VER-155008 induced Hsp70 proteins expression in fish cell cultures while impeding replication of two RNA viruses

The final publication is available at Elsevier via https://doi.org/10.1016/j.antiviral.2019.01.001 © 2019. This manuscript version is made available under the CC-BY-NC-ND 4.0 license http://creativecommons.org/licenses/by-nc-nd/4.0/The heat-shock protein 70 (Hsp70) inhibitor, VER-155008 (VER), was explored as a potential antiviral agent for two RNA viruses important to fish aquaculture, viral hemorrhagic septicemia virus (VHSV) and infectious pancreatic necrosis virus (IPNV). Studies were done at a temperature of 14 °C, and with cell lines commonly used to propagate these viruses. These were respectively EPC from fathead minnow for VHSV and CHSE-214 from Chinook salmon embryo for IPNV. Additionally, both viruses were studied with the Atlantic salmon heart endothelial cell line ASHe. For both VHSV and IPNV, 25 μM VER impeded replication. This was evidenced by delays in the development of cytopathic effect (CPE) and the expression of viral proteins, N for VHSV and VP2 for IPNV, and by less production of viral RNA and of viral titre. As VER inhibits the activity of Hsp70 family members, these results suggest that VHSV and IPNV utilize one or more Hsp70s in their life cycles. Yet neither virus induced Hsp70. Surprisingly VER alone induced Hsp70, but whether this induction modulated VER's antiviral effects is unknown. Exploring this apparent paradox in the future should improve the usefulness of VER as an antiviral agent.Natural Science and Engineering Research Council, Grant 468298 - 14Elanco Canada Limite

Planck-scale quintessence and the physics of structure formation

In a recent paper we considered the possibility of a scalar field providing an explanation for the cosmic acceleration. Our model had the interesting properties of attractor-like behavior and having its parameters of O(1) in Planck units. Here we discuss the effect of the field on large scale structure and CMB anisotropies. We show how some versions of our model inspired by "brane" physics have novel features due to the fact that the scalar field has a significant role over a wider range of redshifts than for typical "dark energy" models. One of these features is the additional suppression of the formation of large scale structure, as compared with cosmological constant models. In light of the new pressures being placed on cosmological parameters (in particular H_0) by CMB data, this added suppression allows our "brane" models to give excellent fits to both CMB and large scale structure data.Comment: 18 pages, 12 figures, submitted to PR

Strategies for the evolution of sex

We find that the hypothesis made by Jan, Stauffer and Moseley [Theory in Biosc., 119, 166 (2000)] for the evolution of sex, namely a strategy devised to escape extinction due to too many deleterious mutations, is sufficient but not necessary for the successful evolution of a steady state population of sexual individuals within a finite population. Simply allowing for a finite probability for conversion to sex in each generation also gives rise to a stable sexual population, in the presence of an upper limit on the number of deleterious mutations per individual. For large values of this probability, we find a phase transition to an intermittent, multi-stable regime. On the other hand, in the limit of extremely slow drive, another transition takes place to a different steady state distribution, with fewer deleterious mutations within the asexual population.Comment: RevTeX, 11 pages, multicolumn, including 12 figure

Hadronic Excitation of the Giant Dipole Resonance in 208-Pb and 40-Ca at E_p = 200 MeV

This research was sponsored by the National Science Foundation Grant NSF PHY-931478

Anti-tumour necrosis factor agent and liver injury : literature review, recommendations for management

Abnormalities in liver function tests, including transient and self-limiting hypertransaminasemia, cholestatic disease and hepatitis, can develop during treatment with anti-tumour-necrosis-factor (TNF) therapy. The optimal management of liver injury related to anti-TNF therapy is still a matter of debate. Although some authors recommend discontinuing treatment in case of both a rise of alanine aminotransferase more than 5 times the upper limit of normal, or the occurrence of jaundice, there are no standard guidelines for the management of anti-TNF-related liver injury. Bibliographical searches were performed in PubMed, using the following key words: inflammatory bowel disease (IBD); TNF inhibitors; hypertransaminasemia; drug-related liver injury; infliximab. According to published data, elevation of transaminases in patients with IBD treated with anti-TNF is a common finding, but resolution appears to be the usual outcome. Anti-TNF agents seem to be safe with a low risk of causing severe drug-related liver injury. According to our centre experience, we found that hypertransaminasemia was a common, mainly self-limiting finding in our IBD cohort and was not correlated to infliximab treatment on both univariate and multivariate analyses. An algorithm for the management of liver impairment occurring during anti-TNF treatment is also proposed and this highlights the need of a multidisciplinary approach and suggests liver biopsy as a key-point in the management decision in case of severe rise of transaminases. However, hepatic injury is generally self-limiting and drug withdrawal seems to be an exception

Hacia un Sistema Inteligente basado en Mapas Conceptuales Evolucionados para la Automatización de un Aprendizaje Significativo. Aplicación a la Enseñanza Universitaria de la Jerarquía de Memoria

El principal objetivo de esta ponencia consiste en plasmar la búsqueda de un sistema inteligente para apoyo a la docencia en un proceso de aprendizaje significativo [9]. Como dominio concreto, hemos elegido el campo de la jerarquía de memoria por su complejidad limitada pero que a la vez constituye un dominio lo suficientemente general para ser enseñado en diferentes asignaturas y grados de detalle. Además, los autores hemos desarrollado varios trabajos en esta área, incluyendo varios simuladores que han sido empleados como recursos docentes. Buscando la mejora continua de la docencia, se llevó a cabo un proceso de investigación-acción, dando como fruto la idea de elaborar el mencionado sistema inteligente, incluso para ser independiente del dominio de aplicación. Para esta aplicación, hemos desarrollado una variación de los tradicionales mapas conceptuales, a la que hemos denominado Grafo Instruccional Conceptual Pedagógico (Pedagogical Concept Instructional Graph, PCIG) que permite la planificación del aprendizaje y la enseñanza de un tema específico. Después de que el profesor haya diseñado el PCIG específico de la materia a enseñar, el sistema experto hará uso de un test adaptivo que generará una serie de preguntas siguiendo la estructura jerárquica descrita en el PCIG. De la respuesta obtenida por cada estudiante se puede obtener un mapa conceptual individualizado que describe lo que cada alumno conoce a priori de la materia a aprender

The Similarity Hypothesis in General Relativity

Self-similar models are important in general relativity and other fundamental theories. In this paper we shall discuss the ``similarity hypothesis'', which asserts that under a variety of physical circumstances solutions of these theories will naturally evolve to a self-similar form. We will find there is good evidence for this in the context of both spatially homogenous and inhomogeneous cosmological models, although in some cases the self-similar model is only an intermediate attractor. There are also a wide variety of situations, including critical pheneomena, in which spherically symmetric models tend towards self-similarity. However, this does not happen in all cases and it is it is important to understand the prerequisites for the conjecture.Comment: to be submitted to Gen. Rel. Gra

Electric current circuits in astrophysics

Cosmic magnetic structures have in common that they are anchored in a dynamo, that an external driver converts kinetic energy into internal magnetic energy, that this magnetic energy is transported as Poynting fl ux across the magnetically dominated structure, and that the magnetic energy is released in the form of particle acceleration, heating, bulk motion, MHD waves, and radiation. The investigation of the electric current system is particularly illuminating as to the course of events and the physics involved. We demonstrate this for the radio pulsar wind, the solar flare, and terrestrial magnetic storms