IEA WIND 2012 Annual Report

Contribution to this annual report of the IEA Wind Implementing Agreement. Here the JRC, as representative of the Commission, exposes the achievements in wind R&D supported by the Commission programmes (FP7, IEE). Subchapters 2, 3 and 4 of chapter 20 are the Commission's responsibility whereas subchapters 1 and 5 are EWEA's responsibilityJRC.F.6-Energy systems evaluatio

Targeting tumor-associated macrophages to increase the efficacy of immune checkpoint inhibitors: a glimpse into novel therapeutic approaches for metastatic melanoma

Immune checkpoint inhibitors (ICIs) represent a promising therapeutic intervention for a variety of advanced/metastatic solid tumors, including melanoma, but in a large number of cases, patients fail to establish a sustained anti-tumor immunity and to achieve a long-lasting clinical benefit. Cells of the tumor micro-environment such as tumor-associated M2 macrophages (M2-TAMs) have been reported to limit the efficacy of immunotherapy, promoting tumor immune evasion and progression. Thus, strategies targeting M2-TAMs have been suggested to synergize with immune checkpoint blockade. This review recapitulates the molecular mechanisms by which M2-TAMs promote cancer immune evasion, with focus on the potential cross-talk between pharmacological interventions targeting M2-TAMs and ICIs for melanoma treatment

Identification of rho as a substrate for botulinum toxin C3-catalyzed ADP-ribosylation

AbstractRecombinant Aplysia rho and a GTP-binding protein purified from human neutrophil membranes (G22K) were ADP-ribosylated by botulinum toxin C3 with stoichiometries of 0.8 and 0.6, respectively. Rho and G22K appeared to be different proteins since (i) rho migrated faster on polyacrylamide gels, (ii) unlike G22K, rho did not require the presence of cytosol to be ADP-ribosylated, (iii) G22K was not recognized by an anti-rho antiserum, and (iv) antibody 142-24E05 recognized G22K effectively but only poorly cross reacted with rho. ADP-ribosylation had no effect on the ability of rho to bind or hydrolyse GTP. Therefore, it appears that there are multiple botulinum toxin C3 substrates and that the toxin exerts its effects on cell function by a mechanism other than modulating the GTPase activity of rho

Estudio de los impactos ambientales de los cruces de gasoductos con ríos vadeables

El río Cigüela y su afluente Valdepineda (Cuenca, España) fueron afectados por el cruce de un gasoducto, en Diciembre de 2001, mediante la técnica convencional "cruce subálveo" que consta de tres fases: instalación de la pista de trabajo, apertura de zanja y rehabilitación. Con el objetivo de evaluar el impacto de las distintas etapas de la obra en el medio acuático, se está llevando a cabo un estudio que se centra en el efecto de los sólidos en suspensión en las comunidades macrobentónicas e ícticas. Se presentan los resultados preliminares obtenidos en la fase de apertura de zanja, donde se observa un valor muy elevado de movilización de sólidos en suspensión (hasta 5000 mg/l), alcanzando las mayores concentraciones en los 100 primeros metros aguas abajo del punto de cruce. Estos sólidos en suspensión podrían ser la causa del aumento significativo de la sedimentación de las partículas de tamaño comprendido entre 50-250 μm y 250-500 μm en los 30 primeros metros aguas abajo del punto de cruce. Por otro lado, no se han observado diferencias en el valor del índice BMWP' en las distintas estaciones de muestreo. Sin embargo, en la fase de rehabilitación, se encuentra una diferencia significativa en la frecuencia de distribución de algunas de las especies de peces presentes en el río, además se observa un claro efecto barrera para la ictiofauna al eliminar la pista de trabajo.The Cigüela River and its tributary, Valdepineda (Cuenca, España) were affected by the crossing of a natural gas pipeline, in December 2001, by means of the conventional technique "open-cut water crossing" that consists of three different works: installation of the right-of-way, excavation and backfill of the pipeline trench, and restoration. In order to assess the impacts of these different activities on the aquatic environment, we are carrying out a study that is focused on the effects of suspended solids in the benthic and fish communities. Preliminary results of this study are presented on the excavation and backfill of the pipeline trench, that indicate that a very high value of suspended solids mobilisation is observed (up to 5000 mg/l), reaching the higher concentrations in the first 100 meters downstream of the crossing site. These suspended solids might be responsible for the significant increase in the sedimentation of the particles of sizes 50-250 μm and 250-500 μm in the 30 first meters downstream of the crossing site. On the other hand, we have not found differences in the values of the BMWP' index at the different sampling sites. Nevertheless, in the restoration phase , there is a significant difference in the distribution frequency of some fish species that appear in the river and also a clear barrier effect is observed for fishes when eliminating the right-of-way

