205 research outputs found

    Fire Emergency Evacuation from a School Building Using an Evolutionary Virtual Reality Platform

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    In the last few years, modern technologies such as numerical simulations, virtual and augmented reality, and agent-based models represented effective tools to study phenomena, which may not be experimentally reproduced due to costs, inherent hazards, or other constraints (e.g., fire or earthquake emergencies and evacuation from buildings). This paper shows how to integrate a virtual reality platform with numerical simulation tools to reproduce an evolutionary fire emergency scenario. It is computed in real time based on the building information model and a fluid dynamic software. A specific software was also used to simulate in real time the crowd dynamic in the virtual environment during the emergency evacuation process. To demonstrate the applicability of the proposed methodology, the emergency fire evacuation process for an existing school building is presented. The results show that the proposed virtual reality-based system can be employed for reproducing fire emergency scenarios. It can be used to help decision-makers to determine emergency plans and to help firefighters as a training tool to simulate emergency evacuation actions

    Mesenchymal stem cell-derived extracellular vesicles protect human corneal endothelial cells from endoplasmic reticulum stress-mediated apoptosis

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    Corneal endothelial dystrophy is a relevant cause of vision loss and corneal transplantation worldwide. In the present study, we analyzed the effect of mesenchymal stem cell (MSC)-derived extracellular vesicles (MSC-EVs) in an in vitro model of corneal dystrophy, characterized by endoplasmic reticulum stress. The effects of MSC-EVs were compared with those of serum-derived EVs, reported to display a pro-angiogenic activity. MSC-EVs were able to induce a significant down-regulation of the large majority of endoplasmic reticulum stress-related genes in human corneal endothelial cells after exposure to serum deprivation and tunicamycin. In parallel, they upregulated the Akt pathway and limited caspase-3 activation and apoptosis. At variance, the effect of the serum EVs was mainly limited to Akt phosphorylation, with minimal or absent effects on endoplasmic reticulum stress modulation and apoptosis prevention. The effects of MSC-EVs were correlated to the transfer of numerous endoplasmic reticulum (ER)-stress targeting miRNAs to corneal endothelial cells. These data suggest a potential therapeutic effect of MSC-EVs for corneal endothelial endoplasmic reticulum stress, a major player in corneal endothelial dystrophy

    An indoor air quality study at the Ambrosiana Art Gallery (Milan)

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    Indoor air quality in historical buildings and museums is receiving increasing concern nowadays among the scientific community. Many sources of pollutants, both gases and particles, are responsible for the accelerated decay of the works of art. Knowing the levels of indoor pollutants is of critical importance to apply conservation and preservation strategies of cultural heritage [1, 2]. Air quality at the Ambrosiana Art Gallery in Milan has been monitored (in the two periods October-November 2017 and March 2018) inside the room where the preparatory cardboard of the School of Athens (1509-1511), one of most important masterpieces by Raffaello Sanzio, is stored. The cardboard is currently undergoing restoration and will be exposed in a new showcase that will be realized according to the specific environmental and microclimatic conditions of the room. The objective of this study was to monitor the concentration and chemical composition of the aerosol particulate matter (PM) up to the nano fraction, which represents the most dangerous fraction for the works of art surfaces. The monitoring campaigns have been carried out in parallel in the Raffaello room (at present not accessible to visitors) and in a nearby room open to visitors. The set of instuments employed included: a TSP sampler (total suspended particles) (Tecora, Pollution Check, Bravo M2); a DustMonit (Contec) analyzer that measures the concentration of dust up to PM1 and provides 13 granulometric classes (up to 300 nm); a NanoScan Nanoparticle sizer 3910 (TSI) instrument that measures particles concentration up to 10 nm; two instruments for the determination of black carbon (BC) in continuous and in particular a SILIIS instrument (Sphere-Integrated Laser Induced Incandescence Spectroscopy) and a micro aethalometer (AE51 Magee Scientific). Quartz fiber filters have been employed to collect TSP samples to be submitted to chemical analysis. The filters have been fully chemically characterized: main ionic constituents and the carbonaceous fraction (i.e organic carbon, OC and elemental carbon, EC) have been analyzed by IC (ion chromatography) and TOT (thermal optical transmittance) respectively. A particles morphological characterization has been carried out on PM collected on polycarbonate filters by means of SEM-EDX (scanning electron microscopy coupled with energy dispersive X-ray spectroscopy). Outdoor PM concentrations, obtained for the two seasons (autumn 2017 and spring 2018) from ARPA monitoring stations placed in the city center, have been correlated with indoor data

