Organocatalytic strategies for the development of the enantioselective inverse-electron-demand hetero-Diels-Alder reaction

Cycloaddition reactions, in particular Diels-Alder reactions, have attracted a lot of attention from organic chemists since they represent one of the most powerful methodologies for the construction of carbon-carbon bonds. In particular, inverse-electron-demand hetero-Diels-Alder reactions have been an important breakthrough for the synthesis of heterocyclic compounds. Among all their variants, the organocatalytic enantioselective version has been widely explored since the asymmetric construction of diversely functionalized scaffolds under reaction conditions encompassed within the green chemistry field is of great interest. In this review, a profound revision on the latest advances on the organocatalytic asymmetric inverse-electron demand hetero-Diels-Alder reaction is shownWe are grateful to the Spanish Government (CTQ2015-64561-R and RTI2018-095038-B-I00), “Comunidad de Madrid” and European Structural Funds (S2018/NMT-4367). J.A.F.-S. thanks the Spanish Government for a Ramón y Cajal contract. V.L.-M. thanks Universidad Autónoma de Madrid for a predoctoral fellowship (FPI-UAM

Sphere rolling on the surface of a cone

We analyse the motion of a sphere that rolls without slipping on a conical surface having its axis in the direction of the constant gravitational field of the Earth. This nonholonomic system admits a solution in terms of quadratures. We exhibit that the only circular of the system orbit is stable and furthermore show that all its solutions can be found using an analogy with central force problems. We also discuss the case of motion with no gravitational field, that is, of motion on a freely falling cone.Comment: 12 pages, 2 figures, to be published in Eur J Phy

Enantioselective inverse-electron demand Aza-Diels-Alder reaction: ipso,α-selectivity of silyl dienol ethers

A highly efficient enantioselective inverse-electron-demand aza-Diels-Alder reaction between aza-sulfonyl-1-aza-1,3-butadienes and silyl (di)enol ethers has been developed. The presented methodology allows the synthesis of benzofuran-fused 2-piperidinol derivatives with three contiguous stereocenters in a highly selective manner, as even the hemiaminal center is completely stereocontrolled. Density functional theory (DFT) calculations support that the hydrogen-bond donor-based bifunctional organocatalyst selectively triggers the reaction through the ipso,α-position of the dienophile, in contrast to the reactivity observed for dienolates in situ generated from β,γ-unsaturated derivatives. Moreover, the calculations have clarified the mechanism of the reaction and the ability of the hydrogen-bond donor core to hydrolyze selectively theEisomer of the dienol ether. Furthermore, to demonstrate the applicability of silyl enol ethers as nucleophiles in the asymmetric synthesis of interesting benzofuran-fused derivatives, the catalytic system has also been implemented for the highly efficient installation of an aromatic ring in the piperidine adductsFinancial support was provided by the European Research Council (ERC-CoG, contract number: 647550), Spanish Government (RTI2018-095038-B-I00), and “Comunidad de Madrid” and European Structural Funds (S2018/NMT-4367

Asymmetric synthesis of Rauhut-Currier-type esters via Mukaiyama-Michael reaction to acylphosphonates under bifunctional catalysis

A highly enantioselective organocatalytic Mukaiyama-Michael reaction of silyloxy dienes and α,β-unsaturated acyl phosphonates under bifunctional organocatalysis is presented. The new reactivity triggered by the catalyst conducted to Rauhut-Currier type esters, via a formal conjugate addition to α,β-unsaturated esters. This protocol proceeds under mild conditions with complete regioselectivity and excellent enantiocontrolWe are grateful to the Spanish Government (CTQ2015-64561-R and CTQ2016-76061-P) and the European Research Council (ERCCG-UNBICAT, contract number: 647550). J. A. F.-S. and V. L.-M. thank the Spanish Government for a Juan de la Cierva Contract and the Universidad Auto´noma de Madrid for a predoctoral fellowship (FPI-UAM), respectively. Financial support from the Spanish Ministry of Economy and Competitiveness, through the ‘‘Maria de Maeztu’’ Program of Excellence in R&D (MDM-2014-0377), is also acknowledged. We acknowledge the generous allocation of computing time at the CCC (UAM

