detected in the hydrogenated samples, indicating that the TiS₂ decomposed and changed into CeS₂ and TiH_1.5 during the hydrogenation reaction. Adding TiS₂ to Mg₉₅Ce₅ alloy could significantly improve the hydrogen absorption and desorption kinetic properties, and the dehydrogenation peak temperature of the composites was reduced from 389.5 °C to 329.7 °C when the TiS₂ content increased from 0 to 10 wt%. However, the addition of TiS₂ inevitably reduced the reversable hydrogen storage capacity of the composites. The hydrogen absorption and desorption thermodynamic measurement results indicate that the TiS₂ catalyst has almost no influence on the enthalpy and entropy changes of the composites during the hydrogenation process. Full article

This research aims to determine the position and the breakthrough trajectory of sustainable energy technologies. Fine-grained insights into these breakthrough positions and trajectories are limited. This research seeks to fill this gap by analyzing sustainable energy technologies’ breakthrough positions and trajectories in terms of development, application, and upscaling. To this end, the breakthrough positions and trajectories of seven sustainable energy technologies, i.e., hydrogen from seawater electrolysis, hydrogen airplanes, inland floating photovoltaics, redox flow batteries, hydrogen energy for grid balancing, hydrogen fuel cell electric vehicles, and smart sustainable energy houses, are analyzed. This is guided by an extensively researched and literature-based model that visualizes and describes these technologies’ experimentation and demonstration stages. This research identifies where these technologies are located in their breakthrough trajectory in terms of the development phase (prototyping, production process and organization, and niche market creation and sales), experiment and demonstration stage (technical, organizational, and market), the form of collaboration (public–private, private–public, and private), physical location (university and company laboratories, production sites, and marketplaces), and scale-up type (demonstrative, and first-order and second-order transformative). For scientists, this research offers the opportunity to further refine the features of sustainable energy technologies’ developmental positions and trajectories at a detailed level. For practitioners, it provides insights that help to determine investments in various sustainable energy technologies. Full article

Background/Objectives: Bempedoic acid (BA) is a novel cholesterol-lowering agent with proven positive effects on cardiovascular endpoints. Because it is an inhibitor of the hepatic transporters OATP1B1 and OATP1B3, two uptake transporters regulating the intrahepatic availability of statins, it increases the systemic exposure of co-administered statins. This interaction could raise the risk of myopathy. We hypothesized that the drug interaction between BA and statins could be mitigated by staggered administration. Methods: This was a single-centre, open-label, randomized, two-arm, cross-over, phase I drug interaction trial in healthy volunteers (EudraCT-No: 2022-001096-13). The primary objective was to evaluate the OATP1B1 inhibitory effect of BA on exposure to pravastatin after simultaneous administration versus different schedules of staggered administration. A secondary objective was to evaluate the impact of SLCO1B1 genotypes (*1, *5, *15, *37) on pravastatin exposure. Pravastatin was administered in single oral doses of 40 mg at six visits. After a baseline visit with pravastatin alone, BA was dosed to steady state at the approved oral dose of 180 mg. Outcome measures were the area under the plasma concentration–time curve, extrapolated to infinity (AUC_∞) and C_max of pravastatin, 3α-hydroxy-pravastatin (pravastatin 3-iso), and pravastatin lactone, and their geometric mean ratios (GMRs) of different schedules of administration. Log-transformed AUC_∞ and C_max were compared with one-way ANOVA with a 90% confidence interval (CI). Results: Fourteen participants completed all visits. At BA steady state, the GMRs of pravastatin AUC_∞ and C_max were 1.80 (90% CI 1.31–2.46) and 1.95 (90% CI 1.40–2.72), respectively, compared to baseline. There was no significant difference in pravastatin exposure between simultaneous vs. staggered administration. There was no statistically significant difference in pravastatin 3-iso or pravastatin lactone between different administration modes. For the AUC_∞ of pravastatin and pravastatin 3-iso, haplotype was a significant source of variation (63% and 20%, respectively), while the type of administration (simultaneous vs. staggered) had no significant impact. Conclusions: The increase in pravastatin exposure with concomitant intake of BA was larger than expected. There was no significant difference between simultaneous vs. staggered administration of pravastatin and BA, possibly due to a population that was heterogenous in SLCO1B1 haplotypes. Full article

