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The COVID-19 pandemic has shaken the world since the beginning of 2020. Spain is among the European countries with the highest incidence of the disease during the first pandemic wave. We established a multidisciplinar consortium to monitor and study the evolution of the epidemic, with the aim of contributing to decision making and stopping rapid spreading across the country. We present the results for 2170 sequences from the first wave of the SARS-Cov-2 epidemic in Spain and representing 12% of diagnosed cases until 14th March. This effort allows us to document at least 500 initial introductions, between early February-March from multiple international sources. Importantly, we document the early raise of two dominant genetic variants in Spain (Spanish Epidemic Clades), named SEC7 and SEC8, likely amplified by superspreading events. In sharp contrast to other non-Asian countries those two variants were closely related to the initial variants of SARS-CoV-2 described in Asia and represented 40% of the genome sequences analyzed. The two dominant SECs were widely spread across the country compared to other genetic variants with SEC8 reaching a 60% prevalence just before the lockdown. Employing Bayesian phylodynamic analysis, we inferred a reduction in the effective reproductive number of these two SECs from around 2.5 to below 0.5 after the implementation of strict public-health interventions in mid March. The effects of lockdown on the genetic variants of the virus are reflected in the general replacement of preexisting SECs by a new variant at the beginning of the summer season. Our results reveal a significant difference in the genetic makeup of the epidemic in Spain and support the effectiveness of lockdown measures in controlling virus spread even for the most successful genetic variants. Finally, earlier control of SEC7 and particularly SEC8 might have reduced the incidence and impact of COVID-19 in our country., This work was funded by the Instituto de Salud Carlos III project COV20/00140, Spanish 593 National Research Council project CSIC-COV19-021 and ERC StG 638553 to IC, and BFU2017- 594 89594R to FGC. MC is supported by Ramón y Cajal program from Ministerio de Ciencia and 595 grants RTI2018-094399-A-I00 and SEJI/2019/011. 596 We gratefully acknowledge Hospital Universitari Vall d'Hebron, Instituto de Salud Carlos 597 III, IrsiCaixa AIDS Research Lab and all the international researchers and institutions that 598 submitted sequenced SARS-CoV-2 genomes to the GISAID’s EpiCov™ Database, as an 599 important part of our analyses have been made possible by the share of their work.

33 páginas, 2 tablas, 4 figuras, Background and aims: The number of plastome sequences has increased exponentially during the last decade. However, there is still little knowledge of the levels and distribution of intraspecific variation. The aims of this study were to estimate plastome diversity within Zea mays and analyse the distribution of haplotypes in connection with the landrace groups previously delimited for South American maize based on nuclear markers. Methods: We obtained the complete plastomes of 30 South American maize landraces and three teosintes by means of next-generation sequencing (NGS) and used them in combination with data from public repositories. After quality filtering, the curated data were employed to search for single-nucleotide polymorphisms, indels and chloroplast simple sequence repeats. Exact permutational contingency tests were performed to assess associations between plastome and nuclear variation. Network and Bayesian phylogenetic analyses were used to infer evolutionary relationships among haplotypes. Key results: Our analyses identified a total of 124 polymorphic plastome loci, with the intergenic regions psbE-rps18, petN-rpoB, trnL_UAG-ndhF and rpoC2-atpI exhibiting the highest marker densities. Although restricted in number, these markers allowed the discrimination of 27 haplotypes in a total of 51 Zea mays individuals. Andean and lowland South American landraces differed significantly in haplotype distribution. However, overall differentiation patterns were not informative with respect to subspecies diversification, as evidenced by the scattered distribution of maize and teosinte plastomes in both the network and Bayesian phylogenetic reconstructions. Conclusions: Knowledge of intraspecific plastome variation provides the framework for a more comprehensive understanding of evolutionary processes at low taxonomic levels and may become increasingly important for future plant barcoding efforts. Whole-plastome sequencing provided useful variability to contribute to maize phylogeographic studies. The structuring of haplotype diversity in the maize landraces examined here clearly reflects the distinction between the Andean and South American lowland gene pools previously inferred based on nuclear markers., This work was supported by the Agencia Nacional de Promoción Científica y Técnica (PICT 2012 0325, PICT 2016 1101), the Consejo Nacional de Investigaciones Científicas y Tecnológicas (PIP 11220120100416CO 2013–2015), the Instituto Nacional de Tecnología Agropecuaria (PNBIO 1131044) and the DEANN Project.

La industria alimentaria alrededor del mundo tiene la necesidad de sustituir los aditivos artificiales o sintéticos por alternativas naturales, debido a la demanda de los consumidores de ingredientes alimentarios naturales. En la búsqueda de proponer alternativas que coadyuven a esta problemática se evaluó la actividad hemolítica, antimicrobiana y antioxidante, así como la concentración de compuestos fenólicos totales y antocianinas monoméricas totales de extractos acuosos de cálices de jamaica de nueve variedades, cultivadas en los estados mexicanos Nayarit, Oaxaca y Puebla. La mayor concentración de compuestos fenólicos totales (CFT), antocianinas monoméricas totales (AMT) y actividad antioxidante por diversos métodos (DPPH·, ABTS·+, FRAP y ORAC) la presentó el extracto de la variedad de jamaica ‘cruza negra’ de Nayarit, la cual a una concentración de 20,000 µg/mL promovió una reducción en la velocidad de crecimiento de una cepa de Escherichia coli hasta en 51 % respecto al control. Por otra parte, la actividad hemolítica se mantuvo cercana al 1% aún con una concentración de 6000 µg de CFT/mL. Por lo anterior, se puede proponer el uso de los extractos acuosos de cálices de jamaica como un aditivo alimentario de origen natural, antioxidante, antimicrobiano y con muy baja actividad hemolítica.

Highly branched neo-fructans (agavins) are natural prebiotics found in Agave plants, with a large capacity to mitigate the development of obesity and metabolic syndrome. Here, we investigated the impact of agavins intake on gut microbiota modulation and their metabolites as well as their effect on metabolic endotoxemia and low-grade inflammation in mice fed high-fat diet. Mice were fed with a standard diet (ST) and high-fat diet (HF) alone or plus an agavins supplement (HF+A) for ten weeks. Gut microbiota composition, fecal metabolite profiles, lipopolysaccharides (LPS), pro-inflammatory cytokines, and systemic effects were analyzed. Agavins intake induced substantial changes in gut microbiota composition, enriching Bacteroides, Parabacteroides, Prevotella, Allobaculum, and Akkermansia genus (LDA > 3.0). l-leucine, l-valine, uracil, thymine, and some fatty acids were identified as possible biomarkers for this prebiotic supplement. As novel findings, agavins supplementation significantly decreased LPS and pro-inflammatory (IL-1α, IL-1β, and TNF-α; p < 0.05) cytokines levels in portal vein. In addition, lipid droplets content in the liver and adipocytes size also decreased with agavins consumption. In conclusion, agavins supplementation mitigate metabolic endotoxemia and low-grade inflammation in association with gut microbiota regulation and their metabolic products, thus inducing beneficial responses on metabolic disorders in high-fat diet-fed mice.

