Expression of the Myxoma Virus Tumor Necrosis Factor Receptor Homologue and M11L Genes Is Required to Prevent Virus-Induced Apoptosis in Infected Rabbit T Lymphocytes

AbstractMyxoma virus is a leporipoxvirus that causes a highly lethal virulent disease known as myxomatosis in the European rabbit. An important aspect of myxoma virus pathogenesis is the ability of the virus to productively infect lymphocytes and spread to secondary sites via lymphatic channels. We investigated the infection of the CD4+T lymphoma cell line RL-5 with myxoma virus and Shope fibroma virus, a related but benign leporipoxvirus, and observed that myxoma virus, but not Shope fibroma virus, was able to productively infect RL-5 cells. We also discovered that infection of RL-5 cells with Shope fibroma virus or attenuated myxoma virus mutants containing disruptions in either the T2 or the M11L gene resulted in the rapid induction of DNA fragmentation, followed by morphological changes and loss in cell integrity characteristic of cell death by apoptosis. Purified exogenous T2 protein was unable to prevent apoptosis, suggesting that T2 functions intracellularly. Thus, myxoma virus T2, originally described as a secreted homologue of the tumor necrosis factor receptor, and M11L, a novel transmembrane species with no known cellular homologue, function to extend virus host range for replication in rabbit T lymphocytes through the inhibition of apoptosis in infected T lymphocytes

Análisis Sísmico de una Edificación de 11 Niveles empleando Disipadores de Energía Shear Link Bozzo en el Distrito de Santiago de Surco

La presente tesis titulada: “Análisis sísmico de una edificación de 11 niveles empleando disipadores de energía Shear Link Bozzo en el distrito de Santiago de Surco” tuvo por objetivo analizar el comportamiento sísmico de una edificación donde se implementó disipadores histeréticos. Se determinó derivas, desplazamiento a causa del sismo lineal dinámico y análisis tiempo historia no lineal, como complemento se realizó una variante de la estructura con fines analíticos. La metodología usada fue de tipo aplicada, ya que buscó mejorar el comportamiento de la estructura con la implementación de los disipadores, con enfoque cuantitativo de nivel descriptivo no experimental con diseño transversal, se consideró un muestreo de tipo no probabilístico por conveniencia. Se evaluó a la edificación son el software Etabs 2019 como principal herramienta de modelación, además se usó Seismo signal, Seismo Match, Autocad y Excel. Se modeló la estructura bajo las normas vigente E.030 - 2018 Norma Diseño Sismorresistente y E.020 – 2004 Norma de Cargas. Finalmente, los principales resultados encontrados fueron que el edificio de muros estructurales estudiado cumplió con las derivas de entrepiso en las direcciones X e Y siendo estas por debajo de la deriva permisible para concreto armado 0.007. Se Incorporó disipadores SLB sobre muros desacoplados en la dirección X donde disipando la energía sísmica en 35.4% y disminuye el periodo en 23%. La variación de la estructura de muros estructurales a pórticos generó irregularidad torsional y derivas máximas sobre la permisible en el eje X e Y, la cual fue corregida implementando disipadores SLB sobre muros desacoplados aportando rigidez a la estructura y disipando la energía sísmica en 42% en el eje Y, 52% en el eje X. Los resultados comprobaron que, con la implementación de los disipadores Shear Link Bozzo, se obtiene una mejor respuesta sísmica de la edificación

In vitro- and ex vivo-derived cytolytic leukocytes from granzyme A x B double knockout mice are defective in granule-mediated apoptosis but not lysis of target cells

Granzyme (gzm) A and gzmB have been implicated in Fas-independent nucleolytic and cytolytic processes exerted by cytotoxic T (Tc) cells, but the underlying mechanism(s) remains unclear. In this study, we compare the potential of Tc and natural killer (NK) cells of mice deficient in both gzmA and B (gzmAxB-/-) with those from single knockout mice deficient in gzmA (-/-), gzmB (-/-), or perforin (-/-) to induce nuclear damage and lysis in target cells. With the exception of perforin-/-, all in vitro- and ex vivo-derived Tc and NK cell populations from the mutant strains induced 51Cr-release in target cells at levels and with kinetics similar to those of normal mice. This contrasts with their capacity to induce apoptotic nuclear damage in target cells. In gzmAxB-/- mice, Tc/NK-mediated target cell DNA fragmentation was not observed, even after extended incubation periods (10 h), but was normal in gzmA-deficient and only impaired in gzmB-deficient mice in short-term (2-4 h), but not long-term (4-10 h), nucleolytic assays. This suggests that gzmA and B are critical for Tc/NK granule- mediated nucleolysis, with gzmB being the main contributor, while target cell lysis is due solely to perforin and independent of both proteases

Impact of distinct poxvirus infections on the specificities and functionalities of CD4+ T cell responses.

