FloodAlert: a simplified radar-based EWS for urban flood warning

In this work we present FloodAlert, a simplified flood Early Warning System [EWS] based on the use of radar observations and radar nowcasting to issue local flood warnings. It is a web-based platform and it is complemented with a flexible and powerful dissemination module.Postprint (author’s final draft

WiBasin: basin management through an integrated platform

In this work we present WiBasin, a cloud platform for basin and dam management. It includes different sources of precipitation (both observed and forecasted), integration over the catchment domain (to provide an aggregated value of potential rainfall accumulated over the basin) , and a complete dissemination environment (web-viewer, capability of issuing hazard warnings with configurable thresholds, SMS, mails, etc.)Peer ReviewedPostprint (author’s final draft

The angiotensin-(1-7)/mas axis counteracts angiotensin II-dependent and -independent pro-inflammatory signaling in human vascular smooth muscle cells

Background and Aims: Targeting inflammation is nowadays considered as a challenging pharmacological strategy to prevent or delay the development of vascular diseases. Angiotensin-(1-7) is a member of the renin-angiotensin system (RAS) that binds Mas receptors and has gained growing attention in the last years as a regulator of vascular homeostasis. Here, we explored the capacity of Ang-(1-7) to counteract human aortic smooth muscle cell (HASMC) inflammation triggered by RAS-dependent and -independent stimuli, such as Ang II or interleukin (IL)-1β. Methods and Results: In cultured HASMC, the expression of inducible nitric oxide synthase (iNOS) and the release of nitric oxide were stimulated by both Ang II and IL-1β, as determined by Western blot and indirect immunofluorescence or the Griess method, respectively. iNOS induction was inhibited by Ang-(1-7) in a concentration-dependent manner. This effect was equally blocked by two different Mas receptor antagonists, A779 and D-Pro7-Ang-(1-7), suggesting the participation of a unique Mas receptor subtype. Using pharmacological inhibitors, the induction of iNOS was proven to rely on the consecutive upstream activation of NADPH oxidase and nuclear factor (NF)-κB. Indeed, Ang-(1-7) markedly inhibited the activation of the NADPH oxidase and subsequently of NF-κB, as determined by lucigenin-derived chemiluminescence and electromobility shift assay, respectively. Conclusion: Ang-(1-7) can act as a counter-regulator of the inflammation of vascular smooth muscle cells triggered by Ang II, but also by other stimuli beyond the RAS. Activating or mimicking the Ang-(1-7)/Mas axis may represent a pharmacological opportunity to attenuate the pro-inflammatory environment that promotes and sustains the development of vascular diseases.This work was funded by grants from Ministerio de Economía y Competitividad (SAF2014-52762-R

The angiotensin-(1-7)/Mas receptor a xis protects from endothelial cell senescence via klotho and Nrf2 activation

Endothelial cell senescence is a hallmark of va scular aging that pre disposes to vascular disease. We aimed to explore the capacity of the renin-angiotensin system (RAS) heptapeptide angiotensin (Ang)-(1-7) to counteract human endothelial cell senescence and to identify intracellular pathways mediati ng its potential protective action. In human umbilical vein endothelial cell (HUVEC) cult ures, Ang II promoted cell senescence, as revealed by the enhancement in se nescence-associated galactosidase (SA- -gal+) positive staining, total and telomeric DNA damage, adhesion molecules expression and human mononuclear adhesion to HUVEC monolaye rs. By activating the G-coupled receptor Mas, Ang-(1-7) inhibit ed the pro-senescence action of Ang II, but also of a non- RAS stressor such as the cytokine IL-1 . Moreover, Ang-(1-7) enhanced endothelial klotho levels, while klotho silencing resulted in th e loss of the anti-senescence action of the heptapeptide. Indeed, both Ang-(1-7) and recombinant klotho activated the cytoprotective Nrf2/heme-oxygenase-1 (HO)-1 pathway. The HO-1 inhibitor tin protoporphyrin IX prevented the anti-senescence action evoked by Ang-(1-7) or recombinant klotho. Overall, the present study ide ntifies Ang-(1-7) as an anti-senescence peptide displaying its protectiv e action beyond the RAS by consecutively activating klotho and Nrf2/HO-1. Ang-(1-7) mimetic dru gs may thus prove useful to prevent endothelial cell senescence and its re lated vascular complications

