DNA-binding determinants promoting NHEJ by human Polm

Non-homologous end-joining (NHEJ), the preferred pathway to repair double-strand breaks (DSBs) in higher eukaryotes, relies on a collection of molecular tools to process the broken ends, including specific DNA polymerases. Among them, Polο is unique as it can catalyze DNA synthesis upon connection of two non-complementary ends. Here, we demonstrate that this capacity is intrinsic to Polο, not conferred by other NHEJ factors. To understand the molecular determinants of its specific function in NHEJ, the interaction of human Polο with DNA has been directly visualized by electromobility shift assay and footprinting assays. Stable interaction with a DNA gap requires the presence of a recessive 5′-P, thus orienting the catalytic domain for primer and nucleotide binding. Accordingly, recognition of the 5′-P is crucial to align the two DNA substrates of the NHEJ reaction. Site-directed mutagenesis demonstrates the relevance of three specific residues (Lys 249, Arg253 and Arg416) in stabilizing the primer strand during end synapsis, allowing a range of microhomology-induced distortions beneficial for NHEJ. Moreover, our results suggest that the Polο BRCT domain, thought to be exclusively involved in interaction with NHEJ core factors, has a direct role in binding the DNA region neighbor to the 5′-P, thus boosting Polο-mediated NHEJ reactions. © 2012 The Author(s).Ministerio de Ciencia y Tecnología; Fundación Ramón Areces;Comunidad Autónoma de MadridPeer Reviewe

La utilización del poliestireno expandido en obras de geotécnia.

Los sistemas modernos de construcción son asociados a tecnologías innovadoras y a los nuevos materiales, sistemas livianos que ofrecen la posibilidad de una mayor rapidez de ejecución por montaje. Estas características influyen en gran medida en el aprovechamiento de los materiales y de la mano de obra, ya que la planificación se hace más sencilla, pudiendo cumplir las metas fijadas en cuanto a los recursos económicos y de tiempo. Los sistemas constructivos convencionales han evolucionado de acuerdo a nuevos criterios para el análisis, desarrollo de procesos y puesta en obra. De esta manera aumenta su utilización, ofreciendo una resistencia y capacidad de carga que le permita un desempeño igual o superior a los sistemas constructivos que actualmente se encuentran en aplicación. Además de ello, estos sistemas también imponen características físicas apropiadas en los materiales. Tras sintetizarse en 1930 el poliestireno a nivel industrial y tras su posterior comercialización a partir de la década de los 50, se le ha dado a este material múltiples aplicaciones; comenzándose su incorporación a la construcción como material aislante, empleándose en las últimas décadas como material aligerante en múltiples elementos estructurales. Si embargo, su difusión como material con posibles aplicaciones en geotecnia no está tan extendida. En este trabajo de investigación se plantea el estudio de algunas soluciones constructivas en el campo de la geotecnia, entendiendo éstas como no limitativas, y en todo caso, como algunas pinceladas en un campo que está prácticamente por descubrir. La primera de estas aplicaciones consistiría en sustituir parcialmente el material de aporte de un terraplén por bloques de poliestireno expandido (EPS), en dos situaciones distintas, una con sección transversal horizontal y la otra en ladera. Como segunda solución constructiva, se analizará un muro de contención en ménsula, sustituyendo parcialmente el relleno del trasdós con bloques de EPS. A partir de aquí nos encontramos con la posibilidad de estudiar un caso real de muro de contención, pero en este caso con una altura muy superior, y que como consecuencia de ello, presentaba una bandeja intermedia. Otra de las posibles aplicaciones que aquí se proponen sería como material ligero en sistemas de contención de tierras, en este caso, en un apantalla discontinua de pilotes. Finalmente se ha analizado un sistema constructivo de aplicación en cimentaciones, consistente en la incorporación de bloques de EPS dentro del canto de una losa de cimentación, a modo de piezas aligerantes, de manera que se reduzca el peso del elemento estructural, sin mermar de forma sustancial su rigidez. Dentro de esta investigación, se realizó una campaña de ensayos experimentales en elementos a escala reducida, de una losa aligerada, comparando ésta con la maciza, desarrollándose una modelo de cálculo por medio del programa estructural SAP2000, ofreciendo resultados favorables. Los resultados obtenidos, permiten afirmar que las soluciones constructivas que aquí se proponen son en general perfectamente viables, y presentan importantes ventajas frente a soluciones tradicionales: reducción de asientos, reducción de empujes laterales y por tanto, aumento de la seguridad frente al deslizamiento, se minimizan los efectos de consolidación en suelos cohesivos, y, por último, en los elementos de cimentación analizados no sólo se reducen los asientos, sino que, además, esto son más uniformes en la superficie de apoyo

