1,819 research outputs found

    Business Faculty Perceptions: Exploring the Underlying Factors of Ethics as a Core Institutional Value

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    Institutions of higher education continue to be challenged by the complexity of academic integrity. In this study, faculty from over 50 different U.S. universities shared their perceptions toward academic integrity issues such as student, administration and faculty behavior. At universities where ethics is considered a core value, the faculty perceives the academic environment as one that values honesty, where dishonest behaviors receive adequate punishment, and where students are held responsible for their behaviors. The study contributes to the body of research as perceived by business faculty on the academic integrity environment underlying the education of future business practitioners. Implications for research and practice are discussed

    Law and Morality in the Han Fei Zi

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    Master'sMASTER OF ART

    Comparative Analysis of Conformational Dynamics and Systematic Characterization of Cryptic Pockets in the SARS-CoV-2 Omicron BA.2, BA.2.75 and XBB.1 Spike Complexes with the ACE2 Host Receptor: Confluence of Binding and Structural Plasticity in Mediating Networks of Conserved Allosteric Sites

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    In the current study, we explore coarse-grained simulations and atomistic molecular dynamics together with binding energetics scanning and cryptic pocket detection in a comparative examination of conformational landscapes and systematic characterization of allosteric binding sites in the SARS-CoV-2 Omicron BA.2, BA.2.75 and XBB.1 spike full-length trimer complexes with the host receptor ACE2. Microsecond simulations, Markov state models and mutational scanning of binding energies of the SARS-CoV-2 BA.2 and BA.2.75 receptor binding domain complexes revealed the increased thermodynamic stabilization of the BA.2.75 variant and significant dynamic differences between these Omicron variants. Molecular simulations of the SARS-CoV-2 Omicron spike full-length trimer complexes with the ACE2 receptor complemented atomistic studies and enabled an in-depth analysis of mutational and binding effects on conformational dynamic and functional adaptability of the Omicron variants. Despite considerable structural similarities, Omicron variants BA.2, BA.2.75 and XBB.1 can induce unique conformational dynamic signatures and specific distributions of the conformational states. Using conformational ensembles of the SARS-CoV-2 Omicron spike trimer complexes with ACE2, we conducted a comprehensive cryptic pocket screening to examine the role of Omicron mutations and ACE2 binding on the distribution and functional mechanisms of the emerging allosteric binding sites. This analysis captured all experimentally known allosteric sites and discovered networks of inter-connected and functionally relevant allosteric sites that are governed by variant-sensitive conformational adaptability of the SARS-CoV-2 spike structures. The results detailed how ACE2 binding and Omicron mutations in the BA.2, BA.2.75 and XBB.1 spike complexes modulate the distribution of conserved and druggable allosteric pockets harboring functionally important regions. The results are significant for understanding the functional roles of druggable cryptic pockets that can be used for allostery-mediated therapeutic intervention targeting conformational states of the Omicron variants

    Evaluation of Abicipar Pegol (an Anti-VEGF DARPin Therapeutic) in Patients With Neovascular Age-Related Macular Degeneration: Studies in Japan and the United States

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    BACKGROUND AND OBJECTIVE: To evaluate comparability of abicipar pegol (abicipar) effects in patients with treatment-naïve neovascular age-related macular degeneration (nAMD) in Japan and the United States. PATIENTS AND METHODS: Phase 2, multicenter, randomized, double-masked, 20-week studies (BAMBOO, Japan; CYPRESS, United States). Patients (n = 25 each study) received three monthly intravitreal injections of abicipar 1 mg or 2 mg or five monthly intravitreal injections of ranibizumab 0.5 mg. RESULTS: Mean best-corrected visual acuity change from baseline at week 16 (primary endpoint) for abicipar 1 mg, abicipar 2 mg, and ranibizumab was +7.8 letters, +8.9 letters, and +17.4 letters (BAMBOO); +4.4 letters, +10.1 letters, and +15.2 letters (CYPRESS). Mean central retinal thickness change from baseline was −187.3 μm, −196.5 μm, and −230.4 μm (BAMBOO); −106.5 μm, −112.8 μm, and −124.4 μm (CYPRESS). Uveitis or vitritis was reported in three abicipar-treated patients. CONCLUSION: Abicipar demonstrated extended duration of effect and safety that were comparable between Japanese and non-Japanese patients with nAMD. Abicipar effectively treated Japanese patients with polypoidal choroidal vasculopathy

