Coping with Poorly Understood Domains: the Example of Internet Trust

The notion of trust, as required for secure operations over the Internet, is important for ascertaining the source of received messages. How can we measure the degree of trust in authenticating the source? Knowledge in the domain is not established, so knowledge engineering becomes knowledge generation rather than mere acquisition. Special techniques are required, and special features of KBS software become more important than in conventional domains. This paper generalizes from experience with Internet trust to discuss some techniques and software features that are important for poorly understood domains

Tumour necrosis factor as a mediator of endotoxaemia

The effects of endotoxaemia are thought to be mediated by endogenous host substances. It has been suggested that the recently isolated cytokine, Tumour Necrosis Factor (TNF), is such a substance. To examine this possibility the effects of TNF were studied in the dog and the findings were compared with known effects of endotoxin. Secondly, to assess the dependence of TNF effects upon endogenous prostaglandin synthesis, TNF was given after administration of the cyclooxygenase inhibitor, Ibuprofen. Further studies questioned whether or not some TNF effects might be due to an increased absorption of endotoxin from the gut. In anaesthetised dogs an infusion of TNF caused falls In systemic, pulmonary, central venous and pulmonary capillary wedge pressures. There was a four fold increase In urine volume and significant pyrexia, tachycardia, hyperventilation and hypermetabolism. In addition, leucopenia and increased circulating concentrations of stress hormones, lactate and pyruvate were observed. Peripheral glucose uptake increased and though glucose production also rose this was insufficient to meet demands. In consequence, blood glucose fell. Urinary nitrogen excretion was increased but this extra nitrogen was not drawn from the periphery, suggesting a visceral source. These alterations occured in the absence of severe hypotension or acidosis. Many of the changes were reproduced in two conscious animals. Pretreatment of anaesthetised animals with Ibuprofen abolished haemodynamic changes whilst attenuating some of the other responses. Studies of TNF administration after removal of the bowel suggest that several TNF effects do not depend upon an increased absorption of gut endotoxin; for many parameters however no firm conclusions could be drawn from the data. These findings support the hypotheses that TNF Is a mediator of endotoxaemia and that some of Its effects are mediated by prostaglandins

Do safeguarding concerns deter young people’s access to condoms? Issues about integrating sexual health services online

Condoms have been distributed freely, and regionally across England, since the ‘Teenage Pregnancy Strategy’ (Social Inclusion Unit, 1999) which highlighted England as having one of the highest rates of unplanned teenage conceptions in Western Europe. With the aim of making more accessible contraception and sex safer resources and protecting against infections, young people can obtain free condoms through selected registration and distribution points (Evans, 2005; Hadley and Evans, 2013). In 2003, England and Wales founded the National Chlamydia Screening Programme (NCSP) in response to high levels of Chlamydia trachomatis found in young people aged between 15 – 24 years (DH, 2012). Key messages for young people in the prevention of Chlamydia infection are: - Consistently use condoms during vaginal, anal or oral sex - Don’t share sex toys without washing them between use or covering with a fresh condom - Consistently use latex dams for cunnilingus (oral sex on a female) and oroanal sex (rimming) (NHS, 2013

Latent entrepreneurship across nations

The paper studies latent entrepreneurship across nations. There are three main findings. First, large numbers of people in the industrial countries say they would prefer to be self-employed. Top of the international ranking of entrepreneurial spirit come Poland (with 80% saying so), Portugal and the USA; bottom of the table come Norway (with 27% saying so), Denmark and Russia. Second, for individuals the probability of preferring to be self-employed is strongly decreasing with age, while the probability of being self-employed is strongly increasing with age. Third, we show that self-employed individuals have noticeably higher job satisfaction than the employed, so people's expressed wish to run their business cannot easily be written off as mistaken. We speculate on why so much entrepreneurial spirit lies dormant

