305 research outputs found

    Leveraging context-awareness to better support the IoT cloud-edge continuum

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    Novel Internet of Things (IoT) requirements derived from a broader interconnection of heterogeneous devices have pushed the horizons of Cloud computing and are giving rise to a wider decentralisation of applications and data centers. An answer to the underlying network concerns, such as the need to lower the resulting latency due to heavy computation needs, or safety aspects, gave rise to Edge/Fog computing, where IoT functionality can be also supported closer to data sources. While it is today feasible to perform some IoT functionality on the Edge, the orchestration of operations between Edge and Cloud requires an automated support, where context-awareness plays a key role in assisting the network in deciding when and where to store data and to perform computation. This work is focused on the application of context-awareness to support a smoother operation of the Edge to Cloud operation, aiming at lowering latency, in particular when real-time or close-to-real-time data exchange is present.info:eu-repo/semantics/publishedVersio

    Role of hydrogeological mapping in groundwater practice: back to basics

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    Maps are of key importance in groundwater professional practice and hydrogeology research, mainly in field data synthesis and communication related to a number of fields: regional hydrogeology, explorationhydrogeology, groundwater engineering, hydrogeophysics, hydrogeomorphology, urban groundwater, military geology/engineering,thermal water resources, planning, management and decision making on thewater resources. This paper highlights the importance and necessity of accurate ground field surveys at several scales, water resources inventory and an integrated groundwater mapping as useful tools to support hydrogeological conceptualisation. Selected sites are highlighted to demonstrate the importance of groundwater mapping for assessment of water resources. Conceptualisation of groundwater systems must be grounded on Earth-based models and mathematical modelling to outline predicting scenarios. Thus, going back to basics is important to create a reliable conceptualisation on groundwater systems establishedon cartographic reasoning

    Prostaglandin E2 receptors in asthma and in chronic rhinosinusitis/nasal polyps with and without aspirin hypersensitivity

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    Chronic rhinosinusitis with nasal polyps (CRSwNP) and asthma frequently coexist and are always present in patients with aspirin exacerbated respiratory disease (AERD). Although the pathogenic mechanisms of this condition are still unknown, AERD may be due, at least in part, to an imbalance in eicosanoid metabolism (increased production of cysteinyl leukotrienes (CysLTs) and reduced biosynthesis of prostaglandin (PG) E2), possibly increasing and perpetuating the process of inflammation. PGE2 results from the metabolism of arachidonic acid (AA) by cyclooxygenase (COX) enzymes, and seems to play a central role in homeostasis maintenance and inflammatory response modulation in airways. Therefore, the abnormal regulation of PGE2 could contribute to the exacerbated processes observed in AERD. PGE2 exerts its actions through four G-protein-coupled receptors designated E-prostanoid (EP) receptors EP1, EP2, EP3, and EP4. Altered PGE2 production as well as differential EP receptor expression has been reported in both upper and lower airways of patients with AERD. Since the heterogeneity of these receptors is the key for the multiple biological effects of PGE2 this review focuses on the studies available to elucidate the importance of these receptors in inflammatory airway diseases

    On a dialogue between hard-rock aquifer mapping and hydrogeological conceptual models: insights into groundwater exploration

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    Groundwater is a dynamic and renewable resource, but in hard-rock terrains its availability is rather limited compared to other types of aquifer formations. Groundwater systems require a comprehensive understanding of geology, morphotectonics and hydrology, which are controlled by ground characteristics like weathering grade, fracturing degree, permeability, slope, drainage pattern and density, land cover, and climate. GIS-based integrative cartography provides an accurate way to improve knowledge on water circulation models and on the global functioning of aquifer systems. The groundwater conceptual model based in Earth systems has proven its value in water resource studies. This approach highlights the importance of groundwater exploration mapping as a useful tool to support hydrogeological conceptualisation of fractured hard-rock terrains, contributing to the sustainability of water resources.info:eu-repo/semantics/publishedVersio

    Site appraisal in fractured rock media: coupling engineering geological mapping and geotechnical modelling

