MicroRNA-155 promotes resolution of hypoxia-inducible factor 1α activity during prolonged hypoxia

The hypoxia-inducible factor (HIF) is a key regulator of the transcriptional response to hypoxia. While the mechanism underpinning HIF activation is well understood, little is known about its resolution. Both the protein and the mRNA levels of HIF-1a (but not HIF-2a) were decreased in intestinal epithelial cells exposed to prolonged hypoxia. Coincident with this, microRNA (miRNA) array analysis revealed multiple hypoxiainducible miRNAs. Among these was miRNA-155 (miR-155), which is predicted to target HIF-1a mRNA. We confirmed the hypoxic upregulation of miR-155 in cultured cells and intestinal tissue from mice exposed to hypoxia. Furthermore, a role for HIF-1a in the induction of miR-155 in hypoxia was suggested by the identification of hypoxia response elements in the miR-155 promoter and confirmed experimentally. Application of miR-155 decreased the HIF-1a mRNA, protein, and transcriptional activity in hypoxia, and neutralization of endogenous miR-155 reversed the resolution of HIF-1a stabilization and activity. Based on these data and a mathematical model of HIF-1a suppression by miR-155, we propose that miR-155 induction contributes to an isoform-specific negative-feedback loop for the resolution of HIF-1a activity in cells exposed to prolonged hypoxia, leading to oscillatory behavior of HIF-1a-dependent transcription. © 2011, American Society for Microbiology.

A strategic activity model of Enterprise System implementation and use:scaffolding fluidity

This paper builds on a Strategic Activity Framework (Jarzabkowski, 2005) and activity based theories of development (Vygotsky, 1978) to model how Enterprise Systems are used to support emerging strategy. It makes three contributions. Firstly, it links fluidity and extensiveness of system use to patterns of strategising. Fluidity - the ability to change system use as needs change - is supported by interactive strategising, where top managers communicate directly with the organisation. Extensiveness requires procedural strategising, embedding system use in structures and routines. Secondly, it relates interactive and procedural strategising to the importance of the system - procedural strategising is more likely to occur if the system is strategically important. Thirdly, using a scaffolding metaphor it identifies patterns in the activities of top managers and Enterprise System custodians, who identify process champions within the organisational community, orient them towards system goals, provide guided support, and encourage fluidity through pacing implementation with learning.© 2013 Published by Elsevier B.V. All rights reserved.

Self-affirmation promotes physical activity

The present study tests whether a self-affirmation intervention (i.e., requiring an individual to focus on a valued aspect of their self-concept, such as honesty) can increase physical activity and change theory of planned behavior (TPB) variables linked to physical activity. Eighty young people completed a longitudinal intervention study. Baseline physical activity was assessed using the Godin Leisure-Time Physical Activity Questionnaire (LTPAQ). Next, participants were randomly allocated to either a self-affirmation or a nonaffirmation condition. Participants then read information about physical activity and health, and completed measures of TPB variables. One week later, participants again completed LTPAQ and TPB items. At follow up, self-affirmed participants reported significantly more physical activity, more positive attitudes toward physical activity, and higher intentions to be physically active compared with nonaffirmed participants. Neither attitudes nor intentions mediated the effects of self-affirmation on physical activity. Self-affirmation can increase levels of physical activity and TPB variables. Self-affirmation interventions have the potential to become relatively simple methods for increasing physical activity levels. © 2014 Human Kinetics, Inc.

