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      • Turbomachinery design by a swarm-based optimization method coupled with a CFD solver

        Ampellio, Enrico,Bertini, Francesco,Ferrero, Andrea,Larocca, Francesco,Vassio, Luca Techno-Press 2016 Advances in aircraft and spacecraft science Vol.3 No.2

        Multi-Disciplinary Optimization (MDO) is widely used to handle the advanced design in several engineering applications. Such applications are commonly simulation-based, in order to capture the physics of the phenomena under study. This framework demands fast optimization algorithms as well as trustworthy numerical analyses, and a synergic integration between the two is required to obtain an efficient design process. In order to meet these needs, an adaptive Computational Fluid Dynamics (CFD) solver and a fast optimization algorithm have been developed and combined by the authors. The CFD solver is based on a high-order discontinuous Galerkin discretization while the optimization algorithm is a high-performance version of the Artificial Bee Colony method. In this work, they are used to address a typical aero-mechanical problem encountered in turbomachinery design. Interesting achievements in the considered test case are illustrated, highlighting the potential applicability of the proposed approach to other engineering problems.

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        Whole-blood hypocoagulable profile correlates with a greater risk of death within 28 days in patients with severe sepsis

        Boscolo Annalisa,Spiezia Luca,Campello Elena,Bertini Diana,Lucchetta Vittorio,Piasentini Eleonora,De Cassai Alessandro,Simioni Paolo 대한마취통증의학회 2020 Korean Journal of Anesthesiology Vol.73 No.3

        Background: Hypocoagulability and impaired platelet function have been associated with a high risk of death in sepsis. The aim of this cohort study was to determine whether sepsis-induced hypocoagulability and platelet dysfunction (assessed by ROTEM® and MULTIPLATE®, respectively) are increased in sepsis patients who died within 28 days after diagnosis compared with patients who died between 29 and 90 days after diagnosis. Methods: Consecutive patients admitted to the intensive care unit of Padova University Hospital from March 2015 to March 2018 for severe sepsis were considered. We collected blood samples from all patients to determine ROTEM® and MULTIPLATE® parameters. Each enrolled patient underwent a 90-day follow-up and the mortality rate was recorded. Results: Of 120 patients, 36 (30%) died within 28 days post-diagnosis (Group A), 23 (19%) died between days 29 and 90 post-diagnosis (Group B), and 61 (51%) were alive after 90 days (survivors). The clotting time in the ROTEM® test and clot formation time in the EXTEM test were significantly more prolonged in Group A than in B. Both groups showed a significantly higher hypocoagulability than survivors in the EXTEM test. MULTIPLATE® platelet function analysis showed that platelet function was significantly lower in Group A than in Group B. Conclusions: The present study showed that the combination of thromboelastometry and impedance aggregometry may help identifying sepsis patients at high risk of short-term death. Larger studies are warranted to corroborate our results.

      • A Mouse Model for Conditional Secretion of Specific Single-Chain Antibodies Provides Genetic Evidence for Regulation of Cortical Plasticity by a Non-cell Autonomous Homeoprotein Transcription Factor

        Bernard, Clé,mence,Vincent, Clé,mentine,Testa, Damien,Bertini, Eva,Ribot, Jé,,me,Di Nardo, Ariel A.,Volovitch, Michel,Prochiantz, Alain Public Library of Science 2016 PLoS genetics Vol.12 No.5

        <▼1><P>During postnatal life the cerebral cortex passes through critical periods of plasticity allowing its physiological adaptation to the environment. In the visual cortex, critical period onset and closure are influenced by the non-cell autonomous activity of the Otx2 homeoprotein transcription factor, which regulates the maturation of parvalbumin-expressing inhibitory interneurons (PV cells). In adult mice, the maintenance of a non-plastic adult state requires continuous Otx2 import by PV cells. An important source of extra-cortical Otx2 is the choroid plexus, which secretes Otx2 into the cerebrospinal fluid. Otx2 secretion and internalization requires two small peptidic domains that are part of the DNA-binding domain. Thus, mutating these “transfer” sequences also modifies cell autonomous transcription, precluding this approach to obtain a cell autonomous-only mouse. Here, we develop a mouse model with inducible secretion of an anti-Otx2 single-chain antibody to trap Otx2 in the extracellular milieu. Postnatal secretion of this single-chain antibody by PV cells delays PV maturation and reduces plasticity gene expression. Induced adult expression of this single-chain antibody in cerebrospinal fluid decreases Otx2 internalization by PV cells, strongly induces plasticity gene expression and reopens physiological plasticity. We provide the first mammalian genetic evidence for a signaling mechanism involving intercellular transfer of a homeoprotein transcription factor. Our single-chain antibody mouse model is a valid strategy for extracellular neutralization that could be applied to other homeoproteins and signaling molecules within and beyond the nervous system.</P></▼1><▼2><P><B>Author Summary</B></P><P>Classically, cell signaling is based on the secretion of molecules that bind cell surface receptors. Lipophilic agents can do without cell-surface receptors due to their ability to diffuse through the plasma membrane, but this is normally not the case for proteins, which cannot pass the membrane barrier. However, homeoprotein transcription factors represent an exception as they are secreted and internalized by live cells owing to two peptidic domains. An important illustration of this novel signaling mechanism is provided by Otx2, a homeoprotein that travels from the choroid plexus to specific inhibitory neurons in the cerebral cortex, where it regulates physiological plasticity throughout life. Because the two transfer peptides are in the DNA-binding domain of Otx2, it is impossible to mutate them without altering both cell signaling and cell-autonomous functions. We have therefore developed a mouse in which a secreted anti-Otx2 single-chain antibody can be induced to trap extracellular Otx2 while leaving its cell autonomous function untouched. We show that neutralizing extracellular Otx2 modifies the expression of plasticity genes in the visual cortex, thus providing the first genetic demonstration for homeoprotein signaling in a mammal.</P></▼2>

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