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Nowadays, one of the main death causes in the world is coronary heart disease. This disease narrows the blood flow forming a plaque of cholesterol and fats in artery, known as atherosclerosis. The impact around the world of the disease lead to research into a solution. A very popular treatment is an angioplasty where a coronary stent is implanted to restore the blood flow. First generation stents, bare-metal stent, are permanently in the body and after a while could lead to a thrombosis. The third-generation stent, bioresorbable stent, after repairing the occlusion over time will degrade bi its own, avoiding later complications in the patient while giving the artery the mechanical support as the other generations to prevent a reocclusion. The bioresorbale stents are a game changer as medical treatment for coronary heart disease but it is still needed more research and analysis of the mechanical properties offered by this type of stents. As an advancement in this research, this project works with 3D biodegradable polymer stents. The biodegradable polymer studied were poly-L-lactic acid (PLLA) and poly(L-lactic-co-ε- caprolactone) (PLCL) with three different designs with strut thickness of 90 μm, 130 μm, and 150 μm. To work with the designs was used the CAD software SOLIDWORKS and for the analysis of the mechanical properties was used SOLIDWORKS Simulation. The simulations of this software are based on finite element analysis. The stent designs were studied through a compression tests and crimping and expansion test. Compression test showed where are ubicated the highest stresses, strains, and displacements for each design; being the stent with more peaks shown a better behaviour throughout the tests. In addition, the crimping and expansion tests showed the stent design with lower strut thickness result as a better expansion Hoy en día, una de las principales causas de muerte en el mundo es la enfermedad coronaria. Esta enfermedad estrecha el flujo sanguíneo formando una placa de colesterol y grasas en las arterias, conocida como aterosclerosis. El impacto de la enfermedad en todo el mundo llevó a la investigación de una solución. Un tratamiento muy popular es una angioplastia donde se implanta un stent coronario para restaurar el flujo sanguíneo. Los stents de primera generación, stent metálico, están permanentemente en el cuerpo y después de un tiempo pueden provocar una trombosis. El stent de tercera generación, el stent bioabsorbible, después de reparar la oclusión con el tiempo se degradará por sí solo, evitando complicaciones posteriores en el paciente al mismo tiempo que le da a la arteria el soporte mecánico como las otras generaciones para evitar una reoclusión. Los stents bioabsorbibles son un cambio de panorama en el tratamiento médico para la enfermedad coronaria, pero aún se necesita más investigación y análisis de las propiedades mecánicas que ofrece este tipo de stents. Como avance en esta investigación, este proyecto trabaja con stents de polímeros biodegradables en 3D. Los polímeros biodegradables estudiados fueron ácido poli-L-ácido láctico (PLLA) y poli(L-láctico-co-ε-caprolactona) (PLCL) con tres diseños diferentes con espesores de hilo de 90 μm, 130 μm y 150 μm. Para trabajar con los diseños se utilizó el software CAD SOLIDWORKS y para el análisis de las propiedades mecánicas se utilizó SOLIDWORKS Simulation. Las simulaciones de este software están basadas en análisis de elementos finitos. Los diseños de los stents fueron estudiados mediante pruebas de compresión y crimpado y expansión. La prueba de compresión mostró dónde se ubican los mayores esfuerzos, deformaciones y desplazamientos para cada diseño; siendo el stent con más picos el que mejor se comportó a lo largo de las pruebas. Además, las pruebas de crimpado y expansión mostraron que el diseño del stent con menor grosor de hilo resultó en una mejor expansión Avui en dia una de les principals causes de mort en el món és la malaltia coronària. Aquesta malaltia estreta del fluxe sanguini formant una placa de colesterol i greixos a les artèries, coneguda com a arterioesclerosi. L’impacte de la malaltia en tot el món va dur a terme una investigació d’una solució. Un tractament molt popular és una angioplàstia on s’implanta un stent coronari per restaurar el fluxe sanguini. Els stents de primera generació, stent metàl·lic, estan permanentment en el cos i després d’un temps poden provocar una trombosi. El stent de tercera generació, el stent bioabsorbible, després de reparar la oclusió amb el temps es degradarà per sí sol, evitant complicacions posteriors en el pacient al mateix temps que li dóna a l’artèria el suport mecànic com les altres generacions per evitar una reoclusió. Els stents bioabsorbibles són un canvi de panorama en el tractament mèdic per la malaltia coronària però encara es necessiten més investigacions i anàlisis de les propietats mecàniques que ofereix aquest tipus de stents. A mesura que vagi evolucionant aquesta investigació aquest projecte treballa amb temps de polímers biodegradables en 3D. Els polímers biodegradables estudiats van ser àcid poli-L- àcid làctic (PLLA) i poli(L-làctic-co-ε--caprolactona (PLCL) amb tres dissenys diferents amb gruixos de fil de 90 μm 130 μm i 150 μm. Per treballar amb els dissenys es va fer servir el CAD SOLIDWORKS i per l’anàlisi de les propietats mecàniques es va fer servir SOLIDWORKS Simulation. Les simulacions d’aquest software estan basades en l’anàlisi d’elements finits. Els dissenys dels stents van ser estudiats mitjançant proves de comprensió i crimpat i expansió. La prova de comprensió va mostrar on s’ubicaven els majors esforços, deformacions i desplaçaments per cada disseny; sent el stent amb més pics el que millor es va comportar al llarg de les proves. A més, les proves de grimpat i expansió van mostrar que el disseny del stent amb menor gruix de fil va resultar en una millor expansió

