1,373 research outputs found

    Stereotype movement recognition in children with ASD

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    The Autism Spectrum Disorders (ASD) covers different events, being one of them body rocking, mouthing, and complex hand and finger movements [1]. The traditional methods for recording the number of occurrences and duration of stereotypes are inadequate and time consuming. Therefore, it was used a commercial system with accelerometers sensors that records the movement of wrist and sends the collected data through a wireless network to the computer. Statistical methods were used to characterize the signal acquired from a previously expressed stereotypy. The parameters that were analyzed are: RMS, Standard Variation, Peaks and Valleys. At the end, the proposed methodology facilitates to identify behavioral patterns special relevant when studying interaction skills in children with ASD

    CO-mediated cytoprotection is dependent on cell metabolism modulation

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    This work was supported by Fundação para a Ciência e Tecnologia (FCT) grant UID/Multi/04462/2013, I&D 2015–2020 iNOVA4Health - Programme in Translacional Medicine. FCT provided individual financial support to CFP (SFRH/BD/106057/2015), DDP (PD/BD/128338/2017), NLS (PD/BD/127819/2016) and HLAV (IF/00185/2012).Carbon monoxide (CO) is a gasotransmitter endogenously produced by the activity of heme oxygenase, which is a stress-response enzyme. Endogenous CO or low concentrations of exogenous CO have been described to present several cytoprotective functions: anti-apoptosis, anti-inflammatory, vasomodulation, maintenance of homeostasis, stimulation of preconditioning and modulation of cell differentiation. The present review revises and discuss how CO regulates cell metabolism and how it is involved in the distinct cytoprotective roles of CO. The first found metabolic effect of CO was its increase on cellular ATP production, and since then much data have been generated. Mitochondria are the most described and studied cellular targets of CO. Mitochondria exposure to this gasotransmitter leads several consequences: ROS generation, stimulation of mitochondrial biogenesis, increased oxidative phosphorylation or mild uncoupling effect. Likewise, CO negatively regulates glycolysis and improves pentose phosphate pathway. More recently, CO has also been disclosed as a regulating molecule for metabolic diseases, such as obesity and diabetes with promising results.publishersversionpublishe

    An experimental and numerical study on aluminum alloy tailor heat treated blanks

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    Information is presented on the conceptualization, experimental study, and numerical process simulation of tailor heat treated aluminum alloy blanks. This concept is intended to improve the forming behavior of aluminum parts in challenging conditions. The implementation requires precise control of laser heat treatment parameters within a suitable industrial framework. The study details material properties, heat treatment parameters, and experimental results for the strength and elongation properties of an AA6063-T6 aluminum alloy. Constitutive modeling is applied using the Hocket–Sherby equation, which allowed us to establish a correlation between laser heat treatment maximum temperature and the corresponding material softening degree. Based on the generated flow stress–strain curves, a numerical simulation of a representative case study was performed with Abaqus finite element software highlighting potential improvements of tailor heat treated blanks (THTB). The influence and effectiveness of heat-affected zone (HAZ) dimensions and material softening were analyzed.This research was funded by Projects I&DT SIT—Softening in Tool, grant number CENTRO02-0853-FEDER-045419 and METRICS (UID/EMS/04077/2020)

    IT Service Management: Sistema de monitorização baseado em ferramentas open source

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    O IT Service Management (ITSM) descreve a forma como uma organização gere os seus serviços de Tecnologias da Informação (TI). Define as funções e responsabilidades de cada departamento e indivíduo em relação aos serviços de TI. Propõe um conjunto de boas práticas e processos, que visam a auxiliar as organizações na gestão eficiente da infraestrutura de TI (i.e., componentes e serviços). Contribui para uma maior produtividade, redução de custos e aumento da satisfação do cliente. O Information Technology Infrastructure Library (ITIL) é uma framework utilizada no contexto da gestão do ITSM. É um conjunto específico de processos e diretrizes para o fornecimento de serviços de TI. Esta apresentação centra-se na implementação de um sistema de monitorização de TI baseado em ferramentas open source, capaz de monitorizar e analisar em tempo real o funcionamento da infraestrutura de TI de uma organização. Este sistema pode desempenhar um papel fundamental na definição da estratégia de TI mais adequada para o negócio. Tem implicação na melhoria da qualidade dos serviços e no aumento do valor agregado ao negócio.info:eu-repo/semantics/publishedVersio

