IL-3 or IL-7 Increases ex Vivo Gene Transfer Efficiency in ADA-SCID BM CD34 + Cells while Maintaining in Vivo Lymphoid Potential

To improve maintenance and gene transfer of human lymphoid progenitors for clinical use in gene therapy of adenosine deaminase (ADA)-deficient SCID we investigated several gene transfer protocols using various stem cell-enriched sources. The lymphoid differentiation potential was measured by an in vitro clonal assay for B/NK cells and in the in vivo SCID-hu mouse model. Ex vivo culture with the cytokines TPO, FLT3-ligand, and SCF (T/F/S) plus IL-3 or IL-7 substantially increased the yield of transduced bone marrow (BM) CD34+ cells purified from ADA-SCID patients or healthy donors, compared to T/F/S alone. Moreover, the use of IL-3 or IL-7 significantly improved the maintenance of in vitro B cell progenitors from ADA-SCID BM cells and allowed the efficient transduction of B and NK cell progenitors. Under these optimized conditions transduced CD34+ cells were efficiently engrafted into SCID-hu mice and gave rise to B and T cell progeny, demonstrating the maintenance of in vivo lymphoid reconstitution capacity. The protocol based on the T/F/S + IL-3 combination was included in a gene therapy clinical trial for ADA-SCID, resulting in long-term engraftment of stem/progenitor cells. Remarkably, gene-corrected BM CD34+ cells obtained from one patient 4 and 11 months after gene therapy were capable of repopulating the lymphoid compartment of SCID-hu hosts

Fundamentos hobbesianos de la economía moderna. Una aproximación

ResumenEste artículo resultado de investigación, busca introducir al lector en los aportes de Thomas Hobbes a la economía como ciencia. Este filósofo, aunque no figura como un autor relevante en los textos tradicionales de pensamiento económico, logró elaborar de manera sólida numerosos conceptos epistemológicos, antropológicos e institucionales recogidos por varias escuelas, entre las que se encuentran los marxistas, neoclásicos y keynesianos, quienes sustentan en ello el control centralizado de la acción humana. Aunque su trabajo originalmente no tuvo un fin eminentemente económico, es posible establecer cómo sus aportes filosóficos tienen alcances en las ciencias sociales, y en especial en la economía. Sus contribuciones se centraron en las nociones de colectivización del individuo y de la planificación centralizada. Además, Hobbes es, al menos en parte, el inspirador del socialismo como modo de orden social centralizado.Recibido: 20/08/2015   Aceptado: 18/11/2015 AbstractThe present essay is the outcome of a research program, and it aims to present the reader the main contributions of Thomas Hobbes to the economic science. Although this thinker has not been considered a relevant author in the traditional textbooks of economic thought, he nevertheless elaborated numerous solid epistemological, anthropological, and institutional concepts which have been incorporated into the theoretical corpus of several schools of thought, like the Marxist, Neoclassical, and Keynesian, concepts that buttress the idea of the centralized control of human action. Despite the fact that his work was not originally intended to be applied in the economic field, it is plausible to admit that his philosophical contributions have had their significance in the social sciences, especially in economics. In particular, these contributions will focus on the notions of collectivization of the individual and central planning. Hobbes is, at least in part, the inspirer of socialism understood as a form of centralized social order.Received: 20/08/2015  Accepted: 18/11/201

