257 research outputs found
Present phases of our so-called Negro problem : open letter to the Right Honorable James Bryce, M. P., of England /
No full textIncludes four letters from the author relating to race relations in the Southern states.Cover title.Mode of access: Internet
Using network inference to discover molecular pathways underlying cytokine synergism and age-related neurodegeneration
No full textThesis: M. Eng. in Computer Science and Molecular Biology, Massachusetts Institute of Technology, Department of Electrical Engineering and Computer Science, 2018.This electronic version was submitted by the student author. The certified thesis is available in the Institute Archives and Special Collections.Cataloged from student-submitted PDF version of thesis.Includes bibliographical references (pages 83-90).New high-throughput "omic" methods can help shed light on molecular pathways underpinning diseases ranging from cancers to neurodegenerative disorders. However, effectively integrating information across these diverse data types is challenging. Network modeling approaches can help bridge this gap. In particular, the Prize- Collecting Steiner Forest approach (PCSF) is a network modeling method that provides high-confidence subnetworks of physically interacting molecules by integrating diverse "omics" data with prior knowledge from protein-protein interaction networks (PPIs). However, PCSF is sensitive to initial parameterization and generating biological hypotheses from the resulting subnetworks can often be difficult. This study increases the interpretability of subnetwork solutions generated PCSF by studying the effect of varying PCSF free parameters and adding annotations for subcellular localization. The PCSF approach is then used to elucidate pathways underlying synergy between cytokines, pro-inflammatory molecules that mediate diverse biological phenomena ranging from anti-viral immunity to autoimmune disorders like inflammatory bowel disease (IBD). In addition, PCSF approach is applied in a cross-species context to integrate information from Drosophila models for neurodegeneration and human Alzheimer's Disease (AD) patients to investigate proximal conserved mechanisms of age-related neurodegeneration.by Bryce Hwang.M. Eng. in Computer Science and Molecular Biolog
Pathogen Dose in Animal Models of Hemorrhagic Fever Virus Infections and the Potential Impact on Studies of the Immune Response
No full textViral hemorrhagic fever viruses come from a wide range of virus families and are a significant cause of morbidity and mortality worldwide each year. Animal models of infection with a number of these viruses have contributed to our knowledge of their pathogenesis and have been crucial for the development of therapeutics and vaccines that have been approved for human use. Most of these models use artificially high doses of virus, ensuring lethality in pre-clinical drug development studies. However, this can have a significant effect on the immune response generated. Here I discuss how the dose of antigen or pathogen is a critical determinant of immune responses and suggest that the current study of viruses in animal models should take this into account when developing and studying animal models of disease. This can have implications for determination of immune correlates of protection against disease as well as informing relevant vaccination and therapeutic strategies
Current research for a vaccine against Lassa hemorrhagic fever virus
No full textBryce M Warner,1 David Safronetz,2 Derek R Stein2 1Department of Medical Microbiology, University of Manitoba, Winnipeg, MB, Canada; 2Zoonotic Diseases and Special Pathogens Program, National Microbiology Laboratory, Public Health Agency of Canada, Winnipeg, MB, Canada Abstract: Lassa virus (LASV) is a rodent-borne arenavirus endemic to several West African countries that causes Lassa fever (LF). LF is typically mild but it can cause severe disease characterized by hemorrhagic fever and multi-organ failure. A current outbreak of LASV in Nigeria has seen greater than 300 cases with a case fatality rate of 22%. Currently, there are limited treatment options and no vaccine candidates are approved to prevent LASV infection. The Coalition for Epidemic Preparedness Innovations has identified LASV as an emerging pathogen of high consequence and this has resulted in a push for several preclinical vaccine candidates to be advanced toward clinical trials. Here, we discuss several important aspects of LASV infection including immunobiology, immune evasion, and correlates of protection against LF, which have been identified through animal models and human infections. In addition, we discuss several vaccine candidates that have shown efficacy in animal models that could be advanced toward clinical trials. The increased fatality rate seen in the recent LASV outbreak in Nigeria highlights the importance of developing effective treatment and prevention strategies against LF. The spike in LASV cases seen in West Africa has the potential for increased mortality and human-to-human transmission, making the development and testing of effective vaccines for LASV critical. Keywords: Lassa virus, Lassa fever, vaccine, therapeutics, prevention, pathogenesi
Marius von Mayenburg and Roland Schimmelpfennig
No full textRoland Schimmelpfennig and Marius von Mayenburg represent a new generation of playwrights to emerge in the German-speaking countries in the late 1990s; other prominent protagonists include Falk Richter, Lukas Bärfuss and Kathrin Röggla, as well as Dea Loher and Sibylle Berg. In this chapter, the author clearly shares some of their approaches, as both revisit and reinvent key conventional dramatic mechanisms, yet from a postdramatic horizon. Fireface, mapped out key themes as well as the (European middle-class) universe that keeps appearing in Mayenburg’s work in a variety of permutations. In Der Hässliche, premiered at Schaubühne Berlin in January 2007, Marius von Mayenburg plays a scathing game with postmodern ideas of the ‘performativity’ of subjectivity and contingency of identity. These academic ideas, in the context of neoliberal capitalism, contribute to an all-encompassing commodification of individuality. In fact, all of Marius von Mayenburg’s plays transcend the hyper-realities of his scenarios into grotesque exposures of absurdities of middle-class life under global capitalism
