266 research outputs found

    NIR reflective finishing coatings with nanoparticle inclusion

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    About 40% of the energy consumption of European countries are attributed to buildings. For the construction sector development, it is necessary to ensure the enhancement of sustainability in buildings, eventually by designing new energy- efficient buildings. To accomplish such goal it is crucial to reduce the amount of solar radiation absorbed by buildings. Several solutions have already been reports in the literature, being the development of coatings with high reflectance of the solar energy for envelope system one of the promising methods to be effective in reducing the thermal gains in buildings. Coatings that contain near-infrared reflective nanomaterials can be applied onto a surface (such as roofs, pavements or, façades) exposed to solar radiation to reducing its radiation absorption. Our study aimed the development of innovative finishing coatings for envelope systems by increasing their solar reflectance through new material formulations with the inclusion of nanoparticles. We studied the reflectance and colour properties by doping a standard black colorant with different types and sizes of nanoparticles (TiO2 in rutile and anatase phase, Al2O3 and CuO), in an acrylic substrate. In particular, such nanoparticles were used with the concentration in the coating being varied (1% to 20%). The results obtained can help formulate new finishing coatings with increased near-infrared reflectance of buildings façades, using, for instance, more than one type of nanoparticles or core-shell structures

    Self-recycling and partially conservative replication of mycobacterial methylmannose polysaccharides

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    The steep increase in nontuberculous mycobacteria (NTM) infections makes understanding their unique physiology an urgent health priority. NTM synthesize two polysaccharides proposed to modulate fatty acid metabolism: the ubiquitous 6-O-methylglucose lipopolysaccharide, and the 3-O-methylmannose polysaccharide (MMP) so far detected in rapidly growing mycobacteria. The recent identification of a unique MMP methyltransferase implicated the adjacent genes in MMP biosynthesis. We report a wide distribution of this gene cluster in NTM, including slowly growing mycobacteria such as Mycobacterium avium, which we reveal to produce MMP. Using a combination of MMP purification and chemoenzymatic syntheses of intermediates, we identified the biosynthetic mechanism of MMP, relying on two enzymes that we characterized biochemically and structurally: a previously undescribed ?-endomannosidase that hydrolyses MMP into defined-sized mannoligosaccharides that prime the elongation of new daughter MMP chains by a rare ?-(1?4)-mannosyltransferase. Therefore, MMP biogenesis occurs through a partially conservative replication mechanism, whose disruption affected mycobacterial growth rate at low temperature

    Synthesis, Bioavailability, and Cytotoxicity Studies

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    Funding Information: This work was supported by Portuguese funds from FCT/MCTES through the Associate Laboratory for Green Chemistry—LAQV (UIDB/50006/2020 and UIDP/50006/2020) and the project numbers PTDC/QUI-QOR/32406/2017 and PTDC/EAM-AMB/2023/2021. Ana R. Jesus and Ana Rita C. Duarte acknowledge the European Research Council (ERC) under the European Union’s Horizon 2020 Research and Innovation Programme, under grant agreement No ERC-2016-CoG 725034. Publisher Copyright: © 2023 by the authors.Thyroid diseases affect a considerable portion of the population, with hypothyroidism being one of the most commonly reported thyroid diseases. Levothyroxine (T4) is clinically used to treat hypothyroidism and suppress thyroid stimulating hormone secretion in other thyroid diseases. In this work, an attempt to improve T4 solubility is made through the synthesis of ionic liquids (ILs) based on this drug. In this context, [Na][T4] was combined with choline [Ch]+ and 1-(2-hydroxyethyl)-3-methylimidazolium [C2OHMiM]+ cations in order to prepare the desired T4-ILs. All compounds were characterized by NMR, ATR-FTIR, elemental analysis, and DSC, aiming to check their chemical structure, purities, and thermal properties. The serum, water, and PBS solubilities of the T4-ILs were compared to [Na][T4], as well as the permeability assays. It is important to note an improved adsorption capacity, in which no significant cytotoxicity was observed against L929 cells. [C2OHMiM][T4] seems to be a good alternative to the commercial levothyroxine sodium salt with promising bioavailability.publishersversionpublishe

