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Background Phospholipids are important structural and signaling molecules in plant membranes. Some fluorescent dyes can stain general lipids of membranes, but labeling and visualization of specific lipid classes have yet to be developed for most components of the membrane. New techniques for visualizing membrane lipids are needed to further delineate their dynamic structural and signaling roles in plant cells. In this study we examined whether propargylcholine, a bioortholog of choline, can be used to label the major membrane lipid, phosphatidylcholine, and other choline phospholipids in plants. We established that propargylcholine is readily taken up by roots, and that its incorporation is not detrimental to plant growth. After plant tissue is harvested and fixed, a click-chemistry reaction covalently links the alkyne group of propargylcholine to a fluorescently-tagged azide, resulting in specific labeling of choline phospholipids. Results Uptake of propargylcholine, followed by click chemistry with fluorescein or Alexa Fluor 594 azide was used to visualize choline phospholipids in cells of root, leaf, stem, silique and seed tissues from Arabidopsis thaliana. Co-localization with various subcellular markers indicated coinciding fluorescent signals in cell membranes, such as the tonoplast and the ER. Among different cell types in the leaf epidermis, guard cells displayed strong labeling. Mass spectrometry-based lipidomic analysis of the various plant tissues revealed that incorporation of propargylcholine was strongest in roots with approximately 50% of total choline phospholipids being labeled, but it was also incorporated in the other tissues including seeds. Phospholipid profiling confirmed that, in each tissue analyzed, incorporation of the bioortholog had little impact on the pool of choline plus choline-like phospholipids or other lipid species. Conclusion We developed and validated a click-chemistry based method for fluorescence imaging of choline phospholipids using a bioortholog of choline, propargylcholine, in various cell-types and tissues from Arabidopsis. This click-chemistry method provides a direct way to metabolically tag and visualize specific lipid molecules in plant cells. This work paves the way for future studies addressing in situ localization of specific lipids in plants. Electronic supplementary material The online version of this article (10.1186/s13007-018-0299-2) contains supplementary material, which is available to authorized users.

Major advances were recently obtained in the exact solution of vehicle routing problems (VRPs). Sophisticated branch-cut-and-price (BCP) algorithms for some of the most classical VRP variants now solve many instances with up to a few hundreds of customers. However, adapting and reimplementing those successful algorithms for other variants can be a very demanding task. This work proposes a BCP solver for a generic model that encompasses a wide class of VRPs. It incorporates the key elements found in the best existing VRP algorithms: ng-path relaxation, rank-1 cuts with limited memory, path enumeration, and rounded capacity cuts; all generalized through the new concepts of “packing set” and “elementarity set”. The concepts are also used to derive a branching rule based on accumulated resource consumption and to generalize the Ryan and Foster branching rule. Extensive experiments on several variants show that the generic solver has an excellent overall performance, in many problems being better than the best specific algorithms. Even some non-VRPs, like bin packing, vector packing and generalized assignment, can be modeled and effectively solved.

