657 research outputs found
The routinisation of management controls in software.
Author's post-print version. Final version published by Springer; available online at http://link.springer.com/Our paper aims to explore management control as complex and intertwining process over time, rather than the (mainstream) fixation on rational, optimising tools for ensuring business success. We set out to contribute towards our understanding of why and how particular management controls evolve over time as they do. We discuss how the management control routines of one organisation emerged and reproduced (through software), and moved towards a situation of becoming accepted and generally unquestioned across much of the industry. The creativity and championing of one particular person was found to be especially important in this unfolding change process. Our case study illuminates how management control (software) routines can be an important carrier of organisational knowledge, both as an engine for continuity but also potentially as a catalyst for change. We capture this process by means of exploring the ‘life-story’ of a piece of software that is adopted in the corrugated container industry
A live RSV vaccine with engineered thermostability is immunogenic in cotton rats despite high attenuation
Respiratory syncytial virus (RSV) is a leading cause of infant hospitalization and there remains no pediatric vaccine. RSV live-attenuated vaccines (LAVs) have a history of safe testing in infants; however, achieving an effective balance of attenuation and immunogenicity has proven challenging. Here we seek to engineer an RSV LAV with enhanced immunogenicity. Genetic mapping identifies strain line 19 fusion (F) protein residues that correlate with pre-fusion antigen maintenance by ELISA and thermal stability of infectivity in live RSV. We generate a LAV candidate named OE4 which expresses line 19F and is attenuated by codon-deoptimization of non-structural (NS1 and NS2) genes, deletion of the small hydrophobic (SH) gene, codon-deoptimization of the attachment (G) gene and ablation of the secreted form of G. OE4 (RSV-A2-dNS1-dNS2-ΔSH-dGm-Gsnull-line19F) exhibits elevated pre-fusion antigen levels, thermal stability, immunogenicity, and efficacy despite heavy attenuation in the upper and lower airways of cotton rats
Has Behavioral Science Tumbled Through the Biological Looking Glass? Will Brief, Evidence-Based Training Return It From the Rabbit Hole?
Time constraints and professional demands leave practicing professionals unlikely to enroll in extended training such as a semester-long graduate course. Thus, the three-hour continuing education format has become a standard for those in practice. One may ask what sorts of training strategies optimize that format. To explore that, a three hour training program for seventy-six practicing mental health professionals, most of whom self-identified as psychologists, was devised. It made use of primarily antecedent techniques that have been shown to bring about changed perceptions on a number of topics. Content focused on two areas of importance to behavior analysts, the culture’s increasing acceptance of the biological causation model of disorders such as attentiondeficit hyperactivity disorder (ADHD), unipolar depression, anxiety disorders, and schizophrenia, and the field’s increasing reliance on medications, often to the exclusion of behavioral methods. Pre-post assessment showed that participants had changed their thinking regarding the two content areas. The authors caution that participants’ changed opinions may serve as setting events to changes in practice, but those changes are verbal. One must not assume changes in practice techniques will automatically occur
Demostración de resultado económico: percepción del comando da aeronáutica de Brasil
No ano de 2010, uma alteração no quadro normativo brasileiro introduziu a Demonstração do Resultado Econômico (DRE) para o setor público, que busca comparar custos internos de produção com valores de mercado, segundo o conceito de custo de oportunidade. Este estudo procura analisar as possÃveis respostas estratégicas dos gestores , buscando perceber se a cultura contábil existente no PaÃs permite a aceitação do novo instrumento. Por meio das percepções dos agentes públicos do Comando da Aeronáutica (Comaer), no Brasil, conclui-se que a resposta estratégica dos entrevistados tende para a atitude de aceitação da nova rotina, demonstrando traços de menor conservadorismo e maior interesse pela evidenciação de resultados.In 2010, a change in the Brazilian accounting regulatory framework introduced the