Effective democratic governance rests on the executive’s ability to forge coalitions that can advance policy and sustain the government against challengers. Scholars have long focused on cabinet appointments to understand how executives build coalitions with their legislative allies. In many democracies, however, cabinet appointments at the ministerial level may only represent the tip of the iceberg. We show that administrative political appointees (APAs) beneath the ministerial level constitute one of the most important ways that cooperation between legislative and executive is forged. Leveraging a unique and comprehensive database of an average 2600 Brazilian APAs per year over two decades, we evaluate their effect on coalition unity in critical legislative votes. We demonstrate that these APAs, which we collectively term the “patronage coalition,” have a significant effect on legislative support and thus are a critical tool for presidents. Our results are particularly relevant to a new emphasis in the political science literature on the “toolbox” that presidents utilize to address the challenges of simultaneously maintaining legislative support while implementing policy. These results demonstrate that the patronage coalition is a fundamental tool that should be more widely integrated into models of legislative-executive bargaining.

Las dos últimas crisis (la financiera desencadenada a partir de 2008 y la actual provocada por la COVID-19) han mostrado dos facetas distintas del sistema bancario: mientras que aquella expuso su vulnerabilidad a los riesgos asumidos, esta última ha mostrado su denodado esfuerzo por atenuar los devastadores efectos económicos, a pesar del riesgo que esa política comporta. Sin embargo, en ambos casos subyace la cuestión sobre cómo fortalecer la arquitectura corporativa de los bancos para mejorar la información que proporcionan. En el presente trabajo estudiamos la relación existente entre la configuración del consejo de administración y la transparencia contable (entendida como reconocimiento del riesgo a través de la dotación a las provisiones por préstamos incobrables) de una muestra de 1.352 bancos de 52 países entre 2000 y 2019. Obtenemos una relación con el tamaño del consejo en forma de U invertida, coherente con la idea de un entorno óptimo del número de consejeros. Asimismo, encontramos un efecto positivo de la independencia, de la permanencia y de la diversidad (en términos de presencia femenina) de los consejos.

Early hematopoiesis is a continuous process in which hematopoietic stem and progenitor cells (HSPCs) gradually differentiate toward specific lineages. Aging and myeloid malignant transformation are characterized by changes in the composition and regulation of HSPCs. In this study, we used single-cell RNA sequencing (scRNA-seq) to characterize an enriched population of human HSPCs obtained from young and elderly healthy individuals.Based on their transcriptional profile, we identified changes in the proportions of progenitor compartments during aging, and differences in their functionality, as evidenced by gene set enrichment analysis. Trajectory inference revealed that altered gene expression dynamics accompanied cell differentiation, which could explain aging-associated changes in hematopoiesis. Next, we focused on key regulators of transcription by constructing gene regulatory networks (GRNs) and detected regulons that were specifically active in elderly individuals. Using previous findings in healthy cells as a reference, we analyzed scRNA-seq data obtained from patients with myelodysplastic syndrome (MDS) and detected specific alterations of the expression dynamics of genes involved in erythroid differentiation in all patients with MDS such as TRIB2. In addition, the comparison between transcriptional programs and GRNs regulating normal HSPCs and MDS HSPCs allowed identification of regulons that were specifically active in MDS cases such as SMAD1, HOXA6, POU2F2, and RUNX1 suggesting a role of these transcription factors (TFs) in the pathogenesis of the disease.In summary, we demonstrate that the combination of single-cell technologies with computational analysis tools enable the study of a variety of cellular mechanisms involved in complex biological systems such as early hematopoiesis and can be used to dissect perturbed differentiation trajectories associated with perturbations such as aging and malignant transformation. Furthermore, the identification of abnormal regulatory mechanisms associated with myeloid malignancies could be exploited for personalized therapeutic approaches in individual patients.

