Evolution of New cis-Regulatory Motifs Required for Cell-Specific Gene Expression in Caenorhabditis

Patterning of C. elegans vulval cell fates relies on inductive signaling. In this induction event, a single cell, the gonadal anchor cell, secretes LIN-3/EGF and induces three out of six competent precursor cells to acquire a vulval fate. We previously showed that this developmental system is robust to a four-fold variation in lin-3/EGF genetic dose. Here using single-molecule FISH, we find that the mean level of expression of lin-3 in the anchor cell is remarkably conserved. No change in lin-3 expression level could be detected among C. elegans wild isolates and only a low level of change-less than 30%-in the Caenorhabditis genus and in Oscheius tipulae. In C. elegans, lin-3 expression in the anchor cell is known to require three transcription factor binding sites, specifically two E-boxes and a nuclear-hormone-receptor (NHR) binding site. Mutation of any of these three elements in C. elegans results in a dramatic decrease in lin-3 expression. Yet only a single E-box is found in the Drosophilae supergroup of Caenorhabditis species, including C. angaria, while the NHR-binding site likely only evolved at the base of the Elegans group. We find that a transgene from C. angaria bearing a single E-box is sufficient for normal expression in C. elegans. Even a short 58 bp cis-regulatory fragment from C. angaria with this single E-box is able to replace the three transcription factor binding sites at the endogenous C. elegans lin-3 locus, resulting in the wild-type expression level. Thus, regulatory evolution occurring in cis within a 58 bp lin-3 fragment, results in a strict requirement for the NHR binding site and a second E-box in C. elegans. This single-cell, single-molecule, quantitative and functional evo-devo study demonstrates that conserved expression levels can hide extensive change in cis-regulatory site requirements and highlights the evolution of new cis-regulatory elements required for cell-specific gene expression

The Socio-Economic Evaluation of a European Project: The Diylab Case

This paper builds on the results of a 3-year long European project, the main aim of which was to deeply and sustainably transform teaching and learning practice in primary and secondary schools and higher education, by introducing Do it Yourself (DIY) philosophy in order to expand digital competence and foster students' agency and collaborative learning. Three universities and three primary and secondary schools have been involved in a Collaborative Action Research (CAR) process in order to analyse their current institutional context and perceive needs, strengths and weaknesses; to undertake professional development activities and the design of DIYLabs; implement DIYLabs in the selected courses; and reflect upon ways of improving the institution's performance. This paper offers a global vision of the research and implementation processes and the results achieved, from the perspective of the socio-economic dimensions involved in a project aiming to make a difference in teaching and learning to meet the challenges of a society highly permeated by digital technology (DT). Keywords: educational change; digital competence; DIY digital objects; autonomous learning; action research; student agency; collaborative researc

Cost effectiveness of daclatasvir/asunaprevir versus peginterferon/ribavirin and protease inhibitors for the treatment of hepatitis c genotype 1b Naïve patients in Chile

© 2015 Vargas et al. Introduction: Daclatasvir and Asunaprevir (DCV/ASV) have recently been approved for the treatment of chronic hepatitis C virus infection. In association, they are more effective and safer than previous available treatments, but more expensive. It is unclear if paying for the additional costs is an efficient strategy considering limited resources. Methods: A Markov model was built to estimate the expected costs in Chilean pesos (CL$) and converted to US dollars (US$) and benefits in quality adjusted life years (QALYs) in a hypothetic cohort of naive patients receiving DCV/ASV compared to protease inhibitors (PIs) and Peginterferon plus Ribavirin (PR). Efficacy was obtained from a mixed-treatment comparison study and costs were estimated from local sources. Utilities were obtained applying the EQ-5D survey to local patients and then valued with the Chilean tariff. A time horizon of 46 years and a discount rate of 3% for costs and outcomes was considered. The ICERs were estimated for a range of DCV/ASV prices. Deterministic and probabilistic sensitivity analyses were performed. Results: PIs were extendedly dominated by DCV/ASV. The ICER of DCV/ASV compared to PR was US$16,635/QALY at a total treatment price of US$ 77,419; US$11,581 /QALY at a price of US$ 58,065; US$6,375/QALY at a price of US$ 38,710; and US$1,364 /QALY at a price of US$ 19,355. The probability of cost-effectiveness at a price of US$38,710 was 91.6$ 19,355. Although the results are sensitive to certain parameters, the ICER did not increase above the suggested threshold of 1 GDP per capita. Conclusions: DCV/ASV can be considered cost-effective at any price of the range studied. These results provide decision makers useful information about the value of incorporating these drugs into the public Chilean healthcare system

