Rocaglates induce gain-of-function alterations to eIF4A and eIF4F

Rocaglates are a diverse family of biologically active molecules that have gained tremendous interest in recent years due to their promising activities in pre-clinical cancer studies. As a result, this family of compounds has been significantly expanded through the development of efficient synthetic schemes. However, it is unknown whether all of the members of the rocaglate family act through similar mechanisms of action. Here, we present a comprehensive study comparing the biological activities of >200 rocaglates to better understand how the presence of different chemical entities influences their biological activities. Through this, we find that most rocaglates preferentially repress the translation of mRNAs containing purine-rich 5' leaders, but certain rocaglates lack this bias in translation repression. We also uncover an aspect of rocaglate mechanism of action in which the pool of translationally active eIF4F is diminished due to the sequestration of the complex onto RNA.P50 GM067041 - NIGMS NIH HHS; R24 GM111625 - NIGMS NIH HHS; R35 GM118173 - NIGMS NIH HHSPublished versio

Standardization as Institutional Work: The Regulatory Power of a Responsible Investment Standard

This paper conceptualizes standardization as institutional work to study the emergence of a standard and the deployment of its regulatory power. We rely on unique access to longitudinal archival data for exploring how the FTSE4Good index, a responsible investment index, emerged as a standard for socially responsible corporate behavior. Our results show how three types of standardization work - calculative framing, engaging and valorizing - support the design, legitimation and monitoring processes whereby a standard acquires its regulatory power. Our findings reveal new facets in the dynamics of standardization by approaching standardization as a product of institutional work and in showing how unintended consequences of that work can be recaptured to strengthen the regulatory power of the standard

Organizational evolution and the Olympic Games: the case of sport climbing

This paper discusses the processes underpinning the evolutionary development of sport climbing in recent decades, with a particular focus on the impact of its inclusion in the Olympic Games. New institutionalism and resource-dependence theory provide an analytical and explanatory framework for this study. The research adopted a qualitative method strategy comprising a series of interviews and the analysis of documents, reports, press and social media. The recent inclusion of the sport in the Tokyo 2020 Olympic programme has created challenges, primarily because of strong values inherent within the sport. The research, however, shows that the values of a sport can expand and develop in order to fit the regulatory legitimacy required by inclusion in the Olympic Games. Nonetheless, the research also shows that involvement with the IOC raises questions about who ‘owns’ the sport

Leadership, the logic of sufficiency and the sustainability of education

The notion of sufficiency has not yet entered mainstream educational thinking, and it still has to make its mark upon educational leadership. However, a number of related concepts – particularly those of sustainability and complexity theory – are beginning to be noticed. This article examines these two concepts and uses them to critique the quasi-economic notion of efficiency, before arguing that the concept of sufficiency arises naturally from this discussion. This concept, originally derived from environmental thinking, has both metaphorical and practical impact for educational organizations and their leadership. An examination of three possible meanings suggests that while an embrace of an imperative concept of sufficiency seems increasingly necessary, its adoption would probably lead to a number of other problems, as it challenges some fundamental societal values and assumptions. Nevertheless, the article argues that these need to be addressed for the sake of both sustainable leadership and a sustainable planet

Handling Uncertainty of Strategic Ambitions—The Use of Organizational Identity as a Risk-Reducing Device

Organizational identity can be designed to reduce the risks of uncertainty about future states of public organizations and the inherent potential issues related to evaluation and assessment. As such, organizational identity may shape a congruent and credible self-representation of the university, where a consistent narrative articulates compliance to diverse institutional frameworks, commitment to organizational distinctiveness, and a sensible rationale for strategic change. By examining the strategic plans of four European universities over a 10-year period of major organizational change, the paper discusses the subtleties of the specific combinations of the three different functions and the implications for institutional leadership

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

Producing persuasive findings: Demystifying ethnographic textwork in strategy and organization research

Despite the importance and proliferation of ethnography in strategy and organization research, the central issue of how to present ethnographic findings has rarely been discussed. Yet, the narratives we craft to share our experience of the field are at the heart of ethnographic papers and provide the primary basis for our theorizing. In this article, we explain the “textwork” involved in writing persuasive findings. We provide an illustrative example of ethnographic data as it is recorded within fieldnotes and explain the necessary conceptual and writing work that must be done to render such data persuasive, drawing on published exemplars of ethnographic articles. This allows us to show how such texts, through various forms of writing and data representation, are transformed from raw fieldnotes to comprehensible findings. We conclude by asserting the value of these specifically ethnographic ways of presenting evidence, which are at odds with the canonical methods of data presentation in management studies

Obstacles and disaster risk reduction: Survey of Memphis organizations

Accepted VersionThe disaster management literature is replete with surveys at the community and household levels. However, few exist at the organizational level. This study attempts to fill this void by examining the effect of organizational obstacles on disaster risk reduction. The data come from a survey of 227 organizations in Memphis, Tennessee. This study investigates three obstacles to disaster risk reduction: lack of organizational support, lack of information, and lack of financial resources. The findings show that organizations are more likely to engage in low-effort activities indirectly related to risk reduction and are less likely to engage in high-effort activities directly related to risk reduction. The most important obstacle is lack of information about the frequency of disasters, magnitude of disasters, or organizational benefits of reducing disaster risks. Lack of financial resources and lack of organizational support are sometimes positively associated with risk-reducing activities, suggesting that, when organizations engage in risk-reducing activities, some obstacles become more apparent. The study concludes with implications, limitations, and future research strategies.National Science Foundatio

Stakeholder integration

This study examines the central contention ofinstrumental stakeholder theory— namely, that firms that breed trust-based, cooperative ties with their stakeholders will have a competitive advantage over firms that do not.Acase study of the introduction ofgenetically modified food products in the Netherlands provided the basis for the empirical analysis. The results support the instrumental stakeholder management thesis, showing that stakeholder integration, through the development ofmutually enforcing relationships with external parties, may result in both organizational learning and societal legitimacy

Are all ‘research fields’ equal? Rethinking practice for the use of data from crowd-sourcing market places

New technologies like large-scale social media sides (e.g., Facebook and Twitter) and crowdsourcing services (e.g., Amazon Mechanical Turk, Crowdflower, Clickworker) impact social science research and provide many new and interesting avenues for research. The use of these new technologies for research has not been without challenges and a recently published psychological study on Facebook led to a widespread discussion on the ethics of conducting large-scale experiments online. Surprisingly little has been said about the ethics of conducting research using commercial crowdsourcing market places. In this paper, I want to focus on the question of which ethical questions are raised by data collection with crowdsourcing tools. I briefly draw on implications of internet research more generally and then focus on the specific challenges that research with crowdsourcing tools faces. I identify fair-pay and related issues of respect for autonomy as well as problems with power dynamics between researcher and participant, which has implications for ‘withdrawal-withoutprejudice’, as the major ethical challenges with crowdsourced data. Further, I will to draw attention on how we can develop a ‘best practice’ for researchers using crowdsourcing tools