3,969 research outputs found

    Pay-Roll Contribution Financed Social Protection Programs in Uruguay

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    In this paper we analyze the recent performance, perspectives and some policy options for two public social security programs in Uruguay: pensions and unemployment insurance. We review the impact of these programs on public expenditure, including recent and expected future trends, and on income inequality. Performing microsimulations, we evaluate the fiscal impact, and in some cases the equity impact, of some policy options.Pensions, Unemployment insurance, Inequality

    Protección y productividad: Causas y consecuencias de aislar sectores en una economía pequeña.

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    This paper aims to identify the productive sectors that can be isolated from international competition, analyzing the impact on productivity arising from a trade liberalization process. We focused on the case of Uruguay and select a basket of goods that show signs of not being competitive on a non-national scale and, at the same time, have a protection tool that takes the form of non-tariff barriers. In turn, we analyze the effects of protection on sector productivity through a difference-in-difference approach, finding that domestic protection in a context of economic liberalization has a negative impact on firms' productivity. Finally, a quick analysis from the political economy reveals that there are winners and losers in the process of trade liberalization. This makes the exclusion of sensitive sectors a viable mechanism for an opening that otherwise would not be a political equilibrium.trade protection, non–tariff barriers, productivity, difference in–difference model

    Sistema de enseñanza/aprendizaje inteligente para grafos

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    La teoría de grafos es un tema de estudio de la Matemática Discreta que por su importancia está presente en asignaturas de la carrera Ciencia de la Computación. Dificultades presentadas con respecto a su aprendizaje, han conducido al diseño e implementación de un Sistema de Enseñanza/Aprendizaje Inteligente (SEAI) que aborde esta temática. Los SEAI se caracterizan por aplicar técnicas de Inteligencia Artificial (IA) al desarrollo de sistemas de enseñanza asistida por computadoras, donde el término “inteligente” se asocia a la capacidad del sistema de adaptarse dinámicamente al desarrollo del aprendizaje del estudiante. El sistema para Grafos ha sido implementado en la Herramienta computacional para Elaborar Sistemas de Enseñanza/Aprendizaje Inteligentes (HESEI), la cual además de utilizar técnicas de IA emplea Mapas Conceptuales. Con la combinación de ambos recursos se logra la adaptación del SEAI con mayor precisión según las características del alumno. Como resultado de este trabajo se obtuvo un Sistema de Enseñanza/Aprendizaje Inteligente para la enseñanza de Grafos, específicamente en lo que se refiere a la terminología básica y ejemplos. El sistema obtenido se ha probado con estudiantes de segundo año de la carrera de Ciencias de la Computación en la Facultad de Matemática, Física y Computación de la Universidad Central de Las Villas

    Centro Comunitário do Mocotó

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    TCC (graduação) - Universidade Federal de Santa Catarina. Centro Tecnológico. ArquiteturaO presente trabalho desenvolve um projeto arquitetônico para um Centro Comunitário no Morro do Mocotó, Florianópolis - SC. Para a elaboração do projeto foi realizada uma breve pesquisa sobre a história do Mocotó e estudos urbanísticos do local e seu entorno imediato. Junto ao líder comunitário que acompanhou e auxiliou o projeto, foi desenvolvida uma metodologia baseada no projeto participativo, visando a colaboração dos moradores no processo de construção coletiva de projetação por meio de oficinas realizadas na comunidade. Foram estudados diferentes terrenos, realizadas visitas e uma oficina. Como produto final, foi entregue um estudo preliminar do projeto elaborado com a comunidade, que servirá de base para as próximas oficinas na busca de adequar o estudo para a realidade, as demandas e desejos dos moradores do Morro do Mocotó

    Searching for nuclear export elements in hepatitis D virus RNA.

