866 research outputs found

    Gender differences in time use across age groups : a study of ten industrialized countries, 2005-2015

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    Altres ajuts: Ramón y Cajal Programme (RYC2018-024808-I) ; Generalitat de Catalunya, CERCAThis study uses large scale cross-national time-diary data from the Multinational Time Use Study (MTUS) (N = 201,972) covering the period from 2005 to 2015 to examine gender differences in time use by age groups. The study compares ten industrialized countries across Asia, Europe, and North America. In all ten countries, gender differences in time use are smaller in personal care, sleeping and meals, followed by leisure time (including screen-based leisure and active leisure), and largest in housework, care work and paid work activities. Gender disparities in time use are higher in South Korea, Hungary, and Italy, followed closely by Spain, with moderate gender gaps in Western European countries like France and Netherlands, and lowest differences in Finland and Anglo-Saxon countries, including Canada, US, and the UK. Gender differences in housework and caring time increase from adolescence (10-17 years) to early adulthood (18-29 years), showing strong gender gaps in early/middle adulthood (30-44 years), but narrow again during late adulthood (65 years or older). However, the age gradient in care work and housework is most pronounced in Italy and South Korea, being less prominent in Canada and Finland. Gender gaps in paid work are larger in early/middle adulthood (30-44) and middle/late adulthood (45-64), with strongest age gradients observed in the Netherlands and weaker gradients for the US. Gender differences in active leisure increase by age, especially in Southern European countries, while screen-based leisure shows more stable gender gaps by age groups across different countries. Overall, this study shows that age and gender intersect strongly in affecting time-use patterns, but also that the national context plays an important role in shaping gender-age interactions in time use allocation

    A hybrid approach based on genetic algorithms to solve the problem of cutting structural beams in a metalwork company

