Enantioselective Synthesis of Functionalized Diazaspirocycles from 4-Benzylideneisoxazol-5(4H)-one derivatives and Isocyanoacetate Esters

Enantioenriched spirocyclic compounds bearing three contiguous stereocenters and high functionalization were obtained through a formal [3+2] cycloaddition reaction catalyzed by a cooperative system. The spiro compounds were synthesized from 4-arylideneisoxazol-5-ones and isocyanoacetate esters using a bifunctional squaramide/Brønsted base organocatalyst derived from a Cinchona alkaloid and silver oxide as Lewis acid. This method afforded two out of the four possible diastereomers with good yields and high enantiomeric excess for both diastereomers

Enantioselective Synthesis of 5‑Trifluoromethyl-2-oxazolines under Dual Silver/Organocatalysis

The first enantioselective formal [3 + 2] cycloaddition between α-isocyanoesters and trifluoromethylketones to give 5-trifluoromethyl-2-oxazolines bearing two contiguous stereogenic centers, one of them being a quaternary stereocenter substituted with a CF3 group, has been developed. The reaction is based upon a multicatalytic approach that combines a bifunctional Brønsted base-squaramide organocatalyst and Ag+ as Lewis acid. The reaction could be achieved with a range of aryl and heteroaryl trifluoromethyl ketones, and the resulting oxazolines were obtained with good to excellent diastereo- and enantioselectivity

Catalytic Diastereo- and Enantioselective Synthesis of 2‑Imidazolinones

Chiral cyclic ureas (2-imidazolinones) were prepared by the reaction of nitrones and isocyanoacetate esters using a multicatalytic system that combines a bifunctional Brønsted base-squaramide organocatalyst and Ag+ as a Lewis acid. The reaction could be achieved with a range of nitrones derived from aryl- and cycloalkylaldehydes with moderate diastereo- and good enantioselectivity. A plausible mechanism involving an initial formal [3 + 3] cycloaddition of the nitrone and isocyanoacetate ester, followed by rearrangement to an aminoisocyanate and cyclization to the imidazolinone, is proposed

Enantioselective synthesis of chiral oxazolines from unactivated ketones and isocyanoacetate esters by synergistic silver/organocatalysis

A multicatalytic approach that combines a bifunctional Brønsted base-squaramide organocatalyst and Ag+ as Lewis acid has been applied in the reaction of unactivated ketones with tert-butyl isocyanoacetate to give chiral oxazolines bearing a quaternary stereocenter. The formal [3+2] cycloaddition provided high yields of the corresponding cis-oxazolines with good diastereoselectivity and excellent enantioselectivity, being applied to aryl-alkyl and alkyl-alkyl ketones

Tissue-specific decellularized endometrial substratum mimicking different physiological conditions influences in vitro embryo development in a rabbit model