A questão racial desempenha um papel estruturante e central no conjunto das desigualdades da sociedade brasileira, como tem sido fartamente documentado (Ipea, s.d.; Ipea e FBSP, 2018; Ipea e Seppir, 2014; Marcondes et al., 2013; Paixão et al., 2010; Silva, 2012). Apesar de o ingresso no setor público exigir, em sua maioria, concurso público – o que poderia levar a pensar que este setor estaria mais protegido dessas desigualdades que estruturam a sociedade e o mercado de trabalho –, elas também se manifestam neste espaço. O acesso, progressão e promoção nas carreiras e cargos, especialmente nos postos de maior prestígio e comando, frequentemente são desfavoráveis à população negra, constituída por pretos e pardos (Silva e Silva, 2014). No início dos anos 2000, implementaram-se as primeiras políticas de ação afirmativa no país. Embora o foco dessas políticas – e do debate público – tenha se voltado para as instituições públicas de ensino superior, nesse período também se difundiram programas de reserva de vagas para negros em concursos públicos. Em 2012, já havia mais de quarenta iniciativas no país, entre estados e municípios (Volpe e Silva, 2016). Cerca de uma década após as primeiras iniciativas, o governo federal implementou iniciativa similar, destinando 20% das vagas em concursos públicos para a população negra, por meio da Lei n° 12.990/2014. Atualmente, medidas equivalentes são adotadas em todos os Poderes e níveis federativos. Após anos de implementação, a exemplo da lei federal citada, há poucas avaliações sobre os resultados alcançados. Com vistas a contribuir para reflexões sobre a implementação do sistema de reserva de vagas para negros no governo federal e, especialmente, sobre a representação da população negra no funcionalismo, esta Nota Técnica apresenta a trajetória e os aspectos da distribuição racial dos postos de trabalho, principalmente no quadro dos servidores civis ativos do Poder Executivo federal (civil). Para tanto, explora dados do Sistema Integrado de Administração de Recursos Humanos (Siape), responsável pela gestão de informações de pessoal no Executivo federal. Apenas recentemente, foram disponibilizadas algumas consultas públicas, ainda limitadas, sobre a cor e raça dos servidores federais. Desse modo, o texto também visa, ao descrever os dados, ampliar o conhecimento público e estimular maior incorporação do tema racial na análise da composição do funcionalismo brasileiro. Por essa razão, a nota tem cunho exploratório e descritivo, com o intento de apresentar um panorama inicial e indicativos para análises futuras. Além desta introdução, o texto conta com uma seção com informações gerais sobre o funcionalismo público, seguida de detalhamentos de alguns dos dados disponíveis no Siape com desagregação por cor ou raça. Por fim, são apresentadas considerações finais e sugestões para novos estudos.

Neste capítulo, analisamos dados sobre a burocracia de alto escalão, utilizando métricas e séries mais detalhadas que aquelas empregadas em Lopez et al. (2015). Tais dados, a nosso ver, contribuem para o debate sobre a lógica de funcionalismo do presidencialismo brasileiro.

The paper is aimed to analyse the most recent and relevant research on boards of directors in BRIC. Existent reviews on the board of directors do not focus on BRIC and do not consider the specifics of their corporate governance model. Therefore, the current review fills this gap by analysing 111 research papers from Scopus/Web of Science published between 2015 and 2020. Firstly, we provide a content analysis of abstracts to find the most frequent research topics and compare them to the developed countries’ studies. Secondly, based on the content analysis findings, we provide a qualitative analysis of three research directions: board composition, social capital, and board functioning, divided further into ten smaller research topics. Thirdly, we compare the research output with the developed countries’ studies and the statistics provided by the Spencer Stuart Board Indexes to analyse whether they are coherent. The results confirm the topicality of board research in BRIC and overlapping topics between the BRIC and the more developed countries. As a result, we formulate a research agenda for further studies on boards in BRIC.