Global Polio Eradication Initiative promotes the introduction of inactivated polio vaccine (IPV) in its programs, with withdrawal of Sabin (bOPV). There is no an economic analysis of the investment related to the incorporation of IPV vaccines together with a whole cell Bordetella pertussis vaccine or combined with acellular hexavalent.An economic model that compares different vaccination schemes for the prevention of polio and pertussis in the first year of life was carried out.Four vaccination scenarios for the primary scheme based on Argentina demographic and costs data were developed: - Scenario 1 (base case): two doses of IPV, one dose of bOPV and three doses of pentavalent (DTwP-HepB-Hib) vaccine; - Scenario 2: three doses of IPV plus three doses of pentavalent; - Scenario 3: three doses of hexavalent; - Scenario 4: two doses of hexavalent plus one dose of pentavalent plus IPV.The incremental cost based on scenario 1 was USD 3.716.671; 19.696.668 and 14.383.341 for scenarios 2, 3 and 4 respectively. In terms of reactogenicity savings was -14.178.240 compared base case with scenario 3.Full IPV introduction investment and costs associated were modified according to the type of vaccine and reactogenicity related with the B. pertussis component.

Approximately 44 million people worldwide live with Alzheimer’s disease (AD) or a related form of dementia. Aggregates of the microtubule-associated protein tau are a common marker of these neurodegenerative diseases collectively termed as tauopathies. However, all therapeutic attempts based on tau have failed, suggesting that tau may only indicate a higher-level causal mechanism. For example, increasing levels of reactive oxygen species (ROS) may trigger protein aggregation or modulate protein degradation. Here we show that type 4 NADPH oxidase (NOX), the most abundant isoform of the only dedicated reactive oxygen producing enzyme family, is upregulated in dementia and AD patients and in a humanized mouse model of tauopathy. Both global knockout and neuronal knockdown of theNox4gene in mice, diminished the accumulation of pathological tau and positively modified established tauopathy by a mechanism that implicates modulation of the autophagy-lysosomal pathway (ALP). Moreover, neuronal-targeted NOX4 knockdown was sufficient to reduce neurotoxicity and prevented cognitive decline, suggesting a direct and causal role for neuronal NOX4. Thus, NOX4 is a previously unrecognized causal, mechanism-based target in tauopathies and blood-brain barrier permeable specific NOX4 inhibitors could have therapeutic potential even in established disease.Graphical abstract

El camote de cerro (Dioscorea sp.) es un tubérculo tropical producido de manera no establecida en México con fines alimenticios y medicinales. Su sobreexplotación potencializa un alto riesgo de pérdida de las variedades endémicas del país, por tal motivo el objetivo del trabajo es rescatar plantas en cultivo in vitro y evaluar diferentes sustratos, así como microorganismos asociados a la producción y brotación del camote de cerro (Dioscorea sp.). En este estudio, evaluamos diferentes porcentajes de dos sustratos (jal y tierra); T1.- 100 %(p/p) jal; T2.- 75 %(p/p) jal y 25 %(p/p) tierra; T3.- 50 %(p/p) jal y 50 %(p/p) tierra; T4.- 25 %(p/p) jal y 75 %(p/p) tierra; T5.-100 %(p/p) tierra; de cada tratamiento se utilizó en versión esterilizada (E) y no esterilizada (NE). El tipo de sustrato y los microorganismos presentes en los mismos juegan un papel importante en la brotación y producción de camote de cerro.

El siguiente artículo presenta la implementación del Estado de Máxima Trascendencia, que es una metodología desarrollada por los autores de manera propia que tendrá como objetivo proponer que el empleado consiga darle un sentido de trascendencia a su vida, desde el punto de vista individual. Se presenta cómo fueron empleadas diferentes herramientas, que permitieron equilibrar distintos ejes fundamentales en la vida de la persona para que éstas tenga una experiencia plena y con un éxito integral. De esta forma se alcanzará niveles de satisfacción y rendimiento en sus diferentes actividades incluyendo la laboral. El diseño del método se basa en el reconocimiento del ser humano, primero como persona, para que éste logre darle el sentido de trascendencia a su vida mediante el trabajo, dándole las herramientas necesarias que por consciencias darán resultado a la empresa, todo esto en un círculo virtuoso, una constante que intentará no romperse. Dicho resumen presenta los resultados que se consiguieron luego de casi un año de investigación y desarrollo de la metodología de manera positiva, logrando una implementación optima en los grupos trabajados.&nbsp

Objective: Several studies have linked metabolic syndrome to the development of osteoarthritis (OA) through hypercholesterolemia, one of its components. However, epidemiological studies showed contradictory results, and it is not clear how hypercholesterolemia itself, or oxidized LDL (oxLDL)-a pathological molecule potentially involved in this relationship-could be affecting OA. The objectives of this study were to investigate the effect of hypercholesterolemia induced by high-fat diet (HFD) in cartilage from OA rabbits, and how oxLDL affect human chondrocyte inflammatory and catabolic responses. Design: New Zealand rabbits were fed with HFD for 18 weeks. On week 6, OA was surgically induced. At the end of the study, cartilage damage and IL-1β, IL-6, MCP-1, MMP-13, and COX-2 expression in articular cartilage were evaluated. In addition, cultured human OA articular chondrocytes were treated with oxLDL at concentrations equivalent to those expected in synovial fluid from HFD rabbits, in the presence of IL-1β and TNFα. The effect of oxLDL on cell viability, nitric oxide production and catabolic and pro-inflammatory gene expression was evaluated. Results: HFD intake did not modify cartilage structure or pro-inflammatory and catabolic gene expression and protein presence, both in healthy and OA animals. OxLDL did not affect human chondrocyte viability, ADAMTS5 and liver X receptor (LXR) α gene expression, but decreased the induction of IL-1β, IL-6, MCP-1, MMP-13, iNOS, and COX-2 gene expression and MMP-13 and COX-2 protein presence, evoked by cytokines. Conclusions: Our data suggest that cholesterol intake per se may not be deleterious for articular cartilage. Instead, cholesterol de novo synthesis and altered cholesterol metabolism could be involved in the associations observed in human disease.

The pandemic caused by the Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) has quickly spread globally, infecting millions and killing hundreds of thousands of people. Herein, to identify potential antiviral agents, 97 natural amide-like compounds known as alkamides and piperamides were tested against SARS-CoV-2 main protease (Mpro) and RNA-dependent RNA polymerase (RdRp), and the human angiotensin-converting enzyme 2 (ACE2) using molecular docking and molecular dynamics simulations. The docking results showed that alkamides and dimeric piperamides from Piper species have a high binding affinity and potential antiviral activity against SARS-CoV-2. The absorption, distribution, metabolism, and excretion (ADME) profile and Lipinski’s rule of five showed that dimeric piperamides have druglikeness potential. The molecular dynamics results showed that pipercyclobutanamide B forms a complex with Mpro at a similar level of stability than N3-I. Our overall results indicate that alkamides and piperamides, and specifically pipercyclobutanamide B, should be further studied as compounds with SARS-CoV-2 antiviral properties.

International audience; P-pyrrole phosphines (R2Ppyr), in which a pyrrole group is directly bonded to the phosphorus atom, act as monodentate k-P ligands towards gold(I) center to afford either neutral or cationic mononuclear complexes as well as neutral dinuclear complexes. All of these new gold(I) complexes have been structurally characterized and their first uses in catalysis have demonstrated their effectiveness as precatalysts for the enyne cycloisomerization reactions.

