29 results on '"Gómez-Fernández, David"'
Search Results
2. A Multi-Target Pharmacological Correction of a Lipoyltransferase LIPT1 Gene Mutation in Patient-Derived Cellular Models.
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Gómez-Fernández, David, Romero-González, Ana, Suárez-Rivero, Juan M., Cilleros-Holgado, Paula, Álvarez-Córdoba, Mónica, Piñero-Pérez, Rocío, Romero-Domínguez, José Manuel, Reche-López, Diana, López-Cabrera, Alejandra, Ibáñez-Mico, Salvador, Castro de Oliveira, Marta, Rodríguez-Sacristán, Andrés, González-Granero, Susana, García-Verdugo, José Manuel, and Sánchez-Alcázar, José A.
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INBORN errors of metabolism ,WESTERN immunoblotting ,IRON overload ,BIOENERGETICS ,MUSCLE tone - Abstract
Mutations in the lipoyltransferase 1 (LIPT1) gene are rare inborn errors of metabolism leading to a fatal condition characterized by lipoylation defects of the 2-ketoacid dehydrogenase complexes causing early-onset seizures, psychomotor retardation, abnormal muscle tone, severe lactic acidosis, and increased urine lactate, ketoglutarate, and 2-oxoacid levels. In this article, we characterized the disease pathophysiology using fibroblasts and induced neurons derived from a patient bearing a compound heterozygous mutation in LIPT1. A Western blot analysis revealed a reduced expression of LIPT1 and absent expression of lipoylated pyruvate dehydrogenase E2 (PDH E2) and alpha-ketoglutarate dehydrogenase E2 (α-KGDH E2) subunits. Accordingly, activities of PDH and α-KGDH were markedly reduced, associated with cell bioenergetics failure, iron accumulation, and lipid peroxidation. In addition, using a pharmacological screening, we identified a cocktail of antioxidants and mitochondrial boosting agents consisting of pantothenate, nicotinamide, vitamin E, thiamine, biotin, and α-lipoic acid, which is capable of rescuing LIPT1 pathophysiology, increasing the LIPT1 expression and lipoylation of mitochondrial proteins, improving cell bioenergetics, and eliminating iron overload and lipid peroxidation. Furthermore, our data suggest that the beneficial effect of the treatment is mainly mediated by SIRT3 activation. In conclusion, we have identified a promising therapeutic approach for correcting LIPT1 mutations. [ABSTRACT FROM AUTHOR]
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- 2024
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3. Mitochondrial Unfolded Protein Response (Mtupr) Activation by Polydatin and Nicotinamide Corrects Pathological Alterations in Cellular Models of Gfm1 Mutations
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Cilleros-Holgado, Paula, primary, Gómez-Fernández, David, additional, Piñero-Pérez, Rocío, additional, Romero-Domínguez, José Manuel, additional, Talaverón-Rey, Marta, additional, Reche-López, Diana, additional, Suárez-Rivero, Juan Miguel, additional, Alvárez-Córdoba, Mónica, additional, Romero-González, Ana, additional, López-Cabrera, Alejandra, additional, Castro de Oliveira, Marta, additional, Rodríguez-Sacristán, Andrés, additional, and Sánchez-Alcázar, José A., additional
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- 2024
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4. Polydatin and Nicotinamide Rescue the Cellular Phenotype of Mitochondrial Diseases by Mitochondrial Unfolded Protein Response (mtUPR) Activation.
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Cilleros-Holgado, Paula, Gómez-Fernández, David, Piñero-Pérez, Rocío, Romero Domínguez, José Manuel, Talaverón-Rey, Marta, Reche-López, Diana, Suárez-Rivero, Juan Miguel, Álvarez-Córdoba, Mónica, Romero-González, Ana, López-Cabrera, Alejandra, Oliveira, Marta Castro De, Rodríguez-Sacristan, Andrés, and Sánchez-Alcázar, José Antonio
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MITOCHONDRIAL DNA , *MITOCHONDRIAL proteins , *DENATURATION of proteins , *UNFOLDED protein response , *NICOTINAMIDE , *ELONGATION factors (Biochemistry) - Abstract
Primary mitochondrial diseases result from mutations in nuclear DNA (nDNA) or mitochondrial DNA (mtDNA) genes, encoding proteins crucial for mitochondrial structure or function. Given that few disease-specific therapies are available for mitochondrial diseases, novel treatments to reverse mitochondrial dysfunction are necessary. In this work, we explored new therapeutic options in mitochondrial diseases using fibroblasts and induced neurons derived from patients with mutations in the GFM1 gene. This gene encodes the essential mitochondrial translation elongation factor G1 involved in mitochondrial protein synthesis. Due to the severe mitochondrial defect, mutant GFM1 fibroblasts cannot survive in galactose medium, making them an ideal screening model to test the effectiveness of pharmacological compounds. We found that the combination of polydatin and nicotinamide enabled the survival of mutant GFM1 fibroblasts in stress medium. We also demonstrated that polydatin and nicotinamide upregulated the mitochondrial Unfolded Protein Response (mtUPR), especially the SIRT3 pathway. Activation of mtUPR partially restored mitochondrial protein synthesis and expression, as well as improved cellular bioenergetics. Furthermore, we confirmed the positive effect of the treatment in GFM1 mutant induced neurons obtained by direct reprogramming from patient fibroblasts. Overall, we provide compelling evidence that mtUPR activation is a promising therapeutic strategy for GFM1 mutations. [ABSTRACT FROM AUTHOR]
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- 2024
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5. Mitochondrial Quality Control via Mitochondrial Unfolded Protein Response (mtUPR) in Ageing and Neurodegenerative Diseases
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Cilleros-Holgado, Paula, primary, Gómez-Fernández, David, additional, Piñero-Pérez, Rocío, additional, Romero-Domínguez, Jose Manuel, additional, Reche-López, Diana, additional, López-Cabrera, Alejandra, additional, Álvarez-Córdoba, Mónica, additional, Munuera-Cabeza, Manuel, additional, Talaverón-Rey, Marta, additional, Suárez-Carrillo, Alejandra, additional, Romero-González, Ana, additional, and Sánchez-Alcázar, Jose Antonio, additional
