3,133 research outputs found

    An unbiased genetic screen reveals the polygenic nature of the influenza virus anti-interferon response.

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    Influenza A viruses counteract the cellular innate immune response at several steps, including blocking RIG I-dependent activation of interferon (IFN) transcription, interferon (IFN)-dependent upregulation of IFN-stimulated genes (ISGs), and the activity of various ISG products; the multifunctional NS1 protein is responsible for most of these activities. To determine the importance of other viral genes in the interplay between the virus and the host IFN response, we characterized populations and selected mutants of wild-type viruses selected by passage through non-IFN-responsive cells. We reasoned that, by allowing replication to occur in the absence of the selection pressure exerted by IFN, the virus could mutate at positions that would normally be restricted and could thus find new optimal sequence solutions. Deep sequencing of selected virus populations and individual virus mutants indicated that nonsynonymous mutations occurred at many phylogenetically conserved positions in nearly all virus genes. Most individual mutants selected for further characterization induced IFN and ISGs and were unable to counteract the effects of exogenous IFN, yet only one contained a mutation in NS1. The relevance of these mutations for the virus phenotype was verified by reverse genetics. Of note, several virus mutants expressing intact NS1 proteins exhibited alterations in the M1/M2 proteins and accumulated large amounts of deleted genomic RNAs but nonetheless replicated to high titers. This suggests that the overproduction of IFN inducers by these viruses can override NS1-mediated IFN modulation. Altogether, the results suggest that influenza viruses replicating in IFN-competent cells have tuned their complete genomes to evade the cellular innate immune system and that serial replication in non-IFN-responsive cells allows the virus to relax from these constraints and find a new genome consensus within its sequence space. IMPORTANCE In natural virus infections, the production of interferons leads to an antiviral state in cells that effectively limits virus replication. The interferon response places considerable selection pressure on viruses, and they have evolved a variety of ways to evade it. Although the influenza virus NS1 protein is a powerful interferon antagonist, the contributions of other viral genes to interferon evasion have not been well characterized. Here, we examined the effects of alleviating the selection pressure exerted by interferon by serially passaging influenza viruses in cells unable to respond to interferon. Viruses that grew to high titers had mutations at many normally conserved positions in nearly all genes and were not restricted to the NS1 gene. Our results demonstrate that influenza viruses have fine-tuned their entire genomes to evade the interferon response, and by removing interferon-mediated constraints, viruses can mutate at genome positions normally restricted by the interferon response

    Collaborative relationships between logistics service providers and humanitarian organizations during disaster relief operations

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    Purpose: this study explores barriers and benefits of establishing relationships between humanitarian organizations (HOs) and logistics service providers (LSPs) in order to improve humanitarian disaster relief operations (DROs). the perceptions of a variety of actors are explored to determine key factors which influence collaboration. Design/ methodology/ approach: This study comprises of quantitative methodological approaches. a comprehensive literature review was undertaken alongside an online survey with a variety of respondents. descriptive statistics, data visualization and qualitative data analysis were implemented to analyse survey results. a follow-up survey and interviews with LSPs validated the results. Findings, the research presents the opinions of a variety of actors involved in DROs and reveals barriers which affect HO/LSP collaboration. explanations for these barriers and possible solutions to mitigate them are disclosed. the findings also uncover gaps between research and practice; providing new insights into behaviour in the humanitarian field. Practical implications: We provide an in-depth understanding of the barriers and challenges faced in this field and suggest a revaluation of corporate decision making in order to increase trust between LSPs and HOs. We identify future research topics including the impact of donors and military organisations on HO decision making, and analysis of variables which may affect the formation of collaborative partnerships. Originality/value: We introduce a unique empirical insight into the perspective of HOs, LSPs and academics and offers suggestions for mitigating the numerous barriers associated with successful collaborative partnerships between HOs and LSPs