[EN] In the last decades, the decellularization (DC) of organs has become an established technique in the field of regenerative medicine to yield complex and vascularized bioscaffolds. Furthermore, it has been demonstrated in vitro that these decellularized scaffolds retain their native tissue-specificity. This is also the case when this tissue-specific extracellular matrix (ECM) is solubilized and used as hydrogels or coatings to create a biomimetic environment. In this study we investigated if this specificity not only remains when applied to distinct tissues but even more, that these differences can be distinguished within the same tissue at different stages of proliferation. To address this question, a sensitive in vitro animal model was used: rabbit embryos at the third day of development were cultured on coatings made from acellular endometrium that was non-proliferating (non-synchronous, NS) and proliferating (synchronous with the embryo, S) and their development was compared. For this, we obtained whole NS and S rabbit uteri and subjected them to an adapted decellularization protocol. The acellular endometrium was carefully separated by microdissection and converted into a pre-gel solution to be used as hydrogels and coatings for in vitro assays. First, the characteristics of these NS and S hydrogels were investigated by proteomic analysis, electron microscopy and gelling kinetics. When used as substrata for day 3 embryos culture, it became apparent that only the acellular ECM from synchronous endometrial coating achieved similar results to the gold standard culture protocols and conditions, possibly because of the slow release of growth factors present in the synchronous/proliferating endometrium. Statement of Significance It has been shown by in vitro culture of stem cells, progenitor cells and primary culture cells that decellularized tissues retain their specific functions and biochemical and structural compositions. The present work demonstrates that using a mild SDS and perfusion based decellularization (DC) protocol not only effectively decellularize whole rabbit uteri, adding to the growing field of reproductive tissue engineering, but more importantly that the differences in the proliferating endometrium are translated after DC. This implies that DC not only retains the interspecificity of tissues but also the intraspecificity of a developing hormonally stimulated tissue. For the first time, we demonstrate that the coating from decellularized synchronous endometrium acts as a biological support for in vitro embryo development, achieving comparable results with the current gold standard that only uses serum-containing media. (C) 2019 Acta Materialia Inc. Published by Elsevier Ltd. This is an open access article under the CC BY-NC-ND license (http://creativecommons.org/licenses/by-nc-nd/4.0/).This study was supported by the following entities: GRISO-LIA/2015/002 (HC); PI17/01039 (IC); Prometeo/2018/137 (IC); AGL2017-85162-C2-1-R; BES-2015-072429 (XGD); ACIF/2017/118 (SLM). The proteomics laboratory is a member of Proteored, PRB3 and is supported by grant PT17/0019, of the PE I + D + i 2013-2016, funded by ISCIII and ERDF.Campo, H.; Garcia-Dominguez, X.; López-Martínez, S.; Faus, A.; Vicente Antón, JS.; Marco-Jiménez, F.; Cervello, I. (2019). Tissue-specific decellularized endometrial substratum mimicking different physiological conditions influences in vitro embryo development in a rabbit model. Acta Biomaterialia. 89:126-138. https://doi.org/10.1016/j.actbio.2019.03.004S1261388

Avanzando hacia el control glucémico en diabetis mellitus tipo 2

INTRODUCCIÓN: La diabetes mellitus tipo 2 (DM2) es la enfermedad metabólica crónica más frecuente en nuestro medio. La prevalencia de DM2 ha crecido exponencialmente en los últimos años, incidiendo directamente en el aumento de la morbimortalidad de la población afectada. En un reciente estudio poblacional realizado en España, se observó que la prevalencia se sitúa en torno al 13,8 % de la población adulta, con un 43,5 % de casos no conocidos ..

La enseñanza del léxico. Reflexiones teóricas y propuestas didácticas

Este volumen recoge diversos trabajos sobre la enseñanza del léxico. Cómo explicar los procesos de adquisición y cómo aprovechar su descripción con una orientación didáctica son las líneas genéricas que vertebran las contribuciones aquí reunidasThis volume includes several papers on the teaching of vocabulary. The basic lines that structure the contributions here made are the explanation of the lexical acquisition process and how to use the description of this process with a didactic approac

JASON-1 CALVAL experiences in Cape of Begur and Ibiza island

The direct and indirect calibration experiences made at the Cape of Begur area in 1999, 2000 and 2002, for Topex/Poseidon and at the Ibiza island in 2003 have contributed to the international campaigns made at Harvest (USA), Corsica (France) and Bass (Australia). The main objective of IBIZA 2003 campaign has been the determination of the instantaneous sea surface/marine geoid gradient along Jason-1 tracks using a GPS catamaran and a network of GPS located in Portinatx and Ibiza and San Antonio harbours. The marine geoid will be used to relate the tide gauge coastal data with the altimeter data. We present the first results obtained with static and kinematic analysis of the data using different softwares.Peer ReviewedPostprint (published version