Plan de implementación de un sistema de matrices IPERC para prevenir peligros y riesgos en la Universidad Nacional José Faustino Sánchez Carrión

La presente investigación, tiene como título: Plan de Implementación de un Sistema de Matrices IPERC para prevenir peligros y riesgos en la Universidad Nacional “José Faustino Sánchez Carrión” – 2021, y contiene, seguidamente, lo siguiente: En el capítulo primero; se enuncia el planteamiento del problema, destacándose la descripción de la realidad problemática, la formulación del problema, los objetivos y la justificación de la investigación. En el capítulo segundo, se desarrolla el marco teórico, como fundamento para la investigación; considerándose, los antecedentes de la investigación, las bases teóricas, la definición de términos básicos y la formulación de hipótesis. En el capítulo tercero, se expone la metodología, seguida para desarrollar el estudio, indicando el diseño metodológico, enfoque del estudio, nivel de la investigación, métodos utilizados, así como la operacionalizacióin de variables y las técnicas e instrumentos de recolección de datos. El cuarto capítulo, presenta los resultados del estudio; destacándose con ello, la situación actual de la seguridad en la infraestructura, mapa de procesos, procedimientos para la solución del problema y la construcción del sistema de matrices IPERC. El capítulo quinto, refiere la discusión del caso, y el capítulo seis, presenta las conclusiones y recomendaciones, inherentes del estudio y el capítulo siete, contiene las referencias de información

The emerging role of Lead Users in the mobile industry

The purpose of this paper is to provide a formal conceptualization of emerging mobile ecosystems as value-creation networks and characterize the role played by external developers, conceptualized as Lead Users (VonHippel 1986), in the evolution of these networks in the mobile industry. Based on quantitative data from a survey conducted between seasoned developers mediation models for panel data are built. The results are triangulated with semi-structured interviews and corporate data as reported by companies. The empirical study confirms that external developers are paramount to absorb external knowledge and transform it into knowledge of explicit nature and therefore of high value for other participants in the network. This paper finds evidence on the influence that external developers, conceptualized as Lead Users (VonHippel 1986), expert on firms’ ability to compete in the mobile industry

Magnetic anomalies of the NW Iberian continental margin and the adjacent abyssal plains

The NW Iberian margin is a hyperextended continental margin, formed during the opening of the North Atlantic Ocean, where a subsequent partial tectonic inversion has undergone during the Alpine Orogeny. This succession of tectonic episodes determines the magnetic signature of the margin. The Spanish Exclusive Economic Zone Project has carried out seven one-month cruises between 2001 and 2009. To extend and densify the spatial coverage, we have used data from the World Digital Magnetic Anomaly Map. Here, we describe the methodology used for the acquisition and data processing of the magnetic field data. The use of diverse instrumentation, a non-complete external field’s cancelation, and the use of different magnetic core field models, contributed to the total error budget. To reduce it, we have used a leveling algorithm which minimizes all these contributions. Finally, a statistical analysis was applied using crossover residuals, showing a resolution better than 28 nT

Different evolution of tensile and compressive strength in concrete affected by acid mine drainage

