An Automated Methodology to Select Functional Co-Simulation Configurations

[Abstract] The development of machinery often requires system-level analysis, in which non-mechanical subsystems, such as hydraulics, need to be considered. Co-simulation allows analysts to divide a problem into subsystems and use tailored software solutions to deal individually with their respective dynamics. On the other hand, these subsystems must be coupled at particular instants in time, called communication points, through the exchange of coupling variables. Between communication points, each subsystem solver carries out the integration of its states without interacting with its environment. This may cause the integration to become unstable, especially when non-iterative co-simulation is used. The co-simulation configuration, i.e., the parameters and simulation options selected by the analyst, such as the way to handle the coupling variables or the choice of subsystem solvers, is often a critical factor regarding co-simulation stability. In practice it is difficult to anticipate which selection is the most appropriate for a particular problem, especially if some inputs come from external sources, such as human operators, and cannot be determined beforehand. We put forward a methodology to automatically determine a stable and computationally efficient configuration for Jacobi-scheme co-simulation. The method uses energy residuals to gain insight into co-simulation stability. The relation between energy residual and communication step-size is exploited to monitor co-simulation accuracy during a series of tests in which the external inputs are replaced with predetermined input functions. The method was tested with hydraulically actuated mechanical examples. Results indicate that the proposed method can be used to find stable and accurate configurations for co-simulation applications.Ministerio de Economía; RYC-2016-2022

Genetic heterogeneity in natural beds of the razor clam "Ensis siliqua" revealed by microsatellites

[Abstract] The aim of this study was to analyse the genetic diversity and population structure in the razor clam Ensis siliqua along the European Atlantic coast taking into account their recent history of exploitation and the ‘Prestige' oil spill. To this end we examined the genetic variability of microsatellite markers in 211 razor clams from five populations in Ireland, Portugal and Spain. Microsatellite data revealed a low genetic differentiation between the Spanish and Portuguese populations (FST = 0–0.032) and a moderate differentiation of these populations and the Irish samples (FST = 0.071–0.100). Although we observed changes in genetic diversity in accordance with the level of exploitation and the distribution of the oil spill, these changes were mild and not significant after Bonferroni correction. This could be the result of a genuine low impact, lack of statistical power and/or the capacity of this species to recolonize quickly after the impact of anthropogenic stressors. Supporting the latter argument we found a significant temporal heterogeneity of allelic frequencies in samples coming from the same sampling locality that could be attributed to the movement of adults or larvae from unaffected source populations

Temporal genetic variation of microsatellite markers in the razor clam "Ensis arcuatus" (Bivalvia: Pharidae)

[Abstract] The aim of this study was to characterize new microsatellite loci in the razor clam Ensis arcuatus (Bivalvia: Pharidae) and examine the temporal genetic variability of a natural bed in Cies Islands (Galicia, north-western Spain) exploited by apnoea divers and affected by the ‘Prestige’ oil tanker spill in November 2002. In this work, we characterized four polymorphic microsatellites using an alternative approach that relies on the amplification and sequencing of ISSR markers. Observed heterozygosities ranged from 0.1053–0.6800 and number of alleles from 4–19. Linkage equilibrium was observed in all loci and two of them showed significant deviations from Hardy–Weinberg equilibrium. Estimators of FST between samples were low (<0.05) and not different from zero with a confidence level of 5%. We did not detect a clear decreasing tendency in genetic diversity although we found a significant change in allelic frequencies among samples (P = 0.0024) after the ‘Prestige’ oil spill. We propose that both phenomena could be related to a high variance in genetic success and/or a movement of adults or larvae from different source populations.Xunta de Galicia; PGIDT03PXIB10302PRXunta de Galicia; PGIDT03MA10301PRXunta de Galicia; IN840DXunta de Galicia; IN809

Assessment of Methods for the Real-Time Simulation of Electronic and Thermal Circuits

[Abstract] Time–domain simulation of electronic and thermal circuits is required by a large array of applications, such as the design and optimization of electric vehicle powertrain components. While efficient execution is always a desirable feature of simulation codes, in certain cases like System-in-the-Loop setups, real-time performance is demanded. Whether real-time code execution can be achieved or not in a particular case depends on a series of factors, which include the mathematical formulation of the equations that govern the system dynamics, the techniques used in code implementation, and the capabilities of the hardware architecture on which the simulation is run. In this work, we present an evaluation framework of numerical methods for the simulation of electronic and thermal circuits from the point of view of their ability to deliver real-time performance. The methods were compared using a set of nontrivial benchmark problems and relevant error metrics. The computational efficiency of the simulation codes was measured under different software and hardware environments, to determine the feasibility of using them in industrial applications with reduced computational power.Ministerio de Economía y Competitividad; RYC-2016-20222Xunta de Galicia; ED431B2016/03

Generation of mice with longer and better preserved telomeres in the absence of genetic manipulations.