Visualidades contemporáneas, ciudadanía y sabiduría digital: Afrontar las posibilidades sin eludir las tensiones

En los últimos años la proliferación de tecnologías digitales (TD) para crear, almacenar, transformar, mezclar, transmitir y acceder a todo tipo de información ha supuesto una auténtica revolución en distintos ámbitos de la vida. La información visual (re)crea estereotipos, modelos, deseos, mundos irreales, posibles e imposibles, que constituyen y proyectan nuestros imaginarios y permean nuestras realidades. Esta revolución de lo visual, esta creciente facilidad, tanto para crear imágenes, como para transmitirlas y acceder a ellas, está teniendo un impacto considerable en la redefinición de los conceptos de ciudadanía y sabiduría y por tanto de la educación. En este contexto, discutimos las cuestiones relacionadas con lo que se ha dado en llamar la ciudadanía y la sabiduría digital, sobre todo en sus dimensiones relacionadas con un uso prudente de las mismas y el derecho (y el deber) del ciudadano de contar con una educación que le permita entender y participar en la sociedad, defender sus derechos y cumplir con sus obligaciones. En este artículo nos centraremos en la caracterización de las visualidades en la era digital, las nociones de ciudadanía y sabiduría en este contexto y sus implicaciones para la educación

Measurement Of Students Attitude Towards Statistics: A Mokken Scales Analysis Of Its Dimensions

 Nowadays, almost all curricula in the social sciences contain at least one course in statistics, given the importance of this discipline as a basic knowledge to understand the modern world. It’s necessary reflects on the student’s attitude to statistics, because it’s could be an obstacle or an advantage in their learning process. To measure the student’s attitude and incentives about statistics, we use a test (Bayot et al., 2005), related to other ones which exists in the specialized literature, that identifies the latent factors relating to students’ motivation and attitude towards statistics. This paper describes the formal and metric characteristics of the non-parametric model of item response theory for the latent factors using an extension of Mokken scales analysis

Governance And Its Impact On Textile Companies

From an economic perspective, the flaws and weaknesses of the government seem to be more evident because of situations such as vagueness of the boundaries between governments and public policies that make it harder work in an attempt to regulate activities of companies to generate small effective numbers and productive trade relations. To know the situation in the textile sector a diagnostic was carried out in 17 companies in production, technological development areas and university services, with an exploratory and quantitative study, and transeccional design. Afterwards were given a qualitative perspective with action research design when applying interviews with government representatives, and advisory councils, chambers of commerce to establish their participation in finding solutions in relations to the problems observed: distrust of the business sector programs offered by the government, minimal participation in training and innovation forums in Consultation Councils and in the decision-making process which prevent the sector increase its development

Validación de un instrumento de medición que analiza la cultura organizacional desde dos perspectivas

La cultura organizacional se entiende como el conjunto de creencias y significados que han sido naturalizados por los miembros de la organización en el marco de un orden hegemónico, convirtiéndose en simbolismo de interpretación, orientador de conductas y prácticas. Con este enfoque, el presente estudio se interesa en validar un instrumento de medición que permite analizar la cultura organizacional desde dos perspectivas: la real e ideal, y reconocer cómo las personas que laboran en una organización entienden e interpretan su experiencia y cómo se conectan en su entorno, es decir, con la comunicación existente, los conflictos, la creatividad, cómo los discursos y prácticas que circulan en la organización están inmersos en relaciones de poder y por supuesto, en la lucha por el control, por lo que se realiza una validez de criterio al correlacionar las puntuaciones de los participantes obteniendo una correlación positiva cercana a la media. En una primera aproximación se comprueba, para 35 casos de estudio, que existe una asociación positiva entre las culturas ideal y real percibida por los integrantes de la organización, posteriormente, y con miras hacia una cultura óptima o necesaria, se hace uso de la distancia de Hamming la que permitió visualizar una mayor apreciación en la administración de conflictos y una menor apreciación para la planeación. Conocer esta relación es fundamental, ya que a partir de la determinación del gap o brecha existente entre ambas culturas se podrán plantear acciones para cerrarla

