Insulin-like growth factor-I gene delivery to astrocytes reduces their inflammatory response to lipopolysaccharide

<p>Abstract</p> <p>Background</p> <p>Insulin-like growth factor-I (IGF-I) exerts neuroprotective actions in the central nervous system that are mediated at least in part by control of activation of astrocytes. In this study we have assessed the efficacy of exogenous IGF-I and IGF-I gene therapy in reducing the inflammatory response of astrocytes from cerebral cortex.</p> <p>Methods</p> <p>An adenoviral vector harboring the rat IGF-I gene and a control adenoviral vector harboring a hybrid gene encoding the herpes simplex virus type 1 thymidine kinase fused to <it>Aequorea victoria </it>enhanced green fluorescent protein were used in this study. Primary astrocytes from mice cerebral cortex were incubated for 24 h or 72 h with vehicle, IGF-I, the IGF-I adenoviral vector, or control vector; and exposed to bacterial lipopolysaccharide to induce an inflammatory response. IGF-I levels were measured by radioimmunoassay. Levels of interleukin 6, tumor necrosis factor-α, interleukin-1β and toll-like receptor 4 mRNA were assessed by quantitative real-time polymerase chain reaction. Levels of IGF-I receptor and IGF binding proteins 2 and 3 were assessed by western blotting. The subcellular distribution of nuclear factor κB (p65) was assessed by immunocytochemistry. Statistical significance was assessed by one way analysis of variance followed by the Bonferroni pot hoc test.</p> <p>Results</p> <p>IGF-I gene therapy increased IGF-I levels without affecting IGF-I receptors or IGF binding proteins. Exogenous IGF-I, and IGF-I gene therapy, decreased expression of toll-like receptor 4 and counteracted the lipopolysaccharide-induced inflammatory response of astrocytes. In addition, IGF-I gene therapy decreased lipopolysaccharide-induced translocation of nuclear factor κB (p65) to the cell nucleus.</p> <p>Conclusion</p> <p>These findings demonstrate efficacy of exogenous IGF-I and of IGF-I gene therapy in reducing the inflammatory response of astrocytes. IGF-I gene therapy may represent a new approach to reduce inflammatory reactions in glial cells.</p

Vegetation water use based on a thermal and optical remote sensing model in the mediterranean region of Doñana

Terrestrial evapotranspiration (ET) is a central process in the climate system, is a major component in the terrestrial water budget, and is responsible for the distribution of water and energy on land surfaces especially in arid and semiarid areas. In order to inform water management decisions especially in scarce water environments, it is important to assess ET vegetation use by differentiating irrigated socio-economic areas and natural ecosystems. The global remote sensing ET product MOD16 has proven to underestimate ET in semiarid regions where ET is very sensitive to soil moisture. The objective of this research was to test whether a modified version of the remote sensing ET model PT-JPL, proven to perform well in drylands at Eddy Covariance flux sites using the land surface temperature as a proxy to the surface moisture status (PT-JPL-thermal), could be up-scaled at regional levels introducing also a new formulation for net radiation from various MODIS products. We applied three methods to track the spatial and temporal characteristics of ET in the World Heritage UNESCO Do&ntilde;ana region: (i) a locally calibrated hydrological model (WATEN), (ii) the PT-JPL-thermal, and (iii) the global remote sensing ET product MOD16. The PT-JPL-thermal showed strong agreement with the WATEN ET in-situ calibrated estimates (&rho; = 0.78, &rho;1month-lag = 0.94) even though the MOD16 product did not (&rho; = 0.48). The PT-JPL-thermal approach has proven to be a robust remote sensing model for detecting ET at a regional level in Mediterranean environments and it requires only air temperature and incoming solar radiation from climatic databases apart from freely available satellite products

Learning Criteria and Evaluation Metrics for Textual Transfer between Non-Parallel Corpora

We consider the problem of automatically generating textual paraphrases with modified attributes or stylistic properties, focusing on the setting without parallel data (Hu et al., 2017; Shen et al., 2017). This setting poses challenges for learning and evaluation. We show that the metric of post-transfer classification accuracy is insufficient on its own, and propose additional metrics based on semantic content preservation and fluency. For reliable evaluation, all three metric categories must be taken into account. We contribute new loss functions and training strategies to address the new metrics. Semantic preservation is addressed by adding a cyclic consistency loss and a loss based on paraphrase pairs, while fluency is improved by integrating losses based on style-specific language models. Automatic and manual evaluation show large improvements over the baseline method of Shen et al. (2017). Our hope is that these losses and metrics can be general and useful tools for a range of textual transfer settings without parallel corpora