    Carbon Monoxide Modulation of Microglia-Neuron Communication: Anti-Neuroinflammatory and Neurotrophic Role

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    This work was financed by FEDER-Fundo Europeu de Desenvolvimento Regional funds through the COMPETE 2020-Operational Programme for Competitiveness and Internationalization (POCI), Portugal 2020, and by Portuguese funds through FCT-Fundação para a Ciência e a Tecnologia/Ministério da Ciência (FCT), Tecnologia e Ensino Superior in the framework of FCT-ANR/NEU-NMC/0022/2012 grant, PTDC/MEC-NEU/28750/2017 grant, Applied Molecular Biosciences Unit-UCIBIO (UID/Multi/04378/2019) grant; LA/P/0140/2020 of the Associate Laboratory Institute for Health and Bioeconomy; and FCT provided individual financial support to NLS (PD/BD/127819/2016), BFM (PD/BD/128336/2017) and HLAV (IF/00185/2012).Microglia, the ‘resident immunocompetent cells’ of the central nervous system (CNS), are key players in innate immunity, synaptic refinement and homeostasis. Dysfunctional microglia contribute heavily to creating a toxic inflammatory milieu, a driving factor in the pathophysiology of several CNS disorders. Therefore, strategies to modulate the microglial function are required to tackle exacerbated tissue inflammation. Carbon monoxide (CO), an endogenous gaseous molecule produced by the degradation of haem, has anti-inflammatory, anti-apoptotic, and pro-homeostatic and cytoprotective roles, among others. ALF-826A, a novel molybdenum-based CO-releasing molecule, was used for the assessment of neuron-microglia remote communication. Primary cultures of rat microglia and neurons, or the BV-2 microglial and CAD neuronal murine cell lines, were used to study the microglia-neuron interaction. An approach based on microglial-derived conditioned media in neuronal culture was applied. Medium derived from CO-treated microglia provided indirect neuroprotection against inflammation by limiting the lipopolysaccharide (LPS)-induced expression of reactivity markers (CD11b), the production of reactive oxygen species (ROS) and the secretion of inflammatory factors (TNF-α, nitrites). This consequently prevented neuronal cell death and maintained neuronal morphology. In contrast, in the absence of inflammatory stimulus, conditioned media from CO-treated microglia improved neuronal morphological complexity, which is an indirect manner of assessing neuronal function. Likewise, the microglial medium also prevented neuronal cell death induced by pro-oxidant tert-Butyl hydroperoxide (t-BHP). ALF-826 treatment reinforced microglia secretion of Interleukin-10 (IL-10) and adenosine, mediators that may protect against t-BHP stress in this remote communication model. Chemical inhibition of the adenosine receptors A2A and A1 reverted the CO-derived neuroprotective effect, further highlighting a role for CO in regulating neuron-microglia communication via purinergic signalling. Our findings indicate that CO has a modulatory role on microglia-to-neuron communication, promoting neuroprotection in a non-cell autonomous manner. CO enhances the microglial release of neurotrophic factors and blocks exacerbated microglial inflammation. CO improvement of microglial neurotrophism under non-inflammatory conditions is here described for the first time.publishersversionepub_ahead_of_prin

    Bioorthogonal labeling reveals different expression of glycans in mouse hippocampal neuron cultures during their development

