A biophysical perspective on receptor-mediated virus entry with a focus on HIV

As part of their entry and infection strategy, viruses interact with specific receptor molecules expressed on the surface of target cells. The efficiency and kinetics of the virus-receptor interactions required for a virus to productively infect a cell is determined by the biophysical properties of the receptors, which are in turn influenced by the receptors' plasma membrane (PM) environments. Currently, little is known about the biophysical properties of these receptor molecules or their engagement during virus binding and entry. Here we review virus-receptor interactions focusing on the human immunodeficiency virus type 1 (HIV), the etiological agent of acquired immunodeficiency syndrome (AIDS), as a model system. HIV is one of the best characterised enveloped viruses, with the identity, roles and structure of the key molecules required for infection well established. We review current knowledge of receptor-mediated HIV entry, addressing the properties of the HIV cell-surface receptors, the techniques used to measure these properties, and the macromolecular interactions and events required for virus entry. We discuss some of the key biophysical principles underlying receptor-mediated virus entry and attempt to interpret the available data in the context of biophysical mechanisms. We also highlight crucial outstanding questions and consider how new tools might be applied to advance understanding of the biophysical properties of viral receptors and the dynamic events leading to virus entry

Overexpression of mitochondrial if1 prevents metastatic disease of colorectal cancer by enhancing anoikis and tumor infiltration of NK cells

Increasing evidences show that the ATPase Inhibitory Factor 1 (IF1), the physiological inhibitor of the ATP synthase, is overexpressed in a large number of carcinomas contributing to metabolic reprogramming and cancer progression. Herein, we show that in contrast to the findings in other carcinomas, the overexpression of IF1 in a cohort of colorectal carcinomas (CRC) predicts less chances of disease recurrence, IF1 being an independent predictor of survival. Bioinformatic and gene expression analyses of the transcriptome of colon cancer cells with differential expression of IF1 indicate that cells overexpressing IF1 display a less aggressive behavior than IF1 silenced (shIF1) cells. Proteomic and functional in vitro migration and invasion assays confirmed the higher tumorigenic potential of shIF1 cells. Moreover, shIF1 cells have increased in vivo metastatic potential. The higher metastatic potential of shIF1 cells relies on increased cFLIP-mediated resistance to undergo anoikis after cell detachment. Furthermore, tumor spheroids of shIF1 cells have an increased ability to escape from immune surveillance by NK cells. Altogether, the results reveal that the overexpression of IF1 acts as a tumor suppressor in CRC with an important anti-metastatic role, thus supporting IF1 as a potential therapeutic target in CRCThis research was funded by grants from Ministerio de Ciencia, Innovación y Universidades (SAF2013-41945-R, SAF2016-75916-R and SAF2016-75452-R), CIBERER-ISCIII (CB06/07/0017) and Fundación Ramón Areces, Spai

Future trends of snowfall days in northern Spain from ENSEMBLES regional climate projections

In a previous study Pons et al. (Clim Res 54(3):197-207, 2010. doi:10.3354/cr01117g) reported a significant decreasing trend of snowfall occurrence in the Northern Iberian Peninsula since the mid 70s. The study was based on observations of annual snowfall frequency (measured as the annual number of snowfall days NSD) from a network of 33 stations ranging from 60 to 1350 m. In the present work we analyze the skill of Regional Climate Models (RCMs) to reproduce this trend for the period 1961-2000 (using both reanalysis- and historical GCM-driven boundary conditions) and the trend and the associated uncertainty of the regional future projections obtained under the A1B scenario for the first half of the twenty-first century. In particular, we consider the regional simulation dataset from the EU-funded ENSEMBLES project, consisting of thirteen state-of-the-art RCMs run at 25 km resolution over Europe. While ERA40 severely underestimates both the mean NSD and its observed trend (-2.2 days/decade), the corresponding RCM simulations driven by the reanalysis appropriately capture the interannual variability and trends of the observed NSD (trends ranging from -3.4 to -0.7, -2.1 days/decade for the ensemble mean). The results driven by the GCM historical runs are quite variable, with trends ranging from -8.5 to 0.2 days/decade (-1.5 days/decade for the ensemble mean), and the greatest uncertainty by far being associated with the particular GCM used. Finally, the trends for the future 2011-2050 A1B runs are more consistent and significant, ranging in this case from -3.7 to -0.5 days/decade (-2.0 days/decade for the ensemble mean), indicating a future significant decreasing trend. These trends are mainly determined by the increasing temperatures, as indicated by the interannual correlation between temperature and NSD (-0.63 in the observations), which is preserved in both ERA40- and GCM-driven simulations.This research has received funding from the European Union’s Seventh Framework Programme under Grant Agreements 606799 (INTACT Project). The RCM simulations used in this study were obtained from the European Union-funded FP6 Integrated Project ENSEMBLES (Contract No. 505539)

