Qualitative Futures

Price, C., Trave-Massuyes, L., Milne, R., Ironi, L., Forbus, K., Bredeweg, B., Lee, M., Struss, P., Snooke, N., Lucas, P., Cavazza, M., Coghill, G. (2006). Qualitative Futures. The Knowledge Engineering Review, 21 (4), 317-334. Sponsorship: MONET European Network on Qualitative and Model-Based Reasoning

Recovering a lost inheritance : The marital economy and its absence from the Prehistory of Economics in Britain

Roberts, Michael. 'Recovering a lost inheritance: the marital economy and its absence from the Prehistory of Economics in Britain', in: 'The Marital Economy in Scandinavia and Britain 1400-1900', (Eds) Argen, Maria., Erickson, Amy Louise., Farnham: Ashgate, 2005, pp.239-256 RAE2008

Accents of Chopin anniversaries in territories annexed by Prussia

This article discusses the way in which the Chopin Year of 1910 was celebrated in Wielkopolska. It presents a script prepared in the nineteenth century and shows similarities with celebrations of Mickiewicz and other Polish heroes and artists. Invariably used in such commemorations was a “symbolic capital” that made it easier to create an intergenerational code, thereby disseminating knowledge of national culture and history. A significant role was played in 1910 by a centenary panel, which produced “Guidelines for popular Chopin celebrations” and also many occasional, popular materials. Chopin’s induction into the national pantheon involved the use of audio material (vocal and instrumental concerts), verbal material (articles, poems, lectures and brochures) and also a visual code (anniversary window stickers, tableaux vivants or tableaux illuminés). Illuminated pictures – recommended by a catalogue of slides produced in Poznań – stimulated the imagination of the masses and served as a guide through the composer’s life and work, and their impact was enhanced by a commentary. Most of the living pictures were probably inspired by Henryk Siemiradzki’s canvas Chopin grający na fortepianie w salonie księcia Radziwiłła [Chopin playing the piano in Prince Radziwiłł’s salon] and Józef Męcina Krzesz’s painting Ostatnie akordy Chopina [Chopin’s last chords]. This combination of codes made it possible to create a model adapted to the times and to the expectations of a mass audience. The Chopin anniversary, in which admiration was inseparably intertwined with manipulation, was a pretext for strengthening the national identity.

Annales del Reyno de Navarra

Signaturas: *6, A-F4, G2, H-Z4, 2A-2Z4, 3A-3Z4, 4A-4Z4, 5A-5D4, 5E2, 5F4 ; *5, A-Z4, 2A-2Z4, 3A-3Y4, Z2, 4A4 ; *5, A-Z4, 2A-2Z4, 3A-3Z4, 4A-4N4, 4O5 ; *5, A-Z4, 2A-2Z4, 3A-3Z4, 4A-4O4, 4P2, 4Q1, 4R4 ; *5, A-Z4, 2A-2Z4, 3A-3M4, *2, A-S4.

Form, fi gure, and the experience of time in seven southern composers of the 1950s-60s