Latent entrepreneurship across nations

The paper studies latent entrepreneurship across nations. There are three main findings. First, large numbers of people in the industrial countries say they would prefer to be self-employed. Top of the international ranking of entrepreneurial spirit come Poland (with 80% saying so), Portugal and the USA; bottom of the table come Norway (with 27% saying so), Denmark and Russia. Second, for individuals the probability of preferring to be self-employed is strongly decreasing with age, while the probability of being self-employed is strongly increasing with age. Third, we show that self-employed individuals have noticeably higher job satisfaction than the employed, so people's expressed wish to run their business cannot easily be written off as mistaken. We speculate on why so much entrepreneurial spirit lies dormant

Biochemical and genetic analysis of the role of the viral polymerase in enterovirus recombination

Funding: Biotechnology and Biological Sciences Research Council [BB/M009343/1] and PhD. studentship funding for AW (to D.J.E.); NIH [R01 AI045818 from NIAID to C.E.C.). Funding for open access charge: Biotechnology and Biological Sciences Research Council and University of St. Andrews.Genetic recombination in single-strand, positive-sense RNA viruses is a poorly understand mechanism responsible for generating extensive genetic change and novel phenotypes. By moving a critical cis-acting replication element (CRE) from the polyprotein coding region to the 3’ non-coding region we have further developed a cell-based assay (the 3’CRE-REP assay) to yield recombinants throughout the non-structural coding region of poliovirus from dually transfected cells. We have additionally developed a defined biochemical assay in which the only protein present is the poliovirus RNA dependent RNA polymerase (RdRp), which recapitulates the strand transfer events of the recombination process. We have used both assays to investigate the role of the polymerase fidelity and nucleotide turnover rates in recombination. Our results, of both poliovirus intertypic and intratypic recombination in the CRE-REP assay and using a range of polymerase variants in the biochemical assay, demonstrate that RdRp fidelity is a fundamental determinant of recombination frequency. High fidelity polymerases exhibit reduced recombination and low fidelity polymerases exhibit increased recombination in both assays. These studies provide the basis for the analysis of poliovirus recombination throughout the non-structural region of the virus genome and provide a defined biochemical assay to further dissect this important evolutionary process.Publisher PDFPeer reviewe

Viruses inhibit CO2 fixation in the most abundant phototrophs on Earth

R.J.P. was the recipient of a NERC studentship and Warwick University IAS fellowship. This work was supported in part by NERC grant NE/J02273X/1 and Leverhulme Trust grant RPG-2014-354 to A.D.M., D.J.E., and D.J.S.Summary. Marine picocyanobacteria of the genera Prochlorococcus and Synechococcus are the most numerous photosynthetic organisms on our planet [1, 2]. With a global population size of 3.6 × 1027 [3], they are responsible for approximately 10% of global primary production [3, 4]. Viruses that infect Prochlorococcus and Synechococcus (cyanophages) can be readily isolated from ocean waters [5–7] and frequently outnumber their cyanobacterial hosts [8]. Ultimately, cyanophage-induced lysis of infected cells results in the release of fixed carbon into the dissolved organic matter pool [9]. What is less well known is the functioning of photosynthesis during the relatively long latent periods of many cyanophages [10, 11]. Remarkably, the genomes of many cyanophage isolates contain genes involved in photosynthetic electron transport (PET) [12–18] as well as central carbon metabolism [14, 15, 19, 20], suggesting that cyanophages may play an active role in photosynthesis. However, cyanophage-encoded gene products are hypothesized to maintain or even supplement PET for energy generation while sacrificing wasteful CO2 fixation during infection [17, 18, 20]. Yet this paradigm has not been rigorously tested. Here, we measured the ability of viral-infected Synechococcus cells to fix CO2 as well as maintain PET. We compared two cyanophage isolates that share different complements of PET and central carbon metabolism genes. We demonstrate cyanophage-dependent inhibition of CO2 fixation early in the infection cycle. In contrast, PET is maintained throughout infection. Our data suggest a generalized strategy among marine cyanophages to redirect photosynthesis to support phage development, which has important implications for estimates of global primary production.Publisher PDFPeer reviewe