# WRAP - latest items

WRAP: Warwick Research Archive Portal: No conditions. Results ordered -Date Deposited.

Interaction of the V-series chemical warfare agent simulant 'VO' with Eu(III) results in selective quenching of the red Eu-based emission component from a dual-luminescent (blue/red) Ir(III)/Eu(III) dyad, resulting in a colour change in the luminescence from red to blue in the presence of the simulant.

The first example of cell imaging using two independent emission components from a dinuclear d/f complex is reported. A water-stable, cell-permeable IrIII/EuIII dyad undergoes partial Ir→Eu energy transfer following two-photon excitation of the Ir unit at 780 nm. Excitation in the near-IR region generated simultaneously green Ir-based emission and red Eu-based emission from the same probe. The orders-of-magnitude difference in their timescales (Ir ca. μs; Eu ca. 0.5 ms) allowed them to be identified by time-gated detection. Phosphorescence lifetime imaging microscopy (PLIM) allowed the lifetime of the Ir-based emission to be measured in different parts of the cell. At the same time, the cells are simultaneously imaged by using the Eu-based emission component at longer timescales. This new approach to cellular imaging by using dual d/f emitters should therefore enable autofluorescence-free sensing of two different analytes, independently, simultaneously and in the same regions of a cell.

Dinuclear (Ir·Ln) and trinuclear (Ir·Ln2) d−f complexes are investigated for cellular imaging. A range of photophysical, spectroscopic, and imaging-based properties are reported, including relaxivity arising from Gd(III) units and the occurrence of Ir(III) → Eu(III) photoinduced energy-transfer. Noninvasive O2 sensing with Ir·Gd (a potential dual probe: MRI + luminescence) is demonstrated in aqueous solution, full cell media and in vitro, via lifetime mapping and two-photon, phosphorescence lifetime imaging microscopy (PLIM).

A new rigid and conjugated ligand structure connecting phenanthroline and poly(amino-carboxylate) binding sites provides d–f complexes which show high potential for use in dual (luminescence + magnetic resonance) imaging and for optimisation of d → f photoinduced energy-transfer.

The hollow cavities of coordination cages can provide an environment for enzyme-like catalytic reactions of small-molecule guests. Here, we report a new example (catalysis of the Kemp elimination reaction of benzisoxazole with hydroxide to form 2-cyanophenolate) in the cavity of a water-soluble M8L12 coordination cage, with two features of particular interest. First, the rate enhancement is among the largest observed to date: at pD 8.5, the value of kcat/kuncat is 2 × 105, due to the accumulation of a high concentration of partially desolvated hydroxide ions around the bound guest arising from ion-pairing with the 16+ cage. Second, the catalysis is based on two orthogonal interactions: (1) hydrophobic binding of benzisoxazole in the cavity and (2) polar binding of hydroxide ions to sites on the cage surface, both of which were established by competition experiments.

Neurodegenerative tauopathies are characterized by accumulation of hyperphosphorylated tau aggregates primarily degraded by autophagy.

The 5'AMP-activated protein kinase (AMPK) is expressed in most cells, including neurons. Alongside its metabolic functions, it is also known to be activated in Alzheimer's brains, phosphorylate tau and be a critical autophagy activator. Whether it plays a neurotoxic or neuroprotective role remains unclear. Complexly in tauopathies, while stress conditions can result in AMPK activation enhancing tau-mediated toxicity, AMPK activation is not always concomitant with autophagic induction.

Using a Drosophila in vivo quantitative approach, we have analysed the impact of AMPK and autophagy on tau-mediated toxicity, recapitulating the AMPK-mediated tauopathy condition: increased tau phosphorylation, without corresponding autophagy activation.

We have demonstrated that AMPK, binding to and phosphorylating tau at Ser-262, a site reported to facilitate soluble tau accumulation, affects its degradation. This phosphorylation results in exacerbation of tau toxicity and is ameliorated via rapamycin-induced autophagy stimulation.

Our findings support the development of combinatorial therapies effective at reducing tau toxicity targeting tau phosphorylation and AMPK-independent autophagic induction. The proposed in vivo tool represents an ideal readout to perform preliminary screening for drugs promoting this process.

Information security breaches have serious consequences for companies. And information security breaches in the defence industry negatively impact national security. Selling information concerning industrial design, organisational strategic plans, customers, experts and other valuable information for monetary benefit, revenge, bribery and embezzlement are just some examples of the human dimension of information security.1

Evidence of inadvertent patient harm due to healthcare staff errors - both within the NHS and in other healthcare providers worldwide - prompted regulator-led changes to eliminate such distressing incidents to patients and medical staff alike. Surgical disciplines, including orthopaedic surgery, became a focus of attention given the scale of the problem within operating theatres.

Orthopaedic theatres are an example of a complex working environment that has been likened to an airplane cockpit whereby the delivery of unsafe and low quality service can lead to highly significant consequences. Around 32.6% of all surgical patient safety incidents reported by the NPSA are related to orthopaedics. Evidence suggests that harm incidents are influenced by the surgical team's non-­‐technical skills, and can occur through an unpredicted combination of small, seemingly innocuous everyday events. It is also suggested that non-technical factors including the non-technical skills of the operating team can influence the technical tasks during surgery.