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- 2023
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6. Actin Polymerization Defects Induce Mitochondrial Dysfunction in Cellular Models of Nemaline Myopathies
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Piñero-Pérez, Rocío, primary, López-Cabrera, Alejandra, additional, Álvarez-Córdoba, Mónica, additional, Cilleros-Holgado, Paula, additional, Talaverón-Rey, Marta, additional, Suárez-Carrillo, Alejandra, additional, Munuera-Cabeza, Manuel, additional, Gómez-Fernández, David, additional, Reche-López, Diana, additional, Romero-González, Ana, additional, Romero-Domínguez, José Manuel, additional, de Pablos, Rocío M., additional, and Sánchez-Alcázar, José A., additional
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- 2023
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7. Antioxidants Prevent Iron Accumulation and Lipid Peroxidation, but Do Not Correct Autophagy Dysfunction or Mitochondrial Bioenergetics in Cellular Models of BPAN
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Suárez-Carrillo, Alejandra, primary, Álvarez-Córdoba, Mónica, additional, Romero-González, Ana, additional, Talaverón-Rey, Marta, additional, Povea-Cabello, Suleva, additional, Cilleros-Holgado, Paula, additional, Piñero-Pérez, Rocío, additional, Reche-López, Diana, additional, Gómez-Fernández, David, additional, Romero-Domínguez, José Manuel, additional, Munuera-Cabeza, Manuel, additional, Díaz, Antonio, additional, González-Granero, Susana, additional, García-Verdugo, José Manuel, additional, and Sánchez-Alcázar, José A., additional
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- 2023
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8. Patient-Derived Cellular Models for Polytarget Precision Medicine in Pantothenate Kinase-Associated Neurodegeneration
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Álvarez-Córdoba, Mónica, primary, Talaverón-Rey, Marta, additional, Povea-Cabello, Suleva, additional, Cilleros-Holgado, Paula, additional, Gómez-Fernández, David, additional, Piñero-Pérez, Rocío, additional, Reche-López, Diana, additional, Munuera-Cabeza, Manuel, additional, Suárez-Carrillo, Alejandra, additional, Romero-González, Ana, additional, Romero-Domínguez, Jose Manuel, additional, López-Cabrera, Alejandra, additional, Armengol, José Ángel, additional, and Sánchez-Alcázar, José Antonio, additional
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- 2023
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9. Patient-Derived Cellular Models for Polytarget Precision Medicine in Pantothenate Kinase-Associated Neurodegeneration
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Ávarez-Córdoba, Mónica, primary, Rey-Talaverón, Marta, additional, Povea-Cabello, Suleva, additional, Cilleros-Holgado, Paula, additional, Gómez-Fernández, David, additional, Piñero-Pérez, Rocío, additional, Reche-López, Diana, additional, Munuera-Cabeza, Manuel, additional, Suárez-Carrillo, Alejandra, additional, Romero-González, Ana, additional, Romero-Domínguez, José Manuel, additional, López-Cabrera, Alejandra, additional, Armengol, José Ángel, additional, and Sánchez-Alcázar, Jose Antonio, additional
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- 2023
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10. Actin Polymerization Defects Induce Mitochondrial Dysfunction in Cellular Models of Nemaline Myopathies
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Universidad de Sevilla. Departamento de Bioquímica y Biología Molecular, Instituto de Salud Carlos III, Junta de Andalucía, Piñero Pérez, Rocío, López Cabrera, Alejandra, Álvarez Córdoba, Mónica, Cilleros Holgado, Paula, Talaverón Rey, Marta, Suárez Carrillo, Alejandra, Munuera Cabeza, Manuel, Gómez Fernández, David, Reche López, Diana, Romero González, Ana Belén, Romero Domínguez, José Manuel, Martínez de Pablos, Rocío, Sánchez Alcázar, José Antonio, Universidad de Sevilla. Departamento de Bioquímica y Biología Molecular, Instituto de Salud Carlos III, Junta de Andalucía, Piñero Pérez, Rocío, López Cabrera, Alejandra, Álvarez Córdoba, Mónica, Cilleros Holgado, Paula, Talaverón Rey, Marta, Suárez Carrillo, Alejandra, Munuera Cabeza, Manuel, Gómez Fernández, David, Reche López, Diana, Romero González, Ana Belén, Romero Domínguez, José Manuel, Martínez de Pablos, Rocío, and Sánchez Alcázar, José Antonio
- Abstract
Nemaline myopathy (NM) is one of the most common forms of congenital myopathy and it is identified by the presence of “nemaline bodies” (rods) in muscle fibers by histopathological examination. The most common forms of NM are caused by mutations in the Actin Alpha 1 (ACTA1) and Nebulin (NEB) genes. Clinical features include hypotonia and muscle weakness. Unfortunately, there is no curative treatment and the pathogenetic mechanisms remain unclear. In this manuscript, we examined the pathophysiological alterations in NM using dermal fibroblasts derived from patients with mutations in ACTA1 and NEB genes. Patients’ fibroblasts were stained with rhodamine–phalloidin to analyze the polymerization of actin filaments by fluorescence microscopy. We found that patients’ fibroblasts showed incorrect actin filament polymerization compared to control fibroblasts. Actin filament polymerization defects were associated with mitochondrial dysfunction. Furthermore, we identified two mitochondrial-boosting compounds, linoleic acid (LA) and L-carnitine (LCAR), that improved the formation of actin filaments in mutant fibroblasts and corrected mitochondrial bioenergetics. Our results indicate that cellular models can be useful to study the pathophysiological mechanisms involved in NM and to find new potential therapies. Furthermore, targeting mitochondrial dysfunction with LA and LCAR can revert the pathological alterations in NM cellular models.
