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The inclusion of students with autism spectrum disorder (ASD) in mainstream education (primary and secondary, in the range of 4-5 to 8-10 years old) is a complex task that has long challenged both educators and health professionals. However, the correct use of digital technologies such as personalization settings and interaction with robots has clearly shown how these new technologies can benefit ASD students. However, it is essential to characterize the profile, problems, and needs of each student, since it is not possible to generalize an accessible approach for all users. The work presented shows the creation and validation, through pilot tests, of an instrument that outlines the main needs of a student with ASD, based on behavioral variables. In a later phase, instructional sequences will be designed and adapted through digital tablets and interaction with a robot to improve specific aspects identified in the initial profile. The results demonstrate the method’s ability to assess and prioritize profiles satisfactorily which helps create a design adjusted to each student. The first pilot tests have been well received by ASD students, who have shown increased interest in the contents and methods used in this approach. Motivation levels and engagement have also increased, and social interactions with their peers have improved.

Abstract Modulation of magnetic properties through voltage-driven ion motion and redox processes, i.e., magneto-ionics, is a unique approach to control magnetism with electric field for low-power memory and spintronic applications. So far, magneto-ionics has been achieved through direct electrical connections to the actuated material. Here we evidence that an alternative way to reach such control exists in a wireless manner. Induced polarization in the conducting material immersed in the electrolyte, without direct wire contact, promotes wireless bipolar electrochemistry, an alternative pathway to achieve voltage-driven control of magnetism based on the same electrochemical processes involved in direct-contact magneto-ionics. A significant tunability of magnetization is accomplished for cobalt nitride thin films, including transitions between paramagnetic and ferromagnetic states. Such effects can be either volatile or non-volatile depending on the electrochemical cell configuration. These results represent a fundamental breakthrough that may inspire future device designs for applications in bioelectronics, catalysis, neuromorphic computing, or wireless communications.

The impact of a 3d divalent substitution for Cu using M^{2+} ions not presenting elongated MO_{5} pyramids has been explored in YBaCuFeO_{5} as a new strategy to upgrade the magnetic properties of this high-temperature spiral magnet and potential multiferroic. In this work we investigate the incidence of the Cu^{2+} with Co^{2+} substitution in YBa(Cu_{1−x}Co_{x})FeO_{5} compounds in which B-site disorder is kept invariant (disorder n_{d}≈36%). The study validates the reduction of the uniaxial elongation distortion at Cu sites as an efficient alternative way to disorder that enables one to enhance the thermal stability of the spiral order. In addition, the rotation plane of the helix is reoriented by the Cu/Co substitution and nearby the triple point (when T_{S} is maximal) the spiral order adopts an almost complete cycloidal magnetic configuration. These results lay the foundation of a new mechanism to tune the stability of the magnetic spirals in layered perovskites based on reducing the uniaxial elongation associated to the (4+1)-coordination of Cu^{2+} ions in square CuO_{5} pyramids.

Summary: Endogenous retroviruses (ERVs) have rewired host gene networks. To explore the origins of co-option, we employed an active murine ERV, IAPEz, and an embryonic stem cell (ESC) to neural progenitor cell (NPC) differentiation model. Transcriptional silencing via TRIM28 maps to a 190 bp sequence encoding the intracisternal A-type particle (IAP) signal peptide, which confers retrotransposition activity. A subset of “escapee” IAPs (∼15%) exhibits significant genetic divergence from this sequence. Canonical repressed IAPs succumb to a previously undocumented demarcation by H3K9me3 and H3K27me3 in NPCs. Escapee IAPs, in contrast, evade repression in both cell types, resulting in their transcriptional derepression, particularly in NPCs. We validate the enhancer function of a 47 bp sequence within the U3 region of the long terminal repeat (LTR) and show that escapee IAPs convey an activating effect on nearby neural genes. In sum, co-opted ERVs stem from genetic escapees that have lost vital sequences required for both TRIM28 restriction and autonomous retrotransposition.

The study examines the effect of replacing vitamin E (VE) with a liquid obtained from alpeorujo, an olive oil by-product rich in hydroxytyrosol (HT), as an antioxidant in broiler chicken feeds on the gene expression, lipid profile, and oxidation in the liver. There were five diets that differed only in the substitution of supplemental VE (0 to 40 mg/kg with differences of 10 mg/kg) by HT (30 to 0 mg/kg with differences of 7.5 mg/kg). A linear decrease (p < 0.05) in α-tocopherol concentration in the liver was observed with the replacement of VE by HT. There were no significant changes in triglyceride, cholesterol, or TBARS concentrations. The hepatic transcriptome showed 378 differentially expressed genes between broilers fed HT15 (20 mg/kg VE and 15 mg/kg HT) and HT0 (40 mg/kg VE) diets (p < 0.05 and fold change less or higher than 1.3). Significant changes in cell cycle, cell nucleus activity, neuroactivity, and necroptosis pathways and functions were observed. It is concluded that the olive oil by-product, rich in HT, could be used to spare VE as an antioxidant in broiler diets without affecting liver lipid and TBARS concentrations. The differential gene expression analysis showed a potential role of olive polyphenols in enhancing the chicken immune response.