Search for heavy stable charged particles in pp collisions at ?s = 7 TeV

The result of a search at the LHC for heavy stable charged particles produced in pp collisions at s?=7TeV is described. The data sample was collected with the CMS detector and corresponds to an integrated luminosity of 3.1 pb?1. Momentum and ionization-energy-loss measurements in the inner tracker detector are used to identify tracks compatible with heavy slow-moving particles. Additionally, tracks passing muon identification requirements are also analyzed for the same signature. In each case, no candidate passes the selection, with an expected background of less than 0.1 events. A lower limit at the 95% confidence level on the mass of a stable gluino is set at 398GeV/c 2, using a conventional model of nuclear interactions that allows charged hadrons containing this particle to reach the muon detectors. A lower limit of 311 GeV/c 2 is also set for a stable gluino in a conservative scenario of complete charge suppression, where any hadron containing this particle becomes neutral before reaching the muon detectors.We are grateful to Anna Kulesza and Michael Krämer for providing the theoretical production cross sections and associated uncertainties at next-to-leading order for pair production of eg and ˜t1. We wish to congratulate our colleagues in the CERN accelerator departments for the excellent performance of the LHC machine. We thank the technical and administrative staff at CERN and other CMS institutes, and acknowledge support from: FMSR (Austria); FNRS and FWO (Belgium); CNPq, CAPES, FAPERJ, and FAPESP (Brazil); MES (Bulgaria); CERN; CAS, MoST, and NSFC (China); COLCIENCIAS (Colombia); MSES (Croatia); RPF (Cyprus); Academy of Sciences and NICPB (Estonia); Academy of Finland, ME, and HIP (Finland); CEA and CNRS/IN2P3 (France); BMBF, DFG, and HGF (Germany); GSRT (Greece); OTKA and NKTH (Hungary); DAE and DST (India); IPM (Iran); SFI (Ireland); INFN (Italy); NRF and WCU (Korea); LAS (Lithuania); CINVESTAV, CONACYT, SEP, and UASLP-FAI (Mexico); PAEC (Pakistan); SCSR (Poland); FCT (Portugal); JINR (Armenia, Belarus, Georgia, Ukraine, Uzbekistan); MST and MAE (Russia); MSTD (Serbia); MICINN and CPAN (Spain); Swiss Funding Agencies (Switzerland); NSC (Taipei); TUBITAK and TAEK (Turkey); STFC (United Kingdom); DOE and NSF (USA)

Search for resonances in the dilepton mass distribution in pp collisions at √s = 7TeV

A search for narrow resonances at high mass in the dimuon and dielectron channels has been performed by the CMS experiment at the CERN LHC, using pp collision data recorded at √s = 7TeV. The event samples correspond to integrated luminosities of 40 pb−1 in the dimuon channel and 35 pb−1 in the dielectron channel. Heavy dilepton resonances are predicted in theoretical models with extra gauge bosons (Z′) or as Kaluza-Klein graviton excitations (GKK) in the Randall-Sundrum model. Upper limits on the inclusive cross section of Z′(GKK) ! ℓ+ℓ− relative to Z ! ℓ+ℓ− are presented. These limits exclude at 95% confidence level a Z′ with standard-model-like couplings below 1140 GeV, the superstring-inspired Z′ ψ below 887 GeV, and, for values of the coupling parameter k/MPl of 0.05 (0.1), Kaluza-Klein gravitons below 855 (1079) GeV.We wish to congratulate our colleagues in the CERN accelerator departments for the excellent performance of the LHC machine. We thank the technical and administrative staff at CERN and other CMS institutes, and acknowledge support from: FMSR (Austria); FNRS and FWO (Belgium); CNPq, CAPES, FAPERJ, and FAPESP (Brazil); MES (Bulgaria); CERN; CAS, MoST, and NSFC (China); COLCIENCIAS (Colombia); MSES (Croatia); RPF (Cyprus); Academy of Sciences and NICPB (Estonia); Academy of Finland, ME, and HIP (Finland); CEA and CNRS/IN2P3 (France); BMBF, DFG, and HGF (Germany); GSRT (Greece); OTKA and NKTH (Hungary); DAE and DST (India); IPM (Iran); SFI (Ireland); INFN (Italy); NRF and WCU (Korea); LAS (Lithuania); CINVESTAV, CONACYT, SEP, and UASLP-FAI (Mexico); PAEC (Pakistan); SCSR (Poland); FCT (Portugal); JINR (Armenia, Belarus, Georgia, Ukraine, Uzbekistan); MST and MAE (Russia); MSTD (Serbia); MICINN and CPAN (Spain); Swiss Funding Agencies (Switzerland); NSC (Taipei); TUBITAK and TAEK (Turkey); STFC (United Kingdom); DOE and NSF (USA)