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    AIM To search for the presence of cis elements in hepatitis D virus (HDV) genomic and antigenomic RNA capable of promoting nuclear export. METHODS We made use of a well characterized chloramphenicol acetyl-transferase reporter system based on plasmid pDM138. Twenty cDNA fragments corresponding to different HDV genomic and antigenomic RNA sequences were inserted in plasmid pDM138, and used in transfection experiments in Huh7 cells. The relative amounts of HDV RNA in nuclear and cytoplasmic fractions were then determined by real-time polymerase chain reaction and Northern blotting. The secondary structure of the RNA sequences that displayed nuclear export ability was further predicted using a web interface. Finally, the sensitivity to leptomycin B was assessed in order to investigate possible cellular pathways involved in HDV RNA nuclear export. RESULTS Analysis of genomic RNA sequences did not allow identifying an unequivocal nuclear export element. However, two regions were found to promote the export of reporter mRNAs with efficiency higher than the negative controls albeit lower than the positive control. These regions correspond to nucleotides 266-489 and 584-920, respectively. In addition, when analyzing antigenomic RNA sequences a nuclear export element was found in positions 214-417. Export mediated by the nuclear export element of HDV antigenomic RNA is sensitive to leptomycin B suggesting a possible role of CRM1 in this transport pathway. CONCLUSION A cis-acting nuclear export element is present in nucleotides 214-417 of HDV antigenomic RNA.publishersversionpublishe

    Materia prima

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    El proceso de escritura de este trabajo de grado me ha llevado a tan diversos paisajes como la obra misma, el conocer cómo se enraízan y entrelazan los hilos de mi proceso artístico, incluso desde mi niñez, me lleva a pensar, quizás muy soñadoramente, que el destino ha conspirado de cierta forma desde mi nacimiento para realizar esta obra que me he propuesto, sin completa seguridad o certeza en un principio, pero que ahora siento sólida. Sólida aunque flote en campos efímeros como los del recuerdo o la memoria.Maestro (a) en Artes VisualesPregrad

    Evidenciação das Compras Públicas nos Websites das Instituições Públicas de Ensino Superior da Região Sudeste

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    The growing advance of information and communication technologies (ICT) has provided a new way for society to develop. This advance has changed the population's access to information, making it easier and faster. These advances have also changed the performance of Public Administration bodies that have been charged for greater transparency in the activities carried out by public managers, including the disclosure of public procurement. Therefore, the objective of this study is to identify and analyze the degree of transparency in the disclosure of public purchases in the institutional websites of the Public Institutions of Higher Education (HEIs) located in the Southeast region of the country. So as to develop the present research, the checklist model developed and employed by Soares and Vicente (2011) and Soares (2013) was applied, focusing on the information relating to public purchases presented on the websites of public HEIs in the Southeast region. The sample of the study is restricted to those institutions that disclose information as to public purchases on the websites, twelve (12) HEIs were used. The methodology adopted for the research consists in a descriptive study of a qualitative-quantitative approach, by means of documentary research. It was verified in the analysis carried out that few institutions have a transparency portal on the institutional site. Despite the fact that legislation demands greater transparency in public procurement, the transparency of the HEIs surveyed in the Southeast is low, having a percentage of less than 50% of purchases disclosed by most institutions.Trabalho de Conclusão de Curso (Graduação)O avanço crescente das tecnologias de informação e comunicação (TIC) tem proporcionado uma nova forma de a sociedade se desenvolver, alterando o acesso da população às informações, tornando-o mais fácil e rápido. Esses avanços modificaram também a atuação dos órgãos da Administração Pública que passaram a ser cobrados quanto à maior transparência nas atividades desempenhadas pelos gestores públicos, inclusive, na divulgação das compras públicas. Assim, o objetivo deste estudo é identificar e analisar o grau de transparência na divulgação de compras públicas nos websites institucionais das Instituições Públicas de Ensino Superior (IPES) da região sudeste. Para o desenvolvimento da presente pesquisa, aplicou-se o modelo de checklist desenvolvido e empregado por Soares e Vicente (2011) e Soares (2013), focando nas informações sobre compras públicas apresentadas nos sites das IPES da região sudeste. A amostra do estudo se restringe àquelas instituições que divulgam nos websites informações sobre as compras públicas, sendo que a amostra final foi composta por doze IPES. A metodologia adotada para a pesquisa consiste em um estudo descritivo de abordagem quali-quantitativa por meio da pesquisa documental. Verificou-se, na análise realizada, que são poucas as instituições que possuem um portal de transparência no site institucional, tendo sido evidenciado ainda que, apesar da legislação exigir uma maior transparência nas compras públicas, a transparência das IPES pesquisadas localizadas na região sudeste é baixa, apresentando, inclusive,percentual menor que 50% de evidenciação de compras na maioria das instituições