阅读表现的习得水平：幼儿教育与小学教育不同年级的比较研究

This study is part of the European Project “Reading Communities from paper books to digital era” (READ-COM) whose purpose is to raise awareness among families, schools, teachers, and university students (future teachers) about the importance of reading and provide innovative resources to improve reading practices at home and at school. In this case, the actions in reading of the students of the last year of the Degrees of Early Childhood Education and Primary Education are examined as a means that facilitates the transit between stages in relation to the learning and consolidation of reading in students of 3-12 years. The levels of acquisition of strategies in reading of fourth-year students of both degrees have been described comparatively. To this end, a quantitative study has been carried out, in which 237 university students have participated, of which 108 students correspond to the Degree of Early Childhood Education and 129 of Primary Education. The language skills acquired at Degrees of Early Childhood Education and Primary Education have been identified. The competencies with the highest prevalence in the level of early childhood education have been the competence in Psychopedagogical Principles and Methodology of Learning and Organization of activities. There is a greater similarity in the scores related to Resources and Evaluation. The differences detected ratify the hypothesis raised in this work, so it is evident the need for the initial training of teachers of these educational stages to enhance actions that connect and interrelate the educational process of students from 3 to 12 years.Este estudio se enmarca en el Proyecto Europeo “Reading Communities from paper books to digital era” (READ-COM) cuya finalidad es sensibilizar a las familias, escuelas, profesorado y estudiantes universitarios (futuros docentes) sobre la importancia de leer y proporcionar recursos innovadores para mejorar las prácticas de lectura en el hogar y en la escuela. En este caso, se examina las actuaciones en lectura de los estudiantes de último curso de los Grados en Educación Infantil y en Educación Primaria como medio que facilite el tránsito entre etapas en relación con el aprendizaje y consolidación de la lectura en alumnado de 3-12 años. Se han descrito comparativamente los niveles de adquisición de estrategias en lectura del alumnado de cuarto curso de ambas titulaciones. Se ha realizado un estudio de corte cuantitativo, en el que han participado 237 estudiantes universitarios, de los cuales 108 estudiantes corresponden al Grado en Educación infantil y 129 en Educación Primaria. Se han identificado las competencias lingüísticas adquiridas en el Grado en Educación infantil y en el Grado en Educación Primaria. Las competencias con mayor prevalencia en el título de Educación Infantil han sido la competencia en Principios Psicopedagógicos y Metodología de Aprendizaje lector y Organización de actividades. Existiendo una mayor similitud en las puntuaciones relativas a los Recursos y Evaluación. Las diferencias detectadas ratifican la hipótesis planteada en este trabajo, por lo que se evidencia la necesidad de que en la formación inicial del profesorado de estas etapas educativas se potencien acciones que conecten e interrelacionen el proceso educativo del alumnado de 3 a 12 años.Введение: данное исследование является частью европейского проекта «Читательские сообщества от бумажных книг к цифровой эре» (READ-COM), целью которого является повышение осведомленности семей, школ, учителей и студентов вузов (будущих учителей) о важности чтения и предоставление инновационных ресурсов для улучшения практики чтения дома и в школе. В данном случае рассматривается читательская деятельность студентов выпускного курса бакалавриата по специальностям «Воспитание детей младшего возраста» и «Начальное образование» как средство содействия переходу между этапами в отношении обучения и закрепления навыков чтения у школьников 3-12 лет. Метод: проведено сравнительное описание уровней овладения стратегиями чтения студентами четвертого курса обеих специальностей. Было проведено количественное исследование, в котором приняли участие 237 студентов университета, из них 108 студентов соответствовали степени бакалавра дошкольного образования и 129 - степени бакалавра начального образования. Результаты: выявлены языковые компетенции, полученные в бакалавриате по специальности “Воспитание детей дошкольного периода” и в бакалавриате по специальности “Начальное образование”. Наиболее распространенными компетенциями в области дошкольного образования оказались компетенции “Психопедагогические принципы и методика обучения чтению” и “Организация деятельности”. Большее сходство наблюдается в оценках по компетенциям “Ресурсы” и “Оценка”. Выводы: выявленные различия подтверждают выдвинутую в данном исследовании гипотезу о необходимости начальной подготовки педагогов на этих этапах обучения для развития действий, обеспечивающих взаимосвязь и взаимообусловленность образовательного процесса учащихся от 3 до 12 лет.本研究是欧洲项目“从纸质书到数字时代的阅读社区”（READ-COM）的一部分，其目的是提高家庭、学校、教师和大学生（未来教师）对阅读和阅读重要性的认识。提供创新资源以改善家庭和学校的阅读实践。在这种情况下，对幼儿教育和小学教育学位最后一年学生的阅读表现进行审查，作为促进 3-12 岁学生学习和巩固阅读相关阶段之间过渡的手段。 研究对这两个教育阶段的四年级学生的阅读策略习得水平进行比较描述，进行了一项定量研究。共有 237 名大学生参与，其中 108 名学生对应幼儿教育阶段，129 名学生对应小学教育阶段。 幼儿教育阶段和初等教育阶段所获得的语言技能已得到确定。幼儿教育中最普遍的能力与心理教育学、阅读学习方法和活动组织的能力相关。与资源和评估相关的分数有更大的相似性。 结论：检测到的差异证实了本研究中提出的假设，该假设表明需要对这些教育阶段的教师进行初步培训，以促进将 3 至 12 岁学生的教育过程联系起来和相互关联的行动

