Human growth hormone and the temptations of biomedical enhancement

It is likely that humans have sought enhancements for themselves or their children for as long as they have recognised that improvements in individuals are a possibility. One genre of self-improvement in modern society can be called 'biomedical enhancements'. These include drugs, surgery and other medical interventions aimed at improving the mind, body or performance. This paper uses the case of human growth hormone (hGH) to examine the social nature of enhancements. Synthetic hGH was developed in 1985 by the pharmaceutical industry and was approved by the FDA for very specific uses, particularly treatment of growth hormone deficiency. However, it has also been promoted for a number of 'off label' uses, most of which can be deemed enhancements. Drugs approved for one treatment pave the way for use as enhancements for other problems. Claims have been made for hGH as a treatment for idiopathic shortness, as an anti-ageing agent and to improve athletic performance. Using the hGH case, we are able to distinguish three faces of biomedical enhancement: normalisation, repair and performance edge. Given deeply ingrained social and individual goals in American society, the temptations of biomedical enhancements provide inducement for individuals and groups to modify their situation. We examine the temptations of enhancement in terms of issues such as unnaturalness, fairness, risk and permanence, and shifting social meanings. In our conclusions, we outline the potentials and pitfalls of biomedical enhancement.

The Development of Entrepreneurial Leadership: The Role of Human, Social and Institutional Capital

This paper contributes to the literature on entrepreneurial leadership development. Leadership studies are characterized by an increasing emphasis given to an individual leader's social and organizational domain. Within the context of human capital and social capital theory, the paper reflects on the emergence of a social capital theory of leadership development. Using a retrospective, interpretivist research method, the authors present the experience of a cohort of business leaders on an executive development programme to uncover the everydayness of leadership development in practice. Specifically, they explore how entrepreneurial leadership develops as a social process and what the role of social capital is in this. The findings suggest that the enhancement of leaders’ human capital only occurred through their development of social capital. There is not, as extant literature suggests, a clear separation between leader development and leadership development. Further, the analysis implies that the social capital theory of leadership is limited in the context of the entrepreneurial small firm, and the authors propose that it should be expanded to incorporate institutional capital, that is, the formal structures and organizations which enhance the role of social capital and go beyond enriching the human capital stock of individual leaders

Klebsiella pneumoniae increases the levels of Toll-like receptors 2 and 4 in human airway epithelial cells

Airway epithelial cells act as the first barrier against pathogens. These cells recognize conserved structural motifs expressed by microbial pathogens via Toll-like receptors (TLRs) expressed on the surface. In contrast to the level of expression in lymphoid cells, the level of expression of TLR2 and TLR4 in airway epithelial cells is low under physiological conditions. Here we explored whether Klebsiella pneumoniae upregulates the expression of TLRs in human airway epithelial cells. We found that the expression of TLR2 and TLR4 by A549 cells and human primary airway cells was upregulated upon infection with K. pneumoniae. The increased expression of TLRs resulted in enhancement of the cellular response upon stimulation with Pam3CSK4 and lipopolysaccharide, which are TLR2 and TLR4 agonists, respectively. Klebsiella-dependent upregulation of TLR expression occurred via a positive IkappaBalpha-dependent NF-kappaBeta pathway and via negative p38 and p44/42 mitogen-activated protein kinase-dependent pathways. We showed that Klebsiella-induced TLR2 and TLR4 upregulation was dependent on TLR activation. An isogenic capsule polysaccharide (CPS) mutant did not increase TLR2 and TLR4 expression. Purified CPS upregulated TLR2 and TLR4 expression, and polymyxin B did not abrogate CPS-induced TLR upregulation. Although no proteins were detected in the CPS preparation by sodium dodecyl sulfate-polyacrylamide gel electrophoresis and colloidal gold staining, we could not rule out the possibility that traces of protein in our CPS preparation could have been responsible, at least in part, for the TLR upregulation.

Effects of Gold Nanoparticle and Enzyme Precipitation on Enhancement of Surface Plasmon Resonance Immunoassay: A Super Sensitive Measurement of Anti- Glutamic Acid Decarboxylase Antibody

Introduction: In this study, colloidal gold nanoparticle and precipitation of an insoluble product formed by HRP-biocatalyzed oxidation of 3,3'-diaminobenzidine (DAB) in the presence of H2O2 were used to enhance the signal obtained from the surface plasmon resonance biosensor.

Methods: The colloidal gold nanoparticle was synthesized as described by Turkevitch et al., and their surface was firstly functionalized with HS(CH2)11(OCH2CH2)3COOH (OEG3¬-COOH) by self assembling technique. Thereafter, those OEG3-COOH functionalized nanoparticles were covalently conjugated with horseradish peroxidase (HRP) and anti-IgG antibody (specific to the Fc portion of all human IgG subclasses) to form an enzyme-immunogold complex. Characterization was performed by several methods: UV-Vis absorption, dynamic light scattering (DLS), transmission electron microscopy (TEM) and FTIR. The as-prepared enzyme-immunogold complex has been applied in enhancement of SPR immunoassay. A sensor chip used in the experiment was constructed by using 1:10 molar ratio of HS(CH2)11(OCH2CH2)6COOH and HS(CH2)11(OCH2CH2)3OH. The capture protein, GAD65 (autoantigen) which is recognized by anti-GAD antibody (autoantibody) in the sera of insulin-dependent diabetes mellitus patients, was immobilized onto the 1:10 surface via biotin-streptavidin interaction.

