Efficient Asymmetric Synthesis of an A-Ring Synthon for Pd-Catalyzed Preparation of 1α-Hydroxyvitamin D Metabolites and Analogs

An efficient Lewis acid-assisted asymmetric carbonyl-ene reaction to set the 1α-hydroxyl functionality of enol-triflate, precursor of the A-ring of the hormone calcitriol and its 1α-hydroxyderivatives, is described. The secondary parallel hypercalcemic effects associated with the treatment of several hyperproliferative diseases with the natural hormone 1α,25-dihydroxyvitamin D3 (calcitriol) and/or known active vitamin D metabolites and analogs, demand the development of efficient and rapid methods for the preparation of vitamin D receptor (VDR) ligands as new selective and non-calcemic agonists. Here we describe an efficient and adaptable multigram-scale synthetic sequence to access an A-ring synthon as useful precursor of the vitamin D triene system of 1α-hydroxylated vitamin D derivatives via Pd-catalyzed carbocyclization/Suzuki–Miyaura cross-coupling reactions in a protic medium. The key step is an asymmetric Lewis acid-promoted carbonyl-ene reaction to a chiral glyosylate ester to establish the 1α-hydroxyl group of 1α,25-dihydroxyvitamin D3 and its derivativesThis research was funded by ENDOTHERM GmbH, Xunta de Galicia (GRC/ED431B/20) and the University of Santiago de Compostela (Spain)S

Studies on the Synthesis of Vitamin D Analogs with Aromatic D-Ring

Herein, we describe our studies on the synthesis of 1α,25-dihydroxyvitamin D3 analogs possessing a benzene ring replacing the natural 5-membered D-ring by the Wittig-Horner and dienyne approaches. A key feature is the synthesis of a Cr(CO)3-complexed previtamin D derivative that enables the construction of vitamin D analogs with aromatic D-ring through a thermal [1,7]-H sigmatropic shift. This study establishes the basis for the design of new vitamin D analogs containing aromatic D-ring, complexed or uncomplexed to Cr(CO)3 type moieties for specific molecular recognition and drug research and developmentWe thank Xunta de Galicia (project GPC2014/001) and for financial support. Silvina Eduardo thanks the Spanish MEC for a fellowship. Rita Sigüeiro thanks Xunta de Galicia for a post-doctoral fellowship (Axudas posdoutorais, plan I2C, mod B)S

Temporal variability of diazotroph community composition in the upwelling region off NW Iberia.

Knowledge of the ecology of N2-fixing (diazotrophic) plankton is mainly limited to oligotrophic (sub)tropical oceans. However, diazotrophs are widely distributed and active throughout the global ocean. Likewise, relatively little is known about the temporal dynamics of diazotrophs in productive areas. Between February 2014 and December 2015, we carried out 9 one-day samplings in the temperate northwestern Iberian upwelling system to investigate the temporal and vertical variability of the diazotrophic community and its relationship with hydrodynamic forcing. In downwelling conditions, characterized by deeper mixed layers and a homogeneous water column, non-cyanobacterial diazotrophs belonging mainly to nifH clusters 1G (Gammaproteobacteria) and 3 (putative anaerobes) dominated the diazotrophic community. In upwelling and relaxation conditions, affected by enhanced vertical stratification and hydrographic variability, the community was more heterogeneous vertically but less diverse, with prevalence of UCYN-A (unicellular cyanobacteria, subcluster 1B) and non-cyanobacterial diazotrophs from clusters 1G and 3. Oligotyping analysis of UCYN-A phylotype showed that UCYN-A2 sublineage was the most abundant (74%), followed by UCYN-A1 (23%) and UCYN-A4 (2%). UCYN-A1 oligotypes exhibited relatively low frequencies during the three hydrographic conditions, whereas UCYN-A2 showed higher abundances during upwelling and relaxation. Our findings show the presence of a diverse and temporally variable diazotrophic community driven by hydrodynamic forcing in an upwelling system

Detection of barriers to mobility in the smart city using Twitter

We present a system that analyzes data extracted from the microbloging site Twitter to detect the occurrence of events and obstacles that can affect pedestrian mobility, with a special focus on people with impaired mobility. First, the system extracts tweets that match certain prede ned terms. Then, it obtains location information from them by using the location provided by Twitter when available, as well as searching the text of the tweet for locations. Finally, it applies natural language processing techniques to con rm that an actual event that affects mobility is reported and extract its properties (which urban element is affected and how). We also present some empirical results that validate the feasibility of our approach.This work was supported in part by the Analytics Using Sensor Data for FLATCity Project (Ministerio de Ciencia, innovación y Universidades/ERDF, EU) funded by the Spanish Agencia Estatal de Investigación (AEI), under Grant TIN2016-77158-C4-1-R, and in part by the European Regional Development Fund (ERDF)

