Scottish Enterprise Research Articles

THE EFFECTS OF GEOGRAPHIC LOCATION ON THE PERFORMANCE AND PERCEPTION OF ENTREPRENEURS

There is a clear gap in the literature, comparing entrepreneurship in urban and rural areas and analysing distinct differences between them, impacting their survival and growth. A case study approach was adopted, with six cases on urban and rural Scottish enterprises. This study aims to find the motivations and classifications of success for urban and rural entrepreneurs. These contrasting motivations and conceptions of success have been linked to the way companies strategise. Our findings contribute to the literature by adding an understanding of the motivations of entrepreneurs in rural and urban businesses, respectively. Further, the study was conducted in Scotland, which adds a further understanding of the motivations of entrepreneurs within the country specifically, which can be used in further research within the country.

Aberdeen, City of Culture?

Aberdeen, City of Culture?

An Invention Promising Less Carbon and Cost Could Allow More Stranded-Gas Development

A promising innovation with a ponderous name, pseudo dry gas (PDG), opens the possibility of developing stranded-gas fields in remote locations by making it possible to build far-longer tiebacks and ultimately produce more gas. But it comes with a major challenge: convincing offshore producers that they can rely on a subsea system that separates natural gas from the condensate and water in the production stream. The benefits are obvious. Being able to move gas and liquids separately is a lot more efficient and avoids problems associated with multiphase flow, particularly slug formation, which requires topsides equipped to catch the slugs. Separation also reduces backpressure, which is expected to increase the ultimate recovery from those fields. In the 4 years since the idea debuted at the Offshore Technology Conference (OTC), a small team in Worley’s Aberdeen office has built and successfully tested a small-scale prototype of a flow loop with the support of an industry partnership including three unnamed energy companies. Even with all of that, they needed to establish an added benefit to win a critical government grant to build and test a full-scale prototype for high-pressure testing. This energy-efficient alternative promises to significantly reduce carbon emissions compared to offshore compression and platforms. “As the energy industry strives toward sustainability, it’s important to support solutions that enable decarbonization,” said Andy McDonald, head of Low Carbon Transition at Scottish Enterprise, which put up £765,000 ($1 million) to support testing, according to a release from Worley. They are currently building a full-scale unit to be tested later this year at the National Engineering Laboratory in Glasgow, pushing the device closer to the technical readiness level that will allow an offshore field test. This new approach is competing against two well-established alternatives—platform-based development and compression. Their counterargument is based on the energy efficiency of separation, which limits the compression required and the steel that goes into platforms. When comparing the energy required, Thomas Lee, lead development engineer at Worley who co-invented PDG, pointed out that the power required for separation is measured in thousands of watts, while compression requires millions of watts. “It effectively decarbonizes upstream gas production. It gets rid of compression from the gas field. The amount of CO2 from this operation is really low,” Lee said. The amount of carbon and cost also depends on the location of the compression equipment. Normally it has been on a platform, which provides power and easy access for maintenance but adds costs and carbon. Worley’s inline separator is built to fit into the space filled by a standard joint of pipe (Fig. 1). Onshore compression is also an option, and Equinor and Shell have shown that compression can be done subsea. Compression has been used in projects around the world, the majority of which are in fields that hold reserves of 10 Tcf or more (Fig. 2).

Urban regeneration indicators: a proxy for assessing common good

Public realm urban regeneration projects aim to provide facilities for the common good such as improved road systems, public parks, museums and cultural institutions. Driven by political priorities, the expected benefits for society comprise of the proposed regeneration outcomes articulated in a masterplan vision. As a philosophical concept, common good in the context of urban regeneration is explored in this study to understand the expectations for major, long-term regeneration projects and the intended project objectives. In the approach to governance, there should be a relationship between monitoring indicators adopted by the regeneration project as part of the governance framework and their alignment with the common good. These concepts are analysed through a case study of the development and reporting of benchmark indicators established at the start of a major 20-year urban redevelopment in 2010. The monitoring and enhancement concept implemented required indicators to be developed and embedded in the regeneration process to, not only monitor, but also enhance sustainability. The longitudinal case study, at the interim point 10 years since the establishment of these indicators, will evaluate the sustainability of the urban regeneration and evaluate current evidence for the common good. The indicators were developed following the principles of a theme orientated framework in line with the UK and Scottish Government approach at that time. The process of indicator development was iterative, refined and finalised through working closely with local authority, Scottish Enterprise and partnership stakeholders (civic oriented organisations) to capture evidence of progress towards the masterplan vision. Ten years on, conclusions examine whether these indicators could be used a proxy for common good. The conclusion will identify the extent to which we would need to revise indicators to address any gaps to become a more accurate measure of common good.

