419 research outputs found

    Application of an additive manufactured hybrid metal/composite shock absorber panel to a military seat ejection system

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    In this work, a preliminary numerical assessment on the application of an additive manufactured hybrid metal/composite shock absorber panels to a military seat ejection system, has been carried out. The innovative character of the shock absorber concept investigated is that the absorbing system has a thickness of only 6 mm and is composed of a pyramid‐shaped lattice core that, due to its small size, can only be achieved by additive manufacturing. The mechanical behaviour of these shock absorber panels has been examined by measuring their ability to absorb and dissipate the energy generated during the ejection phase into plastic deformations, thus reducing the loads acting on pilots. In this paper the effectiveness of a system composed of five hybrid shock absorbers, with very thin thickness in order to be easily integrated between the seat and the aircraft floor, has been numerically studied by assessing their ability to absorb the energy generated during the primary ejection phase. To accomplish this, a numerical simulation of the explosion has been performed and the energy absorbed by the shock‐absorbing mechanism has been assessed. The performed analysis demonstrated that the panels can absorb more than 60% of the energy generated during the explosion event while increasing the total mass of the pilot‐seat system by just 0.8%

    Na+/Ca2+ exchanger isoform 1 takes part to the Ca2+-related prosurvival pathway of SOD1 in primary motor neurons exposed to beta-methylamino-l-alanine

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    Background: The cycad neurotoxin beta-methylamino-l-alanine (L-BMAA), one of the environmental trigger factor for amyotrophic lateral sclerosis/Parkinson-dementia complex (ALS/PDC), may cause neurodegeneration by disrupting organellar Ca2+ homeostasis. Through the activation of Akt/ERK1/2 pathway, the Cu,Zn-superoxide dismutase (SOD1) and its non-metallated form, ApoSOD1, prevent endoplasmic reticulum (ER) stress-induced cell death in motor neurons exposed to L-BMAA. This occurs through the rapid increase of intracellular Ca2+ concentration ([Ca2+]i) in part flowing from the extracellular compartment and in part released from ER. However, the molecular components of this mechanism remain uncharacterized. Methods: By an integrated approach consisting on the use of siRNA strategy, Western blotting, confocal double- labeling immunofluorescence, patch-clamp electrophysiology, and Fura 2-/SBFI-single-cell imaging, we explored in rat motor neuron-enriched cultures the involvement of the plasma membrane proteins Na+/Ca2+ exchanger (NCX) and purinergic P2X7 receptor as well as that of the intracellular cADP-ribose (cADPR) pathway, in the neuroprotective mechanism of SOD1. Results: We showed that SOD1-induced [Ca2+]i rise was prevented neither by A430879, a P2X7 receptor specific antagonist or 8-bromo-cADPR, a cell permeant antagonist of cADP-ribose, but only by the pan inhibitor of NCX, CB-DMB. The same occurred for the ApoSOD1. Confocal double labeling immunofluorescence showed a huge expression of plasmalemmal NCX1 and intracellular NCX3 isoforms. Furthermore, we identified NCX1 reverse mode as the main mechanism responsible for the neuroprotective ER Ca2+ refilling elicited by SOD1 and ApoSOD1 through which they promoted translocation of active Akt in the nuclei of a subset of primary motor neurons. Finally, the activation of NCX1 by the specific agonist CN-PYB2 protected motor neurons from L-BMAA-induced cell death, mimicking the effect of SOD1. Conclusion: Collectively, our data indicate that SOD1 and ApoSOD1 exert their neuroprotective effect by modulating ER Ca2+ content through the activation of NCX1 reverse mode and Akt nuclear translocation in a subset of primary motor neurons. [MediaObject not available: see fulltext.