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- 2023
11. mtUPR Modulation as a Therapeutic Target for Primary and Secondary Mitochondrial Diseases
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Ministerio de Sanidad (España), European Commission, Ministerio de Educación, Cultura y Deporte (España), Junta de Andalucía, Cilleros-Holgado, Paula, Gómez-Fernández, David, Piñero-Perez, Rocío, Reche-López, Diana, Álvarez-Córdoba, Mónica, Munuera, Manuel, Talaverón-Rey, Marta, Povea-Cabello, Suleva, Suárez-Carrillo, Alejandra, Romero-González, Ana, Suarez-Rivero, Juan M., Romero-Domínguez, José Manuel, Sánchez-Alcázar, José Antonio, Ministerio de Sanidad (España), European Commission, Ministerio de Educación, Cultura y Deporte (España), Junta de Andalucía, Cilleros-Holgado, Paula, Gómez-Fernández, David, Piñero-Perez, Rocío, Reche-López, Diana, Álvarez-Córdoba, Mónica, Munuera, Manuel, Talaverón-Rey, Marta, Povea-Cabello, Suleva, Suárez-Carrillo, Alejandra, Romero-González, Ana, Suarez-Rivero, Juan M., Romero-Domínguez, José Manuel, and Sánchez-Alcázar, José Antonio
- Abstract
Mitochondrial dysfunction is a key pathological event in many diseases. Its role in energy production, calcium homeostasis, apoptosis regulation, and reactive oxygen species (ROS) balance render mitochondria essential for cell survival and fitness. However, there are no effective treatments for most primary and secondary mitochondrial diseases to this day. Therefore, new therapeutic approaches, such as the modulation of the mitochondrial unfolded protein response (mtUPR), are being explored. mtUPRs englobe several compensatory processes related to proteostasis and antioxidant system mechanisms. mtUPR activation, through an overcompensation for mild intracellular stress, promotes cell homeostasis and improves lifespan and disease alterations in biological models of mitochondrial dysfunction in age-related diseases, cardiopathies, metabolic disorders, and primary mitochondrial diseases. Although mtUPR activation is a promising therapeutic option for many pathological conditions, its activation could promote tumor progression in cancer patients, and its overactivation could lead to non-desired side effects, such as the increased heteroplasmy of mitochondrial DNA mutations. In this review, we present the most recent data about mtUPR modulation as a therapeutic approach, its role in diseases, and its potential negative consequences in specific pathological situations.
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- 2023
12. Mitochondrial Quality Control via Mitochondrial Unfolded Protein Response (mtUPR) in Ageing and Neurodegenerative Diseases
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Instituto de Salud Carlos III, Ministerio de Sanidad (España), European Commission, Ministerio de Educación, Cultura y Deporte (España), Ministerio de Industria, Energía y Turismo (España), Junta de Andalucía, Fundación Merck Salud, Universidad Pablo de Olavide, Cilleros-Holgado, Paula, Gómez-Fernández, David, Piñero-Perez, Rocío, Romero-Domínguez, José Manuel, Reche-López, Diana, López-Cabrera, Alejandra, Álvarez-Córdoba, Mónica, Munuera, Manuel, Talaverón-Rey, Marta, Suárez-Carrillo, Alejandra, Romero-González, Ana, Sánchez-Alcázar, José Antonio, Instituto de Salud Carlos III, Ministerio de Sanidad (España), European Commission, Ministerio de Educación, Cultura y Deporte (España), Ministerio de Industria, Energía y Turismo (España), Junta de Andalucía, Fundación Merck Salud, Universidad Pablo de Olavide, Cilleros-Holgado, Paula, Gómez-Fernández, David, Piñero-Perez, Rocío, Romero-Domínguez, José Manuel, Reche-López, Diana, López-Cabrera, Alejandra, Álvarez-Córdoba, Mónica, Munuera, Manuel, Talaverón-Rey, Marta, Suárez-Carrillo, Alejandra, Romero-González, Ana, and Sánchez-Alcázar, José Antonio
- Abstract
Mitochondria play a key role in cellular functions, including energy production and oxidative stress regulation. For this reason, maintaining mitochondrial homeostasis and proteostasis (homeostasis of the proteome) is essential for cellular health. Therefore, there are different mitochondrial quality control mechanisms, such as mitochondrial biogenesis, mitochondrial dynamics, mitochondrial-derived vesicles (MDVs), mitophagy, or mitochondrial unfolded protein response (mtUPR). The last item is a stress response that occurs when stress is present within mitochondria and, especially, when the accumulation of unfolded and misfolded proteins in the mitochondrial matrix surpasses the folding capacity of the mitochondrion. In response to this, molecular chaperones and proteases as well as the mitochondrial antioxidant system are activated to restore mitochondrial proteostasis and cellular function. In disease contexts, mtUPR modulation holds therapeutic potential by mitigating mitochondrial dysfunction. In particular, in the case of neurodegenerative diseases, such as primary mitochondrial diseases, Alzheimer’s disease (AD), Parkinson’s disease (PD), Huntington’s disease (HD), Amyotrophic Lateral Sclerosis (ALS), or Friedreich’s Ataxia (FA), there is a wealth of evidence demonstrating that the modulation of mtUPR helps to reduce neurodegeneration and its associated symptoms in various cellular and animal models. These findings underscore mtUPR’s role as a promising therapeutic target in combating these devastating disorders.