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    This work presents a hybrid approach based on the use of genetic algorithms to solve efficiently the problem of cutting structural beams arising in a local metalwork company. The problem belongs to the class of one-dimensional multiple stock sizes cutting stock problem, namely 1-dimensional multiple stock sizes cutting stock problem. The proposed approach handles overproduction and underproduction of beams and embodies the reusability of remnants in the optimization process. Along with genetic algorithms, the approach incorporates other novel refinement algorithms that are based on different search and clustering strategies.Moreover, a new encoding with a variable number of genes is developed for cutting patterns in order to make possible the application of genetic operators. The approach is experimentally tested on a set of instances similar to those of the local metalwork company. In particular, comparative results show that the proposed approach substantially improves the performance of previous heuristics.Gracia Calandin, CP.; Andrés Romano, C.; Gracia Calandin, LI. (2013). A hybrid approach based on genetic algorithms to solve the problem of cutting structural beams in a metalwork company. Journal of Heuristics. 19(2):253-273. doi:10.1007/s10732-011-9187-xS253273192Aktin, T., Özdemir, R.G.: An integrated approach to the one dimensional cutting stock problem in coronary stent manufacturing. Eur. J. Oper. Res. 196, 737–743 (2009)Alves, C., Valério de Carvalho, J.M.: A stabilized branch-and-price-and-cut algorithm for the multiple length cutting stock problem. Comput. Oper. Res. 35, 1315–1328 (2008)Anand, S., McCord, C., Sharma, R., et al.: An integrated machine vision based system for solving the nonconvex cutting stock problem using genetic algorithms. J. Manuf. Syst. 18, 396–415 (1999)Belov, G., Scheithauer, G.: A cutting plane algorithm for the one-dimensional cutting stock problem with multiple stock lengths. Eur. J. Oper. Res. 141, 274–294 (2002)Christofides, N., Hadjiconstantinou, E.: An exact algorithm for orthogonal 2-D cutting problems using guillotine cuts. Eur. J. Oper. Res. 83, 21–38 (1995)Elizondo, R., Parada, V., Pradenas, L., Artigues, C.: An evolutionary and constructive approach to a crew scheduling problem in underground passenger transport. J. Heuristics 16, 575–591 (2010)Fan, L., Mumford, C.L.: A metaheuristic approach to the urban transit routing problem. J. Heuristics 16, 353–372 (2010)Gau, T., Wäscher, G.: CUTGEN1: a problem generator for the standard one-dimensional cutting stock problem. Eur. J. Oper. Res. 84, 572–579 (1995)Gilmore, P.C., Gomory, R.E.: A linear programming approach to the cutting stock problem. Oper. Res. 9, 849–859 (1961)Gilmore, P.C., Gomory, R.E.: A linear programming approach to the cutting stock problem. Part II. Oper. Res. 11, 863–888 (1963)Ghiani, G., Laganà, G., Laporte, G., Mari, F.: Ant colony optimization for the arc routing problem with intermediate facilities under capacity and length restrictions. J. Heuristics 16, 211–233 (2010)Gonçalves, J.F., Resende, G.C.: Biased random-key genetic algorithms for combinatorial optimization. J. Heuristics (2011). doi: 10.1007/s10732-010-9143-1Gradisar, M., Kljajic, M., Resinovic, G., et al.: A sequential heuristic procedure for one-dimensional cutting. Eur. J. Oper. Res. 114, 557–568 (1999)Haessler, R.W.: One-dimensional cutting stock problems and solution procedures. Math. Comput. Model. 16, 1–8 (1992)Haessler, R.W., Sweeney, P.E.: Cutting stock problems and solution procedures. Eur. J. Oper. Res. 54(2), 141–150 (1991)Haessler, R.W.: Solving the two-stage cutting stock problem. Omega 7, 145–151 (1979)Hinterding, R., Khan, L.: Genetic algorithms for cutting stock problems: with and without contiguity. In: Yao, X. (ed.) Progress in Evolutionary Computation. LNAI, vol. 956, pp. 166–186. Springer, Berlin (1995)Holthaus, O.: Decomposition approaches for solving the integer one-dimensional cutting stock problem with different types of standard lengths. Eur. J. Oper. Res. 141, 295–312 (2002)Kantorovich, L.V.: Mathematical methods of organizing and planning production. Manag. Sci. 6, 366–422 (1939) (Translation to English 1960)Liang, K., Yao, X., Newton, C., et al.: A new evolutionary approach to cutting stock problems with and without contiguity. Comput. Oper. Res. 29, 1641–1659 (2002)Poldi, K., Arenales, M.: Heuristics for the one-dimensional cutting stock problem with limited multiple stock lengths. Comput. Oper. Res. 36, 2074–2081 (2009)Suliman, S.M.A.: Pattern generating procedure for the cutting stock problem. Int. J. Prod. Econ. 74, 293–301 (2001)Talbi, E.-G.: A taxonomy of hybrid metaheuristics. J. Heuristics 8, 541–564 (2002)Vahrenkamp, R.: Random search in the one-dimensional cutting stock problem. Eur. J. Oper. Res. 95, 191–200 (1996)Vanderbeck, F.: Exact algorithm for minimizing the number of set ups in the one dimensional cutting stock problems. Oper. Res. 48, 915–926 (2000)Wagner, B.J.: A genetic algorithm solution for one-dimensional bundled stock cutting. Eur. J. Oper. Res. 117, 368–381 (1999)Wäscher, G., Haußner, H., Schumann, H.: An improved typology of cutting and packing problems. Eur. J. Oper. Res. 183, 1109–1130 (2007

    Novel fluorescence-based tools and applications for characterizing emerging pathways of α-synuclein amyloid aggregation, disaggregation and inhibition