Fundamentos hobbesianos de la economía moderna. Una aproximación

ResumenEste artículo resultado de investigación, busca introducir al lector en los aportes de Thomas Hobbes a la economía como ciencia. Este filósofo, aunque no figura como un autor relevante en los textos tradicionales de pensamiento económico, logró elaborar de manera sólida numerosos conceptos epistemológicos, antropológicos e institucionales recogidos por varias escuelas, entre las que se encuentran los marxistas, neoclásicos y keynesianos, quienes sustentan en ello el control centralizado de la acción humana. Aunque su trabajo originalmente no tuvo un fin eminentemente económico, es posible establecer cómo sus aportes filosóficos tienen alcances en las ciencias sociales, y en especial en la economía. Sus contribuciones se centraron en las nociones de colectivización del individuo y de la planificación centralizada. Además, Hobbes es, al menos en parte, el inspirador del socialismo como modo de orden social centralizado.Recibido: 20/08/2015   Aceptado: 18/11/2015 AbstractThe present essay is the outcome of a research program, and it aims to present the reader the main contributions of Thomas Hobbes to the economic science. Although this thinker has not been considered a relevant author in the traditional textbooks of economic thought, he nevertheless elaborated numerous solid epistemological, anthropological, and institutional concepts which have been incorporated into the theoretical corpus of several schools of thought, like the Marxist, Neoclassical, and Keynesian, concepts that buttress the idea of the centralized control of human action. Despite the fact that his work was not originally intended to be applied in the economic field, it is plausible to admit that his philosophical contributions have had their significance in the social sciences, especially in economics. In particular, these contributions will focus on the notions of collectivization of the individual and central planning. Hobbes is, at least in part, the inspirer of socialism understood as a form of centralized social order.Received: 20/08/2015  Accepted: 18/11/201

Aplicación del modelo Léxico-Sintáctico para detectar la polaridad de opiniones sobre profesores

En el presente trabajo se muestran los resultados obtenidos de la aplicación del modelo léxico sintáctico a las opiniones dadas por estudiantes de la Facultad de Ciencias de la Computación de la Benemérita Universidad Autónoma de Puebla, acerca de los profesores que impartieron cursos en verano del 2015. Se confeccionó un corpus categorizado con las opiniones obtenidas de una encuesta aplicada. El corpus obtenido permitió la confección de un modelo de clasificación que permite detectar la polaridad de opinión (positiva, negativa o neutra). Los resultados obtenidos desarrollando el modelo con el 80% de las opiniones y probando con el 20% ofrecieron una precisión del 65%.Palabra(s) Clave(s): análisis de sentimientos, minería de opinión, modelo léxico sintáctico, proceso enseñanza-aprendizaje

Clinical Benefit of Tamsulosin and the Hexanic Extract of Serenoa Repens, in Combination or as Monotherapy, in Patients with Moderate/Severe LUTS-BPH: A Subset Analysis of the QUALIPROST Study

To investigate whether tamsulosin (TAM) and the hexanic extract of Serenoa repens (HESr) are more effective in combination than as monotherapy in men with moderate-to-severe lower urinary tract symptoms associated with benign prostatic hyperplasia (LUTS/BPH). Subset analysis of data from a 6-month, multicenter observational study. Patients received either tamsulosin (0.4 mg/day) or HESr (320 mg/day) alone or in combination. Primary endpoints were change in symptoms and quality of life. Tolerability was also assessed. Seven hundred and nine patients were available for intention to treat (ITT) analysis, 263 treated with tamsulosin, 262 with HESr, and 184 with TAM + HESr. After 6 months, International Prostate Symptom Score (IPSS) scores improved by a mean (standard deviation) of 7.2 (5.0) points in the TAM + HESr group compared to 5.7 (4.3) points with TAM alone and 5.4 (4.6) points with HESr (p < 0.001). Quality of life showed greatest improvement with combination therapy (p < 0.02). Adverse effects were reported by 1.9% of patients receiving HESr, 13.3% receiving TAM, and 12.0% receiving TAM + HESr (p < 0.001). In men with moderate/severe LUTS/BPH, combination treatment with TAM + HESr produced more effective symptom relief and greater improvement in quality of life than with either treatment alone, with acceptable tolerability

