Cloning and Characterization of Two Potent Kunitz Type Protease Inhibitors from Echinococcus granulosus

The tapeworm Echinococcus granulosus is responsible for cystic echinococcosis (CE), a cosmopolitan disease which imposes a significant burden on the health and economy of affected communities. Little is known about the molecular mechanisms whereby E. granulosus is able to survive in the hostile mammalian host environment, avoiding attack by host enzymes and evading immune responses, but protease inhibitors released by the parasite are likely implicated. We identified two nucleotide sequences corresponding to secreted single domain Kunitz type protease inhibitors (EgKIs) in the E. granulosus genome, and their cDNAs were cloned, bacterially expressed and purified. EgKI-1 is highly expressed in the oncosphere (egg) stage and is a potent chymotrypsin and neutrophil elastase inhibitor that binds calcium and reduced neutrophil infiltration in a local inflammation model. EgKI-2 is highly expressed in adult worms and is a potent inhibitor of trypsin. As powerful inhibitors of mammalian intestinal proteases, the EgKIs may play a pivotal protective role in preventing proteolytic enzyme attack thereby ensuring survival of E. granulosus within its mammalian hosts. EgKI-1 may also be involved in the oncosphere in host immune evasion by inhibiting neutrophil elastase and cathepsin G once this stage is exposed to the mammalian blood system. In light of their key roles in protecting E. granulosus from host enzymatic attack, the EgKI proteins represent potential intervention targets to control CE. This is important as new public health measures against CE are required, given the inefficiencies of available drugs and the current difficulties in its treatment and control. In addition, being a small sized highly potent serine protease inhibitor, and an inhibitor of neutrophil chemotaxis, EgKI-1 may have clinical potential as a novel anti-inflammatory therapeutic.

Absorbing new knowledge in small and medium-sized enterprises: A multiple case analysis of Six Sigma

The primary aim of this article is to critically analyse the development of Six Sigma theory and practice within small and medium-sized enterprises (SMEs) using a multiple case study approach. The article also explores the subsequent development of Lean Six Sigma as a means of addressing the perceived limitations of the efficacy of Six Sigma in this context. The overarching theoretical framework is that of absorptive capacity, where Six Sigma is conceptualized as new knowledge to be absorbed by smaller firms. The findings from a multiple case study involving repeat interviews and focus groups informed the development of an analytical model demonstrating the dynamic underlying routines for the absorptive capacity process and the development of a number of summative propositions relating the characteristics of SMEs to Six Sigma and Lean Six Sigma implementation.

Meeting the Requirements of the CDM Regulations: Identification of Critical Success Factors of Small to Medium Sized Contractor’ Compliance in the UK Construction Industry

The Construction Design and Management (CDM) Regulations (2007) is one of the most important set of health and safety regulations in the construction industry today. The aim of this research is to examine critical success factors for CDM compliance in small to medium size contractors in the UK construction industry. The objectives of the research include the identification of critical barriers in doing so along with the identification of success factors where CDM is incorporated. A mixed method approach is adopted in the identification and categorisation of the various factors encompassing a literature review, interviews and questionnaire survey. The key finding which emerge is the lack of knowledge and understanding with regards the CDM regulations with the recommendation to encourage small and medium contractor compliance through illustrating the benefits attainable. The practicality of the research is evident based on the significant uptake in the CDM by larger contractors, yet the research indicates that further insight and guidance is required to educate and inform those working within small to medium sized contractors in the UK. Where such acknowledgement and compliance is adopted, it is envisaged that this sector will benefit from reduced incidents and accidents, increased productivity while ultimately leading to a safer and more productive industry as a whole.

Development of small and medium-sized enterprise horizontal innovation networks: UK agri-food sector study

Within the management literature, there is an emergent discourse on horizontal collaboration among small and medium-sized enterprises (SMEs), whereby individual rivalries are overcome by the need for more resources and innovation, leading to increased competitiveness through joint product development. In particular, a number of these horizontal collaborations between SMEs have occurred within the agri-food sector. As a consequence, this article aims to explore the longitudinal development of horizontal innovation networks within an artisan bakers’ network as part of the UK SME agri-food sector. An interpretivist research approach was used, whereby the development and evolution of an artisan bakers’ horizontal network was studied over a 27-month period. The findings, as summarised in conceptual models which draw upon knowledge-based open innovation and social network constructs, illustrate that a complex three-stage life cycle development occurred within the bakers’ horizontal network.