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    Habitualmente se denomina agregación amiloide a aquel proceso de malplegamiento proteico que comprende la transición de una proteína soluble y funcional a especies oligoméricas intermedias y, en última instancia, fibras insolubles con una estructura característica llamada de lámina β cruzada. Varias enfermedades neurodegenerativas se encuentran asociadas a este proceso, entre las que se encuentra la enfermedad de Párkinson (PD en inglés). Esta se caracteriza por unos depósitos intracelulares, denominados cuerpos o neuritas de Lewy, ricos en α-sinucleína (αS) en forma de agregados amiloides. αS es una proteína intrínsecamente desordenada de 140 aminoácidos que se expresa ampliamente en el cuerpo humano, especialmente en el sistema nervioso central. Su agregación amiloide también está vinculada con otras sinucleinopatías como demencia con cuerpos de Lewy, atrofia sistémica múltiple y enfermedad de Alzheimer (AD en inglés). A pesar de que los factores que provocan el autoensamblado amiloide de αS in vivo son desconocidos, algunos estudios in vitro son capaces de reproducir tal agregación. Habitualmente, lo hacen mediante el uso de interfases de carácter hidrofóbico/hidrofílico que catalizan los primeros contactos entre proteínas en un proceso llamado nucleación primaria. Las estructuras amiloides formadas mediante este mecanismo de nucleación heterogénea poseen una disposición inter-molecular paralela. En este trabajo, hemos logrado inducir y analizar el autoensamblado amiloide de αS en ausencia de interfases bajo condiciones de hidratación limitada. La agregación ocurre en el seno de la disolución mediante una nucleación, por tanto, homogénea. Mediante el empleo de la espectroscopia de fluorescencia de pireno hemos demostrado que, siguiendo este nuevo mecanismo de nucleación, los agregados adoptan una topología antiparalela. Además, hemos observado que este tipo de nucleación podría estar favorecida en el interior de condensados biomoleculares de αS generados a través de separación de fases líquido líquido (LLPS en inglés), donde la hidratación de la proteína se ve reducida. Aplicando una combinación de técnicas biofísicas, hemos estudiado cuantitativamente la capacidad de αS y de la proteína Tau para sufrir LLPS. Entre estas técnicas, hemos empleado microscopía de tiempo de vida fluorescente (FLIM en inglés), al nivel de condensados individuales, para demostrar la maduración en el tiempo de estos, gracias a la exquisita resolución temporal y espacial de FLIM. Hemos descubierto que αS y Tau sí forman condensados biomoleculares mixtos y que, con el tiempo, forman heteroagregados amiloides en el interior de estos coacervados mediante la denominada transición de fases líquido-solido (LSPT en inglés). Cabe destacar que hemos esclarecido que el principal factor que regula esta LSPT es la valencia y ocupación de las interacciones heterotípicas,y no la dinámica de las cadenas polipeptídicas como se ha descrito frecuentemente paraotros sistemas. Nuestros resultados ayudan a establecer un escenario relevante para la co-agregación de ambas proteínas que podría explicar el hecho de que se observen, conjuntamente, tanto en PD como en AD. Además, hemos contribuido al campo de LLPS-LSPT proporcionando una descripción detallada y cuantitativa de sistemas αS/policatión con técnicas avanzadas y complementarias, incluyendo el estudio de coacervados individuales. Esto podría servir como base para el estudio de una amplia variedad de condensados biomoleculares y de especial interés para caracterizar la relación entre estos y la agregación amiloide.Por otra parte, encontrar moléculas con potencial terapéutico o diagnóstico en enfermedades neurodegenerativas es de una importancia extrema. Sin embargo, la complejidad y heterogeneidad en el paisaje conformacional de la agregación amiloide hacen de esta una diana destacablemente complicada para los estudios habituales de cribado de fármacos basados en ensayos de interacción molecular. En esta tesis hemos establecido una estrategia experimental que combina la espectroscopia de correlación cruzada de fluorescencia y la espectroscopia de fluorescencia de partícula individual de dos colores (dcFCCS/dcSPFS en inglés), y la hemos empleado para investigar la unión de pequeñas moléculas a especies amiloides neurotóxicas de αS con resolución de partícula individual y con independencia de las heterogeneidades moleculares del sistema de estudio. Gracias a la observación de los eventos de interacción de uno en uno, hemos resuelto de manera directa la especificidad, afinidad y estequiometría de unión de varios pequeños péptidos inhibidores de la agregación amiloide de αS, entre los cuales se incluye un péptido humano. Hemos descrito en detalle su mecanismo molecular de actuación y desentrañado las propiedades físico-químicas que respaldan la interacción, contribuyendo al diseño racional de otros péptidos candidatos a fármaco.El uso dcFCCS/dcSPFS puede ampliarse a otras situaciones de interacción multiligando/ receptor multimérico y convertirse en una plataforma experimental para el descubrimiento de nuevos fármacos y marcadores diagnósticos específicos de amiloide. Por último, además de inhibir el proceso de autoensamblado, la desagregación de fibras amiloides puede ser una herramienta para combatir la neurodegeneración. Dentro de las células, esta tarea es llevada a cabo sobre fibras de αS por una maquinaria especializada de chaperonas conocida como la desagregasa humana. Sin embargo, el mecanismo preciso por el cual este complejo proteico procesa las fibras, así como el posible vínculo entre la toxicidad y estructura de un agregado y la actividad desagregasa sobre el mismo es un tema todavía bajo intenso debate. Uno de los principales retos es la obtención de datos cinéticos fiables y de calidad de la reacción de desensamblado, debido a artefactos de la técnica más extensamente usada: la fluorescencia de la sonda tioflavina-T. En nuestro trabajo hemos aplicado la fluorescencia de pireno junto con la desextinción de fluorescencia para afrontar este problema. Hemos logrado probar un mecanismo de desagregación de todo o nada, por el cual cada fibra se desensambla y libera monómeros solubles de αS mediante un mecanismo de cremallera. Nuestros datos cinéticos han permitido el modelado cuantitativo del mecanismo de desagregación sobre diferentes estructuras amiloides de αS. Estos resultados han revelado que, probablemente, la desagregasa humana ha evolucionado para actuar específicamente sobre agregados pequeños y citotóxicos.En resumen, hemos implementado nuevas herramientas y aplicaciones de