Natural 2HDMs without FCNCs

Motivated by the fermion mass hierarchy we study the phenomenology of two flavorful two-Higgs-doublet model (2HDM) scenarios. By virtue of the flavor or singular alignment ansatz it is possible to link the mass of a subset of fermions to the vacuum-expectation-value (VEV) of a unique Higgs doublet and to simultaneously avoid flavor-changing-neutral-currents at tree-level. We explicitly construct two models called Type-A and B. There, either the top quark alone or all third generation fermions couple to the doublet with the larger VEV. The other fermions acquire their masses through the small VEV of the other doublet. Thus, more natural values for the Yukawa couplings can be obtained. The main differences between these models and conventional ones are studied including a discussion of both their structure and phenomenological consequences. In particular, as distinctive deviations for the Yukawa couplings of the light fermions are predicted we discuss possible tests at the LHC based on searches for $h\to J/\Psi + \gamma$, $h\to\mu\mu$, and heavy scalar resonances decaying to muon pairs. We find that for a wide region of parameter space this specific set of signatures can be used to distinguish among the new proposed types and the conventional ones

Suppression of planar cell polarity signaling and migration in glioblastoma by Nrdp1-mediated Dvl polyubiquitination.

The lethality of the aggressive brain tumor glioblastoma multiforme (GBM) results in part from its strong propensity to invade surrounding normal brain tissue. Although oncogenic drivers such as epidermal growth factor receptor activation and Phosphatase and Tensin homolog inactivation are thought to promote the motility and invasiveness of GBM cells via phosphatidylinostitol 3-kinase activation, other unexplored mechanisms may also contribute to malignancy. Here we demonstrate that several components of the planar cell polarity (PCP) arm of non-canonical Wnt signaling including VANGL1, VANGL2 and FZD7 are transcriptionally upregulated in glioma and correlate with poorer patient outcome. Knockdown of the core PCP pathway component VANGL1 suppresses the motility of GBM cell lines, pointing to an important mechanistic role for this pathway in glioblastoma malignancy. We further observe that restoration of Nrdp1, a RING finger type E3 ubiquitin ligase whose suppression in GBM also correlates with poor prognosis, reduces GBM cell migration and invasiveness by suppressing PCP signaling. Our observations indicate that Nrdp1 physically interacts with the Vangl1 and Vangl2 proteins to mediate the K63-linked polyubiquitination of the Dishevelled, Egl-10 and Pleckstrin (DEP) domain of the Wnt pathway protein Dishevelled (Dvl). Ubiquitination hinders Dvl binding to phosphatidic acid, an interaction necessary for efficient Dvl recruitment to the plasma membrane upon Wnt stimulation of Fzd receptor and for the propagation of downstream signals. We conclude that the PCP pathway contributes significantly to the motility and hence the invasiveness of GBM cells, and that Nrdp1 acts as a negative regulator of PCP signaling by inhibiting Dvl through a novel polyubiquitination mechanism. We propose that the upregulation of core PCP components, together with the loss of the key negative regulator Nrdp1, act coordinately to promote GBM invasiveness and malignancy

From the abstract to the concrete - Implementation of an innovative tool in home care

Background: The implementation of innovations in practice is a critical factor for change and development processes in health and home care. We therefore analyze how an innovative tool - a mobility agreement to maintain physical mobility of home care clients - was implemented in Finnish home care. Methods: Our study involves ethnographic research of 13 home care visits, two years after the mobility agreement was implemented. We analyze the emergence of contradictions, the motives of the actors and the use of artifacts supporting or inhibiting the implementation. Two in-depth cases illustrate the implementation of the mobility agreement in home care visits. Findings: Our findings show that, first, to achieve practice change and development, the innovation implementation requires the overcoming of contradictions in the implementation process. Second, it calls for the emergence of a shared motive between the actors to transform the abstract concept of an innovation into a concrete practice. Third, artifacts, customary to the clients are important in supporting the implementation process. Fourth, the implementation brings about a modification of the innovation and the adopting social system. Conclusions: Innovation implementation should be seen as a transformation process of an abstract concept into a concrete practice, enabled by the actors involved. Concept design and implementation should be closely linked. In health/home care innovation management, the implementation of innovations needs to be understood as a complex collective learning process. Results can be far reaching - in our case leading to change of home care workers' professional understanding and elderly clients' mobility habits.Peer reviewe

