Novel 2-amino-isoflavones exhibit aryl hydrocarbon receptor agonist or antagonist activity in a species/cell-specific context

The aryl hydrocarbon receptor (AhR) mediates the induction of a variety of xenobiotic metabolism genes. Activation of the AhR occurs through binding to a group of structurally diverse compounds, most notably dioxins, which are exogenous ligands. Isoflavones are part of a family which include some well characterised endogenous AhR ligands. This paper analysed a novel family of these compounds, based on the structure of 2-amino-isoflavone. Initially two luciferase-based cell models, mouse H1L6.1c2 and human HG2L6.1c3, were used to identify whether the compounds had AhR agonistic and/or antagonistic properties. This analysis showed that some of the compounds were weak agonists in mouse and antagonists in human. Further analysis of two of the compounds, Chr-13 and Chr-19, was conducted using quantitative real-time PCR in rat H4IIE and human MCF-7 cells. The results indicated that Chr-13 was an agonist in rat but an antagonist in human cells. Chr-19 was shown to be an agonist in rat but more interestingly, a partial agonist in human. Luciferase induction results not only revealed that subtle differences in the structure of the compound could produce species-specific differences in response but also dictated the ability of the compound to be an AhR agonist or antagonist. Substituted 2-amino-isoflavones represent a novel group of AhR ligands that must differentially interact with the AhR ligand binding domain to produce their species-specific agonist or antagonist activity and future ligand binding analysis and docking studies with these compounds may provide insights into the differential mechanisms of action of structurally similar compounds

A centrality measure for cycles and subgraphs II

In a recent work we introduced a measure of importance for groups of vertices in a complex network. This centrality for groups is always between 0 and 1 and induces the eigenvector centrality over vertices. Furthermore, its value over any group is the fraction of all network flows intercepted by this group. Here we provide the rigorous mathematical constructions underpinning these results via a semi-commutative extension of a number theoretic sieve. We then established further relations between the eigenvector centrality and the centrality proposed here, showing that the latter is a proper extension of the former to groups of nodes. We finish by comparing the centrality proposed here with the notion of group-centrality introduced by Everett and Borgatti on two real-world networks: the Wolfe’s dataset and the protein-protein interaction network of the yeast Saccharomyces cerevisiae. In this latter case, we demonstrate that the centrality is able to distinguish protein complexe

Using email reminders to engage physicians in an Internet-based CME intervention

BACKGROUND: Engaging practicing physicians in educational strategies that reinforce guideline adoption and improve the quality of healthcare may be difficult. Push technologies such as email offer new opportunities to engage physicians in online educational reinforcing strategies. The objectives are to investigate 1) the effectiveness of email announcements in engaging recruited community-based primary care physicians in an online guideline reinforcement strategy designed to promote Chlamydia screening, 2) the characteristics of physicians who respond to email announcements, as well as 3) how quickly and when they respond to email announcements. METHODS: Over a 45-week period, 445 recruited physicians received up to 33 email contacts announcing and reminding them of an online women's health guideline reinforcing CME activity. Participation was defined as physician log-on at least once to the website. Data were analyzed to determine participation, to compare characteristics of participants with recruited physicians who did not participate, and to determine at what point and when participants logged on. RESULTS: Of 445 recruited physicians with accurate email addresses, 47.2% logged on and completed at least one module. There were no significant differences by age, race, or specialty between participants and non-participants. Female physicians, US medical graduates and MDs had higher participation rates than male physicians, international medical graduates and DOs. Physicians with higher baseline screening rates were significantly more likely to log on to the course. The first 10 emails were the most effective in engaging community-based physicians to complete the intervention. Physicians were more likely to log on in the afternoon and evening and on Monday or Thursday. CONCLUSIONS: Email course reminders may enhance recruitment of physicians to interventions designed to reinforce guideline adoption; physicians' response to email reminders may vary by gender, degree, and country of medical training. Repetition of email communications contributes to physician online participation

“<i>I do it because they do it</i>”:social-neutralisation in information security practices of Saudi medical interns

Successful implementation of information security policies (ISP) and IT controls play an important role in safeguarding patient privacy in healthcare organizations. Our study investigates the factors that lead to healthcare practitioners' neutralisation of ISPs, leading to non-compliance. The study adopted a qualitative approach and conducted a series of semi-structured interviews with medical interns and hospital IT department managers and staff in an academic hospital in Saudi Arabia. The study's findings revealed that the MIs imitate their peers' actions and employ similar justifications when violating ISP dictates. Moreover, MI team superiors' (seniors) ISP non-compliance influence MIs tendency to invoke neutralisation techniques. We found that the trust between the medical team members is an essential social facilitator that motivates MIs to invoke neutralisation techniques to justify violating ISP policies and controls. These findings add new insights that help us to understand the relationship between the social context and neutralisation theory in triggering ISP non-compliance

Constraints on Nucleon Decay via "Invisible" Modes from the Sudbury Neutrino Observatory

Data from the Sudbury Neutrino Observatory have been used to constrain the lifetime for nucleon decay to ``invisible'' modes, such as n -> 3 nu. The analysis was based on a search for gamma-rays from the de-excitation of the residual nucleus that would result from the disappearance of either a proton or neutron from O16. A limit of tau_inv > 2 x 10^{29} years is obtained at 90% confidence for either neutron or proton decay modes. This is about an order of magnitude more stringent than previous constraints on invisible proton decay modes and 400 times more stringent than similar neutron modes.Comment: Update includes missing efficiency factor (limits change by factor of 2) Submitted to Physical Review Letter

Review for the generalist: evaluation of anterior knee pain

Anterior knee pain is common in children and adolescents. Evaluation and management is challenging and requires a thorough history and physical exam, and understanding of the pediatric skeleton. This article will review common causes of chronic anterior knee pain in the pediatric population with a focus on patellofemoral pain

320-row CT: does beat-to-beat motion of the coronary arteries affect image quality?

Vascular Biology and Interventio

Digital Work Design

Erworben im Rahmen der Schweizer Nationallizenzen (http://www.nationallizenzen.ch)More and more academic studies and practitioner reports claim that human work is increasingly disrupted or even determined by information and communication technology (ICT) (Cascio and Montealegre 2016). This will make a considerable share of jobs currently performed by humans susceptible to automation (e.g., Frey and Osborne 2017; Manyika et al. 2017). These reports often sketch a picture of ‘machines taking over’ traditional domains like manufacturing, while ICT advances and capabilities seem to decide companies’ fate. Consequently, ICT is often put at the core of innovative efforts. While this applies to nearly all areas of workplace design, a recent popular example of increasing technology centricity is ‘Industry 4.0’, which is often delineated as ‘machines talking to computers’