Dielectric Strength of Nanofluid-Impregnated Transformer Solid Insulation

The interest in developing new fluids that can be used as dielectric liquids for transformers has driven the research on dielectric nanofluids in the last years. A number of authors have reported promising results on the electrical and thermal properties of dielectric nanofluids. Less attention has been paid to the interaction of these fluids with the cellulose materials that constitute the solid insulation of the transformers. In the present study, the dielectric strength of cellulose insulation is investigated, comparing its behavior when it is impregnated with transformer mineral oil and when it is impregnated with a dielectric nanofluid. The study includes the analysis of the AC breakdown voltage and the impulse breakdown voltage of the samples. Large improvements were observed on the AC breakdown voltages of the specimens impregnated with nanofluids, while the enhancements were lower in the case of the impulse tests. The reasons for the increase in AC breakdown voltage were investigated, considering the dielectric properties of the nanofluids used to impregnate the samples of cellulose. The analysis was completed with a finite element study that revealed the effect of the nanoparticles on the electric field distribution within the test cell, and its role in the observed enhancement.This work was supported by the Spanish State Research Agency under grant PID2019- 107126RB-C21/ AEI/10.13039/501100011033 and by the Spanish Ministry of Economy and Competitiveness under grant DPI2015-71219-C2-2-

Effect of Fibrin Concentration on the In Vitro Production of Dermo-Epidermal Equivalents

This article belongs to the Special Issue Advanced Biomaterials for Wound Healing 2021.Human plasma-derived bilayered skin substitutes were successfully used by our group to produce human-based in vitro skin models for toxicity, cosmetic, and pharmaceutical testing. However, mechanical weakness, which causes the plasma-derived fibrin matrices to contract significantly, led us to attempt to improve their stability. In this work, we studied whether an increase in fibrin concentration from 1.2 to 2.4 mg/mL (which is the useful fibrinogen concentration range that can be obtained from plasma) improves the matrix and, hence, the performance of the in vitro skin cultures. The results show that this increase in fibrin concentration indeed affected the mechanical properties by doubling the elastic moduli and the maximum load. A structural analysis indicated a decreased porosity for the 2.4 mg/mL hydrogels, which can help explain this mechanical behavior. The contraction was clearly reduced for the 2.4 mg/mL matrices, which also allowed for the growth and proliferation of primary fibroblasts and keratinocytes, although at a somewhat reduced rate compared to the 1.2 mg/mL gels. Finally, both concentrations of fibrin gave rise to organotypic skin cultures with a fully differentiated epidermis, although their lifespans were longer (25–35%) in cultures with more concentrated matrices, which improves their usefulness. These systems will allow the generation of much better in vitro skin models for the testing of drugs, cosmetics and chemicals, or even to “personalized” skin for the diagnosis or determination of the most effective treatment possible.This research was funded by Programa de Actividades de I+D entre Grupos de Investigación de la Comunidad de Madrid, S2018/BAA-4480, Biopieltec-CM; by Programa Estatal de I+D+i Orientada a los Retos de la Sociedad, RTI2018-101627-B-I00; by Programa de Apoyo a la Realización de Proyectos Interdisciplinares de I+D para Jóvenes Investigadores de la Universidad Carlos III de Madrid (project: BIOMASKIN); and by Cátedra Fundación Ramón Areces

A deletion at Adamts9-magi1 Locus is associated with psoriatic arthritis risk

Objective: Copy number variants (CNVs) have been associated with the risk to develop multiple autoimmune diseases. Our objective was to identify CNVs associated with the risk to develop psoriatic arthritis (PsA) using a genome-wide analysis approach. Methods: A total of 835 patients with PsA and 1498 healthy controls were genotyped for CNVs using the Illumina HumanHap610 BeadChip genotyping platform. Genomic CNVs were characterised using CNstream analysis software and analysed for association using the χ2 test. The most significant genomic CNV associations with PsA risk were independently tested in a validation sample of 1133 patients with PsA and 1831 healthy controls. In order to test for the specificity of the variants with PsA aetiology, we also analysed the association to a cohort of 822 patients with purely cutaneous psoriasis (PsC). Results: A total of 165 common CNVs were identified in the genome-wide analysis. We found a highly significant association of an intergenic deletion between ADAMTS9 and MAGI1 genes on chromosome 3p14.1 (p=0.00014). Using the independent patient and control cohort, we validated the association between ADAMTS9-MAGI1 deletion and PsA risk (p=0.032). Using next-generation sequencing, we characterised the 26 kb associated deletion. Finally, analysing the PsC cohort we found a lower frequency of the deletion compared with the PsA cohort (p=0.0088) and a similar frequency to that of healthy controls (p>0.3). Conclusions: The present genome-wide scan for CNVs associated with PsA risk has identified a new deletion associated with disease risk and which is also differential from PsC risk