As part of the Springer Nature Content Sharing Initiative, you can publicly share full-text access to a view-only version of your paper by using thefollowing SharedIt link: https://rdcu.be/cCd8u; International audience; The study of groundwater resources using pumping test data is usually carried out with the Theis solution, which enables the hydraulic parameters of porous aquifers such as the transmissivity and storage coefficient, to be estimated from the water-level drawdown. However, the data fitting can fail and provide only an indication that the pumped aquifer has a complex structure. Here, a diagnostic plot on log-derivative drawdown is used to identify flow regimes and thus aquifer heterogeneities, leading to plausible conceptual models. Nevertheless, the diagnostic plot is insufficient and must be accompanied by further modelling because of the nonuniqueness of the drawdown log-derivative signal. The proposed approach is applied to an alluvial plain in France, known to be complex because the deposition processes change over time, resulting in channel belts limited by low-permeability deposits in the floodplain or three-dimensional (3D) interconnected structures. Six analytical models were used to simulate drawdown and its derivatives during a three-day transient pumping test. The diagnostic performed on the pumping well showed that four conceptual models, with highly contrasted hydrodynamic behaviours, may correspond to the diagnostic. The joint use of pumping-well and observation-well data allowed the only appropriate model to be identified—a dual-permeability model characterizing a multilayer aquifer. The conceptual model matched the geological observations in boreholes and corroborates the fluvial sequence stratigraphy of the alluvial plain. The pumping test used here is a tool to explore the 3D architecture of the fluvial reservoir at the scale of the depositional sequence in the floodplain.; El estudio de los recursos hídricos subterráneos a partir de los datos de los ensayos de bombeo suele realizarse con la solución de Theis, que permite estimar los parámetros hidráulicos de los acuíferos porosos, como la transmisividad y el coeficiente de almacenamiento, a partir del descenso del nivel del agua. Sin embargo, el ajuste de los datos puede no funcionar y proporcionar sólo una indicación de que el acuífero bombeado tiene una estructura compleja. En este caso, se utiliza un diagrama de diagnóstico de la depresión logarítmica derivada para identificar los regímenes de flujo y, por tanto, las heterogeneidades del acuífero, lo que conduce a modelos conceptuales plausibles. Sin embargo, el diagrama de diagnóstico es insuficiente y debe ir acompañado de una modelización adicional debido a la no unicidad de la señal log-derivada de la depresión. El enfoque propuesto se aplica a una llanura aluvial en Francia, conocida por su complejidad debido a que los procesos de deposición cambian con el tiempo, dando lugar a franjas de canales limitadas por depósitos de baja permeabilidad en la llanura de inundación o a estructuras tridimensionales (3D) interconectadas. Se utilizaron seis modelos analíticos para simular la depresión y sus derivados durante un ensayo de bombeo transitorio de tres días. El diagnóstico realizado en el pozo de bombeo mostró que pueden corresponder cuatro modelos conceptuales, con comportamientos hidrodinámicos muy contrastados. La utilización conjunta de los datos del pozo de bombeo y del pozo de observación permitió identificar el único modelo apropiado: un modelo de doble permeabilidad que caracteriza un acuífero multicapa. El modelo conceptual coincidió con las observaciones geológicas en pozos de sondeo y corrobora la estratigrafía de la secuencia fluvial de la llanura aluvial. El ensayo de bombeo utilizado aquí es una herramienta para explorar la arquitectura 3D del depósito fluvial a escala de la secuencia deposicional en la llanura aluvial.; L’étude des ressources en eau souterraine à partir de données d’essais de pompage est généralement réalisée avec la solution de Theis, qui permet d’estimer les paramètres hydrauliques des aquifères poreux, tels que la transmissivité et le coefficient d’emmagasinement, à partir du rabattement du niveau d’eau. Cependant, l’ajustement des données peut échouer et fournir seulement une indication relative à la complexité de la structure de l’aquifère sollicité par pompage. Ici, un tracé de diagnostic de la dérivé du rabattement selon une échelle logarithmique est utilisé pour identifier les régimes d’écoulement et donc les hétérogénéités de l’aquifère, conduisant à des modèles conceptuels plausibles. Néanmoins, le diagnostic de puits est insuffisant et doit être accompagné d’une modélisation plus poussée en raison de la non-unicité du signal de la dérivée du rabattement selon une échelle logarithmique. L’approche proposée est appliquée à une plaine alluviale en France, connue pour être complexe car les processus de dépôt ont évolué au cours du temps, donnant lieu à des zones de chenaux limitées par des dépôts peu perméables dans la plaine d’inondation ou à des structures tridimensionnelles (3D) interconnectées. Six modèles analytiques ont été utilisés pour simuler le rabattement et ses dérivés pendant un essai de pompage transitoire de trois jours. Le diagnostic réalisé sur le puits de pompage a montré que quatre modèles conceptuels, aux comportements hydrodynamiques très contrastés, peuvent correspondre au diagnostic. L’utilisation conjointe des données des puits de pompage et des puits d’observation a permis d’identifier le seul modèle approprié - un modèle à double perméabilité caractérisant un aquifère multicouche. Le modèle conceptuel correspond aux observations géologiques dans les forages et corrobore la stratigraphie séquentielle fluviale de la plaine alluviale. L’essai de pompage utilisé ici est un outil permettant d’explorer l’architecture 3D du réservoir fluvial à l’échelle de la séquence de dépôt dans la plaine d’inondation.; O estudo dos recursos hídricos subterrâneos utilizando dados de teste de vazão é comumente resolvido por meio da equação de Theis, o que permite que os parâmetros hidráulicos dos aquíferos porosos, como a transmissividade e o coeficiente de armazenamento, possam ser estimados a partir do rebaixamento do nível d’água. Porém, o ajuste dos dados pode falhar, indicando apenas que o aquífero bombeado apresenta uma estrutura complexa. Aqui, um gráfico de diagnóstico da derivada logarítmica do rebaixamento é usado para identificar o regime de fluxo e, portanto, a heterogeneidade do aquífero, levando a modelos conceituais plausíveis. Ainda assim, o gráfico de diagnóstico é insuficiente e deve ser acompanhado de mais modelos, devido ao sinal não único da derivada logarítmica do rebaixamento. A abordagem proposta foi utilizada em uma planície aluvial na França, conhecida por ser complexa, pois os processos de deposição mudam com o tempo, o que resulta em um cinturão de canais limitados por depósitos de baixa permeabilidade na planície de inundação ou por estruturas tridimensionais (3D) interconectadas. Seis modelos analíticos foram utilizados para simular o rebaixamento, e suas funções derivadas, durante um teste de bombeamento transiente de 3 dias. O diagnóstico simulado para o poço de bombeamento mostrou que quatro modelos conceituais, cada um com comportamento hidrodinâmico contrastante, podem corresponder ao diagnóstico. A junção dos dados do poço de bombeamento e dos dados de poço de observação permitiu a identificação do único modelo apropriado – um modelo de permeabilidade dual caracterizando um aquífero multicamadas. O modelo conceitual coincide com as observações da geologia dos poços e corrobora com a sequência estratigráfica fluvial da planície aluvial. O teste de bombeamento utilizado é uma ferramenta para explorar a arquitetura 3D do reservatório fluvial na escala da sequência deposicional da planície de inundação.; 利用抽水试验数据研究地下水资源通常采用 Theis 解, 它可以根据水位降深估算多孔介质含水层的水力参数, 如传导系数和蓄水系数。然而, 数据拟合可能会失败, 并且只能表明抽水含水层具有复杂的结构。在这里, 对数导数降深的诊断图用于识别流态, 从而识别含水层的异质性, 由此可形成合理的概念模型。然而, 由于降深对数导数信号的非唯一性, 仅用诊断图是不够的, 必须再建模分析。所提出的方法应用于法国众所周知复杂的冲积平原, 由于沉积过程随时间变化, 导致河岸带受到漫滩中低渗透性沉积物或三维 (3D) 互连结构的影响。在为期三天的非稳定抽水测试期间, 六个解析解模型用于模拟降深及其导数。抽水井上进行的诊断表明, 具有高度异质的水动力行为的四个概念模型可能与诊断相符。抽水井和观测井数据的联合使用可确定唯一合适的模型, 即表征多层含水层的双渗透模型。概念模型与钻孔中的地质观察相匹配, 并证实了冲积平原的河流相地层。此处使用的抽水试验是在漫滩沉积相尺度上探索冲积相储层 3D 结构的工具。