Urban regeneration indicators: a proxy for assessing common good

Public realm urban regeneration projects aim to provide facilities for the common good such as improved road systems, public parks, museums and cultural institutions. Driven by political priorities, the expected benefits for society comprise of the proposed regeneration outcomes articulated in a masterplan vision. As a philosophical concept, common good in the context of urban regeneration is explored in this study to understand the expectations for major, long-term regeneration projects and the intended project objectives. In the approach to governance, there should be a relationship between monitoring indicators adopted by the regeneration project as part of the governance framework and their alignment with the common good. These concepts are analysed through a case study of the development and reporting of benchmark indicators established at the start of a major 20-year urban redevelopment in 2010. The monitoring and enhancement concept implemented required indicators to be developed and embedded in the regeneration process to, not only monitor, but also enhance sustainability. The longitudinal case study, at the interim point 10 years since the establishment of these indicators, will evaluate the sustainability of the urban regeneration and evaluate current evidence for the common good. The indicators were developed following the principles of a theme orientated framework in line with the UK and Scottish Government approach at that time. The process of indicator development was iterative, refined and finalised through working closely with local authority, Scottish Enterprise and partnership stakeholders (civic oriented organisations) to capture evidence of progress towards the masterplan vision. Ten years on, conclusions examine whether these indicators could be used a proxy for common good. The conclusion will identify the extent to which we would need to revise indicators to address any gaps to become a more accurate measure of common good.

A Simple Label-Free Method Reveals Bacterial Growth Dynamics and Antibiotic Action in Real-Time

Background: Understanding the response of bacteria to environmental stress is hampered by the relative insensitivity of methods to detect growth. This means studies of antibiotic resistance and other physiological methods often exceed 24 hours. Methods: We developed a scattered light and detection system (SLIC) to address this challenge, establishing the LoD (LoD), and the time to growth detection of small inocula. We compared the light-scattering of bacteria grown in different nutrient conditions and the growth dynamics of two closely related organisms. Scattering data was modelled using Gompertz and Broken Stick equations. Bacteria were also exposed to meropenem, gentamicin, and cefoxitin at various concentrations and light-scattering was captured in real-time. Findings: We established the LoD for SLIC to be between 10-100 cfu mL-1 in a volume of 1-2mL. Quantitative measurements of the different nutrient effects on bacteria were obtained in less than four hours and it was possible to rapidly distinguish differences in growth dynamics of Klebsiella pneumoniae strains with and without the BlaKPC gene. There was a dose-dependent difference in the speed of action of each antibiotic tested at supra-MIC concentrations. The lethal effect of gentamicin, lytic effect of meropenem, and the slow bactericidal effect of cefoxitin were demonstrated in real-time. Significantly, strains that were sensitive to antibiotics could be identified in seconds. Interpretation: This research demonstrates the critical importance of improving the sensitivity of bacterial detection. The ability to rapidly assess susceptibility and to capture a wealth of data on bacterial growth dynamics is presented. The rapid bactericidal effect at supra-MIC concentrations is an important finding that needs to be incorporated into pharmacokinetic and pharmacodynamic models. Importantly, enhanced sensitivity of bacterial detection opens the possibility of susceptibility results being reportable clinically in a few minutes. Funding Information: Scottish Enterprise, NESTA Longitude Prize, and the University of St Andrews Declaration of Interests: None to declare.

Tourism Development in the Trentino

Abstract The case study shows the transformation of Trento and its region into a successful tourist destination (from 100,000 overnight stays in 1989 to 1 million in 2015). The economic development was enabled by a progressive strengthening of the bonds between the city and its surrounding territory, the development of a diverse and complementary offering of experiences and business tourism as an important component in the development of the destination. The case study details the development and implementation of the strategy by the destination and its various partners and look at the array of game changers policies and investment undertaken since the 1990s as well as the winning marketing strategies deployed. Information TEAM Tourism Consulting, adapted from cases prepared for STRELKA KB (2020) and Scottish Enterprise (2016). © CAB International 2020