Additive manufacturing and digital warehouses are transforming the way industries manage and maintain their spare parts inventory. Considering digital warehouses and on-demand manufacturing for spare parts during the project phase is a strategic decision that involves trade-offs depending on the operational needs and pricing structure. This paper aims to explore the spare part evaluation process considering both physical and digital warehouse inventories. A case asset is purposefully selected and four spare part management concepts are studied using a simulation modeling approach. The results highlight that the relevant digital warehouse scenario, used in this case, managed to completely reduce all emissions related to global spare parts supply; however, this was at the expense of reducing availability by 15.1%. However, the hybrid warehouse scenario managed to increase availability by 11.5% while completely reducing all emissions related to global spare parts supply. Depending on the demand rate, the digital warehousing may not be sufficient alone to keep the production availability at the highest levels; however, it is effective in reducing the stock amount, simplifying the inventory management, and making the supply process more green and resilient. A generic estimation model for spare parts engineers is provided to determine the optimal specifications of their spare parts supply and inventory while considering digital warehouses and on-demand manufacturing. Full article

A layered double hydroxide (LDH) containing Mg and Al was synthesized from a nitrate solution using a coprecipitation method. The resulting material exhibited a homogeneous structure, which, upon calcination at 450 °C, was converted into a layered double oxide (LDO). When rehydrated in a fluoride-containing aqueous solution, the original hydroxide structure was successfully regenerated, demonstrating the LDH’s memory effect. During this transformation, fluoride anions from the solution were incorporated into the interlayer galleries to maintain electroneutrality, as confirmed by energy-dispersive X-ray spectroscopy (EDS) analysis. Separately, the process was tested in the presence of ethanol, which significantly enhanced the incorporation of fluoride ions into the interlayer spaces. The material’s potential for controlled fluoride release was evaluated by monitoring its release into demineralized water. For comparison, a simple ion-exchange process was carried out using the as-synthesized MgAl LDH. The memory effect mechanism displayed a notably higher fluoride incorporation capacity compared to the ion-exchange process. Among all the specimens, the sample reconstructed in the presence of ethanol exhibited the highest fluoride ion content. Fluoride release studies revealed a two-phase pattern: an initial rapid release within the first three hours, followed by a substantially slower release over time. Full article

The implications of various pH solutions in the gastrointestinal fluid system as solvent-mediated phase transitions on concurrent polymorphism transformation, notably metastable polymorphic forms of Efavirenz (EFV), has never been investigated. The impact will be shifting in the solubility and crystallinity of EFV polymorphisms, particularly metastable Forms II and III. EFV’s metastable form is generated by recrystallization with n-hexane and methanol, which were all immersed in artificial digestion buffer solutions for 10 and 100 h, respectively. Form II showed a 9–13.2% increase in solubility, whereas Form III increased by 2–7.3% over Form I. Interestingly, Form II revealed decreased crystallinity, but Form III tended to retain or slightly increase. In acidic solutions, all metastable polymorphs had the highest solubility and crystallinity. Form III appears to have a lower impact on phase transitions owing to pH variations than Form II. These findings indicate that variability in the pH of digestive secretions are essential steps in developing successful pharmaceutical formulations. Finally, our findings provide information on the complex interaction between solvents, pH variations, and EFV polymorphs. The findings identified the importance of these factors in the development of successful pharmaceutical formulations. Full article

Based on the idea of integrated computational materials Engineering (ICME), this research applies a digital integrated computing platform integrating ProCAST and MATLAB software. The effects of Fe and Zn contents on the microstructure and properties of die-casting Al–10Si–Mg alloy was investigated through numerical simulation and experimental characterization. The results show that with Fe and Zn contents of 1.30 and 0.25 wt.%, respectively, the grain size and porosity of the die-cast parts are the smallest, and the yield strength and tensile strength are 203 MPa and 313 MPa, respectively. Compared with the addition of 0.14 wt.% Fe and 0.01 wt.% Zn, the increase was 16% and 15.5%, respectively. When the Fe content is higher than 1.30 wt.%, the size of the β-Al₅FeSi phase in the alloy matrix increases. Moreover, as the Fe content increases, the morphology of the β-Al₅FeSi transforms from elongated to a needle-like shape, which increases brittleness and reduces elongation, tensile strength, and yield strength. When 0.25 wt.% Zn is added, the segregation phenomenon of eutectic Si in the Al–10Si–Mg alloy is inhibited and the tensile strength and yield strength are improved. However, with the increase in Zn content to 0.95 wt.%, there is the coarsening of eutectic Si, resulting in a decreased elongation and decreased mechanical properties. The optimization method of the integrated computing platform greatly simplifies the computing cycle and improves work efficiency. Full article