After the 1980s it is diffi cult, following stylistic criteria, to draw a map of contemporary academic music. All styles are compossible, and all are practiced. In this context, the geographical entity “South of Italy” does not stand out for a musical identity with special technical-stylistic features. Rather, at a socio-cultural level, the South remains today – in music no less than in all areas where there is a gap between top development and stagnation – a land of emigrants: six out of the seven composers treated (Ivan Fedele, Giuseppe Colardo, Rosario Mirigliano, Giuseppe Soccio, Nicola Cisternino, Biagio Putignano, Paolo Aralla) live in the North of Italy. The positive aspect of this is the affi nity of the South with the transnational and superstructural community of contemporary music, which from European and Western has now become almost global. The composers under consideration belong to the generation of the ‘50s, rooted in the serial and post-serial movements (from which Franco Donatoni, Luciano Berio, Luigi Nono, Salvatore Sciarrino, Giacinto Scelsi, are the principals models, to mention only the Italians), dipped in the general phenomenon of timbrism (particularly spectralism), and acquainted with electronics. They draw from these sources various instruments of compositional technique and aspects of their poetics. In particular these composers, active from the ‘80s, develop new ways of construction of the temporal form of music. They share the goal to establish a new continuity, different from the tonal one but at the same time transcending the serial and post-serial disintegration and fragmentation. The primary means to this end is a new enhancement of the category of fi gure, as a clear and distinct, recognizable aggregate of pitches, intervals, register, durations, timbre, articulation, dynamics, and texture. Each composer elaborates the atonal fi gural material in different ways, emphasizing one aspect or another. For example, Fedele (1953) is a master in the management of form per se, Colardo (1953) in the activation of disturbed harmonic effects, Mirigliano (1950) in the creation of a slight tension from the smallest vibrations of sound, Soccio (1950) in the set up of movement by means of accumulations and discharges of energy, Cisternino (1957) in a Cagean-Scelsian emphasis on sound as such, Putignano (1960) in the suspension of time through the succession and transformation of images, Aralla (1960) in the foundation of form from below, from the concreteness of sound.

The ‘Faust’ or ’Lucifer’ Sonata? On Liszt’s idea of programme music as exemplifi ed by his Piano Sonata in B minor

The musicological tradition places Liszt’s Sonata in B minor within the sphere of compositions inspired by the Faustian myth. Its musical material, its structure and its narrative exhibit certain similarities to the ‘Faust’ Symphony. Yet there has appeared a diff erent and, one may say, a rival interpretation of Sonata in B minor. What is more, it is well-documented from both a musical and a historical point of view. It has been presented by Hungarian pianist and musicologist Tibor Szász. He proposes the thesis that the Sonata in B minor has been in fact inspired by Milton’s Paradise Lost, with its three protagonists: Adam, Satan and Christ. He fi nds their illustrations and even some key elements of the plot in the Sonata’s narrative. But yet Milton’s Paradise Lost and Goethe’s Faust are both stories of the Fall and Salvation, of the cosmic struggle between good and evil. The triads of their protagonists – Adam and Eve, Satan, and Christ; Faust, Mephisto and Gretchen – are homological. Thus both interpretations of the Sonata, the Goethean and the Miltonian, or, in other words, the Faustian and the Luciferian, are parallel and complementary rather than rival. It is also highly probable that both have had their impact on the genesis of the Sonata in B minor.

Preferential Field Coverage Through Detour-Based Mobility Coordination

Controlling the mobility pattern of mobile nodes (e.g., robots) to monitor a given field is a well-studied problem in sensor networks. In this setup, absolute control over the nodes’ mobility is assumed. Apart from the physical ones, no other constraints are imposed on planning mobility of these nodes. In this paper, we address a more general version of the problem. Specifically, we consider a setting in which mobility of each node is externally constrained by a schedule consisting of a list of locations that the node must visit at particular times. Typically, such schedules exhibit some level of slack, which could be leveraged to achieve a specific coverage distribution of a field. Such a distribution defines the relative importance of different field locations. We define the Constrained Mobility Coordination problem for Preferential Coverage (CMC-PC) as follows: given a field with a desired monitoring distribution, and a number of nodes n, each with its own schedule, we need to coordinate the mobility of the nodes in order to achieve the following two goals: 1) satisfy the schedules of all nodes, and 2) attain the required coverage of the given field. We show that the CMC-PC problem is NP-complete (by reduction to the Hamiltonian Cycle problem). Then we propose TFM, a distributed heuristic to achieve field coverage that is as close as possible to the required coverage distribution. We verify the premise of TFM using extensive simulations, as well as taxi logs from a major metropolitan area. We compare TFM to the random mobility strategy—the latter provides a lower bound on performance. Our results show that TFM is very successful in matching the required field coverage distribution, and that it provides, at least, two-fold query success ratio for queries that follow the target coverage distribution of the field.

