Organocatalytically Generated Donor − Acceptor Cyclopropanes in Domino Reactions. One-Step Enantioselective Synthesis of Pyrrolo[1,2 ‑ a ]quinolines

An easy and straightforward procedure has been developed for the synthesis of highly enantioenriched pyrrolo-[1,2-a]quinolines through a one-pot process that comprises a domino cyclopropane ring opening/aza-Michael/aldol reaction followed by acid-promoted lactamization. The key feature of the synthetic approach relies on the ability of conveniently functionalized cyclopropaneacetaldehydes to undergo organocatalytic activation by a chiral secondary amine that enables the catalytic generation of a donor acceptor cyclopropane. This intermediate has the potential to undergo a ring opening that generates an electrophilic alpha,beta-unsaturated iminium ion that subsequently reacts through the already mentioned domino sequence and in which stereochemical information is very efficiently transferred from the amine catalyst to the final products. Moreover, one of the alkoxycarbonyl moieties can be easily removed by standard hydrolysis/decarboxylation, providing access to the target adducts as single stereoisomers.This research was supported by the Spanish MINECO (FEDER-CTQ2014-52107-P), the Basque Government (Grupos IT328-10), and UPV/EHU (fellowship to E.S. and UFI QOSYC 11/22). Membership in the COST action CM1407 (NatChemDrugs) is also acknowledged

Role of drug transporters in the sensitivity of acute myeloid leukemia to sorafenib

[EN]Chemoresistance often limits the success of the pharmacological treatment in acute myeloid leukemia (AML) patients. Although positive results have been obtained with tyrosine kinase inhibitors (TKIs), such as sorafenib, especially in patients with Fms-like tyrosine kinase 3 (FLT3)-positive AML, the success of chemotherapy is very heterogeneous.The sensitivity to sorafenib-induced cell death (MTT test and anexin V/7-AAD method) was evaluated in five different cell lines: MOLM-13, OCI-AML2, HL-60, HEL and K-562. The transportome was characterized by measuring mRNA using RT-qPCR. Drug uptake/efflux was determined by flow cytometry using specific substrates and inhibitors. The cytostatic response to sorafenib was: MOLM-13»OCI-AML2>HL- 60>HEL≈K-562. Regarding efflux pumps, MDR1 was highly expressed in HEL>K- 562≈MOLM-13, but not in OCI-AML2 and HL-60. BCRP and MPR3 expression was low in all cell lines, whereas MRP4 and MRP5 expression was from moderate to high. Flow cytometry studies demonstrated that MRP4, but not MRP5, was functional

Experiencia de 10 años de innovación docente en la Unidad de Laboratorios Docentes (ULD) de la Facultad de Farmacia

[spa]En este trabajo se describe la experiencia de innovación docente desarrollada en la ULD a lo largo de los 10 años de existencia. Se comentan algunos de los indicadores del sistema de gestión de la calidad así como su evolución y los resultados más representativos obtenidos en su alimentación. El objetivo de este proyecto es introducir aspectos de la gestión de la calidad, seguridad, salud y medio ambiente en la formación de los estudiantes para que los apliquen a lo largo del desarrollo de las prácticas. De esta forma, podrán adquirir una formación transversal adicional que difícilmente le será transmitida a través de las diferentes asignaturas de la licenciatura y que mejorará sus competencias y facilitará su acceso al ámbito laboral. También se pretende contribuir en la mejora del funcionamiento y las infraestructuras de los laboratorios de prácticas de la facultad. [eng] In the following work it is summarized the innovative experience carried out by the ULD besides showing the results obtained from the different indicators that allow to evaluate the efficiency of the quality management system. The aim is to improve the management of the practical teaching by introducing aspects of quality management, safety, health and environment in the formation of the students. In such a way, they would be able to acquire a transverse additional formation that difficultly would be transmitted across the different subjects of the degree and that would improve their competitions when acceding to the working world

Theoretical modelling of quaternary GaInAsSb/GaAs self-assembled quantum dots

Trabajo presentado al "Quantum Dot", celebrado en Nottingham (UK) del 26 al 30 de Abril de 2010.InAs/GaAs quantum dots exposed to Sb after growth exhibit spectral changes. We study in the present paper an idealized nanostructure consisting of a homogeneous distribution of the quaternary GaInAsSb surrounded by a barrier of GaAs. We nd that the valence band o set is a critical parameter in modelling its electronic structure. Depending on this value, we predict a transition from type-I to type-II band alignment at a di erent Sb concentration. The addition of Sb to reduce the transition energy while keeping a type-I alignment is only of bene t at low Sb concentrationThis work was supported by the Spanish MICINN (projects TEC2008-06756-C03-01/02/TEC, CONSOLIDER INGENIO 2010 CSD2006-0019 and CSD2009-00013), the Junta de Andalucía (PAI research groups TEP-120 and TIC-145; project P08-TEP-03516) and Comunidad Autónoma de Madrid S2009ESP-1503.Peer reviewe

The Genotype of the Donor for the (GT)n Polymorphism in the Promoter/Enhancer of FOXP3 Is Associated with the Development of Severe Acute GVHD but Does Not Affect the GVL Effect after Myeloablative HLA-Identical Allogeneic Stem Cell Transplantation