Wikipedia-based hybrid document representation for textual news classification

The sheer amount of news items that are published every day makes worth the task of automating their classification. The common approach consists in representing news items by the frequency of the words they contain and using supervised learning algorithms to train a classifier. This bag-of-words (BoW) approach is oblivious to three aspects of natural language: synonymy, polysemy, and multiword terms. More sophisticated representations based on concepts—or units of meaning—have been proposed, following the intuition that document representations that better capture the semantics of text will lead to higher performance in automatic classification tasks. The reality is that, when classifying news items, the BoW representation has proven to be really strong, with several studies reporting it to perform above different ‘flavours’ of bag of concepts (BoC). In this paper, we propose a hybrid classifier that enriches the traditional BoW representation with concepts extracted from text—leveraging Wikipedia as background knowledge for the semantic analysis of text (WikiBoC). We benchmarked the proposed classifier, comparing it with BoW and several BoC approaches: Latent Dirichlet Allocation (LDA), Explicit Semantic Analysis, and word embeddings (doc2vec). We used two corpora: the well-known Reuters-21578, composed of newswire items, and a new corpus created ex professo for this study: the Reuters-27000. Results show that (1) the performance of concept-based classifiers is very sensitive to the corpus used, being higher in the more “concept-friendly” Reuters-27000; (2) the Hybrid-WikiBoC approach proposed offers performance increases over BoW up to 4.12 and 49.35% when classifying Reuters-21578 and Reuters-27000 corpora, respectively; and (3) for average performance, the proposed Hybrid-WikiBoC outperforms all the other classifiers, achieving a performance increase of 15.56% over the best state-of-the-art approach (LDA) for the largest training sequence. Results indicate that concepts extracted with the help of Wikipedia add useful information that improves classification performance for news items.Atlantic Research Center for Information and Communication TechnologiesXunta de Galicia | Ref. R2014/034 (RedPlir)Xunta de Galicia | Ref. R2014/029 (TELGalicia

Wikipedia-based hybrid document representation for textual news classification

Automatic classification of news articles is a relevant problem due to the large amount of news generated every day, so it is crucial that these news are classified to allow for users to access to information of interest quickly and effectively. On the one hand, traditional classification systems represent documents as bag-of-words (BoW), which are oblivious to two problems of language: synonymy and polysemy. On the other hand, several authors propose the use of a bag-of-concepts (BoC) representation of documents, which tackles synonymy and polysemy. This paper shows the benefits of using a hybrid representation of documents to the classification of textual news, leveraging the advantages of both approaches-the traditional BoW representation and a BoC approach based on Wikipedia knowledge. To evaluate the proposal, we used three of the most relevant algorithms in the state-of-the art-SVM, Random Forest and Naïve Bayes-and two corpora: the Reuters-21578 corpus and a purpose-built corpus, Reuters-27000. Results obtained show that the performance of the classification algorithm depends on the dataset used, and also demonstrate that the enrichment of the BoW representation with the concepts extracted from documents through the semantic annotator adds useful information to the classifier and improves their performance. Experiments conducted show performance increases up to 4.12% when classifying the Reuters-21578 corpus with the SVM algorithm and up to 49.35% when classifying the corpus Reuters-27000 with the Random Forest algorithm.Atlantic Research Center for Information and Communication TechnologiesXunta de Galicia | Ref. R2014/034 (RedPlir)Xunta de Galicia | Ref. R2014/029 (TELGalicia

Cross-repository aggregation of educational resources

The proliferation of educational resource repositories promoted the development of aggregators to facilitate interoperability, that is, a unified access that would allow users to fetch a given resource independently of its origin. The CROERA system is a repository aggregator that provides access to educational resources independently of the classification taxonomy utilized in the hosting repository. For that, an automated classification algorithm is trained using the information extracted from the metadata of a collection of educational resources hosted in different repositories, which in turn depends on the classification taxonomy used in each case. Then, every resource will be automatically classified on demand independently of the original classification scheme. As a consequence, resources can be retrieved independently of the original taxonomy utilized using any taxonomy supported by the aggregator, and exploratory searches can be made without a previous taxonomy mapping. This approach overcomes one of the recurring problems in taxonomy mapping, namely the one-to-none matching situation. To evaluate the performance of this proposal two methods were applied. Resource classification in categories existing in all repositories was automatically evaluated, obtaining maximum performance values of 84% (F1 score), 87.8% (area under the receiver operator characteristic curve), 86% (area under the precision-recall curve) and 75.1% (Cohen's κ). In the case of resources not belonging to one of the common categories, human inspection was used as a reference to compute classification performance. In this case, maximum performance values obtained were respectively 69.8%, 73.8%, 75% and 54.3%. These results demonstrate the potential of this approach as a tool to facilitate resource classification, for example to provide a preliminary classification that would require just minor corrections from human classifiers.Xunta de Galicia | Ref. R2014/034 (RedPlir)Xunta de Galicia | Ref. R2014/029 (TELGalicia

