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We make toroidal droplets of nematic liquid crystal and explore the defect-populated stable configurations that appear after heating to the isotropic phase and cooling back to the nematic phase. These configurations, as confirmed by simulations, are made of defect pairs where the positive/negative defect is located in the region of maximum positive/negative Gaussian curvature. Moreover, we demonstrate through experiments and simulations that these defect pairs also appear and are stable in cylinders, which have zero Gaussian curvature, highlighting the crucial role of bulk nematic elasticity in stabilizing these structures.

IntroductionLipid transfer proteins (LTPs) are allergens found in a wide range of plant-foods. Specifically, Pru p 3, the major allergen of peach, is commonly responsible for severe allergic reactions. The need for new alternatives to conventional food allergy treatments, like restrictive diets, suggests allergen immunotherapy as a promising option. It has been demonstrated that sublingual immunotherapy (SLIT) with synthetic glycodendropeptides, such as D1ManPrup3, containing mannose and Pru p 3 peptides induced tolerance in mice and that the persistence of this effect depends on treatment dose (2nM or 5nM). Moreover, it produces changes associated with differential gene expression and methylation profile of dendritic cells, as well as phenotypical changes in regulatory T cells (Treg). However, there are no works addressing the study of epigenetic changes in terms of methylation in the cell subsets that sustain tolerant responses, Treg. Therefore, in this work, DNA methylation changes in splenic-Treg from Pru p 3 anaphylactic mice were evaluated.MethodsIt was performed by whole genome bisulphite sequencing comparing SLIT-D1ManPrup3 treated mice: tolerant (2nM D1ManPrup3), desensitized (5nM D1ManPrup3), and sensitized but not treated (antigen-only), with anaphylactic mice.ResultsMost of the methylation changes were found in the gene promoters from both SLIT-treated groups, desensitized (1,580) and tolerant (1,576), followed by the antigen-only (1,151) group. Although tolerant and desensitized mice showed a similar number of methylation changes, only 445 genes were shared in both. Remarkably, interesting methylation changes were observed on the promoter regions of critical transcription factors for Treg function like Stat4, Stat5a, Stat5b, Foxp3, and Gata3. In fact, Foxp3 was observed exclusively as hypomethylated in tolerant group, whereas Gata3 was only hypomethylated in the desensitized mice.DiscussionIn conclusion, diverse D1ManPrup3 doses induce different responses (tolerance or desensitization) in mice, which are reflected by differential methylation changes in Tregs.

The recent research on asset pricing shows that the higher liquidity that results from the globalization of financial markets has significantly reduced the returns tied to many market anomaly-based strategies. However, in general, that research does not evaluate the effects that the mitigation of market anomalies may imply on the performance of the classic asset pricing models. On this basis, in this paper we study to what extent the lower returns provided by market anomaly-based strategies imply better performance of those models. Hence, the main purpose of our study is to compare the performance over time of some of the most prominent asset pricing models, namely, the CAPM and the Fama and French three- and five-factor models, on the European and US equity markets, using return series that cover more than 30 years. Our results show that, although the CAPM is the model with the worst performance in explaining excess returns in all periods both in Europe and US, the model has increased its explanatory power in the recent years principally due to the attenuation of classic market anomalies, such as the size effect or the value effect. Furthermore, our results show that the CAPM correctly prices the three classic Fama and French factors for the years 2006-2021, which explains the best performance of the model for that time interval. Our results have important implications for investment analysis, as well as for determining the cost of capital.

Abstract To investigate food allergy-tolerance mechanisms induced through allergen-specific immunotherapy we used RNA-Sequencing to measure gene expression in lymph-node-derived dendritic cells from Pru p 3-anaphylactic mice after immunotherapy with glycodendropeptides at 2 nM and 5 nM, leading to permanent tolerance and short-term desensitization, respectively. Gene expression was also measured in mice receiving no immunotherapy (anaphylaxis); and in which anaphylaxis could never occur (antigen-only). Compared to anaphylaxis, the antigen-only group showed the greatest number of expression-changes (411), followed by tolerant (186) and desensitized (119). Only 29 genes changed in all groups, including Il12b, Cebpb and Ifngr1. The desensitized group showed enrichment for genes related to chronic inflammatory response, secretory granule, and regulation of interleukin-12 production; the tolerant group showed genes related to cytokine receptor activity and glucocorticoid receptor binding, suggesting distinct pathways for similar outcomes. We identified genes and processes potentially involved in the restoration of long-term tolerance via allergen-specific immunotherapy, representing potential prognostic biomarkers.