Effects of experimental interventions to improve the biomedical peer-review process. A systematic review and meta-analysis
No full textBACKGROUND: Quality of the peer-review process has been tested only in small studies. We describe and summarize the randomized trials that investigated interventions aimed at improving peer-review process of biomedical manuscripts. METHODS AND RESULTS: All randomized trials comparing different peer-review interventions at author-, reviewer-, and/or editor-level were included. Differences between traditional and intervention-modified peer-review processes were pooled as stand-ardized mean difference (SMD) in quality based on the definitions used in the individual studies. Main outcomes assessed were quality and duration of the peer-review process. Five-hundred and seventy-five studies were retrieved, eventually yielding 24 randomized trials. Eight studies evaluated the effect of interventions at author-level, 16 at reviewer-level, and 3 at editor-level. Three studies investigated interventions at multiple levels. The effects of the interventions were reported as mean change in review quality, duration of the peer-review process, acceptance/rejection rate, manuscript quality, and number of errors detected in 13, 11, 5, 4, and 3 studies, respectively. At network meta-analysis, reviewer-level interventions were associated with a significant improvement in review quality (SMD, 0.20 [0.06 to 0.33]), at the cost of increased duration of the review process (SMD, 0.15 [0.01 to 0.29]), except for reviewer blinding. Author-and editor-level interventions did not significantly impact peer-review quality and duration (respectively, SMD, 0.17 [−0.16 to 0.51] and SMD, 0.19 [−0.40 to 0.79] for quality, and SMD, 0.17 [−0.16 to 0.51] and SMD, 0.19 [−0.40 to 0.79] for duration). CONCLUSIONS: Modifications of the traditional peer-review process at reviewer-level are associated with improved quality, at the price of longer duration. Further studies are needed. REGISTRATION: URL: https://www.crd.york.ac.uk/prospero; Unique identifier: CRD42020187910
Scalable ab initio fragmentation methods based on a truncated expansion of the non-orthogonal molecular orbital model
No full textAn alternative formulation of the non-orthogonal molecular orbital model of electronic structure theory is developed based on the expansion of the inverse molecular orbital overlap matrix. From this model, a hierarchy of ab initio fragment-based quantum chemistry methods, referred to as the nth-order expanded non-orthogonal molecular orbital methods, are developed using a minimal number of approximations, each of which is frequently employed in intermolecular interaction theory. These novel methods are compared to existing fragment-based quantum chemistry methods, and the implications of those significant differences, where they exist, between the methods developed herein and those already existing methods are examined in detail. Computational complexities and theoretical scaling are also analyzed and discussed. Future extensions for the hierarchy of methods, to account for additional intrafragment and interfragment interactions, are outlined.This article is published as Westheimer, Bryce M., and Mark S. Gordon. "Scalable ab initio fragmentation methods based on a truncated expansion of the non-orthogonal molecular orbital model." The Journal of Chemical Physics 155, no. 15 (2021): 154101. DOI: 10.1063/5.0064864 Copyright 2021 The Author(s). Posted with permission.
DOE Contract Number(s): AC02-07CH1133
Emerg Infect Dis
No full textUse of the vesicular stomatitis virus (VSV)-based Ebola virus vaccine during outbreaks and the potential use of a similar VSV-based Lassa virus vaccine has raised questions about the vaccines' stability should the cold chain fail. We demonstrated that current cold chain conditions might tolerate significant variances without affecting efficacy
Los mundos de Un mundo para Julius
No full textThis article analyses the discourse of Un mundo para Julius (1971) based on specific theoretic concepts developed by M. Bakhtin, especially those from “Discourse in the novel” (1934). That is how the different strategies used by the author, Alfredo Bryce Echenique in order to build a parodic picture of the “limeña” society will be exposed and understood.En este artículo se lleva a cabo un análisis del discurso novelesco de Un mundo para Julius (1971), a partir de ciertos conceptos teóricos desarrollados por M. M.Bajtín, sobre todos los presentes en “La palabra en la novela” (1924). Así, son expuestas y explicadas las diferentes estrategias que Alfredo Bryce Echenique utiliza en esta obra para construir un retrato paródico de la sociedad limeña
Biljana Srbljanovic and Ivana Sajko: Voice in the Place of Silence
No full textIn this chapter, the author advances an argument that the local context(s) can be seen to have shaped a very specific type of dramaturgy that is well exemplified by the respective authorial idioms of playwrights Biljana Srbljanovic and Ivana Sajko. She proposes that this work demands to be seen in new ways, rather than by reference to existing taxonomies and discourses. Srbljanovic and Sajko’s post-Brechtain authorial voice abolishes the traditional hierarchies while deploying a more relational form of self-inscription. They make themselves audible within the stage directions to engender a metadialogue with the text and engage the reader/audience in a relationship. Voice has been as integral to the feminist discourses as ecriture feminine, although Briony Lipton and Elizabeth Mackinlay note that the advent of neoliberalism has complicated this agenda and opened up the potential of silence. The chapter opens up avenues for further research at the intersection of voice studies, feminism, trauma, politics, and the Balkans
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