Raman fibre laser based amplification in coherent transmission systems

The thesis presents a detailed study of different Raman fibre laser (RFL) based amplification techniques and their applications in long-haul/unrepeatered coherent transmission systems. RFL based amplifications techniques were characterised from different aspects, including signal/noise power distributions, relative intensity noise (RIN), mode structures of induced Raman fibre lasers, and so on. It was found for the first time that RFL based amplification techniques could be divided into three categories in terms of the fibre laser regime, which were Fabry-Perot fibre laser with two FBGs, weak Fabry-Perot fibre laser with one FBG and very low reflection near the input, and random distributed feedback (DFB) fibre laser with one FBG. It was also found that lowering the reflection near the input could mitigate the RIN of the signal significantly, thanks to the reduced efficiency of the Stokes shift from the FW-propagated pump. In order to evaluate the transmission performance, different RFL based amplifiers were evaluated and optimised in long-haul coherent transmission systems. The results showed that Fabry-Perot fibre laser based amplifier with two FBGs gave >4.15 dB Q factor penalty using symmetrical bidirectional pumping, as the RIN of the signal was increased significantly. However, random distributed feedback fibre laser based amplifier with one FBG could mitigate the RIN of the signal, which enabled the use of bidirectional second order pumping and consequently give the best transmission performance up to 7915 km. Furthermore, using random DFB fibre laser based amplifier was proved to be effective to combat the nonlinear impairment, and the maximum reach was enhanced by >28% in mid-link single/dual band optical phase conjugator (OPC) transmission systems. In addition, unrepeatered transmission over >350 km fibre length using RFL based amplification technique were presented experimentally using DP-QPSK and DP-16QAM transmitter.

Tail gas catalyzed N2O decomposition over Fe-beta zeolite. On the promoting role of framework connected AlO6 sites in the vicinity of Fe by controlled dealumination during exchange

A novel route to prepare highly active and stable N2O decomposition catalysts is presented, based on Fe-exchanged beta zeolite. The procedure consists of liquid phase Fe(III) exchange at low pH. By varying the pH systematically from 3.5 to 0, using nitric acid during each Fe(III)-exchange procedure, the degree of dealumination was controlled, verified by ICP and NMR. Dealumination changes the presence of neighbouring octahedral Al sites of the Fe sites, improving the performance for this reaction. The so-obtained catalysts exhibit a remarkable enhancement in activity, for an optimal pH of 1. Further optimization by increasing the Fe content is possible. The optimal formulation showed good conversion levels, comparable to a benchmark Fe-ferrierite catalyst. The catalyst stability under tail gas conditions containing NO, O2 and H2O was excellent, without any appreciable activity decay during 70 h time on stream. Based on characterisation and data analysis from ICP, single pulse excitation NMR, MQ MAS NMR, N2 physisorption, TPR(H2) analysis and apparent activation energies, the improved catalytic performance is attributed to an increased concentration of active sites. Temperature programmed reduction experiments reveal significant changes in the Fe(III) reducibility pattern with the presence of two reduction peaks; tentatively attributed to the interaction of the Fe-oxo species with electron withdrawing extraframework AlO6 species, causing a delayed reduction. A low-temperature peak is attributed to Fe-species exchanged on zeolitic AlO4 sites, which are partially charged by the presence of the neighbouring extraframework AlO6 sites. Improved mass transport phenomena due to acid leaching is ruled out. The increased activity is rationalized by an active site model, whose concentration increases by selectively washing out the distorted extraframework AlO6 species under acidic (optimal) conditions, liberating active Fe species.

Pensando e agindo estrategicamente:novos desafios para a análise estratégical

Este artigo estabelece uma postura crítica e analítica em relação às abordagens baseadas em microatividades para se entender a estratégia. Argumenta-se que tais abordagens trazem desafios teóricos e empíricos importantes. Argumenta-se também contra a tendência ao reducionismo, sem igual ênfase nas influências contextuais que configuram a estratégia em um nível micro. Finalmente, o artigo defende uma abordagem mais internacional e comparativa para os estudos da estratégia em um nível micro. This paper takes a critical and evaluative stance toward micro-activity-based approaches to understanding strategy. It argues that such approaches bring with them important theoretical and empirical challenges. The paper argues against a tendency to reductionism without equal emphasis to the contextual influences that bound micro-strategising. Finally, the paper argues for a more international and comparative approach to micro-strategy studies than has currently been the case.

Thinking and acting strategically:new challenges for interrogating strategy

This paper takes a critical and evaluative stance toward micro-activity-based approaches to understanding strategy. It argues that such approaches bring with them important theoretical and empirical challenges. The paper argues against a tendency to reductionism without equal emphasis to the contextual influences that bound micro-strategising. Finally, the paper argues for a more international and comparative approach to micro-strategy studies than has currently been the case.