Not thinking straight? A critical discourse analysis of the 2006 Irish High Court ruling in Zappone and Gilligan v. Revenue Commissioners and Attorney General

The recognition and protection of constitutional rights is a fundamental precept. In Ireland, the right to marry is provided for in the equality provisions of Article 40 of the Irish Constitution (1937). However, lesbians and gay men are denied the right to marry in Ireland. The ‘last word’ on this issue came into being in the High Court in 2006, when Katherine Zappone and Ann Louise Gilligan sought, but failed, to have their Canadian marriage recognised in Ireland. My thesis centres on this constitutional court ruling. So as to contextualise the pursuit of marriage equality in Ireland, I provide details of the Irish trajectory vis-à-vis relationship and family recognition for same-sex couples. In Chapter One, I discuss the methodological orientation of my research, which derives from a critical perspective. Chapter Two denotes my theorisation of the principle of equality and the concept of difference. In Chapter Three, I discuss the history of the institution of marriage in the West with its legislative underpinning. Marriage also has a constitutional underpinning in Ireland, which derives from Article 41 of our Constitution. In Chapter Four, I discuss ways in which marriage and family were conceptualised in Ireland, by looking at historical controversies surrounding the legalisation of contraception and divorce. Chapter Five denotes a Critical Discourse Analysis of the High Court ruling in Zappone and Gilligan. In Chapter Six, I critique text from three genres of discourse, i.e. ‘Letters to the Editor’ regarding same-sex marriage in Ireland, communication from legislators vis-à-vis the 2004 legislative impediment to same-sex marriage in Ireland, and parliamentary debates surrounding the 2010 enactment of civil partnership legislation in Ireland. I conclude my research by reflecting on my methodological and theoretical considerations with a view to answering my research questions. Author’s Update: Following the outcome of the 2015 constitutional referendum vis-à-vis Article 41, marriage equality has been realised in Ireland.

Carbon nanotubes as materials in nanotechnology

Carbon nanotubes (CNTs) are hollow tubes of sp2-hybridised carbon with diameters of the order of nanometres. Due to their unique physical properties, which include ballistic transport and high mechanical strength, they are of significant interest for technological applications. The electronic properties of CNTs are of particular interest for use as gas sensors, interconnect materials in the semi-conductor industry and as the channel material in CNT based field effect transistors. The primary difficulty associated with the use of CNTs in electronic applications is the inability to control electronic properties at the growth stage; as grown CNTs consist of a mixture of metallic and semi-conducting CNTs. Doping has the potential to solve this problem and is a focus of this thesis. Nitrogen-doped CNTs typically have defective structures; the usual hollow CNT structure is replaced by a series of compartments. Through density functional theory (DFT) calculations and experimental results, we propose an explanation for the defective structures obtained, based on the stronger binding of N to the growth catalyst in comparison to C. In real electronic devices, CNTs need to be contacted to metal, we generate the current-voltage (IV) characteristics of metal-contacted CNTs considering both the effect of dopants and the structure of the interface region on electronic properties. We find that substitutionally doped CNTs produce Ohmic contacts and that scattering at the interface is strongly influenced by structure. In addition, we consider the effect of the common vacancy defects on the electronic properties of large diameter CNTs. Defects increase scattering in the CNT, with the greatest scattering occurring for the largest defect (555777). We validate the independent scattering approximation for small diameter CNTs, which enables mean free paths in large diameter CNTs to be calculated, with a smaller mean free paths found for larger defects.

The role of mitogen activated protein kinase phosphatase-1 in neurotoxic and inflammatory-induced changes in the development of midbrain dopaminergic neurons: relevance to Parkinson’s disease