UNLABELLED: The factors that determine CD4+ T cell (TCD4+) specificities, functional capacity, and memory persistence in response to complex pathogens remain unclear. We explored these parameters in the C57BL/6 mouse through comparison of two highly related (\u3e92% homology) poxviruses: ectromelia virus (ECTV), a natural mouse pathogen, and vaccinia virus (VACV), a heterologous virus that nevertheless elicits potent immune responses. In addition to elucidating several previously unidentified major histocompatibility complex class II (MHC-II)-restricted epitopes, we observed many qualitative and quantitative differences between the TCD4+ repertoires, including responses not elicited by VACV despite complete sequence conservation. In addition, we observed functional heterogeneity between ECTV- and VACV-specific TCD4+ at both a global and individual epitope level, particularly greater expression of the cytolytic marker CD107a from TCD4+ following ECTV infection. Most striking were differences during the late memory phase where, in contrast to ECTV, VACV infection failed to elicit measurable epitope-specific TCD4+ as determined by intracellular cytokine staining. These findings illustrate the strong influence of epitope-extrinsic factors on TCD4+ responses and memory. IMPORTANCE: Much of our understanding concerning host-pathogen relationships in the context of poxvirus infections stems from studies of VACV in mice. However, VACV is not a natural mouse pathogen, and therefore, the relevance of results obtained using this model may be limited. Here, we explored the MHC class II-restricted TCD4+ repertoire induced by mousepox (ECTV) infection and the functional profile of the responding epitope-specific TCD4+, comparing these results to those induced by VACV infection under matched conditions. Despite a high degree of homology between the two viruses, we observed distinct specificity and functional profiles of TCD4+ responses at both acute and memory time points, with VACV-specific TCD4+ memory being notably compromised. These data offer insight into the impact of epitope-extrinsic factors on the resulting TCD4+ responses

Caspase-Dependent Inhibition of Mousepox Replication by gzmB

BACKGROUND: Ectromelia virus is a natural mouse pathogen, causing mousepox. The cytotoxic T (Tc) cell granule serine-protease, granzyme B, is important for its control, but the underlying mechanism is unknown. Using ex vivo virus immune Tc cells, we have previously shown that granzyme B is able to activate several independent pro-apoptotic pathways, including those mediated by Bid/Bak/Bax and caspases-3/-7, in target cells pulsed with Tc cell determinants. METHODS AND FINDINGS: Here we analysed the physiological relevance of those pro-apoptotic pathways in ectromelia infection, by incubating ectromelia-immune ex vivo Tc cells from granzyme A deficient (GzmB(+) Tc cells) or granzyme A and granzyme B deficient (GzmAxB(-/-) Tc cell) mice with ectromelia-infected target cells. We found that gzmB-induced apoptosis was totally blocked in ectromelia infected or peptide pulsed cells lacking caspases-3/-7. However ectromelia inhibited only partially apoptosis in cells deficient for Bid/Bak/Bax and not at all when both pathways were operative suggesting that the virus is able to interfere with apoptosis induced by gzmB in case not all pathways are activated. Importantly, inhibition of viral replication in vitro, as seen with wild type cells, was not affected by the lack of Bid/Bak/Bax but was significantly reduced in caspase-3/-7-deficient cells. Both caspase dependent processes were strictly dependent on gzmB, since Tc cells, lacking both gzms, neither induced apoptosis nor reduced viral titers. SIGNIFICANCE: Out findings present the first evidence on the biological importance of the independent gzmB-inducible pro-apoptotic pathways in a physiological relevant virus infection model

Incidencia de la aplicación de las sanciones tributarias en la gestión de la mediana empresa durante el año 2012 en la provincia de Trujillo

