RanBP2-Mediated SUMOylation Promotes Human DNA Polymerase Lambda Nuclear Localization and DNA Repair

Cellular DNA is under constant attack by a wide variety of agents, both endogenous and exogenous. To counteract DNA damage, human cells have a large collection of DNA repair factors. Among them, DNA polymerase lambda (Polλ) stands out for its versatility, as it participates in different DNA repair and damage tolerance pathways in which gap-filling DNA synthesis is required. In this work we show that human Polλ is conjugated with Small Ubiquitin-like MOdifier (SUMO) proteins both in vitro and in vivo, with Lys27 being the main target of this covalent modification. Polλ SUMOylation takes place in the nuclear pore complex and is mediated by the E3 ligase RanBP2. This post-translational modification promotes Polλ entry into the nucleus, which is required for its recruitment to DNA lesions and stimulated by DNA damage induction. Our work represents an advance in the knowledge of molecular pathways that regulate cellular localization of human Polλ, which are essential to be able to perform its functions during repair of nuclear DNA, and that might constitute an important point for the modulation of its activity in human cells

Automated generation of computationally hard feature models using evolutionary algorithms

This is the post-print version of the final paper published in Expert Systems with Applications. The published article is available from the link below. Changes resulting from the publishing process, such as peer review, editing, corrections, structural formatting, and other quality control mechanisms may not be reflected in this document. Changes may have been made to this work since it was submitted for publication. Copyright @ 2014 Elsevier B.V.A feature model is a compact representation of the products of a software product line. The automated extraction of information from feature models is a thriving topic involving numerous analysis operations, techniques and tools. Performance evaluations in this domain mainly rely on the use of random feature models. However, these only provide a rough idea of the behaviour of the tools with average problems and are not sufficient to reveal their real strengths and weaknesses. In this article, we propose to model the problem of finding computationally hard feature models as an optimization problem and we solve it using a novel evolutionary algorithm for optimized feature models (ETHOM). Given a tool and an analysis operation, ETHOM generates input models of a predefined size maximizing aspects such as the execution time or the memory consumption of the tool when performing the operation over the model. This allows users and developers to know the performance of tools in pessimistic cases providing a better idea of their real power and revealing performance bugs. Experiments using ETHOM on a number of analyses and tools have successfully identified models producing much longer executions times and higher memory consumption than those obtained with random models of identical or even larger size.European Commission (FEDER), the Spanish Government and the Andalusian Government

Regulation of human Polλ by ATM-mediated phosphorylation during Non-Homologous End Joining

DNA double strand breaks (DSBs) trigger a variety of cellular signaling processes, collectively termed the DNA-damage response (DDR), that are primarily regulated by protein kinase ataxia-telangiectasia mutated (ATM). Among DDR activated processes, the repair of DSBs by non-homologous end joining (NHEJ) is essential. The proper coordination of NHEJ factors is mainly achieved through phosphorylation by an ATM-related kinase, the DNA-dependent protein kinase catalytic subunit (DNA-PKcs), although the molecular basis for this regulation has yet to be fully elucidated. In this study we identify the major NHEJ DNA polymerase, DNA polymerase lambda (Polλ), as a target for both ATM and DNA-PKcs in human cells. We show that Polλ is efficiently phosphorylated by DNA-PKcs in vitro and predominantly by ATM after DSB induction with ionizing radiation (IR) in vivo. We identify threonine 204 (T204) as a main target for ATM/DNA-PKcs phosphorylation on human Polλ, and establish that its phosphorylation may facilitate the repair of a subset of IR-induced DSBs and the efficient Polλ-mediated gap-filling during NHEJ. Molecular evidence suggests that Polλ phosphorylation might favor Polλ interaction with the DNA-PK complex at DSBs. Altogether, our work provides the first demonstration of how Polλ is regulated by phosphorylation to connect with the NHEJ core machinery during DSB repair in human cells.España MINECO y la Comisión Europea (European Regional Development Fund) to J.F.R. RYC-2011-08752, BFU2013-44343-P) and to F.C-L. (SAF2014-55532-R)

