Preliminary Investigation of Peripheral Subsidence Associated with Hurricane Outflow

Synoptic and Nimbus I infrared radiometer data used to investigate peripheral subsidence in hurricane outflo

Development of a Human Cytomegalovirus (HCMV)-Based Therapeutic Cancer Vaccine Uncovers a Previously Unsuspected Viral Block of MHC Class I Antigen Presentation

Human cytomegalovirus (HCMV) induces a uniquely high frequency of virus-specific effector/memory CD8+ T-cells, a phenomenon termed “memory inflation”. Thus, HCMV-based vaccines are particularly interesting in order to stimulate a sustained and strong cellular immune response against cancer. Glioblastoma multiforme (GBM) is the most aggressive primary brain tumor with high lethality and inevitable relapse. The current standard treatment does not significantly improve the desperate situation underlining the urgent need to develop novel approaches. Although HCMV is highly fastidious with regard to species and cell type, GBM cell lines are susceptible to HCMV. In order to generate HCMV-based therapeutic vaccine candidates, we deleted all HCMV-encoded proteins (immunoevasins) that interfere with MHC class I presentation. The aim being to use the viral vector as an adjuvant for presentation of endogenous tumor antigens, the presentation of high levels of vector-encoded neoantigens and finally the repurposing of bystander HCMV-specific CD8+ T cells to fight the tumor. As neoantigen, we exemplarily used the E6 and E7 proteins of human papillomavirus type 16 (HPV-16) as a non-transforming fusion protein (E6/E7) that covers all relevant antigenic peptides. Surprisingly, GBM cells infected with E6/E7-expressing HCMV-vectors failed to stimulate E6-specific T cells despite high level expression of E6/E7 protein. Further experiments revealed that MHC class I presentation of E6/E7 is impaired by the HCMV-vector although it lacks all known immunoevasins. We also generated HCMV-based vectors that express E6-derived peptide fused to HCMV proteins. GBM cells infected with these vectors efficiently stimulated E6-specific T cells. Thus, fusion of antigenic sequences to HCMV proteins is required for efficient presentation via MHC class I molecules during infection. Taken together, these results provide the preclinical basis for development of HCMV-based vaccines and also reveal a novel HCMV-encoded block of MHC class I presentation

Overexpression of Mcl-1 exacerbates lymphocyte accumulation and autoimmune kidney disease in lpr mice

Cell death by apoptosis has a critical role during embryonic development and in maintaining tissue homeostasis. In mammals, there are two converging apoptosis pathways: the ‘extrinsic’ pathway, which is triggered by engagement of cell surface ‘death receptors’ such as Fas/APO-1; and the ‘intrinsic’ pathway, which is triggered by diverse cellular stresses, and is regulated by prosurvival and pro-apoptotic members of the Bcl-2 family of proteins. Pro-survival Mcl-1, which can block activation of the proapoptotic proteins, Bax and Bak, appears critical for the survival and maintenance of multiple haemopoietic cell types. To investigate the impact on haemopoiesis of simultaneously inhibiting both apoptosis pathways, we introduced the vavP-Mcl-1 transgene, which causes overexpression of Mcl-1 protein in all haemopoietic lineages, into Faslpr/lpr mice, which lack functional Fas and are prone to autoimmunity. The combined mutations had a modest impact on myelopoiesis, primarily an increase in the macrophage/monocyte population in Mcl-1tg/lpr mice compared with lpr or Mcl-1tg mice. The impact on lymphopoiesis was striking, with a marked elevation in all major lymphoid subsets, including the non-conventional double-negative (DN) T cells (TCRβ+ CD4– CD8– B220+ ) characteristic of Faslpr/lpr mice. Of note, the onset of autoimmunity was markedly accelerated in Mcl-1tg/lpr mice compared with lpr mice, and this was preceded by an increase in immunoglobulin (Ig)-producing cells and circulating autoantibodies. This degree of impact was surprising, given the relatively mild phenotype conferred by the vavP-Mcl-1 transgene by itself: a two- to threefold elevation of peripheral B and T cells, no significant increase in the non-conventional DN T-cell population and no autoimmune disease. Comparison of the phenotype with that of other susceptible mice suggests that the development of autoimmune disease in Mcl-1tg/lpr mice may be influenced not only by Ig-producing cells but also other haemopoietic cell types

A Proposal for an Alternate Dispute Resolution Process for the Fashion Industry After the Innovative Design Protection and Piracy Prevention Act

This Note will explore the way alternative dispute resolution can be used to ensure that the proposed IDPPPA meets its stated goal without unnecessarily chilling creative efforts of unproven designers. Though the bill is aimed at stopping the proliferation of design copying (knockoffs), insiders are concerned that the bill will dissuade designers from producing designs that merely incorporate elements from other designs ( inspired-by designs). Some believe that the judiciary will interpret the IDPPPA expansively, resulting in the punishment of designers who produce knockoffs as well as those who draw inspiration from other designs. However, a chilling effect could be mitigated if an alternative dispute resolution process is established by the fashion industry. An arbitration panel, equipped with an internal appellate procedure and the ability to appeal decisions to the court system, would enable designers seeking to produce inspired-by designs to quickly secure some guarantee that they will not be liable for copyright infringement. This Note will propose the creation of such a panel and will draw on several models-the National Advertising Review Council, the Uniform Domain Name Dispute Resolution Policy and Professor Michael Carroll\u27s Free Use Board-to suggest the panel structure would preserve the fashion industry\u27s innovative spirit after (despite?) the IDPPPA

