In his early work, Moore argues that business itself was a MacIntyrean practice. He later rejected this view in response to criticisms from Beadle and others. Most subsequent work, including that of Moore, adopted a view of organizations, including firms, as institutions that house a core practice. We first recount Moore's early view, defend and it from various criticisms. We then briefly review research in management and finance arguing that this research supports a view of business consonant with Moore's early view. Thus, we argue that business is a distinct practice that integrates various productive and auxiliary practices to facilitate mutually beneficial transactions. We conclude by discussing implications of this view, noting that it might be viewed as a classical liberal appropriation of the MacIntyrean framework, and arguing that it poses a challenge to MacIntyreans working with a neo-Aristotelian perspective.

Research Article| April 01 2020 On Zeezrom’s Conversion: Rationality, Tradition, and Money Robert Couch Robert Couch Robert Couch is associate professor of Global Management at Earlham College in Richmond, Indiana. He is the author of several articles on the Book of Mormon and economics and serves on the executive board of the Latter-day Saint Theology Seminar. Search for other works by this author on: This Site Google Journal of Book of Mormon Studies (2020) 29: 120–151. https://doi.org/10.5406/jbookmormstud2.29.2020.0120 Cite Icon Cite Share Icon Share Facebook Twitter LinkedIn MailTo Permissions Search Site Citation Robert Couch; On Zeezrom’s Conversion: Rationality, Tradition, and Money. Journal of Book of Mormon Studies 1 April 2020; 29 120–151. doi: https://doi.org/10.5406/jbookmormstud2.29.2020.0120 Download citation file: Zotero Reference Manager EasyBib Bookends Mendeley Papers EndNote RefWorks BibTex toolbar search Search Dropdown Menu toolbar search search input Search input auto suggest filter your search All Scholarly Publishing CollectiveUniversity of Illinois PressJournal of Book of Mormon Studies Search Advanced Search The text of this article is only available as a PDF. Copyright 2020 by the Board of Trustees of the University of Illinois2020 Article PDF first page preview Close Modal You do not currently have access to this content.

Abstract Background The ongoing Middle East respiratory syndrome coronavirus (MERS-CoV) infections pose threats to public health worldwide, making an understanding of MERS pathogenesis and development of effective medical countermeasures (MCMs) urgent. Methods We used homozygous (+/+) and heterozygous (+/−) human dipeptidyl peptidase 4 (hDPP4) transgenic mice to study the effect of hDPP4 on MERS-CoV infection. Specifically, we determined values of 50% lethal dose (LD50) of MERS-CoV for the 2 strains of mice, compared and correlated their levels of soluble (s)hDPP4 expression to susceptibility, and explored recombinant (r)shDPP4 as an effective MCM for MERS infection. Results hDPP4+/+ mice were unexpectedly more resistant than hDPP4+/− mice to MERS-CoV infection, as judged by increased LD50, reduced lung viral infection, attenuated morbidity and mortality, and reduced histopathology. Additionally, the resistance to MERS-CoV infection directly correlated with increased serum shDPP4 and serum virus neutralizing activity. Finally, administration of rshDPP4 led to reduced lung virus titer and histopathology. Conclusions Our studies suggest that the serum shDPP4 levels play a role in MERS pathogenesis and demonstrate a potential of rshDPP4 as a treatment option for MERS. Additionally, it offers a validated pair of Tg mice strains for characterizing the effect of shDPP4 on MERS pathogenesis.

The payback approach to capital budgeting is proposed as a clear and intuitive way to think about fiscal policy and the normative problem of generational equity. Payback has been an enduring tool of corporate capital budgeting decisions and the home mortgage industry. As a clear and resonant conceptual tool, payback measures thus have the potential to mobilize political will for overcoming difficult fiscal policy problems, when they arise. Numerical examples calibrated to U.S. federal budget history illustrate how payback measures can be used in practice.