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- 2023
13. Actin Polymerization Defects Induce Mitochondrial Dysfunction in Cellular Models of Nemaline Myopathies
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Instituto de Salud Carlos III, European Commission, Ministerio de Educación, Cultura y Deporte (España), Junta de Andalucía, Piñero-Perez, Rocío, López-Cabrera, Alejandra, Álvarez-Córdoba, Mónica, Cilleros-Holgado, Paula, Talaverón-Rey, Marta, Suárez-Carrillo, Alejandra, Munuera, Manuel, Gómez-Fernández, David, Reche-López, Diana, Romero-González, Ana, Romero-Domínguez, José Manuel, Pablos, Rocío M. de, Sánchez-Alcázar, José Antonio, Instituto de Salud Carlos III, European Commission, Ministerio de Educación, Cultura y Deporte (España), Junta de Andalucía, Piñero-Perez, Rocío, López-Cabrera, Alejandra, Álvarez-Córdoba, Mónica, Cilleros-Holgado, Paula, Talaverón-Rey, Marta, Suárez-Carrillo, Alejandra, Munuera, Manuel, Gómez-Fernández, David, Reche-López, Diana, Romero-González, Ana, Romero-Domínguez, José Manuel, Pablos, Rocío M. de, and Sánchez-Alcázar, José Antonio
- Abstract
Nemaline myopathy (NM) is one of the most common forms of congenital myopathy and it is identified by the presence of “nemaline bodies” (rods) in muscle fibers by histopathological examination. The most common forms of NM are caused by mutations in the Actin Alpha 1 (ACTA1) and Nebulin (NEB) genes. Clinical features include hypotonia and muscle weakness. Unfortunately, there is no curative treatment and the pathogenetic mechanisms remain unclear. In this manuscript, we examined the pathophysiological alterations in NM using dermal fibroblasts derived from patients with mutations in ACTA1 and NEB genes. Patients’ fibroblasts were stained with rhodamine–phalloidin to analyze the polymerization of actin filaments by fluorescence microscopy. We found that patients’ fibroblasts showed incorrect actin filament polymerization compared to control fibroblasts. Actin filament polymerization defects were associated with mitochondrial dysfunction. Furthermore, we identified two mitochondrial-boosting compounds, linoleic acid (LA) and L-carnitine (LCAR), that improved the formation of actin filaments in mutant fibroblasts and corrected mitochondrial bioenergetics. Our results indicate that cellular models can be useful to study the pathophysiological mechanisms involved in NM and to find new potential therapies. Furthermore, targeting mitochondrial dysfunction with LA and LCAR can revert the pathological alterations in NM cellular models.
- Published
- 2023
14. Neurodegeneration, Mitochondria, and Antibiotics
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Instituto de Salud Carlos III, European Commission, Ministerio de Educación, Cultura y Deporte (España), Ministerio de Economía, Industria y Competitividad (España), Ministerio de Universidades (España), Junta de Andalucía, Suarez-Rivero, Juan M., López-Pérez, Juan, Muela-Zarzuela, Inés, Pastor-Maldonado, Carmen J., Cilleros-Holgado, Paula, Gómez-Fernández, David, Álvarez-Córdoba, Mónica, Munuera, Manuel, Talaverón-Rey, Marta, Povea-Cabello, Suleva, Suárez-Carrillo, Alejandra, Piñero-Perez, Rocío, Reche-López, Diana, Romero-Domínguez, José Manuel, Sánchez-Alcázar, José Antonio, Instituto de Salud Carlos III, European Commission, Ministerio de Educación, Cultura y Deporte (España), Ministerio de Economía, Industria y Competitividad (España), Ministerio de Universidades (España), Junta de Andalucía, Suarez-Rivero, Juan M., López-Pérez, Juan, Muela-Zarzuela, Inés, Pastor-Maldonado, Carmen J., Cilleros-Holgado, Paula, Gómez-Fernández, David, Álvarez-Córdoba, Mónica, Munuera, Manuel, Talaverón-Rey, Marta, Povea-Cabello, Suleva, Suárez-Carrillo, Alejandra, Piñero-Perez, Rocío, Reche-López, Diana, Romero-Domínguez, José Manuel, and Sánchez-Alcázar, José Antonio
- Abstract
Neurodegenerative diseases are characterized by the progressive loss of neurons, synapses, dendrites, and myelin in the central and/or peripheral nervous system. Actual therapeutic options for patients are scarce and merely palliative. Although they affect millions of patients worldwide, the molecular mechanisms underlying these conditions remain unclear. Mitochondrial dysfunction is generally found in neurodegenerative diseases and is believed to be involved in the pathomechanisms of these disorders. Therefore, therapies aiming to improve mitochondrial function are promising approaches for neurodegeneration. Although mitochondrial-targeted treatments are limited, new research findings have unraveled the therapeutic potential of several groups of antibiotics. These drugs possess pleiotropic effects beyond their anti-microbial activity, such as anti-inflammatory or mitochondrial enhancer function. In this review, we will discuss the controversial use of antibiotics as potential therapies in neurodegenerative diseases.
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- 2023
15. Neurodegeneration, Mitochondria, and Antibiotics
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Suárez-Rivero, Juan M., primary, López-Pérez, Juan, additional, Muela-Zarzuela, Inés, additional, Pastor-Maldonado, Carmen, additional, Cilleros-Holgado, Paula, additional, Gómez-Fernández, David, additional, Álvarez-Córdoba, Mónica, additional, Munuera-Cabeza, Manuel, additional, Talaverón-Rey, Marta, additional, Povea-Cabello, Suleva, additional, Suárez-Carrillo, Alejandra, additional, Piñero-Pérez, Rocío, additional, Reche-López, Diana, additional, Romero-Domínguez, José M., additional, and Sánchez-Alcázar, José Antonio, additional
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- 2023
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16. Additional file 1 of Alpha-lipoic acid supplementation corrects pathological alterations in cellular models of pantothenate kinase-associated neurodegeneration with residual PANK2 expression levels
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Talaverón-Rey, Marta, Álvarez-Córdoba, Mónica, Villalón-García, Irene, Povea-Cabello, Suleva, Suárez-Rivero, Juan M., Gómez-Fernández, David, Romero-González, Ana, Suárez-Carrillo, Alejandra, Munuera-Cabeza, Manuel, Cilleros-Holgado, Paula, Reche-López, Diana, Piñero-Pérez, Rocío, and Sánchez-Alcázar, José A.
