Research Ethics in Divided and Violent Societies: Seizing the Ethical Opportunity

This chapter explores how to conduct social research in divided and violent societies by developing the concept of the ‘ethical opportunity’. The ‘ethical opportunity’ is situated in a brief discussion of ‘action’ and feminist approaches to research. It argues that seizing the ethical opportunity requires researchers to: plan for their personal safety, plan for participants’ personal safety and plan how they will communicate and disseminate their results. It draws on the author’s personal experience researching in South Africa, Zimbabwe and Northern Ireland, concluding that it is in the communication and dissemination phase that researchers’ hopes for ‘making a difference’ may be realised or dashed. It cautions would-be researchers to manage their own – and research participants’ – expectations about what social research can achieve. Its effects may not often be as transforming and liberating as idealistic researchers hope for, but that should not dissuade them from striving towards those ends.

Electroless nickel composite (Ni-P/SiC) coating - A study on interface and corrosion characteristic

Surface behaviour is of paramount importance as failure and degradation tend to initiate from the surface. Electroless composite coating (NiP/SiC) was developed using SiC as reinforcing particles. As heat treatment plays a vital role in electroless nickel coating owing to the changes in microstructure, phase structure and mechanical properties, an insight at the interface changes in chemistry and micromechanical behaviour was investigated using scanning electron microscopy (SEM) and energy dispersive X-ray (EDX) and microindentation techniques. Corrosion performance was analysed using electrochemical impedance spectroscopy (EIS). Absence of zinc and migration of copper at the interface was detected. Brittleness and microcracks was seen long the interface when indenting at load of 500 gf (Vickers). Corrosion performance is weaker than particles free coating. However, a thin blanket of NiP could enhance the resistance to corrosive medium.

Sustained inhibition of deacetylases is required for the antitumor activity of the histone deactylase inhibitors panobinostat and vorinostat in models of colorectal cancer

Despite compelling preclinical data in colorectal cancer (CRC), the efficacy of HDACIs has been disappointing in the clinic. The goal of this study was to evaluate the effectiveness of vorinostat and panobinostat in a dose- and exposure-dependent manner in order to better understand the dynamics of drug action and antitumor efficacy. In a standard 72 h drug exposure MTS assay, notable concentration-dependent antiproliferative effects were observed in the IC50 range of 1.2-2.8 μmol/L for vorinostat and 5.1-17.5 nmol/L for panobinostat. However, shorter clinically relevant exposures of 3 or 6 h failed to elicit any significant growth inhibition and in most cases a >24 h exposure to vorinostat or panobinostat was required to induce a sigmoidal dose-response. Similar results were observed in colony formation assays where ≥ 24 h of exposure was required to effectively reduce colony formation. Induction of acetyl-H3, acetyl-H4 and p21 by vorinostat were transient and rapidly reversed within 12 h of drug removal. In contrast, panobinostat-induced acetyl-H3, acetyl-H4, and p21 persisted for 48 h after an initial 3 h exposure. Treatment of HCT116 xenografts with panobinostat induced significant increases in acetyl-H3 and downregulation of thymidylate synthase after treatment. Although HDACIs exert both potent growth inhibition and cytotoxic effects when CRC cells were exposed to drug for ≥ 24 h, these cells demonstrate an inherent ability to survive HDACI concentrations and exposure times that exceed those clinically achievable. Continued efforts to develop novel HDACIs with improved pharmacokinetics/phamacodynamics, enhanced intratumoral delivery and class/isoform-specificity are needed to improve the therapeutic potential of HDACIs and HDACI-based combination regimens in solid tumors.

DNA microarray profiling of genes differentially regulated by the histone deacetylase inhibitors vorinostat and LBH589 in colon cancer cell lines

BACKGROUND: Despite the significant progress made in colon cancer chemotherapy, advanced disease remains largely incurable and novel efficacious chemotherapies are urgently needed. Histone deacetylase inhibitors (HDACi) represent a novel class of agents which have demonstrated promising preclinical activity and are undergoing clinical evaluation in colon cancer. The goal of this study was to identify genes in colon cancer cells that are differentially regulated by two clinically advanced hydroxamic acid HDACi, vorinostat and LBH589 to provide rationale for novel drug combination partners and identify a core set of HDACi-regulated genes.

METHODS: HCT116 and HT29 colon cancer cells were treated with LBH589 or vorinostat and growth inhibition, acetylation status and apoptosis were analyzed in response to treatment using MTS, Western blotting and flow cytometric analyses. In addition, gene expression was analyzed using the Illumina Human-6 V2 BeadChip array and Ingenuity Pathway Analysis.

RESULTS: Treatment with either vorinostat or LBH589 rapidly induced histone acetylation, cell cycle arrest and inhibited the growth of both HCT116 and HT29 cells. Bioinformatic analysis of the microarray profiling revealed significant similarity in the genes altered in expression following treatment with the two HDACi tested within each cell line. However, analysis of genes that were altered in expression in the HCT116 and HT29 cells revealed cell-line-specific responses to HDACi treatment. In addition a core cassette of 11 genes modulated by both vorinostat and LBH589 were identified in both colon cancer cell lines analyzed.