Dialectic tensions in the financial markets: a longitudinal study of pre- and post-crisis regulatory technology

This article presents the findings from a longitudinal research study on regulatory technology in the UK financial services industry. The financial crisis with serious corporate and mutual fund scandals raised the profile of compliance as governmental bodies, institutional and private investors introduced a ‘tsunami’ of financial regulations. Adopting a multi-level analysis, this study examines how regulatory technology was used by financial firms to meet their compliance obligations, pre- and post-crisis. Empirical data collected over 12 years examine the deployment of an investment management system in eight financial firms. Interviews with public regulatory bodies, financial institutions and technology providers reveal a culture of compliance with increased transparency, surveillance and accountability. Findings show that dialectic tensions arise as the pursuit of transparency, surveillance and accountability in compliance mandates is simultaneously rationalized, facilitated and obscured by regulatory technology. Responding to these challenges, regulatory bodies continue to impose revised compliance mandates on financial firms to force them to adapt their financial technologies in an ever-changing multi-jurisdictional regulatory landscape

The Self stepping into the shoes of the Other: Understanding and developing self-perceptions of empathy among prospective physical education teachers through a special school placement

Teachers who demonstrate a high degree of empathy are said to have more positive attitudes towards pupils with disabilities. Therefore, this article sought to explore the influence of a special school placement on prospective teachers’ self-perceptions of empathy. Thirty-two final year undergraduate students participated in focus group interviews and were selected because they aspired to be a physical education teacher and had attended a placement in a special school. Interview transcripts were analysed and the following themes constructed: Stepping into the shoes of the Other; Frustrated ‘for’ not ‘with’ pupils with disabilities; Empathy for planning inclusive lessons and ‘reading’ pupil body language; and Knowing when not to show empathy. All prospective teachers felt that: (a) they could empathise with pupils with disabilities; (b) situated learning experiences within the placement enabled them to reflect on the ways in which their empathy influences their teaching now and could continue to do so in the future; and (c) it was important that teachers demonstrated empathy. Thus, it is recommended that all prospective teachers gain some experience teaching in special schools. Our research also warns against teachers claiming the last, conclusive word about who children with disabilities are, what they think, how they feel and what they want, in myriad contexts and situations

Moving beyond methodising theory in preparing for the profession

For those preparing for outdoor education and related professions, formal theory has an important role to play in terms of informing professional practice and understandings of teaching-learning dynamics. Despite this, surprisingly little is understood about how pre-service outdoor educators (POEs) view and engage with it in their preparation courses. Drawing on findings of a case study in an Australian outdoor education teacher education (OETE) course, this article explores POE theory engagement focussing on a problematic tendency to methodise formal theory, that is, to treat theories as formula for action. The authors argue that this tendency is concerning because it ignores the complexity and problematic nature of both theory-practice relationships and outdoor education pedagogy. The discussion highlights contributing factors and implications for OETE, especially with respect to enabling aspiring outdoor educators in tertiary courses to move beyond methodising theory as they enter the outdoor profession

Mature women and higher education: reconstructing identity and family relationships

Since Edwards’ influential study on mature women students and families in the 1990s, questions have been raised about the effects of Higher Education (HE) on family lives. Edwards maintained that relationships were at risk of breakdown due to the changing identity, increased self-esteem and enhanced confidence levels of women students. Men were perceived negatively as often being unsupportive of their wives’ return to HE, or threatened by the changes they observed in her. This paper is based on qualitative research methods focusing on whether HE changes a woman’s identity and reconstructs family relationships. A narrative line of inquiry was used to build detailed stories of a small group of women students and their husbands. The 11 women students were selected from one Foundation degree in Early Years programme at a further education institution. Data was constructed using mind mapping, focused interviews and a mosaic approach of participant-led research. Research findings showed that HE had the potential to transform a woman’s identity and position within her family relationships. The results also demonstrated that family capital, in the form of practical and emotional strategies of support from both husbands and children, played an instrumental part in the women’s success and participation in HE (though this aspect will be discussed in a subsequent paper)