Mutation testing on an object-oriented framework: An experience report

This is the preprint version of the article - Copyright @ 2011 ElsevierContext The increasing presence of Object-Oriented (OO) programs in industrial systems is progressively drawing the attention of mutation researchers toward this paradigm. However, while the number of research contributions in this topic is plentiful, the number of empirical results is still marginal and mostly provided by researchers rather than practitioners. Objective This article reports our experience using mutation testing to measure the effectiveness of an automated test data generator from a user perspective. Method In our study, we applied both traditional and class-level mutation operators to FaMa, an open source Java framework currently being used for research and commercial purposes. We also compared and contrasted our results with the data obtained from some motivating faults found in the literature and two real tools for the analysis of feature models, FaMa and SPLOT. Results Our results are summarized in a number of lessons learned supporting previous isolated results as well as new findings that hopefully will motivate further research in the field. Conclusion We conclude that mutation testing is an effective and affordable technique to measure the effectiveness of test mechanisms in OO systems. We found, however, several practical limitations in current tool support that should be addressed to facilitate the work of testers. We also missed specific techniques and tools to apply mutation testing at the system level.This work has been partially supported by the European Commission (FEDER) and Spanish Government under CICYT Project SETI (TIN2009-07366) and the Andalusian Government Projects ISABEL (TIC-2533) and THEOS (TIC-5906)

Artifact: virtual environment for evaluating the QoS of distributed mobile applications

Ministerio de Ciencia, Innovación y Universidades RTI2018-094591-B-I00Ministerio de Ciencia, Innovación y Universidades RTI2018-101204-B-C21 (HORATIO)Ministerio de Economía y Competitividad BELI (TIN2015-70560-R)TIN2016-81978-REDTJunta de Extremadura GR18112Junta de Andalucía APOLO (US-1264651)Junta de Extremadura IB1803

Virtual environment for evaluating the QoS of distributed mobile applications

The increasing capabilities of end devices has led to a wider distribution of the computation and the massive deployment of distributed mobile applications. The success of these applications is highly dependent on the Quality of Service they provide. This quality is especially difficult to assess due to the large number of entities involved and their heterogeneity. Current tools are usually focused on evaluating the QoS provided by a single entity. Nevertheless, the QoS of distributed applications not only depend on the QoS of each entity, the interactions among entities has also to be evaluated. Therefore, new techniques are required to perform a comprehensive evaluation of the expected QoS of these applications before their production deployment. This paper presents a framework, called Perses, for launching virtual environments to simulate and test the execution of distributed mobile applications. This simulation provides results of the QoS achieved. Moreover, the framework has been integrated into a DevOps methodology in order to automate its execution. Video showcase- https://youtu.be/wpIApe_sPFE.Ministerio de Ciencia, Innovación y Universidades RTI2018-101204-B-C21 (HORATIO)Ministerio de Economía y Competitividad BELI (TIN2015-70560-R)Interreg V-A España-Portugal (POCTEP) 0499-4IE-PLUS-4-EMinisterio de Ciencia, Innovación y Universidades TIN2016-81978-REDTJunta de Extremadura GR18112Junta de Extremadura IB18030Junta de Andalucía APOLO (US-1264651

A Distributed Solution to Synchronous Multiparty Interaction

Multiparty interactions are the key to describe problems where three or more processes need to collaborate simultaneously in order to solve a problem, and this paper aims to show the way we have implemented this mechanism in a network computer. The main feature of our solution is that it is not bound up with the underlying network, so it is highly portable. We also report some experimental results that showthat our prototype performs quite well on low cost computers

Comprehensive study of the benefits of integrating a sharing energy strategy between prosumers

