Cell-free expression and SMA copolymer encapsulation of a functional receptor tyrosine kinase disease variant, FGFR3-TACC3

Despite their high clinical relevance, obtaining structural and biophysical data on transmembrane proteins has been hindered by challenges involved in their expression and extraction in a homogeneous, functionally-active form. The inherent enzymatic activity of receptor tyrosine kinases (RTKs) presents additional challenges. Oncogenic fusions of RTKs with heterologous partners represent a particularly difficult-to-express protein subtype due to their high flexibility, aggregation propensity and the lack of a known method for extraction within the native lipid environment. One such protein is the fibroblast growth factor receptor 3 fused with transforming acidic coiled-coil-containing protein 3 (FGFR3-TACC3), which has failed to express to sufficient quality or functionality in traditional expression systems. Cell-free protein expression (CFPE) is a burgeoning arm of synthetic biology, enabling the rapid and efficient generation of recombinant proteins. This platform is characterised by utilising an optimised solution of cellular machinery to facilitate protein synthesis in vitro. In doing so, CFPE can act as a surrogate system for a range of proteins that are otherwise difficult to express through traditional host cell-based approaches. Here, functional FGFR3-TACC3 was expressed through a novel cell-free expression system in under 48 h. The resultant protein was reconstituted using SMA copolymers with a specific yield of 300 µg/mL of lysate. Functionally, the protein demonstrated significant kinase domain phosphorylation (t < 0.0001). Currently, there is no published, high-resolution structure of any full-length RTK. These findings form a promising foundation for future research on oncogenic RTKs and the application of cell-free systems for synthesising functional membrane proteins

Supporting self-management with an internet intervention for low back pain in primary care: a RCT (SupportBack 2)

Background Low back pain is highly prevalent and a leading cause of disability. Internet-delivered interventions may provide rapid and scalable support for behavioural self-management. There is a need to determine the effectiveness of highly accessible, internet-delivered support for self-management of low back pain. Objective To determine the clinical and cost-effectiveness of an accessible internet intervention, with and without physiotherapist telephone support, on low back pain-related disability. Design A multicentre, pragmatic, three parallel-arm randomised controlled trial with parallel economic evaluation. Setting Participants were recruited from 179 United Kingdom primary care practices. Participants Participants had current low back pain without indicators of serious spinal pathology. Interventions Participants were block randomised by a computer algorithm (stratified by severity and centre) to one of three trial arms: (1) usual care, (2) usual care + internet intervention and (3) usual care + internet intervention + telephone support. ‘SupportBack’ was an accessible internet intervention. A physiotherapist telephone support protocol was integrated with the internet programme, creating a combined intervention with three brief calls from a physiotherapist. Outcomes The primary outcome was low back pain-related disability over 12 months using the Roland–Morris Disability Questionnaire with measures at 6 weeks, 3, 6 and 12 months. Analyses used repeated measures over 12 months, were by intention to treat and used 97.5% confidence intervals. The economic evaluation estimated costs and effects from the National Health Service perspective. A cost–utility study was conducted using quality-adjusted life-years estimated from the EuroQol-5 Dimensions, five-level version. A cost-effectiveness study estimated cost per point improvement in the Roland–Morris Disability Questionnaire. Costs were estimated using data from general practice patient records. Researchers involved in data collection and statistical analysis were blind to group allocation. Results Eight hundred and twenty-five participants were randomised (274 to usual primary care, 275 to usual care + internet intervention and 276 to the physiotherapist-supported arm). Follow-up rates were 83% at 6 weeks, 72% at 3 months, 70% at 6 months and 79% at 12 months. For the primary analysis, 736 participants were analysed (249 usual care, 245 internet intervention, 242 telephone support). There was a small reduction in the Roland–Morris Disability Questionnaire over 12 months compared to usual care following the internet intervention without physiotherapist support (adjusted mean difference of −0.5, 97.5% confidence interval −1.2 to 0.2; p = 0.085) and the internet intervention with physiotherapist support (−0.6, 97.5% confidence interval −1.2 to 0.1; p = 0.048). These differences were not statistically significant at the level of 0.025. There were no related serious adverse events. Base-case results indicated that both interventions could be considered cost-effective compared to usual care at a value of a quality-adjusted life-year of £20,000; however, the SupportBack group dominated usual care, being both more effective and less costly. Conclusions The internet intervention, with or without physiotherapist telephone support, did not significantly reduce low back pain-related disability across 12 months, compared to usual primary care. The interventions were safe and likely to be cost-effective. Balancing clinical effectiveness, cost-effectiveness, accessibility and safety findings will be necessary when considering the use of these interventions in practice. Trial registration This trial is registered as ISRCTN14736486. Funding This award was funded by the National Institute for Health and Care Research (NIHR) Health Technology Assessment programme (NIHR award ref: 16/111/78) and is published in full in Health Technology Assessment; Vol. 29, No. 7. See the NIHR Funding and Awards website for further award information