Targeted resequencing using the MinION long read sequencing platform

MinION nanopore DNA sequencing is an emerging paradigm in portable, long read, economic sequencing technology. Using a targeted resequencing approach of the rat osteopontin (Spp1) region in the stroke‐prone spontaneously hypertensive (SHRSPGla) and Wistar Kyoto (WKYGla) rats. We aim to develop and validate a variant calling pipeline based on long reads produced by the MinION platform and to corroborate with published SHRSPGla and WKYGla promotor variants using the Rat Genome Database (RGD) (Rnor6.0).Using the Phusion high fidelity DNA polymerase, seven PCR amplifications of defined length were amplified across a 15kb region of the rat Spp1 promoter and gene from liver samples from two individual SHRSPGla and WKYGla animals. The library for MinION sequencing was prepared using Oxford Nanopore Ligation Sequencing Kit and Native Barcoding Expansion 1–12. Purified PCR amplicons were repaired and end‐prepped with dA‐tailing. Barcodes and adapters were ligated to the prepared DNA fragments before loading to the MinION flow cell for sequencing. Two Oxford Nanopore SpotON Flow cells were primed and duplicate prepared samples were each loaded onto flow cells on two separate MinION. The MinION raw data was analysed in real time during sequencing by cloud‐based EPI2ME software (Metrichor). This enabled base calling of raw data to produce DNA sequence from output measurements of current, converting raw fast5 files to base called fastq format. Reads were separated by barcode to identify reads by strain and animal. Quality control metrics for each sample were obtained from the BAM files produced by Samtools Mpileup performed on the merged MinION fastq files mapping to the Spp1 region (Chromosome 14, 6,675,281–6,690,258). A BWA/Bcftools pipeline was used to call variants (Phred>20). Variant calls from the SHRSPGla/WKYGla strains using our MinION pipeline were cross‐referenced with previously published Illumina BWA/GATK calls on RGD for this region (Rnor6.0).The MinION platform produced a mean read count of 1.49×104(± 6.21×103) per sample, with a mean mapping percentage of 49.9% (±10.1). The mean read length was 1130 bases (±132) with a mean quality of base calls of 12.83 (±0.16). Mean depth of coverage of each individual sample was 610x(±180). RGD describes 38 variants in this region of the osteopontin promotor. Across two sequencing runs, 27 of the 38 variants listed on the Rat Genome Database were called and identified several potential novel variants in the region.In conclusion, we confirm the MinION platform can be used as a targeted resequencing platform and variant calls can be made from the long reads produced, although read accuracy is dependent on read coverage.Support or Funding InformationBritish Heart Foundation and Stratified Medicine Scotland Innovation Centre is supported by the Scottish Funding Council, Scottish Enterprise and the Chief Scientist Office of ScotlandThis abstract is from the Experimental Biology 2019 Meeting. There is no full text article associated with this abstract published in The FASEB Journal.

The Business of Religion: Lending and the Church of Scotland in the Eighteenth Century

This article is based on the examination of religion as a social practice. This approach to the history of the eighteenth-century Church of Scotland leads to the uncovering of extensive practices of lending on bond by local church bodies. Two implications of this are analysed in the article: light is shed on the debate about Protestantism and lending at interest; and connections between church bodies and nascent Scottish enterprises are indicated. The article starts by outlining the structure and governance practices of the Church, with particular emphasis on its corporate form and the extensive record keeping which supplies the evidence base for the discussion. There follows a review of the historiography of Protestantism and lending at interest, which frames the detailed discussion of eighteenth- century practice. This discussion outlines the broad framework before it examines some detailed cases, with a particular focus on lending to Glasgow businesses by local church bodies.

Developing the Rural Creative Economy ‘from Below’: Exploring Practices of Market-Building amongst Creative Entrepreneurs in Rural and Remote Scotland

The article draws on material gathered as part of three research projects, the first, ‘Supporting Creative Business’ was funded by the UK Arts and Humanities Research Council, the second, ‘Towards a model of support for the rural creative industries’ was funded by the University of Glasgow’s Knowledge Exchange fund and the third, ‘The effects of improved communications technology of rural creative entrepreneurs’ funded by CREATe, the Research Councils UK Centre for the Study of Copyright and New Business Models in the Creative Economy. Drawing on ethnographic research conducted at a range of sites around the Highlands and Islands of Scotland, this paper argues that despite recent attempts to develop the creative economy in remote and rural Scotland, the current institutional infrastructure is lacking. The paper explores creative practitioners’ responses to the opportunities and challenges posed by ‘place’. Therefore, the paper documents the tactics that creative entrepreneurs employ to aid the development of the creative economy ‘from below’, focusing in particular on the opportunities posed by improved communications technologies.

