ER stress-mediated autophagy promotes Myc-dependent transformation and tumor growth

The proto-oncogene c-Myc paradoxically activates both proliferation and apoptosis. In the pathogenic state, c-Myc-induced apoptosis is bypassed via a critical, yet poorly understood escape mechanism that promotes cellular transformation and tumorigenesis. The accumulation of unfolded proteins in the ER initiates a cellular stress program termed the unfolded protein response (UPR) to support cell survival. Analysis of spontaneous mouse and human lymphomas demonstrated significantly higher levels of UPR activation compared with normal tissues. Using multiple genetic models, we demonstrated that c-Myc and N-Myc activated the PERK/eIF2α/ATF4 arm of the UPR, leading to increased cell survival via the induction of cytoprotective autophagy. Inhibition of PERK significantly reduced Myc-induced autophagy, colony formation, and tumor formation. Moreover, pharmacologic or genetic inhibition of autophagy resulted in increased Myc-dependent apoptosis. Mechanistically, we demonstrated an important link between Myc-dependent increases in protein synthesis and UPR activation. Specifically, by employing a mouse minute (L24+/-) mutant, which resulted in wild-type levels of protein synthesis and attenuation of Myc-induced lymphomagenesis, we showed that Myc-induced UPR activation was reversed. Our findings establish a role for UPR as an enhancer of c-Myc-induced transformation and suggest that UPR inhibition may be particularly effective against malignancies characterized by c-Myc overexpression.

A Review of Indirect Bridge Monitoring Using Passing Vehicles

Indirect bridge monitoring methods, using the responses measured from vehicles passing over bridges, are under development for about a decade. A major advantage of these methods is that they use sensors mounted on the vehicle, no sensors or data acquisition system needs to be installed on the bridge. Most of the proposed methods are based on the identification of dynamic characteristics of the bridge from responses measured on the vehicle, such as natural frequency, mode shapes, and damping. In addition, some of the methods seek to directly detect bridge damage based on the interaction between the vehicle and bridge. This paper presents a critical review of indirect methods for bridge monitoring and provides discussion and recommendations on the challenges to be overcome for successful implementation in practice.

Parades, Flags, Carnivals and Riots: Public Space, Contestation and Transformation in Northern Ireland

This paper explores one of the defining aspects of politics and identity in Northern Ireland: the control and utilization of public space, particularly urban public space. Ethnopolitical conflict consistently reveals itself through contestation over public space. The role of ritual events is important in the development of political identity and group cohesion. The symbolic landscape will be constructed through displays of identity by dominant groups and their ability to control that landscape by inhibiting displays by other groups. This will reveal itself through frequent contests over rituals and symbols. This paper looks at the role of ritual events in civic spaces in Belfast but particularly asks what role they might play in conflict transformation. The 1998 agreement offered political structures that provided for shared power after 30 years of violent conflict. At the same time, there was an increase in contestation over public space as political groups within the previously marginalized Catholic community demanded recognition within the public sphere and a rebalancing of the public space through changes to the previously dominant Protestant and Unionist expression of identity. The paper concludes by suggesting that in “shared space” a new civic identity that spans the political and ethnic divisions has started to develop in Belfast and that this might evolve despite an increased residential division throughout the urban area.

EU Cross-Border Cooperation and Conflict Transformation in the Basque and Irish Border Regions

Comparative research on violent conflict in the Basque Country and Ireland has yielded a sizable body of published academic work. Less well explored is the relationship between conflict transformation and cross-border cooperation in that specific comparative context. This paper provides a comparative examination of Third (not for profit) sector cross-border cooperation as conflict transformation in the Basque (France/Spain) and Irish (UK/Ireland) border regions. To what extent does cross-border cooperation contribute to peacebuilding in the two last violent ethnonationalist conflicts in Western Europe? The comparison is based on the premise that the EU played a different role in both cases. In the Irish case, the EU contributed to the institutionalization of a peace process that included cross-border cooperation between third sector organizations among the policy instruments contributing to conflict transformation. In the Basque case, the unilateral renunciation of violence by ETA (Euskadi eta Askatasuna) in 2010 did not generate the consistent involvement of the EU in a comparable institutional peace process. However, some third sector organizations used EU instruments for cross-border economic, social and cultural cooperation between France and Spain in order to reinforce their cross-border networks, which indirectly impacted on conflict transformation. The effectiveness of this cross-border cooperation for conflict transformation is assessed comparatively. To what extent does this increase in cross-border cooperation “from below” connect to wider institutional and social processes of conflict transformation in Ireland and the Basque Country? Crucially, does the strengthening of cross-border relations on shared issues mollify or sharpen existing identity cleavages? Also considered is the sustainability of such cooperation in these regions in light of the less favourable post-2004 EU funding environment, and the post-2008 economic and political turmoil affecting the relevant EU member states, especially Ireland and Spain.

