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Synthesis, Structural Studies, and Biological Evaluation of Copper(I) and Copper(II) Complexes Supported by Bis(pyrazol-1-yl)acetate Ligand Functionalized with Amantadine for the Treatment of Glioblastoma
No full textThis paper reports the synthesis, structural characterization, and biological evaluation of a novel series of CuI and CuII complexes supported by an amantadine-functionalized bis(pyrazol-1-yl)acetate ligand (LAd) as potential anticancer agents for the treatment of glioblastoma (GBM). Comprehensive spectroscopic and structural investigations, including SR-XPS, XANES/EXAFS, and DFT modeling, confirmed the successful coordination of LAd to copper centers in both oxidation states, affording well-defined molecular architectures with distinct coordination geometries. Among the synthesized compounds, the CuI complexes bearing triphenylphosphine co-ligands (compounds 4 and 5) exhibited the strongest cytotoxicity against U87 MG and LN18 GBM cell lines, showing IC50 values lower than those of cisplatin. These complexes induced a pronounced redox imbalance through reactive oxygen species (ROS) overproduction and glutathione (GSH) depletion, leading to G2/M cell cycle arrest and cell death. Flow cytometry and Western blot analyses demonstrated that cell death occurs via caspase-dependent apoptosis in LN18 cells, as evidenced by PARP cleavage, downregulation of Bcl-xL, release of cytochrome c, and mitochondrial translocation of Bax. Altogether, these findings highlight the potential of lipophilic amantadine-functionalized CuI complexes as promising anticancer candidates targeting glioma cells through mitochondrial dysfunction and redox-mediated pathways
A line planning approach with passenger assignment considering cross-line operations and flexible train composition for a metro network
No full textAs metro systems in most major cities evolve from single-line to network-level operations, passenger accessibility improves significantly. However, interchange stations experience increased pressure due to high transfer demand. Additionally, the non-equilibrium distribution of passenger demand poses significant challenges for operators. One effective strategy to mitigate transfer issues and improve operational flexibility is the implementation of cross-line operations. Furthermore, the flexible train composition mode provides a promising avenue to accommodate imbalanced passenger demand. In light of this, the study focuses on the line planning problem with passenger assignment, considering cross-line operations and the flexible train composition mode. Given that these operational modes require closer cooperation among trains, traditional line planning formulations become inadequate. To tackle this challenge, a novel mathematical model utilizing aggregated decision variables is developed to represent cross-line and flexible train coupling and decoupling operations. Subsequently, we formulate the passenger assignment problem as a multi-commodity flow problem, which effectively captures passenger movements within the metro network. To enhance computational efficiency, this study first employs the Dantzig-Wolfe decomposition method to transform the original formulation into a path-based model. Next, a branch-and-Benders cut approach is proposed to solve the problem. To strengthen the Benders cuts, we further develop a linear programming problem to generate the closest Benders cuts. The proposed approach is validated using a real-world case from the Beijing metro network, which comprises seven operating lines and 14 interchange stations. The computational results demonstrate that our proposed algorithms significantly outperform the commercial optimizer CPLEX. Moreover, the proposed operational modes reduce operating costs by up to 47.56 %, while passenger traveling costs decrease by as much as 4.34 %. The number of used train units decreases by up to 71.48 %
Fixed-Time Formation Hunting Control of Multi-Marine Surface Vehicle System Based on a Novel Deep Reinforcement Learning
No full textDiscovery of High X-Ray Polarization from the Neutron Star Low-mass X-Ray Binary Cyg X-2 on the Horizontal Branch
No full textWe present results from simultaneous X-ray polarimetric and spectroscopic observations of the bright neutron star low-mass X-ray binary Cyg X-2, performed by the Imaging X-ray Polarimetry Explorer (IXPE) and the Nuclear Spectroscopic Telescope Array. IXPE detected significant polarization (15 sigma) from the source in the 2-8 keV energy band with an average polarization degree (PD) of 4.5% +/- 0.3% and a polarization angle (PA) of 128 degrees +/- 2 degrees as the source moved along the horizontal branch of its Z-track. The PD increases with energy reaching 9.9% +/- 2.8% in the 7-8 keV band, with no evidence for energy-dependent variation in the PA. The PA is roughly consistent with previous measurements obtained during the normal and flaring branches and also with the known radio jet axis. From spectropolarimetric analysis, the main contribution to the polarized radiation is due to Comptonized photons, but the polarization is higher than predicted in typical spreading layer geometries. The observed high polarization may be due to a combination of a highly polarized reflected component and a moderately polarized spreading layer on the neutron star surface or produced by electron scattering in an equatorial wind
Metamaterials and Fluid Flows