CONCLUSION: This study identified HDACi-induced alterations in critical genes involved in nucleotide metabolism, angiogenesis, mitosis and cell survival which may represent potential intervention points for novel therapeutic combinations in colon cancer. This information will assist in the identification of novel pathways and targets that are modulated by HDACi, providing much-needed information on HDACi mechanism of action and providing rationale for novel drug combination partners. We identified a core signature of 11 genes which were modulated by both vorinostat and LBH589 in a similar manner in both cell lines. These core genes will assist in the development and validation of a common gene set which may represent a molecular signature of HDAC inhibition in colon cancer.

International Coordination in Cross-Border Bank Bail-ins: Problems and Prospects

Bail-in is quickly becoming a predominant approach to banking resolution. The EU Bank Recovery Resolution Directive and the US Federal Deposit Insurance Corporation’s single point of entry strategy envisage creditors’ recapitalisations
to resolve a failing financial institution. However, this legislation focuses on the domestic aspects of bail-in, leaving the question of how it is applied
to a cross-border banking group open. Cross-border banking resolution has been historically subject to coordination failures, which have resulted in disorderly resolutions with dangerous systemic effects. The goal of this article is to assess whether bail-in is subject to the same coordination problems that affect other resolution tools, and to discuss the logic of international legal cooperation in bail-in policies. We demonstrate that, in spite of the evident benefit in terms of fiscal sustainability, bail-in suffers from complex coordination problems which, if not addressed, might lead to regulatory arbitrage and lengthy court battles, and, ultimately, may disrupt resolutions. We argue that only a binding legal regime can address those problems. In doing so, we discuss the recent Financial Stability
Board’s proposal on cross-border recognition of resolution action, and the role of international law in promoting cooperation in banking resolution.

Laughter and Humour as Conversational Mind-Reading Displays

Laughter and humor are pervasive phenomena in conversa- tional interactions. This paper argues that they function as displays of mind-reading abilities in social interactions–as suggested by the Analogi- cal Peacock Hypothesis (APH). In this view, they are both social bonding signals and can elevate one’s social status. The relational combination of concepts in humor is addressed. However, it is in the inclusion of context and receiver knowledge, required by the APH view, that it contributes the most to existing theories. Taboo and offensive humor are addressed in terms of costly signaling, and implications for human computer inter- action and some possible routes to solutions are suggested.

Catalysing the Irish Energy Transition: Capacities and Challenges

The transition to a “low carbon, climate resilient and environmentally sustainable economy by the end of the 
year 2050” has been conceptualised as the “national transition objective” in the Irish Climate Action and Low Carbon Development Bill, passed in late 2015. This has raised a myriad of questions over how this can be operationalised and resourced and whether it can maintain political momentum. This paper assesses the utility of framings informed by the transitions (MLP) and technological innovation systems perspectives in contributing to transformative societal processes, by examining their application in an Irish case study on policy and technology. Through a qualitative exploration of the broader societal and policy context of the energy sector and a more detailed examination of the innovation systems of selected niche technologies (bioenergy and electric vehicles), the Irish case study sought to identify potential catalysts for a sustainability transition in the energy sector in Ireland: where these exist, how these are being built or enabled, and barriers to change. Following a discussion on the theoretical approaches used, a description will be given of how these were applied in the conducting of the research on transition in Ireland case study and the key findings which emerged. A critical reflection will then be made on the utility of these perspectives (as applied) to contribute to broader processes of societal transformation in Ireland.

Mapping Ireland’s Energy Pathways: Characterizing and Catalyzing Transition

In 2015 Ireland has arguably begun to make its first bold steps in confronting the challenges of energy transition, with the objective of a “low carbon, climate resilient and environmentally sustainable economy by the end of the
year 2050” expressed in the 2015 Climate Action and Low Carbon Development Bill and the 2015 Energy Bill acknowledging that energy transformation relied on a new breed of ‘energy citizens’. These represent the first formal articulation of Ireland’s ambition to engage in a radical, long-term and far-reaching transition process, and raises a myriad of questions over how this can be operationalised, resourced and whether it can maintain political momentum. A range of perspectives on these issues is provided in the growing body of literature on transition theories (Rotmans et al 2001, Markard et al 2012) and the inter-disciplinary EPA-funded CC Transitions project, based at Queen’s University Belfast, represents an attempt to translate this into the context of Ireland’s institutions and technological profile. By relating this to international research on sustainability transitions, which conceptualises transitions as multi-level, multi-phase and multi-actor processes, this paper will explore the opportunities of alternative pathways that could take Ireland towards a more progressing, inclusive and effective low carbon future. Drawing on a number of case studies it will highlight some of the capacities for transition required in Irish society: where these exist, how they are being built or enabled, and the barriers to wider social change.