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    Geotechnical surveys are based on collecting data from fieldwork and are a key element of rock-mass quality assessment in rock engineering. The lessons learned in several engineering projects underline the value of the accuracy of the basic geological and geotechnical data information related to the rock masses description and evaluation. An evaluation based on engineering geosciences, hydraulic and geotechnical features of rock masses involves combining parameters to derive quantitative geomechanical classifications for engineering design. In the present work, two selected sites are highlighted to demonstrate the importance of GIS mapping and models. Mapping and quantifying the on-site measurements’ information content and building a geo-database is vital for decision-making processes and risk assessment on sustainable engineering design with nature and hazards.info:eu-repo/semantics/publishedVersio

    Biotechnological Production of Carotenoids and Their Applications in Food and Pharmaceutical Products

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    Pigments can be divided into four categories: natural, nature-identical, synthetic, and inorganic colors. Artificial colorants are the most used in food and pharmaceutical industries because of their advantages related to color range, price, resistance to oxygen degradation, and solubility. However, many natural pigments present health-promoting activities that make them an interesting option for human use and consumption. Natural colorants are derived from sources such as plants, insects, and microorganisms. Carotenoids are natural pigments with important biological activities, such as antioxidant and pro-vitamin A activity, that can be either extracted from plants and algae or synthesized by various microorganisms, including bacteria, yeasts, filamentous fungi, and microalgae. Advantages of microbial production include the ability of microorganisms to use a wide variety of low cost substrates, the better control of cultivation, and the minimized production time. After fermentation, carotenoids are usually recovered by cell disruption, solvent extraction, and concentration. Subsequent purification steps are followed depending on the application. The most prominent industrial applications of carotenoids, considering their health benefits, are in the food, feed, and pharmaceutical industries

    From engineering geosciences mapping towards sustainable urban planning

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    Maps are of key topical importance in urban geoscience and engineering practice, mainly in field data synthesis and communication related to a number of fields, such as geomatic techniques, applied geology and geomorphology, engineering geology, soil and rock geotechnics, slope geotechnics, subsurface site geotechnical investigations, urban hydrology, hydraulics and sanitation, coastal zones management, urban geoarcheology and heritage, planning and land use. The value of preparing engineering geoscience maps and plans specificallyfor urban engineering purposes are still a challenging task, particularly to end-users and planners. Nowadays, the application of Geographic Information Systems to geosciences and engineering has become more common. This paper emphasises the importance of an accurate ground field survey and inventory at several scales, GIS mapping and databases, and integrated multidisciplinary urban studies as useful tools to support a sustainable land use planning. Some selected sites are highlighted to demonstrate the importance of urban mapping for land use planning. Thus, in this study the significance of a smart urban geoscience approach is stressed.info:eu-repo/semantics/publishedVersio

    Serotonergic signalling suppresses ataxin 3 aggregation and neurotoxicity in animal models of Machado-Joseph disease