- Abstract
Additional file 1. Supplementary figures.
- Published
- 2023
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17. mtUPR Modulation as a Therapeutic Target for Primary and Secondary Mitochondrial Diseases
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Cilleros-Holgado, Paula, primary, Gómez-Fernández, David, additional, Piñero-Pérez, Rocío, additional, Reche-López, Diana, additional, Álvarez-Córdoba, Mónica, additional, Munuera-Cabeza, Manuel, additional, Talaverón-Rey, Marta, additional, Povea-Cabello, Suleva, additional, Suárez-Carrillo, Alejandra, additional, Romero-González, Ana, additional, Suárez-Rivero, Juan Miguel, additional, Romero-Domínguez, Jose Manuel, additional, and Sánchez-Alcázar, Jose Antonio, additional
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- 2023
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18. Alpha-Lipoic acid supplementation corrects pathological alterations in cellular models of pantothenate kinase-associated neurodegeneration with residual PANK2 expression levels
- Author
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Talaverón-Rey, Marta, primary, Álvarez-Córdoba, Mónica, additional, Villalón-García, Irene, additional, Povea-Cabello, Suleva, additional, Suárez-Rivero, Juan M., additional, Gómez-Fernández, David, additional, Romero-González, Ana, additional, Suárez-Carrillo, Alejandra, additional, Munuera-Cabeza, Manuel, additional, Cilleros-Holgado, Paula, additional, Reche-López, Diana, additional, Piñero-Pérez, Rocío, additional, and Alcazar, Jose A Sanchez, additional
- Published
- 2022
- Full Text
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19. Pterostilbene in combination with mitochondrial cofactors improve mitochondrial function in cellular models of mitochondrial diseases
- Author
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Ministerio de Sanidad (España), European Commission, Junta de Andalucía, Suarez-Rivero, Juan M., Pastor-Maldonado, Carmen J., Romero-González, Ana, Gómez-Fernández, David, Povea-Cabello, Suleva, Álvarez-Córdoba, Mónica, Villalón-García, Irene, Talaverón-Rey, Marta, Suárez-Carrillo, Alejandra, Ministerio de Sanidad (España), European Commission, Junta de Andalucía, Suarez-Rivero, Juan M., Pastor-Maldonado, Carmen J., Romero-González, Ana, Gómez-Fernández, David, Povea-Cabello, Suleva, Álvarez-Córdoba, Mónica, Villalón-García, Irene, Talaverón-Rey, Marta, and Suárez-Carrillo, Alejandra
- Abstract
Mitochondrial diseases are genetic disorders caused by mutations in genes in the nuclear DNA (nDNA) and mitochondrial DNA (mtDNA) that encode mitochondrial structural or functional proteins. Although considered “rare” due to their low incidence, such diseases affect thousands of patients’ lives worldwide. Despite intensive research efforts, most mitochondrial diseases are still incurable. Recent studies have proposed the modulation of cellular compensatory pathways such as mitophagy, AMP-activated protein kinase (AMPK) activation or the mitochondrial unfolded protein response (UPRmt) as novel therapeutic approaches for the treatment of these pathologies. UPRmt is an intracellular compensatory pathway that signals mitochondrial stress to the nucleus for the activation of mitochondrial proteostasis mechanisms including chaperones, proteases and antioxidants. In this work a potentially beneficial molecule, pterostilbene (a resveratrol analogue), was identified as mitochondrial booster in drug screenings. The positive effects of pterostilbene were significantly increased in combination with a mitochondrial cocktail (CoC3) consisting of: pterostilbene, nicotinamide, riboflavin, thiamine, biotin, lipoic acid and l-carnitine. CoC3 increases sirtuins’ activity and UPRmt activation, thus improving pathological alterations in mutant fibroblasts and induced neurons.
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- 2022
20. Construcción de un regulador de Watt para el control de un motor de corriente continua
- Author
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Gómez Fernández, David, Feliu Batle, Jorge Juan, Martínez Ruiz, Pablo Alejandro, and Automática, Ingeniería Eléctrica y Tecnología Electrónica
- Subjects
3306.03 Motores Eléctricos ,3313.13 Motores de Combustión Interna (General) ,Equipamiento mecánico ,Energía eléctrica ,Mechanical equipment ,Electric power ,Ingeniería de Sistemas y Automática - Abstract
[SPA]El objetivo del presente proyecto es el diseño y fabricación del regulador de velocidad del ingeniero e inventor James Watt. Este mecanismo, originalmente, nos permitía controlar la velocidad de giro de un motor de vapor, regulando la cantidad de combustible aportada. El reto de este estudio se nos presenta, a la hora de reemplazar el motor de combustión, por un motor eléctrico. [ENG]The objective of this Project is the design and manufacture of the speed controller of engineer and inventor James Watt. This mechanism, originally, allowed us to control the speed of rotation of the steam engine, regulatin the amount of fuel contributed. The retouching of this study is presented, when it comes to replacing the combustión engine, by an electric motor. Escuela Técnica Superior de Ingeniería Industrial Universidad Politécnica de Cartagena
- Published
- 2019
21. Construcción de un regulador de Watt para el control de un motor de corriente continua
- Author
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Feliu Batle, Jorge Juan, Martínez Ruiz, Pablo Alejandro, Automática, Ingeniería Eléctrica y Tecnología Electrónica, Gómez Fernández, David, Feliu Batle, Jorge Juan, Martínez Ruiz, Pablo Alejandro, Automática, Ingeniería Eléctrica y Tecnología Electrónica, and Gómez Fernández, David
- Abstract
[SPA]El objetivo del presente proyecto es el diseño y fabricación del regulador de velocidad del ingeniero e inventor James Watt. Este mecanismo, originalmente, nos permitía controlar la velocidad de giro de un motor de vapor, regulando la cantidad de combustible aportada. El reto de este estudio se nos presenta, a la hora de reemplazar el motor de combustión, por un motor eléctrico. [ENG]The objective of this Project is the design and manufacture of the speed controller of engineer and inventor James Watt. This mechanism, originally, allowed us to control the speed of rotation of the steam engine, regulatin the amount of fuel contributed. The retouching of this study is presented, when it comes to replacing the combustión engine, by an electric motor.