Although not many studies have analysed the effects of acid mine drainage (AMD) on the durability of concrete, it is clear that such an aggressive environment affects the different mechanical parameters of this material. AMD is an environmental problem that affects the five continents and is especially widespread in the south western part of the Iberian Peninsula, in an area known as the Iberian Pyrite Belt. In this work, the effect of AMD on tensile and compressive strength of concrete has been evaluated, analysing the evolution of these two fundamental parameters on this structural material. For this purpose, a series of concrete samples were subjected to a controlled AMD environment in the laboratory, using water with pH 2.8 collected from the Tharsis Mine (SW Spain). The concrete samples were prepared in accordance with the parameters required by various international standards. The samples were subjected to the aggressive environment by AMD for two periods of time (3 and 6 months), after which they were subjected to non-destructive testing and destructive testing until breaking the samples by means of compression and tensile (indirect tensile test). In addition, Emission Scanning Electron Microscopy studies were performed on samples before AMD influence and on samples affected by AMD for six months. The obtained results using the ultrasonic equipment showed a decrease in concrete quality, an increase in porosity and permeability, the reduction of modulus of elasticity that reaches 8.5% after six months, as well as the appearance of microcracks. The destructive the tests showed that tensile strength is much more affected than the compressive strength: the tensile strength went from 4.31 MPa to 3.27 MPa (24%) after six months, while the compressive strength went from 48.22 MPa to 43.83 MPa (9%) in the same period of time. This different evolution means that the formulas used in international standards that relating compressive strength to tensile strength need to be modified by means of a correction factor.This work was supported by MCIN/AEI/10.13039/501100011033/ FEDER, UE (PID2021-123130OB-I00), the Regional Government of Andalucia (FEDER Operational Programme 2014-2020, UHU-202053) and the Huelva University (EPIT 2021, UHUPJ0001-624). Funding for open access charge: University of Huelva / CBU

Evaluation procedure for blowing machine monitoring and predicting bearing SKFNU6322 failure by power spectral density

This work shows the results of the comparative study of characteristic frequencies in terms of Power Spectral Density (PSD) or RMS generated by a blower unit and the SKFNU322 bearing. Data is collected following ISO 10816, using Emonitor software and with speed values in RMS to avoid high and low frequency signal masking. Bearing failure is the main cause of operational shutdown in industrial sites. The difficulty of prediction is the type of breakage and the high number of variables involved. Monitoring and analysing all the vari- ables of the SKFNU322 bearing and those of machine operation for 15 years allowed to de- velop a new predictive maintenance protocol. This method makes it possible to reduce from 6 control points to one, and to determine which of the 42 variables is the most incidental in the correct operation, so equipment performance and efficiency is improved, contributing to increased economic profitability. The tests were carried out on a 500 kW unit of power and It was shown that the rotation of the equipment itself caused the most generating variable of vibrational energy

Bouguer anomalies of the NW Iberian continental margin and the adjacent abyssal plains

The NW Iberian continental margin has a complex structure, resulting from the succession of several rifting episodes close to a ridge triple junction, and a superimposed partial tectonic inversion stage. The wide-ranging physiography matches the diverse tectonic deformation domains related to its evolution. Each deformation domain has a distinctive gravity signal, so the detailed Bouguer anomaly map presented here is a good first approach to the regional study of the whole margin. Moreover, as the presented chart is a complete Bouguer anomaly map (including terrain corrections), its analysis and interpretation can be done in terms of density, geometry and depth variations below the seafloor. This map is mainly based on the dataset obtained during seven one-month surveys carried out in the frame of the Spanish Economic Exclusive Zone project, and also includes two 2 + 3/4D density models illustrating the deep structure of the marginThe marine surveys are supported by the Spanish Defense Ministry, as this is the managing body of the Spanish Exclusive Economic Zone Project (SEEZ). Additionally, the Universidad Complutense de Madrid funds travel expenses of its personnel embarking on the surveys, as does the Instituto Geológico y Minero de España in the frame of the internal project entitled ‘Plan de Investigaciones Geológicas y Geofísicas de la Zona Económica Exclusiva Española (ZEEE)