A novel epigenetic signature for early diagnosis in lung cancer

Purpose: lung cancer remains as the leading cause of cancer-related death worldwide, mainly due to late diagnosis. Cytology is the gold-standard method for lung cancer diagnosis in minimally invasive respiratory samples, despite its low sensitivity. We aimed to identify epigenetic biomarkers with clinical utility for cancer diagnosis in minimally/noninvasive specimens to improve accuracy of current technologies. Experimental design: the identification of novel epigenetic biomarkers in stage I lung tumors was accomplished using an integrative genome-wide restrictive analysis of two different large public databases. DNA methylation levels for the selected biomarkers were validated by pyrosequencing in paraffin-embedded tissues and minimally invasive and noninvasive respiratory samples in independent cohorts. Results: we identified nine cancer-specific hypermethylated genes in early-stage lung primary tumors. Four of these genes presented consistent CpG island hypermethylation compared with nonmalignant lung and were associated with transcriptional silencing. A diagnostic signature was built using multivariate logistic regression model based on the combination of four genes: BCAT1, CDO1, TRIM58, and ZNF177. Clinical diagnostic value was also validated in multiple independent cohorts and yielded a remarkable diagnostic accuracy in all cohorts tested. Calibrated and cross-validated epigenetic model predicts with high accuracy the probability to detect cancer in minimally and noninvasive samples. We demonstrated that this epigenetic signature achieved higher diagnostic efficacy in bronchial fluids as compared with conventional cytology for lung cancer diagnosis. Conclusions: minimally invasive epigenetic biomarkers have emerged as promising tools for cancer diagnosis. The herein obtained epigenetic model in combination with current diagnostic protocols may improve early diagnosis and outcome of lung cancer patients

Grupo español de cirugía torácica asistida por videoimagen: método, auditoría y resultados iniciales de una cohorte nacional prospectiva de pacientes tratados con resecciones anatómicas del pulmón

Introduction: our study sought to know the current implementation of video-assisted thoracoscopic surgery (VATS) for anatomical lung resections in Spain. We present our initial results and describe the auditing systems developed by the Spanish VATS Group (GEVATS). Methods: we conducted a prospective multicentre cohort study that included patients receiving anatomical lung resections between 12/20/2016 and 03/20/2018. The main quality controls consisted of determining the recruitment rate of each centre and the accuracy of the perioperative data collected based on six key variables. The implications of a low recruitment rate were analysed for '90-day mortality' and 'Grade IIIb-V complications'. Results: the series was composed of 3533 cases (1917 VATS; 54.3%) across 33 departments. The centres' median recruitment rate was 99% (25-75th:76-100%), with an overall recruitment rate of 83% and a data accuracy of 98%. We were unable to demonstrate a significant association between the recruitment rate and the risk of morbidity/mortality, but a trend was found in the unadjusted analysis for those centres with recruitment rates lower than 80% (centres with 95-100% rates as reference): grade IIIb-V OR=0.61 (p=0.081), 90-day mortality OR=0.46 (p=0.051). Conclusions: more than half of the anatomical lung resections in Spain are performed via VATS. According to our results, the centre's recruitment rate and its potential implications due to selection bias, should deserve further attention by the main voluntary multicentre studies of our speciality. The high representativeness as well as the reliability of the GEVATS data constitute a fundamental point of departure for this nationwide cohort

Children’s moderate-to-vigorous physical activity on weekdays versus weekend days:A multi-country analysis