Zika virus (ZIKV) establishes persistent infections in multiple human tissues, a phenomenon that likely plays a role in its ability to cause congenital birth defects and neurological disease. Multiple nonstructural proteins encoded by ZIKV, in particular NS5, are known to suppress the interferon (IFN) response by attacking different steps in this critical antiviral pathway. Less well known are the potential roles of structural proteins in affecting the host immune response during ZIKV infection. Capsid proteins of flaviviruses are of particular interest because a pool of these viral proteins is targeted to the nuclei during infection and, as such, they have the potential to affect host cell gene expression. In this study, RNA-seq analyses revealed that capsid proteins from six different flaviviruses suppress expression of type I IFN and IFN-stimulated genes. Subsequent interactome and in vitro ubiquitination assays showed that ZIKV capsid protein binds to and prevents activating ubiquitination of RIG-I CARD domains by TRIM25, a host factor that is important for the induction arm of the IFN response. The other flavivirus capsid proteins also interacted with TRIM25, suggesting that these viral proteins may attenuate antiviral signaling pathways at very early stages of infection, potentially even before nonstructural proteins are produced.

Mayaro virus (MAYV) is an emerging mosquito-transmitted virus that belongs to the genus Alphavirus within the family Togaviridae. Humans infected with MAYV often develop chronic and debilitating arthralgia and myalgia. The virus is primarily maintained via a sylvatic cycle, but it has the potential to adapt to urban settings, which could lead to large outbreaks. The interferon (IFN) system is a critical antiviral response that limits replication and pathogenesis of many different RNA viruses, including alphaviruses. Here, we investigated how MAYV infection affects the induction phase of the IFN response. Production of type I and III IFNs was efficiently suppressed during MAYV infection, and mapping revealed that expression of the viral non-structural protein 2 (nsP2) was sufficient for this process. Interactome analysis showed that nsP2 interacts with DNA-directed RNA polymerase II subunit A (Rpb1) and transcription initiation factor IIE subunit 2 (TFIIE2), which are host proteins required for RNA polymerase II-mediated transcription. Levels of these host proteins were reduced by nsP2 expression and during infection by MAYV and related alphaviruses, suggesting that nsP2-mediated inhibition of host cell transcription is an important aspect of how some alphaviruses block IFN induction. The findings from this study may prove useful in design of vaccines and antivirals, which are currently not available for protection against MAYV and infection by other alphaviruses.

Resumo Quantos são e a quais partidos estão filiados os nomeados para os cargos do alto e médio escalão da burocracia federal brasileira? Há diferenças entre mandatos presidenciais? Para responder essas perguntas, construímos uma base de dados inédita referente aos filiados a partidos políticos em cargos de direção e assessoramento superior (DAS). Nossa análise descritiva aponta que a proporção de filiados aumentou nos governos do Partido dos Trabalhadores (PT) e é maior entre nomeados sem vínculo com o setor público. A concentração de poder entre os partidos - principalmente entre o partido presidencial e os demais - variou de modo significativo entre presidentes. O controle partidário sobre os nomeados filiados é mais brando nos cargos de nível intermediário e maior nos níveis superiores. Entretanto, os filiados são minoria, mesmo nos cargos de mais alto poder político-administrativo. Por isso, sugerimos que, possivelmente, as redes de conexão política que definem os quadros da burocracia decisória também se constroem por meios extrapartidários e compreendê-las se mostra decisivo para dimensionar o peso da política partidária na burocracia ministerial e reinterpretar como o Poder Executivo constrói e gerencia a coalizão de governo e seu apoio no Poder Legislativo. Resumen ¿Cuántos son y a qué partidos están afiliados los nominados para los puestos de rango superior y medio de la burocracia federal brasileña? ¿Hay diferencias entre los mandatos presidenciales? Para responder a estas preguntas, construimos una base de datos inédita referente a los afiliados a partidos políticos que ocupan cargos directivos y de asesoramiento superior (DAS). Nuestro análisis descriptivo muestra que la proporción de afiliados aumentó en los gobiernos del Partido de los Trabajadores (PT) y es mayor entre los nominados sin vínculo con el sector público. La concentración de poder entre los partidos -principalmente entre el partido presidencial y los demás- varió de modo significativo entre presidentes. El control del partido sobre los nominados afiliados es más moderado en los cargos de nivel medio y mayor en los rangos superiores. Sin embargo, los afiliados son minoría, incluso en los puestos de mayor poder político-administrativo. Por lo tanto, sugerimos que posiblemente las redes de conexión política que definen a los cuadros de la burocracia decisoria también se construyan por medios extrapartidarios, y comprenderlas es decisivo para dimensionar el peso de la política partidaria en la burocracia ministerial y reinterpretar cómo el Poder Ejecutivo construye y administra la coalición de gobierno y su apoyo en el Poder Legislativo. Abstract How many are the top and middle-level Brazilian federal bureaucracy appointees, and to which party are they affiliated? Are there differences among presidential mandates regarding the number of these professionals and their party affiliation? This study seeks to answer these questions, by building a new database that gathers the number of party-affiliated public officials that were appointed to Cargos de Direção e Assessoramento Superior (DAS) (position of director and high level consultant). Descriptive analysis found that the proportion of party-affiliated among appointees increased during the Workers’ Party (PT) governments and higher among appointed professionals that were not civil servant. The power-sharing among parties - mainly between the party of the president and the others - varies significantly according to the government. The partisan control over appointees is milder in middle-level and stronger at top-level positions. However, a minority of appointees are party members, even among the top-level bureaucracy. Therefore, we suggest that the political networks go beyond the party affiliations. To understand these networks it is necessary to reassess the role of party politics in shaping the executive agenda and enable reinterpretation of how presidents build and manage the government coalition and the support to their agenda in the legislative arena.