City-level institutions and perceived entrepreneurial ecosystem’s growth orientation

This study uses both secondary and primary data on perceptions of 1789 ecosystem actors from 17 cities in Europe to perform an empirical analysis of three institutional dimensions: regulatory, cultural values and socio-cultural practices – and tests their association with the entrepreneurial ecosystem’s growth orientation. As a result, we develop a framework for the entrepreneurial ecosystem’s factors and provide policy recommendations for those interested in supporting the entrepreneurial ecosystem’s growth orientation in cities. Among other conclusions, the findings suggest a positive association between the socio-cultural practices of environmental sustainability behaviour in businesses with entrepreneurial ecosystem’s growth orientation

Achieving Biodiesel Standards Through Saturation Level Optimisation

Biodiesels made from waste feedstock are viable sustainable fuels for compression ignition engine use. However, biodiesel produced from single waste source do not always comply with the European biodiesel standard. This study investigated the fuel quality and engine performance when two biodiesels with different characteristics were blended at various proportions. Waste cooking oil biodiesel was blended with sheep fat biodiesel which has a lower unsaturated fatty acid content. The engine performance, combustion and exhaust emission characteristics of the neat biodiesels and their blends (at 60/40, 50/50, and 30/70 ratios) were analysed. The results showed that 60/40 and 50/50 blends met the core parameters of BS EN 14214 biodiesel standard and improved the combustion and emission characteristics as compared to their neat biodiesels and diesel. The 50/50 blends gave up to 5% and 14% improvements in the in-cylinder pressure and maximum heat release rate respectively, when compared to the same results for neat biodiesel operation. Reduction of up to 73% in CO, 96% in smoke and 3% in CO2 emissions were observed. However, NOx emission was 2.5% higher than diesel. The results revealed that carefully selected biodiesel-biodiesel blending could meet fuel standards, improve engine performance and reduce exhaust emissions

Impact of loyal and new customer segments on product upgrades: The role of quality differentiation through online reviews

Firms often strive to expand their market share beyond their established customer base by launching quality upgrades in their products. They recognize that customers often gauge product quality through online reviews. We develop an analytical model to examine the quality upgrade strategies of two competing firms, revealing two potential market equilibria. In the unilateral upgrading equilibrium where only one firm upgrades, the upgrading firm sees an initial increase in loyal demand, leading to higher prices. This price adjustment, however, may deter potential new customers who turn to the more affordable non-upgrading competitor, referred to as the substitution effect. Despite attracting more loyal customers, the upgrading firm may experience a net loss in broader market share due to the substitution effect. In the bilateral upgrading equilibrium where both firms upgrade and engage in quality competition, the situation becomes akin to a prisoner’s dilemma if loyal customers show indifference to quality improvements. The gains from loyal customers are outweighed by fierce competition for new customers, ultimately disadvantaging both firms. Furthermore, our findings indicate that review-revealed quality difference between the two products leads to a higher degree of quality improvement effort by the high-quality firm, while reducing that of the low-quality firm. Intriguingly, in the unilateral equilibrium, the high-quality firm may not benefit from its review-revealed superior quality, while the low-quality firm may not be disadvantaged, depending on the substitution effect relatively

Directional Magnetic Field Sensing Based on Few Mode Fiber Long-Period Grating with Spatial Refractive Index Modulation

We present a highly sensitive directional magnetic field sensor based on a long-period fiber grating (LPFG) inscribed in few-mode fiber (FMF) and combined with magnetic fluid (MF). The unique spatial refractive index modulation profile of the FMF-LPFG allows for the simultaneous measurement of magnetic field intensity, direction, and temperature. The interaction between the anisotropic refractive index of the MF and the LPFG is exploited to achieve directional magnetic field sensitivity, with a maximum intensity sensitivity of 717.5 pm/mT at 0° and directional sensitivity of 163.3 pm/degree at 10.7 mT. Temperature cross-talk is mitigated by monitoring independent interference dips, enabling reliable dualparameter sensing. The proposed FMF-LPFG sensor demonstrates excellent intensity sensitivity, precise directional detection, and effective temperature monitoring. This work offers a robust and versatile solution for high-precision magnetic field monitoring in applications ranging from industrial sensing to biomedical diagnostics

