61 research outputs found

    Localización de juegos para móvil

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    Aquest article presenta una introducció a la localització de jocs per a mòbil. Es descriuen els reptes que afronta el traductor d'aquest tipus de jocs i s'inclouen exemples d'errors i solucions sobre aspectes de la internacionalització i localització dels jocs.Este artículo ofrece una introducción a la localización de juegos para móvil. Se describen los retos a los que se enfrenta el traductor en la traducción de este tipo de juegos y se ofrecen ejemplos de errores y soluciones sobre aspectos de la internacionalización y localización del juego.This article offers an introduction to the localisation of games for mobile phones. It describes the challenges that translating such games poses for translators and gives examples of errors and solutions related to aspects of game localisation and internationalisation

    Seismic Risk Scenarios in Puerto Principe (Haiti). A Tool for Reconstruction and Emergency Planning

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    The 12 January 2010, an earthquake hit the city of Port-au-Prince, capital of Haiti. The earthquake reached a magnitude Mw 7.0 and the epicenter was located near the town of Léogâne, approximately 25 km west of the capital. The earthquake occurred in the boundary region separating the Caribbean plate and the North American plate. This plate boundary is dominated by left-lateral strike slip motion and compression, and accommodates about 20 mm/y slip, with the Caribbean plate moving eastward with respect to the North American plate (DeMets et al., 2000). Initially the location and focal mechanism of the earthquake seemed to involve straightforward accommodation of oblique relative motion between the Caribbean and North American plates along the Enriquillo-Plantain Garden fault system (EPGFZ), however Hayes et al., (2010) combined seismological observations, geologic field data and space geodetic measurements to show that, instead, the rupture process involved slip on multiple faults. Besides, the authors showed that remaining shallow shear strain will be released in future surface-rupturing earthquakes on the EPGFZ. In December 2010, a Spanish cooperation project financed by the Politechnical University of Madrid started with a clear objective: Evaluation of seismic hazard and risk in Haiti and its application to the seismic design, urban planning, emergency and resource management. One of the tasks of the project was devoted to vulnerability assessment of the current building stock and the estimation of seismic risk scenarios. The study was carried out by following the capacity spectrum method as implemented in the software SELENA (Molina et al., 2010). The method requires a detailed classification of the building stock in predominant building typologies (according to the materials in the structure and walls, number of stories and age of construction) and the use of the building (residential, commercial, etc.). Later, the knowledge of the soil characteristics of the city and the simulation of a scenario earthquake will provide the seismic risk scenarios (damaged buildings). The initial results of the study show that one of the highest sources of uncertainties comes from the difficulty of achieving a precise building typologies classification due to the craft construction without any regulations. Also it is observed that although the occurrence of big earthquakes usually helps to decrease the vulnerability of the cities due to the collapse of low quality buildings and the reconstruction of seismically designed buildings, in the case of Port-au-Prince the seismic risk in most of the districts remains high, showing very vulnerable areas. Therefore the local authorities have to drive their efforts towards the quality control of the new buildings, the reinforcement of the existing building stock, the establishment of seismic normatives and the development of emergency planning also through the education of the population

    Ultrastructural study of retinal development in the turtle Trachemys scripta elegans

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    The present study was conducted by using light and transmission electron microscopy to examine the morphologic development of turtle retina from embryonic stage 18 (S18) to S26 (hatching). Particular attention was paid to the formation of functional structures such as neurites, synapses, photoreceptors, among others, and the moment that chemical synapses appear in the outer and inner plexiform layers. The results show that retinal differentiation in the turtle follows the vitreal to scleral morphological differentiation of retinal cells. Moreover, the central region of the optic cup is most advanced compared to the peripheral parts. Early functional plexiform layers, based on appearance of synapses, precede the complete differentiation of photoreceptors. The first synaptic structures occur in the inner plexiform layer before the outer plexiform layer. Receptor outer segments and first synaptic ribbon in receptor synaptic terminals initiate the differentiation at the same time, but final maturation includes dendritic invaginations of bipolar and horizontal cells in the receptor terminals. We assume that at birth, the turtle retina has achieved the ability to see.This research was supported by University of Alicante VIGROB-186

    Importance and development of psychologist competences on the last year of university students.

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    La presente investigación tuvo como objetivo identificar la importancia y el grado de desarrollo de las competencias profesionales del psicólogo en estudiantes de psicología de último semestre, y comparar los resultados en función del sexo de los estudiantes. Participaron 72 estudiantes de octavo semestre de la licenciatura en psicología de una institución educativa al noroeste de México con una edad promedio de 22 años, 72.22% mujeres y 27.77% hombres, quienes respondieron un instrumento que evalúo la importancia y grado de desarrollo de las competencias profesionales específicas y transversales del psicólogo. Entre los resultados destaca que los estudiantes consideran a todas las competencias como bastante importantes y bastante desarrolladas durante su formación universitaria, reportando la ética y evaluación psicológica como las competencias más importantes, y la ética y competencias transversales como las más desarrolladas. Respecto a la comparación, se encontraron diferencias significativas en el grado de desarrollo de las competencias en función del sexo de los estudiantes, donde las mujeres presentaron mayor grado de desarrollo, en las competencias de evaluación e intervención psicológica