Metal-doped imine frameworks for the oxygen reduction reaction in acidic media

11 pags., 7 figs., 2 tabs.The overall performance of proton exchange membrane fuel cells is limited by the sluggish kinetics of the oxygen-reduction reaction (ORR). Among the most active PGM-free ORR electrocatalysts are metal-nitrogen-carbon (M-N-C), such as Fe–N–C. The Fe–N4 ensembles in these PGM-free catalysts, present in different configurations, are proposed to be the active sites for the ORR in acid. In this work, we have synthesized a Fe/N/C catalyst via thermal treatment of a polymeric CxNy precursor obtained by the wet-polymerization of melamine (a nitrogen rich molecule) and terephthaldehyde. The materials obtained (Im-FeNC-1HT and Im-FeNC-2HT) display high ORR activity in acid electrolyte compared to other Fe–N–C catalysts prepared with precursors different than 2-methylimidazole or ZIF-8. Characterization data indicate the formation of high- and low-spin Fe-Nx ensembles, with a site density of 4.4·1019 sitesFe·g−1 estimated by electrochemical stripping of NO. The ORR activity was evaluated in a RRDE configuration in 0.1 M HClO4 and in MEA configuration in a single cell.Financial support from PID2020-116712RB-C21 funded by MCIN/AEI/10.13039/501100011033 is acknowledged. The Deputyship for Research & Innovation, Ministry of Education of Saudi Arabia is acknowledged for funding this research work through the project number 341. We also thank the Consejería de Educación, Juventud y Deporte of the Comunidad de Madrid for the Ayuda Destinada a la Atracción de Talento Investigador (2020-T2/AMB-19927) granted to Álvaro Tolosana Moranchel. The single-cell testing was possible thanks to the Margarita Salas grant (REGAGE21e00017738309) given to Álvaro García Corral, distributed by the Spanish Ministry of Universities in the frame of the NextGenerationEU program. This work was carried out with the support of Diamond Light Source, Beamline B07 B branch (proposal SI30338).Peer reviewe

Identification of Predictive Biomarkers of Response to HSP90 Inhibitors in Lung Adenocarcinoma

Heat shock protein 90 (HSP90) plays an essential role in lung adenocarcinoma, acting as a key chaperone involved in the correct functioning of numerous highly relevant protein drivers of this disease. To this end, HSP90 inhibitors have emerged as promising therapeutic strategies, even though responses to them have been limited to date. Given the need to maximize treatment efficacy, the objective of this study was to use isobaric tags for relative and absolute quantitation (iTRAQ)-based proteomic techniques to identify proteins in human lung adenocarcinoma cell lines whose basal abundances were correlated with response to HSP90 inhibitors (geldanamycin and radicicol derivatives). From the protein profiles identified according to response, the relationship between lactate dehydrogenase B (LDHB) and DNA topoisomerase 1 (TOP1) with respect to sensitivity and resistance, respectively, to geldanamycin derivatives is noteworthy. Likewise, rhotekin (RTKN) and decaprenyl diphosphate synthase subunit 2 (PDSS2) were correlated with sensitivity and resistance to radicicol derivatives. We also identified a relationship between resistance to HSP90 inhibition and the p53 pathway by glucose deprivation. In contrast, arginine biosynthesis was correlated with sensitivity to HSP90 inhibitors. Further study of these outcomes could enable the development of strategies to improve the clinical efficacy of HSP90 inhibition in patients with lung adenocarcinoma

Pharmacological Blockade of NLRP3 Inflammasome/IL1β-Positive Loop Mitigates Endothelial Cell Senescence and Dysfunction

