A static scheduling approach to enable safety-critical OpenMP applications

Parallel computation is fundamental to satisfy the performance requirements of advanced safety-critical systems. OpenMP is a good candidate to exploit the performance opportunities of parallel platforms. However, safety-critical systems are often based on static allocation strategies, whereas current OpenMP implementations are based on dynamic schedulers. This paper proposes two OpenMP-compliant static allocation approaches: an optimal but costly approach based on an ILP formulation, and a sub-optimal but tractable approach that computes a worst-case makespan bound close to the optimal one.This work is funded by the EU projects P-SOCRATES (FP7-ICT-2013-10) and HERCULES (H2020/ICT/2015/688860), and the Spanish Ministry of Science and Innovation under contract TIN2015-65316-P.Peer ReviewedPostprint (author's final draft

A double safety lock tumor-specific device for suicide gene therapy in breast cancer

Producción CientíficaThe complexity and continuous evolution of cancer make the design of novel strategies of treatment a constant challenge in biomedicine. Moreover, most of cancer treatments are still not tumor-specific and provoke high systemic toxicity. Herein we have developed a novel selective nanodevice to eliminate tumor cells while leaving healthy ones intact. To achieve this objective, a polyplex carrier, comprising an elastin like-recombinamer covalently conjugated to an aptamer and complexed with therapeutic DNA, was tested. This carrier forms a double-lock multifunctional device due to specific binding to a tumor cell marker and the selective expression of therapeutic DNA inside human breast-cancer cells. Due to the stability provided by ELRs, the homogeneous population of polyplexes obtained showed selective toxicity against cancer cells in in vitro and in vivo assay. Inhibition of tumor progression was detected early being very significant at the end point, with a dose-dependent reduction in tumor mass. Histological studies revealed a specific reduction in tumor parenchyma and in specific tumor cell markers. These results represent an important step toward the rational development of an efficient, safe and more specialized gene-delivery device for tumor therapy.Fondo Social Europeo - FEDER- Unión Europea (project MP-2014-646075Ministerio de Economía, Industria y Competitividad (project PCIN-2015-010 / MAT2015-68901-R / MAT2016-78903-R)Junta de Castilla y León (project VA317P18

ACOSO SEXUAL CALLEJERO EN MUJERES DE UNA INSTITUCIÓN PRIVADA Y UNA INSTITUCIÓN PÚBLICA, LAMBAYEQUE

Esta investigación se realizó con el objetivo de determinar si existen diferencias respecto al acoso sexual callejero sufrido por mujeres de una institución privada y mujeres de una institución pública, además de las diferencias en las dimensiones acoso expresivo, acoso verbal, acoso físico, persecusiones y exhibicionismo. La cual se realizó con ayuda de 100 universitarias mujeres, cuyas edades oscilaron entre los 17 y 23 años (M=19,94, DE=1,728); 50 jóvenes de la institución privada y 50 de la institución pública, de las escuelas de enfermería y psicología. Se les evaluó a través de la escala de acoso sexual callejero (EASC), creada en el contexto peruano. Los resultados hallados en esta investigación revelan que a nivel general existen diferencias entre el acoso sexual callejero sufrido por mujeres de una institución privada y mujeres de una institución pública; siendo las mujeres de la institución privada quienes soportan mayor acoso en las calles. Sin embargo al compararlas por dimensiones, las cuales son, acoso expresivo, acoso verbal, acoso físico, persecuciones y exhibicionismo; se encontró que no existen diferencias. Así mismo los resultados de esta investigación permitieron concluir que la totalidad de las participantes de esta investigación sufrieron acoso sexual callejero alguna vez en sus vidas. Finalmente se reveló que la prenda de vestir con la que sufren mayormente este acoso es el short

Herramientas para la capacitación en reforzamiento con malla de cuerdas de viviendas de adobe autoconstruidas en áreas sísmicas