To determine if a hypersensitive-type lung pathology might occur when mice were given an inactivated MERS-CoV vaccine and challenged with infectious virus as was seen with SARS-CoV vaccines, we prepared and vaccinated mice with an inactivated MERS-CoV vaccine. Neutralizing antibody was induced by vaccine with and without adjuvant and lung virus was reduced in vaccinated mice after challenge. Lung mononuclear infiltrates occurred in all groups after virus challenge but with increased infiltrates that contained eosinophils and increases in the eosinophil promoting IL-5 and IL-13 cytokines only in the vaccine groups. Inactivated MERS-CoV vaccine appears to carry a hypersensitive-type lung pathology risk from MERS-CoV infection that is similar to that found with inactivated SARS-CoV vaccines from SARS-CoV infection.

To better understand the systemic response to naturally acquired acute respiratory viral infections, we prospectively enrolled 1610 healthy adults in 2009 and 2010. Of these, 142 subjects were followed for detailed evaluation of acute viral respiratory illness. We examined peripheral blood gene expression at 7 timepoints: enrollment, 5 illness visits and the end of each year of the study. 133 completed all study visits and yielded technically adequate peripheral blood microarray gene expression data. Seventy-three (55%) had an influenza virus infection, 64 influenza A and 9 influenza B. The remaining subjects had a rhinovirus infection (N = 32), other viral infections (N = 4), or no viral agent identified (N = 24). The results, which were replicated between two seasons, showed a dramatic upregulation of interferon pathway and innate immunity genes. This persisted for 2-4 days. The data show a recovery phase at days 4 and 6 with differentially expressed transcripts implicated in cell proliferation and repair. By day 21 the gene expression pattern was indistinguishable from baseline (enrollment). Influenza virus infection induced a higher magnitude and longer duration of the shared expression signature of illness compared to the other viral infections. Using lineage and activation state-specific transcripts to produce cell composition scores, patterns of B and T lymphocyte depressions accompanied by a major activation of NK cells were detected in the acute phase of illness. The data also demonstrate multiple dynamic gene modules that are reorganized and strengthened following infection. Finally, we examined pre- and post-infection anti-influenza antibody titers defining novel gene expression correlates.

ABSTRACT Characterized animal models are needed for studying the pathogenesis of and evaluating medical countermeasures for persisting Middle East respiratory syndrome-coronavirus (MERS-CoV) infections. Here, we further characterized a lethal transgenic mouse model of MERS-CoV infection and disease that globally expresses human CD26 (hCD26)/DPP4. The 50% infectious dose (ID50) and lethal dose (LD50) of virus were estimated to be <1 and 10 TCID50 of MERS-CoV, respectively. Neutralizing antibody developed in the surviving mice from the ID50/LD50 determinations, and all were fully immune to challenge with 100 LD50 of MERS-CoV. The tissue distribution and histopathology in mice challenged with a potential working dose of 10 LD50 of MERS-CoV were subsequently evaluated. In contrast to the overwhelming infection seen in the mice challenged with 105 LD50 of MERS-CoV, we were able to recover infectious virus from these mice only infrequently, although quantitative reverse transcription-PCR (qRT-PCR) tests indicated early and persistent lung infection and delayed occurrence of brain infection. Persistent inflammatory infiltrates were seen in the lungs and brain stems at day 2 and day 6 after infection, respectively. While focal infiltrates were also noted in the liver, definite pathology was not seen in other tissues. Finally, using a receptor binding domain protein vaccine and a MERS-CoV fusion inhibitor, we demonstrated the value of this model for evaluating vaccines and antivirals against MERS. As outcomes of MERS-CoV infection in patients differ greatly, ranging from asymptomatic to overwhelming disease and death, having available both an infection model and a lethal model makes this transgenic mouse model relevant for advancing MERS research. IMPORTANCE Fully characterized animal models are essential for studying pathogenesis and for preclinical screening of vaccines and drugs against MERS-CoV infection and disease. When given a high dose of MERS-CoV, our transgenic mice expressing hCD26/DPP4 viral receptor uniformly succumbed to death within 6 days, making it difficult to evaluate host responses to infection and disease. We further characterized this model by determining both the ID50 and the LD50 of MERS-CoV in order to establish both an infection model and a lethal model for MERS and followed this by investigating the antibody responses and immunity of the mice that survived MERS-CoV infection. Using the estimated LD50 and ID50 data, we dissected the kinetics of viral tissue distribution and pathology in mice challenged with 10 LD50 of virus and utilized the model for preclinical evaluation of a vaccine and drug for treatment of MERS-CoV infection. This further-characterized transgenic mouse model will be useful for advancing MERS research.