A Risky Business? The Role of Incentives and Runaway Production in Securing a Screen Industries Production Base in Scotland

A Risky Business? The Role of Incentives and Runaway Production in Securing a Screen Industries Production Base in Scotland

Problems and Perspectives of Implementation of Cluster Initiatives in Business in Developing Countries

1. Introduction Under the modern economic conditions, the issues related to competitiveness and sustainability of development of country, region, or specific enterprise become very important. At that, regional competition is a very significant factor which stipulates the increase of efficiency of national economy. It is obvious that sustainability and competitiveness of country or specific region is determined by the level of technological development. Experience of the most economically developed and competitive countries of the world show that one of the most efficient mechanisms which facilitate the increase of sustainability of territories is implementation of cluster initiatives in business. There is constant and quick exchange of information between cluster members which facilitates the increase of competitiveness of not only enterprises of cluster but of economy of region (country) on the whole. Cluster approach views such categories as interconnection and cooperation of state, business, science, and education; competitiveness; informational and communicational networks. Advantage of cluster approach consists in presence of effective tools which allow stimulating economic development of region which consists in creation of new jobs, increase of assignments to the budget (regional and federal), growth of GRP, development of investment potential of region, increase of competitiveness of region, etc. However, this direction in economic practice of developing countries received insufficient distribution, which determined the necessity for development of methodological issues of usage of cluster approach to sustainable development of developing countries--which is viewed in this research. At present, many countries of the world pay a lot of attention to the issue of clustering. This is due to the fact that clusters are viewed as a tool for increasing competitiveness and investment attractiveness of country, region, and entrepreneur, and as a tool for stimulation of innovative activities. An important tool for support for cluster initiatives in business is regional policy, role of state bodies, and mechanism of their influence on development and functioning of cluster. Cluster initiative, as a rule, is understood as coordinated actions aimed at the increase of competitiveness and growth of regional sectorial cluster with direct participation of key members of cluster: companies, associations, educational establishments, etc. 2. Methods Being a new project-oriented approach to stimulation of cluster development, cluster initiatives are a specific tool of cluster policy. As experience of developed countries shows, support for cluster initiatives is provided by all levels of authorities--federal, regional, and municipal, but the forms of support are different at each of the above mentioned levels. Let us view some examples of the most successful development of cluster initiatives. Cluster initiatives within regional policy of Austria (Upper Austria) have a character of non-financial support for information flows, preparation of staff, and cooperation of cluster companies with R&D laboratories. Regional cluster policy of Belgium (Flanders) has been conducted since 1994. The policy is conducted in two stages. At the first stage, the Flanders government registers clusters, and then noncommercial organizations of cluster can receive subsidies from government for covering operational expenses. At the second stage, cluster companies can receive grants and credits for R&D, as well as for implementation of innovational projects (Anfinsen et al., 2014). Regional policy of support for industrial clusters in Great Britain (Scotland) is performed within the program Networks of Scottish enterprises. Four directions of clustering were chosen: biotechnology, food industry, oil and gas production, and semi-conductor industry (Alberti et al. …

The Effectiveness of Augmented Reality in Enhancing the Experience of Visual Impact Assessment for Wind Turbine Development

A Visual Impact Assessment (VIA) is a formal requirement for proposed building developments likely to significantly affect the landscape. A key component of a VIA is the production of visual materials illustrating the development. But how effective are they? 67 Participants were told about a planned wind turbine development near our University and that the proposed site could be viewed from a location on campus. The illustrations used were: a printed static photograph simulating the proposed development (adhering to current UK guidelines), the same photograph presented on the screen of a laptop and an augmented reality simulation on a tablet computer which included an animated wind turbine superimposed on the scene. Participants were asked to rate various aspects of these simulations (e.g. clarity, trustworthiness) as well as to state their overall preference. The augmented reality simulation was rated as best in all ratings and the most preferred. The reasons given included that the animation gave a better idea of what the wind turbine would look like “in situ” and that it was easier to alternate viewing between the real scene and the simulated scene. These results will inform future government guidelines on materials used in VIAs. Supported by an Encompass First Step Award from Scottish Enterprise in partnership with the University of Glasgow and Linknode Ltd. (http://www.linknode.co.uk/)