- Published
- 2019
22. Proyecto de construcción : polideportivo en Los Corrales de Buelna
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Gómez Fernández, David, Cañizal Berini, Fernando, and Universidad de Cantabria
- Subjects
Edificio - Abstract
Máster en Ingeniería de Caminos, Canales y Puertos
- Published
- 2017
23. Uso de técnicas de Network Coding y Multipath para la mejora de las comunicaciones sobre redes malladas inalámbricas
- Author
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Gómez Fernández, David, Agüero Calvo, Ramón, and Universidad de Cantabria
- Subjects
Wireless communications ,Wireless mesh networks ,Wireless channel models ,Redes malladas multi-salto ,Multipath TCP (MPTCP) ,Comunicaciones inalámbricas ,Simulación ,TCP ,Network Coding ,Simulation ,Modelos de canal inalámbrico - Abstract
RESUMEN: Partiendo de los problemas que surgen de la combinación de redes inalámbricas y TCP, el objetivo principal de esta Tesis se sitúa en el estudio de diversas técnicas que buscan mejorar el rendimiento de TCP sobre entornos inalámbricos, utilizando dos aproximaciones diferentes: por un lado, se estudiará el comportamiento del protocolo MPTCP, que nace como una versión evolucionada de TCP, que posibilita la transferencia de información a través de varios subflujos de manera simultánea. Aprovechando el hecho de que los dispositivos portátiles incluyen de manera habitual múltiples interfaces, permitiéndoles la conexión a través de diferentes tecnologías, aparece la posibilidad de dividir el tráfico en varios subflujos, lo que permitiría mejorar las prestaciones del TCP tradicional, tanto en su rendimiento como en su robustez. Por otra parte, se utilizará una nueva filosofía en la operación y funcionalidad de los nodos intermedios, los cuales no sólo redirigirán la información sin más, sino que además tendrán la capacidad de procesarla y combinarla, en función de una serie de criterios y restricciones. A estas técnicas se las conoce en la literatura como NC. En concreto, se estudiarán dos soluciones de características opuestas: en primer lugar se combinarán los paquetes pertenecientes a diferentes flujos (NC inter-flujo); por otro lado, como segunda alternativa se contemplará el uso de esquemas de codificación aleatorios para mezclar el tráfico correspondiente a un único flujo. Por otra parte, hay que destacar que la mayor parte de los desarrollos y análisis llevados a cabo en el marco de esta Tesis se han hecho sobre el simulador ns-3 como herramienta básica. Uno de los principales problemas que se les achaca a este tipo de plataformas es que no son capaces de reflejar de manera fidedigna los efectos observados en transmisiones sobre entornos inalámbricos reales, condicionando en gran medida la validez de los resultados obtenidos. Esta Tesis también presenta un exhaustivo análisis del comportamiento de un enlace inalámbrico en un entorno de interiores, basado en el estándar IEEE 802.11. Dicho estudio se utilizará para proponer dos modelos de canal alternativos que, utilizando enfoques diferentes, son capaces de reflejar el comportamiento observado. ABSTRACT: In this PhD we take as a starting point the weak relationship between TCP and Wireless Networks. The main objective of this work focus on the study of different alternatives that could yield to a better behavior than the one achieved by TCP over this sort of hostile links, presenting two rather different approaches: on the first hand, we thoroughly study the performance of the MPTCP protocol, which was conceived as an evolved version of TCP that allows the division of the traffic flow among multiple and simultaneous data subflows. By exploiting the more and more common trend of manufacturers to incorporate more than one physical interface in their devices, the possibility of dividing the load between them is arisen, which might lead to enhance the performance shown by traditional TCP single-flow connections. On the other hand, we deal with one of the most promising routing paradigms, in which intermediate nodes not only just store-and-forward the packets they receive, but also have the capacity to parse and transform the information along the path between the source and the destination. These techniques are commonly referred to in the literature as Network Coding (NC). Namely, we split our analysis into two different NC approaches with rather opposite basis: whilst the first one encodes packets that belong to different TCP connections (inter-flow NC), the second option deals with the joint operation of a random coding scheme to mix the traffic belonging to a single flow, using UDP as the transport level solution. Moreover, it is worth highlighting that the vast majority of the assessments carried out in this PhD have been made over the ns-3 simulation platform. However, one of the main drawbacks that blame this sort of environments is that they are not able to trustworthily reflect all the effects that are observed over real wireless channels, thus notably limiting the validity of their results. In order to address this limitation, this PhD also presents an extensive analysis of the behavior of a real indoor wireless channel based on the IEEE 802.11 standard. Such assessment will be the basis for the configuration of two different wireless channel models which, starting from opposite approaches, are able to adequately mimic the behavior observed over real transmissions.