Results and conclusions: In the research, we reported the influences of gold nanoparticle and enzyme precipitation on the enhancement of SPR signal. Gold nanoparticle showed its enhancement as being consistent with other previous studies, while the enzyme precipitation using DAB substrate was applied for the first time and greatly amplified the SPR detection. As the results, anti-GAD antibody could be detected at pg/ml level which is far higher than that of commercial ELISA detection kit. This study indicates another way to enhance SPR measurement, and it is generally applicable to other SPR-based immunoassays.

Sequential treatment with flavopiridol synergistically enhances pyrrolo-1,5-benzoxazepine-induced apoptosis in human chronic myeloid leukaemia cells including those resistant to imatinib treatment

The Bcr-Abl kinase inhibitor, imatinib mesylate, is the front line treatment for chronic myeloid leukaemia (CML), but the emergence of imatinib resistance has led to the search for alternative drug treatments and the examination of combination therapies to overcome imatinib resistance. The pro-apoptotic PBOX compounds are a recently developed novel series of microtubule targeting agents (MTAs) that depolymerise tubulin. Recent data demonstrating enhanced MTA-induced tumour cell apoptosis upon combination with the cyclin dependent kinase (CDK)-1 inhibitor flavopiridol prompted us to examine whether this compound could similarly enhance the effect of the PBOX compounds. We thus characterised the apoptotic and cell cycle events associated with combination therapy of the PBOX compounds and flavopiridol and results showed a sequence dependent, synergistic enhancement of apoptosis in CML cells including those expressing the imatinib-resistant T315I mutant. Flavopiridol reduced the number of polyploid cells formed in response to PBOX treatment but only to a small extent, suggesting that inhibition of endoreplication was unlikely to play a major role in the mechanism by which flavopiridol synergistically enhanced PBOX-induced apoptosis. The addition of flavopiridol following PBOX-6 treatment did however result in an accelerated exit from the G2/M transition accompanied by an enhanced downregulation and deactivation of the CDK1/cyclin B1 complex and an enhanced degradation of the inhibitor of apoptosis protein (IAP) survivin. In conclusion, results from this study highlight the potential of these novel series of PBOX compounds, alone or in sequential combination with flavopiridol, as an effective therapy against CML.

Understanding Graduate Recruitment, Development and Retention for the Enhancement of Talent Management: Sharpening “the edge” of Graduate Talent

Graduates are deemed to be a key source of talent within many organisations and thus recruiting, developing and retaining them is viewed as a logical talent management (TM) strategy. However, there has been little attention paid to university graduates as part of an organisation’s TM strategy. Such a specific focus addresses the need for further research into the segmentation of talent pools and the specific challenges different talent pools are likely to create. This research, which utilised a qualitative data collection strategy, examined the experiences and practices of six large UK organisations in relation to graduate TM. Drawing from Gallardo-Gallardo, Dries and González-Cruz’s (2013. What is the meaning of ‘talent’ in the world of work? Human Resource Management Review, 23, 290–300.) framework for the conceptualisation of talent, the findings from this research indicate and explain why graduate employers are frequently compelled to use the object approach (talent as characteristics of people) due to the unique characteristics that recent graduates possess, even though other studies have found that a subject approach (talent as people and what they do) is preferred by most employers. Ultimately, employers conceptualise graduate talent by what they describe as ‘the edge’ which needs to be ‘sharpened’ to fully realise the potential that graduates offer.

Sustainability Enhancement of a Turbine Vane Manufacturing Cell through Digital Simulation based Design

Modern manufacturing systems should satisfy emerging needs related to sustainable development. The design of sustainable manufacturing systems can be valuably supported by simulation, traditionally employed mainly for time and cost reduction. In this paper, a multi-purpose digital simulation approach is proposed to deal with sustainable manufacturing systems design through Discrete Event Simulation (DES) and 3D digital human modelling. DES models integrated with data on power consumption of the manufacturing equipment are utilized to simulate different scenarios with the aim to improve productivity as well as energy efficiency, avoiding resource and energy waste. 3D simulation based on digital human modelling is employed to assess human factors issues related to ergonomics and safety of manufacturing systems. The approach is implemented for the sustainability enhancement of a real manufacturing cell of the aerospace industry, automated by robotic deburring. Alternative scenarios are proposed and simulated, obtaining a significant improvement in terms of energy efficiency (−87%) for the new deburring cell, and a reduction of energy consumption around −69% for the coordinate measuring machine, with high potential annual energy cost savings and increased energy efficiency. Moreover, the simulation-based ergonomic assessment of human operator postures allows 25% improvement of the workcell ergonomic index.