In educational environments, technological adoption in the last 10 years has enabled a data-driven and decisionmaking paradigm in organizations. The integration of cloud services in schools and universities is a positive shift in the field of learning, but it also presents threats to all academic roles that need to be discussed in terms of protection, privacy, and confidentiality. Cloud storage brings the ubiquity of data to this technical transition and a delusive opportunity for cost savings. In many cases, this suggests that certain actors, beyond the control of schools and colleges, collect, handle and treat educational data on private servers and data centers. This privatization enables the manipulation of stored records, leaks, and unauthorized access. In this article, we expose the possibilities that open from the viewpoint of local technology adoption. We seek to reduce or even totally solve the detrimental effects of using cloud-based instructional and analytical technology, mixing or only using local technology. Technological methods that conform to this alternate viewpoint and new lines of study are also being suggested and created.

The transcripts generated by frameshifts and indels in cancer are frequently degraded by nonsense mediated decay. Here, the authors show that some of these transcripts can escape this degradation mechanism and their prevalence correlates with tumour response to immunotherapy.

This study aimed to investigate the effects of supplementing broiler chicken diets with an encapsulated product based on capsicum and other spice (black pepper and ginger) extracts on growth performance, nutrient digestibility, digestive enzyme activity and antioxidant response. To this end, 480 1-day-old male chicks were randomly assigned to two experimental treatments (12 pens/treatment; 20 birds/pen). Dietary treatments included a basal diet with no additives (CONTROL) and a basal diet supplemented with 250 ppm of the spice additive (SPICY; Lucta S.A., Spain). Supplementation of SPICY increased body weight (p < 0.05) compared with CONTROL at 7 d of age and improved (p < 0.01) ADG from 0 to 7 d of age. The apparent ileal digestibility of dry matter, gross energy and crude protein was higher (p < 0.05) in birds fed the SPICY diet compared with the CONTROL diet. Birds fed SPICY showed lower (p < 0.05) plasma catalase (CAT) activity, and the hepatic gene expression of CAT and Nrf2 was down-regulated (p < 0.05) compared with the CONTROL. In conclusion, the inclusion of 250 ppm of SPICY in broiler diets improved growth performance at 7 d of age and positively affected nutrient digestibility and antioxidant response.

In this work, we report a systematic study of the influence of film thickness on the structural and magnetic properties of epitaxial thin films of Pr2−δNi1−xMn1+xO6−y (PNMO) double perovskite grown on top of two different (001)-SrTiO3 and (001)-LaAlO3 substrates by RF magnetron sputtering. A strong dependence of the structural and magnetic properties on the film thickness is found. The ferromagnetic transition temperature (TC) and saturation magnetization (Ms) are found to decrease when reducing the film thickness. In our case, the thinnest films show a loss of ferromagnetism at the film-substrate interface. In addition, the electronic structure of some characteristic PNMO samples is deeply analyzed using X-ray absorption spectroscopy (XAS) and X-ray magnetic circular dichroism (XMCD) measurements and compared with theoretical simulations. Our results show that the oxidation states of Ni and Mn ions are stabilized as Ni2+ and Mn4+, thus the ferromagnetism is mainly due to Ni2+-O-Mn4+ superexchange interactions, even in samples with poor ferromagnetic properties. XMCD results also make evident large variations on the spin and orbital contributions to the magnetic moment as the film’s thickness decreases.

Palm oil has supplied more than 30% of vegetable oil consumption worldwide. Rising demand has pushed oil palm plantations to increase the yield. It is well known that genetic has played a significant role in phenotypic performance. Moreover, in recent years, genomic data has emerged tremendously. Unfortunately on the gene related to oil palm yield. Therefore, a preliminary study to classify and select oil palm candidate genes associated with characteristic by scanning existing genes in oil palm or other in-silico species were conducted. Based on Blast2Go results, 22 genes related to oil biosynthesis, two specifically related to fruit number and fruit weight were analysed. Furthermore, 19 candidate genes were able to amplify.

Eukaryotic genomes fold into topologically associated domains (TAD). Here the authors characterise a TAD regulatory architecture underlying lineage-specific gene regulation, finding that stripe TADs are associated with poised and active chromatin landscapes and linked to the cells functional state.

Background: Recent studies show that there are differences in female fertility in different ethnic groups with ovarian aging and IVF treatment outcomes. Advanced maternal age is a known risk factor for miscarriage, accounting largely due to genetically abnormal fetus. Aims and Objectives: This study investigates if there are any differences in rates of embryo aneuploidy based on age and indications for preimplantation genetic screening (PGS) between Indian and Spanish women. Materials and Methods: This multicenter study was carried out at fertility centers in India and Spain. Data from autologous IVF cycles of women

La rendición de cuentas de los medios de comunicación constituye en un mecanismo de transparencia y proximidad con las audiencias para avanzar hacia la participación, pluralidad y diversidad, se sustenta en la ética y se complementa con normas para procurar modelos de corregulación. La presente investigación toma la tipología de instrumentos propuesta en el proyecto MediaACES para establecer la percepción de los periodistas y los ciudadanos ecuatorianos sobre los instrumentos de rendición de cuentas impulsados de forma interna y externa a los medios de comunicación social. El análisis es de tipo descriptivo y relacional, se emplea metodología cualitativa y cuantitativa a través de encuestas y un foro de discusión virtual. Los instrumentos de rendición de cuentas más apreciados son los tradicionales externos a las empresas de medios tanto en autorregulación, participación y transparencia, se aprecia la intención de emplear aquellos mecanismos de amplio conocimiento a través de los cuales los medios pueden mostrar sus buenas prácticas, se evidencia además una fuerte impregnación de la Ley de Participación respecto a la rendición de cuentas, se la concibe como un deber legal, en ello influye lo sucedido con la Superintendencia de Comunicación durante el gobierno del presidente Rafael Correa.