Role of SOS1 in potassium nutrition

Comunicación oral presentada al FESPB celebrado del 4-9 de julio, 2010, en Valencia, España.Peer reviewe

Multiple sclerosis treatment and melanoma development

Therapy of multiple sclerosis (MS) with disease-modifying agents such as natalizumab or fingolimod has been associated with the development of cutaneous melanoma. Here we briefly revise literature data and report of a case of a 48-year old woman who developed a melanoma and several atypical naevi after sub sequential treatment with natalizumab (1 year) and fingolimod (7 years). By immunohistochemistry we observed the presence of T cells and leukocyte infiltration as well as of vascular endothelial growth factor (VEGF)-A expression in the patient melanoma biopsy. Then, we analyzed proliferation, migration and VEGF-A expression in three melanoma cell lines and found out that both natalizumab and fingolimod inhibited tumor cell proliferation but promoted or blocked cell migration depending on the cell line examined. VEGF-A secretion was augmented in one melanoma cell line only after fingolimod treatment. In conclusion, our in vitro data do not support the hypothesis of a direct action of natalizumab or fingolimod on melanoma progression but acting on the tumor microenvironment these treatments could indirectly favor melanoma evolution

At the cutting edge against cancer: A perspective on immunoproteasome and immune checkpoints modulation as a potential therapeutic intervention