ABSTRACTThe emergence of Middle East respiratory syndrome-coronavirus (MERS-CoV) in the Middle East since 2012 has caused more than 900 human infections with ∼40% mortality to date. Animal models are needed for studying pathogenesis and for development of preventive and therapeutic agents against MERS-CoV infection. Nonhuman primates (rhesus macaques and marmosets) are expensive models of limited availability. Although a mouse lung infection model has been described using adenovirus vectors expressing human CD26/dipeptidyl peptidase 4 (DPP4), it is believed that a transgenic mouse model is needed for MERS-CoV research. We have developed this transgenic mouse model as indicated in this study. We show that transgenic mice globally expressing hCD26/DPP4 were fully permissive to MERS-CoV infection, resulting in relentless weight loss and death within days postinfection. High infectious virus titers were recovered primarily from the lungs and brains of mice at 2 and 4 days postinfection, respectively, whereas viral RNAs were also detected in the heart, spleen, and intestine, indicating a disseminating viral infection. Infected Tg+mice developed a progressive pneumonia, characterized by extensive inflammatory infiltration. In contrast, an inconsistent mild perivascular cuffing was the only pathological change associated with the infected brains. Moreover, infected Tg+mice were able to activate genes encoding for many antiviral and inflammatory mediators within the lungs and brains, coinciding with the high levels of viral replication. This new and unique transgenic mouse model will be useful for furthering knowledge of MERS pathogenesis and for the development of vaccine and treatments against MERS-CoV infection.IMPORTANCESmall and economical animal models are required for the controlled and extensive studies needed for elucidating pathogenesis and development of vaccines and antivirals against MERS. Mice are the most desirable small-animal species for this purpose because of availability and the existence of a thorough knowledge base, particularly of genetics and immunology. The standard small animals, mice, hamsters, and ferrets, all lack the functional MERS-CoV receptor and are not susceptible to infection. So, initial studies were done with nonhuman primates, expensive models of limited availability. A mouse lung infection model was described where a mouse adenovirus was used to transfect lung cells for receptor expression. Nevertheless, all generally agree that a transgenic mouse model expressing the DPP4 receptor is needed for MERS-CoV research. We have developed this transgenic mouse model as indicated in this study. This new and unique transgenic mouse model will be useful for furthering MERS research.

Using an effectuation theory lens, we study reverse stock splits in the biotech industry where significant uncertainty makes specific scenarios of success difficult to predict. We conjecture and find that, in contrast to other environments where there is less uncertainty, reverse stock splits in the biotech industry are followed by positive abnormal returns over the subsequent 1- to 12-months. Also consistent with our effectuation-based predictions, we find that these returns are positively related to the reverse split ratio, size, cash holding, and long-term debt, and negatively related to the market-to-book ratio and firm age. We also find that liquidity increases after a reverse stock split. These results suggest that the concept of effectuation theory is better suited to analyzing reverse stock splits in the biotech industry.Â

The effectiveness of trivalent influenza vaccines may be reduced in older versus younger adults because of age-related immunosenescence. The use of an adjuvant in such a vaccine is one strategy that may combat immunosenescence, potentially by bolstering T-cell mediated responses.

