Flux through a time-periodic gate: Monte Carlo test of a homogenization result

We investigate via Monte Carlo numerical simulations and theoretical considerations the outflux of random walkers moving in an interval bounded by an interface exhibiting channels (pores, doors) which undergo an open/close cycle according to a periodic schedule. We examine the onset of a limiting boundary behavior characterized by a constant ratio between the outflux and the local density, in the thermodynamic limit. We compare such a limit with the predictions of a theoretical model already obtained in the literature as the homogenization limit of a suitable diffusion problem

In silico study of airway/lung mechanics in normal human breathing

The airway/lung mechanics is usually represented with nonlinear 0-D models based on a pneumatic-electrical analogy. The aim of this work is to provide a detailed description of the human respiratory mechanics in healthy and diseased conditions. The model used for this purpose employs some known constitutive functions of the main components of the respiratory system. We give a detailed mathematical description of these functions and subsequently derive additional key ones. We are interested not only in the main output such as airflow at the mouth or alveolar pressure and volume, but also in other quantities such as resistance and pressure drop across each element of the system and even recoil and compliance of the chest wall. Pathological conditions are simulated by altering the parameters of the constitutive functions. Results show that increased upper airway resistance induces airflow reduction with concomitant narrowing of volume and pressure ranges without affecting lung compliance. Instead, increased elastic recoil leads to low volumes and decreased lung compliance. The model could be used in the study of the interaction between respiratory and cardiovascular systems in pathophysiological conditions

Therapeutic efficacy of adipose-derived MSC in chronic experimental autoimmune encephalomyelitis

Le cellule staminali mesenchimali (CSM) rappresentano un promettente approccio terapeutico per le patologie neurologiche a carattere autoimmune. In lavori precedenti è stato dimostrato che il trattamento con CSM da midollo osseo in un modello di encefalite autoimmune sperimentale (EAS), modello animale di sclerosi multipla, ha un effetto immunomodulate ed è in grado di ridurre la gravità della malattia. In questo lavori dimostriamo che la somministrazione di CSM da tessuto adiposo (CSA) prima dell'insorgenza della malattia è in grado di ridurre significativamente la gravità della malattia, diminuendo infiammazione e demielinizzazione a livello del midollo attraverso un effetto immunomodulante. Le CSA migrano preferibilmente negli organi linfoidi, ma sono in grado di penetrare anche nel sistema nervoso centrale (SNC). Ancora più importante, la somministrazione di CSA in fase cronica di EAS migliora significativamente l'andamento clinico e riduce sia demielinizzazione che perdita assonale, e induce uno shift delle cellule T verso un fenotipo Th2. Abbiamo evidenziato inoltre che una consistente sottopopolazione di CSA esprime l’integrina α4 attivata e tramite microscopia intravitale abbiamo visto che le CSA sono in grado di aderire ai vasi cerebrali infiammati. La bioluminescence imaging conferma che l’inegrina α4 regola la migrazione delle CSA nel SNC infiammato. Dopo esser migrate nelle lesioni di EAS, le CSA portano ad un aumento significativo del numero dei progenitori degli oligodendrociti endogeni. Per quanto riguarda i meccanismo molecolari che stanno alla base di questo effetto, abbiamo visto che le CSA sono in grado di produrre in coltura vascular endothelial growth factor, insulin growth factor-I, basic fibroblast growth factor, brain-derived growth factor e platelet-derived growth factor-AB, sia in condizioni basali che dopo stimoli infiammatori. E’ interessante notare che tutte queste molecole sono coinvolte nella proliferazione sia dei precursori degli oligodendrociti che delle CSA stesse. In conclusione, abbiamo mostrato che le CSA presentano un chiaro effetto terapeutico attraverso un duplice meccanismo: sono in grado sia di sopprimere la risposta immunitaria nelle prime fasi della malattia, sia di indurre una neuro-rigenerazione locale agendo sui progenitori endogeni quando la malattia ha raggiunto una fase cronica. I nostri dati suggeriscono quindi che le CSA possano rappresentare un valido strumento per le terapie cellulari nel trattamento di patologie infiammatorie croniche del SNC.Mesenchymal stem cells (MSC) represent a promising therapeutic approach for neurological autoimmune diseases; previous studies have shown that treatment with bone marrow-derived MSC induces immune modulation and reduces disease severity in experimental autoimmune encephalomyelitis (EAE), an animal model of multiple sclerosis. Here we show that intravenous administration of adipose-derived MSC (ASC) before disease onset significantly reduces the severity of EAE and decreases spinal cord inflammation and demyelination by immune modulation. ASC preferentially home into lymphoid organs, but migrates also inside the central nervous system (CNS). Most importantly, administration of ASC in chronic established EAE significantly ameliorates the disease course and reduces both demyelination and axonal loss, and induces a Th2-type cytokine shift in T cells. Interestingly, a relevant subset of ASC expresses activated α4 integrins and adheres to inflamed brain venules in intravital microscopy experiments. Bioluminescence imaging confirms that α4 integrins control ASC accumulation in inflamed CNS. After penetration within EAE lesions, ASC induce a significant increase of the number of endogenous oligodendrocyte progenitors. As for the mechanisms responsible for such effect, we found that ASC cultures produce vascular endothelial growth factor, insulin growth factor-I, basic fibroblast growth factor, brain-derived growth factor and platelet-derived growth factor-AB both in basal condition and after inflammatory stimulus. Interestingly, these molecules are all involved in the proliferation of both oligodendrocyte precursors and ASC themselves. In conclusion, we show that ASC display clear therapeutic effect by a bimodal mechanism, by suppressing the autoimmune response in early phases of disease as well as by inducing local neuro-regeneration by activating endogenous progenitors in animals with established disease. Overall our data suggest that ASC represent a valuable tool for stem cell-based therapy in chronic inflammatory diseases of the CNS