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    The following are available online. Scheme S1: Synthesis of peracetylated azidomannose (Ac4ManNAz); Scheme S2: Alternative synthesis of GlcNAz using chloroacetic anhydride and NaOH as a base; Scheme S3: Synthesis of peracetylated azidofucose (Ac4FucAz); Figure S1: 1H-NMR spectra of ManNAz (D2O, 300 MHz); Figure S2: 1H-NMR spectra of Ac4ManNAz (CDCl3 , 300 MHz), mixture of anomers; Figure S3: HPLC chromatogram of purified Ac4ManNAz showing the two anomers; Figure S4: 1H-NMR spectra of GlcNAz (D2O, 300MHz); Figure S5: 1H-NMR spectra of Ac4GlcNAz (CDCl3 , 300 MHz), mixture of anomers; Figure S6: HPLC chromatogram of purified Ac4GlcNAz showing the two anomers; Figure S7: 1H-NMR spectra of 6-azido-1,2,3,4-tetra-O-acetyl-6-deoxy-α,β-L-galactopyranose Ac4FucAz (CDCl3 , 300 MHz): mixture of anomers; Table S1: Primer sequences used in qRT-PCR.The expression of different glycans at the cell surface dictates cell interactions with their environment and other cells, being crucial for the cell fate. The development of the central nervous system is associated with tremendous changes in the cell glycome that is tightly regulated. Herein, we have employed biorthogonal Cu-free click chemistry to image temporal distribution of different glycans in live mouse hippocampal neurons during their maturation in vitro. We show development-dependent glycan patterns with increased fucose and decreased mannose expression at the end of the maturation process. We also demonstrate that this approach is biocompatible and does not affect glycan transport although it relies on an administration of modified glycans. The applicability of this strategy to tissue sections unlocks new opportunities to study the glycan dynamics under more complex physiological conditions.This research was funded by the European Union Framework Programme for Research and Innovation Horizon 2020 under grant agreement n.º 668983—FoReCaST, by European Union’s Horizon 2020 Research and Innovation programme, under the Grant Agreement number 739572–The Discoveries CTR, and the project NORTE-01-0145-FEDER-000023, supported by the Northern Portugal Regional Operational Programme (NORTE 2020), under the Portugal 2020 Partnership Agreement, through the European Regional Development Fund (FEDER)

    Evaluation of the potential of fucoidan-based microparticles for diabetes treatment