    An evolutionary driver of interspersed segmental duplications in primates

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    Background The complex interspersed pattern of segmental duplications in humans is responsible for rearrangements associated with neurodevelopmental disease, including the emergence of novel genes important in human brain evolution. We investigate the evolution of LCR16a, a putative driver of this phenomenon that encodes one of the most rapidly evolving human–ape gene families, nuclear pore interacting protein (NPIP). Results Comparative analysis shows that LCR16a has independently expanded in five primate lineages over the last 35 million years of primate evolution. The expansions are associated with independent lineage-specific segmental duplications flanking LCR16a leading to the emergence of large interspersed duplication blocks at non-orthologous chromosomal locations in each primate lineage. The intron-exon structure of the NPIP gene family has changed dramatically throughout primate evolution with different branches showing characteristic gene models yet maintaining an open reading frame. In the African ape lineage, we detect signatures of positive selection that occurred after a transition to more ubiquitous expression among great ape tissues when compared to Old World and New World monkeys. Mouse transgenic experiments from baboon and human genomic loci confirm these expression differences and suggest that the broader ape expression pattern arose due to mutational changes that emerged in cis. Conclusions LCR16a promotes serial interspersed duplications and creates hotspots of genomic instability that appear to be an ancient property of primate genomes. Dramatic changes to NPIP gene structure and altered tissue expression preceded major bouts of positive selection in the African ape lineage, suggestive of a gene undergoing strong adaptive evolution

    Host Glycan Sugar-Specific Pathways in Streptococcus pneumonia:Galactose as a Key Sugar in Colonisation and Infection

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    The human pathogen Streptococcus pneumoniae is a strictly fermentative organism that relies on glycolytic metabolism to obtain energy. In the human nasopharynx S. pneumoniae encounters glycoconjugates composed of a variety of monosaccharides, which can potentially be used as nutrients once depolymerized by glycosidases. Therefore, it is reasonable to hypothesise that the pneumococcus would rely on these glycan-derived sugars to grow. Here, we identified the sugar-specific catabolic pathways used by S. pneumoniae during growth on mucin. Transcriptome analysis of cells grown on mucin showed specific upregulation of genes likely to be involved in deglycosylation, transport and catabolism of galactose, mannose and N acetylglucosamine. In contrast to growth on mannose and N-acetylglucosamine, S. pneumoniae grown on galactose re-route their metabolic pathway from homolactic fermentation to a truly mixed acid fermentation regime. By measuring intracellular metabolites, enzymatic activities and mutant analysis, we provide an accurate map of the biochemical pathways for galactose, mannose and N-acetylglucosamine catabolism in S. pneumoniae. Intranasal mouse infection models of pneumococcal colonisation and disease showed that only mutants in galactose catabolic genes were attenuated. Our data pinpoint galactose as a key nutrient for growth in the respiratory tract and highlights the importance of central carbon metabolism for pneumococcal pathogenesis

    Pan-cancer Alterations of the MYC Oncogene and Its Proximal Network across the Cancer Genome Atlas

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    Although theMYConcogene has been implicated incancer, a systematic assessment of alterations ofMYC, related transcription factors, and co-regulatoryproteins, forming the proximal MYC network (PMN),across human cancers is lacking. Using computa-tional approaches, we define genomic and proteo-mic features associated with MYC and the PMNacross the 33 cancers of The Cancer Genome Atlas.Pan-cancer, 28% of all samples had at least one ofthe MYC paralogs amplified. In contrast, the MYCantagonists MGA and MNT were the most frequentlymutated or deleted members, proposing a roleas tumor suppressors.MYCalterations were mutu-ally exclusive withPIK3CA,PTEN,APC,orBRAFalterations, suggesting that MYC is a distinct onco-genic driver. Expression analysis revealed MYC-associated pathways in tumor subtypes, such asimmune response and growth factor signaling; chro-matin, translation, and DNA replication/repair wereconserved pan-cancer. This analysis reveals insightsinto MYC biology and is a reference for biomarkersand therapeutics for cancers with alterations ofMYC or the PMN

    Determination of σ(e+eπ+π)\sigma(e^+e^-\to \pi^+ \pi^-) from radiative processes at DAΦ\PhiNE