The triple helix in action in the fitness sector: A case study of Chi & Co

Glasgow, like many cosmopolitan cities, is in search of new ways to promote economic activity. Today’s local government schemes are expected to fulfill an entrepreneurial role in the economic development of our cities and towns. However, to succeed in such an endeavor requires a formula that marshals collaborative effort into goal achievement. An example of such a multidisciplinary project can be found in the case of Chi & Co, a Glasgow-based yoga studio and instructor school and which is presented in this paper. The source and nature of enterprise supporting initiatives vary in intent, requirement, resources available and are often transient in availability. These limitations require that there be a strategic fit between the company need, academic expertise and drive as well as an enterprise agent, what we have labelled a formula for success. Meanwhile, success in commercialising fitness-related activities is the primary focus here, towards the goal of continued regeneration with an underlying socioeconomic agenda. Government support initiatives vary considerably, with the Princess Scottish Youth Business Trust awarding its innovation award in 2010 to a new start-up company selling golf experiences in Scotland, heralding the start of a focus on supporting innovations in sport and exercise as a commercial product. In addition, over the last three years, The Sporting Chance Initiative has helped more than 500 small businesses and innovators in Scotland to develop new products and services for sports markets, which include growth areas in fitness, leisure, adventure tourism and health/wellness by leveraging the expertise in our Higher Education Institutes, but this has not been easy. Meanwhile, Scottish Enterprise has started initiatives to promote innovations in mountain biking, leading to a more recent rapid rise in incremental innovations in the cycling market. Empirical consideration of fitness-related products developed through public–private body partnerships in a so-called triple helix partnership, is lacking. This paper discusses mechanisms of Open Innovation, which appear valuable in the context of the fitness industry and are illustrated within the Chi & Co. case study, as we develop a three-step framework as a formula for success.

Evaluating the evidence – a move to more Realistic Evaluation: A case study of Regional Selective Assistance in Scotland

This article considers how evaluation practice can improve so that the support offered to decision makers is a better reflection of the reality being evaluated. The article examines a number of evaluations of the same intervention, Regional Selective Assistance administered by Scottish Enterprise, one of Scotland’s two public sector economic development agencies. The assumptions underpinning the evaluations have changed over time. The earlier ones assumed that it was possible to evaluate the intervention in isolation: ignoring the factors that Realistic Evaluation highlights as affecting impacts: Context, Mechanisms and the Outcome Configuration. Later evaluations implicitly acknowledged these factors. However, the evaluations produced different results so that, rather than triangulation resulting in a degree of consensus, policy makers were presented with different views as to the effectiveness of the same intervention. The conclusion is that both evaluators and policy makers need to explicitly accept the Realistic Evaluation agenda and realize that causality is far more complicated than is often assumed. This would be aided if there was more transparency in evaluation methodologies and the use of different approaches to evaluate the same intervention so that any findings were triangulated.

Scyphozoan jellyfish provide short-term reproductive habitat for hyperiid amphipods in a temperate near-shore environment