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    Abstract INTRODUCTION: Marine organisms have in their constitution materials with a wide range of properties and characteristics inspiring their application within the biomedical field. One important example is fucoidan (Fu), an underexploited sulfated polysaccharide extracted from the cell wall of the brown seaweeds, with high solubility in water1. Fucoidan is composed of L- fucose and glucuronic acid including sulfate groups and has important bioactive properties such as antioxidative, anticoagulant, anticancer and in the reduction of blood glucose1,2. In this work, the biomedical potential of fucoidan was assessed by processing modified fucoidan (MFu) into microparticles by photocrosslinking using superhydrophobic surfaces and visible light3,4. Biological performance on the developed constructs using human pancreatic beta cells is currently under investigation. METHODS: To design the materials structures, fucoidan was modified by methacrylation reaction3. Briefly, Fu aqueous solution 4% w/v was mixed with methacrylated anhydride (MA) in volume of 12% v/v at 50oC to react for 6h. Further, MFu particles with and without insulin (0.5% w/v) were produced by pipetting a solution of 5% MFu v/v with triethanolamine and eosin-y (photoinitiators) onto superhydrophobic surfaces4 (Fig. 1A) and then photocrosslinking using visible light4. MFu and developed particles were characterized using 1HNMR, turbidimetry and SEM to assess their chemistry and morphology, respectively. Moreover, the insulin release was evaluated in phosphate buffered saline (PBS) solution at pH 7and simulated intestinal fluid (SIF) at pH 5. The ability of the developed materials to support adhesion and proliferation of cells was assessed by suspension culture of human pancreatic cells 1.1B4 (3.5x105 cells/ml) in contact with MFu microparticles during up to 7 days. RESULTS: The chemical modification performed on Fu was confirmed by the presence of vinyl and additional methyl peaks in the 1HNMR of modified fucoidan, not present in Fu spectrum. Methacrylated fucoidan was obtained with a methacrylation degree of 17%. The produced fucoidan particles have round shape and average diameter of 1.53 mm (Fig. 1B). The insulin release in PBS and SIF demonstrate that the particles can release insulin in a sustained manner under the studied period. It seems that the insulin release is slower for SIF (pH5, Fig. 1C), than for PBS. The biological tests regarding the culture of pancreatic beta cells demonstrate that cells show a round-like shape and tend to form pseudo-islets during the culture period studied (Fig. 1D). DISCUSSION & CONCLUSIONS: This work demonstrates the successful production of fucoidan- based-microparticles through the methacrylation of fucoidan, using visible light and superhydrophobic surfaces. The covalent crosslinking methacrylated fucoidan through visible light represents a promising method to obtain biocompatible fucoidan particles with a uniform round shape. The obtained insulin release profiles are sensitive to different pH (pH7 and pH5), mimicking the normal physiological pathway for insulin release. Furthermore, the results suggest these systems could be used for treatment of type I diabetes mellitus as they sustain beta cells viability and proliferation. The response also suggested, that the MFu particles could be a good candidate as drug delivery vehicles for the diabetes mellitus treatment. REFERENCES: 1 Silva TH et al (2012), Biomatter 2(4): 278:289. 2Sezer Alidemir et al (2011), Fucoidan: A versatile biopolymer for biomedical applicatons (Springer Ber.Heid).pp377-406. 3Mihaila S.et al (2013), Adv. Health. Mat. 2(6): 895-907. 4Rial Hermida et al, Acta Biomater.(2014) 10(10) 4314-4322. ACKNOWLEDGEMENTS: This work was partially funded by projects 0687_NOVOMAR_1_P (POCTEP), CarbPol_u_Algae (EXPL/MAR- BIO/0165/2013), ComplexiTE (ERC-2012-ADG 20120216-321266). Portuguese Foundation for Science and Technology is also gratefully acknowledged for doctoral grants of L. Reys and N. Oliveira and post- doctoral grants of S.S. Silva and D. Soares da Costafunded by projects 0687_NOVOMAR_1_P (POCTEP), CarbPol_u_Algae (EXPL/MARBIO/0165/2013) , ComplexiTE(ERC-2012-ADG 20120216-321266). Portuguese Foundation for Science and Technologyinfo:eu-repo/semantics/publishedVersio

    IT service management: concepts and processes

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    Num mundo cada vez mais tecnológico, a alta disponibilidade dos sistemas é cada vez mais exigente aos serviços de Tecnologias de Informação (TI). O Information Technology Service Management (ITSM) pode ter um papel fundamental na gestão de TI, auxiliando clientes e parceiros para que o serviço prestado apresente a melhor relação custo/benefício, e diminuindo o tempo de inatividade e as interrupções dos serviços. Procura-se potenciar o valor do negócio. Neste contexto, o Information Technology Infrastructure Library (ITIL) aparece como uma framework que tem como objetivo auxiliar e facilitar a definição do negócio e a implementação da gestão de ITSM. Este artigo centra-se na análise e discussão dos conceitos inerentes aos processos de TI,auxiliando quem está a dar os primeiros passos nesta área. Ao longo do documento serão descritas as fases que compõem o ITSM e o ITIL, sob a forma de um guia orientador.In an increasingly technological world, high availability of systems is increasingly demanding of Information Technology (IT) services. Information Technology Service Management (ITSM) can play a key role in IT management, helping customers and partners to provide the most cost-effective service and reducing downtime and service interruptions. The aim is to enhance business value. In this context, the Information Technology Infrastructure Library (ITIL) appears as a framework that aims to assist and facilitate the business definition and implementation of ITSM management. This article focuses on the analysis and discussion of the concepts inherent to IT processes, helping those who are taking their first steps in this area. Throughout the document the phases that make up ITSM and ITIL will be described, in the form of a guiding guide.info:eu-repo/semantics/publishedVersio

