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Reference protocol to assess analytical performance of higher order structural analysis measurements: results from an interlaboratory comparison
Get PDFMeasurements of protein higher order structure (HOS) provide important information on stability, potency, efficacy, immunogenicity, and biosimilarity of biopharmaceuticals, with a significant number of techniques and methods available to perform these measurements. The comparison of the analytical performance of HOS methods and the standardization of the results is, however, not a trivial task, due to the lack of reference protocols and reference measurement procedures. Here, we developed a protocol to structurally alter and compare samples of somatropin, a recombinant biotherapeutic, and describe the results obtained by using a number of techniques, methods and in different laboratories. This, with the final aim to provide tools and generate a pool of data to compare and benchmark analytical platforms and define method sensitivity to structural changes. Changes in somatropin HOS, induced by the presence of zinc at increasing concentrations, were observed, both globally and at more localized resolution, across many of the methods utilized in this study and with different sensitivities, suggesting the suitability of the protocol to improve understanding of inter- and cross-platform measurement comparability and assess analytical performance as appropriate
Spontaneous assembly of redox-active iron-sulfur clusters at low concentrations of cysteine
Get PDFIron-sulfur (FeS) proteins are ancient and fundamental to life, being involved in electron transfer and CO2 fixation. FeS clusters have structures similar to the unit-cell of FeS minerals such as greigite, found in hydrothermal systems linked with the origin of life. However, the prebiotic pathway from mineral surfaces to biological clusters is unknown. Here we show that FeS clusters form spontaneously through interactions of inorganic Fe2+/Fe3+ and S2− with micromolar concentrations of the amino acid cysteine in water at alkaline pH. Bicarbonate ions stabilize the clusters and even promote cluster formation alone at concentrations >10 mM, probably through salting-out effects. We demonstrate robust, concentration-dependent formation of [4Fe4S], [2Fe2S] and mononuclear iron clusters using UV-Vis spectroscopy, 57Fe-Mössbauer spectroscopy and 1H-NMR. Cyclic voltammetry shows that the clusters are redox-active. Our findings reveal that the structures responsible for biological electron transfer and CO2 reduction could have formed spontaneously from monomers at the origin of life
'Dominance, defence and diminishing returns'? Theresa May’s leadership capital July 2016 to July 2018
Get PDFTheresa May’s first two years in office illustrate Anthony King’s (1991) observation that premierships can vary within themselves. Her premiership divides into two distinct phases, before and after the snap general election of June 2017, with a final coda after July 2017 when her premiership unravelled. Whilst the disastrous election looked like the crucial event, analysis using the Leadership Capital Index (LCI) suggests that, contrary to popular assumptions, before the election May was weaker than she appeared and afterwards not quite as diminished as assumed. The LCI analysis we present here (focusing on the year before and the year after the 2017 general election) shows that May’s capital fell, but not as far as presented by prevailing narratives. May went from being, in LCI terms, an ‘exceptional leader’ to a ‘medium capital leader’ facing obstacles, but still capable of action. May’s resilience after 2017 was a result of Brexit, the poor polling of her opponents and her unexpected poll strength, bolstered by the weakness of her internal challengers. Even a poorly positioned prime minister has considerable resources to call upon
Mothering in the frame
No full textIn a child’s life, “how early do important things happen?” asked child psychoanalyst D.W.Winnicott in 1945. A number of his colleagues believed that the camera might provide an answer to that question. Katie Joice explores the history of using film as a means of deciphering the mother-infant relationship
State shaming and the social theory of peremptory norms in international law: the possibility of the prohibition of nuclear proliferation as a Jus Cogens norm
No full textPeremptory norms in international law, often referred to as jus cogens, refers to practices, such as genocide, torture and slavery which the international community at large wishes to prevent. The proliferation of nuclear weapons is a practice that the international community at large sees an interest in preventing given the existence of the non-proliferation treaty and numerous UN Security Council and General Assembly resolutions on the subject. Yet, the proliferation of nuclear weapons or their acquisition is not necessarily considered jus cogens. Using recent constructivist accounts of jus cogens this chapter argues that nuclear proliferation raises questions separate from the prohibition of use of force which makes it analogous to the subject matter of other existing jus cogens norms
What challenges did junior doctors face while working during the COVID-19 pandemic? A qualitative study
Get PDFObjectives: This paper reports findings exploring junior doctors’ experiences of working during the COVID-19 pandemic in the UK.
Design: Qualitative study using in-depth interviews with 15 junior doctors. Interviews were audio-recorded, transcribed, anonymised and imported into NVivo V.12 to facilitate data management. Data were analysed using reflexive thematic analysis.
Setting National Health Service (NHS) England.
Participants: A purposive sample of 12 female and 3 male junior doctors who indicated severe depression and/or anxiety on the DASS-21 questionnaire or high suicidality on Paykel’s measure were recruited. These doctors self-identified as having lived experience of distress due to their working conditions.
Results: We report three major themes. First, the challenges of working during the COVID-19 pandemic, which were both personal and organisational. Personal challenges were characterised by helplessness and included the trauma of seeing many patients dying, fears about safety and being powerless to switch off. Work-related challenges revolved around change and uncertainty and included increasing workloads, decreasing staff numbers and negative impacts on relationships with colleagues and patients. The second theme was strategies for coping with the impact of COVID-19 on work, which were also both personal and organisational. Personal coping strategies, which appeared limited in their usefulness, were problem and emotion focused. Several participants appeared to have moved from coping towards learnt helplessness. Some organisations reacted to COVID-19 collaboratively and flexibly. Third, participants reported a positive impact of the COVID-19 pandemic on working practices, which included simplified new ways of working—such as consistent teams and longer rotations—as well as increased camaraderie and support.
Conclusions: The trauma that junior doctors experienced while working during COVID-19 led to powerlessness and a reduction in the benefit of individual coping strategies. This may have resulted in feelings of resignation. We recommend that, postpandemic, junior doctors are assigned to consistent teams and offered ongoing support
Mapping the distribution of Internet of Things competences across European regions
Get PDFDigital transformation is a key strategic issue for countries and regions aiming to boost economic
growth, job creation, technology development and innovation. With a focus on the Internet of
Things (IoT) the paper maps the potential of IoT technologies across European regions, using
textual analysis applied to the description of companies’ activities. Results identify three
categories of regions (IoT leaders, co-designers and suppliers) capturing their potential to harness
opportunities in IoT, based on the variety of IoT competences that are present. This mapping can
support regional policies, particularly in the context of smart specialization strategies building on
IoT systems
Social capital and sport organisations
No full textBook synopsis: Drawing on primary research within voluntary sports clubs in the UK and secondary analysis of the wider international literature on social capital, this text focuses on the micro-processes of social capital development and how they play out in specific social settings. In so doing, it adds to existing research by developing a rich, contextualised, process-based view of social capital in action.
Critically reviewing theoretical and empirical literature on social capital, the book highlights the key current debates. The empirical core of the book draws on ethnographic observation over 18 months at voluntary sports clubs in the UK, including in-depth interviews with sports club members and organisers. The text explicitly seeks to set this empirical work in its wider context, by considering the findings in relation to other international studies of social capital in both sports clubs and other types of organisation. The book draws on international research from a whole range of countries: UK, USA, Australia, Canada, Norway, Denmark, Netherlands, Japan, Vanuatu, Czech Republic, Germany, and many others. The book establishes a transferable, process-based understanding of how social capital develops – both within sports clubs and beyond.
This is an illuminating reading for policymakers, practitioners, and researchers with an interest in the sociology of sport, sport development, sport management, sport policy, social theory, social policy, or social networks
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