fluorescencia, incluyendo técnicas de fluorescencia resueltas en el tiempo y de partícula única de dos colores, para el estudio detallado de la agregación amiloide, transición de fases, inhibición y desagregación de αS. En conjunto, nuestros resultados contribuyen a responder preguntas clave de la agregación amiloide de αS y de la búsqueda de estrategias terapéuticas contra las sinucleinopatías. Además, los enfoques experimentales presentados en esta tesis se pueden aplicar para comprender y actuar sobre otros sistemas amiloides, siendo por tanto herramientas metodológicas relevantes en el campo de la agregación amiloide y la neurodegeneración.Amyloid aggregation is typically referred to as a protein misfolding process involving the transition from a functional, soluble protein into oligomeric intermediates and, eventually, insoluble fibrils with a hallmark cross-β structure. A number of neurodegenerative diseases are associated to this process, including Parkinson’s disease (PD), which is characterized by intracellular deposits rich in α-synuclein (αS) in the form of amyloid aggregates, which are referred to as Lewy bodies (LB) or neurites. αS is an intrinsically disordered 140-aminoacid protein widely expressed throughout the body, particularly in the central nervous system. Its amyloid aggregation is also associated with other synucleinopathies such as dementia with Lewy bodies (DLB), multiple system atrophy (MSA) or Alzheimer’s disease (AD). While the factors triggering the amyloid self-assembly of αS in vivo are still obscure, in vitro studies are able to reproduce the aggregation, typically using hydrophobic/hydrophilic interfaces to trigger the first protein-protein contacts, a process termed primary nucleation. The amyloid structures resulting from this (heterogeneous) nucleation show a parallel inter-molecular arrangement. In this work, we were able to induce and analyze the amyloid self-assembly of αS in the absence of interfaces in the bulk of the solution (homogeneous nucleation) under limited hydration conditions. By using pyrene fluorescence spectroscopy we proved that, via this new type of nucleation, the aggregates adopt an antiparallel topology. Moreover, we have observed that this type of nucleation could be favorable in the interior of αS condensates generated by liquid-liquid phase separation (LLPS). By using a combination of biophysical techniques, we quantitatively interrogated the ability of αS and the protein Tau to undergo LLPS. Among these techniques, we used fluorescence lifetime imaging microscopy (FLIM) down to the single-coacervate level, to resolve their maturation without ambiguity, owing to the exquisite temporal and spatial resolution of FLIM. We found that, indeed, αS and Tau form mixed biomolecular condensates by complex elecotrostatic coacervation and, over time, they form amyloid heteroaggregates through liquid-to-solid phase transition (LSPT) in the interior of the condensates. Interestingly, we proved that the valence and occupancy of the heterotypic interactions, and not the polypeptide dynamics, are the main factor governing LSPT. Our results help establishing a relevant scenario for the co-aggregation of both proteins which could explain their joint presence in both PD and AD. Besides, we have contributed to the LLPS-LSPT field by providing a thourough, quantitative description of αS/polycation systems with advanced and complementary techniques and by looking at single coacervates. This could serve as a framework to be used in a wide array of biomolecular condensates, and of particular interest for characterizing the link between these and amyloid aggregation. Finding molecules with therapeutic or diagnosic potential in neurodegenerative disorders is of utter importance. However, the complexity and heterogeneity of the amyloid conformational landscape, makes amyloid aggregation a tremendously challenging target for typical drug screens based in molecular interaction assays. Here, we established an experimental strategy which combines dual-color fluorescence correlation spectroscopy and single-particle fluorescence spectroscopy (dcFCCS/dcSPFS) to investigate the binding of small molecules to amyloid species of αS with single-particle resolution and regardless of molecular heterogeneity. By observing binding events individually, we gained direct access to the binding specificity, affinity and stoichiometry of several small amyloid inhibitory peptides, including a human peptidic molecule. We demonstrated its molecular mechanism of action and disentangled the minimum physico-chemical properties behind the binding properties, thus aiding in the rational design of other peptide drug candidates. dcFCCS/dcSPFS could be extended to other multi-ligand/multimeric receptor interaction scenarios and serve as a platform for finding new drugs and amyloid-specific diagnostic probes. Besides inhibiting the self-assembly process, the disaggregation of amyloid fibrils can be a tool for fighting neurodegeneration. In the cell, such task is performed on αS fibrils by an evolutionary refined chaperone machinery termed the human disaggregase. However, the exact mechanism by which this proteic complex processes the fibrils as well as what is the relationship between aggregate toxicity, structure and disaggregase activity remains under debate. A major challenge is to obtain reliable kinetic data of the disassembly reaction due to artifacts related to the most commonly used amyloid probe, thioflavin-T (ThT). In our work, we have applied pyrene fluorescence together with fluorescence dequenching to solving this problem. We demonstrated an all-or-none disassembly mechanism, where a fibril disassembles entirely into soluble monomers by an unzipping mechanism. Our kinetic data enabled to quantitatively model the disaggregation mechanism on different amyloid assemblies of αS. Our results revealed that the chaperone machinery has likely evolved to tackle small cytotoxic aggregates specifically. In summary, we have implemented new fluorescence-based tools and applications, including time-resolved and single-particle dual-color fluorescence techniques, to the detailed investigation of amyloid aggregation, phase separation, inhibition and disaggregation of αS. Collectively, our results help to understand key questions of αS amyloid aggregation and potential therapeutic strategies against synucleinopathies. In addition, the experimental approaches presented in this thesis can be also easily extended to understand and tackle other amyloid systems, representing important methodological tools in the fields of amyloid aggregation and neurodegeneration.<br /

