HARMONIA: strategy of an integrated resilience assessment platform (IRAP) with available tools and geospatial services

The huge amount of the available data nowadays has raised some major challenges which are related to the storage, fusion, structure, streaming and processing of these data. In this paper, we present the development of a holistic framework, entitled HARMONIA, that encompasses State-of-The-Art solutions for the emerging issues related to Climate Change, natural and/or man-made hazards and urban/peri-urban risks. The Horizon 2020 HARMONIA project is developing an Integrated Resilience Assessment Platform (IRAP) which plans to provide targeted services for different groups of end-users. In particular, it will actively support urban decision-makers in strategic decisions and planning and citizens in facing daily effects and risks of Climate Change. Additionally, the platform will be a place to interconnect cities which end up facing similar Climate Change effects. HARMONIA IRAP leverages cuttingedge technologies (i.e., explainable Artificial Intelligence, Data Mining, multi-criteria analysis, dynamic programming) and services (ie., Virtual Machines, Containers) in order to provide solutions considering the complexity and diversity of extreme earth and non-earth data. In addition, this platform includes a Decision Support System providing early-warning feedback and recommendations to the end-users. In this way the HARMONIA IRAP design tends to address these challenges by offering the corresponding dynamic, scalable and robust mechanisms with the aim to provide useful integrated tools for the related users. Datacubes architecture, which is a major part of the IRAP, offers the opportunity to investigate more sophisticated correlations among the data and provide a more tangible representation of the extracted information

OCT2013, an ischaemia-activated antiarrhythmic prodrug, devoid of the systemic side effects of lidocaine

Background and Purpose Sudden cardiac death (SCD) caused by acute myocardial ischaemia and ventricular fibrillation (VF) is an unmet therapeutic need. Lidocaine suppresses ischaemia-induced VF, but its utility is limited by side effects and a narrow therapeutic index. Here, we characterise OCT2013, a putative ischaemia-activated prodrug of lidocaine. Experimental Approach The rat Langendorff-perfused isolated heart, anaesthetised rat and rat ventricular myocyte preparations were utilised in a series of blinded and randomised studies to investigate the antiarrhythmic effectiveness, adverse effects and mechanism of action of OCT2013, compared with lidocaine. Key Results In isolated hearts, OCT2013 and lidocaine prevented ischaemia-induced VF equi-effectively, but OCT2013 did not share lidocaine's adverse effects (PR widening, bradycardia and negative inotropy). In anaesthetised rats, i.v. OCT2013 and lidocaine suppressed VF and increased survival equi-effectively; OCT2013 had no effect on cardiac output even at 64 mg·kg⁻¹ i.v., whereas lidocaine reduced it even at 1 mg·kg⁻¹. In adult rat ventricular myocytes, OCT2013 had no effect on Ca²⁺ handling, whereas lidocaine impaired it. In paced isolated hearts, lidocaine caused rate-dependent conduction slowing and block, whereas OCT2013 was inactive. However, during regional ischaemia, OCT2013 and lidocaine equi-effectively hastened conduction block. Chromatography and MS analysis revealed that OCT2013, detectable in normoxic OCT2013-perfused hearts, became undetectable during global ischaemia, with lidocaine becoming detectable. Conclusions and Implications OCT2013 is inactive but is bio-reduced locally in ischaemic myocardium to lidocaine, acting as an ischaemia-activated and ischaemia-selective antiarrhythmic prodrug with a large therapeutic index, mimicking lidocaine's benefit without adversity

The contrasted phytoplankton dynamics across a frontal system in the southwestern Mediterranean Sea

Numerical simulations have shown that finescale structures such as fronts are often suitable places for the generation of vertical velocities, transporting subsurface nutrients to the euphotic zone and thus modulating phytoplankton abundance and community structure. In these structures, direct in situ estimations of the phytoplankton growth rates are rare; although difficult to obtain, they provide precious information on the ecosystem functioning. Here, we consider the case of a front separating two water masses characterized by several phytoplankton groups with different abundances in the southwestern Mediterranean Sea. In order to estimate possible differences in growth rates, we measured the phytoplankton diurnal cycle in these two water masses as identified by an adaptive and Lagrangian sampling strategy. A size-structured population model was then applied to these data to estimate the growth and loss rates for each phytoplankton group identified by flow cytometry, showing that these two population parameters are significantly different on the two sides of the front and consistent with the relative abundances. Our results introduce a general method for estimating growth rates at frontal systems, paving the way for in situ exploration of finescale biophysical interactions.</p