The benefit of autologous stem cell transplantation (ASCT) in newly diagnosed myeloma patients, apart from supporting high dose chemotherapy, may include effects on T cell function in the bone marrow (BM). We report our exploratory findings on marrow infiltrating T cells early post-ASCT (day+100), examining phenotype and T cell receptor (TCR) repertoire, seeking correlations with timing of relapse. Compared to healthy donors (HD), we observed an increase in regulatory T cells (CD4+FoxP3+, Tregs) with reduction in CD4 T cells, leading to lower CD4:8 ratios. Compared to paired pre-treatment marrow, both CD4 and CD8 compartments showed a reduction in naïve, and increase in effector memory subsets, suggestive of a more differentiated phenotype. This was supported by increased levels of several immune-regulatory and activation proteins (ICOS, PD-1, LAG-3, CTLA-4 and GzmB) when compared with HD. Unsupervised analysis identified a patient subgroup with shorter PFS (p=0.031) whose BM contained increased Tregs, and higher immune-regulatory markers (ICOS, PD-1, LAG-3) on effector T cells. Using single feature analysis, higher frequencies of marrow PD-1+ on CD4+FoxP3- cells and Ki67+ on CD8 cells were independently associated with early relapse. Finally, studying paired pre-treatment and post-ASCT BM (n=5), we note reduced abundance of TCR sequences at day+100, with a greater proportion of expanded sequences indicating a more focused persistent TCR repertoire. Our findings indicate that, following induction chemotherapy and ASCT, marrow T cells demonstrate increased activation and differentiation, with TCR repertoire focusing. Pending confirmation in larger series, higher levels of immune-regulatory proteins on T cell effectors at day+100 may indicate early relapse.

Single-phase epitaxial Hf0.5Zr0.5O2 films with non-centrosymmetric orthorhombic structure have been grown directly on electrode-free corundum (α-Al2O3) substrates by pulsed laser deposition. A combination of high-resolution X-ray diffraction and X-ray absorption spectroscopy confirms the epitaxial growth of high-quality films belonging to the Pca21 space group, with [111] out-of-plane orientation. The surface of a 7-nm-thick sample exhibits an atomic step-terrace structure with a corrugation of the order of one atomic layer, as proved by atomic force microscopy. Scanning transmission electron microscopy reveals that it consists of grains with around 10 nm lateral size. The polar nature of this film has been corroborated by pyroelectric measurements. These results shed light on the mechanisms of the epitaxial stabilization of the ferroelectric phase of hafnia.

In recent years, there has been a significant increase in whole genome sequencing data of individual genomes produced by research projects as well as direct to consumer service providers. While many of these sources provide their users with an interpretation of the data, there is a lack of free, open tools for generating reports exploring the data in an easy to understand manner. GenomeChronicler was developed as part of the Personal Genome Project UK (PGP-UK) to address this need. PGP-UK provides genomic, transcriptomic, epigenomic and self-reported phenotypic data under an open-access model with full ethical approval. As a result, the reports generated by GenomeChronicler are intended for research purposes only and include information relating to potentially beneficial and potentially harmful variants, but without clinical curation. GenomeChronicler can be used with data from whole genome or whole exome sequencing, producing a genome report containing information on variant statistics, ancestry and known associated phenotypic traits. Example reports are available from the PGP-UK data page (personalgenomes.org.uk/data). The objective of this method is to leverage existing resources to find known phenotypes associated with the genotypes detected in each sample. The provided trait data is based primarily upon information available in SNPedia, but also collates data from ClinVar, GETevidence, and gnomAD to provide additional details on potential health implications, presence of genotype in other PGP participants and population frequency of each genotype. The analysis can be run in a self-contained environment without requiring internet access, making it a good choice for cases where privacy is essential or desired: any third party project can embed GenomeChronicler within their off-line safe-haven environments. GenomeChronicler can be run for one sample at a time, or in parallel making use of the Nextflow workflow manager. The source code is available from GitHub (https://github.com/PGP-UK/GenomeChronicler), container recipes are available for Docker and Singularity, as well as a pre-built container from SingularityHub (https://singularity-hub.org/collections/3664) enabling easy deployment in a variety of settings. Users without access to computational resources to run GenomeChronicler can access the software from the Lifebit CloudOS platform (https://lifebit.ai/cloudos) enabling the production of reports and variant calls from raw sequencing data in a scalable fashion.