Axions are a natural consequence of the Peccei-Quinn mechanism, the most compelling solution to the strong-CP problem. Similar axion-like particles (ALPs) also appear in a number of possible extensions of the Standard Model, notably in string theories. Both axions and ALPs are very well motivated candidates for Dark Matter, and in addition, they would be copiously produced at the sun's core. A relevant effort during the last decade has been the CAST experiment at CERN, the most sensitive axion helioscope to-date. The International Axion Observatory (IAXO) is a large-scale 4th generation helioscope. As its primary physics goal, IAXO will look for solar axions or ALPs with a signal to background ratio of about 5 orders of magnitude higher than CAST. Recently the IAXO collaboration has proposed and intermediate experimental stage, BabyIAXO, conceived to test all IAXO subsystems (magnet, optics, detectors and sun-tracking systems) at a relevant scale for the final system and thus serve as pathfinder for IAXO but at the same time as a fully-fledged helioscope with record and relevant physics reach in itself with potential for discovery. BabyIAXO was endorsed by the Physics Review committee of DESY last May 2019. Here we will review the status and prospects of BabyIAXO and its potential to probe the most physics motivated regions of the axion & ALPs parameter space., 6 pages, ICHEP 2020 Virtual conference

Despite statin therapy, many patients with atherosclerotic cardiovascular disease (ASCVD) still suffer from ASCVD events. Predictors of residual ASCVD risk are not well-delineated. We aimed to develop an ASCVD risk prediction model for patients with prior ASCVD on statin use. We utilized statin-treated patients with ASCVD from the AIM-HIGH trial cohort. A 5-year risk score for subsequent ASCVD events with known ASCVD was developed using Cox regression, including potential risk factors with age, sex, and race forced in the model. Internal discrimination and calibration were evaluated. We included 3,271 patients with ASCVD (85.4% male, mean age 63.6 years, 65% on moderate and 24% on high-intensity statin) with complete risk factor data and mean follow-up of 4.18 years. Overall, the estimated 5-year ASCVD risk was 21.1%: 10.2% of patients had a 5-year risk of >30%, and 38.8% had risk of between 20-30%. In the model, male sex, hemoglobin A1c, alcohol use (inversely), family history of cardiovascular disease, body mass index, serum creatinine, homocysteine, history of heart failure, history of carotid artery disease and lipoprotein(a) predicted residual ASCVD risk. Niacin treatment status did not enter the model. A C-statistic of 0.59 was obtained, with the Greenwood-Nam-D’Agostino test showing excellent calibration. We developed a risk prediction risk model for predicting 5-year residual ASCVD risk in statin-treated patients with known ASCVD that may help in identifying such persons at the highest risk of recurrent events. Validation in larger samples with patients on high-intensity statin is needed.

In statin-treated persons with atherosclerotic cardiovascular disease (ASCVD) the further ASCVD risk that diabetes mellitus (DM) adds is not well-quantified. We examined this residual risk for initial and total recurrent ASCVD events.We studied 3271 patients with ASCVD on statin therapy in the AIM-HIGH clinical trial cohort. Cox regression and the Prentice, Williams, and Peterson model examined the excess risk of initial and total recurrent ASCVD events associated with DM over a 3- year mean follow-up. Predictors of first and total ASCVD events in those with and without DM were also examined.Of our cohort with ASCVD on statin therapy 40% also had DM. Those with vs. without DM were older, were less likely to be male or white. They had higher systolic blood pressure, lower HDL-C, LDL-C, lipoprotein (a), but higher triglycerides and BMI (all p 0.01). Adjusted HRs were 1.21 (95% CI; 1.01-1.46, p = 0.038) and 1.23 (95% CI: 1.05-1.44, p = 0.012) for first and total recurrent ASCVD events, respectively. Homocysteine and lipoprotein(a) most strongly predicted events in those with and without DM, respectively.In statin-treated patients with ASCVD, DM was associated with significantly greater residual risk over ASCVD alone for both first and total recurrent ASCVD events.