How can LVAD support influence ventricular energetics parameters in advanced heart failure patients? A retrospective study

Background and objective: Here we present a retrospective analysis of six heart failure patients previously discussed at a multidisciplinary team meeting. Only three out of six patients underwent LVAD insertion as the most appropriate management option. Methods: We sought to reproduce the baseline conditions of these patients on hospital admission using our cardiovascular software simulator (CARDIOSIM ©). Subsequently, we simulated the effects of LVAD support and drug administration on left and right ventricular energetics parameters. LVAD assistance was delivered by CARDIOSIM ©based on the module reproducing the behaviour of the Berlin Heart INCOR pump. Results: The results of our simulations were in agreement with the multidisciplinary team meeting out- come. The analysis of ventricular energetics parameters based on external work and pressure volume area confirmed LVAD support as a beneficial therapeutic option for the three patients considered eligible for this type of treatment. The effects induced by LVAD support and drugs administration showed specific patterns between the two groups of patients. Conclusion: A quantitative approach with the ability to predict outcome during patient’s assessment may well be an aid and not a substitute for clinical decision-making

Comparative elemental analysis of dairy milk and plant-based milk alternatives

Together with essential elements, toxic elements can also be found in food. In this study, we analysed the content of 41 elements in milk from mammals (cow, goat, and donkey) and plant-based milk alternatives (from soy, rice, oat, spelt, almond, coconut, hazelnut, walnut, cashew, hemp, and quinoa) using inductively coupled plasma mass spectrometry and cold vapour generation atomic fluorescence (for Hg). The analytical methods were validated using both milk certified reference materials and recovery experiments for different milk samples, obtaining satisfactory results in all cases. Only cow and goat milks were important sources of all major mineral elements like Ca, K, Mg, Na and P, and some minor elements like Se and Zn, while soy milk contained significant amounts of Cu and Fe, coconut milk contained Cr and Se, and hemp milk contained Mo. The level of toxic trace elements, including As, Cd, Hg, and Pb was very low in all analysed samples and did not pose any threat to consumers. The study is of significance for consumers of plant-based beverages from nutritional and food safety point of view. © 2020 Elsevier Lt

Monte Carlo study of gating and selection in potassium channels

The study of selection and gating in potassium channels is a very important issue in modern biology. Indeed such structures are known in all types of cells in all organisms where they play many important functional roles. The mechanism of gating and selection of ionic species is not clearly understood. In this paper we study a model in which gating is obtained via an affinity-switching selectivity filter. We discuss the dependence of selectivity and efficiency on the cytosolic ionic concentration and on the typical pore open state duration. We demonstrate that a simple modification of the way in which the selectivity filter is modeled yields larger channel efficiency

a method to estimate the total voc emission of furniture products

Abstract In the last decade, the environmental sustainability has become an important issue that drives more and more the consumer decisions. Consequently, industrial companies are called to meet the growing demand for more sustainable products. Especially in the furniture sector, customers pay serious attention to the emissions that negatively affect human health and so they request products with low volatile organic compounds (VOCs) emissions. This represents a big challenge because it requires the strictly control of each component provided by all the supply chain actors through expensive laboratory tests. For this aim, the present paper proposes a method to estimate the total VOCs emissions of furniture products starting from the characteristics of all semi-finished products (e.g., geometric features, product composition, process information and functionality) and through the definition of an appropriate impact scale based on historical data. It allows making the supply chain (SC) more sustainable, limiting costly chamber tests

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