Montera: A Framework for Efficient Execution of Monte Carlo Codes on Grid Infrastructures

he objective of this work is to improve the performance of Monte Carlo codes on Grid production infrastructures. To do so, the codes and the grid sites are characterized with simple parameters to model their behaviors. Then, a new performance model for grid infrastructures is proposed, and an algorithm that employs this information is described. This algorithm dynamically calculates the number and size of tasks to execute on each site to maximize the performance and reduce makespan. Finally, a newly developed framework called Montera is presented. Montera deals with the execution of Monte Carlo codes in an unattended way, isolating the complexity of the problem from the final user. By employing two fusion Monte Carlo codes as example cases, along with the described characterizations and scheduling algorithm, a performance improvement up to 650 % over current best results is obtained on a real production infrastructure, together with enhanced stability and robustness

The Medianet Project: Integration of Multimedia Services for the next Generations Business oriented Internet

This work is at: 10th IEEE International Symposium on Parallel and Distributed Processing with Applications, took place July 10-13, 2012 in Madrid, Spain.This article gathers the foundational premises of the MEDIANET project as well as intermediate results obtained along its firsts two years. MEDIANET is a Spanish project founded by the Comunidad de Madrid government, which strives for a significant scientific advance in the future media Internet where important advances are necessary to allow end-users to perceive a good quality of experience. The network technologies objectives consist of the definition and validation of new proposals for the efficient transport of high bandwidth, real-time data flows in a decentralized way where the network provides mechanisms to seamlessly request and configure devices to increase the quality of experience perceived by end-users. Furthermore, new experiences with layer 2 networks and a cross-layer design will be tested with high bandwidth demanding media services. An important objective is to develop, evaluate in depth and implement on diverse platforms , a new low latency transparent bridge protocol based in on-demand path set up, suitable for campus and data center networks. The global result will be an integrated and independent advancement in future media Internet protocols, algorithms, switching architectures and standards.The funds for the MEDIANET project are provided by the Comunidad de Madrid government under reference number S2009/TIC-1468.Publicad

Cultural diversity, educational achievements and school. Arguments from educational community

Questo studio costituisce la prima fase di un lavoro più ampio la cui i nalità è quella di contribuire al miglioramento della scuola attraverso l’identii cazione, elaborazione e dif usione di una casistica di buone pratiche scolastiche in contesti culturalmente diversi. Questa ricerca incomincia revisionando il concetto di “successi educativi” e “buone pratiche” da una doppia prospettiva: analizzando la letteratura specii ca per quanto riguarda i contributi più signii cativi degli ultimi anni sul miglioramento dell’ei cacia scolastica e, in aggiunta, analizzando le opinioni dei rappresentanti dei diversi collettivi che hanno a che fare con la materia e denominati in questo studio, “esperti” (docenti, assessori, famiglie, accademici, tecnici e agenti socioculturali). L’articolo si focalizza sulla descrizione del supporto metodologico che ci ha permesso di portare avanti questo processo di consultazione (il metodo Delphi) e sulla presentazione dei principali risultati. In dei nitiva, presentiamo i punti d’accordo e le discrepanze trovate in riferimento al concetto di “successo educativo”. Il processo Delphi sviluppato in questo lavoro è stato iterattivo e interattivo. Nel processo si è garantito l’anonimato dei partecipanti, la retro alimentazione costante e controllata e la presenza, nel risultato i nale, di tutte le opinioni individuali. Lo strumento per la raccolta d’informazione è stato il questionario. Nella prima fase di consulenza, ci sono state domande aperte che hanno permesso di fare un’analisi qualitativa delle risposte. Partendo da questa analisi abbiamo elaborato un secondo questionario di tipo scalare la cui analisi ha permesso di conoscere il grado di consenso sulle questioni sottoposte a dibattito. La ricerca del consenso e la stabilità sono stati i criteri che hanno guidato le analisi realizzate sull’informazione raccolta nelle due fasi di consultazione e anche i criteri di saturazione di questa.h is paper is the i rst stage of a broader study that intents to improve schooling ei cacy by identifying, describing and disseminating the best practices developed in Spanish schools from diverse cultural backgrounds. It reviewed two main concepts – “educational achievement” and “best school practices” – from a double perspective: i rst, analyzing the most meaningful research contributions made in this area over the last ten years; and second, taking into account the opinions of experts (teachers, educational advisors, families, students, theorists, social players…) on these subjects. h e paper had two main objectives: describing the methodological framework used in the expert consultation process (the Delphi method) and presenting the main points of consensus and discrepancy regarding the concept of “educational achievement in culturally diverse educational contexts”. h e Delphi consultation carried out was an iterative and interactive process. h e process was coni dential and special care was taken to ensure continuous feedback and representation of all individual opinions in the i nal results. Information was collected using questionnaires. In the i rst consultation round, the questionnaire included openended questions, whose responses were analyzed using a qualitative approach. A second questionnaire was designed on the basis of this information. It provided quantitative information that was useful to measure the level of agreement on the various issues discussed. h e search for consensus and stability and information saturation were the basic criteria that guided the analysis of information provided by the experts consulted