Potassium and Sodium Transport in Yeast

[EN] As the proper maintenance of intracellular potassium and sodium concentrations is vital for cell growth, all living organisms have developed a cohort of strategies to maintain proper monovalent cation homeostasis. In the model yeast Saccharomyces cerevisiae, potassium is accumulated to relatively high concentrations and is required for many aspects of cellular function, whereas high intracellular sodium/potassium ratios are detrimental to cell growth and survival. The fact that S. cerevisiae cells can grow in the presence of a broad range of concentrations of external potassium (10 M–2.5 M) and sodium (up to 1.5 M) indicates the existence of robust mechanisms that have evolved to maintain intracellular concentrations of these cations within appropriate limits. In this review, current knowledge regarding potassium and sodium transporters and their regulation will be summarized. 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Post-Franco Theatre

In the multiple realms and layers that comprise the contemporary Spanish theatrical landscape, “crisis” would seem to be the word that most often lingers in the air, as though it were a common mantra, ready to roll off the tongue of so many theatre professionals with such enormous ease, and even enthusiasm, that one is prompted to wonder whether it might indeed be a miracle that the contemporary technological revolution – coupled with perpetual quandaries concerning public and private funding for the arts – had not by now brought an end to the evolution of the oldest of live arts, or, at the very least, an end to drama as we know it

Development of hyaluronic acid/plasma derived fibrin hydrogels for the optimization of dermo-epidermal skin substitutes

Mención Internacional en el título de doctorSkin is one of the largest organs of the body and covers almost its entire surface. Its main functions are protecting the body against the hostile environment, regulating the body temperature, inhibiting water loss and also functioning as sensory organ. Skin damage thus is presented as a potential threat to the maintenance of the homeostasis between the body and its surroundings. Full-thickness wounds resulting from acute damage, severe burns and other chronic conditions like diabetic foot ulcer represent a huge medical burden due to the difficulty to treat them and the high cost, fact that will make the skin wound care market to reach a $12.45 billion dollars market capitalization by 2022. Classical solutions to skin damage have been the use of autografts and allografts to transplant healthy skin parts into the wounded area. However, drawbacks associated to these techniques have rendered them of limited utility and the emergence of skin tissue engineering and more precisely of dermo-epidermal constructs has opened the possibility to fully treat these wounds in an effective manner. In this thesis, we use a solution previously developed in our laboratory consisting on a dermo-epidermal skin equivalent comprised of a plasma-derived fibrin dermal scaffold containing embedded human primary fibroblast and a layer of keratinocytes seeded on top to form the epidermis. Although this matrix has been proven to be effective for the treatment of severe and extensive burned patients in Spain, several persisting issues associated with this solution still remain unsolved. Furthermore, its use as an in vitro platform for disease modelling and drug testing has been hindered by its reduced stability. Here we perform a complete characterisation of the plasma-derived matrices and the effects of different concentrations and environments on them in terms of contractile behaviour and mechanical endurance, to later propose a solution to the issues related to them in the form of poor mechanical properties and excessive degradation rates. A new research trend proposes the combination of biological components and biomaterials with different properties to form enhanced scaffolds that are able to overcome the aforementioned issues. In that context, this thesis shows that hyaluronic acid (HA), a glycosaminoglycan naturally present in the skin, in combination with fibrin-based matrices is capable of better mimicking the wound healing environment, reducing the shrinking rates and enhancing the mechanical properties. HA at physiological levels (0.05%-0.2%) was used in combination with a crosslinker polyethylene (glycol) diacrylate (PEGDA) to better reinforce the plasma-derived matrices. The results obtained for the preliminary characterisation studies were satisfactory in terms of mechanical and biological properties for a HA content of 0.05% w/v and 2:1 crosslinking ratio (moles of thiol to moles of acrylate). Organotypic skins formed in vitro with these conditions showed to be up to three times thicker than the plasma controls evidencing the reduction in contraction while they also showed a better and more homogeneous Keratin 10 (K10) expression in the supra-basal layer of the epidermis. Furthermore, filaggrin expression showed the formation of an enhanced stratum corneum for the constructs containing HA. The next step is transplanting this new dermo-epidermal equivalent into the backs of nude immunodeficient mice in order to check the integration and viability of the construct in vivo. If successful, this finding might open the possibility to use these matrices in patients in the future leading to improved outcomes and better handling for the surgeons. Furthermore, our findings can be useful for reducing the time and costs associated to the technique while also serving as a potential in vitro testing platform for the study and development of new pharmacological products.Programa de Doctorado en Ciencia e Ingeniería de Materiales por la Universidad Carlos III de MadridPresidente: José Pérez Rigueiro.- Secretario: Lucía Martínez Santamaría.- Vocal: Abhay Shashikant Pandi