Background There are few studies reporting on self-medication, perceptions or difficulties older adults have with their medications. This study aimed to describe the uses and the perceptions of medications among older adults in France and to identify patient groups based on that information. Methods We used data from the 2020 ‘French Health Barometer’ – a nationally-representative cross-sectional survey. We assessed polypharmacy (five or more medications), self-medication, and patient perceptions of medications. Robust Poisson regression was used to investigate socio-demographic and health-related factors associated with the outcomes. Latent class analysis was used to identify patient groups classified by the use and the perceptions of medications. Factors associated with group assignment were investigated by multinomial logistic regression. All analyses were weighted. Results The study sample comprised 1,623 respondents aged 70–85 years. Polypharmacy and self-medication were reported in 23.5 and 48.7% of the older population, respectively. Polypharmacy was associated with increasing age, low education, and impaired health status. Self-medication was associated with female sex and high education. Among individuals taking at least 1 medication, 8.2% reported not to understand all their medications, and 9.7% having difficulty taking medications as prescribed. Among individuals taking at least 2 medications, 23.2% thought that they took too many medications. Three patient groups were identified: ‘Non-polypharmacy, positive perceptions’ (62.5%), ‘Polypharmacy, positive perceptions’ (28.0%), and ‘Negative perceptions’ (9.5%). Conclusions Polypharmacy and self-medication are common in French older adults. One segment of people reported negative perceptions of their medications regardless of their polypharmacy status. This underlines the difference between the objective and perceived measures of polypharmacy.