    Analysis of a Local HIV-1 Epidemic in Portugal Highlights Established Transmission of non-B and -G Subtypes

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    The existing data supports Portugal as the Western Europe country with highest HIV-1 subtype diversity. However, detailed phylogenetic studies of Portuguese HIV-1 epidemics are still scarce. Thus, our main goal was to analyze the phylodynamics of a local HIV-1 infection in the Portuguese region of Minho. Molecular epidemiological analysis was applied to data from 289 HIV-1 infected individuals followed in the reference Hospital of the province of Minho, Portugal, in which isolated viruses had been sequenced between 2000 and 2012. Viruses of the G (29.1%) and B (27.0%) subtypes were the most frequent, followed by recombinant forms (17.6%), C (14.5%), F1 (7.3%) and A1 (4.2%) subtypes. Multinomial logistic regression revealed that the odds of being infected with A1 and F1 subtype increased over the years when compared with B, G, C or recombinant viruses. As expected, polyphyletic patterns suggesting multiple and old introductions of subtypes B and G were found. However, transmission clusters of non-B and -G viruses among native individuals were also found with the dates of the most recent common ancestor estimated to the early 2000s. Our study supports that the HIV-1 subtype diversity in the Portuguese region of Minho is high and has been increasing in a manner that is apparently driven by factors other than immigration and international travel. Infections with A1 and F1 viruses in the region of Minho are becoming established and were mainly found in sexually transmitted clusters, reinforcing the need for more efficacious control measures targeting this infection route

    Potential impact on stroke

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    Funding Information: The funding agency that supported the work \u201CFunda\u00E7\u00E3o para a Ci\u00EAncia e Tecnologia\u201D (FCT) with four projects: Applied Molecular Biosciences Unit-UCIBIO (UID/Multi/04378/2019), iNOVA4Health - Programme in Translational Medicine (UID/Multi/04462/2013), LA/P/0140/2020 of the Associate Laboratory Institute for Health and Bioeconomy and PTDC/MEC-NEU/28750/2017 and the PhD scholarship for NLS (PD/BD/127819/2016). Publisher Copyright: © 2024 The AuthorsRemote ischemic conditioning (RIC) is a procedure consisting of short cycles of ischemia applied in a limb that activates endogenous protection in distant organs, such as the brain. Despite the promising outcomes of RIC, the biochemical factors governing inter-organ communication remain largely unexplored, particularly in humans. A pilot study on 20 healthy humans was performed to identify potential circulating biochemical factors involved in RIC signalling. Blood was collected before and immediately, 4 and 22 h after the end of RIC. To characterize the responses triggered by RIC, a combination of biochemical and proteomic analysis, along with functional in vitro tests in human cells, were performed. RIC did not alter the levels of nitric oxide, bilirubin and cell-free mitochondrial DNA. In contrast, carboxyhaemoglobin levels increased following RIC at all time points and young subset, suggesting endogenous production of carbon monoxide that is a cytoprotective gasotransmitter. Additionally, the levels of glutathione and cysteinylglycine bound to proteins also increased after RIC, while glutathione catabolism decreased. Plasma proteomic analysis identified overall 828 proteins. Several steps of statistical analysis (Student's t-test, repeated measures ANOVA, with Holm corrected pairwise p-values <0.05 threshold and fold change higher or lower than 100 %) leaded to the identification of 9 proteins with altered circulating levels in response to RIC at 4h and 22h. All 9 proteins are from extracellular space or exosomes, being involved in inflammation, angiogenesis or metabolism control. In addition, RIC-conditioned plasma from young subjects protected microglial cell culture against inflammatory stimuli, indicating an anti-inflammatory effect of RIC. Nevertheless, other functional tests in neurons or endothelial cells had no effect. Overall, we present some evidence for RIC-induced anti-inflammatory and antioxidant responses in healthy human subjects, in particular in young subjects. This study is a first step towards the disclosure of signalling factors involved in RIC-mediated inter-organ communication.publishersversionpublishe
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