    Therapy Prospects for Mitochondrial DNA Maintenance Disorders

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    Esgotament; Teràpia gènica; MitocondrisMitochondria; Depletion; Gene therapyAgotamiento; Terapia génica; MitocondriasMitochondrial DNA depletion and multiple deletions syndromes (MDDS) constitute a group of mitochondrial diseases defined by dysfunctional mitochondrial DNA (mtDNA) replication and maintenance. As is the case for many other mitochondrial diseases, the options for the treatment of these disorders are rather limited today. Some aggressive treatments such as liver transplantation or allogeneic stem cell transplantation are among the few available options for patients with some forms of MDDS. However, in recent years, significant advances in our knowledge of the biochemical pathomechanisms accounting for dysfunctional mtDNA replication have been achieved, which has opened new prospects for the treatment of these often fatal diseases. Current strategies under investigation to treat MDDS range from small molecule substrate enhancement approaches to more complex treatments, such as lentiviral or adenoassociated vector-mediated gene therapy. Some of these experimental therapies have already reached the clinical phase with very promising results, however, they are hampered by the fact that these are all rare disorders and so the patient recruitment potential for clinical trials is very limited

    Estimación del riesgo sísmico en Puerto Príncipe (Haití) como base para la elaboración de planes de emergencia

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    En este trabajo se realiza una propuesta de cálculo de riesgo sísmico en términos de daño físico para un escenario realista en Puerto Prínicpe (Haití). Los resultados del modelo propuesto se calibran con datos del sismo de enero de 2010

    Efficacy of adeno-associated virus gene therapy in a MNGIE murine model enhanced by chronic exposure to nucleosides

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    Preclinical studies have shown that gene therapy is a feasible approach to treat mitochondrial neurogastrointestinal encephalomyopathy (MNGIE). However, the genetic murine model of the disease (Tymp/Upp1 double knockout, dKO) has a limited functional phenotype beyond the metabolic imbalances, and so the studies showing efficacy of gene therapy have relied almost exclusively on demonstrating correction of the biochemical phenotype. Chronic oral administration of thymidine (dThd) and deoxyuridine (dUrd) to dKO mice deteriorates the phenotype of the animals, providing a better model to test therapy approaches. dKO mice were treated with both dThd and dUrd in drinking water from weaning until the end of the study. At 8 - 11 weeks of age, mice were treated with several doses of adeno-associated virus (AAV) serotype 8 vector carrying the human TYMP coding sequence under the control of different liver-specific promoters (TBG, AAT, or HLP). The biochemical profile and functional phenotype were studied over the life of the animals. Nucleoside exposure resulted in 30-fold higher plasma nucleoside levels in dKO mice compared with non-exposed wild type mice. AAV-treatment provided elevated TP activity in liver and lowered systemic nucleoside levels in exposed dKO mice. Exposed dKO mice had enlarged brain ventricles (assessed by magnetic resonance imaging) and motor impairment (rotarod test); both were prevented by AAV treatment. Among all promoters tested, AAT showed the best efficacy. Our results show that AAV-mediated gene therapy restores the biochemical homeostasis in the murine model of MNGIE and, for the first time, demonstrate that this treatment improves the functional phenotype. This work was funded in part by the Spanish Instituto de Salud Carlos III, and the Generalitat de Catalunya. The disclosed funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript

    Most mitochondrial dGTP is tightly bound to respiratory complex I through the NDUFA10 subunit

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    Biochemistry; Molecular medicineBioquímica; Medicina molecularBioquímica; Medicina molecularImbalanced mitochondrial dNTP pools are known players in the pathogenesis of multiple human diseases. Here we show that, even under physiological conditions, dGTP is largely overrepresented among other dNTPs in mitochondria of mouse tissues and human cultured cells. In addition, a vast majority of mitochondrial dGTP is tightly bound to NDUFA10, an accessory subunit of complex I of the mitochondrial respiratory chain. NDUFA10 shares a deoxyribonucleoside kinase (dNK) domain with deoxyribonucleoside kinases in the nucleotide salvage pathway, though no specific function beyond stabilizing the complex I holoenzyme has been described for this subunit. We mutated the dNK domain of NDUFA10 in human HEK-293T cells while preserving complex I assembly and activity. The NDUFA10E160A/R161A shows reduced dGTP binding capacity in vitro and leads to a 50% reduction in mitochondrial dGTP content, proving that most dGTP is directly bound to the dNK domain of NDUFA10. This interaction may represent a hitherto unknown mechanism regulating mitochondrial dNTP availability and linking oxidative metabolism to DNA maintenance.We thank Dr, Luke Formosa (Department of Biochemistry and Molecular Biology, Monash Biomedicine Discovery Institute, Monash University, Melbourne, Australia) for his valuable advice and assistance on NDUFA10 molecular studies and Dr. Francesc Canals and his team (Proteomics Laboratory, Vall d’Hebron Institute of Oncology [VHIO], Universitat Autònoma de Barcelona, Barcelona, Spain) for their assistance with LC-MS/MS analyses. This work was supported by the Spanish Ministry of Industry, Economy and Competitiveness [grants BFU2014-52618-R, SAF2017-87506, and PID2020-112929RB-I00 to Y.C.], by the Spanish Instituto de Salud Carlos III [grants PI21/00554 and PMP15/00025 to R.M.], co-financed by the European Regional Development Fund (ERDF), and by an NHMRC Project grant to M.R. (GNT1164459)