Aim: The association between visual impairment and mild cognitive impairment (MCI) has not been investigated to date. Thus, we assessed this association among older adults from six low- and middle-income countries (LMICs) (China, India, Ghana, Mexico, Russia, and South Africa) using nationally representative datasets. Methods: Cross-sectional, community-based data from the WHO Study on global AGEing and adult health (SAGE) were analyzed. Visual acuity was measured using the tumbling ElogMAR chart, and vision impairment (at distance and near) was defined as visual acuity worse than 6/18 (0.48 logMAR) in the better-seeing eye. The definition of MCI was based on the National Institute on Aging-Alzheimer’s Association criteria. Multivariable logistic regression was conducted. Results: Data on 32,715 individuals aged ≥ 50years [mean (SD) age 62.1 (15.6) years; 51.2% females] were analyzed. Compared to those without far or near vision impairment, those with near vision impairment but not far vision impairment (OR = 1.33; 95% CI = 1.16–1.52), and those with both far and near vision impairment (OR = 1.70; 95% CI = 1.27–2.29) had significantly higher odds for MCI. Only having far vision impairment was not significantly associated with MCI. Conclusions: Visual impairment is associated with increased odds for MCI among older adults in LMICs with the exception of far vision impairment only. Future longitudinal and intervention studies should examine causality and whether improvements in visual acuity, or early intervention, can reduce risk for MCI and ultimately, dementia. © 2021, The Author(s), under exclusive licence to Springer Nature Switzerland AG part of Springer Nature.

International audience; This work deals with the multi-scale optimisation of composite structures by adopting a general global-local (GL) modelling strategy to assess the structure responses at different scales. The GL modelling approach is integrated into the multi-scale two-level optimisation strategy (MS2LOS) for composite structures. The resulting design strategy is, thus, called GL-MS2LOS and aims at proposing a very general formulation of the design problem, without introducing simplifying hypotheses on the laminate stack and by considering, as design variables, the full set of geometric and mechanical parameters defining the behaviour of the composite structure at each pertinent scale. By employing a GL modelling approach, most of the limitations of well-established design strategies, based on analytical or semi-empirical models, are overcome. The GL-MS2LOS makes use of the polar formalism to describe the anisotropy of the composite at the macroscopic scale (where it is modelled as an equivalent homogeneous anisotropic plate). In this work, deterministic algorithms are exploited during the solution search phase. The challenge, when dealing with such a design problem, is to develop a suitable formulation and dedicated operators, to link global and local models physical responses and their gradients. Closed-form expressions of structural responses gradients are rigorously derived by taking into account for the coupling effects when passing from global to local models. The effectiveness of the GL-MS2LOS is proven on a meaningful benchmark: the least-weight design of a cantilever wing subject to different design requirements. Constraints include maximum allowable displacements, maximum allowable strains, blending, manufacturability requirements and buckling factor.; This work deals with the multi-scale optimisation of composite structures by adopting a general global-local (GL) modelling strategy to assess the structure responses at different scales. The GL modelling approach is integrated into the multi-scale two-level optimisation strategy (MS2LOS) for composite structures. The resulting design strategy is, thus, called GL-MS2LOS and aims at proposing a very general formulation of the design problem, without introducing simplifying hypotheses on the laminate stack and by considering, as design variables, the full set of geometric and mechanical parameters defining the behaviour of the composite structure at each pertinent scale. By employing a GL modelling approach, most of the limitations of well-established design strategies, based on analytical or semi-empirical models, are overcome. The GL-MS2LOS makes use of the polar formalism to describe the anisotropy of the composite at the macroscopic scale (where it is modelled as an equivalent homogeneous anisotropic plate). In this work, deterministic algorithms are exploited during the solution search phase. The challenge, when dealing with such a design problem, is to develop a suitable formulation and dedicated operators, to link global and local models physical responses and their gradients. Closed-form expressions of structural responses gradients are rigorously derived by taking into account for the coupling effects when passing from global to local models. The effectiveness of the GL-MS2LOS is proven on a meaningful benchmark: the least-weight design of a cantilever wing subject to different design requirements. Constraints include maximum allowable displacements, maximum allowable strains, blending, manufacturability requirements and buckling factor.