MEPS Marine Ecology Progress Series Contact the journal Facebook Twitter RSS Mailing List Subscribe to our mailing list via Mailchimp HomeLatest VolumeAbout the JournalEditorsTheme Sections MEPS 510:229-240 (2014) - DOI: https://doi.org/10.3354/meps10896 Scyphozoan jellyfish provide short-term reproductive habitat for hyperiid amphipods in a temperate near-shore environment Nicholas E. C. Fleming1,2,*, Chris Harrod1,3,4, Donal C. Griffin1, Jason Newton5, Jonathan D. R. Houghton1,2 1School of Biological Sciences, Queen’s University Belfast, Medical Biology Centre, 97 Lisburn Road, Belfast BT9 7BL, UK 2Queen’s University Belfast Marine Laboratory, 12-13 The Strand, Portaferry, Co. Down, BT22 1PF, UK 3Instituto de Ciencias Naturales Alexander Von Humboldt, Universidad de Antofagasta, Avenida Angamos 601, Antofagasta, Chile 4School of Biological and Chemical Sciences, Queen Mary University of London, Mile End Road, London E1 4NS, UK 5NERC Life Sciences Mass Spectrometry Facility, Scottish Universities Environmental Research Centre, Scottish Enterprise, Technology Park, East Kilbride G75 0QF, UK *Corresponding author: nfleming05@qub.ac.uk ABSTRACT: Hyperiid amphipods (Order Amphipoda, Suborder Hyperiidea) are known to infest gelatinous zooplankton. However, the temporal backdrop to these associations is less clear, given that data are often gathered during discrete sampling events rather than over time. In general, hyperiids are considered to be pelagic: however, for individuals associated with metagenic jellyfishes in temperate shallow shelf seas, this may not always be the case, as the majority of their gelatinous hosts are present in the water column from spring to the onset of autumn. Here, we explored the temporal patterns of colonisation and overall duration of the association between Hyperia galba and 3 scyphozoan jellyfish species (Aurelia aurita, Cyanea capillata and C. lamarckii) in a temperate coastal system (Strangford Lough, Northern Ireland) during 2010 and 2012. Concomitantly, we used carbon and nitrogen stable isotope ratios to examine whether hyperiid infestation represented a permanent association with their host or was part of a more complex life history. We found that jellyfish were colonised by H. galba ca. 2 mo after they are first observed in the lough and that H. galba reached 100% prevalence in the different jellyfish species shortly before the medusae of each species disappeared from the water column. It is possible that some jellyfish overwintered in deeper water, prolonging the association between H. galba and their hosts. However, all the medusae sampled during the spring and early summer (whether they were newly emerged or had overwintered from the previous season) were not infected with hyperiids, suggesting that such behaviour was uncommon or that individuals had become dissociated from their host during the winter. Further evidence of temporary association came from stable isotope data, where δ13C and δ15N isotope ratios were indicative of feeding outside of their host prior to jellyfish colonisation. In combination, these findings suggest alternating habitat associations for H. galba, with the amphipods spending the majority of the year outside of the 3 scyphozoan species considered here. KEY WORDS: Hyperiid amphipod · Scyphozoan · Medusae · Stable isotope analysis · Diet composition · Bayesian analysis Full text in pdf format Supplementary material PreviousNextCite this article as: Fleming NEC, Harrod C, Griffin DC, Newton J, Houghton JDR (2014) Scyphozoan jellyfish provide short-term reproductive habitat for hyperiid amphipods in a temperate near-shore environment. Mar Ecol Prog Ser 510:229-240. https://doi.org/10.3354/meps10896 Export citation RSS - Facebook - Tweet - linkedIn Cited by Published in MEPS Vol. 510. Online publication date: September 09, 2014 Print ISSN: 0171-8630; Online ISSN: 1616-1599 Copyright © 2014 Inter-Research.

Clinically relevant enhancement of human sperm motility using compounds with reported phosphodiesterase inhibitor activity.