PURPOSE: The Structured Days Hypothesis (SDH) posits that children's behaviors associated with obesity - such as physical activity - are more favorable on days that contain more 'structure' (i.e., a pre-planned, segmented, and adult-supervised environment) such as school weekdays, compared to days with less structure, such as weekend days. The purpose of this study was to compare children's moderate-to-vigorous physical activity (MVPA) levels on weekdays versus weekend days using a large, multi-country, accelerometer-measured physical activity dataset. METHODS: Data were received from the International Children's Accelerometer Database (ICAD) July 2019. The ICAD inclusion criteria for a valid day of wear, only non-intervention data (e.g., baseline intervention data), children with at least 1 weekday and 1 weekend day, and ICAD studies with data collected exclusively during school months, were included for analyses. Mixed effects models accounting for the nested nature of the data (i.e., days within children) assessed MVPA minutes per day (min/day MVPA) differences between weekdays and weekend days by region/country, adjusted for age, sex, and total wear time. Separate meta-analytical models explored differences by age and country/region for sex and child weight-status. RESULTS/FINDINGS: Valid data from 15 studies representing 5794 children (61% female, 10.7 ± 2.1 yrs., 24% with overweight/obesity) and 35,263 days of valid accelerometer data from 5 distinct countries/regions were used. Boys and girls accumulated 12.6 min/day (95% CI: 9.0, 16.2) and 9.4 min/day (95% CI: 7.2, 11.6) more MVPA on weekdays versus weekend days, respectively. Children from mainland Europe had the largest differences (17.1 min/day more MVPA on weekdays versus weekend days, 95% CI: 15.3, 19.0) compared to the other countries/regions. Children who were classified as overweight/obese or normal weight/underweight accumulated 9.5 min/day (95% CI: 6.9, 12.2) and 10.9 min/day (95% CI: 8.3, 13.5) of additional MVPA on weekdays versus weekend days, respectively. CONCLUSIONS: Children from multiple countries/regions accumulated significantly more MVPA on weekdays versus weekend days during school months. This finding aligns with the SDH and warrants future intervention studies to prioritize less-structured days, such as weekend days, and to consider providing opportunities for all children to access additional opportunities to be active

Thermal architecture for the QUBIC cryogenic receiver

QUBIC, the QU Bolometric Interferometer for Cosmology, is a novel forthcoming instrument to measure the B-mode polarization anisotropy of the Cosmic Microwave Background. The detection of the B-mode signal will be extremely challenging; QUBIC has been designed to address this with a novel approach, namely bolometric interferometry. The receiver cryostat is exceptionally large and cools complex optical and detector stages to 40 K, 4 K, 1 K and 350 mK using two pulse tube coolers, a novel 4He sorption cooler and a double-stage 3He/4He sorption cooler. We discuss the thermal and mechanical design of the cryostat, modelling and thermal analysis, and laboratory cryogenic testing.Fil: May, A. J.. University of Manchester; Reino UnidoFil: Chapron, C.. Astroparticule et Cosmologie; Francia. Centre National de la Recherche Scientifique; FranciaFil: Coppi, G.. University of Manchester; Reino UnidoFil: D’Alessandro, G.. Università di Roma; ItaliaFil: de Bernardis, P.. Università di Roma; ItaliaFil: Masi, S.. Università di Roma; ItaliaFil: Melhuish, S.. University of Manchester; Reino UnidoFil: Piat, M.. Astroparticule et Cosmologie; Francia. Centre National de la Recherche Scientifique; FranciaFil: Piccirillo, L.. University of Manchester; Reino UnidoFil: Schillaci, A.. Università di Roma; ItaliaFil: Thermeau, J. P.. Astroparticule et Cosmologie; Francia. Centre National de la Recherche Scientifique; FranciaFil: Bonaparte, J.. Comisión Nacional de Energía Atómica; ArgentinaFil: Di Donato, Andrés Leonardo. Comisión Nacional de Energía Atómica; ArgentinaFil: Fasciszewski Zeballos, Alejandro Miguel. Comisión Nacional de Energía Atómica; ArgentinaFil: Gamboa Lerena, Martín Miguel. Universidad Nacional de La Plata. Facultad de Ciencias Astronómicas y Geofísicas; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - La Plata; ArgentinaFil: Garcia, Beatriz Elena. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Parque Centenario. Instituto de Tecnología en Detección y Astropartículas. Comisión Nacional de Energía Atómica. Instituto de Tecnología en Detección y Astropartículas. Universidad Nacional de San Martín. Instituto de Tecnología en Detección y Astropartículas; ArgentinaFil: Etchegoyen, Alberto. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Parque Centenario. Instituto de Tecnología en Detección y Astropartículas. Comisión Nacional de Energía Atómica. Instituto de Tecnología en Detección y Astropartículas. Universidad Nacional de San Martín. Instituto de Tecnología en Detección y Astropartículas; ArgentinaFil: Gomez Berisso, Mariano. Comisión Nacional de Energía Atómica; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas; ArgentinaFil: González, M.. Comisión Nacional de Energía Atómica; ArgentinaFil: Harari, Diego Dario. Comisión Nacional de Energía Atómica; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas; ArgentinaFil: Kristukat, C.. Universidad Nacional de San Martín; ArgentinaFil: Medina, Maria Clementina. Provincia de Buenos Aires. Gobernación. Comisión de Investigaciones Científicas. Instituto Argentino de Radioastronomía. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - La Plata. Instituto Argentino de Radioastronomía; ArgentinaFil: Ringegni, P.. Universidad Nacional de la Plata. Facultad de Ingeniería. Uidet Grupo de Ensayos Mecanicos Aplicados.; ArgentinaFil: Romero, Gustavo Esteban. Provincia de Buenos Aires. Gobernación. Comisión de Investigaciones Científicas. Instituto Argentino de Radioastronomía. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - La Plata. Instituto Argentino de Radioastronomía; ArgentinaFil: Suarez, C.. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Parque Centenario. Instituto de Tecnología en Detección y Astropartículas. Comisión Nacional de Energía Atómica. Instituto de Tecnología en Detección y Astropartículas. Universidad Nacional de San Martín. Instituto de Tecnología en Detección y Astropartículas; ArgentinaFil: Mundo, Luis Mariano. Universidad Nacional de la Plata. Facultad de Ingeniería. Uidet Grupo de Ensayos Mecanicos Aplicados.; ArgentinaFil: Watson, B.. University of Manchester; Reino UnidoFil: Wicek, F.. Laboratoire de l’Accélérateur Linéaire; FranciaFil: Zannoni, M.. Università degli Studi di Milano; ItaliaFil: Zullo, A.. Istituto Nazionale Di Fisica Nucleare; ItaliaMillimeter, Submillimeter, and Far-Infrared Detectors and Instrumentation for Astronomy IXEstados UnidosSociety of Photographic Instrumentation Engineer