    Forecasting Causes of Death in Northern Iraq Using Neural Network

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    The availability of models for predicting future events is essential for enhancing the efficiency of systems. This paper attempts to predict demographic variation by employing multi-layer perceptron network. Here we present the implementation of a system for predicting the number and causes of deaths, for a future 2-year period. The system was built using predictive models and data that is as accurate as possible under the current conditions of the northern Region of Iraq (the Autonomous Region of Kurdistan). Our predictive model is based on quarterly periods, with the intention of providing predictions on the number of deaths, classified by gender, cause of death, age at death, administrative district (governorate), and hospital where the death occurred. The data was collected from birth and death registry bureaus and forensic medicine departments for the years 2009-2020. The python programming language was used to test the designed multi-layer perceptron network with backpropagation training algorithm. With learning rate 0.01 and 500 epochs we were able to obtain good results, as the neural network was able to represent the string, and predict future values well, with a mean squared error of 0.43, and we found that number of deaths is quite stable, with a slight increase

    Deuterium retention and erosion in liquid Sn samples exposed to D2 and Ar plasmas in GyM device

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    The use of tin (Sn) as a liquid metal for plasma facing components has been recently proposed as a solution to the high heat load issue on the divertor target plates in nuclear fusion reactors. Due to its low vapor pressure, low reactivity with hydrogen and good resilience to neutron impact, tin is a good candidate as plasma facing component. However its high atomic number poses concerns about plasma contamination.In this paper two fundamental aspects have been investigated: deuterium retention and erosion fluxes from the Sn surface towards the plasma. The samples were exposed to plasma inside the linear machine GyM in magnetic cusp configuration. This setup permits to expose free liquid specimens without the need for the Capillary Porous System. Moreover it permits to lower the magnetic field in order to increase Sn Larmor radius and consequently limit Sn re-deposition in erosion experiments.Ex-situ analyses by ion beam diagnostics on solid samples exposed to deuterium plasma have proved that the amount of retained atomic deuterium is very low, approximately 0.18 at% estimated by Nuclear Reaction Analysis and 0.25 at% estimated by Elastic Recoil Detection Analysis.In the framework of erosion studies, the spectroscopic parameter S/XB was evaluated in Ar plasma for the SnI line at 380.1 nm by Optical Emission Spectroscopy and mass loss measurements in the 5–11 eV Te range, at a density ne ∼ 1.5 × 1011 cm−3. An average value of 150 ± 23 was obtained. Keywords: Liquid metals, Deuterium retention, Erosion, Double-cusp magnetic configuration, Ion beam diagnostics, S/XB spectroscopic paramete

    Shwachman-Bodian-Diamond syndrome (SBDS) protein is a direct inhibitor of protein phosphatase 2A (PP2A) activity and overexpressed in acute myeloid leukaemia.

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    Protein phosphatase 2A (PP2A) is a serine/threonine phosphatase inactivated in many cancers including acute myeloid leukaemia (AML). Activation of PP2A is emerging as a therapeutic strategy, however the mechanisms underpinning PP2A inhibition are not well understood. Using myeloid progenitor cells harbouring oncogenic mutant c-KIT and characterised by PP2A inhibition, we have identified the ribosome biogenesis protein SBDS, as a target of the PP2A activating drugs FTY720 and AAL(S). We show SBDS binds to PP2A complexes comprised of the B55α regulatory subunit of PP2A. shRNA mediated knockdown of SBDS increased PP2A activity and induced apoptosis. At diagnosis, AML patients expressed significantly more SBDS mRNA than healthy controls, with relapsed patients expressing significantly more SBDS mRNA than both healthy controls and patients at diagnosis. Together, our data presents a role for SBDS in the dysregulation of PP2A in AML

    Effect of mobile telephones on sperm quality: A systematic review and meta-analysis.

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    types: REVIEWThis is an open access article that is freely available in ORE or from the publisher's web site. Please cite the published version.© 2014 The Authors. Published by Elsevier Ltd.Mobile phones are owned by most of the adult population worldwide. Radio-frequency electromagnetic radiation (RF-EMR) from these devices could potentially affect sperm development and function. Around 14% of couples in high- and middle-income countries have difficulty conceiving, and there are unexplained declines in semen quality reported in several countries. Given the ubiquity of mobile phone use, the potential role of this environmental exposure needs to be clarified. A systematic review was therefore conducted, followed by meta-analysis using random effects models, to determine whether exposure to RF-EMR emitted from mobile phones affects human sperm quality. Participants were from fertility clinic and research centres. The sperm quality outcome measures were motility, viability and concentration, which are the parameters most frequently used in clinical settings to assess fertility. We used ten studies in the meta-analysis, including 1492 samples. Exposure to mobile phones was associated with reduced sperm motility (mean difference -8.1% (95% CI -13.1, -3.2)) and viability (mean difference -9.1% (95% CI -18.4, 0.2)), but the effects on concentration were more equivocal. The results were consistent across experimental in vitro and observational in vivo studies. We conclude that pooled results from in vitro and in vivo studies suggest that mobile phone exposure negatively affects sperm quality. Further study is required to determine the full clinical implications for both sub-fertile men and the general population.Open Access funded by Natural Environment Research CouncilJessica Elliott-Friend is supported by a Natural Environment Research Council PhD scholarship NE/J500185/