Evaluation of the EURO-CORDEX Regional Climate Models Over the Iberian Peninsula: Observational Uncertainty Analysis

ABSTRACT: This work evaluates the daily precipitation and mean temperature of eight CORDEX-EUR11 ERA-Interim-driven simulations of EURO-CORDEX over the Iberian Peninsula (IP) for the period 1989-2008. To this aim, three observational data sets (Iberia01, E-OBS-v19e, and MESAN-0.11) were considered as reference and compared with the models by means of several indices reflecting the mean and extreme regimes over the IP. For precipitation the Lamb weather types were considered to identify synoptic conditions related with higher observational uncertainty. RCMs are able to reproduce the spatial pattern and the variability observed in the IP. However, there is a higher agreement between models and observations for mean temperature than for precipitation, decreasing when extremes are analyzed. For the observational uncertainty analysis, also extreme daily temperatures were considered to obtain a wider picture of this topic. A higher dependence on the observational data set has been found for precipitation than for temperature. This uncertainty is particularly significant when the 50-year return value is considered for which the observational uncertainty doubles the model uncertainty. Only the wet-day frequency presents values lower than 0.5 for all seasons, with most of the rest of values reflecting a similar contribution of both components to the uncertainty. In the case of temperatures, the main contribution of the observations has been found when the lower (MAE01) and upper (MAE99) extremes are considered, with values lower than 0.5. For precipitation the observational uncertainty increases when synoptic patterns affecting the Mediterranean Basin are considered, reflecting the difficulty to properly capture the Mediterranean precipitation regimes.This work was partially funded by the Spanish Government R&D Programme (Exp. CGL2010-21869 and CGL2010-22158-C02) and the European Comission (INDECIS: H2020-690462). Pedro M. M. Soares and Rita M. Cardoso wish to acknowledge the SOLAR (PTDC/GEOMET/7078/2014) Project and the funding by the Instituto Dom Luiz (Project FCT UID/GEO/50019/2019)

Experience with the use of Rituximab for the treatment of rheumatoid arthritis in a tertiary Hospital in Spain: RITAR study

There is evidence supporting that there are no relevant clinical differences between dosing rituximab 1000 mg or 2000 mg per cycle in rheumatoid arthritis (RA) patients in clinical trials, and low-dose cycles seem to have a better safety profile. Our objective was to describe the pattern of use of rituximab in real-life practice conditions. Methods: Rituximab for RA in clinical practice (RITAR) study is a retrospective cohort study from 2005 to 2015. Eligibility criteria were RA adults treated with rituximab for active articular disease. Response duration was the main outcome defined as months elapsed from the date of rituximab first infusion to the date of flare. A multivariable analysis was performed to determine the variables associated with response duration. Results: A total of 114 patients and 409 cycles were described, 93.0% seropositive and 80.7% women. Rituximab was mainly used as second-line biological therapy. On demand retreatment was used in 94.6% of cases versus fixed 6 months retreatment in 5.4%. Median response duration to on demand rituximab cycles was 10 months (interquartile range, 7–13). Multivariable analysis showed that age older than 65 years, number of rituximab cycles, seropositivity, and first- or second-line therapy were associated with longer response duration. The dose administered at each cycle was not significantly associated with response duration. Conclusions: Our experience suggests that 1000 mg rituximab single infusion on demand is a reasonable schedule for long-term treatment of those patients with good response after the first cycles, especially in seropositive patients and when it is applied as a first- or second-line biological therap

Experiments on a videotape atom chip: fragmentation and transport studies

This paper reports on experiments with ultra-cold rubidium atoms confined in microscopic magnetic traps created using a piece of periodically-magnetized videotape mounted on an atom chip. The roughness of the confining potential is studied with atomic clouds at temperatures of a few microKelvin and at distances between 30 and 80 microns from the videotape-chip surface. The inhomogeneities in the magnetic field created by the magnetized videotape close to the central region of the chip are characterized in this way. In addition, we demonstrate a novel transport mechanism whereby we convey cold atoms confined in arrays of videotape magnetic micro-traps over distances as large as ~ 1 cm parallel to the chip surface. This conveying mechanism enables us to survey the surface of the chip and observe potential-roughness effects across different regions.Comment: 29 pages, 22 figures

Analyzing the social factors that influence willingness to pay for the management of invasive alien species under two different strategies: eradication and prevention

This an accepted author's manuscript (AAM) version of an article published in Environmental Management, 48 (2011): 418-43