IntroductionAllergen-specific immunotherapy (AIT) is applied as treatment to rise tolerance in patients with food allergies. Although AIT is thoroughly used, the underlying epigenetic events related to tolerant induction are still unknown. Thus, we aim to investigate epigenetic changes that could be related to tolerance in dendritic cells (DCs) from anaphylactic mice to lipid transfer proteins, Pru p 3, in the context of a sublingual immunotherapy (SLIT) with a glycodendropeptide (D1ManPrup3) that has demonstrated tolerant or desensitization responses depending on the treatment dose.MethodsChanges in DNA methylation in CpG context were determined comparing Sensitized (Antigen-only) animals and two groups receiving SLIT with the D1ManPrup3 nanostructure (D1ManPrup3-SLIT): Tolerant (2nM D1ManPrup3) and Desensitized (5nM D1ManPrup3), against anaphylactic animals. DNA from lymph nodes-DCs were isolated and then, Whole Genome Bisulphite Sequencing was performed to analyze methylation.ResultsMost differentially methylated regions were found on the area of influence of gene promoters (DMPRs). Compared to the Anaphylactic group, the highest value was found in Desensitized mice (n = 7,713 DMPRs), followed by Tolerant (n = 4,091 DMPRs) and Sensitized (n = 3,931 DMPRs) mice. Moreover, many of these epigenetic changes were found in genes involved in immune and tolerance responses (Il1b, Il12b, Il1a, Ifng, and Tnf) as shown by functional enrichment (DCs regulation, B cell-mediated immunity, and effector mechanisms).DiscussionIn conclusion, different doses of D1ManPrup3-SLIT induce different DNA methylation changes, which are reflected in the induction of distinct responses, tolerance, or desensitization.

Este trabajo se hace eco de un animado debate, que está presente en los últimos años en el ámbito de la educación superior, sobre si hay que permitir o se debe prohibir el uso de dispositivos móviles por los estudiantes en el aula. A fin de facilitar una toma de decisiones más informada, se revisa en profundidad la evidencia empírica existente hasta la fecha sobre la relación entre el uso de dispositivos móviles en las aulas y el rendimiento académico de los estudiantes. Se proporciona también nueva evidencia empírica sobre dicha relación, considerando ciertos aspectos que han sido ignorados por la investigación previa, como son la asignatura que se enseña, las características/intereses de los docentes, el año de estudio o el tamaño de la clase. Los resultados dispares del análisis empírico realizado, así como de la evidencia disponible, sugieren que el uso de estos dispositivos móviles y su relación con el rendimiento académico es un asunto complejo que debe ser analizado cuidadosamente. Se sugiere que la cuestión de si el uso de dispositivos móviles debe permitirse o prohibirse en el aula debería reemplazarse por cómo los docentes pueden sacar el mejor partido posible del uso de tales dispositivos en sus clases. Además, se presentan otras propuestas que pueden ser especialmente útiles en un contexto educativo como el actual, que está muy condicionado por la crisis de la COVID-19.

The Generalized Pareto Distribution (GPD) is used for modeling exceedances over thresholds. The general form of the GPD depends on three parameters: the location parameter µ; the scale parameter (β > 0); and the shape parameter (−∞ < ξ < ∞). This work restricts attention to the case where µ = 0 and shows that, as ξ decreases while β is kept fixed, the family of GPD(ξ, β) distributions increases in the usual stochastic order. This property is used for testing the significance of trends in the size of the exceedances over high thresholds in a time series consisting of ozone measurements.