Full list of authors: Bonoli, S.; Marín-Franch, A.; Varela, J.; Vázquez Ramió, H.; Abramo, L. R.; Cenarro, A. J.; Dupke, R. A.; Vílchez, J. M.; Cristóbal-Hornillos, D.; González Delgado, R. M.; Hernández-Monteagudo, C.; López-Sanjuan, C.; Muniesa, D. J.; Civera, T.; Ederoclite, A.; Hernán-Caballero, A.; Marra, V.; Baqui, P. O.; Cortesi, A.; Cypriano, E. S.; Daflon, S.; de Amorim, A. L.; Díaz-García, L. A.; Diego, J. M.; Martínez-Solaeche, G.; Pérez, E.; Placco, V. M.; Prada, F.; Queiroz, C.; Alcaniz, J.; Alvarez-Candal, A.; Cepa, J.; Maroto, A. L.; Roig, F.; Siffert, B. B.; Taylor, K.; Benitez, N.; Moles, M.; Sodré, L.; Carneiro, S.; Mendes de Oliveira, C.; Abdalla, E.; Angulo, R. E.; Aparicio Resco, M.; Balaguera-Antolínez, A.; Ballesteros, F. J.; Brito-Silva, D.; Broadhurst, T.; Carrasco, E. R.; Castro, T.; Cid Fernandes, R.; Coelho, P.; de Melo, R. B.; Doubrawa, L.; Fernandez-Soto, A.; Ferrari, F.; Finoguenov, A.; García-Benito, R.; Iglesias-Páramo, J.; Jiménez-Teja, Y.; Kitaura, F. S.; Laur, J.; Lopes, P. A. A.; Lucatelli, G.; Martínez, V. J.; Maturi, M.; Overzier, R. A.; Pigozzo, C.; Quartin, M.; Rodríguez-Martín, J. E.; Salzano, V.; Tamm, A.; Tempel, E.; Umetsu, K.; Valdivielso, L. ; von Marttens, R.; Zitrin, A.; Díaz-Martín, M. C.; López-Alegre, G.; López-Sainz, A.; Yanes-Díaz, A.; Rueda-Teruel, F.; Rueda-Teruel, S.; Abril Ibañez, J.; L Antón Bravo, J.; Bello Ferrer, R.; Bielsa, S.; Casino, J. M.; Castillo, J.; Chueca, S.; Cuesta, L.; Garzarán Calderaro, J.; Iglesias-Marzoa, R.; Íniguez, C.; Lamadrid Gutierrez, J. L.; Lopez-Martinez, F.; Lozano-Pérez, D.; Maícas Sacristán, N.; Molina-Ibáñez, E. L.; Moreno-Signes, A.; Rodríguez Llano, S.; Royo Navarro, M.; Tilve Rua, V.; Andrade, U.; Alfaro, E. J.; Akras, S.; Arnalte-Mur, P.; Ascaso, B.; Barbosa, C. E.; Beltrán Jiménez, J.; Benetti, M.; Bengaly, C. A. P.; Bernui, A.; Blanco-Pillado, J. J.; Borges Fernandes, M.; Bregman, J. N.; Bruzual, G.; Calderone, G.; Carvano, J. M.; Casarini, L.; Chaves-Montero, J.; Chies-Santos, A. L.; Coutinho de Carvalho, G.; Dimauro, P.; Duarte Puertas, S.; Figueruelo, D.; González-Serrano, J. I.; Guerrero, M. A.; Gurung-López, S.; Herranz, D.; Huertas-Company, M.; Irwin, J. A.; Izquierdo-Villalba, D.; Kanaan, A.; Kehrig, C.; Kirkpatrick, C. C.; Lim, J.; Lopes, A. R.; Lopes de Oliveira, R.; Marcos-Caballero, A.; Martínez-Delgado, D.; Martínez-González, E.; Martínez-Somonte, G.; Oliveira, N.; Orsi, A. A.; Penna-Lima, M.; Reis, R. R. R.; Spinoso, D.; Tsujikawa, S.; Vielva, P.; Vitorelli, A. Z.; Xia, J. Q.; Yuan, H. B.; Arroyo-Polonio, A.; Dantas, M. L. L.; Galarza, C. A.; Gonçalves, D. R.; Gonçalves, R. S.; Gonzalez, J. E.; Gonzalez, A. H.; Greisel, N.; Jiménez-Esteban, F.; Landim, R. G.; Lazzaro, D.; Magris, G.; Monteiro-Oliveira, R.; Pereira, C. B.; Rebouças, M. J.; Rodriguez-Espinosa, J. M.; Santos da Costa, S.; Telles, E., The Javalambre-Physics of the Accelerating Universe Astrophysical Survey (J-PAS) will scan thousands of square degrees of the northern sky with a unique set of 56 filters using the dedicated 2:55m Javalambre Survey Telescope (JST) at the Javalambre Astrophysical Observatory. Prior to the installation of the main camera (4:2 deg2 field-of-view with 1.2 Gpixels), the JST was equipped with the JPAS-Pathfinder, a one CCD camera with a 0:3 deg2 field-of-view and plate scale of 0.23 arcsec pixel?1. To demonstrate the scientific potential of J-PAS, the JPAS-Pathfinder camera was used to perform miniJPAS, a _1 deg2 survey of the AEGIS field (along the Extended Groth Strip). The field was observed with the 56 J-PAS filters, which include 54 narrow band (FWHM _ 145 ) and two broader filters extending to the UV and the near-infrared, complemented by the u; g; r; i SDSS broad band filters. In this miniJPAS survey overview paper, we present the miniJPAS data set (images and catalogs), as we highlight key aspects and applications of these unique spectro-photometric data and describe how to access the public data products. The data parameters reach depths of magAB ' 22?23:5 in the 54 narrow band filters and up to 24 in the broader filters (5_ in a 300 aperture). The miniJPAS primary catalog contains more than 64 000 sources detected in the r band and with matched photometry in all other bands. This catalog is 99% complete at r = 23:6 (r = 22:7) mag for point-like (extended) sources. We show that our photometric redshifts have an accuracy better than 1% for all sources up to r = 22:5, and a precision of _0:3% for a subset consisting of about half of the sample. On this basis, we outline several scientific applications of our data, including the study of spatially-resolved stellar populations of nearby galaxies, the analysis of the large scale structure up to z _ 0:9, and the detection of large numbers of clusters and groups. Sub-percent redshift precision can also be reached for quasars, allowing for the study of the large-scale structure to be pushed to z 2. The miniJPAS survey demonstrates the capability of the J-PAS filter system to accurately characterize a broad variety of sources and paves the way for the upcoming arrival of J-PAS, which will multiply this data by three orders of magnitude. © 2021 EDP Sciences. All rights reserved., Funding for OAJ, UPAD, and CEFCA has been provided by the Governments of Spain and Aragon through the Fondo de Inversiones de Teruel; the Aragon Government through the Research Groups E96, E103, and E16_17R; the Spanish Ministry of Science, Innovation and Universities (MCIU/AEI/FEDER, UE) with grant PGC2018-097585-B-C21; the Spanish Ministry of Economy and Competitiveness (MINECO/FEDER, UE) under AYA2015-66211-C2-1-P, AYA2015-66211-C2-2, AYA2012-30789, and ICTS2009-14; and European FEDER funding (FCDD10-4E-867, FCDD13-4E-2685). This work has made used of CEFCA's Scientific High Performance Computing system which has been funded by the Governments of Spain and Aragon through the Fondo de Inversiones de Teruel, and the Spanish Ministry of Economy and Competitiveness (MINECO-FEDER, grant AYA2012-30789). Funding for the J-PAS project has been provided also by the Brazilian agencies FINEP, FAPESP, FAPERJ and by the National Observatory of Brazil. Additional funding was also provided by the Tartu Observatory and by the Chinese Consortium from the Academy of Sciences SB acknowledges partial support from the project PGC2018-097585-B-C22. R.A.D. acknowledges support from the Conselho Nacional de Desenvolvimento Cientifico e Tecnologico -CNPq through BP grant 308105/2018-4, and the Financiadora de Estudos e Projetos -FINEP grants REF. 1217/13 -01.13.0279.00 and REF 0859/10 -01.10.0663.00 and also FAPERJ PRONEX grant E-26/110.566/2010 for hardware funding support for the J-PAS project through the National Observatory of Brazil and Centro Brasileiro de Pesquisas Fisicas. LRA acknowledges financial support from CNPq (306696/2018-5) and FAPESP (2015/17199-0). VMthanks CNPq (Brazil) and FAPES (Brazil) for partial financial support and the H2020 project No 888258. L.A.D.G. and K.U. acknowledge support from the Ministry of Science and Technology of Taiwan (grant MOST 106-2628-M-001-003-MY3) and from the Academia Sinica (grant AS-IA-107-M01). J.M.D. and D.H acknowledge the support of project PGC2018-101814-B-100. MQ thanks CNPq (Brazil) and FAPERJ (Brazil) for financial support. PC acknowledges financial support from FAPESP (2018/05392-8) and CNPq (310041/2018-0). AAC acknowledges support from FAPERJ (E26/203.186/2016), CNPq (304971/2016-2 and 401669/2016-5), and the Universidad de Alicante (contract UATALENTO1802). C.Q. acknowledges support from FAPESP (2015/11442-0 and 2019/067661). V.M.P. is supported by NOIRLab, which is managed by AURA under a cooperative agreement with the NSF. P.B acknowledges support from CAPES -Finance Code 001. IAA researchers acknowledge financial support from the State Agency for Research of the Spanish MCIU through the "Center of Excellence Severo Ochoa" award to the Instituto de Astrofisica de Andalucia (SEV-2017-0709). Authors acknowledge support from the Generalitat Valenciana project of excellence Prometeo/2020/085. RGD, GMS, JRM, RGB, EP acknowledge financial support from the project AyA2016-77846-P. TC is supported by the INFN INDARK PD51 and PRIN-MIUR 2015W7KAWC. MAR and ALM acknowledge support from the MINECO project FIS2016-78859P(AEI/FEDER, UE). ET, AT and JL acknowledge the support by ETAg grants IUT40-2 and by EU through the ERDF CoE grant TK133 and MOBTP86. CK, JMV, JIP acknowledge financial support from project AYA2016-79724C4-4P. PAAL thanks the support of CNPq (309398/2018-5). LC thanks CNPq for partial support. Y.J-T acknowledges financial support from the FAPERJ (E26/202.835/2016), and from the Horizon 2020 Marie Sklodowska-Curie grant agreement No 898633. DMD acknowledges financial support from the SFB 881 of the DFG and from the MINECO grant AYA2016-81065-C2-2. FP acknowledges support of the project PGC2018-101931-B-I00. JC acknowledges support of the project E AYA2017-88007-C3-1-P, and co-financed by the FEDER. JIGs acknowledges support of projects of reference AYA2017-88007-C3-3-P, and PGC2018-099705-B-I00 and co-financed by the FEDER. EMG and PV would like to acknowledge financial support from the project ESP2017-83921C2-1-R. GMS acknowleges financial support from a predoctoral contract, ref. PRE2018-085523 (MCIU/AEI/FSE, UE). S.C. is partially supported by CNPq. R.G.L. acknowledges CAPES (process 88881.162206/2017-01) and Alexander von Humboldt Foundation for the financial support. JSA acknowledges support from FAPERJ (E26/203.024/2017), CNP (310790/2014-0 and 400471/2014-0) and FINEP (1217/13 -01.13.0279.00 and Ref. 0859/10 -01.10.0663.00). RvM acknowledges support from CNPq. AFS, PAM, VJM and FJB acknowledge support from project AYA2016-81065-C2-2. PAM acknowledges support from the "Subprograma Atraccio de Talent -Contractes Postdoctorals de la Universitat de Valencia". ESC acknowledges support from CNPq (308539/20184) and FAPESP (2019/19687-2). CMdO acknowledges support from CNPq (grant 312333/2014-5) and FAPESP (grant 2009/54202-8). LSJ acknowledges support from CNPq (grant 304819/2017-4) and FAPESP (grant 2012/008004). JMC acknowledges support from CNPq (grant 310727/2016-2). C.H.-M. and N. Greisel also acknowledge the support of the European Union via the Career Integration Grant CIG-PCIG9-GA-2011-294183. JJBP and AMC would like to acknowledge the support from the grant PGC2018-094626-B-C21 and the Basque Government grant IT-979-16. AMC acknowledges the postdoctoral contract from the University of the Basque Country UPV/EHU "Especializacioon de personal investigador doctor" program. MLLD acknowledges CAPES -Finance Code 001; and CNPq (142294/2018-7). GB acknowledges financial support from the UNAM through grant DGAPA/PAPIIT IG100319, from CONACyT through grant CB2015-252364, and from FAPESP projects 2017/02375-2 and 2018/05392-8. M.J. Reboucas acknowledges the support of FAPERJ under a CNE E-26/202.864/2017 grant, and CNPq. Support by CNPq (305409/2016-6) and FAPERJ (E-26/202.841/2017) is acknowledged by DL. AB acknowledges a CNPq fellowship. C.A.G.acknowledges support from CAPES. EA acknowledges support from FAPESP (2011/18729-1). AC acknowledges support from PNPD/CAPES. ABA and FSK acknowledge the Severo Ochoa program SEV-2015-0548. FSK also thanks the AYA2017-89891-P and the RYC2015-18693 grants. DF acknowledges support from the Atraccion del Talento Cientifico en Salamanca programme and the project PGC2018-096038B-I00.

