Bioprocess applications of model-based estimation techniques

The last decade has seen the development of a number of approaches for estimating those variables which are difficult to measure on-line in industrial process situations. Whilst a range of techniques is available, a common element is the use of process knowledge in the form of a system model. In the case of bioprocess systems, although a large range of models has been presented in the literature, their use in estimation schemes on an industrial scale has been limited. A number of reasons can be identified for their low level of utilisation. Of particular significance is the uncertainty which exists in quantifying system performance and the process-model mismatch which inevitably results. The level of ‘pre-defined model’ uncertainty, together with the knowledge gained during the course of the fermentation, serves to dictate estimator structure. The paper considers a range of estimation strategies and contrasts, through industrial applications, their performance characteristics and utility.     

Oxidation protection for carbon fibre composites

Carbon fibre-reinforced ceramic matrix composites are promising candidate materials for high-temperature structural applications such as gas turbine blades. In oxidizing environments at temperatures above 400°C, however, carbon fibres are rapidly oxidized. There is, therefore, a need to coat the composite in order to protect it against oxidation. This review identifies the requirements of an effective oxidation protection system for carbon fibre-reinforced ceramics and summarizes the work which has been carried out towards this goal over the last 50 years. The most promising coatings are those composed of several ceramic layers designed to protect against erosion, spallation and corrosion, in addition to possessing a self-healing capability by the formation of glassy phases on exposure to oxygen.     

Out-of-Field Hippocampus from Partial-Body Irradiated Mice Displays Changes in Multi-Omics Profile and Defects in Neurogenesis

The brain undergoes ionizing radiation exposure in many clinical situations, particularly during radiotherapy for brain tumors. The critical role of the hippocampus in the pathogenesis of radiation-induced neurocognitive dysfunction is well recognized. The goal of this study is to test the potential contribution of non-targeted effects in the detrimental response of the hippocampus to irradiation and to elucidate the mechanisms involved. C57Bl/6 mice were whole body (WBI) or partial body (PBI) irradiated with 0.1 or 2.0 Gy of X-rays or sham irradiated. PBI consisted of the exposure of the lower third of the mouse body, whilst the upper two thirds were shielded. Hippocampi were collected 15 days or 6 months post-irradiation and a multi-omics approach was adopted to assess the molecular changes in non-coding RNAs, proteins and metabolic levels, as well as histological changes in the rate of hippocampal neurogenesis. Notably, at 2.0 Gy the pattern of early molecular and histopathological changes induced in the hippocampus at 15 days following PBI were similar in quality and quantity to the effects induced by WBI, thus providing a proof of principle of the existence of out-of-target radiation response in the hippocampus of conventional mice. We detected major alterations in DAG/IP3 and TGF-β signaling pathways as well as in the expression of proteins involved in the regulation of long-term neuronal synaptic plasticity and synapse organization, coupled with defects in neural stem cells self-renewal in the hippocampal dentate gyrus. However, compared to the persistence of the WBI effects, most of the PBI effects were only transient and tended to decrease at 6 months post-irradiation, indicating important mechanistic difference. On the contrary, at low dose we identified a progressive accumulation of molecular defects that tended to manifest at later post-irradiation times. These data, indicating that both targeted and non-targeted radiation effects might contribute to the pathogenesis of hippocampal radiation-damage, have general implications for human health.     

BallotMaps: detecting name bias in alphabetically ordered ballot papers

The relationship between candidates' position on a ballot paper and vote rank is explored in the case of 5000 candidates for the UK 2010 local government elections in the Greater London area. This design study uses hierarchical spatially arranged graphics to represent two locations that affect candidates at very different scales: the geographical areas for which they seek election and the spatial location of their names on the ballot paper. This approach allows the effect of position bias to be assessed; that is, the degree to which the position of a candidate's name on the ballot paper influences the number of votes received by the candidate, and whether this varies geographically. Results show that position bias was significant enough to influence rank order of candidates, and in the case of many marginal electoral wards, to influence who was elected to government. Position bias was observed most strongly for Liberal Democrat candidates but present for all major political parties. Visual analysis of classification of candidate names by ethnicity suggests that this too had an effect on votes received by candidates, in some cases overcoming alphabetic name bias. The results found contradict some earlier research suggesting that alphabetic name bias was not sufficiently significant to affect electoral outcome and add new evidence for the geographic and ethnicity influences on voting behaviour. The visual approach proposed here can be applied to a wider range of electoral data and the patterns identified and hypotheses derived from them could have significant implications for the design of ballot papers and the conduct of fair elections.     

Mild body cooling impairs attention via distraction from skin cooling

Many contemporary workers are routinely exposed to mild cold stress, which may compromise mental function and lead to accidents. A study investigated the effect of mild body cooling of 1.0 degree C rectal temperature (Tre) on vigilance (i.e. sustained attention) and the orienting of spatial attention (i.e. spatially selective processing of visual information). Vigilance and spatial attention tests were administered to 14 healthy males and six females at four stages (pre-immersion, deltaTre = 0, -0.5 and - 1.0 degree C ) of a gradual, head-out immersion cooling session (18-25 deltaC water), and in four time-matched stages of a contrast session, in which participants sat in an empty tub and no cooling took place. In the spatial attention test, target discrimination times were similar for all stages of the contrast session, but increased significantly in the cooling phase upon immersion (deltaTre = 0 degrees C), with no further increases at deltaTre = -0.5 and - 1.0 degree C. Despite global response slowing, cooling did not affect the normal pattern of spatial orienting. In the vigilance test, the variability of detection time was adversely affected in the cooling but not the contrast trials: variability increased at immersion but did not increase further with additional cooling. These findings suggest that attentional impairments are more closely linked to the distracting effects of cold skin temperature than decreases in body core temperature.     

Managing empowerment and control in an intranet environment

Abstract. An intranet increases in sophistication and complexity as it evolves. This evolution leads to an increasing need for control over the intranet. However, this is a contentious issue, as an intranet is deemed to be an empowering technology. Consequently, intranet control systems must balance empowerment and control so as not to negate each other. This paper investigates intranet control activities and their effect on users' perceptions of empowerment throughout the evolution of an intranet in Hewlett Packard (Ireland). The growth of the intranet is charted as a six-stage model that illustrates an evolution of purpose, control and empowerment. The control strategies for managing the intranet implemented at each stage are investigated, and their resultant effects on empowerment are evaluated. The study reveals the importance of balancing control strategies with empowerment initiatives in managing intranet environments. Based on the evidence available, the study recommends the implementation of specific controls at particular stages in the evolution of an intranet in order to achieve control systems that balance empowerment and control.     

Structure and Substrate Recognition of the Bottromycin Maturation Enzyme BotP

The bottromycins are a family of highly modified peptide natural products, which display potent antimicrobial activity against Gram‐positive bacteria, including methicillin‐resistant Staphylococcus aureus. Bottromycins have recently been shown to be ribosomally synthesized and post‐translationally modified peptides (RiPPs). Unique amongst RiPPs, the precursor peptide BotA contains a C‐terminal “follower” sequence, rather than the canonical N‐terminal “leader” sequence. We report herein the structural and biochemical characterization of BotP, a leucyl‐aminopeptidase‐like enzyme from the bottromycin pathway. We demonstrate that BotP is responsible for the removal of the N‐terminal methionine from the precursor peptide. Determining the crystal structures of both apo BotP and BotP in complex with Mn²⁺ allowed us to model a BotP/substrate complex and to rationalize substrate recognition. Our data represent the first step towards targeted compound modification to unlock the full antibiotic potential of bottro‐ mycin.