Abstract: In the Cognitive Linguistics paradigm it is well known that conceptual metaphor and metonymy, among their various functions, are two important tools of lexical creation. Nevertheless, the literature on the topic is almost exclusively concerned with the analysis of well-established and formal varieties of language to the detriment of informal speech. This paper attempts to fill this void by describing some current informal speech expressions in Spanish which may be considered the result of these two cognitive operations; additionally, whenever possible, we offer their English counterparts. We thus explore the way in which these analytic tools play a crucial role in the proper understanding of expressions such as “estoy de bajón” (UNHAPPY IS DOWN), “vas ciego esta noche” (KNOWLEDGE IS VISION), “ya vienen los pitufos” (COLOUR OF UNIFORM FOR POLICEMAN), “esa chica está cañón” (BEING ATTRACTIVE IS HAVING PHYSICAL FORCE), etc. The expressions under consideration have been mainly obtained on the basis of Google searches and from Spanish newspapers. Resumen: En el paradigma de la Lingüística Cognitiva es bien sabido que tanto la metáfora como la metonimia son, entre sus varias funciones, importantes mecanismos de creación léxica. Sin embargo, los estudios llevados a cabo sobre el tema se centran esencialmente en el análisis de variedades lingüísticas formales y bien asentadas, relegando a un segundo plano el lenguaje informal. Con el fin de llenar este vacío, el presente artículo analiza algunas expresiones de la lengua española informal que pueden ser consideradas fruto de estas operaciones mentales; además, siempre que sea factible, incluimos los equivalentes en inglés. Para ello, exploraremos cómo estas herramientas analíticas juegan un papel crucial en la correcta comprensión de varias expresiones como “estoy de bajón” (UNHAPPY IS DOWN), “vas ciego esta noche” (KNOWLEDGE IS VISION), “ya vienen los pitufos” (COLOUR OF UNIFORM FOR POLICEMAN), “esa chica está cañón” (BEING ATTRACTIVE IS HAVING PHYSICAL FORCE), etc. Los ejemplos han sido extraídos de diversos periódicos españoles y de búsquedas en Google.

Abstract: This paper resumes the series related to metaphors in fairy tales started by HERRERO in 2005 (cf. HERRERO, 2005, 2006, 2007, 2008). In this case, the study is based on how the conceptual metaphors LIFE IS A JOURNEY and THE DIVIDED-SELF may explain the structure and the basic meaning of more than twenty popular tales, which in turn accounts for some of the uncanny of tales. The tales, which are representative of various cultures, were compiled by the British author Andrew Lang (1844-1912), and have been downloaded from the Project Gutenberg online library. Our research also casts some light on the fact that tales are akin in varying socio-cultural contexts: their solid experiential grounding may not only have contributed to a uniform plot, but also to an easier transmission of the stories in diverse, remote settings. Resumen: Este artículo continúa la serie relacionada con las metáforas en los cuentos tradicionales comenzada por HERRERO en 2005 (véase HERRERO, 2005, 2006, 2007, 2008). En este caso el estudio se centra en cómo a través de las metáforas conceptuales LIFE IS A JOURNEY y THE DIVIDED-SELF se puede explicar la estructura y el significado de más de veinte cuentos populares, lo que a su vez da cuenta de parte de “lo maravilloso” que se da en ellos. Los cuentos, representativos de varias culturas, fueron recopilados por el autor británico Andrew Lang (1844-1912) y han sido extraídos del Proyecto Gutenberg. Nuestra investigación apoya además la idea de que los cuentos son similares en contextos socioculturales diferentes: el hecho de que estén firmemente basados en la experiencia puede haber contribuido tanto a que sus argumentos sean parecidos como a que se hayan transmitido fácilmente en entornos lejanos y diversos.

Abstract: This paper studies how several conceptual metaphors (e.g. MORALITY IS LIGHT, MORALITY IS CLEANLINESS, MORAL FREEDOM IS PHYSICAL FREEDOM, DOING IMMORAL DEEDS IS ACCUMULATING DEBT) are able to account for the basic meaning and interpretation of punishments and moral issues in more than twenty popular tales, thus allowing us to explain some of the uncanny elements of tales. The stories, representative of various cultures, have been extracted from the Project Gutenberg online library and belong to the British compiler Andrew Lang (1844-1912). We also suggest that these metaphors, because of their strong experiential grounding, may have contributed to an easier transmission of many fairy tales, and also to make tales alike in different socio-cultural settings. Keywords: Conceptual metaphor, moral and punishment, experiential, uncanny, culture, fairy tales. Resumen: En este artículo tratamos de estudiar cómo varias metáforas conceptuales (p.ej. MORALITY IS LIGHT, MORALITY IS CLEANLINESS, MORAL FREEDOM IS PHYSICAL FREEDOM, DOING IMMORAL DEEDS IS ACCUMULATING DEBT) pueden explicar el significado básico y la interpretación de los castigos y la moralidad en más de veinte cuentos populares, lo que nos permite explicar parte de “lo maravilloso” de los cuentos. Los cuentos, representativos de varias culturas, han sido extraídos de la biblioteca electrónica Project Gutenberg y pertenecen al compilador británico Andrew Lang (1844-1912). También sugerimos que estas metáforas, dado su marcado carácter experiencial, pueden haber contribuido a una transmisión más fácil de muchos cuentos de hadas y a que los cuentos sean similares en diferentes contextos socioculturales. Palabras clave: Metáfora conceptual, moralidad y castigo, experiencial, “lo maravilloso”, cultura, cuentos de hadas.