Parkinson’s disease (PD) is a progressive neurodegenerative disorder characterised by the loss of midbrain dopaminergic neurons from the substantia nigra pars compacta(SNpc), which results in motor, cognitive and psychiatric symptoms. Evidence supports a role for the mitogen-activated protein kinase p38 in the demise of dopaminergic neurons, while mitogen-activated protein kinase phosphatase-1 (MKP-1), which negatively regulates p38 activity, has not yet been investigated in this context. Inflammation may also be associated with the neuropathology of PD due to evidence of increased levels of proinflammatory cytokines such as interleukin-1β (IL-1β) within the SNpc. Because of the specific loss of dopaminergic neurons in a discreet region of the brain, PD is considered a suitable candidate for cell replacement therapy but challenges remain to optimise dopaminergic cell survival and morphological development. The present thesis examined the role of MKP-1 in neurotoxic and inflammatory-induced changes in the development of midbrain dopaminergic neurons. We show that MKP-1 is expressed in dopaminergic neurons cultured from embryonic day (E) 14 rat ventral mesencephalon (VM). Inhibition of dopaminergic neurite growth induced by treatment of rat VM neurons with the dopaminergic neurotoxin 6- hydroxydopamine (6-OHDA) is mediated by p38, and is concomitant with a significant and selective decrease in MKP-1 expression in these neurons. Dopaminergic neurons transfected to overexpress MKP-1 displayed a more complex morphology and contributed to neuroprotection against the effects of 6-OHDA. Therefore, MKP-1 expression can promote the growth and elaboration of dopaminergic neuronal processes and can help protect them from the neurotoxic effects of 6-OHDA. Neural precursor cells (NPCs) have emerged as promising alternative candidates to fetal VM for cell replacement strategies in PD. Here we show that phosphorylated (and thus activated) p38 and MKP-1 are expressed at basal levels in untreated E14 rat VM NPCs (nestin, DCX, GFAP and DAT-positive cells) following proliferation as well as in their differentiated progeny (DCX, DAT, GFAP and βIII-tubulin) in vitro. Challenge with 6-OHDA or IL-1β changed the expression of endogenous phospho-p38 and MKP-1 in these cells in a time-dependent manner, and so the dynamic balance in expression may mediate the detrimental effects of neurotoxicity and inflammation in proliferating and differentiating NPCs. We demonstrate that there was an up-regulation in MKP-1 mRNA expression in adult rat midbrain tissue 4 days post lesion in two rat models of PD; the 6-OHDA medial forebrain bundle (MFB) model and the four-site 6-OHDA striatal lesion model. This was concomitant with a decrease in tyrosine hydroxylase (TH) mRNA expression at 4 and 10 days post-lesion in the MFB model and 10 and 28 days post-lesion in the striatal lesion model. There was no change in mRNA expression of the pro-apoptotic gene, bax and the anti-apoptotic gene, bcl-2 in the midbrain and striatum. These data suggest that the early and transient upregulation of MKP-1 mRNA in the midbrain at 4 days post-6-OHDA administration may be indicative of an attempt by dopaminergic neurons in the midbrain to protect against the neurotoxic effects of 6-OHDA at later time points. Collectively, these findings show that MKP-1 is expressed by developing and adult dopaminergic neurons in the midbrain, and can promote their morphological development. MKP-1 also exerts neuroprotective effects against dopaminergic neurotoxins in vitro, and its expression in dopaminergic neurons can be modulated by inflammatory and neurotoxic insults both in vitro and in vivo. Thus, these data contribute to the information needed to develop therapeutic strategies for protecting midbrain dopaminergic neurons in the context of PD.

Novel ingredients from brewers' spent grain - bioactivity in cell culture model systems and bioactivity retention in fortified food products