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    Polyglutamine diseases are a class of dominantly inherited neurodegenerative disorders for which there is no effective treatment. Here we provide evidence that activation of serotonergic signalling is beneficial in animal models of Machado-Joseph disease. We identified citalopram, a selective serotonin reuptake inhibitor, in a small molecule screen of FDA-approved drugs that rescued neuronal dysfunction and reduced aggregation using a Caenorhabditis elegans model of mutant ataxin 3-induced neurotoxicity. MOD-5, the C. elegans orthologue of the serotonin transporter and cellular target of citalopram, and the serotonin receptors SER-1 and SER-4 were strong genetic modifiers of ataxin 3 neurotoxicity and necessary for therapeutic efficacy. Moreover, chronic treatment of CMVMJD135 mice with citalopram significantly reduced ataxin 3 neuronal inclusions and astrogliosis, rescued diminished body weight and strikingly ameliorated motor symptoms. These results suggest that small molecule modulation of serotonergic signalling represents a promising therapeutic target for Machado-Joseph disease.This work was supported by Fundação para a Ciência e Tecnologia (FCT) and COMPETE through the projects ‘[PTDC/SAU-GMG/112617/2009] (to P.M.) and [EXPL/ BIM-MEC/0239/2012] (to A.T.C.)’, by National Ataxia foundation (to P.M.), by Ataxia UK (to P.M.), by National Institutes of Health (NIH) ‘[GM038109, GM081192, AG026647, and NS047331] (to R.I.M.)’, by The Chicago Biomedical Consortium (to R.I.M.) and by the Ellison Medical Foundation (to R.I.M.). A.T.C., A.J., S.E., L.S.S., C.B., S.D.S., A.S.F. and A.N.C. were supported by the FCT individual fellowships SFRH/BPD/79469/2011, SFRH/BD/76613/2011, SFRH/BD/78554/2011, SFRH/BD/ 84650/2012, SFRH/BPD/74452/2010, SFRH/BD/78388/ 2011, SFRH/BPD/91562/2012 and SFRH/BD/51059/2010, respectively. FCT fellowships are co-financed by POPH, QREN, Governo da República Portuguesa and EU/FSE.info:eu-repo/semantics/publishedVersio

    A selective p53 activator and anticancer agent to improve colorectal cancer therapy

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    Impairment of the p53 pathway is a critical event in cancer. Therefore, reestablishing p53 activity has become one of the most appealing anticancer therapeutic strategies. Here, we disclose the p53-activating anticancer drug (3S)-6,7-bis(hydroxymethyl)-5-methyl-3-phenyl-1H,3H-pyrrolo[1,2-c]thiazole (MANIO). MANIO demonstrates a notable selectivity to the p53 pathway, activating wild-type (WT)p53 and restoring WT-like function to mutant (mut)p53 in human cancer cells. MANIO directly binds to the WT/mutp53 DNA-binding domain, enhancing the protein thermal stability, DNA-binding ability, and transcriptional activity. The high efficacy of MANIO as an anticancer agent toward cancers harboring WT/mutp53 is further demonstrated in patient-derived cells and xenograft mouse models of colorectal cancer (CRC), with no signs of undesirable side effects. MANIO synergizes with conventional chemotherapeutic drugs, and in vitro and in vivo studies predict its adequate drug-likeness and pharmacokinetic properties for a clinical candidate. As a single agent or in combination, MANIO will advance anticancer-targeted therapy, particularly benefiting CRC patients harboring distinct p53 status.We thank PT national funds (FCT/MCTES, Fundação para a Ciência e a Tecnologia, and Ministério da Ciência, Tecnologia e Ensino Superior) through grants UIDB/50006/2020, UID/BIO/04469/2019, UIDB/04539/2020, and UIDP/04539/2020 (CIBB); BioTecNorte operation (NORTE-01-0145-FEDER000004) and Porto Neurosciences and Neurologic Disease Research Initiative at I3S (Norte-01-0145-FEDER-000008) funded by the European Regional Development Fund under the scope of Norte2020 - Programa Operacional Regional do Norte; Masaryk University (Project MUNI/A/1127/2019) and Ministry of Education, Youth and Sports of the Czech Republic (project nos. LQ1605 and LM2018125); FCT financial support through the fellowships SFRH/BD/119144/2016 (H.R.) and SFRH/BD/117949/2016 (L.R.); Fondazione AIRC (IG#18985, A.I.); and the Programa Operacional Potencial Humano (POCH), specifically the BiotechHealth Programme (Doctoral Programme on Cellular and Molecular Biotechnology Applied to Health Sciences, PD/00016/2012). We thank Dario Rizzotto for assistance in preparing the libraries for RNA sequencing. Funding: This work was supported by PT National Funds (FCT/MCTES, Fundação para a Ciência e Tecnologia, and Ministério da Ciência, Tecnologia e Ensino Superior) via the projects UIDB/50006/2020 (LAQV/REQUIMTE), UIDB/00313/2020, and UIDP/00313/2020, co-funded by COMPETE2020-UE.info:eu-repo/semantics/publishedVersio
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