Most single-factor and multifactor asset pricing models constitute special cases of the consumption-based asset pricing theory, in which investors' marginal utility is the key determinant of asset prices. However, in recent years, production-based asset pricing models have been extraordinarily successful in correctly pricing a wide range of anomaly portfolios that are typically mispriced in previous research. In parallel, research on conditioning information has contributed to significantly improve the performance of classic consumption-based asset pricing models. On this basis, in this paper we conduct an in-depth research on the performance of consumption and production-based asset pricing models on the Tokyo Stock Exchange, for the period from 1992 to 2018, in order to test to what extent consumer confidence helps consumption models to correctly capture shifts in the investment opportunity set of investors. To overcome the constraints imposed by the periodicity of macroeconomic data, we use a factor-mimicking portfolio approach that allows us to test the performance of the models into consideration at different frequencies. Our results suggest that the consumer confidence index for Japan helps consumption-based asset pricing models outperform production-based models for different anomaly portfolios. Conversely, in those cases where consumption models perform worse, the production models also perform poorly. These results help to partially reconcile the results provided by the consumption and production models, and constitute a step forward for the purpose of identifying the fundamental risk factors that drive asset prices.

The reduction in construction and maintenance costs per MW of renewable energy facilities, together with low interest rates, have led to a significant growth in the purchase prices paid for these facilities in the Spanish market. This trend is shared by other European countries, especially for projects that hedge energy price risk incorporating power purchase agreements with third parties. In this framework, questions arise about the economic rationale of the purchase prices paid for these projects. Consequently, we develop a project evaluation model that forecasts expected cash flow and time-varying required rates of return for a standard photovoltaic plant, in order to study the extent to which foreseeable market conditions—interest rates and equity risk premia, among others—translate into economically viable buyouts. Our results suggest that purchase prices paid for these initiatives often lead to buyer returns below those that would be reasonable according to market conditions. Indeed, we find that only facilities that reach a production 23% higher than the number of hours considered in the base case provide returns that compensate long-term financing costs. However, specialised investors can exploit their relatively low cost of financing to pay prices up to 73% higher than those affordable by classic investors.

Recent literature shows that many testing procedures used to evaluate asset pricing models result in spurious rejection probabilities. Model misspecification, the strong factor structure of test assets, or skewed test statistics largely explain this. In this paper we use the relative entropy of pricing kernels to provide an alternative framework for testing asset pricing models. Building on the fact that the law of one price guarantees the existence of a valid pricing kernel, we study the relationship between the mean-variance efficiency of a model’s factor-mimicking portfolio, as measured by the cross-sectional generalized least squares (GLS) R 2 statistic, and the relative entropy of the pricing kernel, as determined by the Kullback–Leibler divergence. In this regard, we suggest an entropy-based decomposition that accurately captures the divergence between the factor-mimicking portfolio and the minimum-variance pricing kernel resulting from the Hansen-Jagannathan bound. Our results show that, although GLS R 2 statistics and relative entropy are strongly correlated, the relative entropy approach allows us to explicitly decompose the explanatory power of the model into two components, namely, the relative entropy of the pricing kernel and that corresponding to its correlation with asset returns. This makes the relative entropy a versatile tool for designing robust tests in asset pricing.

Recent literature shows that market anomalies have significantly diminished, while research on market factors has largely improved the performance of asset pricing models. In this paper we study the extent to which data envelopment analysis (DEA) techniques can help improve the performance of multifactor models. Specifically, we test the explanatory power of the Fama and French three-factor model, combined with an additional factor based on DEA, on a sample of 2101 European equity funds, for the period from 2001 to 2016. Accordingly, we first form the fund portfolios that constitute our test assets and create the efficiency factor. Secondly, we estimate the prices of risk tied to the four factors using ordinary least squares (OLS) on a two-stage cross-sectional regression. Finally, we use the R-squared statistic estimated by generalized least squares (GLS), as well as the Gibbons Ross and Shanken test and the J-test for overidentifying restrictions in order to study the performance of the model, including and omitting the efficiency factor. The results show that the efficiency factor improves the performance of the model and reduces the pricing errors of the assets under consideration, which allows us to conclude that the efficiency index may be used as a factor in asset pricing models.