Hyaluronic acid-fibrin hydrogels show improved mechanical stability in dermo-epidermal skin substitutes

Human plasma-derived bilayered skin substitutes have been successfully used by our group in different skin tissue engineering applications. However, several issues associated with their poor mechanical properties were observed, and they often resulted in rapid contraction and degradation. In this sense, hydrogels composed of plasma-derived fibrin and thiolated-hyaluronic acid (HA-SH, 0.05–0.2% w/v) crosslinked with poly(ethylene glycol) diacrylate (PEGDA, 2:1, 6:1, 10:1 and 14:1 mol of thiol to moles of acrylate) were developed to reduce the shrinking rates and enhance the mechanical properties of the plasma-derived matrices. Plasma/HA-SH-PEGDA hydrogels showed a decrease in the contraction behaviour ranging from 5% to 25% and an increase in Young's modulus. Furthermore, the results showed that a minimal amount of the added HA-SH was able to escape the plasma/HA-SH-PEGDA hydrogels after incubation in PBS. The results showed that the increase in rigidity of the matrices as well as the absence of adhesion cellular moieties in the second network of HA-SH/PEGDA, resulted in a decrease in contraction in the presence of the encapsulated primary human fibroblasts (hFBs), which may have been related to an overall decrease in proliferation of hFBs found for all hydrogels after 7 days with respect to the plasma control. The metabolic activity of hFB returned to the control levels at 14 days except for the 2:1 PEGDA crosslinking ratio. The metabolic activity of primary human keratinocytes (hKCs) seeded on the hydrogels showed a decrease when high amounts of HA-SH and PEGDA crosslinker were incorporated. Organotypic skins formed in vitro after 21 days with plasma/HA-SH-PEGDA hydrogels with an HA content of 0.05% w/v and a 2:1 crosslinking ratio were up to three times thicker than the plasma controls, evidencing a reduction in contraction, while they also showed better and more homogeneous keratin 10 (K10) expression in the supra-basal layer of the epidermis. Furthermore, filaggrin expression showed the formation of an enhanced stratum corneum for the constructs containing HA. These promising results indicate the potential of using these biomimetic hydrogels as in vitro skin models for pharmaceutical products and cosmetics and future work will elucidate their potential functionality for clinical treatment.We kindly thank Rebeca Hernández for their guidance with the rheological experiments and Cristina Moral for her technical assistance with the SEM. This work was supported by Programa de Actividades de I+D entre Grupos de Investigación de la Comunidad de Madrid, S2018/BAA-4480, Biopieltec-CM, Programa Estatal de I+D+i Orientada a los Retos de la Sociedad, RTI2018-101627-B-I00, Madrid Government (Comunidad de Madrid) under the Multiannual Agreement with UC3M in the line of "Fostering Young Doctors Research" (BIOMASKIN-CM-UC3M) and in the context of the V PRICIT (Regional Programme of Research and Technological Innovation) and Cátedra Fundación Ramón Areces.Publicad

Identification of IRX1 as a Risk Locus for Rheumatoid Factor Positivity in Rheumatoid Arthritis in a Genome-Wide Association Study.