Alzheimer&rsquo, s disease is a chronic and irreversible pathological process that has become the most prevalent neurodegenerative disease. Currently, it is considered a multifactorial disease where oxidative stress and chronic neuroinflammation play a crucial role in its onset and development. Its characteristic neuronal loss has been related to the formation of neurofibrillary tangles mainly composed by hyperphosphorylated tau protein. Hyperphosphorylation of tau protein is related to the over-activity of GSK-3&beta, a kinase that participates in several pathological mechanisms including neuroinflammation. Neuronal loss is also related to cytosolic Ca2+ homeostasis dysregulation that triggers apoptosis and free radicals production, contributing to oxidative damage and, finally, neuronal death. Under these premises, we have obtained a new family of 4,7-dihydro-2H-pyrazolo[3&ndash, b]pyridines as multitarget directed ligands showing potent antioxidant properties and able to scavenge both oxygen and nitrogen radical species, and also, with anti-inflammatory properties. Further characterization has demonstrated their capacity to inhibit GSK-3&beta, and to block L-type voltage dependent calcium channels. Novel derivatives have also demonstrated an interesting neuroprotective profile on in vitro models of neurodegeneration. Finally, compound 4g revokes cellular death induced by tau hyperphosphorylation in hippocampal slices by blocking reactive oxygen species (ROS) production. In conclusion, the multitarget profile exhibited by these compounds is a novel therapeutic strategy of potential interest in the search of novel treatments for Alzheimer&rsquo, s disease.

We use the H\'enon-Heiles system as a paradigmatic model for chaotic scattering to study the Lorentz factor effects on its transient chaotic dynamics. In particular, we focus on how time dilation occurs within the scattering region by measuring the time with a clock attached to the particle. We observe that the several events of time dilation that the particle undergoes exhibit sensitivity to the initial conditions. However, the structure of the singularities appearing in the escape time function remains invariant under coordinate transformations. This occurs because the singularities are closely related to the chaotic saddle. We then demonstrate using a Cantor-like set approach that the fractal dimension of the escape time function is relativistic invariant. In order to verify this result, we compute by means of the uncertainty dimension algorithm the fractal dimensions of the escape time functions as measured with an inertial frame and a frame comoving with the particle. We conclude that, from a mathematical point of view, chaotic transient phenomena are equally predictable in any reference frame and that transient chaos is coordinate invariant.

Hypoxylon species are distributed worldwide and have been isolated from different habitats. The endophyte Hypoxylon anthochroum strain Gseg1 was isolated from healthy leaves of Gliricidia sepium. A chemical study of the culture medium and mycelium organic extracts of the endophytic fungus H. anthochroum Gseg1 led to the isolation of three known isobenzofuranones, 7-hydroxy-4,6-dimethyl-3H-isobenzofuran-1-one, 1, 7-methoxy-4,6-dimethyl-3H-isobenzofuran-1-one, 2, 6-formyl-4-methyl-7-methoxy-3H-isobenzofuran-1-one, 3, and one compound was isolated for the first time as a natural product, 7-methoxy-4-methyl-3H-isobenzofuran-1-one, 4. In addition, the chemical synthesis of 1 and 2, and a derivative, 7-methoxy-6-methyl-3H-isobenzofuran-1-one, 5, was performed. The isobenzofuranones showed antifungal and antioomycete activities. Compounds 1-5 inhibited the growth of Fusarium oxysporum, Alternaria alternata, Pythium aphanidermatum, and Phytophthora capsici, in addition, 1, 2 and 5 interrupted the respiration and caused electrolyte leakage due to cell membrane damage. Compound 2 was the most active, inhibiting the growth of the four microorganisms, affecting the respiration and increasing the relative conductivity due to electrolyte leakage. Compounds 1-4 also induce morphological changes in the plant pathogens' mycelia and hyphae. These compounds could be useful for the control of plant pathogenic fungi and oomycetes of agricultural relevance.