    Uncovering and Functional Analysis of Novel Genes and Potential Genetic Modifiers for Neuromuscular Disorders

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    The inherited Neuromuscular Disorders (NMDs) is an umbrella term that encompasses a plethora of diseases that affect the functioning of the muscles and/or their underlying nervous system control. Although individually uncommon, NMDs collectively are no longer considered rare diseases. Only in Europe, approximately 300,000 people are yearly diagnosed with one NMD. The diagnosis of a neuromuscular condition –successful in less than 50% of the cases- is often devastating to patients and their relatives. No cure is available for most of these disorders, and the few available treatments will at best delay disease progression. To find treatments and to develop methods for the early diagnosis of NMDs is a goal of highest importance, and the recent advances in the NGS technologies are the platform to reach this objective. Particularly, the implementation of WES has not only minimized the time and costs of genetic diagnostics but also provided unique opportunities for the exploration of gene function in NMDs pathogenesis. The uppermost goal of this PhD project was to identify and characterize novel NMDs-causative genes. Thereby, two novel NMD-causative genes were investigated in this thesis. First, CHP1 (Calcineurin Homologous Protein-1) was identified as a novel causing gene of Autosomal Recessive Cerebellar Ataxia (ARCA) and second, VAChT (Vesicular Acetylcholine Transporter, encoded by SLC18A3) was analysed in the context of distal Hereditary Motor Neuropathy (dHMN). Following a combination of WES and linkage analysis, we identified a biallelic 3-bp deletion (p.K19del) in CHP1 that co-segregates with a complex ARCA in two siblings of a consanguineous family exhibiting motor neuropathy, cerebellar atrophy and spastic paraparesis. CHP1 was selected as a top disease candidate since: (I) the mutation affects an amino acid highly conserved across species, (II) a point mutation in murine Chp1, causing aberrant splicing and reduced full-length Chp1 transcripts, leads to Purkinje cells loss and ataxia, (III) CHP1 assists posttranscriptional glycosylation and membrane localization of NHE1, a major neuronal Na+/H+ exchanger, (IV) KO of mouse Nhe1 cause ataxia and loss-of-function mutation in NHE1 (encoded by SLC19A1) cause ataxia-deafness Lichtenstein-Knorr syndrome (LINKS). Therefore, we hypothesized that a mutation in CHP1, as a crucial regulator of NHE1, could impair expression and targeting of the exchanger resembling the pathogenesis in mice and humans. To further uncover other families carrying CHP1 mutations, we performed a focused screening for CHP1 variants in two large ARCA and NMD cohorts (approximately 1000 exomes). No additional variants fulfilling or selection criteria were found, which emphasizes on the scarcity of CHP1 variants and the reduced tolerability of CHP1 for mutations. With the purpose to assess the functional consequences of the CHP1-K19del mutation on protein function, size exclusion chromatography (SEC), protein fractionation, 3D-protein modelling, fluorescence microscopy and in vivo zebrafish modelling were performed. We demonstrated that mutant CHP1 fails to integrate into functional protein complexes and is prone to aggregate, thereby leading to diminished levels of soluble CHP1 and reduced membrane targeting of NHE1 both in neuronal and non-neuronal cells. To analyze the pathogenic consequences of the hypomorphic CHP1-K19del mutation in vivo, we used morpholinos (MOs) to inhibit chp1 translation in zebrafish. Closely resembling the clinical features of the ARCA-affected siblings, chp1 downregulation in zebrafish led to cerebellar hypoplasia, Caudal Primary Motor Neuron (CaP-MN) defects and spastic trunk movements. All defects were ameliorated by co-injection with WT, but not mutant, human CHP1 mRNA, hence demonstrating both the specificity of the chp1-MO-induced phenotypes and validating the effect of CHP1-K19del on protein expression and/or function in vivo. Altogether, our results identified CHP1 as a novel ataxia-causative gene in humans, further expanding the spectrum of ARCA-causative loci, and highlight the crucial role of NHE1 within the pathogenesis of these disorders. Moreover, we conducted functional analyses to ascertain the functional basis of a dHMN presented by a family with cranial nerves palsy and vocal cord paresis as an initial feature of a non-progressive infantile onset dominant dHMN. WES analysis of this family led to the identification of a de novo dominant missense mutation (c.439 G>A, p.D147N) in VAChT. The mutation occurred first in the affected mother and was inherited by her affected daughter. VAChT controls the storage of the neurotransmitter Acetylcholine (ACh) by synaptic vesicles, hence it plays a fundamental role in cholinergic neurotransmission and therefore, in the plethora of processes reliant on it, which include: neuronal development and maturation, synaptic transmission and plasticity, patterning of the neuromuscular junction (NMJ), among others. The potential effect of the D147N mutation on VAChT subcellular distribution was analysed in neuron-like NSC-34 cells transiently overexpressing WT or mutant VAChT-GFP tagged proteins. No significant differences were observed in protein expression or localization, thus a detrimental effect of VAChT-D147N mutation at this level was not possible. This prompted us to further examine potential defects either in MN development and axonal outgrowth. Capitalizing once again on the advantages of the zebrafish for the modelling of human neurodegenerative disorders and further considering the evolutionary conservation of both VAChT and the D147 residue across species, the effect of WT and VAChT-D147N OE on CaP-MN outgrowth was analysed in detail. Although our findings were not conclusive at discerning the pathogenicity of the VAChT–D147N in vivo, we observed an axonal migration phenotype that could potentially underlie impairments at the NMJ level. In the light of the novel association of VAChT mutations as causative of myasthenia syndromes, follow-up studies will be performed in order to conclusively confirm the pathogenicity of the VAChT-D147N in a CaP-MN-independent context. The biological function of CHP1 was of further relevance within the scope of this doctoral project, since CHP1 is currently subject of study as potential modifier of Spinal Muscular Atrophy (SMA). Pre-existing evidence from our research group indicates that Chp1 downregulation –within a certain threshold- restores neurite outgrowth and impaired endocytosis (a key pathway disturbed in SMA) in Smn1-depleted NSC-34 cells. Thereupon, this thesis further aimed to validate reduction of Chp1 as potential SMA protective modifier in a zebrafish model of SMA, as a first in vivo approach. Here, we demonstrate that Chp1 downregulation ameliorates the CaP-MN axonal outgrowth defects of Smn-deficient fish larvae. These findings are in concordance with prior validation studies of two other human SMA modifiers –PLS3 and NCALD- in zebrafish, which despite their different function and mode of action (upregulation or downregulation, respectively) exert similar effects on CaP-MN morphology whereby restoring the CaP-MN phenotype of smn morphants in a highly comparable range. Altogether, our findings together with the preliminary findings aforementioned, strongly support CHP1 reduction as a promising therapeutic target for a combinatorial treatment, i.e. together with SMN restoration, counteracting SMA pathology

