Experimental analysis of the powder flow in a continuous coaxial nozzle for laser metal deposition Lorenzo Pedrolli, Jon Iñaki Arrizubieta Arrate, Giulio Bonifazi, Aitzol Lamikiz, Beatriz Achiaga, Alejandro Lopez Progress in Additive Manufacturing, 2026 This work presents an experimental analysis of the powder flow from a continuous coaxial nozzle for Laser Metal Deposition (LMD), demonstrating the ability to identify the transients and high-speed process flow dynamics. High-speed video tracking of individual particles enabled detailed analysis of size, spatial distribution, and velocities, revealing significant flowrate variations over time of up to $$20\\%$$ , which may compromise deposition quality. These oscillations emerge from the large number of interactions among particles, carrier gas, and nozzle walls, reflecting complex, self-excited flow dynamics not captured by time-averaged measurements. The standoff distance, defined as the optimal distance between the nozzle and the workpiece, was determined with unprecedented temporal resolution. In the most representative case, the average standoff distance was found to be approximately $$16.0~\\textrm{mm}$$ , with oscillations over time of up to $$19\\%$$ , due to variations in both particle trajectories and quantity over time. The particle size distribution was consistent with the manufacturer’s specifications, a good indication of the method’s accuracy, and an error estimation is performed to determine the expected precision of the measurements. A key aspect of this work, and its main contribution, is the development of a workflow capable of tracking individual particles to determine the instantaneous powder mass flowrate, providing a reliable approach to monitor and optimize powder delivery in the LMD process.
A nonlinear meccano for Alzheimer's emergence by amyloid β-mediated glutamatergic hyperactivity Giulio Bonifazi, Celia Luchena, Adhara Gaminde-Blasco, Carolina Ortiz-Sanz, Estibaliz Capetillo-Zarate, Carlos Matute, Elena Alberdi, Maurizio De Pittà Neurobiology of Disease, 2024 The pathophysiological process of Alzheimer's disease (AD) is believed to begin many years before the formal diagnosis of AD dementia. This protracted preclinical phase offers a crucial window for potential therapeutic interventions, yet its comprehensive characterization remains elusive. Accumulating evidence suggests that amyloid-β (Aβ) may mediate neuronal hyperactivity in circuit dysfunction in the early stages of AD. At the same time, neural activity can also facilitate Aβ accumulation through intricate feed-forward interactions, complicating elucidating the conditions governing Aβ-dependent hyperactivity and its diagnostic utility. In this study, we use biophysical modeling to shed light on such conditions. Our analysis reveals that the inherently nonlinear nature of the underlying molecular interactions can give rise to the emergence of various modes of hyperactivity. This diversity in the mechanisms of hyperactivity may ultimately account for a spectrum of AD manifestations.
A theoretical approach for the electrochemical characterization of ciliary Epithelium Riccardo Sacco, Giovanna Guidoboni, Joseph W. Jerome, Giulio Bonifazi, Nicholas M. Marazzi, Alice C. Verticchio Vercellin, Matthew S. Lang, Alon Harris Life, 2020 The ciliary epithelium (CE) is the primary site of aqueous humor (AH) production, which results from the combined action of ultrafiltration and ionic secretion. Modulation of ionic secretion is a fundamental target for drug therapy in glaucoma, and therefore it is important to identify the main factors contributing to it. As several ion transporters have been hypothesized as relevant players in CE physiology, we propose a theoretical approach to complement experimental methods in characterizing their role in the electrochemical and fluid-dynamical conditions of CE. As a first step, we compare two model configurations that differ by (i) types of transporters included for ion exchange across the epithelial membrane, and by (i) presence or absence of the intracellular production of carbonic acid mediated by the carbonic anhydrase enzyme. The proposed model configurations do not include neurohumoral mechanisms such as P2Y receptor-dependent, cAMP, or calcium-dependent pathways, which occur in the ciliary epithelium bilayer and influence the activity of ion transporters, pumps, and channels present in the cell membrane. Results suggest that one of the two configurations predicts sodium and potassium intracellular concentrations and transmembrane potential much more accurately than the other. Because of its quantitative prediction power, the proposed theoretical approach may help relate phenomena at the cellular scale, that cannot be accessed clinically, with phenomena occurring at the scale of the whole eye, for which clinical assessment is feasible.