Demonstração do Resultado Econômico (DRE) [Economic Income Statement] for the public sector, which seeks to compare the internal costs of production to market values, according to the concept of opportunity cost. This study aims to analyse the possible strategic responses of managers and tries to understand if the existing accounting culture in Brazil facilitates the introduction of the new statement. By means of perceptions of officials of the Aeronautical Command (Comaer), in Brazil, it is possible to conclude that the strategic response of respondents is closer to acceptance of the new routine, showing traces of less conservatism and greater interest for displaying results.En el año 2010, una modificación del cuadro normativo brasileño introdujo la Demostración del Resultado Económico (DRE) para el sector público, que busca comparar los costos internos de producción con los valores del mercado, según el concepto de costo de oportunidad. Este estudio tiene como objetivo analizar las posibles respuestas estratégicas de los gestores, con el fin de percibir si la cultura contable existente en el paÃs permite la aceptación del nuevo instrumento. Por medio de las percepciones de los agentes públicos del Comando da Aeronáutica (Comaer), en Brasil, se concluyó que la respuesta estratégica de los entrevistados tiende a aceptar la nueva rutina, mostrando rasgos de menos conservadurismo y más interés por la manifestación de resultados.Fundação para a Ciência e a Tecnologia (FCT
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Cryo-EM structures of the SARS-CoV-2 endoribonuclease Nsp15 reveal insight into nuclease specificity and dynamics.
Nsp15, a uridine specific endoribonuclease conserved across coronaviruses, processes viral RNA to evade detection by host defense systems. Crystal structures of Nsp15 from different coronaviruses have shown a common hexameric assembly, yet how the enzyme recognizes and processes RNA remains poorly understood. Here we report a series of cryo-EM reconstructions of SARS-CoV-2 Nsp15, in both apo and UTP-bound states. The cryo-EM reconstructions, combined with biochemistry, mass spectrometry, and molecular dynamics, expose molecular details of how critical active site residues recognize uridine and facilitate catalysis of the phosphodiester bond. Mass spectrometry revealed the accumulation of cyclic phosphate cleavage products, while analysis of the apo and UTP-bound datasets revealed conformational dynamics not observed by crystal structures that are likely important to facilitate substrate recognition and regulate nuclease activity. Collectively, these findings advance understanding of how Nsp15 processes viral RNA and provide a structural framework for the development of new therapeutics
Bacteriophage Lysin Mediates the Binding of Streptococcus mitis to Human Platelets through Interaction with Fibrinogen
The binding of bacteria to human platelets is a likely central mechanism in the pathogenesis of infective endocarditis. We have previously found that platelet binding by Streptococcus mitis SF100 is mediated by surface components encoded by a lysogenic bacteriophage, SM1. We now demonstrate that SM1-encoded lysin contributes to platelet binding via its direct interaction with fibrinogen. Far Western blotting of platelets revealed that fibrinogen was the major membrane-associated protein bound by lysin. Analysis of lysin binding with purified fibrinogen in vitro confirmed that these proteins could bind directly, and that this interaction was both saturable and inhibitable. Lysin bound both the Aα and Bβ chains of fibrinogen, but not the γ subunit. Binding of lysin to the Bβ chain was further localized to a region within the fibrinogen D fragment. Disruption of the SF100 lysin gene resulted in an 83±3.1% reduction (mean ± SD) in binding to immobilized fibrinogen by this mutant strain (PS1006). Preincubation of this isogenic mutant with purified lysin restored fibrinogen binding to wild type levels. When tested in a co-infection model of endocarditis, loss of lysin expression resulted in a significant reduction in virulence, as measured by achievable bacterial densities (CFU/g) within vegetations, kidneys, and spleens. These results indicate that bacteriophage-encoded lysin is a multifunctional protein, representing a new class of fibrinogen-binding proteins. Lysin appears to be cell wall-associated through its interaction with choline. Once on the bacterial surface, lysin can bind fibrinogen directly, which appears to be an important interaction for the pathogenesis of endocarditis
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