Openness, knowledge, innovation and growth in UK business services

We explore the causal links between service firms' knowledge investments, their innovation outputs and business growth based on a bespoke survey of around 1100 UK service businesses. We combine the activity based approach of the innovation value chain with firms' external links at each stage of the innovation process. This introduces the concept of 'encoding' relationships through which learning improves the effectiveness of firms' innovation processes. Our econometric results emphasise the importance of external openness in the initial, exploratory phase of the innovation process and the significance of internal openness (e.g. team working) in later stages of the process. In-house design capacity is strongly linked to a firm's ability to absorb external knowledge for innovation. Links to customers are important in the exploratory stage of the innovation process, but encoding linkages with private and public research organisations are more important in developing innovation outputs. Business growth is related directly to both the extent of firms' service innovation as well as the diversity of innovation, reflecting marketing, strategic and business process change.

Application of genomics, proteomics and metabolomics in drug discovery, development and clinic

Genomics, proteomics and metabolomics are three areas that are routinely applied throughout the drug-development process as well as after a product enters the market. This review discusses all three 'omics, reporting on the key applications, techniques, recent advances and expectations of each. Genomics, mainly through the use of novel and next-generation sequencing techniques, has advanced areas of drug discovery and development through the comparative assessment of normal and diseased-state tissues, transcription and/or expression profiling, side-effect profiling, pharmacogenomics and the identification of biomarkers. Proteomics, through techniques including isotope coded affinity tags, stable isotopic labeling by amino acids in cell culture, isobaric tags for relative and absolute quantification, multidirectional protein identification technology, activity-based probes, protein/peptide arrays, phage displays and two-hybrid systems is utilized in multiple areas through the drug development pipeline including target and lead identification, compound optimization, throughout the clinical trials process and after market analysis. Metabolomics, although the most recent and least developed of the three 'omics considered in this review, provides a significant contribution to drug development through systems biology approaches. Already implemented to some degree in the drug-discovery industry and used in applications spanning target identification through to toxicological analysis, metabolic network understanding is essential in generating future discoveries.

Application of genomics, proteomics and metabolomics in drug discovery, development and clinic

Genomics, proteomics and metabolomics are three areas that are routinely applied throughout the drug-development process as well as after a product enters the market. This review discusses all three 'omics, reporting on the key applications, techniques, recent advances and expectations of each. Genomics, mainly through the use of novel and next-generation sequencing techniques, has advanced areas of drug discovery and development through the comparative assessment of normal and diseased-state tissues, transcription and/or expression profiling, side-effect profiling, pharmacogenomics and the identification of biomarkers. Proteomics, through techniques including isotope coded affinity tags, stable isotopic labeling by amino acids in cell culture, isobaric tags for relative and absolute quantification, multidirectional protein identification technology, activity-based probes, protein/peptide arrays, phage displays and two-hybrid systems is utilized in multiple areas through the drug development pipeline including target and lead identification, compound optimization, throughout the clinical trials process and after market analysis. Metabolomics, although the most recent and least developed of the three 'omics considered in this review, provides a significant contribution to drug development through systems biology approaches. Already implemented to some degree in the drug-discovery industry and used in applications spanning target identification through to toxicological analysis, metabolic network understanding is essential in generating future discoveries.

Superior gas-sensing performance of amorphous CdO nanoflake arrays prepared at room temperature

Highly sensitive and selective detection of volatile organic compounds (VOCs) with fast response time is imperative based on safety requirements, yet often remains a challenge. Herein, we propose an effective solution, preparing a novel gas sensor comprised of amorphous nanoflake arrays (a-NFAs) with specific surface groups. The sensor was produced via an extremely simple process in which a-NFAs of CdO were deposited directly onto an interdigital electrode immersed in a chemical bath under ambient conditions. Upon exposure to a widely used VOC, diethyl ether (DEE), the sensor exhibits excellent performance, more specifically, the quickest response, lowest detection limit and highest selectivity ever reported for DEE as a target gas. The superior gas-sensing properties of the prepared a-NFAs are found to arise from their open trumpet-shaped morphology, defect-rich amorphous nature, and surface CO groups.