9 páginas, 4 figuras. All data needed to evaluate the conclusions in the paper are present in the paper and/or the Supplementary Materials. Additional data related to this paper may be requested from the authors. Sequencing reads have been submitted to the European Nucleotide Archive (EMBL-EBI) under study accession PRJEB34582 and PRJEB34609. The analysis scripts used in this study are available online at GitHub (https://github.com/StopTB/Single_Colony_Project)., Mycobacterium tuberculosis (Mtb) infection results in a spectrum of clinical and histopathologic manifestations. It has been proposed that the environmental and immune pressures associated with different contexts of infection have different consequences for the associated bacterial populations, affecting drug susceptibility and the emergence of resistance. However, there is little concrete evidence for this model. We prospectively collected sputum samples from 18 newly diagnosed and treatment-naïve patients with tuberculosis and sequenced 795 colony-derived Mtb isolates. Mutant accumulation rates varied considerably between different bacilli isolated from the same individual, and where high rates of mutation were observed, the mutational spectrum was consistent with reactive oxygen species-induced mutagenesis. Elevated bacterial mutation rates were identified in isolates from HIV-negative but not HIV-positive individuals, suggesting that they were immune-driven. These results support the model that mutagenesis of Mtb in vivo is modulated by the host environment, which could drive the emergence of variants associated with drug resistance in a host-dependent manner., This work was supported by the National Natural Science Foundation of China (91631301 and 81661128043 to Q.G., 81701975 to Q.L., and 31771416 to X.L.), the National Science and Technology Major Project of China (2017ZX10201302 to Q.G. and 2018ZX10714002-001-005 to Z.Z.), the Sanming Project of Medicine in Shenzhen (SZSM201611030 to Q.G.), European Research Council 638553-TB-AcCELERATE (to I.C.), the Key Research Program of the Chinese Academy of Sciences (KFZD-SW-220-1 to X.L.), and the CAS Light of West China Program (to X.L.). Y.F. is supported in part by NIH R01HG009524. Support was also received from NIH awards P01 AI132130 and AI142793 to S.M.F.

In the first paragraph of section 4, the sentence “Without loss of generality, we assume the CP-conserving scenario” is incorrect.

El presente trabajo aborda el pensamiento de Prebisch y de la escuela estructuralista latinoamericana. Se destaca que mucho de dicho pensamiento, aunque similar a la visión de Keynes para solventar crisis y mantener el nivel de actividad económica, se distingue porque considera una de las restricciones más importantes que una economía en desarrollo por lo general enfrenta: la restricción externa. Es en este sentido que el trabajo intenta rescatar los aportes de dicho pensamiento y señalar su vigencia en la persecución de metas de crecimiento y desarrollo económico.

Subtalar arthrodesis is a surgical stabilization procedure in the isolated pathology of the subastragaline joint that does not respond to conservative treatment, its goal is to obtain a solid fusion of the joint to eliminate or improve pain and function, normalizing the distribution of foot loads and alignment of the foot. There are studied variables that interfere with the surgical outcome of patients treated with subtalar arthrodesis such as: smoking, age, sex, osteoarthritis, BMI, rehabilitation, osteosynthesis material and surgical technique.To know the prognostic factors associated with the results of subastragaline arthrodesis.Retrospective, longitudinal, descriptive study with review of files and conducting descriptive statistics of treated cases of August 2012- Jan 2016 with subtalar arthrodesis to identify predictive factors affecting the outcome.29 feet were analyzed, reporting a successful arthrodesis in 21 cases (72.4%), in 82.8% the surgical technique was adequate. The complication rate was 20.7% On the AOFAS scale 55.2% were reported as a very good result, 27.6% good and only 17.2% regular. The factors associated with good outcome were sex and postoperative rehabilitation.The subtalar arthrodesis provides improvement in pain and alignment, at our service this procedure presents a success rate of 72.4%, among the factors associated with statistical significance was rehabilitation and sex.La artrodesis subastragalina o astrágalo calcánea, es un procedimiento de estabilización quirúrgica en la patología aislada de la articulación subastragalina que no responde a tratamiento conservador, su objetivo es obtener una fusión sólida de la articulación para eliminar o aminorar el dolor y mejorar la función, normalizando la distribución de cargas del pie y su alineación. Existen variables estudiadas que interfieren en el resultado quirúrgico de los pacientes tratados con artrodesis subastragalina como son: el tabaquismo, edad, sexo, artrosis, IMC, rehabilitación, material de osteosíntesis y la técnica quirúrgica.Conocer los factores pronósticos asociados a los resultados de la artrodesis subastragalina.Estudio retrospectivo, longitudinal, descriptivo con revisión de expedientes y elaboración de estadística descriptiva de casos tratados de Agosto de 2012 a Enero de 2016 con artrodesis subastragalina para identificar factores pronósticos que afecten el resultado.Se analizaron 29 pies, reportándose una artrodesis exitosa en 21 casos (72.4%), en 82.8% la técnica quirúrgica fue adecuada. La tasa de complicaciones fue de 20.7%. En la escala de la Sociedad Ortopédica Americana de Pie y Tobillo (AOFAS) 55.2% se reportaron como resultado muy bueno, 27.6% bueno y sólo 17.2% regular, se encontraron como factores asociados el sexo y la rehabilitación postoperatoria al buen resultado.La artrodesis subastragalina brinda alivio en cuanto al dolor y mejoría en alineación, en nuestro servicio este procedimiento presenta una tasa de éxito de 72.4%, entre los factores asociados con significancia estadística fue la rehabilitación y el sexo.

Panicum coloratum L. cv Verde es una especie con buenas características en cuanto a rendimiento de forraje y valor nutritivo, la cual ha comenzado a difundirse en la Región Semiárida Pampeana. Sin embargo, se dispone de escasa informaci6n sobre el manejo y utilización de esta especie. El objetivo de este estudio fue determinar el efecto del intervalo entre cortes sobre la acumulación de forraje de Panicum coloratum L. cv Verde. El estudio se realiz6 en el Área de Producción Animal de la Facultad de Agronomía de la UNLPam (36° 46' S; 64° 16' W; 210 msnm), durante la temporada de crecimiento 2001/2002. Se utilizó una pastura monofítica de Panicum coloratum L. cv Verde implantada en noviembre de 1994. Al finalizar el periodo de latencia invernal de la pastura (principios de septiembre) se elimin6 el material senescente mediante la utilización del fuego. El 25/10/01 (Ti = 1) se realizó un corte de emparejamiento y se fertilizó con 60 Kg de urea/ha. Los intervalos entre cortes de 14,21,28,35 y 49 dfas, se establecieron en un diseño en bloques aleatorios (con 3 repeticiones) con un tamaño de parcela de 1,8 por 6 m. La altura de corte fue de 5 cm. La acumulaci6n de forraje se estimó para cada tratamiento y repetición, sobre parcelas independientes entre cortes, mediante la cosecha de áreas de 0.6 por 5 m (3 m2) a nivel del suelo. Los datos se analizaron mediante ANOVA, test de Tukey (alfa = 0.05) y regresión polinomial. Los resultados muestran que en el intervalo de corte de 14 días la masa forrajera acumulada fue mayor (p

Calcium homeostasis modulator 1 (CALHM1) is a calcium channel involved in the regulation of cytosolic Ca2+ levels. From a physiological point of view, the open state of CALHM1 depends not only on voltage but also on the extracellular concentration of calcium ([Ca2+]) ions. At low [Ca2+]e or depolarization, the channel is opened, allowing Ca2+ influx, however, high extracellular [Ca2+]e or hyperpolarization promote its resting state. The unique Ca2+ permeation of CALHM1 relates to the molecular events that take place in brain ischemia, such as depolarization and extracellular changes in [Ca2+]e, particularly during the reperfusion phase after the ischemic insult. In this study, we attempted to understand its role in an in vitro model of ischemia, namely oxygen and glucose deprivation, followed by reoxygenation (OGD/Reox). To this end, hippocampal slices from wild-type Calhm1+/+, Calhm1+/&minus, and Calhm1&minus, /&minus, mice were subjected to OGD/Reox. Our results point out to a neuroprotective effect when CALHM1 is partially or totally absent. Pharmacological manipulation of CALHM1 with CGP37157 reduced cell death in Calhm1+/+ slices but not in that of Calhm1&minus, mice after exposure to the OGD/Reox protocol. This ionic protection was also verified by measuring reactive oxygen species production upon OGD/Reox in Calhm1+/+ and Calhm1&minus, mice, resulting in a downregulation of ROS production in Calhm1&minus, hippocampal slices and increased expression of HIF-1&alpha, Taken together, we can conclude that genetic or pharmacological inhibition of CALHM1 results in a neuroprotective effect against ischemia, due to an attenuation of the neuronal calcium overload and downregulation of oxygen reactive species production.