Objective: To evaluate the usefulness of preimplantation genetic screening (PGS) using array comparative genomic hybridization (aCGH) in the Indian population. Materials and Methods: This is a retrospective, multicenter study including 235 PGS cycles following intracytoplasmic sperm injection performed at six different infertility centers from September 2013 to June 2015. Patients were divided as per maternal age in several groups (40 years) and as per indication for undergoing PGS. Indications for performing PGS were recurrent miscarriage, repetitive implantation failure, severe male factor, previous trisomic pregnancy, and advanced maternal age (≥35). Day 3 embryo biopsy was performed and analyzed by aCGH followed by day 5 embryo transfer in the same cycle or the following cycle. Outcomes such as pregnancy rates (PRs)/transfer, implantation rates, miscarriage rates, percentage of abnormal embryos, and number of embryos with more than one aneuploidy and chaotic patterns were recorded for all the treated subjects based on different age and indication groups. Results: aCGH helped in identifying aneuploid embryos, thus leading to consistent implantation (range: 33.3%-42.9%) and PRs per transfer (range: 31.8%-54.9%) that were obtained for all the indications in all the age groups, after performing PGS. Conclusion: Aneuploidy is one of the major factors which affect embryo implantation. aCGH can be successfully employed for screening of aneuploid embryos. When euploid embryos are transferred, an increase in PRs can be achieved irrespective of the age or the indication.

BACKGROUND: Embryonic aneuploidy may result in miscarriage, implantation failure, or birth defects. Thus, it is clinically necessary to avoid the selection of aneuploid embryos during in vitrofertilization treatment. AIM: The aim of this study was to identify the morphokinetic differences by analyzing the development of euploid and aneuploid embryos using a time-lapse technology. We also checked the accuracy of a previously described model for selection of euploid embryos based on morphokinetics in our study population. MATERIALS AND METHODS: It is a retrospective study of 29 cycles undergoing preimplantation genetic screening from October 2013 to April 2015 at our center. Of 253 embryos, 167 suitable for biopsy embryos were analyzed for their chromosomal status using array-comparative genome hybridization (CGH). The morphokinetic behavior of these embryos was further analyzed in embryoscope using time-lapse technology. RESULTS: Among the analyzed embryos, 41 had normal and 126 had abnormal chromosome content. No significant difference in morphokinetics was found between euploid and aneuploid embryos. The percentage of embryos with blastulation was similar in the euploid (65.85%, 27/41) and aneuploid (60.31%, 76/126) embryos (P = 0.76). Although hard to define, majority of the chromosomal defects might be due to meiotic errors. On applying embryo selection model from Basile et al., embryos falling within optimal ranges for time to division to 5 cells (t5), time period of the third cell cycle (CC3), and time from 2 cell division to 5 cell division (t5-t2) exhibited greater proportion of normal embryos than those falling outside the optimal ranges (28.6%, 25.9%, and 26.7% vs. 17.5%, 20.8%, and 14.3%). CONCLUSION: Keeping a track of time interval between two stages can help us recognize aneuploid embryos at an earlier stage and prevent their selection of transfer. However, it cannot be used as a substitute for array CGH to select euploid embryos for transfer.

This paper resumes the series devoted to metaphors in fairy tales (cf. Herrero 2005a, 2006, 2007, 2008, and 2010). We attempt to show how five conceptual metaphors (PEOPLE ARE ANIMALS, PEOPLE ARE PLANTS, IMPERFECT IS IRREGULAR, LOVE IS MAGIC, and REAL PEOPLE ARE FICTITIOUS CHARACTERS) and their variants may occur at a local level in the narration, allowing us to understand the magical depiction of characters and some of the relationships they may establish in the tales under analysis. The tales, which were compiled by the British author Andrew Lang (1844-1912), are representative of different cultures and have been downloaded from the Project Gutenberg online library. Our research also supports Herrero’s claims that (1) conceptual metaphor may serve as a taxonomic criterion for tales, and that (2) although many of these stories belong to different socio-cultural settings, they are coincident with the same plots and local metaphors employed, which may be a result of their strong experiential basis.

Run of river (RoR) hydropower systems, despite being one of the most cost-effective and environmentally benign energy technologies, have the disadvantage that production is not constant because it is subject to a high variability in precipitation and snow cover. In addition, the management of RoR plants has to comply with some particular operating conditions, but also with some environmental flow requirements. This work presents the assessment of the main inputs included in a climate service, historical local data and the seasonal forecast of water inflow to RoR plants, which are used to predict the operability and the expected energy production. The analysis is presented through the application in a pilot RoR system located in the south of Spain, in a semi-arid Mediterranean area impacted by snow, where seasonal forecasting is especially challenging. The results show the high interannual variability of the operation in this kind of facilities. The outcomes indicate that seasonal climate forecast information would improve the prediction of observed river streamflow by 7.4% in reliability and 3.2% in sharpness compared to the current operational forecast based on historical data. The climate forecasts thus provide valuable information for the exploitation of available water resources, which generates a significant value for the operation of the plant and the energy production market.

The operation feasibility of small hydropower plants in mountainous sites is subjected to the run-of-river flow, which is also dependent on a high variability in precipitation and snow cover. Moreover, the management of this kind of system has to be performed with some particular operation conditions of the plant (e.g., turbine minimum and maximum discharge) but also some environmental flow requirements. In this context, a technological climate service is conceived in a tight connection with end users, perfectly answering the needs of the management of small hydropower systems in a pilot area, and providing a forecast of the river streamflow together with other operation data. This paper presents an overview of the service but also a set of lessons learnt related to the features, requirements, and considerations to bear in mind from the point of view of climate service developers. In addition, the outcomes give insight into how this kind of service could change the traditional management (normally based on past experience), providing a probability range of the future river flow based on future weather scenarios according to the range of future weather possibilities. This highlights the utility of the co-generation process to implement climate services for water and energy fields but also that seasonal climate forecasting could improve the business as usual of this kind of facility.