Prevalencia del Síndrome de Burnout en el personal de Enfermería de dos Hospitales del Estado de México

Objetivos: Determinar la prevalencia del Síndrome de Burnout en el personal de enfermería de dos Hospitales del Estado de México. Hacer una comparación de la prevalencia del Síndrome de Burnout en ambos hospitales; así como describir los factores que lo ocasionan. Material y método: Se realizó una investigación de tipo descriptiva; con un estudio transversal, prospectivo y comparativo. El estudio se llevó a cabo en el personal de enfermería, con una población de 407 enfermeros, mediante un muestreo no probabilístico e intencional se obtuvo una muestra de 122 enfermeras, se utilizó el instrumento de Maslach Burnout Inventory (MBI) que mide los 3 aspectos del síndrome: cansancio emocional, despersonalización y falta de realización personal. El análisis estadístico es de tipo descriptivo, con el programa SPSS versión 13. Resultados: La prevalencia de Síndrome de Burnout en el Hospital Ecatepec es de 27% y en el Hospital de Cuautitlán de 24%. El Síndrome de Burnout de nivel alto en la muestra del estudio se obtuvo el 88% en Ecatepec en comparación el 82% el hospital de Cuautitlán. Entre los principales factores de este síndrome, es el turno, el servicio, el enlace de turno, ausentismo, la gravedad del paciente, y supervisión por jefes de servicio

Using high-throughput virtual screening to explore the optoelectronic property space of organic dyes; finding diketopyrrolopyrrole dyes for dye-sensitized water splitting and solar cells

Organic dyes based on conjugated chromophores such as diketopyrrolopyrrole (DPP) have a large range of uses beyond providing colour to other materials, such as in dye-sensitized solar cells, dye-sensitized photoelectrochemical cells, dye-sensitized colloidal photocatalysts and organic photovoltaics. We perform a high-throughput virtual screening using the xTB family of density functional tight-binding methods to map the optoelectronic property space of ∼45 000 DPP dyes. The large volume of data at our disposal allows us to probe the difference between symmetric and asymmetric dyes and to identify the apparent boundaries of the optoelectronic property space for these dyes, as well as which substituents give access to particular combinations of properties. Finally, we use our dataset to screen for DPP dyes that can drive the reduction of protons to molecular hydrogen when illuminated as part of dye-sensitized photoelectrochemical cells or dye-sensitized colloidal photocatalysts, or as dyes for TiO2-based dye-sensitized solar cells

Economic evaluation of sunitinib versus pazopanib and best supportive care for the treatment of metastatic renal cell carcinoma in Chile: cost-effectiveness analysis and a mixed treatment comparison

© 2019, © 2019 Informa UK Limited, trading as Taylor & Francis Group. Background: Sunitinib and Pazopanib are two metastatic renal cell carcinoma (MRCC) treatment alternatives, however the health system in Chile does not consider coverage for any. The cost-effectiveness versus relevant comparator was assessed to support evidence-based decision making. Methods: A four health states Markov model was built: first, second line treatments, BSC and death. Benefits were measured in QALYs, and efficacy estimates were obtained from an indirect treatment comparison. A 10-year time horizon and a 3% undifferentiated discount rate were considered. Deterministic and probabilistic sensitivity analyses were performed. Results: The costs of treating MRCC with Sunitinib were higher than Pazopanib and BSC. When comparing Sunitinib versus Pazopanib, the incremental benefit is small favoring Sunitinib (0.03 QALYs). The base case scenario shows an average ICER of PA versus BSC of US$62,327.11/QALY and of US$85,885/QALY for Sunitinib versus Pazopanib. The ICER was most sensitive to the OS relative to BSC, where evidence was associated to important bias. Conclusions: Sunitinib or Pazopanib can be considered cost-effective if a 3 GDP per-capita threshold is assumed. The decision between SU or PA is highly sensitive to the price of the drugs, rather than the outcomes. Therefore, the decision might be made based on cost-minimization exercise