Rheumatoid factor (RF) is a well-established diagnostic and prognostic biomarker in rheumatoid arthritis (RA). However, ∼20% of RA patients are negative for this anti-IgG antibody. To date, only variation at the HLA-DRB1 gene has been associated with the presence of RF. This study was undertaken to identify additional genetic variants associated with RF positivity. A genome-wide association study (GWAS) for RF positivity was performed using an Illumina Quad610 genotyping platform. A total of 937 RF-positive and 323 RF-negative RA patients were genotyped for >550,000 single-nucleotide polymorphisms (SNPs). Association testing was performed using an allelic chi-square test implemented in Plink software. An independent cohort of 472 RF-positive and 190 RF-negative RA patients was used to validate the most significant findings. In the discovery stage, a SNP in the IRX1 locus on chromosome 5p15.3 (SNP rs1502644) showed a genome-wide significant association with RF positivity (P = 4.13 × 10(-8) , odds ratio [OR] 0.37 [95% confidence interval (95% CI) 0.26-0.53]). In the validation stage, the association of IRX1 with RF was replicated in an independent group of RA patients (P = 0.034, OR 0.58 [95% CI 0.35-0.97] and combined P = 1.14 × 10(-8) , OR 0.43 [95% CI 0.32-0.58]). To our knowledge, this is the first GWAS of RF positivity in RA. Variation at the IRX1 locus on chromosome 5p15.3 is associated with the presence of RF. Our findings indicate that IRX1 and HLA-DRB1 are the strongest genetic factors for RF production in RA

Benito Pérez Galdós

In Galdós\u27 time, the tensions between such diverse phenomena as coins and credit, free trade and protectionist tariffs, factory work and domestic economy, masculine and feminine, and private and public exacerbated friction among peoples—those of pueblo and rural origins, whose voices rasped and whose bright colors raked the eye, and a nascent, insecure bourgeosie who, fearful of the masses, strove to imitate the aristocracy. Old and new converged also with the question of suffrage and citizenship to aggravate social malaise and political upheavals—Carlist wars, palace intrigues, the Revolution of 1868 and overthrow of Queen Isabel, the brief reign of Amadeo of Savoy, the aborted First Republic and the Bourbon Restoration (1875-1885), which reached Spain from England in the imported person of Alfonso XII. These turbulent events undergird the cultural, historical, and political events of the novels by Benito Pérez Galdós (1843–1920) to be discussed in this chapter. Galdós is the author of seventy-seven novels, twenty-six original plays, and numerous occasional pieces, written between 1867 and 1920. These divide into two main categories: the historical and the contemporary social novels, now more appropriately described as novels of modernity The forty-six historical novels, called Episodios nacionales, make up five series, each consisting of ten interconnected novels, except the fifth series, left unfinished. The thirty-one novels of modernity, published between 1870 and 1915, also divide into two groups: Novelas de la primera época ( Novels of the Early Period, 1870–1879) and Las novelas de la serie contemporánea ( The Contemporary Social Novels, 1881–1915). The novels of the early period comprise Galdós\u27 first attempts at novel writing, as well as four so-called thesis novels : Doña Perfecta (1876), the sequel Gloria (1876–1877), Marianela (1878), and La familia de León Roch ( The Family of León Roch, 1878–1879). The next group of novels represents what Galdós called his segunda manera —his second style, a different kind of writing ... a more sophisticated and varied mode of narrative presentation

Juntas / Juntes

Multitud d'autores i autors aporten píndoles de microliteratura, de gèneres diversos, al tercer volum amb què l'Institut Universitari d'Estudis Feministes i de Gènere Purificación Escribano vol respondre al desafiament per l'eradicació de la violència contra les dones.Tercer desafío por la erradicación de la violencia contra las mujeres del Institut Universitari d'Estudis Feministes i de Gènere Purificación Escribano de la Universitat Jaume I a través de microliteratura