Este trabajo de tesis se realizó con el objetivo de dar a conocer la incidencia de la aplicación de las sanciones tributarias en la gestión de la mediana empresa durante el año 2012 en la Provincia de Trujillo. Hoy en día, se observa que se presentan diversas modificaciones en el ordenamiento jurídico tributario, a veces encontramos situaciones, que sin estar definidas y tipificadas como tales, representan verdaderas sanciones, se trataría de sanciones implícitas, a las cuales, en doctrina, se les denomina como sanciones anómalas, impropias, indirectas o atípicas. Si bien la consecuencia directa del incumplimiento de un deber formal: La infracción tributaria; es la sanción, adicionalmente a ésta, en algunos casos, aparecen otros efectos jurídicos sancionadores que están directa o indirectamente relacionados con la infracción. Como problema principal, se plantea la incidencia en la gestión de las empresas sancionadas. El presente trabajo de investigación se ha desarrollado teniendo como objetivo principal de dar a conocer cuál es el impacto en las empresas ante una sanción tributaria. Revisando anteriores trabajos relacionados con el tema no se encontró alguno que evalúe el impacto en la empresa ante una sanción tributaria, si se mejoró el accionar empresarial o se sigue incurriendo en lo mismo. Desarrollando el presente trabajo se pudo determinar el impacto en la gestión empresarial, ya que la gestión que tenga la empresa es la clave fundamental para su éxito. A través del presente trabajo se logró determinar cuál es la incidencia de aplicar las sanciones tributarias por parte la administración tributaria. Se analizó las diferentes sanciones tributarias aplicadas a las medianas empresas así como la gran variedad de normas tributarias que se aplican a las diversas actividades que desarrollan las empresas para la determinación de los impuestos. El procedimiento sancionatorio que se aplica a las infracciones tributarias, vale decir desde que se inicia con la infracción hasta que se le aplica la sanción que deberán cumplir los contribuyentes. Asimismo se da a conocer los resultados que se tiene con la aplicación de las diferentes sanciones tributarias a las infracciones cometidas por la Medianas Empresas de la Provincia de Trujillo. Finalmente se plantea las conclusiones y recomendaciones del presente trabajo, con el fin de dar a conocer la incidencia que se tiene al aplicar las sanciones y de qué manera las empresas podrían mejorar su gestión.This work was carried out in order to inform the incidence of the tax penalties in the medium business management for the year 2012 in the province of Trujillo. Today, there are various changes in tax law, sometimes we find situations without finding is defined and characterized as such, representing real sanctions, be implied sanctions which doctrine, are called as abnormal, improper, indirect or atypical sanctions. While the direct consequence of the breach of a formal duty, i.e. tax; infringement it is the penalty, in addition to this, in some cases, other punitive legal effects that are directly or indirectly related to the offence are. As a major problem arises the incidence in sanctioned company management. This research work has been developed with the aim to know what the impact on businesses to a tax penalty. Reviewing previous work related to the topic not found any that assess the impact on the company before a penalty tax, if improved action business or still incurring the same. Developing this work could be determined the impact on business, management since having the company management is the key to your success. In this work over managed to determine the incidence of tax management applied tax penalties for part. I discuss the different tax penalties imposed on medium-sized enterprises as well as the variety of tax rules apply to the activities developed by enterprises for the determination of the tax. The penal procedure that applies to tax violations, since the start in the breach until applies the sanction shall comply with taxpayers. It also gives the results to the application of the different tax penalties to the infringements committed by the medium enterprises in the Province of Trujillo. Finally there is the conclusions and recommendations of the present work, in order to give to know the impact that it has to implement the sanctions and the ways in which businesses could improve its managemen

Políticas de seguridad de la información en la Universidad Tecnológica Intercontinental

Information is an asset which, like other assets of the institution, needs to be adequately protected. This research stems fromthe need to develop policies of information security for the Department of Information Technology UTIC. It is therefore proposed to describe the reality presented by UTIC for building a policy of security for information. It was thought that the investigative officials of the Central Regional Headquarters compose the core, the population of which was composed of 84 (eighty four) officers which manage information systems and ten (10) members of the Department of Information Technology. This research is of aquantitative approach, on a descriptive level, and whose design is not experimental. The result showed an overall ratio with respect of insecure information management of 55.95% to safe handling of 44.05%. As a recommendation, the manual of security policies for information security implementation is presented.La información institucional es un activo que, como otros activos de la institución, es esencial que sea protegido adecuadamente. Esta investigación nace de la necesidad de elaborar políticas de seguridad de la información para el Departamento de Tecnología Informática de la Universidad Tecnológica Intercontinental (UTIC). Por ello, se propone describir la realidad que ésta presenta para la construcción de una política de seguridad de la información. Se contempló como núcleo investigativo a los funcionarios de la Sedes de la Regional Central, con lo que la población quedó conformada por 84 (ochenta y cuatro) funcionarios que manejan sistemas de informaciones y 10 (diez) funcionarios del Departamento de Tecnología Informática. Esta investigación es de un enfoque cuantitativo, de nivel descriptivo, el diseño es no experimental. El resultado demostró una proporción global con respecto al manejo de la información de manera insegura 55,95 % y una proporción del manejo seguro de 44,05 %. Como recomendación se presenta el manual de políticas de seguridad de la información para su implementación política