The effects of supplementing chicken diets with an olive pomace extract (OE) from Olea europaea on performance and gut health after a challenge of intestinal permeability (IP) increase were studied. Treatments included a control diet with no additives (CF), and diets supplemented with 100 ppm of monensin (MF) or with 500 (OE500F) and 1500 ppm (OE1500F) of an OE. At 14 d, all birds, except those allocated in a control group (CNF), were submitted to a 15.5 h short-term fasting period to induce IP increase. Fasting increased (p < 0.05) lactulose/mannitol ratio and Alpha 1 Acid Glycoprotein concentration, and reduced (p < 0.001) villus/crypt ratio. Moreover, a down-regulation of Claudin-1 (p < 0.05), an up-regulation of TLR4 and IL-8 (p < 0.05) ileal gene expression was observed in CF birds compared to CNF. OE500F treatment reduced duodenal crypt depth compared to CF (p < 0.05; OE linear effect). Mannitol concentration and ileal IL-8 expression were reduced in OE500F compared to CF and OE1500F (p = 0.05). Fasting challenge induced an increase in IP triggering an inflammatory response. Supplementation of OE up to 1500 ppm did not affect growth performance and alleviated some of the negative effects of the fasting challenge.

In the context of cancer immunotherapy, agents that target the immune system to cancer cells need to fulfil two criteria: 1) that they are only expressed on the desired target cell and 2) that they can elicit a potent immunological response. Cancer Testis Antigens are a large disparate family of factors ordinarily expressed in the germ-line but aberrantly expressed across multiple types of cancer. The ability to enforce their expression on tumour cells is an attractive strategy that could render such cells potent targets of the immune system, but very little is known about their regulation. We describe the generation of an mCherry reporter cell line using HCT116 colorectal carcinoma cells that we anticipate will be useful for screen-based approaches to identify novel regulators of CTA expression. Discoveries arising from their use could in future be exploited to enhance tumour cell immunogenicity and improve cancer immuno-therapy.

Summary:. The authors aimed to present an introduction of patient-specific model in rhinoplasty by introducing a 3D printed surgical guide designed and adapted in an individualized manner for guiding dorsal hump reduction. To introduce the tool, we have designed a six step workflow. First, we obtain a digital 3D model of patient anatomy using computed tomography (CT) images. Second, we conduct a surgical preoperative planning of the rhinoplasty on the mentioned model. Third step consists of designing the guide, while taking into account nasal anthropometries and resection objectives. Fourth step is printing the guide and sterilizing it. Fifth step is performing the surgery. The last step is analyzing the main outcomes of the surgery. Our surgical guide allowed us to perform only 1 step osteotomy instead of the usual multistep osteotomy and remove exactly the amount of dorsum that we decided to remove during the preoperative planning. The duration of intervention was considerably shorter than conventional osteotomy. Using the guide was technically easier than the conventional method and reduced the learning curve from years to minutes (once the guide is printed). Moreover, the patient understanding of the procedure was significantly better after showing the 3D model of the surgery. The surgical guide allows a surgeon to transfer with extreme simplicity the presurgical planning to the surgical field. We have to point out that the design of the study does not allow us to quantify predictability, so future studies are needed to demonstrate an accuracy benefit over the former techniques.

El objetivo de este trabajo fue analizar el ciberbullying en estudiantes universitarios y cómo esto puede afectar al abandono universitario. Para lograr este objetivo, se diseñó y aplicó un cuestionario a la muestra piloto. Los resultados muestran que el ciberbullying ocurre con menos frecuencia que en otros niveles educativos. Además, se muestra una correlación entre cibervictimización y rendimiento académico, sentimiento de pertenencia y percepción de apoyo que el estudiante tiene. Todavía hay pocos estudios sobre este tema, pero se debe continuar investigando en esta línea, para poder comparar estos resultados con otros de trabajos sobre este tema.

Metabolic changes within the cell and its niche affect cell fate and are involved in many diseases and disorders including cancer and viral infections. Kaposi's sarcoma-associated herpesvirus (KSHV) is the etiological agent of Kaposi's sarcoma (KS). KSHV latently infected cells express only a subset of viral genes, mainly located within the latency-associated region, among them 12 microRNAs. Notably, these miRNAs are responsible for inducing the Warburg effect in infected cells. Here we identify a novel mechanism enabling KSHV to manipulate the metabolic nature of the tumour microenvironment. We demonstrate that KSHV infected cells specifically transfer the virus-encoded microRNAs to surrounding cells via exosomes. This flow of genetic information results in a metabolic shift toward aerobic glycolysis in the surrounding non-infected cells. Importantly, this exosome-mediated metabolic reprogramming of neighbouring cells supports the growth of infected cells, thereby contributing to viral fitness. Finally, our data show that this miRNA transfer-based regulation of cell metabolism is a general mechanism used by other herpesviruses, such as EBV, as well as for the transfer of non-viral onco-miRs. This exosome-based crosstalk provides viruses with a mechanism for non-infectious transfer of genetic material without production of new viral particles, which might expose them to the immune system. We suggest that viruses and cancer cells use this mechanism to shape a specific metabolic niche that will contribute to their fitness.