    Estrategia de adquisición en compras públicas: ¿cómo reducir el precio pagado por el Estado? El caso de Uruguay

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    El objetivo central del sistema de contratación pública es maximizar la eficiencia y garantizar la transparencia en el uso de los fondos públicos. El precio pagado por las adquisiciones públicas constituye una dimensión fundamental de la eficiencia. En el presente documento se analizan los impactos de la estrategia de adquisición pública en el precio pagado por los bienes y servicios que el Estado, en particular la Administración Central, adquiere en forma habitual. Se propone un modelo de determinantes de eficiencia de las compras públicas basado en los desarrollos de Borges de Oliveira, A., Fabregas, A. & Fazekas, M. (2019) que estima los efectos sobre el precio pagado de distintas variables vinculadas al proceso de adquisición que son controladas por el comprador público: tipo de procedimiento, plazo de convocatoria, costo de los pliegos, período del año en que se adquiere y utilización de la plataforma electrónica. Se utilizan datos oficiales de compras públicas de Uruguay para el período 2014-2019. El análisis se centra exclusivamente en la adquisición de bienes y servicios relativamente homogéneos, donde el precio corriente es una variable relevante en la decisión de adquisición. Los resultados muestran ahorros significativos si se opta por procedimientos de compra ágiles y abiertos, plazos suficientes de convocatoria, procedimiento electrónico para oferta en línea y si se suaviza la estacionalidad temporal de la demanda trasladando adquisiciones desde el final del año hacia el tercer trimestre
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