New Frontiers and The Impact of Artificial Intelligence and the Digital Revolution on the Future of Intellectual Property Laws

Before the Covid pandemic hit, artificial intelligence (AI) had already embedded itself into our everyday lives. AI as an assistive tool adequately responds to humans’ needs, such as virtual digital assistance, almost everyone will have Apple Siri, Alexa and or Google Home, as voice recognition systems. Relying on artificial intelligence systems such as Spotify to provide a recommended list of music based on your existing music choices and preferences is commonplace, and likewise, for producing works of art. Most notably, a project team behind The Next Rembrandt designed algorithms that allowed a computer to create a painting in the style of the 17th century Dutch artist and is known as the Rembrandt 2.0 . Artificial intelligence can produce works which could be considered as copyright works however international law has yet to acknowledge AI as a copyright owner . Humans working in creative, innovative and legal sectors are discussing the consequence of AI systems when it comes to who will own the intellectual property, more importantly, who will the economic rights belong to. Artificial intelligence systems are developing at a significant pace and as a result, reshaping the whole creative and innovative sectors that are protected in the existing intellectual property systems. Therefore, it is necessary to identify the AI systems at present, defining and distinguishing between the concepts of “AI-assisted” and “AI-generated”, to outline the direction of AI development in the context of intellectual property law

Elite status-seeking and class reproduction in civil society: an analysis of corporate elite appointments to charity boards

This article examines the relationship between economic elites and civil society by analysing the appointments of corporate elites to the boards of charitable companies in the UK. Whilst previous research has usually focused on who among the corporate elite hold positions in key civil society organisations, and the extent to which these organisations are integrated into corporate networks, we use data on the nature and operations of civil society organisations to identify which are more likely to attract corporate elites as board members. Using a dataset of over thirty-one thousand UK incorporated companies registered with the Charity Commission of England and Wales, we examine the appointments of corporate elite to these organisations over a ten-year period. Based on these appointments, we are able to offer insights into the social networks, values and interests of the corporate elite as a whole. We find that the UK corporate elite are more likely to join the boards of larger, high-status charities, and those that support traditional upper-class culture and class reproduction. We also find they are relatively more likely to join organisations that seek to shape politics and society – such as foundations distributing grants, or think tanks undertaking public policy research and advocacy – than those involved in the provision of welfare and social services. Taken together, the findings are suggestive of a status-seeking, culturally highbrow and secular economic elite, that is more traditional than meritocratic, and more concerned with shaping policy and supporting the institutions of their class, than directly supporting disadvantaged groups

Circular Economy in Small and Medium-Sized Enterprises—Current Trends, Practical Challenges and Future Research Agenda

The Circular Economy (CE) has evolved as a philosophy to transform industrial supply chains to become greener to combat climate change issues. Countries’ target of achieving Net Zero will never be fulfilled unless, along with larger organizations, small and medium-sized enterprises (SMEs) are decarbonized, as more than 90% of the world’s businesses are SMEs. Although, recently, there have been many studies on SMEs’ sustainability practices and performance covering drivers, bottlenecks, and opportunities, the holistic approach for embedding circular economy and sustainability covering design, planning, implementation, and operations is missing. This research bridges this knowledge gap by revealing trends and theories of circular economy adoption in SMEs. Additionally, this research derives the drivers/enablers, issues, and challenges and determines strategies, resources, and competencies for CE adoption in SMEs. This study concludes with a consolidated framework comprising factors and methods for CE implementation in SMEs. This entire piece of research has been undertaken using the secondary data analysis method through the content analysis of 188 published articles in highly ranked peer-reviewed journals

A review of the empirical literature on ‘engagement’ within the context of entrepreneurship and small business management

Previous reviews on (work/job/employee) ‘engagement’ have neglected research within the context of entrepreneurship and small and medium-sized enterprises (SMEs). We present a systematic narrative review of the empirical literature on ‘engagement’ within this industrial and employment context. Our aims are to a) determine the scope of research conducted, b) identify key insights, and c) uncover key gaps and problems. We searched four databases for material published between 2010 and 2023. From systematic sifting of 1155 items, 40 articles met our quality and relevance criteria. These articles derive from various disciplines, yet mainly adopt a psychological focus. However, the literature lacks methodological pluralism and cultural contextualization, and an underplaying of institutional/market factors. We find two distinct streams: i) studies focusing on employee engagement with SMEs, and ii) studies focusing on entrepreneurial engagement. There are opportunities to connect these streams in a more interdisciplinary way as well as to develop each in more meaningful ways