Characterization and Comparison of Mesoporous Silica Particles for Optimized Drug Delivery

In this study we have investigated the suitability of a number of different mesoporous silica nanoparticle structures for carrying a drug cargo. We have fully characterized the nanoparticles in terms of their physical parameters; size, surface area, internal pore size and structure. These data are all required if we are to make an informed judgement on the suitability of the structure for drug delivery in vivo. With these parameters in mind, we investigated the loading/unloading profile of a model therapeutic into the pore structure of the nanoparticles. We demonstrate that the release can be controlled by capping the pores on the nanoparticles to achieve temporal control of the unloading. We have also examined the rate and mechanism of the degradation of the nanoparticles over an extended period of time. The eventual dissolution of the nanoparticles after cargo release is a desirable property for a drug delivery system

All work and no pay: consequences of unpaid work experience in the creative industries

This research note evaluates the benefits and pitfalls of unpaid work as an entry route into employment in the creative industries and investigates the consequences of this practice for those who already work in the sector. Based on a qualitative study of perspectives of stakeholders in unpaid work, this article argues that the social capital thesis, often used as a rationale for unpaid work, inadequately explains the practice of unpaid work experience, primarily because it does not take cognisance of the consequences of this practice for other people working in the sector. The study also highlights methodological issues that need to be considered in the future. As well as the importance of a plurality of stakeholder perspectives, the study emphasizes the need to consider the perspectives of those who are excluded from unpaid work and those who are potentially displaced by it

Mitochondrial survivin reduces oxidative phosphorylation in cancer cells by inhibiting mitophagy

Survivin is a cancer-associated protein that is pivotal for cellular life and death: it is an essential mitotic protein and an inhibitor of apoptosis. In cancer cells, a small pool of survivin localises to the mitochondria, the function of which remains to be elucidated. Here, we report that mitochondrial survivin inhibits the selective form of autophagy, called “mitophagy”, causing an accumulation of respiratory defective mitochondria. Mechanistically the data reveal that survivin prevents recruitment of the E3-ubiquitin ligase Parkin to mitochondria and their subsequent recognition by the autophagosome. The data also demonstrate that as a consequence of this blockade cells expressing high levels of survivin have an increased dependency on anaerobic glycolysis. As these effects were found exclusively in cancer cells they suggest that the primary act of mitochondrial survivin is to force cells to implement the “Warburg Effect” by inhibiting mitochondrial turnover, which gives them a survival advantage

The N-terminus of survivin is a mitochondrial-targeting sequence and Src regulator

Survivin is a cancer-associated protein that exists in several locations in the cell. Its cytoplasmic residence in interphase cells is governed by CRM1-mediated nuclear exportation, and its localisation during mitosis to the centromeres and midzone microtubules is that of a canonical chromosomal passenger protein. In addition to these well-established locations, survivin is also a mitochondrial protein, but how it gets there and its function therein is presently unclear. Here we show that the first 10 amino acids at the NH2 terminus of survivin are sufficient to target GFP to the mitochondria in vivo, and ectopic expression of this decapeptide decreases cell adhesion and accelerates proliferation. The data support a signalling mechanism in which mitochondrial survivin activates the tyrosine kinase, C-Src, leading to reduced focal adhesion plaques and disruption of F-actin organisation. This strongly suggests that the NH2 terminus of survivin is a mitochondrial targeting sequence that regulates C-Src, and that survivin acts in concert with C-Src to promote tumorigenesis

The employee as 'Dish of the Day’:human resource management and the ethics of consumption

This article examines the ethical implications of the growing integration of consumption into the heart of the employment relationship. Human resource management (HRM) practices increasingly draw upon the values and practices of consumption, constructing employees as the ‘consumers’ of ‘cafeteria-style’ benefits and development opportunities. However, at the same time employees are expected to market themselves as items to be consumed on a corporate menu. In relation to this simultaneous position of consumer/consumed, the employee is expected to actively engage in the commodification of themselves, performing an appropriate organizational identity as a necessary part of being a successful employee. This article argues that the relationship between HRM and the simultaneously consuming/consumed employee affects the conditions of possibility for ethical relations within organizational life. It is argued that the underlying ‘ethos’ for the integration of consumption values into HRM practices encourages a self-reflecting, self-absorbed subject, drawing upon a narrow view of individualised autonomy and choice. Referring to Levinas’ perspective that the primary ethical relation is that of responsibility and openness to the Other, it is concluded that these HRM practices affect the possibility for ethical being