UV spectrophotometry method for the monitoring of galacto-oligosaccharides production

Monitoring the industrial production of galacto-oligosaccharides (GOS) requires a fast and accurate methodology able to quantify, in real time, the substrate level and the product yield. In this work, a simple, fast and inexpensive UV spectrophotometric method, together with partial least squares regression (PLS) and artificial neural networks (ANN), was applied to simultaneously estimate the products (GOS) and the substrate (lactose) concentrations in fermentation samples. The selected multiple models were trained and their prediction abilities evaluated by cross-validation and external validation being the results obtained compared with HPLC measurements. ANN models, generated from absorbance spectra data of the fermentation samples, gave, in general, the best performance being able to accurately and precisely predict lactose and total GOS levels, with standard error of prediction lower than 13 g kg 1 and coefficient of determination for the external validation set of 0.93–0.94, showing residual predictive deviations higher than five, whereas lower precision was obtained with the multiple model generated with PLS. The results obtained show that UV spectrophotometry allowed an accurate and non-destructive determination of sugars in fermentation samples and could be used as a fast alternative method for monitoring GOS production.Fundação para a Ciência e a Tecnologia (FCT) - Bolsa de doutouramento SFRH/BDE/15510/2004Agência da Inovação – Programa IDEIA (Potugal

Prebiotic feeding elevates central brain derived neurotrophic factor, N-methyl-D-aspartate receptor subunits and D-serine

The influence of the gut microbiota on brain chemistry has been convincingly demonstrated in rodents. In the absence of gut bacteria, the central expression of brain derived neurotropic factor, (BDNF), and N-methyl-d-aspartate receptor (NMDAR) subunits are reduced, whereas, oral probiotics increase brain BDNF, and impart significant anxiolytic effects. We tested whether prebiotic compounds, which increase intrinsic enteric microbiota, also affected brain BDNF and NMDARs. In addition, we examined whether plasma from prebiotic treated rats released BDNF from human SH-SY5Y neuroblastoma cells, to provide an initial indication of mechanism of action. Rats were gavaged with fructo-oligosaccharides (FOS), galacto-oligosaccharides (GOS) or water for five weeks, prior to measurements of brain BDNF, NMDAR subunits and amino acids associated with glutamate neurotransmission (glutamate, glutamine, and serine and alanine enantiomers). Prebiotics increased hippocampal BDNF and NR1 subunit expression relative to controls. The intake of GOS also increased hippocampal NR2A subunits, and frontal cortex NR1 and d-serine. Prebiotics did not alter glutamate, glutamine, l-serine, l-alanine or d-alanine concentrations in the brain, though GOSfeeding raised plasma d-alanine. Elevated levels of plasma peptide YY (PYY) after GOS intake was observed. Plasma from GOS rats increased the release of BDNF from SH-SY5Y cells, but not in the presence of PYY antisera. The addition of synthetic PYY to SH-SY5Y cell cultures, also elevated BDNF secretion. We conclude that prebiotic-mediated proliferation of gut microbiota in rats, like probiotics, increases brain BDNF expression, possibly through the involvement of gut hormones. The effect of GOS on components of central NMDAR signalling was greater than FOS, and may reflect the proliferative potency of GOS on microbiota. Our data therefore, provide a sound basis to further investigate the utility of prebiotics in the maintenance of brain health and adjunctive treatment of neuropsychiatric disorders

CLSM method for the dynamic observation of pH change within polymer matrices for oral delivery

If acid-sensitive drugs or cells are administered orally, there is often a reduction in efficacy associated with gastric passage. Formulation into a polymer matrix is a potential method to improve their stability. The visualization of pH within these materials may help better understand the action of these polymer systems and allow comparison of different formulations. We herein describe the development of a novel confocal laser-scanning microscopy (CLSM) method for visualizing pH changes within polymer matrices and demonstrate its applicability to an enteric formulation based on chitosan-coated alginate gels. The system in question is first shown to protect an acid-sensitive bacterial strain to low pH, before being studied by our technique. Prior to this study, it has been claimed that protection by these materials is a result of buffering, but this has not been demonstrated. The visualization of pH within these matrices during exposure to a pH 2.0 simulated gastric solution showed an encroachment of acid from the periphery of the capsule, and a persistence of pHs above 2.0 within the matrix. This implies that the protective effect of the alginate-chitosan matrices is most likely due to a combination of buffering of acid as it enters the polymer matrix and the slowing of acid penetration