STUDY QUESTIONCan we identify compound(s) with reported phosphodiesterase inhibitor (PDEI) activity that could be added to human spermatozoa in vitro to enhance their motility without compromising other sperm functions?SUMMARY ANSWERWe have identified several compounds that produce robust and effective stimulation of sperm motility and, importantly, have a positive response on patient samples.WHAT IS KNOWN ALREADYFor >20 years, the use of non-selective PDEIs, such as pentoxifylline, has been known to influence the motility of human spermatozoa; however, conflicting results have been obtained. It is now clear that human sperm express several different phosphodiesterases and these are compartmentalized at different regions of the cells. By using type-specific PDEIs, differential modulation of sperm motility may be achieved without adversely affecting other functions such as the acrosome reaction (AR).STUDY DESIGN, SIZE, DURATIONThis was a basic medical research study examining sperm samples from normozoospermic donors and subfertile patients attending the Assisted Conception Unit (ACU), Ninewells Hospital Dundee for diagnostic semen analysis, IVF and ICSI. Phase 1 screened 43 commercially available compounds with reported PDEI activity to identify lead compounds that stimulate sperm motility. Samples were exposed (20 min) to three concentrations (1, 10 and 100 µM) of compound, and selected candidates (n = 6) progressed to Phase 2, which provided a more comprehensive assessment using a battery of in vitro sperm function tests.PARTICIPANTS/MATERIALS, SETTING, METHODSAll healthy donors and subfertile patients were recruited at the Medical Research Institute, University of Dundee and ACU, Ninewells Hospital Dundee (ethical approval 08/S1402/6). In Phase 1, poor motility cells recovered from the 40% interface of the discontinuous density gradient were used as surrogates for patient samples. Pooled samples from three to four different donors were utilized in order to reduce variability and increase the number of cells available for simultaneous examination of multiple compounds. During Phase 2 testing, semen samples from 23 patients attending for either routine diagnostic andrology assessment or IVF/ICSI were prepared and exposed to selected compounds. Additionally, 48 aliquots of prepared samples, surplus to clinical use, were examined from IVF (n = 32) and ICSI (n = 16) patients to further determine the effects of selected compounds under clinical conditions of treatment. Effects of compounds on sperm motility were assessed by computer-assisted sperm analysis. A modified Kremer test using methyl cellulose was used to assess sperm functional ability to penetrate into viscous media. Sperm acrosome integrity and induction of apoptosis were assessed using the acrosomal content marker PSA-FITC and annexin V kit, respectively.MAIN RESULTS AND THE ROLE OF CHANCEIn Phase 1, six compounds were found to have a strong effect on poor motility samples with a magnitude of response of ≥60% increase in percentage total motility. Under capacitating and non-capacitating conditions, these compounds significantly (P ≤ 0.05) increased the percentage of total and progressive motility. Furthermore, these compounds enhanced penetration into a cervical mucus substitute (P ≤ 0.05). Finally, the AR was not significantly induced and these compounds did not significantly increase the externalization of phosphatidylserine (P = 0.6, respectively). In general, the six compounds maintained the stimulation of motility over long periods of time (180 min) and their effects were still observed after their removal. In examinations of clinical samples, there was a general observation of a more significant stimulation of sperm motility in samples with lower baseline motility. In ICSI samples, compounds #26, #37 and #38 were the most effective at significantly increasing total motility (88, 81 and 79% of samples, respectively) and progressive motility (94, 93 and 81% of samples, respectively). In conclusion, using a two-phased drug discovery screening approach including the examination of clinical samples, 3/43 compounds were identified as promising candidates for further study.LIMITATIONS, REASONS FOR CAUTIONThis is an in vitro study and caution must be taken when extrapolating the results. Data for patients were from one assessment and thus the robustness of responses needs to be established. The n values for ICSI samples were relatively small.WIDER IMPLICATIONS OF THE FINDINGSWe have systematically screened and identified several compounds that have robust and effective stimulation (i.e. functional significance with longevity and no toxicity) of total and progressive motility under clinical conditions of treatment. These compounds could be clinical candidates with possibilities in terms of assisted reproductive technology options for current or future patients affected by asthenozoospermia or oligoasthenozoospermia.STUDY FUNDING/COMPETING INTEREST(S)This study was funded primarily by the MRC (DPFS) but with additional funding from the Wellcome Trust, Tenovus (Scotland), University of Dundee, NHS Tayside and Scottish Enterprise. The authors have no competing interests. A patent (#WO2013054111A1) has been published containing some of the information presented in this manuscript.

Intracellular translocation and differential accumulation of cell-penetrating peptides in bovine spermatozoa: evaluation of efficient delivery vectors that do not compromise human sperm motility

Do cell penetrating peptides (CPPs) translocate into spermatozoa and, if so, could they be utilized to deliver a much larger protein cargo? Chemically diverse polycationic CPPs rapidly and efficiently translocate into spermatozoa. They exhibit differential accumulation within intracellular compartments without detrimental influences upon cellular viability or motility but they are relatively ineffective in transporting larger proteins. Endocytosis, the prevalent route of protein internalization into eukaryotic cells, is severely compromised in mature spermatozoa. Thus, the translocation of many bioactive agents into sperm is relatively inefficient. However, the delivery of bioactive moieties into mature spermatozoa could be significantly improved by the identification and utility of an efficient and inert vectorial delivery technology. CPP translocation efficacies, their subsequent differential intracellular distribution and the influence of peptides upon viability were determined in bovine spermatozoa. Temporal analyses of sperm motility in the presence of exogenously CPPs utilized normozoospermic human donor samples. CPPs were prepared by manual, automated and microwave-enhanced solid phase synthesis. Confocal fluorescence microscopy determined the intracellular distribution of rhodamine-conjugated CPPs in spermatozoa. Quantitative uptake and kinetic analyses compared the translocation efficacies of chemically diverse CPPs and conjugates of biotinylated CPPs and avidin. 3-(4,5-dimethylthiazol-2-yl)-5-(3-carboxymethoxyphenyl)-2-(4-sulfophenyl)-2H-tetrazolium, inner salt (MTS) conversion assays were employed to analyse the influence of CPPs upon sperm cell viability and sperm class assays determined the impact of CPPs on motility in capacitated and non-capacitated human samples. Chemically heterogeneous CPPs readily translocated into sperm to accumulate within discrete intracellular compartments. Mitoparan (INLKKLAKL(Aib)KKIL), for example, specifically accumulated within the mitochondria located in the sperm midpiece. The unique plasma membrane composition of sperm is a critical factor that directly influences the uptake efficacy of structurally diverse CPPs. No correlations in efficacies were observed when comparing CPP uptake into sperm with either uptake into fibroblasts or direct translocation across a phosphatidylcholine membrane. These comparative investigations identified C105Y (CSIPPEVKFNKPFVYLI) as a most efficient pharmacokinetic modifier for general applications in sperm biology. Significantly, CPP uptake induced no detrimental influence upon either bovine sperm viability or the motility of human sperm. As a consequence of the lack of endocytotic machinery, the CPP-mediated delivery of much larger protein complexes into sperm is relatively inefficient when compared with the similar process in fibroblasts. It is possible that some CPPs could directly influence aspects of sperm biology and physiology that were not analysed in this study. CPP technologies have significant potential to deliver selected bioactive moieties and so could modulate the biology and physiology of human sperm biology both prior- and post-fertilization.