 Graphitization of Small Carbonate Samples for Paleoceanographic Research at the Godwin Radiocarbon Laboratory, University of Cambridge

A new radiocarbon preparation facility was set up in 2010 at the Godwin Laboratory for Palaeoclimate Research, at the University of Cambridge. Samples are graphitized via hydrogen reduction on an iron powder catalyst before being sent to the Chrono Centre, Belfast, or the Australian National University for accelerator mass spectrometry (AMS) analysis. The experimental setup and procedure have recently been developed to investigate the potential for running small samples of foraminiferal carbonate. By analyzing background values of samples ranging from 0.04 to 0.6 mg C along with similar sized secondary standards, the setup and experimental procedures were optimized for small samples. “Background” modern 14C contamination has been minimized through careful selection of iron powder, and graphitization has been optimized through the use of “small volume” reactors, allowing samples containing as little as 0.08 mg C to be graphitized and accurately dated. Graphitization efficiency/fractionation is found not to be the main limitation on the analysis of samples smaller than 0.07 mg C, which rather depends primarily on AMS ion beam optics, suggesting further improvements in small sample analysis might yet be achieved with our methodology.

Nile blue-based nano-sized pH sensors for simultaneous far-red and near-infrared live bioimaging

Diblock copolymer vesicles are tagged with pH-responsive Nile Blue-based labels and used as a new type of pH-responsive colorimetric/fluorescent biosensor for far-red and near-infrared imaging of live cells. The diblock copolymer vesicles described herein are based on poly(2-(methacryloyloxy)ethyl phosphorylcholine-block-2-(diisopropylamino)ethyl methacrylate) [PMPC-PDPA]: the biomimetic PMPC block is known to facilitate rapid cell uptake for a wide range of cell lines, while the PDPA block constitutes the pH-responsive component that enables facile vesicle self-assembly in aqueous solution. These biocompatible vesicles can be utilized to detect interstitial hypoxic/acidic regions in a tumor model via a pH-dependent colorimetric shift. In addition, they are also useful for selective intracellular staining of lysosomes and early endosomes via subtle changes in fluorescence emission. Such nanoparticles combine efficient cellular uptake with a pH-responsive Nile Blue dye label to produce a highly versatile dual capability probe. This is in marked contrast to small molecule dyes, which are usually poorly uptaken by cells, frequently exhibit cytotoxicity, and are characterized by intracellular distributions invariably dictated by their hydrophilic/hydrophobic balance.

Secure Full-Duplex Small-Cell Networks in a Spectrum Sharing Environment

In this paper, we propose three relay selection schemes for full-duplex heterogeneous networks in the presence of multiple cognitive radio eavesdroppers. In this setup, the cognitive small-cell nodes (secondary network) can share the spectrum licensed to the macro-cell system (primary network) on the condition that the quality-of-service of the primary network is always satisfied subjected to its outage probability constraint. The messages are delivered from one small-cell base station to the destination with the help of full-duplex small-cell base stations, which act as relay nodes. Based on the availability of the network’s channel state information at the secondary information source, three different selection criteria for full-duplex relays, namely: 1) partial relay selection; 2) optimal relay selection; and 3) minimal self-interference relay selection, are proposed. We derive the exact closed-form and asymptotic expressions of the secrecy outage probability for the three criteria under the attack of non-colluding/colluding eavesdroppers. We demonstrate that the optimal relay selection scheme outperforms the partial relay selection and minimal self-interference relay selection schemes at the expense of acquiring full channel state information knowledge. In addition, increasing the number of the full-duplex small-cell base stations can improve the security performance. At the illegitimate side, deploying colluding eavesdroppers and increasing the number of eavesdroppers put the confidential information at a greater risk. Besides, the transmit power and the desire outage probability of the primary network have great influences on the secrecy outage probability of the secondary network.