4,693 research outputs found

    Passivity-based control applied of a reaction wheel pendulum: An IDA-PBC approach

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    This paper presents the development of a nonlinear controller for the reaction wheel pendulum (RWP) via an interconnection and damping assignment passivity-based control (IDA-PBC) approach. The IDA-PBC approach works with the port-Hamiltonian open-loop dynamics of the RWP to propose a nonlinear controller that preserves the Hamiltonian structure in closed-loop by guaranteeing stability properties in the sense of Lyapunov. Numerical results confirm the theoretical development presented throughout simulations in Simulink package from MATLAB. Comparison with a Lyapunov-based approach is also provide

    Identification of Potential Muscle Biomarkers in McArdle Disease: Insights from Muscle Proteome Analysis

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    McArdle disease; Proteomics; Skeletal muscleEnfermedad de McArdle; Proteómica; Músculo esqueléticoMalaltia de McArdle; Proteòmica; Múscul esquelèticGlycogen storage disease type V (GSDV, McArdle disease) is a rare genetic myopathy caused by deficiency of the muscle isoform of glycogen phosphorylase (PYGM). This results in a block in the use of muscle glycogen as an energetic substrate, with subsequent exercise intolerance. The pathobiology of GSDV is still not fully understood, especially with regard to some features such as persistent muscle damage (i.e., even without prior exercise). We aimed at identifying potential muscle protein biomarkers of GSDV by analyzing the muscle proteome and the molecular networks associated with muscle dysfunction in these patients. Muscle biopsies from eight patients and eight healthy controls showing none of the features of McArdle disease, such as frequent contractures and persistent muscle damage, were studied by quantitative protein expression using isobaric tags for relative and absolute quantitation (iTRAQ) followed by artificial neuronal networks (ANNs) and topology analysis. Protein candidate validation was performed by Western blot. Several proteins predominantly involved in the process of muscle contraction and/or calcium homeostasis, such as myosin, sarcoplasmic/endoplasmic reticulum calcium ATPase 1, tropomyosin alpha-1 chain, troponin isoforms, and alpha-actinin-3, showed significantly lower expression levels in the muscle of GSDV patients. These proteins could be potential biomarkers of the persistent muscle damage in the absence of prior exertion reported in GSDV patients. Further studies are needed to elucidate the molecular mechanisms by which PYGM controls the expression of these proteins.This research was funded by Instituto de Salud Carlos III (ISCIII) y FEDER (ERDF) funds “a way to construct Europe”; Ministerio de Ciencia e Innovación (Madrid, Spain), grant numbers (PI17/02052 and PI19/01313). G.N.-G is supported by a ISCIII contract CPII19/00021. P.S.-L. is supported by a ISCIII-CIBERER contract

    A cross-sectional study of Leishmania infantum infection in stray cats in the city of Zaragoza (Spain) using serology and PCR

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    Background: Feline leishmaniosis is a vector-borne parasitic disease caused by Leishmania spp. Leishmania infection in dogs is prevalent in the Mediterranean basin, but in other animals, such as cats, it could also play a role in the epidemiology of the disease. Information on the geographical distribution and epidemiological features of L. infantum infection in cats is scarce, particularly in urban stray cats living in regions where canine leishmaniosis is endemic. As diagnosis can be challenging, combining different serological and molecular methods is a useful approach. Our aim was to investigate the prevalence of infection of L. infantum in apparently healthy stray cats in an endemic region of Spain (Zaragoza city) using serological and molecular methods, and to compare the results of the different techniques. Methods: The prevalence of Leishmania infection was studied in stray cats captured in urban and peri-urban areas of Zaragoza. Blood was collected from each animal for serology and molecular analysis. Three serological methods, namely the immunofluorescent antibody test (IFAT), enzyme-linked immunosorbent assay (ELISA) and western blot (WB), were used to detect L. infantum antibodies and a real-time PCR (qPCR) assay was used to detect L. infantum DNA. The results were analyzed by Fisher’s exact test and Cohen’s kappa statistic (¿) to assess the level of agreement between the diagnostic techniques. Results: Serological analysis of blood samples from 180 stray cats revealed 2.2% (4/179) Leishmania infection positivity by IFAT, 2.8% (5/179) by ELISA and 14.5% (26/179) by WB. Leishmania DNA was detected by qPCR in 5.6% (10/179) of the cats. Sixteen cats (8.9%) tested positive by only one serological technique and four tested positive by all three serological methods used. The overall rate of infected cats (calculated as the number of cats seropositive and/or qPCR positive) was 15.6%, and only two cats tested positive by all the diagnostic methods. A significant association was found between male cats and a positive qPCR result. Comparison of the techniques revealed a fair agreement in seropositivity between blood qPCR and IFAT (¿ = 0.26), blood qPCR and ELISA (¿ = 0.24), WB and ELISA (¿ = 0.37) and WB and IFAT (¿ = 0.40). The highest agreement between seropositive results was between IFAT and ELISA (¿ = 0.89), and the lowest was between blood qPCR and WB (¿ = 0.19). The prevalence of the feline leukemia virus antigen was 4.49% (8/178 cats) and that of the feline immunodeficiency virus (FIV) antibody was 6.74% (12/178), while co-infection with both retroviruses was observed in one female cat (1/178). Leishmania ELISA and IFAT seropositivity were statistically associated with FIV status by the chi-square test. Conclusions: The results obtained in this study, using serological tests and qPCR, indicate the existence of L. infantum asymptomatic infection in apparently healthy stray cats in the city of Zaragoza, an endemic area in Spain. [Figure not available: see fulltext.