    Pseudonymization risk analysis in distributed systems

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    In an era of big data, online services are becoming increasingly data-centric; they collect, process, analyze and anonymously disclose growing amounts of personal data in the form of pseudonymized data sets. It is crucial that such systems are engineered to both protect individual user (data subject) privacy and give back control of personal data to the user. In terms of pseudonymized data this means that unwanted individuals should not be able to deduce sensitive information about the user. However, the plethora of pseudonymization algorithms and tuneable parameters that currently exist make it difficult for a non expert developer (data controller) to understand and realise strong privacy guarantees. In this paper we propose a principled Model-Driven Engineering (MDE) framework to model data services in terms of their pseudonymization strategies and identify the risks to breaches of user privacy. A developer can explore alternative pseudonymization strategies to determine the effectiveness of their pseudonymization strategy in terms of quantifiable metrics: i) violations of privacy requirements for every user in the current data set; ii) the trade-off between conforming to these requirements and the usefulness of the data for its intended purposes. We demonstrate through an experimental evaluation that the information provided by the framework is useful, particularly in complex situations where privacy requirements are different for different users, and can inform decisions to optimize a chosen strategy in comparison to applying an off-the-shelf algorithm

    Microbial diversity drives carbon use efficiency in a model soil

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    © The Author(s), 2020. This article is distributed under the terms of the Creative Commons Attribution License. The definitive version was published in Domeignoz-Horta, L. A., Pold, G., Liu, X. A., Frey, S. D., Melillo, J. M., & DeAngelis, K. M. Microbial diversity drives carbon use efficiency in a model soil. Nature Communications, 11(1), (2020): 3684, doi:10.1038/s41467-020-17502-z.Empirical evidence for the response of soil carbon cycling to the combined effects of warming, drought and diversity loss is scarce. Microbial carbon use efficiency (CUE) plays a central role in regulating the flow of carbon through soil, yet how biotic and abiotic factors interact to drive it remains unclear. Here, we combine distinct community inocula (a biotic factor) with different temperature and moisture conditions (abiotic factors) to manipulate microbial diversity and community structure within a model soil. While community composition and diversity are the strongest predictors of CUE, abiotic factors modulated the relationship between diversity and CUE, with CUE being positively correlated with bacterial diversity only under high moisture. Altogether these results indicate that the diversity × ecosystem-function relationship can be impaired under non-favorable conditions in soils, and that to understand changes in soil C cycling we need to account for the multiple facets of global changes.Funding for this project was provided by the Department of Energy grant DE-SC0016590 to K.M.D. and S.D.F., and an American Association of University Women Dissertation fellowship to G.P. We would also like to thank Stuart Grandy and Kevin Geyer for the fruitful discussions and Mary Waters, Courtney Bly and Ana Horta for their help with samples processing

    Linkage disequilibrium blocks, haplotype structure, and htSNPs of human CYP7A1 gene

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    BACKGROUND: Cholesterol 7-alpha-hydroxylase (CYP7A1) is the rate limiting enzyme for converting cholesterol into bile acids. Genetic variations in the CYP7A1 gene have been associated with metabolic disorders of cholesterol and bile acids, including hypercholesterolemia, hypertriglyceridemia, arteriosclerosis, and gallstone disease. Current genetic studies are focused mainly on analysis of a single nucleotide polymorphism (SNP) at A-278C in the promoter region of the CYP7A1 gene. Here we report a genetic approach for an extensive analysis on linkage disequilibrium (LD) blocks and haplotype structures of the entire CYP7A1 gene and its surrounding sequences in Africans, Caucasians, Asians, Mexican-Americans, and African-Americans. RESULT: The LD patterns and haplotype blocks of CYP7A1 gene were defined in Africans, Caucasians, and Asians using genotyping data downloaded from the HapMap database to select a set of haplotype-tagging SNPs (htSNP). A low cost, microarray-based platform on thin-film biosensor chips was then developed for high-throughput genotyping to study transferability of the HapMap htSNPs to Mexican-American and African-American populations. Comparative LD patterns and haplotype block structure was defined across all test populations. CONCLUSION: A constant genetic structure in CYP7A1 gene and its surrounding sequences was found that may lead to a better design for association studies of genetic variations in CYP7A1 gene with cholesterol and bile acid metabolism
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