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 Parametric Study of a Drive by Bridge Inspection System Based on the Morlet Wavelet

Many of the bridges currently in use worldwide are approaching the end of their design lives. However, rehabilitating and extending the lives of these structures raises important safety issues. There is also a need for increased monitoring which has considerable cost implications for bridge management systems. Existing structural health monitoring (SHM) techniques include vibration-based approaches which typically involve direct instrumentation of the bridge and are important as they can indicate the deterioration of the bridge condition. However, they can be labour intensive and expensive. In the past decade, alternative indirect vibration-based approaches which utilise the response of a vehicle passing over a bridge have been developed. This paper investigates such an approach; a low-cost approach for the monitoring of bridge structures which consists of the use of a vehicle fitted with accelerometers on its axles. The approach aims to detect damage in the bridge while obviating the need for direct instrumentation of the bridge. Here, the effectiveness of the approach in detecting damage in a bridge is investigated using a simplified vehicle-bridge interaction (VBI) model in theoretical simulations and a scaled VBI model in a laboratory experiment. In order to identify the existence and location of damage, the vehicle accelerations are recorded and processed using a continuous Morlet wavelet transform and a damage index is established. A parametric study is carried out to investigate the effect of parameters such as the bridge span length, vehicle speed, vehicle mass, damage level and road surface roughness on the accuracy of results.

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.

Wavelet entropy of Doppler ultrasound blood velocity flow waveforms distinguishes nitric oxide-modulated states

Wavelet entropy assesses the degree of order or disorder in signals and presents this complex information in a simple metric. Relative wavelet entropy assesses the similarity between the spectral distributions of two signals, again in a simple metric. Wavelet entropy is therefore potentially a very attractive tool for waveform analysis. The ability of this method to track the effects of pharmacologic modulation of vascular function on Doppler blood velocity waveforms was assessed. Waveforms were captured from ophthalmic arteries of 10 healthy subjects at baseline, after the administration of glyceryl trinitrate (GTN) and after two doses of N(G)-nitro-L-arginine-methyl ester (L-NAME) to produce vasodilation and vasoconstriction, respectively. Wavelet entropy had a tendency to decrease from baseline in response to GTN, but significantly increased after the administration of L-NAME (mean: 1.60 ± 0.07 after 0.25 mg/kg and 1.72 ± 0.13 after 0.5 mg/kg vs. 1.50 ± 0.10 at baseline, p < 0.05). Relative wavelet entropy had a spectral distribution from increasing doses of L-NAME comparable to baseline, 0.07 ± 0.04 and 0.08 ± 0.03, respectively, whereas GTN had the most dissimilar spectral distribution compared with baseline (0.17 ± 0.08, p = 0.002). Wavelet entropy can detect subtle changes in Doppler blood velocity waveform structure in response to nitric-oxide-mediated changes in arteriolar smooth muscle tone.

A wavelet based drive-by bridge inspection system

This paper investigates a low-cost wavelet-based approach for the preliminary monitoring of bridge structures, consisting of the use of a vehicle fitted with accelerometers on its axles. The approach aims to reduce the need for direct instrumentation of the bridge. A time-frequency analysis is carried out in order to identify the existence and location of damage from vehicle accelerations. Firstly, in theoretical simulations, a simplified vehicle-bridge interaction model is used to investigate the effectiveness of the approach. A number of damage indicators are evaluated and compared. A range of parameters such as the bridge span, vehicle speed, damage level and location, signal noise and road roughness are varied in simulations. Secondly, a scaled laboratory experiment is carried out to validate the results of the theoretical analysis and assess the ability of the selected damage indicators to detect changes in the bridge response from vehicle accelerations. 

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.

Planning and design in postindustrial land transformation: east bank Arade river, Lagoa - case study

Tese de dout., Ciências e Tecnologias do Ambiente (Planeamento Urbano), Faculdade de Ciências e Tecnologia, Univ. do Algarve, 2011