5,842 research outputs found

    Stability of the transthyretin molecule as a key factor in the interaction with a-beta peptide--relevance in Alzheimer's disease

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    Transthyretin (TTR) protects against A-Beta toxicity by binding the peptide thus inhibiting its aggregation. Previous work showed different TTR mutations interact differently with A-Beta, with increasing affinities correlating with decreasing amyloidogenecity of the TTR mutant; this did not impact on the levels of inhibition of A-Beta aggregation, as assessed by transmission electron microscopy. Our work aimed at probing differences in binding to A-Beta by WT, T119M and L55P TTR using quantitative assays, and at identifying factors affecting this interaction. We addressed the impact of such factors in TTR ability to degrade A-Beta. Using a dot blot approach with the anti-oligomeric antibody A11, we showed that A-Beta formed oligomers transiently, indicating aggregation and fibril formation, whereas in the presence of WT and T119M TTR the oligomers persisted longer, indicative that these variants avoided further aggregation into fibrils. In contrast, L55PTTR was not able to inhibit oligomerization or to prevent evolution to aggregates and fibrils. Furthermore, apoptosis assessment showed WT and T119M TTR were able to protect against A-Beta toxicity. Because the amyloidogenic potential of TTR is inversely correlated with its stability, the use of drugs able to stabilize TTR tetrameric fold could result in increased TTR/ABeta binding. Here we showed that iododiflunisal, 3-dinitrophenol, resveratrol, [2-(3,5-dichlorophenyl)amino] (DCPA) and [4- (3,5-difluorophenyl)] (DFPB) were able to increase TTR binding to A-Beta; however only DCPA and DFPB improved TTR proteolytic activity. Thyroxine, a TTR ligand, did not influence TTR/A-Beta interaction and A-Beta degradation by TTR, whereas RBP, another TTR ligand, not only obstructed the interaction but also inhibited TTR proteolytic activity. Our results showed differences between WT and T119M TTR, and L55PTTR mutant regarding their interaction with A-Beta and prompt the stability of TTR as a key factor in this interaction, which may be relevant in AD pathogenesis and for the design of therapeutic TTR-based therapies

    Sub-shot-noise photon-number correlation in mesoscopic twin-beam of light

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    We demonstrate sub-shot-noise photon-number correlations in a (temporal) multimode mesoscopic (103\sim 10^3 detected photons) twin-beam produced by ps-pulsed spontaneous non-degenerate parametric downconversion. We have separately detected the signal and idler distributions of photons collected in twin coherence areas and found that the variance of the photon-count difference goes below the shot-noise limit by 3.25 dB. The number of temporal modes contained in the twin-beam, as well as the size of the twin coherence areas, depends on the pump intensity. Our scheme is based on spontaneous downconversion and thus does not suffer from limitations due to the finite gain of the parametric process. Twin-beams are also used to demonstrate the conditional preparation of a nonclassical (sub-Poissonian) state.Comment: 5 pages, 5 (low-res) figures, to appear on PR

    Creating shared value in Rock in Rio business model: case study

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    This discourse will attempt to discuss `Creation of Shared Value' (CSV) through the case study of the music festival "Rock in Rio" (RIR) in order to further understand the company's sustainability program. The main goal is to clearly recognize if RIR uses a genuine practice of CSV to accomplish their social policies. To commence, we started with the State of Art, studying the CSV theory created by Porter and Kramer, as well as the authors that were either in support of, or against, the strategy. Qualitative Research Method was used, thus focusing the enterprise case study, by analysing media interviews given by the managerial staff of RIR. Content analysis was used to process data and deliver results. The main limitation of the study was the lack of institutional information, due to an absence of responses, to the survey in sufficient time by RIR's managers, subsequently a triangulation of the information acquired could not be achieved.info:eu-repo/semantics/acceptedVersio

    A Knowledge Based System for Supporting Sustainable Industrial Management in a Clothes Manufacturing Company Based on a Data Fusion Model

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    In this paper we propose a knowledge based system (KBS), based on smart objects and a data fusion model to support industrial management decision making applied to a clothes manufacturing enterprise. The management processes cover factory-production levels to higher decision-making levels. Therefore, the proposed KBS contributes to solving different kind of decision problems, including factory supervision, production planning and control, productivity management, real-time monitoring, and data acquisition and processing. The web access via different middleware devices and tools at different process levels, along with the use of integrated algorithms, decision methods, and smart objects, promote an optimized use of knowledge and resources. In this paper the proposed KBS is introduced and an example of its use is illustrated with an example of a clothes manufacturing resources selection, using the embedded dynamic multi-criteria fusion model.This work was supported by FCT “Fundação para a Ciência e a Tecnologia” under the program: PEST2015-2020, reference: UID/CEC/00319/2013.info:eu-repo/semantics/publishedVersio

    Zircon dating and inheritance of a pre-Variscan granite, SW Iberia

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    The Portalegre pluton is an aligned series of Pre-Variscan granitoids located along the boundary of the Central Iberian/ Ossa Morena Zones (SW Iberian Massif, Portugal). Singlezircon geochronology (U-Pb SHRIMP and Pb/Pb stepwise evaporation) yield an Upper Cambrian/Lower Ordovician age (492.7 ± 3.5 Ma) interpreted as the magmatic crystallization age. The inherited zircon cores indicate the involvement of sources with a wide range age-components: an important Late Neoproterozoic (548 ± 7 Ma and c. 611-681 Ma) population and a Mesoproterozoic (c. 0.95-1.1 Ga) and older (c. 2.6 Ga) components. Younger zircon ages of 358 ± 36 and 387 ± 7 Ma were also found and interpreted as the record of a Variscan metamorphic event. The presence of Grenvillian zirconforming events in the protholiths of Portalegre granites is significant in the regional geodynamic context of the Iberian Massif (Central Iberian affinity?). At present, the Grenvillian ages are not noticeable in the Late Neoproterozoic/Early Cambrian record of the Ossa-Morena Zone, that has been correlated with West African Craton [1]. These data suggests that the Central Iberian Zone and Ossa-Morena Zone were independent peri-gondwana terrains with diferent paleogeographic affinities before the Ordovician times. The overall chemistry for the Portalegre granites shows they are very differentiated (SiO2=74-76 wt %), peraluminous (A/CNK=1.1–1.4); have low Zr=36-125ppm, Th/Ta=2-10, ΣREE= 22-134 and 1000Ga/Al >3. Their isotopic signatures (87Sr/86Sr)493=0.7050-0.7065, εNd493(-2.88 to -0.85) and δ18O=10.5-10.8‰, are compatible with partial melting of relatively young recycled metaigneous ± enriched mantle sources. The age pattern from the inherited zircon cores in the Portalegre granites shows that the late Neoproterozoic age (Cadomian) basement was actively involved in their magma generation. The Grenvillian and Archaean zircons can be accounted for by that source component but they do not imply the presence of an older pre-Neoproterozoic basement rocks beneath SW Iberia
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