Durante las últimas décadas se han desarrollado diversas técnicas de reforzamiento para mejorar la seguridad estructural de las viviendas de tierra ubicadas en áreas sísmicas. Sin embargo, ninguna de estas técnicas ha sido adoptada masivamente por las personas a quienes van dirigidas, debido principalmente a su alto costo y a la falta de difusión. En consecuencia, resulta necesario desarrollar proyectos de transferencia tecnológica y de capacitación en construcción sismorresistente con tierra para mitigar el inaceptable riesgo sísmico de muchas poblaciones rurales. Este proyecto de tesis presenta el diseño y la aplicación de herramientas de transferencia tecnológica para la capacitación de una comunidad andina en construcción sismorresistente con adobe. Se eligió para este proyecto el distrito de Pullo (Ayacucho), ubicado en una zona altamente sísmica, donde más del 80% de pobladores reside en casas de adobe y más del 50% vive en condiciones de pobreza o pobreza extrema. El proyecto consistió en trabajar con los pobladores para que tomen conciencia de la vulnerabilidad de sus viviendas de adobe no reforzado y para que aprendan en forma práctica la técnica de refuerzo con mallas de cuerdas de nylon. Se espera que el proyecto pueda ser aplicado con la misma efectividad en otras poblaciones ubicadas en zonas sísmicas donde la construcción en adobe sea predominante. El documento presenta primero las herramientas y la metodología de capacitación empleados en el proyecto: una mesa vibradora portátil para demostrar la efectividad del refuerzo propuesto y un manual de construcción sismorresistente en adobe. Luego se describe la experiencia de capacitación de la población de Pullo, y finalmente se discuten las conclusiones obtenidas sobre la efectividad del proceso de capacitación y la posibilidad de réplica del proyecto en otras comunidades en riesgo sísmico.Tesi

An Analysis of Lazy and Eager Limited Preemption Approaches under DAG-Based Global Fixed Priority Scheduling

DAG-based scheduling models have been shown to effectively express the parallel execution of current many-core heterogeneous architectures. However, their applicability to real-time settings is limited by the difficulties to find tight estimations of the worst-case timing parameters of tasks that may arbitrarily be preempted/migrated at any instruction. An efficient approach to increase the system predictability is to limit task preemptions to a set of pre-defined points. This limited preemption model supports two different preemption approaches, eager and lazy, which have been analyzed only for sequential task-sets. This paper proposes a new response time analysis that computes an upper bound on the lower priority blocking that each task may incur with eager and lazy preemptions. We evaluate our analysis with both, synthetic DAG-based task-sets and a real case-study from the automotive domain. Results from the analysis demonstrate that, despite the eager approach generates a higher number of priority inversions, the blocking impact is generally smaller than in the lazy approach, leading to a better schedulability performance.This work was funded by the EU projects P-SOCRATES (FP7-ICT-2013-10) and HERCULES (H2020/ICT/2015/688860), and the Spanish Ministry of Science and Innovation under contract TIN2015-65316-P.Peer ReviewedPostprint (author's final draft

Revisiting the ENSO Teleconnection to the Tropical North Atlantic

One of the most robust remote impacts of El Niño–Southern Oscillation (ENSO) is the teleconnection to tropical North Atlantic (TNA) sea surface temperature (SST) in boreal spring. However, important questions still remain open. In particular, the timing of the ENSO–TNA relationship lacks understanding. The three previously proposed mechanisms rely on teleconnection dynamics involving a time lag of one season with respect to the ENSO mature phase in winter, but recent results have shown that the persistence of ENSO into spring is necessary for the development of the TNA SST anomalies. Likewise, the identification of the effective atmospheric forcing in the deep TNA to drive the regional air–sea interaction is also lacking. In this manuscript a new dynamical framework to understand the ENSO–TNA teleconnection is proposed, in which a continuous atmospheric forcing is present throughout the ENSO decaying phase. Observational datasets in the satellite era, which include reliable estimates over the ocean, are used to illustrate the mechanism at play. The dynamics rely on the remote Gill-type response to the ENSO zonally compensated heat source over the Amazon basin, associated with perturbations in the Walker circulation. For El Niño conditions, the anomalous diabatic heating in the tropical Pacific is compensated by anomalous diabatic cooling, in association with negative rainfall anomalies and descending motion over northern South America. A pair of anomalous cyclonic circulations is established at upper-tropospheric levels in the tropical Atlantic straddling the equator, displaying a characteristic baroclinic structure with height. In the TNA region, the mirrored anomalous anticyclonic circulation at lower-tropospheric levels weakens the northeasterly trade winds, leading to a reduction in evaporation and of the ocean mixed layer depth, hence to positive SST anomalies. Apart from the dominance of latent heat flux anomalies in the remote response, sensible heat flux and shortwave radiation anomalies also appear to contribute. The “lagged” relationship between mature ENSO in winter and peaking TNA SSTs in spring seems to be phase locked with the seasonal cycle in both the location of the mechanism’s centers of action and regional SST variance.This work has been supported by the EU/H2020-funded MSCA-IF-EF DPETNA project (GA 655339) and JG-S was partially supported by the Spanish MINECO-funded DANAE Project (CGL2015-68342-R). Technical support at BSC (Computational Earth Sciences group) is sincerely acknowledged. The authors are grateful to the anonymous reviewers for their comments, which helped to improve the scope of the manuscript.Peer ReviewedPostprint (published version