The FOXP3 gene encodes for a protein (Foxp3) involved in the development and functional activity of regulatory T cells (CD4+/CD25+/Foxp3+), which exert regulatory and suppressive roles over the immune system. After allogeneic stem cell transplantation, regulatory T cells are known to mitigate graft versus host disease while probably maintaining a graft versus leukemia effect. Short alleles (≤(GT)15) for the (GT)n polymorphism in the promoter/enhancer of FOXP3 are associated with a higher expression of FOXP3, and hypothetically with an increase of regulatory T cell activity. This polymorphism has been related to the development of auto- or alloimmune conditions including type 1 diabetes or graft rejection in renal transplant recipients. However, its impact in the allo-transplant setting has not been analyzed. In the present study, which includes 252 myeloablative HLA-identical allo-transplants, multivariate analysis revealed a lower incidence of grade III-IV acute graft versus host disease (GVHD) in patients transplanted from donors harboring short alleles (OR = 0.26, CI 0.08-0.82, p = 0.021); without affecting chronic GVHD or graft versus leukemia effect, since cumulative incidence of relapse, event free survival and overall survival rates are similar in both groups of patients

The Spanish Infrared Camera onboard the EUSO-BALLOON (CNES) flight on August 24, 2014

The EUSO-Balloon (CNES) campaign was held during Summer 2014 with a launch on August 24. In the gondola, next to the Photo Detector Module (PDM), a completely isolated Infrared camera was allocated. Also, a helicopter which shooted flashers flew below the balloon. We have retrieved the Cloud Top Height (CTH) with the IR camera, and also the optical depth of the nonclear atmosphere have been inferred with two approaches: The first one is with the comparison of the brightness temperature of the cloud and the real temperature obtained after the pertinent corrections. The second one is by measuring the detected signal from the helicopter flashers by the IR Camera, considering the energy of the flashers and the location of the helicopter

State of Fisheries in Catalonia 2020. Part 1: Methods and Results (ICATMAR, 21-02)

513 pages, 416 figures, 77 tablesThis document presents the State of Fisheries in Catalonia between October 2019 and December 2020, both inclusive. It was produced by the Catalan Institute for Ocean Governance Research (ICATMAR), which is a cooperation organism between the Directorate-General of Maritime Policy & sustainable fisheries of the Government of Catalonia and the Institute of Marine Sciences (ICM) of the Spanish National Research Council (CSIC)Peer reviewe

The atmospheric science of JEM-EUSO

An Atmospheric Monitoring System (AMS) is critical suite of instruments for JEM-EUSO whose aim is to detect Ultra-High Energy Cosmic Rays (UHECR) and (EHECR) from Space. The AMS comprises an advanced space qualified infrared camera and a LIDAR with cross checks provided by a ground-based and airborne Global Light System Stations. Moreover the Slow Data Mode of JEM-EUSO has been proven crucial for the UV background analysis by comparing the UV and IR images. It will also contribute to the investigation of atmospheric effects seen in the data from the GLS or even to our understanding of Space Weather

Role of age and comorbidities in mortality of patients with infective endocarditis

[Purpose]: The aim of this study was to analyse the characteristics of patients with IE in three groups of age and to assess the ability of age and the Charlson Comorbidity Index (CCI) to predict mortality. [Methods]: Prospective cohort study of all patients with IE included in the GAMES Spanish database between 2008 and 2015.Patients were stratified into three age groups:<65 years,65 to 80 years,and ≥ 80 years.The area under the receiver-operating characteristic (AUROC) curve was calculated to quantify the diagnostic accuracy of the CCI to predict mortality risk. [Results]: A total of 3120 patients with IE (1327 < 65 years;1291 65-80 years;502 ≥ 80 years) were enrolled.Fever and heart failure were the most common presentations of IE, with no differences among age groups.Patients ≥80 years who underwent surgery were significantly lower compared with other age groups (14.3%,65 years; 20.5%,65-79 years; 31.3%,≥80 years). In-hospital mortality was lower in the <65-year group (20.3%,<65 years;30.1%,65-79 years;34.7%,≥80 years;p < 0.001) as well as 1-year mortality (3.2%, <65 years; 5.5%, 65-80 years;7.6%,≥80 years; p = 0.003).Independent predictors of mortality were age ≥ 80 years (hazard ratio [HR]:2.78;95% confidence interval [CI]:2.32–3.34), CCI ≥ 3 (HR:1.62; 95% CI:1.39–1.88),and non-performed surgery (HR:1.64;95% CI:11.16–1.58).When the three age groups were compared,the AUROC curve for CCI was significantly larger for patients aged <65 years(p < 0.001) for both in-hospital and 1-year mortality. [Conclusion]: There were no differences in the clinical presentation of IE between the groups. Age ≥ 80 years, high comorbidity (measured by CCI),and non-performance of surgery were independent predictors of mortality in patients with IE.CCI could help to identify those patients with IE and surgical indication who present a lower risk of in-hospital and 1-year mortality after surgery, especially in the <65-year group