    Motorized circular rail with RGB-D sensor on cart for physical rehabilitation

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    This paper introduces a motorized circular rail managing the movement of two carts equipped with an RGB-D sensor each. The proposal is aimed at continuously tracking a person who is undergoing a series of physical rehabilitation exercises from two different viewpoints to monitor if the exercises are being correctly conducted. More concretely, this work offers all details of the trajectory calculation for safe movement of both carts on the motorized circular rail. Then, two study cases are presented to show the efficiency of the control algorithms implemented.AEI - Agencia Estatal de Investigação(TIN2016-79100-R)This work was partially supported by Ministerio de Ciencia, Innovación y Universidades, Agencia Estatal de Investigación (AEI) / European Regional Development Fund (FEDER, UE) under DPI2016-80894-R and TIN2016-79100-R grants

    Assisting dependent people at home through autonomous unmanned aerial vehicles

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    This work describes a proposal of autonomous unmanned aerial vehicles (AUAVs) for home assistance of dependent people. AUAVs will monitor and recognize human activities during flight to improve their quality of life. However, before bringing such AUAV assistance to real homes, several challenges must be faced to make them viable and practical. Some challenges are technical and some others are related to human factors. In particular, several technical aspects are described for AUAV assistance: (1) flight control, based on our active disturbance rejection control algorithm, (2) flight planning (navigation in obstacle environments), and, (3) processing signals, acquired both from flight-control and monitoring sensors. From the assisted person’s viewpoint, our research focuses on three cues: (1) the user’s perception about AUAV assistance, (2) the influence on human acceptance of AUAV appearance and behavior at home, and (3) the human-robot interaction between assistant AUAV and assisted person. Finally, virtual reality environments are proposed to carry out preliminary tests and user acceptance evaluations.This work has been partially supported by Spanish Ministerio de Ciencia, Innovación y Universidades, Agencia Estatal de Investigaci´on (AEI) / European Regional Development Fund (FEDER, UE) under DPI2016-80894-R grant, and by CIBERSAM of the Instituto de Salud Carlos III. Lidia M. Belmonte holds FPU014/05283 scholarship from Spanish Ministerio de Educaci´on y Formación Profesional

    Anomalous material-dependent transport of focused, laser-driven proton beams.

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    Intense lasers can accelerate protons in sufficient numbers and energy that the resulting beam can heat materials to exotic warm (10 s of eV temperature) states. Here we show with experimental data that a laser-driven proton beam focused onto a target heated it in a localized spot with size strongly dependent upon material and as small as 35 μm radius. Simulations indicate that cold stopping power values cannot model the intense proton beam transport in solid targets well enough to match the large differences observed. In the experiment a 74 J, 670 fs laser drove a focusing proton beam that transported through different thicknesses of solid Mylar, Al, Cu or Au, eventually heating a rear, thin, Au witness layer. The XUV emission seen from the rear of the Au indicated a clear dependence of proton beam transport upon atomic number, Z, of the transport layer: a larger and brighter emission spot was measured after proton transport through the lower Z foils even with equal mass density for supposed equivalent proton stopping range. Beam transport dynamics pertaining to the observed heated spot were investigated numerically with a particle-in-cell (PIC) code. In simulations protons moving through an Al transport layer result in higher Au temperature responsible for higher Au radiant emittance compared to a Cu transport case. The inferred finding that proton stopping varies with temperature in different materials, considerably changing the beam heating profile, can guide applications seeking to controllably heat targets with intense proton beams

    Effectiveness of individualized inhaler technique training on low adherence (LowAd) in ambulatory patients with COPD and asthma

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    © 2022. This document is made available under the CC-BY 4.0 license http://creativecommons.org/licenses/by /4.0/ This document is the published version of a published work that appeared in final form in npj primary care respiratory medicineTo analyze whether there is improvement in adherence to inhaled treatment in patients with COPD and asthma after an educational intervention based on the teach-to-goal method. This is a prospective, non-randomized, single-group study, with intervention and before-after evaluation. The study population included 120 patients (67 females and 53 males) diagnosed with asthma (70.8%) and COPD (29.1%). The level of adherence (low and optimal) and the noncompliance behavior pattern (erratic, deliberate and unwitting) were determined by the Test of the adherence to Inhalers (TAI). This questionnaire allows you to determine the level of adherence and the types of noncompliance. Low Adherence (LowAd) was defined as a score less than 49 points. All patients received individualized educational inhaler technique intervention (IEITI). Before the IEITI, 67.5% of the patients had LowAd. Following IEITI, on week 24, LowAd was 55% (p = 0.024). Each patient can present one or more types of noncompliance. The most frequent type was forgetting to use the inhaler (erratic), 65.8%. The other types were deliberate: 43.3%, and unwitting: 57.5%. All of them had decreased on the final visit: 51.7% (p = 0.009), 25.8% (p = 0.002), 39.2% (p = 0.002). There were no significant differences in adherence between asthma and COPD patients at the start of the study. The only predicting factor of LowAd was the female gender. An individualized educational intervention, in ambulatory patients with COPD and asthma, in real-world clinical practice conditions, improves adherence to the inhaled treatment