This archive contains an "interactive" version of data associated with the eLife paper "Integrative genomic analysis of the human immune response to influenza vaccination" by Luis M Franco, Kristine L Bucasas, Janet M Wells, Diane Niño, Xueqing Wang, Gladys E Zapata, Nancy Arden, Alexander Renwick, Peng Yu, John M Quarles, Molly S Bray, Robert B Couch, John W Belmont, Chad A Shaw http://dx.doi.org/10.7554/eLife.00299 (doi:10.7554/eLife.00299) Installation: (1) Download the rar file, link available from the paper. (2) Unrar the file: Mac OS X: Use UnRarX - http://www.unrarx.com Linux : unrar command - http://en.wikipedia.org/wiki/Unrar (3) Open the file "vaxgenomics.htm" in your favorite browser use File>Open : Once opened in your browser, you should see a "Circos"-style circular plot of the data, and links to the tables and figures used in this application. Each table includes a link-out from GeneID to the Entrez entry for that Gene as well as additional links to the data. The link to Entrez requires access to NCBI, so will only work if you have Internet availability for this to work. All other links point to content contained within the application/archive. (4) Figures: High-resolution copies of the figures included in the paper. Fig 1: eQTL profile of flu vaccination response. Markers associated with cis gene expression identified in the discovery cohort were replicated in a vaidation cohort and -log10 p-values for both data sets are shown in the genome wide circularized graphic. Fig 2: Effect of the treatment on eQTL assocation. We observed that the pattern of association between gene expression and SNP changed over time after vaccination. Panel A of this figure shows this phenomena for a single gene NECAB2. Panel B shows the aggregate character of this phenomena across large numbers of markers. The change in R2 compared to the initial time point is depicted; this change in R squared appears to correspond to an increase the magnitude of the slope (additive association with genotype). Fig 3: Pathways and processes identified as enriched in our candidates. Both Ingenuity IPA Analysis and GO and KEGG pathway databases were used. Heavily implicated immunologic response classes are repsresented. Fig 4: Human immune response as measured by our Antibody Response scores are correlated with gene expression changes, and these patterns are recapituoated in discovery and validation (male/female) cohorts. Fig 5: Immune cellular context of the genes identifeies in our eQTL and immune response analysis. A striking number of our validated genes occuue in the antigen processing and presentatio pnthway. Fig 6: Q-Q plot depicting that the strength of association between genotype and phenotype (titer response) is stronger for markers that have a SNP association with expression and where expression is associated with titer response than would be expected for random SNPs. Fig 7: Causal and Reactive Model Analyses. Three-way association between genotype, expression and trait. Our data are more consistent with a causal relationship compared to reactive, but the results are not definitive. We explored the sample size necessary to investigate this in the supplement. Fig 8: Diagram demonstrating the experimental design of this study. Fig 9: Population structure analysis performed on our cohort using the genome wide SNP data confirms the European ancestry and ethnic homogeoneity of our ty sample Fig 10: Schematic of the eQTL analysis. The time course of gene expression change is integrated with a single model considering effects of Day, Genotype, Day-Genotype interaction and random effects for each individual to account for the longitudinal nature of the design. email: cashaw@bcm.edu with questions or comments.

It is generally accepted that human influenza viruses bind glycans containing sialic acid linked α2-6 to the next sugar, that avian influenza viruses bind glycans containing the α2-3 linkage, and that mutations that change the binding specificity might change the host tropism. We noted that human H3N2 viruses showed dramatic differences in their binding specificity, and so we embarked on a study of representative human H3N2 influenza viruses, isolated from 1968 to 2012, that had been isolated and minimally passaged only in mammalian cells, never in eggs. The 45 viruses were grown in MDCK cells, purified, fluorescently labeled and screened on the Consortium for Functional Glycomics Glycan Array. Viruses isolated in the same season have similar binding specificity profiles but the profiles show marked year-to-year variation. None of the 610 glycans on the array (166 sialylated glycans) bound to all viruses; the closest was Neu5Acα2-6(Galβ1-4GlcNAc)3 in either a linear or biantennary form, that bound 42 of the 45 viruses. The earliest human H3N2 viruses preferentially bound short, branched sialylated glycans while recent viruses bind better to long polylactosamine chains terminating in sialic acid. Viruses isolated in 1996, 2006, 2010 and 2012 bind glycans with α2-3 linked sialic acid; for 2006, 2010 and 2012 viruses this binding was inhibited by oseltamivir, indicating binding of α2-3 sialylated glycans by neuraminidase. More significantly, oseltamivir inhibited virus entry of 2010 and 2012 viruses into MDCK cells. All of these viruses were representative of epidemic strains that spread around the world, so all could infect and transmit between humans with high efficiency. We conclude that the year-to-year variation in receptor binding specificity is a consequence of amino acid sequence changes driven by antigenic drift, and that viruses with quite different binding specificity and avidity are equally fit to infect and transmit in the human population.