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is the causative agent of the ongoing coronavirus disease 2019 (COVID-19) pandemic. While previous studies have shown that several SARS-CoV-2 proteins can antagonize the interferon (IFN) response, some of the mechanisms by which they do so are not well understood. In this study, we describe two novel mechanisms by which SARS-CoV-2 blocks the IFN pathway. Type I IFNs and IFN-stimulated genes (ISGs) were poorly induced during SARS-CoV-2 infection, and once infection was established, cells were highly resistant to ectopic induction of IFNs and ISGs. Levels of two key IFN signaling pathway components, Tyk2 and STAT2, were significantly lower in SARS-CoV-2-infected cells. Expression of nonstructural protein 1 (NSP1) or nucleocapsid in the absence of other viral proteins was sufficient to block IFN induction, but only NSP1 was able to inhibit IFN signaling. Mapping studies suggest that NSP1 prevents IFN induction in part by blocking IRF3 phosphorylation. In addition, NSP1-induced depletion of Tyk2 and STAT2 dampened ISG induction. Together, our data provide new insights into how SARS-CoV-2 successfully evades the IFN system to establish infection. IMPORTANCE SARS-CoV-2 is the causative agent of COVID-19, a serious disease that can have a myriad of symptoms from loss of taste and smell to pneumonia and hypercoagulation. The rapid spread of SARS-CoV-2 can be attributed in part to asymptomatic transmission, where infected individuals shed large amounts of virus before the onset of disease. This is likely due to the ability of SARS-CoV-2 to effectively suppress the innate immune system, including the IFN response. Indeed, we show that the IFN response is efficiently blocked during SARS-CoV-2 infection, a process that is mediated in large part by nonstructural protein 1 and nucleocapsid. Our study provides new insights on how SARS-CoV-2 evades the IFN response to successfully establish infection. These findings should be considered for the development and administration of therapeutics against SARS-CoV-2.

Myelodysplastic syndromes (MDS) are clonal hematopoietic stem cell (HSC) malignancies characterized by ineffective hematopoiesis with increased incidence in elderly individuals. Genetic alterations do not fully explain the molecular pathogenesis of the disease, indicating that other types of lesions may play a role in its development. In this work, we analyzed the transcriptional lesions of human HSCs, demonstrating how aging and MDS are characterized by a complex transcriptional rewiring that manifests as diverse linear and non-linear transcriptional dynamisms. While aging-associated lesions seemed to predispose elderly HSCs to myeloid transformation, disease-specific alterations may be involved in triggering MDS development. Among MDS-specific lesions, we detected the overexpression of the transcription factor DDIT3. Exogenous upregulation of DDIT3 in human healthy HSCs induced an MDS-like transcriptional state, and a delay in erythropoiesis, with an accumulation of cells in early stages of erythroid differentiation, as determined by single-cell RNA-sequencing. Increased DDIT3 expression was associated with downregulation of transcription factors required for normal erythropoiesis, such as KLF1, TAL1 or SOX6, and with a failure in the activation of their erythroid transcriptional programs. Finally, DDIT3 knockdown in CD34+ cells from MDS patients was able to restore erythropoiesis, as demonstrated by immunophenotypic and transcriptional profiling. These results demonstrate that DDIT3 may be a driver of MDS transformation, and a potential therapeutic target to restore the inefficient erythropoiesis characterizing these patients. KEY POINTSO_LIHuman HSCs undergo a complex transcriptional rewiring in aging and MDS that may contribute to myeloid transformation. C_LIO_LIDDIT3 overexpression induces a failure in the activation of erythroid transcriptional programs, leading to inefficient erythropoiesis. C_LI