Innate acting memory Th1 cells modulate heterologous diseases

Through immune memory, infections have a lasting effect on the host. While memory cells enable accelerated and enhanced responses upon rechallenge with the same pathogen, their impact on susceptibility to unrelated diseases is unclear. We identify a subset of memory T helper 1 (Th1) cells termed innate acting memory T (TIA) cells that originate from a viral infection and produce IFN-γ with innate kinetics upon heterologous challenge in vivo. Activation of memory TIA cells is induced in response to IL-12 in combination with IL-18 or IL-33 but is TCR independent. Rapid IFN-γ production by memory TIA cells is protective in subsequent heterologous challenge with the bacterial pathogen Legionella pneumophila. In contrast, antigen-independent reactivation of CD4+ memory TIA cells accelerates disease onset in an autoimmune model of multiple sclerosis. Our findings demonstrate that memory Th1 cells can acquire additional TCR-independent functionality to mount rapid, innate-like responses that modulate susceptibility to heterologous challenges

Regional differences in modelled net production and shallow remineralization in the North Atlantic subtropical gyre

© The Author(s), 2012. This article is distributed under the terms of the Creative Commons Attribution License. The definitive version was published in Biogeosciences 9 (2012): 2831-2846, doi:10.5194/bg-9-2831-2012.We used 5-yr concomitant data of tracer distribution from the BATS (Bermuda Time-series Study) and ESTOC (European Station for Time-Series in the Ocean, Canary Islands) sites to build a 1-D tracer model conservation including horizontal advection, and then compute net production and shallow remineralization rates for both sites. Our main goal was to verify if differences in these rates are consistent with the lower export rates of particulate organic carbon observed at ESTOC. Net production rates computed below the mixed layer to 110 m from April to December for oxygen, dissolved inorganic carbon and nitrate at BATS (1.34±0.79 mol O2 m−2, −1.73±0.52 mol C m−2 and −125±36 mmol N m−2) were slightly higher for oxygen and carbon compared to ESTOC (1.03±0.62 mol O2 m−2, −1.42±0.30 mol C m−2 and −213±56 mmol N m−2), although the differences were not statistically significant. Shallow remineralization rates between 110 and 250 m computed at ESTOC (−3.9±1.0 mol O2 m−2, 1.53±0.43 mol C m−2 and 38±155 mmol N m−2) were statistically higher for oxygen compared to BATS (−1.81±0.37 mol O2 m−2, 1.52±0.30 mol C m−2 and 147±43 mmol N m−2). The lateral advective flux divergence of tracers, which was more significant at ESTOC, was responsible for the differences in estimated oxygen remineralization rates between both stations. According to these results, the differences in net production and shallow remineralization cannot fully explain the differences in the flux of sinking organic matter observed between both stations, suggesting an additional consumption of non-sinking organic matter at ESTOC.B. Mourino was supported by the Ramon y Cajal program from the Spanish Minister of Science and Technology. Funding for this study was provided by the Xunta de Galicia under the research project VARITROP (09MDS001312PR, PI B. Mourino) and by the Ministerio de Ciencia e Innovation MOMAC project (CTM2008-05914/MAR)

Importance of N2 fixation vs. nitrate diffusion along a latitudinal transect in the Atlantic Ocean

We present ocean, basin-scale simultaneous measurements of N2-fixation, nitrate diffusion, and primary production along a south–north transect in the Atlantic Ocean crossing three biogeographic provinces: the south subtropical Atlantic (SSA; , 31uS–12uS), the equatorial Atlantic (EA; , 12uS–16uN), and the north subtropical Atlantic (NSA, , 16uN–9uN) in April–May 2008. N2-fixation and primary production were measured as 15N2 and 14C uptake, respectively. Dissipation rates of turbulent kinetic energy (e) were measured with a microstructure profiler. The vertical input of nitrate through eddy diffusion was calculated from the product of diffusivity, derived from e, and the gradient of nanomolar nitrate concentration across the base of the euphotic zone. The mean N2-fixation rate in EA was 56 6 49 mmol N m22 d21, whereas SSA and NSA had much lower values (, 10 mmol N m22 d21). Because of the large spatial variability in nitrate diffusion (34 6 50, 405 6 888, and 844 6 1258 mmol N m22 d21 in SSA, EA, and NSA, respectively), the contribution of N2-fixation to new production in the SSA, EA, and NSA was 44% 6 30%, 22% 6 19%, and 2% 6 2%, respectively. The differences between SSA and NSA in the contribution of N2 fixation were partly due to the contrasting seasonal forcing in each hemisphere, which likely affected both N2 fixation rates and vertical nitrate diffusion. The variability in the nitrogen budget of the Atlantic subtropical gyres was unexpectedly high and largely uncoupled from relatively constant phytoplankton standing stocks and primary production rates.CTM2004-05174-C02 CTM2007-28295-E/MAR Programa I. Parga-Ponda