ActS activates peptidoglycan amidases during outer membrane stress in <i>Escherichia coli</i>

The integrity of the cell envelope of E. coli relies on the concerted activity of multi-protein machineries that synthesize the peptidoglycan (PG) and the outer membrane (OM). Our previous work found that the depletion of lipopolysaccharide (LPS) export to the OM induces an essential PG remodeling process involving LD-transpeptidases (LDTs), the glycosyltransferase function of PBP1B and the carboxypeptidase PBP6a. Consequently, cells with defective OM biogenesis lyse if they lack any of these PG enzymes. Here we report that the morphological defects, and lysis associated with a ldtF mutant with impaired LPS transport, are alleviated by the loss of the predicted OM-anchored lipoprotein ActS (formerly YgeR). We show that ActS is an inactive member of LytM-type peptidoglycan endopeptidases due to a degenerated catalytic domain. ActS is capable of activating all three main periplasmic peptidoglycan amidases, AmiA, AmiB, and AmiC, which were previously reported to be activated only by EnvC and/or NlpD. Our data also suggest that in vivo ActS preferentially activates AmiC and that its function is linked to cell envelope stress

Timing characterization of OpenMP4 tasking model

OpenMP is increasingly being supported by the newest high-end embedded many-core processors. Despite the lack of any notion of real-time execution, the latest specification of OpenMP (v4.0) introduces a tasking model that resembles the way real-time embedded applications are modeled and designed, i.e., as a set of periodic task graphs. This makes OpenMP4 a convenient candidate to be adopted in future real-time systems. However, OpenMP4 incorporates as well features to guarantee backward compatibility with previous versions that limit its practical usability in real-time systems. The most notable example is the distinction between tied and untied tasks. Tied tasks force all parts of a task to be executed on the same thread that started the execution, whereas a suspended untied task is allowed to resume execution on a different thread. Moreover, tied tasks are forbidden to be scheduled in threads in which other non-descendant tied tasks are suspended. As a result, the execution model of tied tasks, which is the default model in OpenMP to simplify the coexistence with legacy constructs, clearly restricts the performance and has serious implications on the response time analysis of OpenMP4 applications, making difficult to adopt it in real-time environments. In this paper, we revisit OpenMP design choices, introducing timing predictability as a new and key metric of interest. Our first results confirm that even if tied tasks can be timing analyzed, the quality of the analysis is much worse than with untied tasks. We thus reason about the benefits of using untied tasks, deriving a response time analysis for this model, and so allowing OpenMP4 untied model to be applied to real-time systems

An iPSC-derived vascular model of Marfan syndrome identifies key mediators of smooth muscle cell death.

Marfan syndrome (MFS) is a heritable connective tissue disorder caused by mutations in FBN1, which encodes the extracellular matrix protein fibrillin-1. To investigate the pathogenesis of aortic aneurysms in MFS, we generated a vascular model derived from human induced pluripotent stem cells (MFS-hiPSCs). Our MFS-hiPSC-derived smooth muscle cells (SMCs) recapitulated the pathology seen in Marfan aortas, including defects in fibrillin-1 accumulation, extracellular matrix degradation, transforming growth factor-β (TGF-β) signaling, contraction and apoptosis; abnormalities were corrected by CRISPR-based editing of the FBN1 mutation. TGF-β inhibition rescued abnormalities in fibrillin-1 accumulation and matrix metalloproteinase expression. However, only the noncanonical p38 pathway regulated SMC apoptosis, a pathological mechanism also governed by Krüppel-like factor 4 (KLF4). This model has enabled us to dissect the molecular mechanisms of MFS, identify novel targets for treatment (such as p38 and KLF4) and provided an innovative human platform for the testing of new drugs.This work was supported by Evelyn Trust, the NIHR Cambridge Biomedical Research Centre and the British Heart Foundation (FS/13/29/30024, RM/l3/3/30159, FS/11/77/29327).This is the author accepted manuscript. The final version is available from Nature Publishing Group via https://doi.org/10.1038/ng.372