No full textUnderstanding and controlling the dynamic interactions between fluid flows and solid materials and structures—a field known as fluid-structure interaction—is central not only to established disciplines such as aerospace and naval engineering, but also to emerging technologies such as energy harvesting, soft robotics, and biomedical devices. In recent years, the advent of metamaterials has provided exciting opportunities to rethink and redesign fluid-structure interactions. The idea of engineering the internal structure of materials that interface with fluid flows opens a new horizon for the precise and effective manipulation and control of coupled fluidic, acoustic, and elastodynamic responses. This review focuses on this relatively unexplored interdisciplinary theme with broad technological significance. Salient potential applications, such as fuel consumption in transport systems, efficiency of renewable energy extraction, noise mitigation, and resilience against structural fatigue, depend on controlling interactions among flow, acoustic, and vibration mechanisms. Flow control, for example, which spans a wealth of regimes such as laminar, transitional, turbulent, and unsteady separated flows, is strongly influenced by fluid-structure interaction. This review surveys and discusses conceptual frameworks that describe the interplay between fluids and elastic solids, with a focus on contemporary and emerging concepts. The paper is organised into three main sections: flow-structure and fluid-phonon interactions, flow and acoustic interactions with metamaterials, and exotic metamaterial concepts with potential impact on fluid-structure interaction. It concludes with perspectives on current challenges and future directions in this rapidly expanding area of research
La nuova disciplina dei contratti pubblici della Santa Sede e dello Stato della Città del Vaticano
No full textNell’ambito di un ormai ventennale processo di profondo rinnovamento normativo, la Santa Sede e lo Stato della Città del Vaticano hanno recentemente completato la propria disciplina in materia di contratti pubblici adottando il regolamento attuativo delle norme introdotte nel 2020. Al di là di talune omonimie e affinità, tale disciplina è contraddistinta da valori in parte differenti da quelli eurounitari, e dunque italiani, oltre che da una logica di fondo che rispecchia molte delle peculiarità dell’ordinamento vaticano.Within a more than twenty-year-long process of profound regulatory reform, the Holy See and the Vatican City State have recently completed their regulations on public contracts by adopting the implementing regulation for the rules introduced in 2020. Beyond certain similarities, these regulations are characterized by values that differ in part from those of the European Union, and therefore Italy, as well as by an underlying logic that reflects many of the peculiarities of the Vatican legal system
From laboratory validation to field ecology: biologging and dead-reckoning reveal amphibians’ movement
No full textGli anfibi sono tra i vertebrati più minacciati al mondo, ma la comprensione della loro ecologia del movimento su scala fine è ancora limitata da vincoli tecnici e metodologici. Questa tesi integra una revisione globale della letteratura, esperimenti comportamentali controllati e applicazioni di tecnologie di biologging miniaturizzate per migliorare l’affidabilità dei metodi di tracciamento negli anuri e valutare la rilevanza ecologica dei dati raccolti. Una revisione della telemetria elettronica applicata ad anfibi e rettili (1970-2023) evidenzia forti bias geografici, un uso predominante dei radiotrasmettitori e una generale mancanza di test sperimentali sugli effetti dei dispositivi, sottolineando la necessità di protocolli etici e metodologici standardizzati. Esperimenti comportamentali mostrano che dispositivi esterni e sensori inerziali possono essere utilizzati con effetti limitati sulla locomozione e sull’uso dello spazio in diverse specie di anuri, con variazioni principalmente individuali. L’accelerometria consente inoltre una classificazione comportamentale altamente accurata. Applicazioni sul campo dimostrano la fattibilità di integrare radiotelemetria VHF e sensori inerziali per ricostruire traiettorie di movimento tramite dead-reckoning, rivelando pattern di attività notturna, finestre termiche ristrette e variazioni stagionali nel comportamento spaziale. Questo approccio permette di ottenere traiettorie molto più dettagliate rispetto ai soli punti di localizzazione. Nel complesso, i risultati mostrano che il biologging, se accompagnato da validazione sperimentale e adeguata progettazione dei dispositivi, può fornire nuove conoscenze sull’ecologia del movimento degli anfibi e contribuire direttamente alla conservazione identificando habitat critici, pattern di attività e requisiti ecologici di specie minacciate.Amphibians are among the most threatened vertebrate groups worldwide, yet their fine-scale movement ecology remains poorly understood due to technical and methodological constraints. This thesis combines a global literature review, controlled behavioural experiments, and applications of miniaturised biologging technologies to improve the reliability of tracking methods in anurans and evaluate the ecological relevance of the movement data they produce. A comprehensive review of electronic telemetry in amphibians and reptiles (1970-2023) reveals strong geographical biases, a predominant use of radio transmitters, and a general lack of experimental testing of device effects, highlighting the need for standardised ethical and methodological protocols. Controlled behavioural experiments demonstrate that external devices and inertial sensors can be deployed with limited effects on locomotion and space use across different anuran species, with most variation occurring at the individual level. Accelerometer data also enable highly accurate behavioural classification. Field applications show that integrating VHF radiotelemetry with inertial sensors allows the reconstruction of continuous movement paths through dead-reckoning. This approach reveals nocturnal activity patterns, narrow thermal activity windows, and seasonal variation in spatial behaviour, producing trajectories that are far more detailed than those derived from positional fixes alone. Overall, the results demonstrate that biologging, when supported by experimental validation and careful device design, can substantially advance our understanding of amphibian movement ecology and provide valuable information for conservation by identifying critical habitats, activity patterns, and ecological requirements of threatened species
