Competitive fitness in coronaviruses is not correlated with size or number of double-membrane vesicles under reduced-temperature growth conditions.

Positive-stranded viruses synthesize their RNA in membrane-bound organelles, but it is not clear how this benefits the virus or the host. For coronaviruses, these organelles take the form of double-membrane vesicles (DMVs) interconnected by a convoluted membrane network. We used electron microscopy to identify murine coronaviruses with mutations in nsp3 and nsp14 that replicated normally while producing only half the normal amount of DMVs under low-temperature growth conditions. Viruses with mutations in nsp5 and nsp16 produced small DMVs but also replicated normally. Quantitative reverse transcriptase PCR (RT-PCR) confirmed that the most strongly affected of these, the nsp3 mutant, produced more viral RNA than wild-type virus. Competitive growth assays were carried out in both continuous and primary cells to better understand the contribution of DMVs to viral fitness. Surprisingly, several viruses that produced fewer or smaller DMVs showed a higher fitness than wild-type virus at the reduced temperature, suggesting that larger and more numerous DMVs do not necessarily confer a competitive advantage in primary or continuous cell culture. For the first time, this directly demonstrates that replication and organelle formation may be, at least in part, studied separately during infection with positive-stranded RNA virus. IMPORTANCE The viruses that cause severe acute respiratory syndrome (SARS), poliomyelitis, and hepatitis C all replicate in double-membrane vesicles (DMVs). The big question about DMVs is why they exist in the first place. In this study, we looked at thousands of infected cells and identified two coronavirus mutants that made half as many organelles as normal and two others that made typical numbers but smaller organelles. Despite differences in DMV size and number, all four mutants replicated as efficiently as wild-type virus. To better understand the relative importance of replicative organelles, we carried out competitive fitness experiments. None of these viruses was found to be significantly less fit than wild-type, and two were actually fitter in tests in two kinds of cells. This suggests that viruses have evolved to have tremendous plasticity in the ability to form membrane-associated replication complexes and that large and numerous DMVs are not exclusively associated with efficient coronavirus replication.

Structure-function analyses of {\it PAX6\/} and the molecular bases of aniridia

PAX6 is a transcription activator that regulates eye development in animals ranging from Drosophila to human. The C-terminal region of PAX6 is proline/serine/threonine-rich (PST) and functions as a potent transactivation domain when attached to a heterologous DNA-binding domain of the yeast transcription factor, GAL4. The PST region comprises 152 amino acids encoded by four exons. The transactivation function of the PST region has not been defined and characterized in detail by in vitro mutagenesis. I dissected the PST domain in two independent systems, a heterologous system using a GAL4 DNA-binding site and the native system of PAX6. In both systems, the results show consistently that all four constituent exons of the PST domain are responsible for the transactivation function. The four exon fragments act cooperatively to stimulate transcription, although none of them can function individually as an independent transactivation domain. Combinations of two or more exon fragments can reconstitute substantial transactivation activity when fused to the DNA-binding domain of GAL4, but they surprisingly do not produce much activity in the context of native PAX6 even though the mutant PAX6 proteins are stable and their DNA-binding function remains unaffected. I conclude that the PAX6 protein contains an unusually large transactivation domain that is evolutionarily conserved to a high degree, and that its full transactivation activity relies on the cooperative action of the four exon fragments.^ Most PAX6 mutations detected in patients with aniridia result in truncations of the protein. Some of the truncation mutations occur in the PST region of PAX6, resulting in mutant proteins that retain their DNA-binding ability but have no significant transactivation activity. It is not clear whether such mutants are true loss-of-function or dominant-negative mutants. I show that these mutants are dominant-negative if they are coexpressed with wild-type PAX6 in cultured cells and that the dominant-negative effects result from enhanced DNA-binding ability of these mutants due to removal of the PST domain. These mutants are able to repress the wild-type PAX6 activity not only at target genes with paired domain binding sites but also at target genes with homeodomain binding sites.^ Mutations in the human PAX6 gene produce various phenotypes, including aniridia, Peters' anomaly, autosomal dominant keratitis, and familial foveal dysplasia. The various phenotypes may arise from different mutations in the same gene. To test this theory, I performed a functional analysis of two missense mutations in the paired domain: the R26G mutation reported in a case of Peters' anomaly, and the I87R mutation identified in a patient with aniridia. While both the R26 and the I87 positions are conserved in the paired boxes of all known PAX genes, X-ray crystallography has shown that only R26 makes contact with DNA. I found that the R26G mutant failed to bind a subset of paired domain binding sites but, surprisingly, bound other sites and successfully transactivated promoters containing those sites. In contrast, the I87R mutant had lost the ability to bind DNA at all tested sites and failed to transactivate promoters. My data support the haploinsufficiency hypothesis of aniridia, and the hypothesis that R26G is a hypomorphic allele. ^