Factors controlling the community structure of picoplankton in contrasting marine environments

The effect of inorganic nutrients on planktonic assemblages has traditionally relied on concentrations rather than estimates of nutrient supply. We combined a novel dataset of hydrographic properties, turbulent mixing, nutrient concentration, and picoplankton community composition with the aims of (i) quantifying the role of temperature, light, and nitrate fluxes as factors controlling the distribution of autotrophic and heterotrophic picoplankton subgroups, as determined by flow cytometry, and (ii) describing the ecological niches of the various components of the picoplankton community. Data were collected at 97 stations in the Atlantic Ocean, including tropical and subtropical open-ocean waters, the northwestern Mediterranean Sea, and the Galician coastal upwelling system of the northwest Iberian Peninsula. A generalized additive model (GAM) approach was used to predict depth-integrated biomass of each picoplankton subgroup based on three niche predictors: sea surface temperature, averaged daily surface irradiance, and the transport of nitrate into the euphotic zone, through both diffusion and advection. In addition, niche overlap among different picoplankton subgroups was computed using nonparametric kernel density functions. Temperature and nitrate supply were more relevant than light in predicting the biomass of most picoplankton subgroups, except for Prochlorococcus and low-nucleic-acid (LNA) prokaryotes, for which irradiance also played a significant role. Nitrate supply was the only factor that allowed the distinction among the ecological niches of all autotrophic and heterotrophic picoplankton subgroups. Prochlorococcus and LNA prokaryotes were more abundant in warmer waters (>20 ∘C) where the nitrate fluxes were low, whereas Synechococcus and high-nucleic-acid (HNA) prokaryotes prevailed mainly in cooler environments characterized by intermediate or high levels of nitrate supply. Finally, the niche of picoeukaryotes was defined by low temperatures and high nitrate supply. These results support the key role of nitrate supply, as it not only promotes the growth of large phytoplankton, but it also controls the structure of marine picoplankton communities.Ministerio de Economía y Competitividad | Ref. CTM2012-30680Ministerio de Economía y Competitividad | Ref. CTM2008-0626I-C03-01Ministerio de Economía y Competitividad | Ref. REN2003-09532-C03-01Ministerio de Economía y Competitividad | Ref. CTM2004-05174 -C02Ministerio de Economía y Competitividad | Ref. CTM2011-25035Xunta de Galicia | Ref. 09MMA027604PRXunta de Galicia | Ref. EM2013/021European Commission | Ref. FP7, n. 261860Ministerio de Economía y Competitividad | Ref. FJCI-641 2015-2571

Effectiveness of influenza vaccination programme in preventing hospital admissions, Valencia, 2014/15 early results

Preliminary results for the 2014/15 season indicate low to null effect of vaccination against influenza A(H3N2)-related disease. As of week 5 2015, there have been 1,136 hospital admissions, 210 were due to influenza and 98% of subtype A strains were H3. Adjusted influenza vaccine effectiveness was 33% (range: 6–53%) overall and 40% (range: 13% to 59%) in those 65 years and older. Vaccination reduced by 44% (28–68%) the probability of admission with influenza.The study was funded by a contract between FISABIO and Sanofi-Pasteur