- Published
- 2015
24. On the design and implementation of a platform to provide seamless vertical handovers for multi-RAT devices
- Author
-
Gómez Fernández, David, Agüero Calvo, Ramón, and Universidad de Cantabria
- Abstract
Máster en Tecnologías de la Información y Comunicaciones en Redes Móviles (TICRM)
- Published
- 2011
25. Diseño de una antorcha en instalaciones de regasificación de GNL
- Author
-
Gómez Fernández, David, Villa Briongos, Javier, and Universidad Carlos III de Madrid. Departamento de Ingeniería Térmica y de Fluidos
- Subjects
Mecánica de fluidos ,Sistemas de seguridad ,Instalaciones de regasificación ,Ingeniería Industrial - Abstract
El porqué de este proyecto fin de carrera, es la necesidad de trasegar y aliviar un caudal de gas natural en una instalación de regasificación en situaciones excepcionales o de emergencia, en las que el resto de sistemas del proceso, no han sido capaces de absorber dicho caudal de gas natural vaporizado. La antorcha es por consiguiente el sistema de seguridad encargado de procesar todo ese excedente de gas natural, evitando además, su emisión directa a la atmósfera, ya que el venteo es sustituido por una combustión. Por lo tanto, este dispositivo, además de tener una función de seguridad, cumple también con una función medioambiental. Con el objetivo de diseñar adecuadamente la antorcha, en base a las especificaciones del cliente, y cumpliendo con la legislación vigente, se ha procedido a calcular las dimensiones básicas del sistema basándose en la radiación térmica máxima de diseño a pie de antorcha, y la presión disponible a la entrada de la misma. Para ello, se han utilizado correlaciones de la fluidomecánica extraídas de la fuente bibliográfica CRANE “Flujo de fluidos en válvulas, accesorios y tuberías”, junto con el procedimiento y recomendaciones que define el estándar “API Recommended Practice 521”. También se ha hecho el cálculo para el nivel de presión acústica propio del funcionamiento de la antorcha, y con el objetivo de cumplir con la legislación de ruido. Para esta parte, se han empleado los fundamentos y ecuaciones de la acústica de la asignatura Mecánica Industrial, de la titulación cursada por el autor del proyecto, además de las correlaciones específicas provenientes del know how del sector específico del fabricante de antorchas. De igual manera, se ha hecho uso de la aplicación del modelo de dispersión estadístico gaussiano ISC3 (Industrial Source Complex Model), para realizar la estimación de las concentraciones en el ambiente de contaminantes producidas por la antorcha, y con la finalidad de cumplir con las directrices medioambientales de la prestigiosa U.S. Environmental Protection Agency. En el presente proyecto, también se han descrito las principales aplicaciones del sistema dentro de las diferentes instalaciones industriales o plantas de proceso, donde son instaladas las antorchas, y se ha hecho hincapié en el funcionamiento de una instalación de regasificación de GNL típica. A continuación, se ha desarrollado una exposición exhaustiva de todo lo referente al sistema antorcha, concretamente sus funciones, los tipos de antorchas existentes en el mercado, sus componentes y diferentes dispositivos anejos, junto con una descripción de los mismos. Se ha incluido también un glosario de términos, para entender el argot del sector que se ha utilizado en el documento. Además, se ha hecho un análisis descriptivo de la influencia de los diferentes parámetros involucrados en el proceso sobre la radiación a nivel de suelo, como son el caudal, la temperatura, el tipo de gas procesado, la geometría de la antorcha, etc. Por último, se ha desarrollado un estudio económico detallado. Ingeniería Técnica en Mecánica
- Published
- 2010
26. Desenvolupament d’una blogosfera
- Author
-
Universitat Politècnica de Catalunya. Departament de Llenguatges i Sistemes Informàtics, Col·legi Oficial d'Enginyers Industrials de Catalunya, Raurell Guxens, Xavier, Daude Ventura, Jordi, Gómez Fernández, David, Universitat Politècnica de Catalunya. Departament de Llenguatges i Sistemes Informàtics, Col·legi Oficial d'Enginyers Industrials de Catalunya, Raurell Guxens, Xavier, Daude Ventura, Jordi, and Gómez Fernández, David
- Abstract
Aquest projecte pretén desenvolupar una blogosfera partint d’una eina base, WordPress. La blogosfera ha de ésser adaptada i dedicada per un col·lectiu de persones dintre d’un àmbit concret, els col·legiats del Col·legi d’Enginyers Industrials de Catalunya. Partint d’un blog normal, tracta de crear un portal web adaptat a les necessitats del col·lectiu abans esmentat. Explica com dur a terme una feina dintre d’un ambient de treball, amb problemes reals a resoldre i amb la mancança d’informació que això comporta. També s’explica el perquè fer-ho amb WordPress i no amb altres eines, com integrar-lo dintre d’un sistema ja implementat i com connectar una eina de blogs a una totalment diferent per tal de transferir informació entre elles.
- Published
- 2011
27. Combinación de técnicas de Network Coding y codificación lineal aleatoria sobre redes malladas inalámbricas
- Author
-
Rodríguez Maza, Eduardo, Agüero Calvo, Ramón, Gómez Fernández, David, and Universidad de Cantabria
- Subjects
Network coding ,Network simulator 3 ,Random linear coding ,UDP ,Wireless mesh network - Abstract
RESUMEN: En este documento se describe el estudio que se ha desarrollado para analizar la influencia de las técnicas de network coding, combinadas con codificación lineal aleatoria, en el rendimiento en servicios de transmisión fiables sobre malladas inalámbricas. Concretamente, se aplicarán sobre un único flujo de datos (intra-flow) y utilizando UDP como protocolo de transporte. Este tipo de técnicas se basan en que los nodos intermedios dejan de tener un papel pasivo, fomentando una mejora del rendimiento e incrementando la robustez de la transmisión. El fuerte crecimiento en el uso de tecnologías inalámbricas ha propiciado constantes avances en este campo. Entre ellos destacan las redes malladas inalámbricas, que se han consolidado como una alternativa barata y sencilla para extender la cobertura de despliegues tradicionales. Sus características hacen que puedan beneficiarse de las ventajas ofrecidas por network coding. Sin embargo, este tipo de técnicas no son aún maduras y no existen numerosos estudios sobre las posibilidades reales de su uso. Para poder conocer los beneficios y problemas que supone el uso de técnicas de network coding, se ha hecho uso de la herramienta ns-3. Tras una extensa campaña de simulaciones, se han observado mejoras, en términos de throughput, de hasta un 200% en comparación con TCP. ABSTRACT: This report presents a study of the benefits brought about by the use of network coding techniques, together with random linear coding, regarding the performance of reliable communication services over