The analysis of the basketball coach speech during the moments of game and pause in relation to the performance in competition

In the area of the professional competition, the coach is a fundamental part in the management of a team and more concretely in the game planning. During the competition, the management of the times of pause and times out as well as the conduct of the coach during the same ones is an aspect to analyze in the sports performance. It is for this that it becomes necessary to know some of the behaviors that turn out to be more frequent by the coach and that are more related to a positive performance of his players. For it there has been realized a study of 7 cases of expert coaches in those that his verbal behavior has observed during 4 games. It has focused on the content of the information only to verbal level, on his meaning. The information that have been obtained in the study shows a major quantity of information elaborated during the pauses of the games and a major tactical content with regard to the moments of game. On the other hand, a relation exists between a major number of questions and a minor number of psychological instructions when the score is adverse, whereas in case of victory, a direct relation does not exist with any category. The rest of categories of the speech do not meet influenced directly for the result, for what it is not possible to consider a direct and immediate relation between the coach verbal behavior during the pauses and the result of the game, except in punctual moments.

Twelve lectures in illustration and defence of Christian Unitarianism: : delivered in the Meeting-House of the First Presbyterian Congregation, Belfast. /

What it is, and what it is not -- The faith of the Old Testament -- The faith of our Lord Jesus Christ -- The faith of the Apostles. Part I -- The faith of the Apostles. Part II -- The faith of the primitive church -- A rational faith -- A devotional faith -- A benevolent faith -- A holy faith -- A consolatory faith -- A progressive faith.

Integrated Marketing Communication (IMC): New Discipline with an Old Learning Approach: A Syllabi Analysis

Marketing communications as a discipline has changed significantly in both theory and practice over the past decade. But has our teaching of IMC kept pace with the discipline changes? The purpose of this paper is to explore how far the evolving concepts of IMC are reaching university learners. By doing this, the paper offers an approach to assessing how well marketing curricula are fulfilling their purpose. The course outlines (syllabi) for all IMC courses in 30 universities in Australia and five universities in New Zealand were analyzed. The findings suggest that most of what is taught in the units is not IMC. It is not directed by the key constructs of IMC, nor by the research informing the discipline. Rather, it appears to have evolved little from traditional promotion management units and is close in content and structure to many introductory advertising courses. This paper suggests several possible explanations for this, including: (1) a tacit rejection of IMC as a valid concept; (2) a lack of information about what IMC is and what it is not; and (3) a scarcity of teaching and learning materials that are clearly focused on key constructs and research issues of IMC.

Labor-Management Cooperation

[Excerpt] In analyzing labor-management cooperation, it is important to be clear on what it is not. It is not an absence of strikes or conflict. Cooperation is not synonymous with industrial peace. Cooperation may take place even when bargaining leads to work stoppages; conversely, the mere absence of strikes is no evidence that there is labor-management cooperation. In the current period, there is a tendency to equate concessionary bargaining with labor-management cooperation. Demand for and acceptance of "givebacks" reflect economic pressures and relative bargaining strength and ought not to be interpreted as evidence of a cooperative relationship.

Exposi����o cambial: o impacto do c��mbio nas a����es das empresas brasileiras internacionalizadas

O aumento da internacionaliza����o das economias emergentes e a tend��ncia de financeiriza����o da economia mundial motivaram este estudo que tem como principal objetivo analisar estatisticamente o impacto das varia����es cambiais no retorno das a����es das principais empresas brasileiras internacionalizadas, segundo o ranking realizado pela Funda����o Dom Cabral, no per��odo entre 2000 e 2012. Al��m disso, buscou-se, tamb��m, descrever o processo inicial de internacionaliza����o dessas mesmas companhias. Para isso, foi realizada uma pesquisa descritiva e quantitativa, por meio da utiliza����o do m��todo estat��stico de regress��o linear m��ltipla. Constatou-se que nas 28 empresas analisadas n��o h�� correla����o entre varia����es nas taxas de c��mbio e varia����es no retorno das a����es das empresas brasileiras internacionalizadas, evidenciando assim, que outras vari��veis s��o as respons��veis por impactarem o retorno dessas a����es. Verificou-se, ainda, que a maior parte das empresas brasileiras iniciam seu processo de internacionaliza����o por meio da instala����o de linhas de produ����o no exterior, seguida de exporta����o e fus��es e aquisi����es com outras companhias.