The polarization of CD4+ T cells into distinct T helper cell lineages is essential for protective immunity against infection, but aberrant T cell polarization can cause autoimmunity. The transcription factor T-bet (TBX21) specifies the Th1 lineage and represses alternative T cell fates. Genome-wide association studies have identified single nucleotide polymorphisms (SNPs) that may be causative for autoimmune diseases. The majority of these polymorphisms are located within non-coding distal regulatory elements. It is considered that these genetic variants contribute to disease by altering the binding of regulatory proteins and thus gene expression, but whether these variants alter the binding of lineage-specifying transcription factors has not been determined. Here, we show that SNPs associated with the mucosal inflammatory diseases Crohn's disease, ulcerative colitis (UC) and celiac disease, but not rheumatoid arthritis or psoriasis, are enriched at T-bet binding sites. Furthermore, we identify disease-associated variants that alter T-bet binding in vitro and in vivo. ChIP-seq for T-bet in individuals heterozygous for the celiac disease-associated SNPs rs1465321 and rs2058622 and the IBD-associated SNPs rs1551398 and rs1551399, reveals decreased binding to the minor disease-associated alleles. Furthermore, we show that rs1465321 is an expression quantitative trait locus (eQTL) for the neighboring gene IL18RAP, with decreased T-bet binding associated with decreased expression of this gene. These results suggest that genetic polymorphisms may predispose individuals to mucosal autoimmune disease through alterations in T-bet binding. Other disease-associated variants may similarly act by modulating the binding of lineage-specifying transcription factors in a tissue-selective and disease-specific manner.

Inflammatory breast cancer (IBC) is a rare, aggressive form of breast cancer associated with HER2 amplification, with high risk of metastasis and an estimated median survival of 2.9 y. We performed an open-label, single-arm phase II clinical trial (ClinicalTrials.gov NCT01325428) to investigate the efficacy and safety of afatinib, an irreversible ErbB family inhibitor, alone and in combination with vinorelbine in patients with HER2-positive IBC. This trial included prospectively planned exome analysis before and after afatinib monotherapy.HER2-positive IBC patients received afatinib 40 mg daily until progression, and thereafter afatinib 40 mg daily and intravenous vinorelbine 25 mg/m2 weekly. The primary endpoint was clinical benefit; secondary endpoints were objective response (OR), duration of OR, and progression-free survival (PFS). Of 26 patients treated with afatinib monotherapy, clinical benefit was achieved in 9 patients (35%), 0 of 7 trastuzumab-treated patients and 9 of 19 trastuzumab-naïve patients. Following disease progression, 10 patients received afatinib plus vinorelbine, and clinical benefit was achieved in 2 of 4 trastuzumab-treated and 0 of 6 trastuzumab-naïve patients. All patients had treatment-related adverse events (AEs). Whole-exome sequencing of tumour biopsies taken before treatment and following disease progression on afatinib monotherapy was performed to assess the mutational landscape of IBC and evolutionary trajectories during therapy. Compared to a cohort of The Cancer Genome Atlas (TCGA) patients with HER2-positive non-IBC, HER2-positive IBC patients had significantly higher mutational and neoantigenic burden, more frequent gain-of-function TP53 mutations and a recurrent 11q13.5 amplification overlapping PAK1. Planned exploratory analysis revealed that trastuzumab-naïve patients with tumours harbouring somatic activation of PI3K/Akt signalling had significantly shorter PFS compared to those without (p = 0.03). High genomic concordance between biopsies taken before and following afatinib resistance was observed with stable clonal structures in non-responding tumours, and evidence of branched evolution in 8 of 9 tumours analysed. Recruitment to the trial was terminated early following the LUX-Breast 1 trial, which showed that afatinib combined with vinorelbine had similar PFS and OR rates to trastuzumab plus vinorelbine but shorter overall survival (OS), and was less tolerable. The main limitations of this study are that the results should be interpreted with caution given the relatively small patient cohort and the potential for tumour sampling bias between pre- and post-treatment tumour biopsies.Afatinib, with or without vinorelbine, showed activity in trastuzumab-naïve HER2-positive IBC patients in a planned subgroup analysis. HER2-positive IBC is characterized by frequent TP53 gain-of-function mutations and a high mutational burden. The high mutational load associated with HER2-positive IBC suggests a potential role for checkpoint inhibitor therapy in this disease.ClinicalTrials.gov NCT01325428.

The present paper elaborates on some of the ideas in Ruiz de Mendoza and Díez (2002), where it is argued that conceptual interaction is fully regulated and constrained by a limited set of interactional patterns. This paper attempts to provide further evidence in support of this thesis through the analysis and exploration of several "eye expressions" (among others to keep an eye on someone, to turn a blind eye to something, to feast one's eyes on something, to be the owner of somebody's eyes, to be the apple of somebody's eyes, etc.), representative of various interactional patterns, and that have been extracted after an exhaustive analysis of more than 500 instances from both the BNC and the Oxford Superlex Dictionary database.On the basis of the analysis of the various patterns, we postulate two possible interaction operations, sequencing and integration, and argue that understanding these two operations sheds light on the definitional relationship between metaphor and metonymy. We also claim that the form sequential arrangement takes in an interactional pattern is related to the ontological status of the result of an integration process.