Eficiencia del Método de Tecnología Anaerobia en el tratamiento de efluentes industriales en la industria papelera ATLAS, para su uso potencial como agua de riego

Los efluente industriales que salen de la producción de las Industrias Papeleras, son los que hoy en día, la mayoría de las empresas, busca el método de tratamiento adecuado para tratarlos y de esa manera poder reutilizar dichas aguas, como por ejemplo, en la Industria Papelera Atlas reutilizan el 60% de sus efluentes y son tratados mediante su propia planta de tratamiento, los mismo que son reutilizados en la producción de papel reciclado, y el otro 40% restante lo vierten directamente al río Rímac, es por esa razón que esta investigación tiene como objetivo principal, determinar la eficiencia de la aplicación del método de tecnología anaerobia, en el tratamiento de efluentes industriales para su uso potencial como agua de riego, para el logro de dicho objetivo, se armó un reactor anaerobio de tipo ascendente (RAFA), con una capacidad de contener 20 litros de efluente industrial, de donde se tomaron 2 muestras representativas; una inicial directamente de la fuente, extrayendo 4 litros por cada muestra, se aplicó el tratamiento en el reactor anaerobio de flujo ascendente con los 16 litros de efluente restante y una muestra final después del tratamiento, luego se efectuaron los análisis físicos, químicos y microbiológicos en los laboratorios certificados por la Universidad Agraria de la Molina, obteniendo resultados favorables, lo que se explica más adelante en la parte estadística del desarrollo de la tesis

Master and novice secondary science teachers' understandings and use of the learning cycle.

The learning cycle paradigm had been used in science classrooms for nearly four decades. This investigation seeks to reveal how the 1earning cycle, as originally designed, is currently understood and implemented by teachers in authentic classroom settings. The specific purposes of this study were: (1) to describe teachers who use the learning cycle and compare their understandings and perceptions of the learning cycle procedure in instruction; (2) to elicit novice and master teacher perspectives on their instruction and determine their perception of the process by which learning cycles are implemented in the science classroom; (3) to describe the context of science instruction in the novice and master teacher's classroom to ascertain how the teacher facilitates implementation of the learning cycle paradigm in their authentic classroom setting. The study used a learning cycle survey, interviews and classroom observations using the Learning Cycle Teacher Behavior Instruments and the Verbal Interaction Category System to explore these features of learning cycle instruction. The learning cycle survey was administered to a sample of teachers who use the learning cycle, including master and novice learning cycle teachers. One master and one novice learning cycle teacher were selected from this sample for further study. Analysis of the surveys showed no significant differences in master and novice teacher understandings of the learning cycle as assessed by the instrument. However, interviews and observations of the selected master and novice learning cycle teachers showed several differences in how the paradigm is understood and implemented in the classroom. The master learning cycle teacher showed a more developed teaching philosophy and had more engaged, extensive interactions with students. The novice learning cycle teacher held a more naive teaching philosophy and had fewer, less developed interactions with students. The most significant difference was seen in the use of questioning and discussion. The master teacher used diverse questioning techniques and guided students in discussion of their findings while the novice teachers used more rote response questions and controlled the discussion. The findings of this study have implications for science teacher education, especially in the preparation of teachers in science methods courses and student teaching, and in in-service education programs

El sentenciado por delito de terrorismo y el derecho a trabajar libremente con relación a la Ley Nº 30794, Lima, 2019

La presente investigación, “El Sentenciado por Delito de Terrorismo y el Derecho a Trabajar Libremente con Relación a la Ley Nº 30794, Lima 2019”, cuyo objetivo fue Analizar de qué manera el sentenciado por el delito de terrorismo tiene derecho a trabajar libremente con relaciona a la Ley 30794. Ley que establece como requisito para prestar servicios en el sector público, no haber tenido condena por terrorismo, apología del delito de terrorismo y otros delitos. La metodología utilizada para nuestra investigación es de enfoque cualitativo, de tipo básico, diseño de teoría fundamentada y el nivel de nuestra investigación es descriptiva – correlacional. Asimismo, se utilizó guías de entrevista para la recolección de datos y guía de análisis documental. La conclusión a la que se ha llegado es que los sentenciados por delito de terrorismo, tienen derecho a trabajar libremente con relación a la Ley Nº 30794. Debido a que se trata de un derecho fundamental contemplado en nuestra Constitución Política del Perú y ratificados en tratados internacionales, como la Declaración Universal de los Derechos Humanos y el Pacto Internacional de Derechos Económicos, Sociales y Culturales. Que la no rehabilitación o inhabilitación de los sentenciados por el delito de terrorismo afecta su derecho a trabajar libremente. Finalmente, que la reinserción social de los sentenciados por delito de terrorismo tiene limitación laboral contenida en la ley Nº 30794