Heritage

This article examines the concepts, definitions, policies, and practices of heritage in a contemporary context. Within recent years, there have been significant shifts in our understandings and applications of heritage concepts and policies in the modern world. ���Heritage��� emerged as a buzz word in international policy arenas in the 1980s and early 1990s, and has since weathered the vagaries of turbulent definitional and governance���nomenclature storms, as traditional debates about ���what it is and what it is not��� reverberate around academia and state agencies alike. Policy and funding structures for heritage are determined by the classifications used to define them in various countries. Typically, reference is made to ���built heritage���, ���natural heritage���, and ���intangible heritage���, loosely reflecting buildings, landscapes, and culture. Aspects of heritage are used by the cultural and tourism industries to add economic value, through heritage tourism sites, museums, and other activities. The cultural tourism product is often anchored around notions of heritage, and in postmodern, post-tourist societies, boundaries between culture, (travel) space, and identities are increasingly blurred. Issues of authenticity become important in the representation of heritage, and questions are asked about the validity of nostalgia versus realism. The role of heritage is examined in the context of identity formulation at individual and nation-state levels, and the political aspects of this are also discussed. Finally, heritage conservation is assessed through an examination of UNESCO���s World Heritage Site listing and protection strategy. In a changing world, new constructs of heritage, identity, authenticity, and representation will continue to emerge as meanings are constantly renegotiated over time and space.

Ciudad y espacio p��blico, perspectivas complementarias y nuevos desaf��os

La ciudad y los procesos que ��sta desencadena en su entorno territorial han variado, de acuerdo con el momento hist��rico y contexto geogr��fico donde ocurri��, est�� ocurriendo o suceder��, por lo tanto, lo primero y lo segundo, son tan cambiantes, como lo son los elementos constitutivos de ese espacio ocupado, apropiado y gobernado.Son pocos los asuntos sobre los cuales coinciden las distintas comunidades acad��micas y disciplinas que se encargan del estudio de los procesos urbanos, como urbanistas, arquitectos, ge��grafos, soci��logos, polit��logos, ingenieros o planificadores; por ejemplo, con relaci��n a la definici��n de lo urbano o lo qu�� podemos entender por ciudad; tal vez hay mayor acuerdo por lo que no es, como se constata con los espacios dedicados, exclusiva o principalmente a las actividades productivas agropecuarias. De la misma manera, sobre lo que se considera como espacio p��blico, ya que algunos le dan un ��nfasis estructural y f��sico, como uno de los elementos r��gidos que constituyen el espacio ocupado, mientras que otros, adem��s de lo f��sico, rescatan de ��l referentes hist��ricos, culturales y simb��licos.En la actualidad viene ganando audiencia la postura que combina lo f��sico y material de la ciudad y el espacio p��blico, con lo inmaterial y simb��lico de los mismos, lo que le confiere un nuevo sentido. De este tipo de convergencias, surge el escenario que contribuye a construir el ciudadano que requiere y demanda la ciudad.De acuerdo con lo anterior, el an��lisis que aqu�� se presenta se aborda a partir de tres aspectos relevantes: en primer lugar, se reiteran algunos de los caminos andados, para esbozar algunas de las nuevas perspectivas sobre la ciudad y el espacio p��blico, tal como se sugiere en el t��tulo del art��culo; en segundo lugar, relacionar aspectos hist��ricos, conceptuales y aplicados sobre la ciudad y de esta con el espacio p��blico, con base en el caso de Bogot�� y finalmente plantear algunos de los desaf��os que surgen de esta interacci��n, a partir de algunas reflexiones que buscan vincular esta tem��tica con las ciencias sociales y en particular con la ciencia pol��tica.-----The city and the processes triggered by the city in its territorial environment have changed, according to the historical moment and the geographical context in which it happened, is happening, or will happen; therefore, the former and the latter are as changing as the elements of that occupied, appropriated, and governed space.There are very few subjects on which there is an agreement among the different academic communities and disciplines that study urban processes, such as town planners, architects, geographers, sociologists, political scientists, engineers, or planners. For example, regarding the definition of the urban matters or what we may understand as a city, a greater agreement may be found on what it is not, as shown with spaces exclusively or mainly dedicated to the productive agricultural/livestock activities. Likewise, regarding what is deemed as public space, because some people stress the structural and physical aspect as one of the rigid elements that comprise the occupied space, while others rescue, in addition to the physical, the historical, cultural, and symbolic references.The position that considers the physical and material city and public space combined with their immaterial and symbolic aspects has been gaining terrain lately, providing them with a whole new sense. From these convergences arises the scenario that contributes to the building of the citizenship required and demanded by the city.According to the foregoing, the analysis presented here is addressed from three relevant aspects: First, reiterating some of the already treated topics to outline some new perspectives on the city and the public space, as suggested in the title of this article; second, relating historical, conceptual, and applied aspects of the city and such aspects of the city related to the public space, based on the case of Bogot��; and finally, formulating some challenges arising form this interaction, based on certain thoughts that seek to link this topic with the Social Sciences and, in particular, with the Political Sciences.