Coke formation in the oxidative dehydrogenation of ethylbenzene to styrene by TEOM

A packed bed microbalance reactor setup (TEOM-GC) is used to investigate the formation of coke as a function of time-on-stream on γ-Al2O3 and 3P/SiO2 catalyst samples under different conditions for the ODH reaction of ethylbenzene to styrene. All samples show a linear correlation of the styrene selectivity and yield with the initial coverage of coke. The COX production increases with the coverage of coke. On the 3 wt% P/SiO2 sample, the initial coke build-up is slow and the coke deposition rate increases with time. On alumina-based catalyst samples, a fast initial coke build-up takes place, decreasing with time-on-stream, but the amount of coke does not stabilize. A higher O2 : EB feed ratio results in more coke, and a higher temperature results in less coke. This coking behaviour of Al2O3 can be described by existing "monolayer-multilayer" models. Further, the coverage of coke on the catalyst varies with the position in the bed. For maximal styrene selectivity, the optimal coverage of coke should be sufficient to convert all O2, but as low as possible to prevent selectivity loss by COX production. This is in favour of high temperature and low O2 : EB feed ratios. The optimal coke coverage depends in a complex way on all the parameters: temperature, the O2 : EB feed ratio, reactant concentrations, and the type of starting material. This journal is

Building bridges for future sustainability? Breaching the research-teaching nexus in engineering education

The relationship between research and learning and teaching represents what has been described as amongst the most intellectually tangled, managerially complex and politically contentious issues in mass higher education (Scott, 2005, p 53). Despite this, arguments that in order to achieve high quality scholarly outcomes, university teachers need to adopt an approach to teaching similar to that of research (founded upon academic rigour and evidence), has long been discussed in the literature. However, the practicalities of promoting an empirical and evidence-based approach to teaching in engineering education make dealing with the research / teaching nexus a somewhat challenging proposition. Using a phenomenographic approach, bringing together and applying the findings of a mixed methodological study, the workshop will adopt an activity based, interactive approach to encourage staff to consider the challenges and benefits of adopting an evidence-based approach to learning and teaching through the utilisation of research to inform their own practice. © 2009 Authors.

Dispensing activity in a community pharmacy-based repeat dispensing pilot project

Objective: To measure changes in dispensing activity in a UK repeat dispensing pilot study and to estimate any associated cost savings. Method: Patients were provided with two successive three-monthly repeat prescriptions containing all of the items on their "repeat medicines list" and valid at a study pharmacy. Pharmacists consulted with patients at the time of supply and completed a patient-monitoring form. Prescriptions with pricing data were returned by the UK Prescription Pricing Authority. These data were used to calculate dispensing activity, the cost of dispensed items and an estimate of cost savings on non-dispensed items. A retrospective identification of items prescribed during the six months prior to the project was used to provide a comparison with those dispensed during the project and thus a more realistic estimate of changes. Setting: 350 patients from two medical practices in a large English City, with inner city and suburban locations, and served by seven pharmacies. Key findings: There were methodological challenges in establishing a robust framework for calculating changes. Based on all of the items that patients could have obtained from their repeat list, 23.8% were not dispensed during the intervention period. A correction was then made to allow for a comparison with usage in the six months prior to the study. Based on the corrected data, there was an estimated 11.3% savings in drug costs compared with the pre-intervention period. There was a marked difference in changes between the two practices, the pharmacies and individual patients. The capitation-based remuneration method was acceptable to all but one of the community pharmacists. Conclusion: The repeat dispensing system reduced dispensing volume in comparison with the control period. A repeat dispensing system with a focus on patients' needs and their use of medicines might be cost neutral.

Improving the response time of polymer optical fibre Bragg grating water activity sensors

In this work we investigate the effect of temperature and diameter size on the response time of a poly(methyl methacrylate) based, polymer optical fibre Bragg grating water activity sensor. The unstrained and etched sensor was placed in an environmental chamber to maintain controlled temperature and humidity conditions and subjected to step changes in humidity. The data show a strong correlation between decrease in diameter and shorter response time. A decrease in response time was also observed with an increase in temperature.