Background Dyslipidemia guidelines recommend non‐high‐density lipoprotein cholesterol (non‐ HDL ‐C) and apolipoprotein B (ApoB) as additional targets of therapy and consider lipoprotein(a) a significant cardiovascular risk marker. The current analysis evaluates the effects of evolocumab on these parameters in various patient populations over time. Methods and Results Data from 7690 patients, 4943 of whom received at least 1 dose of evolocumab, in 15 phase 2 and phase 3 studies with a duration ranging from 12 weeks to 5 years were pooled based on study length, patient population, and ezetimibe or placebo comparator groups. Patients could receive intensive statin therapy but not in the statin intolerance and monotherapy studies. The effects of evolocumab on percent change from baseline for non‐ HDL ‐C, ApoB, and lipoprotein(a) and achievement of treatment goals for non‐ HDL ‐C and ApoB were examined. Compared with placebo, evolocumab at both approved dosing regimens substantially reduced mean non‐ HDL ‐C (Q2W dose: −49% to −56%, monthly dose: −48% to −52%), mean ApoB (Q2W dose: −46% to −52%, monthly dose: −40% to −48%), and median lipoprotein(a) (Q2W dose: −22% to −38%, monthly dose: −20% to −33%) at 12 weeks. Effects on all 3 parameters persisted over 5 years. Lipid‐lowering effects were consistent among the patient populations examined (hypercholesterolemia/mixed dyslipidemia, statin intolerance, heterozygous familial hypercholesterolemia, and type 2 diabetes mellitus). Conclusions In this pooled analysis, evolocumab substantially reduced non‐ HDL ‐C, ApoB, and lipoprotein(a) compared with placebo. The effect was consistent and maintained in various patient populations over 5 years.

The use of silver nanoparticles stabilized with citrate and polyvinylpyrrolidone as a sensor for aluminum ions determination is proposed in this paper. These non-functionalized and specific nanoparticles provide a highly selective and sensitive detection system for aluminum in acidic solutions. The synthesized nanoparticles were characterized by transmission electron microscopy. Surface plasmon band deconvolution analysis was applied to study the interaction between silver nanoparticles and aluminum ions in solution. The interaction band in the UV-visible region was used as an analytical signal for quantitation purposes. The proposed detection system offers an effective AND wide linearity range (0.1&ndash, 103 nM), specificity for Al(III) in THE presence of other metallic ions in solution, as well as high sensitivity (limit of detection = 40.5 nM). The proposed silver-nanoparticles-based sensor WAS successfully used for detecting Al(III) in real water samples.

7 p.-2 fig., Leucine-rich repeat kinase 2 (LRRK2) is a protein kinase whose activity plays an important role in neurodegenerative diseases. Although mutations in LRRK2 gene are the most common cause of monogenic Parkinson's disease, it has been reported that LRRK2 may promote Tau phosphorylation, increasing its aggregation. Thus, the modulation of LRRK2 activity by small molecules able to inhibit this kinase activity could be an innovative therapeutic strategy for different tauopathies. We examined the therapeutic effects of a new benzothiazole-based LRRK2 inhibitor, known as JZ1.40, in a mouse model of tauopathy. Mice were injected in the right hippocampus with an adeno-associated vector expressing human-TAUP301L and treated daily with JZ1.40 (10 mg/kg, i.p) or vehicle for three weeks. JZ1.40 reaches the brain and modulates RAB10 and Tau phosphorylation at the epitopes modified by LRRK2. Moreover, JZ1.40 treatment ameliorates the cognitive impairment induced by TAUP301L overexpression, which correlates with prevention of granular cell layer degeneration by improving synaptic plasticity. These data show that JZ1.40 is neuroprotective in vivo, which is translated into cognition enhancement., This work was supported by MINECO (Competitiveness Grants SAF2016-76520-R to ILB, SAF2016-76693-R to AM, and RTI2018-095793-B-I00 to MGL), MECD (FPU grant FPU13-003262 to JZD), SCS is beneficiary of the call for predoctoral contracts for the training of research personnel 2018 (FPI-UAM) and Fundación Tatiana Pérez de Guzmán el Bueno to EL.

We study the logarihtnmic asymptotic of multiple orthogonal polynomials arising in a mixed type Hermite-Pad\'e approximation problem associated with the rational perturbation of a Nikishin system of functions. The formulas obtained allow to give exact estimates of the rate of convergence of the corresponding Hermite-Pad\'e approximants., Comment: 17 pages. arXiv admin note: text overlap with arXiv:1904.00126

Aspergillus flavus is a filamentous, saprophytic fungus, whose colonization occurs mainly in cereal grains and oilseeds once harvested. Under certain conditions, it could produce mycotoxins called aflatoxins, known as powerful human liver carcinogens. The aim of the present study was to describe the antifungal activity of extracts of Peltophorum dubium, a species from northern Argentina (Oriental Chaco), against A. flavus. The antifungal activities of different collection sites are reported. The extracts exhibited a minimum inhibitory concentration of 125 µg/mL, and the differences between the treatments and the inoculum control were 11 mm of P. dubium A and 10 mm of P. dubium F in colony growth. Moreover, hyphae treated with the extracts stained blue with Evans blue showed alterations in the membrane and/or cell wall, allowing the dye income. Bio-guided fractionation, High Performance Liquid Chromatography diode array ultraviolet/visible (HPLC UV/VIS DAD), and Ultra-High Performance Liquid Chromatography Electrospray Ionization Mass Spectrometry (UPLC ESI-MS) analyses were conducted to characterize the extracts and their active fractions. The HPLC UV/VIS DAD analysis allowed the determination of the presence of flavonoids (flavonols and flavones), coumarins, terpenes, and steroids. UPLC ESI/MS analysis of active fractions revealed the presence of Kaempferol, Apigenin, Naringenin, Chrysin and Daidzein.

The present paper deals with the convergence properties of multi-level Hermite-Pad\'e approximants for a class of meromorphic functions given by rational perturbations with real coefficients of a Nikishin system of functions, and study the zero location of the corresponding multiple orthogonal polynomials., Comment: 18 pages

En este trabajo se estudio el reemplazo de agregados reciclados y su efecto en la durabilidad, mediante el ensayo de migracion de iones cloruro (NordTest 492) y el desarrollo de resistencia del concreto utilizando remplazos de30%, 50%, 75% y 100% de la fraccion fina de los agregados. Los resultados mostraron que es factible el desarrollo de resistencias en concretos con reemplazos de 30% y 100%, del agregado normal por agregado fino reciclado; los porcentajes de reemplazo influyeron en la absorcion capilar y en la migracion de iones cloruro, modificando el comportamiento ante pruebas de durabilidad. Abstract In this work, the replacement of recycled aggregates and its effect on durability were studied through the chloride ion migration test (NordTest 492) and the development of concrete strength using replacements of 30%, 50%, 75% and 100% of the fine fraction of the aggregates. The results showed that it is feasible to develop resistances in concrete with 30% and 100% replacements, from normal aggregate to recycled fine aggregate; the replacement percentages influenced the capillary absorption and the migration of chloride ions, modifying the behavior before durability tests.

