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Multiple Stiffened Deck Profiles
CAN/CSA-S136-M89 and the AISI Specification on Cold Formed Steel Design use different methods to determine the effective width of multiple stiffened compressive elements when no local buckling in the sub-elements occurs. Both methods replace the multiple stiffened element with a flat plate element centered at the neutral axis of the multiple stiffened element. The methods differ in assigning an equivalent thickness to the straight line element. The AISI method provides sufficient thickness to match the moment of inertia of the multiple stiffened element, while the S136 method makes use of orthotropic plate theory, however, dealing only with the elastic buckling component. For a given geometry, they predict different effective widths. In this paper, experimental data is compared with the predicted values of each method and conclusions are drawn from these comparisons. Representative hat sections were subjected to uniformly distributed loads using a vacuum chamber. Profiles with one, two, three and four· intermediate stiffeners were tested, using three material thicknesses for each configuration of stiffeners
Cerebrospinal fluid findings in an adult with human metapneumovirus–associated encephalitis
__To the Editor:__
Acute encephalitis/encephalopathy associated with human metapneumovirus (HMPV) has been documented in children. Recently, Fok et al. described an encephalitis case in an adult but were unable to test cerebrospinal fluid (CSF) for HMPV. Following authors’ recommendations, we performed diagnostic testing on the CSF of an adult with HMPV-associated encephalitis.
A previously healthy 61-year-old man came to our institution with headache and seizures 5 days after onset of an influenza-like illness. A lumbar puncture on admission revealed pleocytosis (36 cells/μL) and a mononuclear predominance of 98%. Results of magnetic resonance imaging and computed tomography of the head and chest radiography on admission were inconclusive. The patient was treated in the intensive care unit for possible viral and bacterial meningoencephalitis. Although results of routine CSF-workup for infectious causes were unremarkable, total CSF protein level was elevated at 1.39 g/L (reference range 0.2–0.4 g/L). A nasopharyngeal swab specimen was positive for HMPV (cycle threshold 28.6) using duplex reverse transcription PCR (r-gene; Biomérieux, Marcy l’Etoile, France).
However, HMPV reverse transcription PCR results were negative in the concurrent CSF sample. Immunofluorescence assays demonstrated HMPV IgG (serum titer 1:8,192; CSF titers 1:64 and 1:32). Indices calculated using the formula (IgGCSF HMPV/IgGSerum HMPV)/(IgGCSF total/IgGSerum total) were lower than the cut-off value of 4, indicating absence of intrathecal IgG against HMPV (Table).
As in the study by Fok et al., our case supports consideration of HMPV as a causative agent of acute encephalitis after respiratory tract infection in adults. We could not demonstrate direct or indirect evidence of HMPV CSF invasion as the cause for HMPV-associated encephalitis in an adult, in contrast to a case in a child in which detection of HMPV in CSF suggested a causative role in acute encephalitis. Our data may point toward the role of nonspecific inflammatory response as the main pathogenic factor in HMPV-related encephalitis in adults
Replicating viral vector platform exploits alarmin signals for potent CD8<sup>+</sup> T cell-mediated tumour immunotherapy.
Viral infections lead to alarmin release and elicit potent cytotoxic effector T lymphocyte (CTL <sup>eff</sup> ) responses. Conversely, the induction of protective tumour-specific CTL <sup>eff</sup> and their recruitment into the tumour remain challenging tasks. Here we show that lymphocytic choriomeningitis virus (LCMV) can be engineered to serve as a replication competent, stably-attenuated immunotherapy vector (artLCMV). artLCMV delivers tumour-associated antigens to dendritic cells for efficient CTL priming. Unlike replication-deficient vectors, artLCMV targets also lymphoid tissue stroma cells expressing the alarmin interleukin-33. By triggering interleukin-33 signals, artLCMV elicits CTL <sup>eff</sup> responses of higher magnitude and functionality than those induced by replication-deficient vectors. Superior anti-tumour efficacy of artLCMV immunotherapy depends on interleukin-33 signalling, and a massive CTL <sup>eff</sup> influx triggers an inflammatory conversion of the tumour microenvironment. Our observations suggest that replicating viral delivery systems can release alarmins for improved anti-tumour efficacy. These mechanistic insights may outweigh safety concerns around replicating viral vectors in cancer immunotherapy
Non-neutralizing antibodies elicited by recombinant Lassa-Rabies vaccine are critical for protection against Lassa fever
Lassa fever (LF), caused by Lassa virus (LASV), is a viral hemorrhagic fever for which no approved vaccine or potent antiviral treatment is available. LF is a WHO priority disease and, together with rabies, a major health burden in West Africa. Here we present the development and characterization of an inactivated recombinant LASV and rabies vaccine candidate (LASSARAB) that expresses a codon-optimized LASV glycoprotein (coGPC) and is adjuvanted by a TLR-4 agonist (GLA-SE). LASSARAB elicits lasting humoral response against LASV and RABV in both mouse and guinea pig models, and it protects both guinea pigs and mice against LF. We also demonstrate a previously unexplored role for non-neutralizing LASV GPC-specific antibodies as a major mechanism of protection by LASSARAB against LF through antibody-dependent cellular functions. Overall, these findings demonstrate an effective inactivated LF vaccine and elucidate a novel humoral correlate of protection for LF.NIH grants R01 AI105204 to M.J.S., by the Jefferson Vaccine Center, and by the Fundação para a Ciência e Tecnologia (FCT) scholarship PD/BD/105847/2014 (to T.A.-M.). This work was also funded in part through the NIAID Division of Intramural Research and the NIAID Division of Clinical Research, Battelle Memorial Institute’s prime contract with the U.S. National Institute of Allergy and Infectious Diseases (NIAID) under Contract No. HHSN272200700016Iinfo:eu-repo/semantics/publishedVersio
Sport, War and Democracy in Classical Athens
This article concerns the paradox of athletics in classical Athens. Democracy may have opened up politics to every class of Athenian but it had little impact on sporting participation. The city’s athletes continued to drawn predominantly from the upper class. It comes as a surprise then that lower-class Athenians actually esteemed athletes above every other group in the public eye, honoured them very generously when they won, and directed a great deal of public and private money to sporting competitions and facilities. In addition athletics escaped the otherwise persistent criticism of upper-class activities in the popular culture of the democracy. The research of social scientists on sport and aggression suggests this paradox may have been due to the cultural overlap between athletics and war under the Athenian democracy. The article concludes that the practical and ideological democratization of war by classical Athens legitimized and supported upper-class sport
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