Nitrogen inputs influence on biomass and trophic structure of ocean plankton: a study using biomass and stable isotope size-spectra.

Large scale patterns in planktonic food web structure were studied by applying continuous size-scaled models of biomass and δ15N to plankton samples, collected at 145 stations during the Malaspina-2010 Expedition across three ocean basins and including major biomes. Carbon biomass and δ15N were determined in size-fractionated samples (40 to 5000 μm) collected by vertical hauls (0-200 m). Biomass-normalized size-spectra were constructed to summarize food web structure and spatial patterns in spectral parameters were analyzed using geographically-weighted regression analysis. Except in the northwestern Atlantic, size-spectra showed low variability, reflecting a large homogeneity in nitrogen sources and food web structure for the central oceans. Estimated predator-to-prey mass ratios 20% (Trades and Westerlies biomes) suggested that oceanic plankton food webs could support a larger number of trophic levels than current estimates based on high efficiency values. The largest changes in spectral parameters and nitrogen sources were related to inputs of atmospheric nitrogen, either from diazotrophic organisms or dust deposition. These results suggest geographic homogeneity in the net transfer of nitrogen up the food web.CONSOLIDER-INGENIO 2010 (CSD2008-00077) ; EURO-BASIN (FP7-ENV-2010 264933)Preprint1,749

Nitrogen fixation in the upwelling region off NW Iberia

Comunicación oralPicoplankton are the most abundant organisms in the ocean, often dominate planktonic biomass and primary production, and they could represent a substantial contribution to the global export of carbon. Nowadays, we have a limited understanding about the factors that control the picoplankton community structure. A recent analysis indicates that light and temperature are the main factors explaining Prochlorococcus and Synechococcus distributions, whereas nutrient concentrations play a minor role (Flombaum et al., PNAS 2013). Methodological difficulties to quantify mixing in the marine enviroments have motivated the use of indirect approaches to determine the input of nutrients into the euphotic zone, however, nutrient concentrations are not necessarily a proxy of nutrient supply. We present a large data set, including open-ocean and coastal regions, of simultaneous measurements of picoplankton abundance, temperature and irradiance, together with estimates of nutrient supply. The transport of nutrients across the nutricline was computed combining nutrient concentrations and small-scale turbulence observations collected with a microstructure profiler. Our preliminary results indicate that nutrient supply also plays a role in the distribution of functional groups of picoplankton in the ocean

26,26,26,27,27,27-Hexadeuterated-1,25-Dihydroxyvitamin D3 (1,25D-d6) As Adjuvant of Chemotherapy in Breast Cancer Cell Lines

It has been demonstrated that 1,25-dihydroxyvitamin D3 (1,25D) and some of its analogues have antitumor activity. 1,25D labeled with deuterium (26,26,26,27,27,27-hexadeuterated 1a,25-dihydroxyvitamin D3, or 1,25D-d6) is commonly used as internal standard for 1,25D liquid chromatography-mass spectrometry (LC-MS) quantification. In the present study using human breast cancer cell lines, the biological activity of 1,25D-d6 administered alone and in combination with two commonly used antineoplastic agents, 5-fluorouracil and etoposide, was evaluated. Using an MTT assay, flow cytometry, and western blots, our data demonstrated that 1,25D-d6 has effects similar to the natural hormone on cell proliferation, cell cycle, and apoptosis. Furthermore, the combination of 1,25D-d6 and etoposide enhances the antitumoral effects of both compounds. Interestingly, the antitumoral effect is higher in the more aggressive MDA-MB-231 breast cancer cell line. Our data indicate that 1,25D-d6 administered alone or in combination with chemotherapy could be a good experimental method for accurately quantifying active 1,25D levels in cultures or in biological fluids, on both in vitro breast cancer cell lines and in vivo animal experimental models.Ministerio de Economía y Competividad; SAF2012-38240Ministerio de Educación e Innovación. MEI; SAF2010-15291Xunta de Galicia; CN2012/074Xunta de Galicia; INCITE08PXIB209130P