Utilidad de la relaci��n estrat��gica comunitaria y el marketing en empresas el sector salud

La necesidad de involucrar el concepto de comunidad y sus estrategias con el sector salud, generan el problema de investigaci��n de determinar ��Cu��l es la utilidad de la relaci��n estrat��gica comunitaria y el marketing en empresas del sector salud? El sector salud ha apartado las actividades relacionales con sus clientes, el cual es caracterizado por la atracci��n, desarrollo y mantenimiento de relaciones con los clientes. El objetivo de la investigaci��n es determinar cu��l es la utilidad de la relaci��n estrat��gica comunitaria y el marketing en empresas del sector salud y los objetivos espec��ficos son: describir el uso de comunidad e Identificar la utilidad de aplicar las estrategias comunitarias en el sector. La metodolog��a es la investigaci��n y an��lisis de caso, estudiando una organizaci��n relevante dentro del sector salud, anexando fuentes de informaci��n secundarias como que aporten a los resultados. El an��lisis arroja una brecha entre la teor��a y la utilizaci��n de comunidad, donde la organizaci��n la define como sus clientes y empleados. Posteriormente cabe determinar si son aplicadas las estrategias comunitarias por la compa����a, donde se encontr�� que algunas lo son. Al encontrar el uso de estrategias cabe estudiar si generan utilidad a los resultados demostrando que conservar y mejorar relaciones con los clientes es de beneficio para la compa����a, sin dejar de atraer nuevos clientes para ampliar las posibilidades de ser una compa����a rentable y perdurable. Finalmente se establece un eje estrat��gico que genere un impacto positivo a la empresa - comunidad para crear relaciones m��s efectivas y rentables.

Tipos de l��gica utilizadas en la toma de decisiones estrat��gicas de marketing

Para el administrador el proceso de la toma de decisiones es uno de sus mayores retos y responsabilidades, ya que en su desarrollo se debe definir el camino m��s acertado en un sin n��mero de alternativas, teniendo en cuenta los obst��culos sociales, pol��ticos y econ��micos del entorno empresarial. Para llegar a la decisi��n adecuada no hay que perder de vista los objetivos y metas propuestas, adem��s de tener presente el proceso l��gico, detectando, analizando y demostrando el porqu�� de esa elecci��n. Consecuentemente el an��lisis que propone esta investigaci��n aportara conocimientos sobre los tipos de l��gica utilizados en la toma de decisiones estrat��gicas al administrador para satisfacer las demandas asociadas con el mercadeo para que de esta manera se pueda generar y ampliar eficientemente las competencia id��neas del administrador en la inserci��n internacional de un mercado laboral cada vez mayor (Valero, 2011). A lo largo de la investigaci��n se pretende desarrollar un estudio te��rico para explicar la relaci��n entre la l��gica y la toma de decisiones estrat��gicas de marketing y como estos conceptos se combinan para llegar a un resultado final. Esto se llevara a cabo por medio de un an��lisis de planes de marketing, iniciando por conceptos b��sicos como marketing, l��gica, decisiones estrat��gicas, direcci��n de marketing seguido de los principios l��gicos y contradicciones que se pueden llegar a generar entre la fundamentaci��n te��rica