International audience; An important yet largely unexamined issue is how the interaction between deforestation and pollution affects economic and environmental sustainability.This article seeks to bridge the gap by introducing a dynamic model of pollution accumulation where polluting emissions can be mitigated and the absorption efficiency of pollution sinks can be restored. We assume that emissions are due to a production activity, and we include deforestation both as an additional source of emissions and as a cause of the exhaustion of environmental absorption efficiency. To account for the fact that the switching of natural sinks to a pollution source can be either possible, and in such a case even reversible, or impossible, we consider that restoration efforts can be either independent from or dependent on environmental absorption efficiency, i.e., state-independent versus state-dependent restoration efforts. We determine (i) whether production or deforestation is the most detrimental from environmental and social welfare perspectives, and (ii) how state-dependent restoration process affects pollution accumulation and deforestation policies and the related environmental and social welfare consequences.

Single-molecule localization microscopy (SMLM) describes a family of powerful imaging techniques that dramatically improve spatial resolution over standard, diffraction-limited microscopy techniques and can image biological structures at the molecular scale. In SMLM, individual fluorescent molecules are computationally localized from diffraction-limited image sequences and the localizations are used to generate a super-resolution image or a time course of super-resolution images, or to define molecular trajectories. In this Primer, we introduce the basic principles of SMLM techniques before describing the main experimental considerations when performing SMLM, including fluorescent labelling, sample preparation, hardware requirements and image acquisition in fixed and live cells. We then explain how low-resolution image sequences are computationally processed to reconstruct super-resolution images and/or extract quantitative information, and highlight a selection of biological discoveries enabled by SMLM and closely related methods. We discuss some of the main limitations and potential artefacts of SMLM, as well as ways to alleviate them. Finally, we present an outlook on advanced techniques and promising new developments in the fast-evolving field of SMLM. We hope that this Primer will be a useful reference for both newcomers and practitioners of SMLM. This Primer explains the central concepts of single-molecule localization microscopy (SMLM) before discussing experimental considerations regarding fluorophores, optics and data acquisition, processing and analysis. The Primer further describes recent high-impact discoveries made by SMLM techniques and concludes by discussing emerging methodologies.

International audience; Key message: A novel multi-environment competition individual-tree mixed model resulted in better fit, and greater individual narrow- and broad-sense heritabilities than the model without competition, notably for traits showing competition. In multi-environment tests, the proposed model would allow tree breeders to select genotypes with the best performance in both additive direct and competition breeding values, increasing forest productivity. Context: Genetic merit of trees is known to be affected and interact with local competition effects as well as changes across environmental conditions. Recent studies showed that competition genetic effects can affect the genetic variance and bias the tree breeding values, and its covariance with direct breeding values has been variable across traits. Aims: The present paper extends a mixed-model methodology to the problem of accounting for competition in a multi-environment set of forest genetic trials and exploring its impact on genetic variances as well as the multi-environment genetic correlation. Methods: The proposed model is illustrated using data from two full-sib trials of Pinus elliottii var. elliottii × Pinus caribaea var. hondurensis F1. Dispersion parameters and (co)variance of total breeding values were estimated for diameter at breast height, total tree height, and stem straightness at age 10. Results: For traits showing competition effects (diameter at breast height and total tree height), the proposed multi-environment competition model gave better fit than the simpler model. Accounting for competition increased the direct additive variance, reduced the residual variances, and did not change significantly the across-site additive genetic correlation. However, for diameter at breast height, top 5% best genetic rankings showed differences. Conclusion: When traits are strongly affected by inter-tree competition, the use of the proposed model in multi-environment analyses can efficiently identify the phenomenon with general benefits in the fitting of genetic components and open the door to select on the basis of competitiveness.