    Efecto de la temperatura de termotratamiento en el comportamiento eléctrico de la madera de Pino radiata

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    En el presente trabajo se analiza el efecto de la temperatura del termotratamiento sobre la conductividad eléctrica de la madera de pino radiata. Sobre probetas de madera de pino radiata de procedencia País Vasco (España), termotratada a 190ºC y 210ºC por el método Thermowood así como sobre piezas testigo de la misma especie, procedencia y dimensiones, acondicionadas todas ellas hasta masa constante a 20ºC/40%HR, 20ºC/65%HR y 20ºC/90%HR se evaluó la resistencia eléctrica (longitudinal y transversal) y, posteriormente, se ajustó el modelo Samuelsson para modelizar en cada tipo de material la relación humedad de la madera-resistencia eléctrica. Se concluye que la temperatura empleada en el tratamiento térmico de la madera afecta no sólo a la humedad de equilibrio sino, también, a su conductividad eléctrica, siendo máximo este efecto en el tratamiento efectuado a 210ºC. AbstractThis paper analyzes the effect of heat treatment temperature on the electrical conductivity of radiata pine wood. On specimens of radiata pine of the Basque Country provenance (Spain), heat treated at 190°C and 210°C by the method Thermowood as well as not treated matched samples, conditioned up to constant mass at the standard conditions of 20°C/40%; 20°C/65% and 20°C/90% RH the electrical resistance (longitudinal and transverse) was measured and a Samuelsson model fitted to describe the relationship between the electrical resistance and moisture content of each material. From the data is concluded that the temperature employed in the thermal treatment timber not only affects equilibrium moisture content of wood but also to its electrical conductivity, being this effect  maximum in the processing performed at 210°C

    Short-Term Changes in Algometry, Inclinometry, Stabilometry, and Urinary pH Analysis After a Thoracolumbar Junction Manipulation in Patients with Kidney Stones

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    Objectives: To determine the efficacy of a high-velocity low-amplitude manipulation of the thoracolumbar junction in different urologic and musculoskeletal parameters in subjects suffering from renal lithiasis. Design: Randomized, controlled blinded clinical study. Settings/Location: The Nephrology departments of two hospitals and one private consultancy of physiotherapy in Valencia (Spain). Subjects: Forty-six patients suffering from renal lithiasis. Interventions: The experimental group (EG, n¿=¿23) received a spinal manipulation of the thoracolumbar junction, and the control group (CG, n¿=¿23) received a sham procedure. Outcome measures: Pressure pain thresholds (PPTs) of both quadratus lumborum and spinous processes from T10 to L1, lumbar flexion range of motion, stabilometry, and urinary pH were measured before and immediately after the intervention. A comparison between pre- and postintervention phases was performed and an analysis of variance for repeated measures using time (pre- and postintervention) as intrasubject variable and group (CG or EG) as intersubject variable. Results: Intragroup comparison showed a significant improvement for the EG in the lumbar flexion range of motion (p¿<¿0.001) and in all the PPT (p¿<¿0.001 in all cases). Between-group comparison showed significant changes in PPT in quadratus lumborum (p¿<¿0.001), as well as in the spinous processes of all of the evaluated levels (p¿<¿0.05). No changes in urinary pH were observed (p¿=¿0.419). Conclusion: Spinal manipulation of the thoracolumbar junction seems to be effective in short term to improve pain sensitivity, as well as to increase the lumbar spine flexion
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