Abstract platforms of computation

Computational formalisms have been pushing the boundaries of the field of computing for the last 80 years and much debate has surrounded what computing entails; what it is, and what it is not. This paper seeks to explore the boundaries of the ideas of computation and provide a framework for enabling a constructive discussion of computational ideas. First, a review of computing is given, ranging from Turing Machines to interactive computing. Then, a variety of natural physical systems are considered for their computational qualities. From this exploration, a framework is presented under which all dynamical systems can be considered as instances of the class of abstract computational platforms. An abstract computational platform is defined by both its intrinsic dynamics and how it allows computation that is meaningful to an external agent through the configuration of constraints upon those dynamics. It is asserted that a platform���s computational expressiveness is directly related to the freedom with which constraints can be placed. Finally, the requirements for a formal constraint description language are considered and it is proposed that Abstract State Machines may provide a reasonable basis for such a language.

Termotect��nica por tra��os de fiss��o em apatitas dos altos estrutrais de Pitanga, Pau d'��lho e Jib��ia - centro do Estado de S��o Paulo

Funda����o de Amparo �� Pesquisa do Estado de S��o Paulo (FAPESP)

El acceso a la informaci��n p��blica y los archivos en Uruguay

El art��culo analiza la situaci��n actual de los archivos en Uruguay en relaci��n a las leyes de Acceso a la Informaci��n P��blica y de Sistema Nacional de Archivos, normativas que surge cuando el Estado uruguayo inicia una fase de reordenaci��n de su gesti��n promoviendo cambios que fomentan la democratizaci��n y la eficiencia, a la vez que anulan la opacidad y extrema reserva en su administraci��n. Se analiza c��mo los profesionales archiv��logos estuvieron estrechamente involucrados en el proceso de gestaci��n de ambas leyes, dando inicio a una etapa de consecuci��n de fuertes voluntades pol��ticas que apoyaran los proyectos, convencidos que la premisa evidente del Derecho de Acceso es que el documento al que se pretenda acceder exista y sea recuperable. Se estudia como la coexistencia de ambas normas implicaban un cambio cultural, una evoluci��n en el comportamiento de las organizaciones que no acompa���� a la puesta en marcha de los instrumentos legales. Se concluye que el Derecho de Acceso a la Informaci��n P��blica est�� basado en el principio fundamental de transparencia de los ��rganos del Estado, por lo que no es de extra��ar que una ley que obliga a brindar informaci��n tenga el riesgo de devenir en letra muerta. El Archivo debe ser "condici��n" administrativa, lo que exige una nueva dimensi��n de ellos y de sus profesionales dentro de los organismos del Estado, de forma tal que se conviertan en una inmejorable herramienta para el cumplimiento de los objetivos de la Ley de Derecho de Acceso a la Informaci��n P��blica

El acceso a la informaci��n p��blica y los archivos en Uruguay

El art��culo analiza la situaci��n actual de los archivos en Uruguay en relaci��n a las leyes de Acceso a la Informaci��n P��blica y de Sistema Nacional de Archivos, normativas que surge cuando el Estado uruguayo inicia una fase de reordenaci��n de su gesti��n promoviendo cambios que fomentan la democratizaci��n y la eficiencia, a la vez que anulan la opacidad y extrema reserva en su administraci��n. Se analiza c��mo los profesionales archiv��logos estuvieron estrechamente involucrados en el proceso de gestaci��n de ambas leyes, dando inicio a una etapa de consecuci��n de fuertes voluntades pol��ticas que apoyaran los proyectos, convencidos que la premisa evidente del Derecho de Acceso es que el documento al que se pretenda acceder exista y sea recuperable. Se estudia como la coexistencia de ambas normas implicaban un cambio cultural, una evoluci��n en el comportamiento de las organizaciones que no acompa���� a la puesta en marcha de los instrumentos legales. Se concluye que el Derecho de Acceso a la Informaci��n P��blica est�� basado en el principio fundamental de transparencia de los ��rganos del Estado, por lo que no es de extra��ar que una ley que obliga a brindar informaci��n tenga el riesgo de devenir en letra muerta. El Archivo debe ser "condici��n" administrativa, lo que exige una nueva dimensi��n de ellos y de sus profesionales dentro de los organismos del Estado, de forma tal que se conviertan en una inmejorable herramienta para el cumplimiento de los objetivos de la Ley de Derecho de Acceso a la Informaci��n P��blica