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    We have measured the cross section σ(e+eπ+πγ)\sigma(e^+e^-\to\pi^+\pi^-\gamma) with the KLOE detector at DAΦ\PhiNE, at an energy W=Mϕ=1.02W=M_\phi=1.02 GeV. From the dependence of the cross section on m(π+π)=W22WEγm(\pi^+\pi^-)=\sqrt{W^2-2WE_\gamma}, where EγE_\gamma is the energy of the photon radiated from the initial state, we extract σ(e+eπ+π)\sigma(e^+e^-\to\pi^+\pi^-) for the mass range 0.35<m2(π+π)<0.950.35<m^2(\pi^+\pi^-)<0.95 GeV2^2. From our result we extract the pion form factor and the hadronic contribution to the muon anomaly, aμa_\mu.Comment: Contributed paper to EPS 2003 and LP 200

    SARS-CoV-2 introductions and early dynamics of the epidemic in Portugal

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    Genomic surveillance of SARS-CoV-2 in Portugal was rapidly implemented by the National Institute of Health in the early stages of the COVID-19 epidemic, in collaboration with more than 50 laboratories distributed nationwide. Methods By applying recent phylodynamic models that allow integration of individual-based travel history, we reconstructed and characterized the spatio-temporal dynamics of SARSCoV-2 introductions and early dissemination in Portugal. Results We detected at least 277 independent SARS-CoV-2 introductions, mostly from European countries (namely the United Kingdom, Spain, France, Italy, and Switzerland), which were consistent with the countries with the highest connectivity with Portugal. Although most introductions were estimated to have occurred during early March 2020, it is likely that SARS-CoV-2 was silently circulating in Portugal throughout February, before the first cases were confirmed. Conclusions Here we conclude that the earlier implementation of measures could have minimized the number of introductions and subsequent virus expansion in Portugal. This study lays the foundation for genomic epidemiology of SARS-CoV-2 in Portugal, and highlights the need for systematic and geographically-representative genomic surveillance.We gratefully acknowledge to Sara Hill and Nuno Faria (University of Oxford) and Joshua Quick and Nick Loman (University of Birmingham) for kindly providing us with the initial sets of Artic Network primers for NGS; Rafael Mamede (MRamirez team, IMM, Lisbon) for developing and sharing a bioinformatics script for sequence curation (https://github.com/rfm-targa/BioinfUtils); Philippe Lemey (KU Leuven) for providing guidance on the implementation of the phylodynamic models; Joshua L. Cherry (National Center for Biotechnology Information, National Library of Medicine, National Institutes of Health) for providing guidance with the subsampling strategies; and all authors, originating and submitting laboratories who have contributed genome data on GISAID (https://www.gisaid.org/) on which part of this research is based. The opinions expressed in this article are those of the authors and do not reflect the view of the National Institutes of Health, the Department of Health and Human Services, or the United States government. This study is co-funded by Fundação para a Ciência e Tecnologia and Agência de Investigação Clínica e Inovação Biomédica (234_596874175) on behalf of the Research 4 COVID-19 call. Some infrastructural resources used in this study come from the GenomePT project (POCI-01-0145-FEDER-022184), supported by COMPETE 2020 - Operational Programme for Competitiveness and Internationalisation (POCI), Lisboa Portugal Regional Operational Programme (Lisboa2020), Algarve Portugal Regional Operational Programme (CRESC Algarve2020), under the PORTUGAL 2020 Partnership Agreement, through the European Regional Development Fund (ERDF), and by Fundação para a Ciência e a Tecnologia (FCT).info:eu-repo/semantics/publishedVersio

    Disrupted Functional Connectivity with Dopaminergic Midbrain in Cocaine Abusers

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    Background: Chronic cocaine use is associated with disrupted dopaminergic neurotransmission but how this disruption affects overall brain function (other than reward/motivation) is yet to be fully investigated. Here we test the hypothesis that cocaine addicted subjects will have disrupted functional connectivity between the midbrain (where dopamine neurons are located) and cortical and subcortical brain regions during the performance of a sustained attention task. Methodology/Principal Findings: We measured brain activation and functional connectivity with fMRI in 20 cocaine abusers and 20 matched controls. When compared to controls, cocaine abusers had lower positive functional connectivity of midbrain with thalamus, cerebellum, and rostral cingulate, and this was associated with decreased activation in thalamus and cerebellum and enhanced deactivation in rostral cingulate. Conclusions/Significance: These findings suggest that decreased functional connectivity of the midbrain interferes with the activation and deactivation signals associated with sustained attention in cocaine addicts