A set of alkyl aluminum complexes supported by non-symmetric ferrocenyl amidine ligands were used as catalysts for the preparation of cyclic carbonates from epoxides and carbon dioxide using Bu4NI as a co-catalyst. A modified method for the synthesis of aminoferrocene allowed us to obtain this precursor in quantitative yield. Treatment of aminoferrocene with the corresponding acetimidoyl chloride afforded the desired ferrocenyl amidine ligands L1H, (E)-N-(2,6-diisopropylphenyl)-N'-(ferrocenyl)acetimidamide, and L2H, (E)-N-(2,6-dimethylphenyl)-N'-(ferrocenyl)acetimidamide. The reaction of these ligands with 1.0 or 0.5 equiv. of AlMe3 led to the synthesis of aminoferrocene based aluminum complexes ((L1)AlMe2 (1), (L2)AlMe2 (2), (L1)2AlMe (3), and (L2)2AlMe (4)) in excellent yields, which were characterized by spectroscopic and X-ray diffraction methods. In addition, we have studied their electrochemical properties and complex 1 was found to be the most active catalyst for the formation of cyclic carbonates 6a-j from their corresponding epoxides 5a-j and CO2.

Evolutionary Algorithms (EAs) and other kind of metaheuristics are utilized to either design or optimize the architecture of Artificial Neural Networks (ANNs) in order to adapt them for solving a specific problem; these generated ANNs are known as Evolutionary Artificial Neural Networks (EANNs). Their architecture components, including number of neurons or their kind of transfer functions, connectivity pattern, etc., can be defined through direct or indirect encoding schemes; the former, directly codifies ANN architecture components into the genotype of solutions, meanwhile the last one, requires to transform the solution’s genotype through mapping processes to generate an ANN architecture. In this work, architectures of three-layered feed-forward ANNs are designed by using both encoding schemes to solve several well-known benchmark datasets of supervised classification problems. The results of designed ANNs by using direct and indirect encoding schemes are compared.

Mineralogical studies on platinum-group minerals found in placer deposits from the Río Santiago (Ecuador) are scarce. In this investigation, one sample collected from the Río Santiago alluvial placer was studied via a multi-disciplinary approach, including optical microscopy, scanning electron microscopy, electron microprobe, and Raman spectroscopy. Whole-rock geochemistry data of the sample confirms elevated Au and platinum-group elements contents and the chondrite-normalized pattern reveals pronounced positive Ir and Pt anomalies. Free grains of platinum-group minerals were separated via hydroseparation techniques and identified as: i) Pt-Fe alloy (Pt3Fe), ii) tulameenite (Pt2FeCu) and iii) hongshiite (PtCu). The most abundant platinum-group mineral is Pt-Fe alloy (85%) that occasionally hosts cuprorhodsite (CuRh2S4) inclusions. Although the primary source remains unknown, the geochemical and mineralogical data suggests that the source of platinum-group minerals in the Río Santiago alluvial placer is a mafic-ultramafic Ural-Alaska type complex. Possible primary sources are the mafic and ultramafic rocks found in the mafic basement of the coastal region and the Western Cordillera (Piñón, San Juan and Pallatanga units), which derive from the Late Cretaceous Caribbean Colombia Oceanic Plateau (CCOP).

International audience; Background: People living with human immunodeficiency virus (PLHIV) are at higher risk of atherosclerotic cardiovascular disease (ASCVD) due to traditional and HIV- or antiretroviral treatment (ART)-related risk factors. The use of high-intensity statin therapy is often limited by comorbidities and drug-drug interactions with ART. Herein, we present the design and baseline characteristics of the BEIJERINCK study, which will assess the safety and efficacy of evolocumab in PLHIV and hypercholesterolemia/mixed dyslipidemia.Methods: Randomized, double-blind, placebo-controlled, multinational trial that investigates monthly subcutaneous evolocumab 420 mg versus placebo in PLHIV with hypercholesterolemia/mixed dyslipidemia who are treated with maximally-tolerated statin therapy. The primary outcome is the baseline to week 24 percent change in low density lipoprotein cholesterol (LDL-C). Secondary outcomes include achievement of LDL-C < 70 mg/dL and percent change in other plasma lipid and lipoprotein levels. Safety will also be examined.Results: This study enrolled and dosed 464 patients who had a mean age of 56.4 years and were mostly male (82.5%). Mean duration with HIV was 17.4 years, and, by design, HIV viral load at screening was ≤50 copies/mL. ASCVD was documented in 35.6% of patients. Mean LDL-C of enrolled patients at baseline was 133.3 mg/dL. Statin use was prevalent (79.3% overall) with 74.6% receiving moderate or high-intensity statins. In total, 20.7% of patients did not receive statins due to intolerance/contraindications.Conclusions: The BEIJERINCK study is the first clinical trial to examine the lipid-lowering efficacy and safety of a fully human PCSK9 monoclonal antibody inhibitor in a moderate/high cardiovascular risk population of PLHIV.

The aim of this article is to analyse the presence of Guinea in the trade fairs that were held in Valencia during the 1940s, in which, according to the doctrine of Hispanicity, the colony was delimited as a territory to be ‘civilized’, namely Christian­ized and Hispanicized. The rhetoric of National-Catholicism was of vital importance in the public discourse linking trade and mission. To that end, the strategy chosen by organizers was to put the spotlight on the natural resources of the colony and its inhabitants, in particular the Fang people of continental Guinea. The interest of the Valencian trade fairs is twofold. On the one hand, they allow us to understand the dynamics set in motion by the Francoist government in its bid to arouse Spanish enthusiasm for colo­nial affairs in the years immediately following the end of the Spanish Civil War and during World War II. On the other, they are another piece in a puzzle that seemed to have been completed in Spain with the ethnological exhibitions of the Guineans at the Ibero-American Exposition of Seville in 1929. El propósito de este artículo es analizar la presencia de Guinea en las ferias muestrario que se celebraron en Valencia durante la década de 1940. En ellas, de acuerdo con la doctrina de la Hispanidad, la colonia se delimitó como un territorio a civi­lizar –cristianizar y españolizar–, siendo de vital importancia en el discurso público la retórica nacionalcatolicista que entreveraba negocio y misión. Para ello, los organizadores optaron por la estrategia de poner en escena los recursos naturales de la colonia y a sus habitantes, especialmente a los fang de la Guinea continental. El interés del caso valenciano es doble. Por un lado, nos permite entender las dinámicas puestas en marcha por el gobierno franquista para despertar el interés de los españoles por los asuntos coloniales en los años inmediatamente posteriores al final de la Guerra Civil española y en plena Segunda Guerra Mundial. Por otro, es una pieza más de un rompecabezas que parecía haberse terminado en España con las exhibiciones etnológicas de los guineanos en la Exposición Iberoamericana de Sevilla de 1929.