Overview of recent TJ-II stellarator results

The main results obtained in the TJ-II stellarator in the last two years are reported. The most important topics investigated have been modelling and validation of impurity transport, validation of gyrokinetic simulations, turbulence characterisation, effect of magnetic configuration on transport, fuelling with pellet injection, fast particles and liquid metal plasma facing components. As regards impurity transport research, a number of working lines exploring several recently discovered effects have been developed: the effect of tangential drifts on stellarator neoclassical transport, the impurity flux driven by electric fields tangent to magnetic surfaces and attempts of experimental validation with Doppler reflectometry of the variation of the radial electric field on the flux surface. Concerning gyrokinetic simulations, two validation activities have been performed, the comparison with measurements of zonal flow relaxation in pellet-induced fast transients and the comparison with experimental poloidal variation of fluctuations amplitude. The impact of radial electric fields on turbulence spreading in the edge and scrape-off layer has been also experimentally characterized using a 2D Langmuir probe array. Another remarkable piece of work has been the investigation of the radial propagation of small temperature perturbations using transfer entropy. Research on the physics and modelling of plasma core fuelling with pellet and tracer-encapsulated solid-pellet injection has produced also relevant results. Neutral beam injection driven Alfvénic activity and its possible control by electron cyclotron current drive has been examined as well in TJ-II. Finally, recent results on alternative plasma facing components based on liquid metals are also presentedThis work has been carried out within the framework of the EUROfusion Consortium and has received funding from the Euratom research and training programme 2014–2018 under Grant Agreement No. 633053. It has been partially funded by the Ministerio de Ciencia, Inovación y Universidades of Spain under projects ENE2013-48109-P, ENE2015-70142-P and FIS2017-88892-P. It has also received funds from the Spanish Government via mobility grant PRX17/00425. The authors thankfully acknowledge the computer resources at MareNostrum and the technical support provided by the Barcelona S.C. It has been supported as well by The Science and Technology Center in Ukraine (STCU), Project P-507F