Although telomere length is genetically determined, mouse embryonic stem (ES) cells with telomeres of twice the normal size have been generated. Here, we use such ES cells with ‘hyper-long’ telomeres, which also express green fluorescent protein (GFP), to generate chimaeric mice containing cells with both hyper-long and normal telomeres. We show that chimaeric mice contain GFP-positive cells in all mouse tissues, display normal tissue histology and normal survival. Both hyper-long and normal telomeres shorten with age, but GFP-positive cells retain longer telomeres as mice age. Chimaeric mice with hyper-long telomeres also accumulate fewer cells with short telomeres and less DNA damage with age, and express lower levels of p53. In highly renewing compartments, such as the blood, cells with hyper-long telomeres are longitudinally maintained or enriched with age. We further show that wound-healing rates in the skin are increased in chimaeric mice. Our work demonstrates that mice with functional, longer and better preserved telomeres can be generated without the need for genetic manipulations, such as TERT overexpression.post-print3240 K

Heterogeneous nature and distribution of interruptions in dinucleotides may indicate the existence of biased substitutions underlying microsatellite evolution

[Abstract] Some aspects of microsatellite evolution, such as the role of base substitutions, are far from being fully understood. To examine the significance of base substitutions underlying the evolution of microsatellites we explored the nature and the distribution of interruptions in dinucleotide repeats from the human genome. The frequencies that we inferred in the repetitive sequences were statistically different from the frequencies observed in other noncoding sequences. Additionally, we detected that the interruptions tended to be towards the ends of the microsatellites and 5′-3′ asymmetry. In all the estimates nucleotides forming the same repetitive motif seem to be affected by different base substitution rates in AC and AG. This tendency itself could generate patterning and similarity in flanking sequences and reconcile these phenomena with the high mutation rate found in flanking sequences without invoking convergent evolution. Nevertheless, our data suggest that there is a regional bias in the substitution pattern of microsatellites. The accumulation of random substitutions alone cannot explain the heterogeneity and the asymmetry of interruptions found in this study or the relative frequency of different compound microsatellites in the human genome. Therefore, we cannot rule out the possibility of a mutational bias leading to convergent or parallel evolution in flanking sequences

Oligonucleotide-based therapy for FTD/ALS caused by the C9orf72 repeat expansion: a perspective

Amyotrophic lateral sclerosis (ALS) is a progressive and lethal disease of motor neuron degeneration, leading to paralysis of voluntary muscles and death by respiratory failure within five years of onset. Frontotemporal dementia (FTD) is characterised by degeneration of frontal and temporal lobes, leading to changes in personality, behaviour, and language, culminating in death within 5–10 years. Both of these diseases form a clinical, pathological, and genetic continuum of diseases, and this link has become clearer recently with the discovery of a hexanucleotide repeat expansion in the C9orf72 gene that causes the FTD/ALS spectrum, that is, c9FTD/ALS. Two basic mechanisms have been proposed as being potentially responsible for c9FTD/ALS: loss-of-function of the protein encoded by this gene (associated with aberrant DNA methylation) and gain of function through the formation of RNA foci or protein aggregates. These diseases currently lack any cure or effective treatment. Antisense oligonucleotides (ASOs) are modified nucleic acids that are able to silence targeted mRNAs or perform splice modulation, and the fact that they have proved efficient in repeat expansion diseases including myotonic dystrophy type 1 makes them ideal candidates for c9FTD/ALS therapy. Here, we discuss potential mechanisms and challenges for developing oligonucleotide-based therapy for c9FTD/ALS

Development of Microsatellite Markers in the Razor Clam Solen Marginatus (Bivalvia: Solenidae)

[Abstract] Four microsatellite loci in the razor clam Solen marginatus are described. Loci were isolated from the sequences of intersimple sequence repeat (ISSR) markers and an enriched library. Detailed analysis of these sequences led to the design of eight primer pairs. Allelic variation was assessed in 20 individuals from Redondela, Spain. The genetic variation observed in the markers presented here will be useful for future studies on the population structure of Solen marginatus in the wild and for aquaculture of this species.Xunta de Galicia; PGIDT03MA10301PR

Isolation and characterization of polymorphic microsatellite loci in the razor clam "Ensis siliqua"

[Abstract] Five polymorphic microsatellite loci in the razor clam Ensis siliqua are described. A collection consisting of 34 individuals from Finisterre, Spain, was analysed. Loci were isolated from the sequences of intersimple sequence repeat (ISSR) markers. Detailed analysis of 42 ISSR markers led to the design of 16 primer pairs. Five of these yielded consistent and polymorphic products. The number of alleles ranged from five to 23 per locus with the observed heterozygosity ranging from 0.46 to 0.94. Linkage equilibrium was observed in all loci and three of them showed significant deviations from Hardy–Weinberg equilibrium