Functional food ingredients, with scientifically proven and validated bioactive effects, present an effective means of inferring physiological health benefits to consumers to reduce the risk of certain diseases. The search for novel bioactive compounds for incorporation into functional foods is particularly active, with brewers’ spent grain (BSG, a brewing industry co-product) representing a unique source of potentially bioactive compounds. The DNA protective, antioxidant and immunomodulatory effects of phenolic extracts from both pale (P1 - P4) and black (B1 – B4) BSG were examined. Black BSG extracts significantly (P < 0.05) protected against DNA damage induced by hydrogen peroxide (H2O2) and extracts with the highest total phenolic content (TPC) protected against 3-morpholinosydnonimine hydrochloride (SIN-1)-induced oxidative DNA damage, measured by the comet assay. Cellular antioxidant activity assays were used to measured antioxidant potential in the U937 cell line. Extracts P1 – P3 and B2 - B4 demonstrated significant (P < 0.05) antioxidant activity, measured by the superoxide dismutase (SOD) activity, catalase (CAT) activity and gluatathione (GSH) content assays. Phenolic extracts P2 and P3 from pale BSG possess anti-inflammatory activity measured in concanavalin-A (conA) stimulated Jurkat T cells by an enzyme-linked immunosorbent assay (ELISA); significantly (P < 0.05) reducing production of interleukin-2 (IL-2), interleukin-4 (IL-4, P2 only), interleukin-10 (IL-10) and interferon-γ (IFN-γ). Black BSG phenolic extracts did not exhibit anti-inflammatory effects in vitro. Hydroxycinnamic acids (HA) have previously been shown to be the phenolic acids present at highest concentration in BSG; therefore the HA profile of the phenolic extracts used in this research, the original barley (before brewing) and whole BSG was characterised and quantified using high performance liquid chromatography (HPLC). The concentration of HA present in the samples was in the order of ferulic acid (FA) > p-coumaric acid (p-CA) derivatives > FA derivatives > p-CA > caffeic acid (CA) > CA derivatives. Results suggested that brewing and roasting decreased the HA content. Protein hydrolysates from BSG were also screened for their antioxidant and anti-inflammatory potential. A total of 34 BSG protein samples were tested. Initial analyses of samples A – J found the protein samples did not exert DNA protective effects (except hydrolysate H) or antioxidant effects by the comet and SOD assays, respectively. Samples D, E, F and J selectively reduced IFN-γ production (P < 0.05) in Jurkat T cells, measured using enzyme linked immunosorbent assay (ELISA). Further testing of hydrolysates K – W, including fractionated hydrolysates with molecular weight < 3, < 5 and > 5 kDa, found that higher molecular weight (> 5 kDa) and unfractionated hydrolysates demonstrate greatest anti-inflammatory effects, while fractionated hydrolysates were also shown to have antioxidant activity, by the SOD activity assay. A commercially available yogurt drink (Actimel) and snack-bar and chocolate-drink formulations were fortified with the most bioactive phenolic and protein samples – P2, B2, W, W < 3 kDa, W < 5 kDa, W > 5 kDa. All fortified foods were subjected to a simulated gastrointestinal in vitro digestion procedure and bioactivity retention in the digestates was determined using the comet and ELISA assays. Yogurt fortified with B2 digestate significantly (P < 0.05) protected against H2O2-induced DNA damage in Caco-2 cells. Greatest immunomodulatory activity was demonstrated by the snack-bar formulation, significantly (P < 0.05) reducing IFN-γ production in con-A stimulated Jurkat T cells. Hydrolysate W significantly (P < 0.05) increased the IFN-γ reducing capacity of the snack-bar. Addition of fractionated hydrolysate W < 3 kDa and W < 5 kDa to yogurt also reduced IL-2 production to a greater extent than the unfortified yogurt (P < 0.05).

Legal regulation of the software "patentable subject matter" requirement in the US and in Europe: The need for certainty, predictability and uniformity

This thesis critically investigates the divergent international approaches to the legal regulation of the patentability of computer software inventions, with a view to identifying the reforms necessary for a certain, predictable and uniform inter-jurisdictional system of protection. Through a critical analysis of the traditional and contemporary US and European regulatory frameworks of protection for computer software inventions, this thesis demonstrates the confusion and legal uncertainty resulting from ill-defined patent laws and inconsistent patent practices as to the scope of the “patentable subject matter” requirement, further compounded by substantial flaws in the structural configuration of the decision-making procedures within which the patent systems operate. This damaging combination prevents the operation of an accessible and effective Intellectual Property (IP) legal framework of protection for computer software inventions, capable of securing adequate economic returns for inventors whilst preserving the necessary scope for innovation and competition in the field, to the ultimate benefit of society. In exploring the substantive and structural deficiencies in the European and US regulatory frameworks, this thesis develops to ultimately highlight that the best approach to the reform of the legal regulation of software patentability is two-tiered. It demonstrates that any reform to achieve international legal harmony first requires the legislature to individually clarify (Europe) or restate (US) the long-standing inadequate rules governing the scope of software “patentable subject matter”, together with the reorganisation of the unworkable structural configuration of the decision-making procedures. Informed by the critical analysis of the evolution of the “patentable subject matter” requirement for computer software in the US, this thesis particularly considers the potential of the reforms of the European patent system currently underway, to bring about certainty, predictability and uniformity in the legal treatment of computer software inventions.