    Preclinical and clinical evaluation of German-sourced ONC201 for the treatment of H3K27M-mutant diffuse intrinsic pontine glioma

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    Background Diffuse intrinsic pontine glioma (DIPG) is a fatal childhood brainstem tumor for which radiation is the only treatment. Case studies report a clinical response to ONC201 for patients with H3K27M-mutant gliomas. Oncoceutics (ONC201) is only available in the United States and Japan; however, in Germany, DIPG patients can be prescribed and dispensed a locally produced compound-ONC201 German-sourced ONC201 (GsONC201). Pediatric oncologists face the dilemma of supporting the administration of GsONC201 as conjecture surrounds its authenticity. Therefore, we compared GsONC201 to original ONC201 manufactured by Oncoceutics Inc. Methods Authenticity of GsONC201 was determined by high-resolution mass spectrometry and nuclear magnetic resonance spectroscopy. Biological activity was shown via assessment of on-target effects, in vitro growth, proliferation, and apoptosis analysis. Patient-derived xenograft mouse models were used to assess plasma and brain tissue pharmacokinetics, pharmacodynamics, and overall survival (OS). The clinical experience of 28 H3K27M+ mutant DIPG patients who received GsONC201 (2017-2020) was analyzed. Results GsONC201 harbored the authentic structure, however, was formulated as a free base rather than the dihydrochloride salt used in clinical trials. GsONC201 in vitro and in vivo efficacy and drug bioavailability studies showed no difference compared to Oncoceutics ONC201. Patients treated with GsONC201 (n = 28) showed a median OS of 18 months (P = .0007). GsONC201 patients who underwent reirradiation showed a median OS of 22 months compared to 12 months for GsONC201 patients who did not (P = .012). Conclusions This study confirms the biological activity of GsONC201 and documents the OS of patients who received the drug; however, GsONC201 was never used as a monotherapy

    The relationship between seminal leukocytes, oxidative status in the ejaculate, and apoptotic markers in human spermatozoa

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    The aim of this study was to investigate the relationship between seminal leukocytes, reactive oxygen species (ROS) production in the ejaculate, and markers of apoptosis in human spermatozoa. Semen samples were collected from 60 patients attending fertility clinics at the Reproductive Biology Unit at Tygerberg Academic Hospital and Vincent Pallotti Hospital, Cape Town, South Africa. The concentration of seminal leukocytes was determined and was correlated with ROS production in the ejaculate, the percentage of superoxide (·O2 )- and hydrogen peroxide (H2O2)-positive spermatozoa, glutathione activation in the ejaculate, and with markers of apoptosis in spermatozoa, namely cysteine-dependent aspartate-directed proteases (caspase)-3/7 activation, mitochondrial membrane potential (ΔΨm), and the percentage of terminal deoxynucleotidyl transferase-mediated dUTP-biotin nick end labeling (TUNEL)-positive sperm. Significant correlations with the concentration of seminal leukocytes were found for ROS production in the ejaculate, the percentage of ·O2 -positive spermatozoa, and caspase-3/7 activation in the ejaculate. Leukocytospermic samples showed significantly higher ROS production, percentage of ·O2 -positive sperm, GSH activation, and caspase-3/7 activation compared to non-leukocytospermic samples. The percentage of ·O2 -positive sperm was significantly correlated with sperm ΔΨm and caspase-3/7 activation in the ejaculate. Sperm ΔΨm and TUNEL-positive sperm did not correlate with seminal leukocyte concentration. Data demonstrate that high seminal leukocyte concentrations that leads to increased seminal ROS production, and is also associated with caspase activation in the male germ cell and increased mitochondrial ROS production. The latter could possibly be a result of disturbed ΔΨm. The activation of caspase-3/7 could then follow the increased intrinsic superoxide levels due to depleted intrinsic glutathione (GSH). These cellular events might not directly and immediately lead to DNA fragmentation as an endpoint of apoptosis because of topological hindrances.Web of Scienc
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