    Nonstandard work schedules in 29 European countries, 2005-15: differences by education, gender, and parental status

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    Data from the European Working Conditions Surveys from 2005, 2010, and 2015 for 29 European countries show that the prevalence of nonstandard work schedules (evenings, nights, weekends, and rotating shifts) differs markedly across European regions with different public policies. Working nonstandard schedules also differs by education, gender, and parental status across Europe

    Integración Regional en África: La CEDEAO como un Área de Moneda Única

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    Globalisation is a phenomenon that has increased the commercial transactions volume, allowing countries to benefit and to have access to a wide number of markets. However, this process, along with the increasing complex geopolitical and economic environment among countries and regions of the world, has led the governments to seek solutions that combine the needs and priorities of that areas, easing in this way the economic transactions. The different alternatives to achieve integration and regional coordination include the creation of institutions and supranational and international organizations. The Economic Community of West African States (ECOWAS) is one of these organizations created to overtake the existing political, economic, historic, and social issues in West Africa through the creation of a single monetary area among the fifteen member states in order to achieve acceptable economic growth levels and sustainable development in the region. Following the Economic and Monetary Union (EMU) model, it would be explained why a monetary integration and creation of a new currency is needed, in order to end the colonial vestiges in Africa, as well as the path to be followed to place the region as a competitive market in the context of the international economy.<br /