International audience; Reports of the Intergovernmental Panel on Climate Change (IPCC) employ an evolving framework of calibrated language for assessing and communicating degrees of certainty in findings. A persistent challenge for this framework has been ambiguity in the relationship between multiple degree-of-certainty metrics. We aim to clarify the relationship between the likelihood and confidence metrics used in the Fifth Assessment Report (2013), with benefits for mathematical consistency among multiple findings and for usability in downstream modeling and decision analysis. We discuss how our proposal meshes with current and proposed practice in IPCC uncertainty assessment.

Cellular therapies have been increasingly applied to diverse human diseases. Intracoronary infusion of bone marrow-derived mononuclear cells (BMMNC) has demonstrated to improve ventricular function after acute myocardial infarction. However, less information is available about the role of BMMNC therapy for the treatment of dilated myocardiopathies (DCs) of non-ischemic origin. This article presents the methodological description of a study aimed at investigating the efficacy of intracoronary injection of autologous BMMNCs in the improvement of the ventricular function of patients with DC. This randomised, placebo-controlled, double-blinded phase IIb clinical trial compares the improvement on ventricular function (measured by the changes on the ejection fraction) of patients receiving the conventional treatment for DC in combination with a single dose of an intracoronary infusion of BMMNCs, with the functional recovery of patients receiving placebo plus conventional treatment. Patients assigned to both treatment groups are monitored for 24 months. This clinical trial is powered enough to detect a change in Left Ventricular Ejection Fraction (LVEF) equal to or greater than 9%, although an interim analysis is planned to re-calculate sample size. The study protocol was approved by the Andalusian Coordinating Ethics Committee for Biomedical Research (Comite Coordinador de Etica en Investigacion Biomedica de Andalucia), the Spanish Medicines and Medical Devices Agency (Agencia Espanola de Medicamentos y Productos Sanitarios), and is registered at the EU Clinical Trials Register (EudraCT: 2013–002015-98). The publication of the trial results in scientific journals will be performed in accordance with the applicable regulations and guidelines to clinical trials. ClinicalTrials.gov Identifier NCT02033278 (First Posted January 10, 2014): https://clinicaltrials.gov/ct2/show/NCT02033278 ; EudraCT number: 2013–002015-98, EU CT Register: https://www.clinicaltrialsregister.eu/ctr-search/search?query=2013-002015-98 . Trial results will also be published according to the CONSORT statement at conferences and reported peer-reviewed journals.

We systematically investigated the effect of film-forming polyvinyl alcohol and crosslinkers, glyoxal and ammonium zirconium carbonate, on the optical and surface properties of films produced from TEMPO-oxidized cellulose nanofibers (TOCNFs). In this regard, UV-light transmittance, surface roughness and wetting behavior of the films were assessed. Optimization was carried out as a function of film composition following the “random forest” machine learning algorithm for regression analysis. As a result, the design of tailor-made TOCNF-based films can be achieved with reduced experimental expenditure. We envision this approach to be useful in facilitating adoption of TOCNF for the design of emerging flexible electronics, and related platforms.

Human mobility is known to be distributed across several orders of magnitude of physical distances, which makes it generally difficult to endogenously find or define typical and meaningful scales. Relevant analyses, from movements to geographical partitions, seem to be relative to some ad-hoc scale, or no scale at all. Relying on geotagged data collected from photo-sharing social media, we apply community detection to movement networks constrained by increasing percentiles of the distance distribution. Using a simple parameter-free discontinuity detection algorithm, we discover clear phase transitions in the community partition space. The detection of these phases constitutes the first objective method of characterising endogenous, natural scales of human movement. Our study covers nine regions, ranging from cities to countries of various sizes and a transnational area. For all regions, the number of natural scales is remarkably low (2 or 3). Further, our results hint at scale-related behaviours rather than scale-related users. The partitions of the natural scales allow us to draw discrete multi-scale geographical boundaries, potentially capable of providing key insights in fields such as epidemiology or cultural contagion where the introduction of spatial boundaries is pivotal.