BACKGROUND Serum antibody to the hemagglutinin (HA) of influenza viruses is a correlate and predictor of immunity to influenza in humans; the relative values of other correlates are uncertain. METHODS Serum and nasal secretions (NS) were collected in fall and spring of 2009-2011 from healthy adults who were monitored for acute respiratory illness (ARI). Serum samples were tested for hemagglutination-inhibition (HAI) antibody increase and secretions for virus if ill; enrollment sera were also tested for neuraminidase-inhibiting (NI) antibody and NS for neutralizing (neut), NI, immunoglobulin A (IgA), and immunoglobulin G (IgG) anti-HA antibody. RESULTS Serum anti-HA and anti-neuraminidase (NA) antibody titers to 2009(H1N1) pandemic influenza virus (pH1N1) correlated with titers in NS (including IgA and IgG antibody). Increasing anti-HA and anti-NA titers in serum and NS tests all correlated with reducing infection and infection-associated illness. Multivariate analyses indicated serum HAI and NI each independently predicted immunity to infection and infection-associated illness. Only serum NI independently predicted reduced illness among infected subjects. CONCLUSIONS Increasing anti-HA and NA antibody in serum and secretions correlated with reducing pH1N1 influenza virus infection and illness in healthy young adults. Both anti-HA and anti-NA antibody are independent predictors of immunity to influenza; ensuring induction of both by vaccination is desirable.

Identification of the host genetic factors that contribute to variation in vaccine responsiveness may uncover important mechanisms affecting vaccine efficacy. We carried out an integrative, longitudinal study combining genetic, transcriptional, and immunologic data in humans given seasonal influenza vaccine. We identified 20 genes exhibiting a transcriptional response to vaccination, significant genotype effects on gene expression, and correlation between the transcriptional and antibody responses. The results show that variation at the level of genes involved in membrane trafficking and antigen processing significantly influences the human response to influenza vaccination. More broadly, we demonstrate that an integrative study design is an efficient alternative to existing methods for the identification of genes involved in complex traits.

Background Concern for a pandemic caused by a newly emerged avian influenza A virus has led to clinical trials with candidate vaccines as preparation for such an event. Most trials have involved vaccines for influenza A (H5N1), A (H7N7) or A (H9N2). Objective To evaluate dosage-related safety and immunogenicity of an inactivated influenza A (H7N7) vaccine in humans. Design One hundred twenty-five healthy young adults were randomized to receive two doses intramuscularly of placebo or 7.5, 15, 45 or 90 µg of HA of an inactivated subunit influenza A (H7N7) vaccine (25 per group), four weeks apart. Reactogenicity was evaluated closely for one week and for any adverse effect for six months after each dose. Serum hemagglutination-inhibiting and neutralizing antibody responses were determined four weeks after each dose and at six months. Results Reactogenicity evaluations indicated the vaccinations were well tolerated. Only one subject developed a ≥4-fold serum hemagglutination-inhibition (HAI) antibody response and a final titer of ≥1∶40 four weeks after dose two and only five subjects developed a neutralizing antibody rise and a final titer of ≥1∶40 in tests performed at a central laboratory. Four of the five were given the 45 or 90 µg HA dosage. A more sensitive HAI assay at the study site revealed a dose-response with increasing HA dosage but only 36% in the 90 µg HA group developed a ≥4-fold rise in antibody in this test and only one of these achieved a titer of ≥1∶32. Conclusion This inactivated subunit influenza A (H7N7) vaccine was safe but poorly immunogenic in humans. Trials Registration ClinicalTrials.gov NCT00546585