Use of a continuous culture fermentation system to investigate the effect of GanedenBC30 (Bacillus coagulans GBI-30, 6086) supplementation on pathogen survival in the human gut microbiota

Single-stage continuous fermentation systems were employed to examine the effects of GanedenBC30 supplementation on the human gastrointestinal microbiota in relation to pathogen challenge in vitro. Denaturing gradient gel electrophoresis analysis demonstrated that GanedenBC30 supplementation modified the microbial profiles in the fermentation systems compared with controls, with profiles clustering according to treatment. Overall, GanedenBC30 supplementation did not elicit major changes in bacterial population counts in vitro, although notably higher Bcoa191 counts were seen following probiotic supplementation (compared to the controls). Pathogen challenge did not elicit significant modification of the microbial counts in vitro, although notably higher Clit135 counts were seen in the control system post-Clostridium difficile challenge than in the corresponding GanedenBC30-supplemented systems. Sporulation appears to be associated with the anti-microbial activity of GanedenBC30, suggesting that a bi-modal lifecycle of GanedenBC30 in vivo may lead to anti-microbial activity in distal regions of the gastrointestinal tract.

Knowledge and information evaluation practice: an exploratory study in a construction firm

There are a number of challenges associated with managing knowledge and information in construction organizations delivering major capital assets. These include the ever-increasing volumes of information, losing people because of retirement or competitors, the continuously changing nature of information, lack of methods on eliciting useful knowledge, development of new information technologies and changes in management and innovation practices. Existing tools and methodologies for valuing intangible assets in fields such as engineering, project management and financial, accounting, do not address fully the issues associated with the valuation of information and knowledge. Information is rarely recorded in a way that a document can be valued, when either produced or subsequently retrieved and re-used. In addition there is a wealth of tacit personal knowledge which, if codified into documentary information, may prove to be very valuable to operators of the finished asset or future designers. This paper addresses the problem of information overload and identifies the differences between data, information and knowledge. An exploratory study was conducted with a leading construction consultant examining three perspectives (business, project management and document management) by structured interviews and specifically how to value information in practical terms. Major challenges in information management are identified. An through-life Information Evaluation methodology (IEM) is presented to reduce information overload and to make the information more valuable in the future.

Modulation of pro-survival Akt/protein kinase B and ERK1/2 signaling cascades by quercetin and its in vivo metabolites underlie their action on neuronal viability

Much recent interest has focused on the potential of flavonoids to interact with intracellular signaling pathways such as with the mitogen-activated protein kinase cascade. We have investigated whether the observed strong neurotoxic potential of quercetin in primary cortical neurons may occur via specific and sensitive interactions within neuronal mitogen-activated protein kinase and Akt/protein kinase B (PKB) signaling cascades, both implicated in neuronal apoptosis. Quercetin induced potent inhibition of both Akt/PKB and ERK phosphorylation, resulting in reduced phosphorylation of BAD and a strong activation of caspase-3. High quercetin concentrations (30 microM) led to sustained loss of Akt phosphorylation and subsequent Akt cleavage by caspase-3, whereas at lower concentrations (<10 microM) the inhibition of Akt phosphorylation was transient and eventually returned to basal levels. Lower levels of quercetin also induced strong activation of the pro-survival transcription factor cAMP-responsive element-binding protein, although this did not prevent neuronal damage. O-Methylated quercetin metabolites inhibited Akt/PKB to lesser extent and did not induce such strong activation of caspase-3, which was reflected in the lower amount of damage they inflicted on neurons. In contrast, neither quercetin nor its O-methylated metabolites had any measurable effect on c-Jun N-terminal kinase phosphorylation. The glucuronide of quercetin was not toxic and did not evoke any alterations in neuronal signaling, probably reflecting its inability to enter neurons. Together these data suggest that quercetin and to a lesser extent its O-methylated metabolites may induce neuronal death via a mechanism involving an inhibition of neuronal survival signaling through the inhibition of both Akt/PKB and ERK rather than by an activation of the c-Jun N-terminal kinase-mediated death pathway.

The 'Shatton and Windup' Affair: Beckett's dealings with the firm of Chatto & Windus, 'Wholesale, Retail and for Exportation'

This essay looks in detail at the brief history of Samuel Beckett's relations with Charles Prentice and the publishing firm of Chatto & Windus. It examines the fate of two of Beckett's early publications - his essay on Proust in the Dolphin Books and his volume of short stories More Pricks than Kicks - against the backdrop of the cultural, ideological and economic context of publishing in the 1930s.