    Trends in h2s-donors chemistry and their effects in cardiovascular diseases

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    Hydrogen sulfide (H2S) is an endogenous gasotransmitter recently emerged as an important regulatory mediator of numerous human cell functions in health and in disease. In fact, much evidence has suggested that hydrogen sulfide plays a significant role in many physio-pathological processes, such as inflammation, oxidation, neurophysiology, ion channels regulation, cardiovascular protection, endocrine regulation, and tumor progression. Considering the plethora of physiological effects of this gasotransmitter, the protective role of H2S donors in different disease models has been extensively studied. Based on the growing interest in H2S-releasing compounds and their importance as tools for biological and pharmacological studies, this review is an exploration of currently available H2S donors, classifying them by the H2S-releasing-triggered mechanism and highlighting those potentially useful as promising drugs in the treatment of cardiovascular diseases

    The impact of COVID-19 on radiological findings in patients accessing the emergency department: a multicentric study

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    The aim of this multicentric study is to illustrate how the COVID-19 pandemic lockdown affected the workload and outcomes of radiological examinations in emergency radiology

    H2s donors and their use in medicinal chemistry

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    Hydrogen sulfide (H2S) is a ubiquitous gaseous signaling molecule that has an important role in many physiological and pathological processes in mammalian tissues, with the same importance as two others endogenous gasotransmitters such as NO (nitric oxide) and CO (carbon monoxide). Endogenous H2S is involved in a broad gamut of processes in mammalian tissues including inflammation, vascular tone, hypertension, gastric mucosal integrity, neuromodu-lation, and defense mechanisms against viral infections as well as SARS-CoV-2 infection. These results suggest that the modulation of H2S levels has a potential therapeutic value. Consequently, synthetic H2S-releasing agents represent not only important research tools, but also potent therapeutic agents. This review has been designed in order to summarize the currently available H2S donors; furthermore, herein we discuss their preparation, the H2S-releasing mechanisms, and their-biological applications

    New Insights into the Structure-Activity Relationship and Neuroprotective Profile of Benzodiazepinone Derivatives of Neurounina-1 as Modulators of the Na+/Ca2+Exchanger Isoforms

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    Due to the neuroprotective role of the Na+/Ca2+ exchanger (NCX) isoforms NCX1 and NCX3, we synthesized novel benzodiazepinone derivatives of the unique NCX activator Neurounina-1, named compounds 1-19. The derivatives are characterized by a benzodiazepinonic nucleus linked to five- or six-membered cyclic amines via a methylene, ethylene, or acetyl spacer. The compounds have been screened on NCX1/NCX3 isoform activities by a high-throughput screening approach, and the most promising were characterized by patch-clamp electrophysiology and Fura-2AM video imaging. We identified two novel modulators of NCX: compound 4, inhibiting NCX1 reverse mode, and compound 14, enhancing NCX1 and NCX3 activity. Compound 1 displayed neuroprotection in two preclinical models of brain ischemia. The analysis of the conformational and steric features led to the identification of the molecular volume required for selective NCX1 activation for mixed NCX1/NCX3 activation or for NCX1 inhibition, providing the first prototypal model for the design of optimized isoform modulators

    No Dynamics in the Extremal Kerr Throat

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    Motivated by the Kerr/CFT conjecture, we explore solutions of vacuum general relativity whose asymptotic behavior agrees with that of the extremal Kerr throat, sometimes called the Near-Horizon Extreme Kerr (NHEK) geometry. We argue that all such solutions are diffeomorphic to the NHEK geometry itself. The logic proceeds in two steps. We first argue that certain charges must vanish at all times for any solution with NHEK asymptotics. We then analyze these charges in detail for linearized solutions. Though one can choose the relevant charges to vanish at any initial time, these charges are not conserved. As a result, requiring the charges to vanish at all times is a much stronger condition. We argue that all solutions satisfying this condition are diffeomorphic to the NHEK metric.Comment: 42 pages, 3 figures. v3: minor clarifications and correction

    First Italian outbreak of VIM-producing Serratia marcescens in an adult polyvalent intensive care unit, August-October 2018: A case report and literature review

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    Carbapenem-resistant Enterobacteriaceae has become a significant public health concern as hospital outbreaks are now being frequently reported and these organisms are becoming difficult to treat with the available antibiotics
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