Constraining the invisible neutrino decay with KM3NeT-ORCA

Several theories of particle physics beyond the Standard Model consider that neutrinos can decay. In this work we assume that the standard mechanism of neutrino oscillations is altered by the decay of the heaviest neutrino mass state into a sterile neutrino and, depending on the model, a scalar or a Majoron. We study the sensitivity of the forthcoming KM3NeT-ORCA experiment to this scenario and find that it could improve the current bounds coming from oscillation experiments, where three-neutrino oscillations have been considered, by roughly two orders of magnitude. We also study how the presence of this neutrino decay can affect the determination of the atmospheric oscillation parameters sin^2(θ_23) and Δm^2_31, as well as the sensitivity to the neutrino mass ordering

Maximum rainfall intensity analysis using L-moments in Spain

Proceedings of the Seventh International Conference on Hydroscience and Engineering, Philadelphia, PA, September 2006. http://hdl.handle.net/1860/732Flood predictions are frequently the basis for engineering works, structures design, and land use planning, but quite often there are no gauged stations and consequently hydrometeorological models become an essential tool. These models require maximum rainfall intensity estimations -for different durations and return periods -an IDF law-. The IDF law actually used in Spain was developed in the seventies and it was based on an at-site analysis on the 21 available gauged stations in that moment, using Gumbel distribution for adjustment. Last paragraph is an invitation to revising methodology and updating data as nowadays there are more gauged stations with sufficient records in the Spanish peninsular area. However, classical approach to the regionalization technique cannot be used due to scarce stations -there are 63 stations in 500.000 km2- and great climate variability in short distances -from semi-arid in the southeast to Atlantic climate in the north-. Thus, authors propose an “intra-station” regionalization, it is to say, a regionalization in the same station. Besides, they suggest new expressions in order to extend results to the rest of the territory. According to practical character of this study, a GIS (geographical information system) application was developed –MAXIN- and it is available in: http://www.forestales.upm.es/hidraulica/paginas/programas/programas.ht

Effect of dietary free fatty acid content on growth and hepatic morphology in sole (Solea Senegalensis) juveniles

Utilization in aquaculture of unusual meals with unbalanced lipid content or inadequate previous treatment may result in harmful state for fish. This research studied the effects caused by different dietary free fatty acid (FFA) content on growth performance and hepatic morphology in liver in sole juveniles. Results revealed an inverse relationship between dietary FFA content and ability of fish to grow. Moreover, hepatic morphology analysis indicated an overall healthier status in hepatocytes of fish fed with low dietary FFA content. Dietary fatty acids must be esterified to glycerols seem an absolutely necessary requisite in sole, allowing a proper energy storing and its latter mobilisation to gain biomass.This work was supported by Interreg Project 0251_ECOAQUA_5_E, financed by the EDRF (European Regional Development Fund). www.juntadeandalucia.es/agriculturaypesca/ifapa/ecoaquaLa utilizaci&oacute;n en la acuicultura de dietas inusuales con contenido lip&iacute;dico desequilibrados o tratamientos previos inadecuados puede resultar nocivo para los peces. Esta investigaci&oacute;n estudi&oacute; los efectos causados por distintas dietas con diferente contenido en &aacute;cidos grasos libres (FFA) en el crecimiento y la morfolog&iacute;a hep&aacute;tica en juveniles de lenguado. Los resultados revelaron una relaci&oacute;n inversa entre el contenido de FFA en la dieta y la capacidad de los peces para crecer. Por otra parte, el an&aacute;lisis de la morfolog&iacute;a hep&aacute;tica indic&oacute; un estado m&aacute;s saludable en los hepatocitos de los peces alimentados con una dieta baja en FFA . La esterificaci&oacute;n con glicerina de &aacute;cidos grasos es un requisito indispensable en lenguados, lo que permite un adecuado almacenamiento de energ&iacute;a y su posterior movilizaci&oacute;n para ganar biomasa.Este trabajo fue apoyado por el proyecto Interreg 0251_ECOAQUA_5_E , financiado por el FEDER (Fondo Europeo de Desarrollo Regional). www.juntadeandalucia.es/agriculturaypesca/ifapa/ecoaqua.</p