Preface

It is a privilege to act as the conference editor for this issue of Pure and Applied Chemistry. The 11 papers in this issue constitute selected contributions from the 23rd International Congress on Heterocyclic Chemistry, which was held in the Scottish Exhibition and Conference Centre in Glasgow between 31 July and 4 August 2011. This congress of the International Society of Heterocyclic Chemistry was attended by over 400 participants from over 40 different countries.The conference papers in this issue arise from plenary (Profs. Magid Abou-Gharbia and David O’Hagan), invited (Profs. Janine Cossy, Keiji Maruoka, Ganesh Pandey, Philippe Renaud, and Vinod Singh), and some selected exciting contributions from younger participants (Dr. David Barker, Prof. Tom Pettus, Dr. Jun Shimokawa, and Dr. Michael Smietana). These contributions reflect the main congress themes:- Synthetic methodology- Synthesis- Natural product and complex molecule synthesis materials- Medicinal chemistry- Nanochemistry- Chemical biology/biosynthesis- Chemical biology/DNA and nucleoside analoguesIt is a pleasure to acknowledge the valuable contributions made to the highly successful conference, especially by the conference chair, Prof. Colin Suckling, the local organizing and scientific advisory committees, and the sponsors of the event: Edward C. and Virginia Taylor, Astra Zeneca, Chemical Sciences Scotland, Eisai, EPSRC, Glasgow City Council, GSK, IUPAC, Pfizer, Scottish Enterprise, Syngenta, and the University of Strathclyde. The professional conference organizers, Meeting Makers, did a sterling service in keeping everything on track and the organizers in check.Of course, no conference is possible without the willing participation of the contributors to the scientific program, speakers and poster presenters, session chairs as well as the audience. I would also like to thank the contributors to this issue for agreeing to provide manuscripts and for their timely efforts and to the editorial staff for their valuable help.Colin GibsonConference Editor[Back to Contents]

Knowledge assimilation processes of rapidly internationalising firms

PurposeThe accumulation of knowledge and learning by firms has been identified as being critical to their internationalisation. This paper aims to explore the knowledge assimilation processes of rapidly internationalising small to medium‐sized enterprises (SMEs).Design/methodology/approachThis is a qualitative enquiry in two stages. First, four case studies were selected from firms that were participating in an internationalisation programme run by Scottish Enterprise, the regional development agency. Data collection involved semi‐structured interviews with chief executive officers (CEOs) and programme providers, and archival data. Second, two focus groups were held with six CEOs participating in the programme.FindingsThe findings indicate that knowledge sharing is important for rapidly internationalising SMEs and that firms adopted high levels of formality in assimilating knowledge. Two key aspects of formality were identified as important; formal planned events to share explicit and tacit knowledge and the codification of tacit to explicit knowledge. Knowledge may be assimilated less formally by the retention of tacit knowledge as tacit, while utilising elements of formality. The paper finds that learning for internationalisation can be transferred to support domestic growth.Practical implicationsIt is important for firms to develop appropriate knowledge assimilation processes within their management systems to support internationalisation. The CEO and management team need to take the lead in marshalling commitment to learning processes and in cultivating an organisational culture that is supportive of learning.Originality/valueThis research contributes to international entrepreneurship by providing insights into the knowledge assimilation processes employed by rapidly internationalising SMEs to manage the tensions between the need for greater formality to be efficient at learning, and informality to enable speedy decision making.