Early biomarkers to predict grade of encephalopathy following hypoxic ischaemic injury

The standard early markers for identifying and grading HIE severity, are not sufficient to ensure all children who would benefit from treatment are identified in a timely fashion. The aim of this thesis was to explore potential early biomarkers of HIE. Methods: To achieve this a cohort of infants with perinatal depression was prospectively recruited. All infants had cord blood samples drawn and biobanked, and were assessed with standardised neurological examination, and early continuous multi-channel EEG. Cord samples from a control cohort of healthy infants were used for comparison. Biomarkers studied included; multiple inflammatory proteins using multiplex assay; the metabolomics profile using LC/MS; and the miRNA profile using microarray. Results: Eighty five infants with perinatal depression were recruited. Analysis of inflammatory proteins consisted of exploratory analysis of 37 analytes conducted in a sub-population, followed by validation of all significantly altered analytes in the remaining population. IL-6 and IL-6 differed significantly in infants with a moderate/severely abnormal vs. a normal-mildly abnormal EEG in both cohorts (Exploratory: p=0.016, p=0.005: Validation: p=0.024, p=0.039; respectively). Metabolomic analysis demonstrated a perturbation in 29 metabolites. A Cross- validated Partial Least Square Discriminant Analysis model was developed, which accurately predicted HIE with an AUC of 0.92 (95% CI: 0.84-0.97). Analysis of the miRNA profile found 70 miRNA significantly altered between moderate/severely encephalopathic infants and controls. miRNA target prediction databases identified potential targets for the altered miRNA in pathways involved in cellular metabolism, cell cycle and apoptosis, cell signaling, and the inflammatory cascade. Conclusion: This thesis has demonstrated that the recruitment of a large cohortof asphyxiated infants, with cord blood carefully biobanked, and detailed early neurophysiological and clinical assessment recorded, is feasible. Additionally the results described, provide potential alternate and novel blood based biomarkers for the identification and assessment of HIE.

Characterization of the degradation of wild-type and mutant HFE proteins during stress signalling in the endoplasmic reticulum

HFE is a transmembrane protein that becomes N-glycosylated during transport to the cell membrane. It acts to regulate cellular iron uptake by interacting with the Type 1 transferrin receptor and interfering with its ability to bind iron-loaded transferrin. There is also evidence that HFE regulates systemic iron levels by binding to the Type II transferrin receptor although the mechanism by which this occurs is still not well understood. Mutations to HFE that disrupt this function, or physiological conditions that decrease HFE protein levels, are associated with increased iron uptake, and its accumulation in tissues and organs. This is exemplified by the point mutation that results in conversion of cysteine residue 282 to tyrosine (C282Y), and gives rise to the majority of HFE-related hemochromatoses. The C282Y mutation prevents the formation of a disulfide bridge and disrupts the interaction with its co-chaperone β2-microglobulin. The resulting misfolded protein is retained within the endoplasmic reticulum (ER) where it activates the Unfolded Protein Response (UPR) and is subjected to proteasomal degradation. The absence of functional HFE at the cell surface leads to unregulated iron uptake and iron loading. While the E3 ubiquitin ligase involved in the degradation of HFE-C282Y has been identified, the mechanism by which it is targeted for degradation remains relatively obscure. The primary objective of this project was to further our understanding of how the iron regulatory HFE protein is targeted for degradation. Our studies suggest that the glycosylation status, and the active process of deglycosylation, are central to this process. We identified a number of additional factors that can contribute towards degradation and explored their regulation during ER stress conditions.