Edition electronic support of didactic material for interactive self-learning

The creation of a new social-virtual space for human interrelations is necessary for new information and communication technologies. This new environment, which is being developed in the area of education, enables new processes of learning and transmission of knowledge through modern communication networks. All this invites us to support ourselves in the principles of hypertext education and autonomous learning together with the collective and cooperative. The aim is to reinforce learning through an interactive learning technique based on problems and selfevaluation. To achieve these objectives, it would be necessary to combine teacher-guided learning, the personal work of the learners and the working group. The project consists of the interactive didactic material electronic edition related to the subjects dealt with in the subject Geological Foundations (Degree of Engineering in Exploitation of Mines and Energy Resources) and Geology, (Degree in Engineering in Exploitation of Mines and Energy Resources). For this purpose, all the contents are integrated into a digital document with digital with sufficient links for the student to navigate throughout the subject. The objectives are: Compilation of the theoretical and practical contents of the subjects; Development and updating of a set of activities for the assimilation of the contents; Integration of all contents in a digital format document with sufficient links for student navigation throughout the subject; Incorporate links to websites of interest that allow the extension of the contents of the subject; Familiarize students with learning. To achieve the objectives proposed in the project, the following methodology is proposed: Phase I. Preparation of teaching material; Phase II Creation of an interactive virtual platform with the didactic material developed: Once all the didactic material has been developed and available, a navigation environment will be programmed with Frontpage (or similar) with which the student can easily access the developed contents. In this way, once all the didactic material has been prepared and available in digital format, a navigation environment will be programmed with which the student can be able to easily access the developed contents. With this didactic material, a publication will be made which will be easily accessible for all interested students. The student will have the theoretical contents developed, as well as a collection of representative problems solved, which will serve as a guide for the study of the subjects mentioned above. In addition, interactive tests will be carried out that allow the student to self-evaluate the theoretical-practical concepts worked on. In this way, this work can be considered as a first phase of the total virtualization of all the subjects

Experimental analysis of slabs foundation by scale models: lightweight slabs by expanded polystyrene blocks opposite solid slabs

El objetivo del presente artículo es confirmar el distinto comportamiento que presenta la solución tradicional de losa maciza frente a una aligerada, empleando bloques de poliestireno expandido (EPS) como material aligerante, uniéndose las zonas macizas bajo pilares mediante nervios. Se mantienen por tanto, dos placas, superior e inferior, alrededor de los bloques aligerantes de EPS. Para ello se ha realizado dos modelos a escala, sometiendo cada uno de ellos a una serie de ensayos. Esto se ha podido analizar comparativamente con otros modelos hechos en ordenador, empleando para ello programas de Elementos Finitos. Los resultados obtenidos permiten afirmar que, en situaciones de suelos blandos, con posibles problemas de asientos, la solución planteada presenta importantes ventajas, al disminuir esos asientos en un porcentaje que variará en función de las condiciones particulares. Además de esto, se reducen en gran medida los asientos diferenciales entre apoyos, por lo que la alternativa planteada presenta un comportamiento más uniforme, así como ventajas constructivas.The aim of this work is to confirm the different behavior of traditional solid slab versus lightened solution, using expanded polystyrene (EPS) blocks as a lightening material, joining solid areas under pillars with grating beams. Therefore there are two plates, one of them on the top and the other one on the bottom, covering the EPS blocks. For this purpose, two scale models have been performed, each of them being subjected to a series of tests. These have been able to comparatively analyze with models made in computer, using Finite Element programs. The results obtained allow us to assert that in situations of soft soils, with possible problems of settlements, the proposed solution has significant advantages by reducing this settlement on a percentage it will vary depending on specific conditions. Besides this, it significantly reduces the differential settlements among supports, so this alternative has a more uniform behavior, as well as constructive advantages