European Union Cross-Border Cooperation as Conflict Transformation:Potential and Limits

Cross-border cooperation as conflict transformation provides a potential strategy for the European Union (EU) to help realise its founding peacebuilding objective. A wealth of cross-border cooperation activity sponsored by the EU spans a quarter of a century. Although the conflict transformation capacity of that cooperation is questionable in some border regions there is evidence to suggest that it has delivered peacebuilding dividends in other border regions. However, EU cross-border cooperation as conflict transformation faces a number of significant twenty-first century challenges including: ghost borders of the communal imagination; EU external border securitization; perceptions of EU and Russian empire-building; and the Mediterranean transmigrant/refugee crisis. It is argued that these challenges pose significant obstacles to EU cross-border cooperation as conflict transformation and undermine the peacebuilding objective of European integration.

Petals of Resonance: A performance system for the transformation of small body sounds

A system of software and hardware that combines signal processing and contact microphones using normally inaudible body sounds, including heartbeat/pulse, respiration and internal sounds from the vocal tract that can be heard internally by the performer but not externally by others, to drive resonant filters. Performance at SARC Sonic Lab, Belfast, 19 Feb 2015 in collaboration with Birgit Ulher.

Production of extended-spectrum β-lactamases and the potential indirect pathogenic role of Prevotella isolates from the cystic fibrosis respiratory microbiota

Extended-spectrum β-lactamase (ESBL) production and the prevalence of the β-lactamase-encoding gene blaTEM were determined in Prevotella isolates (n=50) cultured from the respiratory tract of adults and young people with cystic fibrosis (CF). Time-kill studies were used to investigate the concept of passive antibiotic resistance and to ascertain whether a β-lactamase-positive Prevotella isolate can protect a recognised CF pathogen from the action of ceftazidime in vitro. The results indicated that approximately three-quarters (38/50; 76%) of Prevotella isolates produced ESBLs. Isolates positive for ESBL production had higher minimum inhibitory concentrations (MICs) of β-lactam antibiotics compared with isolates negative for production of ESBLs (P<0.001). The blaTEM gene was detected more frequently in CF Prevotella isolates from paediatric patients compared with isolates from adults (P=0.002), with sequence analysis demonstrating that 21/22 (95%) partial blaTEM genes detected were identical to blaTEM-116. Furthermore, a β-lactamase-positive Prevotella isolate protected Pseudomonas aeruginosa from the antimicrobial effects of ceftazidime (P=0.03). Prevotella isolated from the CF respiratory microbiota produce ESBLs and may influence the pathogenesis of chronic lung infection via indirect methods, including shielding recognised pathogens from the action of ceftazidime.

Electron-impact excitation of Fe2: a comparison of intermediate coupling frame transformation, Breit-Pauli and Dirac R-matrix calculations

Modeling the spectral emission of low-charge iron group ions enables the diagnostic determination of the local physical conditions of many cool plasma environments such as those found in H II regions, planetary nebulae, active galactic nuclei etc. Electron-impact excitation drives the population of the emitting levels and, hence, their emissivities. By carrying-out Breit-Pauli and intermediate coupling frame transformation (ICFT) R-matrix calculations for the electron-impact excitation of Fe$^{2+}$ which both use the exact same atomic structure and the same close-coupling expansion, we demonstrate the validity of the application of the powerful ICFT method to low-charge iron group ions. This is in contradiction to the finding of Bautista et al. [Ap.J.Lett, 718, L189, (2010)] who carried-out ICFT and Dirac R-matrix calculations for the same ion. We discuss possible reasons.

Bringing down the walls: Is the notion of ‘promoting shared space’ commensurate with effective transformation of contested places in Belfast?

This article is a reflexive and critical examination of recent empirical research on effective practice in the management and ‘transformation’ of contested urban space at sectarian interfaces in Belfast. By considering the development of interfaces, the areas around them and policy responses to their persistence, the reality of contested space in the context of ‘peace building’ is apparent; with implications for local government as central to the statutory response. Belfast has developed an inbuilt absence of connectivity; where freedom of movement is particularly restricted and separation of contested space is the policy default position. Empirical research findings focus attention on the significance of social and economic regeneration and fall into three specific areas that reflect both long-term concerns within neighbourhoods and the need for adequate policy responses and action ‘on the ground’. Drawing on Elden and Sassen we reconfigure the analytical framework by which interfaces are defined, with implications for policy and practice in post-conflict Belfast. Past and current policy for peace-building in Northern Ireland, and transforming the most contested space, at interfaces in Belfast, is deliberately ambiguous and offers little substance having failed to advance from funding-led linguistic compliance to a sustainable peace-building methodology.