wireless mesh networks. In particular, we work with a single data flow (intra-flow) and we use UDP as the transport layer protocol. This kind of techniques foster the intermediate nodes to take a more active role, helping to improve the achieve performance and the reliability of the communications. The remarkable growth of wireless technologies usage has contributed to continuous progresses in this field. An outstanding example is the so-called wireless mesh networks, which have be come a cheap and simple alternative to extend the coverage of traditional network deployments. Their characteristics make them appropriate to assess the advantages offered by network coding techniques. However, this type of solutions are not mature enough and there do not exist many studies on the real possibilities of their performance. In order to understand the benefits and problems related to network coding, we have used the ns-3 simulator. By means of a thorough simulation study, we have assessed throughput improvements up to 200 %, as compared with the legacy TCP. Ingeniería de Telecomunicación
- Published
- 2014
28. Comunicaciones fiables sobre redes inalámbricas mediante la combinación de UDP y codificación lineal aleatoria
- Author
-
Saiz Santos, Ramón, Agüero Calvo, Ramón, Gómez Fernández, David, and Universidad de Cantabria
- Subjects
NS-3 ,Network coding ,Protocolo UDP ,UDP protocol ,Redes inalámbricas ,Wireless networks ,Codificación de red - Abstract
RESUMEN: Durante los últimos años se ha producido un crecimiento exponencial en cuanto a lo que se refiere a las necesidades y exigencias del usuario a la hora de utilizar redes inalámbricas. Esto ha supuesto que vayan surgiendo multitud de técnicas y mecanismos que tratan de mejorar el rendimiento de dichas redes, tratando de acercarse a las prestaciones ofrecidas por las redes cableadas. A lo largo de este documento se presenta un estudio de la influencia que tienen las técnicas de codificación sobre redes inalámbricas, con el fin de conseguir mejoras en el rendimiento, en términos de throughput. En particular se analizará el mecanismo MORE sobre tráfico UDP, con el fin de cuantificar y valorar los beneficios obtenidos mediante la codificación aleatoria de la información por parte del nodo transmisor. Se realizará una comparación entre dichos resultados y los conseguidos con el protocolo TCP. Para analizar los beneficios y posibles inconvenientes de la aplicación de esta técnica, en este proyecto se ha hecho uso de la herramienta NS-3. Tras la implementación de la nueva entidad (MORE), y tras realizar un gran número de simulaciones, se ha observado un incremento del rendimiento respecto a una solución más tradicional, basada en el protocolo TCP. Es importante destacar que, a pesar de que existen diferentes estudios similares, han sido pocos los que se han centrado en redes inalámbricas, ya que la mayoría son trabajos llevados a cabo sobre redes cableadas. ABSTRACT: In the latest years, the needs and requests from the users of wireless networks have experienced an exponential growth. This has brought about the appearance of several new techniques , aimed at improving the performance of such networks, trying to get closer to the performances o ered by wired networks. This project studies the in uence that coding techniques might have over wireless networks, in order to improve their performance. In particular, we carry out an analysis of the MORE mechanism over the UDP protocol, assesing the bene ts of using random coding at transmitter. A comparison between such results and the ones obtained using the legacy TCP protocol will be also presented in this document. In order to analyze the bene ts and potential drawbacks of this technique, we have used the NS-3 tool. After developing the new entity (MORE) and performing a large number of simulations, we have seen observed a performance improvement in comparison with a more traditional solution based on the TCP protocol. It is worth mentioning that, although there ara several similar studies, those have focused on wired networks. Ingeniería de Telecomunicación
- Published
- 2014
29. Mejora del comportamiento del protocolo UDP sobre redes inalámbricas multi-salto a través de técnicas de Network coding
- Author
-
Puente Pomposo, Mario, Agüero Calvo, Ramón, Gómez Fernández, David, and Universidad de Cantabria
- Subjects
NS-3 ,Network coding ,Redes inalámbricas ,Wireless networks ,Codificación de red - Abstract
RESUMEN: En la actualidad existen multitud de técnicas y mecanismos para mejorar el rendimiento en redes de comunicación cableadas. Sin embargo, en la última década, la repercusión de los sistemas inalámbricos obliga a satisfacer la demanda de una calidad cada vez mayor por parte de los usuarios, intentando alcanzar un comportamiento comparable al de las redes cableadas. En este documento se presenta un análisis de la mejora sobre comunicaciones basadas en tráfico UDP al trabajar con técnicas de codificación de red (Network Coding) sobre redes inalámbricas multi-salto. Los nodos intermedios realizan la codificación de información de varios flujos, para enviarla hacia sus destinos correspondientes, logrando un incremento del rendimiento de la transmisión. Los avances tecnológicos en materia de codificación pretenden, además, obtener mejoras respecto a la seguridad de la comunicación. Para analizar los beneficios y problemas de la aplicación de estas técnicas, en este proyecto se ha hecho uso de la herramienta NS-3. Tras la implementación de la nueva entidad, Network Coding, y realizando un alto número de simulaciones sobre varios escenarios, se ha observado un incremento del rendimiento en torno al 50% en canales ideales. ABSTRACT: At present there are several technics and mechanisms to improve efficiency on wi-red communication networks. However, during last decade, the repercussion of wireless systems obliges to satisfy an increasing demand of quality from users, in an attempt of reaching behaviour comparable to wired networks. This document portrays an analysis of the enhancement of communications based on UDP traffic when working using Network Coding techniques over wireless mesh networks. Intermediate nodes make the coding of various flows information, to send it to corres- ponding destination, achieving a transmission capacity upturn. In addition, technological progress in matters of coding expects to obtain improvements in communication security. For the purpose of evaluating the advantages and disadvantages of applying these technics, the NS-3 tool has been used. Following the implementation of the new identity, Network Coding, and making numerous simulations over different scenarios, it has been observed an increase of performance around 50 % in ideal channels. Ingeniería de Telecomunicación
- Published
- 2013
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