This contribution focuses its objective in describing the design and implementation of an innovative system to provide cognitive rehabilitation. People who will take advantage of this platform suffer from a post-stroke disease called Apraxia and Action Disorganisation Syndrome (AADS). The platform has been integrated at Universidad Politécnica de Madrid and tries to reduce the stay in hospital or rehabilitation center by supporting self-rehabilitation at home. So, the system acts as an intelligent machine which guides patients while executing Activities of Daily Living (ADL), such as preparing a simple tea, by informing them about the errors committed and possible actions to correct them. A short introduction to other works related to stroke, patients to work with, how the system works and how it is implemented are provided in the document. Finally, some relevant information from experiment made with healthy people for technical validation is also shown.

Vaccination strategies based on dendritic cells (DCs) armed with specific tumor antigens have been widely exploited due the properties of these immune cells in coordinating an innate and adaptive response. Here, we describe the convergent synthesis of the bifunctional multivalent glycodendron 5, which contains nine residues of mannose for DC targeting and one residue of an immunogenic mimetic of a carbohydrate melanoma associated antigen. The immunological assays demonstrated that the glycodendron 5 is able to induce human immature DC activation in terms of a phenotype expression of co-stimulatory molecules expression and MHCII. Furthermore, DCs activated by the glycodendron 5 stimulate T lymphocytes to proliferate in a mixed lymphocytes reaction (MLR).

The integration of rehabilitation systems in an ambient assisted living environment can provide a powerful and versatile tool for long-term stroke rehabilitation goals. This paper introduces a novel concept of a personalized cognitive rehabilitation system in a naturalistic setting. The proposed platform was developed within the CogWatch project, with the intent of fostering independence in activities of daily living in patients with apraxia and action disorganization syndrome. Technical usability was evaluated in a series of pilot experiments, which illustrate how this approach may help to retrain patients in activities of daily living. The first system prototype has been tested with 36 participants divided into three groups, providing an exploratory evaluation of the usability of this solution and its acceptability. The technical solutions used within the CogWatch project are targeted to meet both the end users’ needs from the interaction and usability point of views and the clinical requirements associated with the use of such systems. The challenges behind the development of ambient assisted living systems for cognitive rehabilitation are discussed.

The key role of carbohydrates in many biological events has attracted the interest of the scientific community. This fact has demanded the access to new tools necessary to understand this role and the interaction of carbohydrates with their corresponding receptors, lectins. Glycodendrimers and glycodendritic structures in general, have demonstrated to be very efficient and interesting tools to intervene in those processes where carbohydrates participate. In this review, we discuss the different glycodendritic structures that have been used to interfere with DC-SIGN, a very attractive lectin involved in infection processes and in the regulation of the immune response.

This article presents research focused on tracking manual tasks that are applied in cognitive rehabilitation so as to analyze the movements of patients who suffer from Apraxia and Action Disorganization Syndrome (AADS). This kind of patients find executing Activities of Daily Living (ADL) too difficult due to the loss of memory and capacity to carry out sequential tasks or the impossibility of associating different objects with their functions. This contribution is developed from the work of Universidad Politécnica de Madrid and Technical University of Munich in collaboration with The University of Birmingham. The KinectTM for Windows© device is used for this purpose. The data collected is compared to an ultrasonic motion capture system. The results indicate a moderate to strong correlation between signals. They also verify that KinectTM is very suitable and inexpensive. Moreover, it turns out to be a motion-capture system quite easy to implement for kinematics analysis in ADL.

The synthesis of two new D-galactose-based dimers having a 1,4-butanediamine spacer is reported aiming at the evaluation of their interaction with the Erythrina cristagalli lectin. The title compounds were prepared in four and five steps from 2,3,4,6-tetra-O-acetyl-β-D-galactopyranoside bromide, in 20 % and 15 % overall yield, respectively, using the Doebner modification of the Koenavenagel reaction as the key sep. The lectin-carbohydrate interaction could be evaluated for only one dimer, due to solubility problems. A twofold enhancement of affinity was observed, compared to the corresponding monovalent ligand.

El trabajo presenta el ahorro gallego y el uso que hace de éste el sistema financiero. Después de un repaso por el pasado y por los cambios producidos hasta la situación actual, se comentan las variables que afectarán a su evolución.