Developing switchable and multifunctional metasurfaces is essential for high-integration photonics. However, most previous studies encountered challenges such as limited degrees of freedom, simple tuning of predefined functionality, and complicated control systems. Here, we develop a general strategy to construct switchable and multifunctional metasurfaces. Two spin-modulated wave-controls are enabled by the proposed high-efficiency metasurface, which is designed using both resonant and geometric phases. Furthermore, the switchable wavefront tailoring can also be achieved by flexibly altering the lattice constant and reforming the phase retardation of the metasurfaces based on the “rotating square” (RS) kirigami technique. As a proof of concept, a kirigami metasurface is designed that successfully demonstrates dynamic controls of three-channel beam steering. In addition, another kirigami metasurface is built for realizing tri-channel complex wavefront engineering, including straight beam focusing, tilted beam focusing, and anomalous reflection. By altering the polarization of input waves as well as transformation states, the functionality of the metadevice can be switched flexibly among three different channels. Microwave experiments show good agreement with full-wave simulations, clearly demonstrating the performance of the metadevices. This strategy exhibits advantages such as flexible control, low cost, and multiple and switchable functionalities, providing a new pathway for achieving switchable wavefront engineering. Full article

The bursa of Fabricius (BF) plays crucial roles in the goslings’ immune system. During waterfowl breeding, the presence of lipopolysaccharides (LPSs) in the environment can induce inflammatory damage in geese. Polysaccharides of Atractylodes macrocephala Koidz (PAMKs), as the main active component of the Chinese medicine Atractylodes macrocephala, have significant immune-enhancing effects. Accordingly, this study intended to investigate the effect of PAMKs on LPS-induced BF injury in goslings. Two hundred 1-day-old goslings (half male and half female) were selected and randomly divided into control, PAMK, LPS, and PAMK + LPS groups. The control and LPS groups were fed the basal diet, and the PAMK and PAMK + LPS groups were fed the basal diet containing PAMKs at 400 mg/kg. The goslings in the LPS and PAMK + LPS groups were injected intraperitoneally with LPS at a concentration of 2 mg/kg on days 24, 26, and 28 of this study. The control and PAMK groups were injected with equal amounts of saline. On the 28th day, 1 h after the LPS injection, the BF and serum were collected and analyzed for organ indices, cytokines, antioxidant indicators, and histological observations. Histological examination and HE staining demonstrated that the PAMK treatment ameliorated the LPS-induced BF atrophy, structural damage, increased cellular exudation, and reticulocyte hyperplasia in the goslings. The cytokine and antioxidant marker analyses in the BF cells demonstrated that the PAMK treatment mitigated the LPS-induced increase in the interleukin-1β (IL-1β), malondialdehyde (MDA), and inducible nitric oxide synthase (iNOS) levels, as well as the decrease in the transforming growth factor-β (TGF-β) and superoxide dismutase (SOD) activities. Further transcriptome sequencing identified a total of 373 differentially expressed genes (DEGs) between the LPS and PAMK + LPS groups. The KEGG enrichment pathway analysis showed that the DEGs were significantly enriched in the Toll-like receptor, p53, MAPK, GnRH, and ErbB signaling pathways. Among them, EREG played key roles in the activation of the MAPK, GnRH, and ErbB signaling pathways. Further research showed that the addition of PAMKs significantly inhibited the LPS-induced EREG expression, increased the cell viability, promoted the cell cycle entry into the S and G2 phases, and inhibited apoptosis. Meanwhile, PAMKs can reduce the protein expression of p-JNKs and c-FOS by inhibiting EREG. In summary, this study found that PAMKs could alleviate LPS-induced BF injury in goslings by inhibiting the expression of EREG. Full article