    Velocity-Based Heuristic Evaluation for Path Planning and Vehicle Routing for Victim Assistance in Disaster Scenarios

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    Published in "Robot 2019: Fourth Iberian Robotics Conference. Advances in Intelligent Systems and Computing, Vol 1093. Silva M., Luís Lima J., Reis L., Sanfeliu A., Tardioli D. (eds)" published by Springer, Cham. Avalaible online at: https://doi.org/10.1007.987-3-030-36150-1_10Natural and human-made disasters require effective victim assistance and last-mile relief supply operations with teams of ground vehicles. In these applications, digital elevation models (DEM) can provide accurate knowledge for safe vehicle motion planning but grid representation results in very large search graphs. Furthermore, travel time, which becomes a crucial cost optimization criterion, may be affected by inclination and other challenging terrain characteristics. In this paper, our goal is to evaluate a search heuristic function based on anisotropic vehicle velocity restrictions for building the cost matrix required for multi-vehicle routing on natural terrain and disaster sites. The heuristic is applied to compute the fastest travel times between every pair of matrix elements by means of a path planning algorithm. The analysis is based on a case study on the ortophotographic-based DEM of natural terrain with different target points, where theUniversidad de Málaga. Campus de Excelencia Internacional Andalucía Tech. This work has received funding from the national project RTI2018-093421-B-I00 (Spanish Government), the University of Malaga (Andalucía Tech) and the grant BES-2016-077022 of the European Social Fund

    Physical interactions between MCM and Rad51 facilitate replication fork lesion bypass and ssDNA gap filling by non-recombinogenic functions

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    The minichromosome maintenance (MCM) helicase physically interacts with the recombination proteins Rad51 and Rad52 from yeast to human cells. We show, in Saccharomyces cerevisiae, that these interactions occur within a nuclease-insoluble scaffold enriched in replication/repair factors. Rad51 accumulates in a MCM- and DNA-binding-independent manner and interacts with MCMhelicases located outside of the replication origins and forks. MCM, Rad51, and Rad52 accumulate in this scaffold in G1 and are released during the S phase. In the presence of replication-blocking lesions, Cdc7 prevents their release from the scaffold, thus maintaining the interactions. We identify a rad51 mutant that is impaired in its ability to bind to MCM but not to the scaffold. This mutant is proficient in recombination but partially defective in single-stranded DNA (ssDNA) gap filling and replication fork progression through damaged DNA. Therefore, cells accumulate MCM/Rad51/Rad52 complexes at specific nuclear scaffolds in G1 to assist stressed forks through non-recombinogenic functions.Cancer Signaling networks and Molecular Therapeutic

    Targeted Next-Generation Sequencing in a Large Cohort of Genetically Undiagnosed Patients with Neuromuscular Disorders in Spain

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    This article belongs to the Special Issue Genetic Advances in Neuromuscular Disorders: From Gene Identification to Gene Therapy.The term neuromuscular disorder (NMD) includes many genetic and acquired diseases and differential diagnosis can be challenging. Next-generation sequencing (NGS) is especially useful in this setting given the large number of possible candidate genes, the clinical, pathological, and genetic heterogeneity, the absence of an established genotype-phenotype correlation, and the exceptionally large size of some causative genes such as TTN, NEB and RYR1. We evaluated the diagnostic value of a custom targeted next-generation sequencing gene panel to study the mutational spectrum of a subset of NMD patients in Spain. In an NMD cohort of 207 patients with congenital myopathies, distal myopathies, congenital and adult-onset muscular dystrophies, and congenital myasthenic syndromes, we detected causative mutations in 102 patients (49.3%), involving 42 NMD-related genes. The most common causative genes, TTN and RYR1, accounted for almost 30% of cases. Thirty-two of the 207 patients (15.4%) carried variants of uncertain significance or had an unidentified second mutation to explain the genetic cause of the disease. In the remaining 73 patients (35.3%), no candidate variant was identified. In combination with patients’ clinical and myopathological data, the custom gene panel designed in our lab proved to be a powerful tool to diagnose patients with myopathies, muscular dystrophies and congenital myasthenic syndromes. Targeted NGS approaches enable a rapid and cost-effective analysis of NMD- related genes, offering reliable results in a short time and relegating invasive techniques to a second tier.This study was granted by FIS PI15/01898, funded by ISCIII and FEDER, ‘Una manera de hacer Europa’ and by Fundación Mutua Madrileña in the “Convocatoria de ayudas a la Investigación en Salud 2015”. It was also funded by an ACCI grant from CIBERER. Daniel Natera-de Benito is the recipient of a grant from the Instituto de Salud Carlos III (Contrato Rio Hortega, CM17/00044)
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