    A first approach to earthquake damage estimation in Haiti: advices to minimize the seismic risk

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    This study is in the frame of the cooperative line that several Spanish Universities and other foreign partners started with the Haitian government in 2010. According to our studies (Benito et al. in An evaluation of seismic hazard in La Hispaniola, after the 2010 Haiti earthquake, 33rd General Assembly of the European Seismological Commission, Moscow, Russia, 2012) and recent scientific literature, the earthquake hazard in Haiti remains high (Calais et al. in Nat Geosci 3:794–799, 2010). In view of this, we wonder whether the country is currently ready to face another earthquake. In this sense, we estimated several damage scenarios in Port-au-Prince and Cap-Haitien associated to realistic possible major earthquakes. Our findings show that almost 50 % of the building stock of both cities would result uninhabitable due to structural damage. Around 80 % of the buildings in both cities have reinforced concrete structure with concrete block infill; however, the presence of masonry buildings becomes significant (between 25 and 45 % of the reinforced concrete buildings) in rural areas and informal settlements on the outskirts, where the estimated damage is higher. The influence of the soil effect on the damage spatial distribution is evident in both cities. We have found that the percentage of uninhabitable buildings in soft soil areas may be double the percentage obtained in nearby districts located in hard soil. These results reveal that a new seismic catastrophe of similar or even greater consequences than the 2010 Haiti earthquake might happen if the earthquake resilience is not improved in the country. Nowadays, the design of prevention actions and mitigation policies is the best instrument the society has to face seismic risk. In this sense, the results of this research might contribute to define measures oriented to earthquake risk reduction in Haiti, which should be a real priority for national and international institutions.This work was developed thanks to the financial support of the Technical University of Madrid, through the series of projects SISMO-HAITI

    Age-related metabolic changes limit efficacy of deoxynucleoside-based therapy in thymidine kinase 2-deficient mice

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    Thymidine kinase 2 (TK2) catalyses the phosphorylation of deoxythymidine (dThd) and deoxycytidine (dCtd) within mitochondria. TK2 deficiency leads to mtDNA depletion or accumulation of multiple deletions. In patients, TK2 mutations typically manifest as a rapidly progressive myopathy with infantile onset, leading to respiratory insufficiency and encephalopathy in the most severe clinical presentations. TK2-deficient mice develop the most severe form of the disease and die at average postnatal day 16. dThd+dCtd administration delayed disease progression and expanded lifespan of a knockin murine model of the disease. We daily administered TK2 knockout mice (Tk2 KO) from postnatal day 4 with equimolar doses of dThd+dCtd, dTMP+dCMP, dThd alone or dCtd alone. We monitored body weight and survival and studied different variables at 12 or 29 days of age. We determined metabolite levels in plasma and target tissues, mtDNA copy number in tissues, and the expression and activities of enzymes with a relevant role in mitochondrial dNTP anabolism or catabolism. dThd+dCtd treatment extended average lifespan of Tk2 KO mice from 16 to 34 days, attenuated growth retardation, and rescued mtDNA depletion in skeletal muscle and other target tissues of 12-day-old mice, except in brain. However, the treatment was ineffective in 29-day-old mice that still died prematurely. Bioavailability of dThd and dCtd markedly decreased during mouse development. Activity of enzymes catabolizing dThd and dCtd increased with age in small intestine. Conversely, the activity of the anabolic enzymes decreased in target tissues during mouse development. We also found that administration of dThd alone had the same impact on survival to that of dThd+dCtd, whereas dCtd alone had no influence on lifespan. dThd+dCtd treatment recruits alternative cytosolic salvage pathways for dNTP synthesis, suggesting that this therapy would be of benefit for any Tk2 mutation. dThd accounts for the therapeutic effect of the combined treatment in mice. During the first weeks after birth, mice experience marked tissue-specific metabolic regulations and ontogenetic changes in dNTP metabolism-related enzymes that limit therapeutic efficacy to early developmental stages. This study was funded by grants from the Spanish Ministry of Industry, Economy and Competitiveness, the Spanish Instituto de Salud Carlos III, the Fundación Inocente, Inocente, AFM Téléthon and the Generalitat de Catalunya. The disclosed funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript
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