The clinical relevance of IL-1β in chronic inflammation underlying atherosclerosis has been reinforced by recent evidence associating pharmacological inhibition of the cytokine with lower cardiovascular risk. Previously, we have demonstrated a direct involvement of IL-1β in endothelial senescence. Therefore, this can be a key mechanism contributing to the sterile inflammatory milieu associated with aging, termed inflammaging. In the present study, we have evaluated whether a positive feedback of IL-1β in the NLRP3 inflammasome via NF-κB could promote human endothelial senescence in vitro and murine endothelial dysfunction in vivo. Our results indicate that the NLRP3 inflammasome is pivotal in mediating the detrimental effects of IL-1β, showing that auto-activation is a crucial feature boosting endothelial cell senescence in vitro, which is paralleled by vascular dysfunction in vivo. Hence, the inhibitor of NLRP3 inflammasome assembly, MCC 950, was able to disrupt the aforementioned positive loop, thus alleviating inflammation, cell senescence and vascular dysfunction. Besides, we explored alternative NLRP3 inflammasome inhibitory agents such as the RAS heptapeptide Ang-(1-7) and the anti-aging protein klotho, both of which demonstrated protective effects in vitro and in vivo. Altogether, our results highlight a fundamental role for the hereby described NLRP3 inflammasome/IL-1β positive feedback loop in stress-induced inflammaging and the associated vascular dysfunction, additionally providing evidence of a potential therapeutic use of MCC 950, Ang-(1-7) and recombinant klotho to block this loop and its deleterious effectsThis work has been supported by funding from 1) Plan Nacional I+D (PID2020-115590RB100/AEI/ 10.13039/501100011033) to C.P. and C.F.S-F; 2) Talent Advanced Researchers' Grant from Comunidad Autónoma de Madrid (2019-T1/IND-13794) to F.C., and 3) FONDECYT 1130300 to G.D.A. P.D. is recipient of a European social fund and Comunidad Autónoma de Madrid fellowship (PEJ-2018-AI/SAL-9955). I.V. is supported by an FPU-MECD fellowship (FPU16/02612

Clinical evaluation of antiseptic mouth rinses to reduce salivary load of SARS-CoV-2

Most public health measures to contain the COVID-19 pandemic are based on preventing the pathogen spread, and the use of oral antiseptics has been proposed as a strategy to reduce transmission risk. The aim of this manuscript is to test the efficacy of mouthwashes to reduce salivary viral load in vivo. This is a multi-centre, blinded, parallel-group, placebo-controlled randomised clinical trial that tests the effect of four mouthwashes (cetylpyridinium chloride, chlorhexidine, povidone-iodine and hydrogen peroxide) in SARS-CoV-2 salivary load measured by qPCR at baseline and 30, 60 and 120 min after the mouthrinse. A fifth group of patients used distilled water mouthrinse as a control. Eighty-four participants were recruited and divided into 12-15 per group. There were no statistically significant changes in salivary viral load after the use of the different mouthwashes. Although oral antiseptics have shown virucidal effects in vitro, our data show that salivary viral load in COVID-19 patients was not affected by the tested treatments. This could reflect that those mouthwashes are not effective in vivo, or that viral particles are not infective but viral RNA is still detected by PCR. Viral infectivity studies after the use of mouthwashes are therefore required

Reliability of a novel electro-medical device for wheal size measurement in allergy skin testing: An exploratory clinical trial

Skin prick testing (SPT) is the cornerstone of IgE-mediated allergy diagnosis,1 due to its high sensitivity and specificity.2 However, a uniform method for wheal measurement does not exist. Ansotegui et al.2 recommends to measure wheals in millimeters with a ruler, in many centers they are outlined with a pen and transfer by tape to a paper and then measured. Subsequently, the specialist is able to manually measure the maximum (MD) and orthogonal diameter (OD) of the wheal. This procedure is time consuming and makes repro-ducible measurements difficult.2,3 Knowing the wheal's area could help make a more accurate diagnosis.4 Over the last 30 years, many attempts have been made to develop a device to measure the size of SPT.3 Nexkin DSPT® (Figure S1A,B) is a novel mechatronic system based on 3D laser technology, that automatically locates allergen's wheal and measures its size (MD, OD and area in square millimeters) (Figure S1C)

Assessing management models for off-grid renewable energy electrification projects using the Human Development approach: Case study in Peru

Electrification systems based on renewable energy have proven suitable for providing electricity autonomously to rural communities, thus reducing poverty. When implementing these systems, a management model is usually designed to maximise technical and financial sustainability. Different evaluations of management models have been made that usually centre on products and final utilities. However, this excessively utilitarian vision of development restricts an analysis of the impact that these projects may have on people s lives. To overcome these limitations, we have used the Human Development approach to evaluate the management model of five electrification projects that use different technologies in Cajamarca (Peru). This approach enables a broader assessment of various key dimensions of development that should be considered in the management model. The results show the weaknesses of the design and implementation process of the management model. Several ideas are proposed to avoid these weaknesses and to maximise the chance of success.Lillo Rodrigo, P.; Ferrer Martí, L.; Boni Aristizábal, A.; Fernández-Baldor, Á. (2015). Assessing management models for off-grid renewable energy electrification projects using the Human Development approach: Case study in Peru. Energy for Sustainable Development. 25:17-26. doi:10.1016/j.esd.2014.11.003S17262