Mediterranean mountainous regions constitute a climate change hotspot where snow plays a crucial role in water resources. The characteristic snow-patched distribution over these areas makes spatial resolution the limiting factor for its correct representation. This work assesses the estimation of snow cover area and the contribution of the patchy areas to the seasonal and annual regime of the snow in a semiarid mountainous range, the Sierra Nevada Mountains in southern Spain, by means of Landsat imagery combined with terrestrial photography (TP). Two methodologies were tested: (1) difference indexes to produce binary maps; and (2) spectral mixture analysis (SMA) to obtain fractional maps; their results were validated from “ground-truth” data by means of TP in a small monitored control area. Both methods provided satisfactory results when the snow cover was above 85% of the study area; below this threshold, the use of spectral mixture analysis is clearly recommended. Mixed pixels can reach up to 40% of the area during wet and cold years, their importance being larger as altitude increases, proving the usefulness of TP for assessing the accuracy of remote data sources. Mixed pixels identification allows for determining the more vulnerable areas facing potential changes of the snow regime due to global warming and climate variability.

Albedo plays an important role in snow evolution modeling quantifying the amount of solar radiation absorbed and reflected by the snowpack, especially in mid-latitude regions with semiarid conditions. Satellite remote sensing is the most extensive technique to determine the variability of snow albedo over medium to large areas; however, scale effects from the pixel size of the sensor source may affect the results of snow models, with different impacts depending on the spatial resolution. This work presents the evaluation of snow albedo values retrieved from (1) Landsat images, L (16-day frequency with 30 × 30 m pixel size) and (2) SPOT VEGETATION albedo products, SV (10-day frequency with 1 × 1 km pixel size) in the Sierra Nevada mountain range in South Spain, a Mediterranean site representative of highly heterogeneous conditions. Daily snow albedo map series were derived from both sources, and used as input for the snow module in the WiMMed (Watershed Integrated Management in Mediterranean Environment) hydrological model, which was operational at the study area for snow monitoring for two hydrological years, 2011–2012 and 2012–2013, in the Guadalfeo river basin in Sierra Nevada. The results showed similar albedo trends in both data sources, but with different values, the shift between both sources being distributed in space according to the altitude. This difference resulted in lower snow cover fraction values in the SV-simulations that affected the rest of snow variables included in the simulation. This underestimation, mainly due to the effects of mixed pixels composed by both snow and snow-free areas, produced higher divergences from both sources during the melting periods when the evapo-sublimation and melting fluxes are more relevant. Therefore, the selection of the albedo data source in these areas, where snow evapo-sublimation plays a very important role and the presence of snow-free patches is very frequent, can condition the final accuracy of the simulations of operational models; Landsat is the recommended source if the monitoring of the snowpack is the final goal of the modeling, whereas the SV product may be advantageous when water resource planning in the medium and long term is intended. Applications of large pixel size albedo sources need further assessment for short-term operational objectives.

A synergistic combination of two next-generation sequencing platforms with a detailed comparative BAC physical contig map provided a cost-effective assembly of the genome sequence of the domestic turkey (Meleagris gallopavo). Heterozygosity of the sequenced source genome allowed discovery of more than 600,000 high quality single nucleotide variants. Despite this heterozygosity, the current genome assembly (∼1.1 Gb) includes 917 Mb of sequence assigned to specific turkey chromosomes. Annotation identified nearly 16,000 genes, with 15,093 recognized as protein coding and 611 as non-coding RNA genes. Comparative analysis of the turkey, chicken, and zebra finch genomes, and comparing avian to mammalian species, supports the characteristic stability of avian genomes and identifies genes unique to the avian lineage. Clear differences are seen in number and variety of genes of the avian immune system where expansions and novel genes are less frequent than examples of gene loss. The turkey genome sequence provides resources to further understand the evolution of vertebrate genomes and genetic variation underlying economically important quantitative traits in poultry. This integrated approach may be a model for providing both gene and chromosome level assemblies of other species with agricultural, ecological, and evolutionary interest.

A día de hoy, en España hay multitud de aficionados al deporte-espectáculo a los que les gusta ver una competición deportiva por televisión al mismo tiempo que escuchan ese mismo acontecimiento por la radio. Con este artículo se pretende realizar un acercamiento, a través de un estudio del caso, para conocer cuáles pueden ser las diferencias existentes entre esos dos medios: radio y televisión. El ejemplo del que parte el estudio son las retransmisiones realizadas, en España, por Cuatro (televisión) y la cadena SER (radio) de la final de la Eurocopa 2008 de fútbol que disputaron España y Alemania el 29 de junio de 2008. A partir de esas dos retransmisiones, el primero de los objetivos se centra en la estructura del equipo de retransmisión. El segundo abarca las cualidades sonoras de los narradores principales. El tercero de los objetivos hace referencia al apartado semántico empleado por los diferentes integrantes que componen el equipo de retransmisión, atendiendo especialmente a las variables de la subjetividad e incorrecciones lingüísticas. Dentro de este objetivo, se medirán también las diferencias de la velocidad de dicción. Tras plantear una metodología concreta, se alcanzan unos resultados que invitan a reflexionar especialmente sobre las, cada vez menos existentes, diferencias entre las locuciones de televisión y radio.

Esta nota pone de base una obra de Henrique C. De Lima Vaz compuesta en los artículos entre 1963 y 1984. El aspecto central de su obra desarrolla su idea de cómo el cristianismo, desde su inteligencia, puede responder a los planteamientos de la razón moderna.