Inferring transient dynamics of human populations from matrix non-normality

This is the final version of the article. Available from Springer Verlag via the DOI in this record.In our increasingly unstable and unpredictable world, population dynamics rarely settle uniformly to long-term behaviour. However, projecting period-by-period through the preceding fluctuations is more data-intensive and analytically involved than evaluating at equilibrium. To efficiently model populations and best inform policy, we require pragmatic suggestions as to when it is necessary to incorporate short-term transient dynamics and their effect on eventual projected population size. To estimate this need for matrix population modelling, we adopt a linear algebraic quantity known as non-normality. Matrix non-normality is distinct from normality in the Gaussian sense, and indicates the amplificatory potential of the population projection matrix given a particular population vector. In this paper, we compare and contrast three well-regarded metrics of non-normality, which were calculated for over 1000 age-structured human population projection matrices from 42 European countries in the period 1960 to 2014. Non-normality increased over time, mirroring the indices of transient dynamics that peaked around the millennium. By standardising the matrices to focus on transient dynamics and not changes in the asymptotic growth rate, we show that the damping ratio is an uninformative predictor of whether a population is prone to transient booms or busts in its size. These analyses suggest that population ecology approaches to inferring transient dynamics have too often relied on suboptimal analytical tools focussed on an initial population vector rather than the capacity of the life cycle to amplify or dampen transient fluctuations. Finally, we introduce the engineering technique of pseudospectra analysis to population ecology, which, like matrix non-normality, provides a more complete description of the transient fluctuations than the damping ratio. Pseudospectra analysis could further support non-normality assessment to enable a greater understanding of when we might expect transient phases to impact eventual population dynamics.This work was funded by Wellcome Trust New Investigator 103780 to TE, who is also funded by NERC Fellowship NE/J018163/1. JB gratefully acknowledges the ESRC Centre for Population Change ES/K007394/1

Towards Critical Human Resource Management Education (CHRME): a sociological imagination approach

This article explores the professional standing of the discipline of human resource management (HRM) in business schools in the post-financial crisis period. Using the prism of the sociological imagination, it explains the learning to be gained from teaching HRM that is sensitive to context, power and inequality. The context of crisis provides ideal circumstances for critical reflexivity and for integrating wider societal issues into the HRM curriculum. It argues for Critical Human Resource Management Education or CHRME, which, if adopted, would be an antidote to prescriptive practitioner-oriented approaches. It proceeds to set out five principles for CHRME: using the ‘sociological imagination’ prism; emphasizing the social nature of the employment relationship; investigating paradox within HRM; designing learning outcomes that encourage students to appraise HRM outcomes critically; and reflexive critique. Crucially, CHRME offers a teaching strategy that does not neglect or marginalize the reality of structural power, inequality and employee work experiences

Entrepreneurial sons, patriarchy and the Colonels' experiment in Thessaly, rural Greece

Existing studies within the field of institutional entrepreneurship explore how entrepreneurs influence change in economic institutions. This paper turns the attention of scholarly inquiry on the antecedents of deinstitutionalization and more specifically, the influence of entrepreneurship in shaping social institutions such as patriarchy. The paper draws from the findings of ethnographic work in two Greek lowland village communities during the military Dictatorship (1967–1974). Paradoxically this era associated with the spread of mechanization, cheap credit, revaluation of labour and clear means-ends relations, signalled entrepreneurial sons’ individuated dissent and activism who were now able to question the Patriarch’s authority, recognize opportunities and act as unintentional agents of deinstitutionalization. A ‘different’ model of institutional change is presented here, where politics intersects with entrepreneurs, in changing social institutions. This model discusses the external drivers of institutional atrophy and how handling dissensus (and its varieties over historical time) is instrumental in enabling institutional entrepreneurship