Neutrino masses and their ordering: global data, priors and models

We present a full Bayesian analysis of the combination of current neutrino oscillation, neutrinoless double beta decay and Cosmic Microwave Background observations. Our major goal is to carefully investigate the possibility to single out one neutrino mass ordering, namely Normal Ordering or Inverted Ordering, with current data. Two possible parametrizations (three neutrino masses versus the lightest neutrino mass plus the two oscillation mass splittings) and priors (linear versus logarithmic) are exhaustively examined. We find that the preference for NO is only driven by neutrino oscillation data. Moreover, the values of the Bayes factor indicate that the evidence for NO is strong only when the scan is performed over the three neutrino masses with logarithmic priors; for every other combination of parameterization and prior, the preference for NO is only weak. As a by-product of our Bayesian analyses, we are able to (a) compare the Bayesian bounds on the neutrino mixing parameters to those obtained by means of frequentist approaches, finding a very good agreement; (b) determine that the lightest neutrino mass plus the two mass splittings parametrization, motivated by the physical observables, is strongly preferred over the three neutrino mass eigenstates scan and (c) find that logarithmic priors guarantee a weakly-to-moderately more efficient sampling of the parameter space. These results establish the optimal strategy to successfully explore the neutrino parameter space, based on the use of the oscillation mass splittings and a logarithmic prior on the lightest neutrino mass, when combining neutrino oscillation data with cosmology and neutrinoless double beta decay. We also show that the limits on the total neutrino mass ∑ mν can change dramatically when moving from one prior to the other. These results have profound implications for future studies on the neutrino mass ordering, as they crucially state the need for self-consistent analyses which explore the best parametrization and priors, without combining results that involve different assumptions

Strong-LAMP Assay Based on a Strongyloides spp.-Derived Partial Sequence in the 18S rRNA as Potential Biomarker for Strongyloidiasis Diagnosis in Human Urine Samples

Human strongyloidiasis a soil-transmitted infection caused by Strongyloides stercoralis is one of the most neglected amongst the so-called Neglected Tropical Diseases (NTDs). S. stercoralis is a nematode, which is distributed worldwide; it has been estimated that it could affect millions of people, mainly in tropical and subtropical endemic regions. The difficulties of diagnosis lead to infection rates being underreported. Asymptomatic patients have chronic infections that can lead to severe hyperinfection syndrome or disseminated strongyloidiasis in immunocompromised patients. Strongyloidiasis can easily be misdiagnosed because conventional faecal-based techniques lack of sensitivity for the morphological identification of infective larvae in faeces. None of the currently used molecular methods have used urine samples as an alternative to faecal samples for diagnosing strongyloidiasis. This study was thus aimed at comparing, for the first time, the use of a new loop-mediated isothermal amplification (LAMP) molecular assay (Strong-LAMP) to traditional methods on patients' urine samples. Twenty-four urine samples were taken from patients included in a study involving two Spanish hospitals for strongyloidiasis screening using parasitological and serological tests. Strongyloides larvae were found in 11 patients' faecal samples, thereby ascertaining that they had the disease. Other patients had high antibody titres but no larvae were found in their faeces. All urine samples were analysed by PCR and Strong-LAMP assay. No amplification occurred when using PCR. Strong-LAMP led to detecting S. stercoralis DNA in urine samples from patients having previously confirmed strongyloidiasis by parasitological tests and/or a suspicion of being infected by serological ones. The Strong-LAMP assay is a useful molecular tool for research regarding strongyloidiasis in human urine samples. After further validation, the Strong-LAMP assay could also be used for complementary and effective diagnosis of strongyloidiasis in a clinical setting