Simple Summary:& nbsp;Immunoproteasome plays a key role in the generation of antigenic peptides. Immune checkpoints therapy is a front-line treatment of advanced/metastatic tumors, and to improve its efficacy, a broader knowledge of the dynamics of antigen repertoire processing by cancer cells is mandatory. The scope of this review is to offer a picture of the role of immunoproteasome in antigen presentation to fuel the hypothesis of novel therapeutic interventions based on the modulation of this proteolytic complex and immune checkpoints.Immunoproteasome is a noncanonical form of proteasome with enzymological properties optimized for the generation of antigenic peptides presented in complex with class I MHC molecules. This enzymatic property makes the modulation of its activity a promising area of research. Nevertheless, immunotherapy has emerged as a front-line treatment of advanced/metastatic tumors providing outstanding improvement of life expectancy, even though not all patients achieve a long-lasting clinical benefit. To enhance the efficacy of the currently available immunotherapies and enable the development of new strategies, a broader knowledge of the dynamics of antigen repertoire processing by cancer cells is needed. Therefore, a better understanding of the role of immunoproteasome in antigen processing and of the therapeutic implication of its modulation is mandatory. Studies on the potential crosstalk between proteasome modulators and immune checkpoint inhibitors could provide novel perspectives and an unexplored treatment option for a variety of cancers

Antitumor activity of a novel anti-vascular endothelial growth factor receptor-1 monoclonal antibody that does not interfere with ligand binding

Vascular endothelial growth factor receptor-1 (VEGFR-1) is a tyrosine kinase transmembrane receptor that has also a soluble isoform containing most of the extracellular ligand binding domain (sVEGFR-1). VEGF-A binds to both VEGFR-2 and VEGFR-1, whereas placenta growth factor (PlGF) interacts exclusively with VEGFR-1. In this study we generated an anti-VEGFR-1 mAb (D16F7) by immunizing BALB/C mice with a peptide that we had previously reported to inhibit angiogenesis and endothelial cell migration induced by PlGF. D16F7 did not affect binding of VEGF-A or PlGF to VEGFR-1, thus allowing sVEGFR-1 to act as decoy receptor for these growth factors, but it hampered receptor homodimerization and activation. D16F7 inhibited both the chemotactic response of human endothelial, myelomonocytic and melanoma cells to VEGFR-1 ligands and vasculogenic mimicry by tumor cells. Moreover, D16F7 exerted in vivo antiangiogenic effects in a matrigel plug assay. Importantly, D16F7 inhibited tumor growth and was well tolerated by B6D2F1 mice injected with syngeneic B16F10 melanoma cells. The antitumor effect was associated with melanoma cell apoptosis, vascular abnormalities and decrease of both monocyte/macrophage infiltration and myeloid progenitor mobilization. For all the above, D16F7 may be exploited in the therapy of metastatic melanoma and other tumors or pathological conditions involving VEGFR-1 activation

Ellagic acid inhibits bladder cancer invasiveness and in vivo tumor growth

Ellagic acid (EA) is a polyphenolic compound that can be found as a naturally occurring hydrolysis product of ellagitannins in pomegranates, berries, grapes, green tea and nuts. Previous studies have reported the antitumor properties of EA mainly using in vitro models. No data are available about EA influence on bladder cancer cell invasion of the extracellular matrix triggered by vascular endothelial growth factor-A (VEGF-A), an angiogenic factor associated with disease progression and recurrence, and tumor growth in vivo. In this study, we have investigated EA activity against four different human bladder cancer cell lines (i.e., T24, UM-UC-3, 5637 and HT-1376) by in vitro proliferation tests (measuring metabolic and foci forming activity), invasion and chemotactic assays in response to VEGF-A and in vivo preclinical models in nude mice. Results indicate that EA exerts anti-proliferative effects as a single agent and enhances the antitumor activity of mitomycin C, which is commonly used for the treatment of bladder cancer. EA also inhibits tumor invasion and chemotaxis, specifically induced by VEGF-A, and reduces VEGFR-2 expression. Moreover, EA down-regulates the expression of programmed cell death ligand 1 (PD-L1), an immune checkpoint involved in immune escape. EA in vitro activity was confirmed by the results of in vivo studies showing a significant reduction of the growth rate, infiltrative behavior and tumor-associated angiogenesis of human bladder cancer xenografts. In conclusion, these results suggest that EA may have a potential role as an adjunct therapy for bladder cancer