    Data acquisition and monitoring for the KLOE detector

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    none77siThe Data Acquisition system for the KLOE experiment, presently running at the Laboratori Nazionali di Frascati DAPhiNE collider, has been designed to sustain an acquisition throughput of 50 Mbyte/s for an event rate of 10 kHz. its two major components are the front end data readout, based on custom buses, and a complex network of computers and storage devices hosting a set of distributed processes. The end result is a seamless data transport from the readout system to the storage library, accompanied by concurrent on line calibrations and data quality control.openA. ALOISIO; F. AMBROSINO; S. CAVALIERE; F. CEVENINI; C. DI DONATO; A. DORIA; D. FIORE; L. MEROLA; G. PIROZZI; G. SARACINO; M. ANTONELLI; F. BOSSI; P. CIAMBRONE; P. DE SIMONE; S. DELL'AGNELLO; M.L. FERRER; G. FINOCCHIARO; C. FORTI; C. GATTI; S. GIOVANNELLA; W. GRANDEGGER; G. LANFRANCHI; B. MARTINI; W. MEI; S. MISCETTI; M. MOULSON; F. MURTAS; M. PALUTAN; L. PASSALACQUA; F. PELUCCHI; P. SANTANGELO; B. SCIASCIA; I. SFILIGOI; J. SHAN; T. SPADARO; P. VALENTE; Y ZHOU; C. BINI; V. BOCCI; G. CABIBBO; R. CALOI; A. CARDINI; E. DE LUCIA; A. DI DOMENICO; P. GAUZZI; E. PASQUALUCCI; M. PASSASEO; D. PICCA; L. PONTECORVO; E. VALENTE; S. VENEZIANO; P. BRANCHINI; E. GRAZIANI; A. PASSERI; A. FERRARI; E. SPIRITI; C. STANESCU; L. TORTORA; M. CASARSA; G. CATALDI; E. GORINI; M. PRIMAVERA; A. VENTURA; G. DE ROBERTIS; P. GUARNACCIA; A. DENIG; CHEN-CHENG KUO; S. MULLER; B. VALERIANI; S. DI FALCO; M. INCAGLI; G. VENANZONI; R. MESSI; L. PACCIANI; E. SANTOVETTI; J. LEE-FRANZINI; M. MARTEMIANOVA., Aloisio; F., Ambrosino; S., Cavaliere; F., Cevenini; C., DI DONATO; A., Doria; D., Fiore; L., Merola; G., Pirozzi; G., Saracino; M., Antonelli; F., Bossi; P., Ciambrone; P., DE SIMONE; S., Dell'Agnello; M. L., Ferrer; G., Finocchiaro; C., Forti; C., Gatti; S., Giovannella; W., Grandegger; G., Lanfranchi; B., Martini; W., Mei; S., Miscetti; M., Moulson; F., Murtas; M., Palutan; L., Passalacqua; F., Pelucchi; P., Santangelo; B., Sciascia; I., Sfiligoi; J., Shan; T., Spadaro; P., Valente; Y., Zhou; C., Bini; V., Bocci; G., Cabibbo; R., Caloi; A., Cardini; E., DE LUCIA; A., DI DOMENICO; P., Gauzzi; E., Pasqualucci; M., Passaseo; D., Picca; L., Pontecorvo; E., Valente; S., Veneziano; P., Branchini; E., Graziani; A., Passeri; A., Ferrari; E., Spiriti; C., Stanescu; L., Tortora; M., Casarsa; G., Cataldi; Gorini, Edoardo; Primavera, Margherita; Ventura, Andrea; G., DE ROBERTIS; P., Guarnaccia; A., Denig; CHEN CHENG, Kuo; S., Muller; B., Valeriani; S., DI FALCO; M., Incagli; G., Venanzoni; R., Messi; L., Pacciani; E., Santovetti; J., LEE FRANZINI; M., Martemiano