    Characterisation of Amyloid Aggregation and Inhibition by Diffusion-Based Single-Molecule Fluorescence Techniques

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    Protein amyloid aggregation has been associated with more than 50 human disorders, including the most common neurodegenerative disorders Alzheimer’s and Parkinson’s disease. Interfering with this process is considered as a promising therapeutic strategy for these diseases. Our understanding of the process of amyloid aggregation and its role in disease has typically been limited by the use of ensemble-based biochemical and biophysical techniques, owing to the intrinsic heterogeneity and complexity of the process. Single-molecule techniques, and particularly diffusion-based single-molecule fluorescence approaches, have been instrumental to obtain meaningful information on the dynamic nature of the fibril-forming process, as well as the characterisation of the heterogeneity of the amyloid aggregates and the understanding of the molecular basis of inhibition of a number of molecules with therapeutic interest. In this article, we reviewed some recent contributions on the characterisation of the amyloid aggregation process, the identification of distinct structural groups of aggregates in homotypic or heterotypic aggregation, as well as on the study of the interaction of amyloid aggregates with other molecules, allowing the estimation of the binding sites, affinities, and avidities as examples of the type of relevant information we can obtain about these processes using these techniques

    PRODUCT DESIGN, DEVELOPMENT AND VIABILITY ANALYSIS MOTORCYCLE HELMET. LIGHT SECURITY SYSTEM “DragonFlight”

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    Every single one of us have heard ones or know someone who have had a bad experience with a motorbike, maybe it was his or her fault, perhaps it was originated due to the mistake of other vehicle or just was a simple distraction that caused as a result that small fright or that horrible accident. All the people who ride motorcycles assume that when an impact comes, our body is the chassis, our own body is in jeopardy to the unexpected just protected with a helmet and some protection clothes. The main goal of this project will be to try to reduce the possibilities of motorcycle users of having a fatality accident or at least reduce the gravity of them. We are going to create and develop a device to install in our helmets that turn on lights if the helmet and obviously “the biker” is decelerating. We will set up an emergency system as well in cases when the biker falls when we’ll show up as much lights as possible. The number of lights and as a result the intensity of the view are going to increase with the percentage of deceleration, this means that if the biker do an small deceleration we are just going to show a little light up however if the biker do a huge deceleration we will show an alarming and easy to see light in our helmet reducing then the perception and reaction time of the vehicles behind us. Our objective is to create a portable dispositive to be able to use it in more than one helmet so you as biker only have to buy one for all your helmets or to share with your family and friends

    Efficient online update of model predictive control in embedded systems using first-order methods

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    Model Predictive Control (MPC) is typically characterized for being computationally demanding, as it requires solving optimization problems online; a particularly relevant point when considering its implementation in embedded systems. To reduce the computational burden of the optimization algorithm, most solvers perform as many offline operations as possible, typically performing the computation and factorization of its expensive matrices offline and then storing them in the embedded system. This improves the efficiency of the solver, with the disadvantage that online changes on some of the ingredients of the MPC formulation require performing these expensive computations online. This article presents an efficient algorithm for the factorization of the key matrix used in several first-order optimization methods applied to linear MPC formulations, allowing its prediction model and cost function matrices to be updated online at the expense of a small computational cost. We show results comparing the proposed approach with other solvers from the literature applied to a linear time-varying system.Comment: (6 pages, 2 figures

    Efficient implementation of MPC for tracking using ADMM by decoupling its semi-banded structure

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    Model Predictive Control (MPC) for tracking formulation presents numerous advantages compared to standard MPC, such as a larger domain of attraction and recursive feasibility even when abrupt changes in the reference are produced. As a drawback, it includes some extra decision variables in its related optimization problem, leading to a semi-banded structure that differs from the banded structure encountered in standard MPC. This semi-banded structure prevents the direct use of the efficient algorithms available for banded problems. To address this issue, we present an algorithm based on the alternating direction method of multipliers that explicitly takes advantage of the underlying semi-banded structure of the MPC for tracking
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