Publicado en IECON 2017 - 43rd Annual Conference of the IEEE Industrial Electronics Society, Beijing, 2017, pp. 3609-3614, doi: 10.1109/IECON.2017.8216612La actualización de los sistemas de energía en los últimos años debido a la proliferación de la generación distribuida con fuentes de energía renovables, usuarios activos y vehículos eléctricos se ha convertido en un desafío. En este nuevo escenario, los prosumidores juegan un papel importante para amortiguar la curva de consumo y, por lo tanto, contribuir a los requisitos de la red. Los conjuntos fotovoltaicos (PV) integrados en edificios residenciales atraen una atención especial, ya que pueden complementarse con sistemas de almacenamiento de energía (ESS), como baterías o ultracondensadores (UC) o incluso una combinación de ambos, con el objetivo de lograr que los clientes puedan administrar su energía. Las razones anteriores justifican la necesidad de un sistema de gestión de energía (EMS) que coordine el funcionamiento de los dispositivos de almacenamiento de energía de manera optimizada, ya que son caros. En este documento, se propone un sistema de control integral para intercambiar energía entre los dispositivos de almacenamiento híbridos (baterías y UC) de dos viviendas con instalaciones fotovoltaicas con el fin de aumentar la disponibilidad de sus ESS y soportar los requisitos de energía durante el mayor tiempo posible, optimizando tamaños y costos, y evitando la saturación.The upgrade of power systems in the last years due to the proliferation of distributed generation with renewable energy sources, active users and electric vehicles has become a challenge. In this new scenario, prosumers play an important role in order to buffer the consumption curve and, therefore, contributing to the grid requirements. Special attention is attracted by photovoltaic (PV) arrays integrated in residential buildings, because they can be complemented with energy storage systems (ESSs), such as batteries or ultracapacitors (UCs) or even a combination of both, with the aim to achieve that customers could manage their energy. The above reasons justify the need of an energy management system (EMS) that coordinates the operation of the energy storage devices in an optimized way, as they are expensive. In this paper, a comprehensive control system is proposed to exchange energy between the hybrid storage devices (batteries and UCs) of two dwells with PV installations in order to increase the availability of their ESSs and support the energy requirements during the most time possible, optimizing sizes and costs and avoiding saturation.peerReviewe

Automated Generation of Computationally Hard Feature Models Using Evolutionary Algorithms

A feature model is a compact representation of the products of a software product line. The automated extraction of information from feature models is a thriving topic involving numerous analysis operations, techniques and tools. Performance evaluations in this domain mainly rely on the use of random feature models. However, these only provide a rough idea of the behaviour of the tools with average problems and are not sufficient to reveal their real strengths and weaknesses. In this article, we propose to model the problem of finding computationally hard feature models as an optimization problem and we solve it using a novel evolutionary algorithm for optimized feature models (ETHOM). Given a tool and an analysis operation, ETHOM generates input models of a predefined size maximizing aspects such as the execution time or the memory consumption of the tool when performing the operation over the model. This allows users and developers to know the performance of tools in pessimistic cases providing a better idea of their real power and revealing performance bugs. Experiments using ETHOM on a number of analyses and tools have successfully identified models producing much longer executions times and higher memory consumption than those obtained with random models of identical or even larger size.CICYT TIN2009-07366CICYT TIN2012-32273Junta de Andalucía TIC-5906Junta de Andalucía P12-TIC-186

!Agree Studio: a Platform to Edit and Validate Ws-Agreement Documents

The widespread use of SLA-regulated Cloud services, in which the violation of SLA terms may imply a penalty for the parties, have increased the importance and complexity of systems supporting the SLA lifecycle. Although these systems can be very different from each other, ranging from service monitoring platforms to auto-scaling solutions according to SLAs, they all share the need of having machine-processable and semantically valid SLAs. in this paper we present iAgree studio, the first application, up to our knowledge, that is able to edit and semantically validate agreement documents that are compliant with the WS–Agreement specification by checking properties such as its consistency, and the compliance between templates and agreement offers. in addition, it reports explanations when documents are not valid. Moreover, it allows users to combine the validation and explanation operations by means of a scenarios develope