In elective orthopaedic surgery, one important technical task during TKA surgery is achieving a neutral limb alignment making it a suitable surrogate for technical success and quality indicator for intra-operative performance. The impact of malalignment on patient outcomes is not fully understood. A systematic review of the literature demonstrated that although malalignment appears to associate with poor procedure outcomes however, the evidence in the literature to support this conclusion is subject to several limitations. There is also variability in the assessment methods qualities and a checklist to assess the radiological assessment methods is presented. Malalignment on the coronal plane is regarded as the most significant in determining long term implant survival. A novel X-­‐ray method using custom made jig and trigonometry principles designed during this thesis has demonstrated higher agreement with CT scan than the commonly used conventional short leg X-­‐rays in assessing coronal malalignment; (95% Limits of agreement = -­‐3.616867 to 3.616867 for novel technique versus -­‐6.333201 to 5.754254 for conventional short leg X-­‐rays).

In order to explore the relationship between non-­‐technical factors and technical success, successive TKAs were observed to collect data on surgical team's non-­‐ technical performance and the number of unwanted events. 3D malalignment was assessed using a low dose CT. Parson's correlation and regression analysis showed that better overall limb alignment following TKA correlates significantly with better intra-­‐operative non-­‐technical skills measured using the Oxford NOTECHS II score (r=-­‐ 0.407, p=0.01), and not with eventless procedures (measured by the glitch count). The surgical teams' non-­‐technical skills play a significant role in the team's ability to carry out technical tasks. If we are to provide optimal patient care we need to invest in improving non-­‐technical skills in the theatre.

This book presents a collection of essays on key topics and new perspectives on the EU's Area of Freedom, Security and Justice (AFSJ) and has a Foreword by the President of the Court of Justice of the European Union, Prof. Dr. Koen Lenaerts.

This collection asks a direct but complex question: is the EU humane enough? The implementation of EU law and policy and its balance between economic and social values continues to provoke debate. Providing fresh insight, Nuno Ferreira and Dora Kostakopoulou present a novel analytical framework, centred on the notion of humaneness, for assessing EU law and policy. This innovative approach leads to recommendations for policy change towards a more humanistic philosophy for the EU. Broad in its scope, this remarkable volume draws together interdisciplinary perspectives from contributors who examine key EU law and policy fields, including economic integration, asylum and free movement, citizenship and development, and security. This book is essential reading for scholars, students and policy-makers seeking new ways of exploring the economic versus social values debate in EU law.

In this thesis we study low-dimensional stochastic volatility interest rate models for pricing and hedging exotic derivatives. In particular we develop a stochastic volatility Markov-functional model. In order to implement the model numerically, we further propose a general algorithm by working with basis functions and conditional moments of the driving Markov process. Motivated by a data driven study, we choose a SABR type model as a driving process. With this choice we specify a pre-model and develop an approximation to evaluate conditional moments of the SABR driver which serve as building blocks for the practical algorithm.

Having discussed how to set up a stochastic volatility Markov-functional model next we study the calibration of a LIBOR based version of the model with the SABR type driving process. We consider a link between separable SABR LIBOR market models and stochastic volatility LIBOR Markov-functional models. Based on the link we propose a calibration routine to feed in SABR marginals by calibrating to the market vanilla options. Moreover we choose the parameters of the SABR driver by fitting to the market correlation structure.

We compare the stochastic volatility Markov-functional model developed in the thesis with one-dimensional (non-stochastic-volatility) swap Markov-functional models in terms of pricing and hedging Bermudan type products. By doing so we investigate effects of correlation structure, implied volatility smiles and the introduction of stochastic volatility on Bermudan type products.

Finally we compare Quasi-Gaussian models with Markov-functional models in terms of specification and calibration. In particular we study Quasi-Gaussian models formulated in the Markov-functional model framework to make clear the relationship between the two models.

A handful of white dwarfs with helium-dominated atmospheres contain exceptionally large masses of hydrogen in their convection zones, with the metal-polluted white dwarf GD 16 being one of the earliest recognized examples. We report the discovery of a similar star: the white dwarf coincidentally named GD 17. We obtained medium-resolution spectroscopy of both GD 16 and GD 17 and calculated abundances and accretion rates of photospheric H, Mg, Ca, Ti, Fe and Ni. The metal abundance ratios indicate that the two stars recently accreted debris, which is Mg-poor compared to the composition of bulk Earth. However, unlike the metal pollutants, H never diffuses out of the atmosphere of white dwarfs and we propose that the exceptionally high atmospheric H content of GD 16 and GD 17 (2.2 × 1024 and 2.9 × 1024 g, respectively) could result from previous accretion of water bearing planetesimals. Comparing the detection of trace H and metal pollution among 729 helium atmosphere white dwarfs, we find that the presence of H is nearly twice as common in metal-polluted white dwarfs compared to their metal-free counterparts. This highly significant correlation indicates that, over the cooling age of the white dwarfs, at least some fraction of the H detected in many He atmospheres (including GD 16 and GD 17) is accreted alongside metal pollutants, where the most plausible source is water. In this scenario, water must be common in systems with rocky planetesimals.

This collection asks a direct but complex question: is the EU humane enough? The implementation of EU law and policy and its balance between economic and social values continues to provoke debate. Providing fresh insight, Nuno Ferreira and Dora Kostakopoulou present a novel analytical framework, centred on the notion of humaneness, for assessing EU law and policy. This innovative approach leads to recommendations for policy change towards a more humanistic philosophy for the EU. Broad in its scope, this remarkable volume draws together interdisciplinary perspectives from contributors who examine key EU law and policy fields, including economic integration, asylum and free movement, citizenship and development, and security. This book is essential reading for scholars, students and policy-makers seeking new ways of exploring the economic versus social values debate in EU law.

We present a synthetic spectral analysis of the HST COS spectrum of the U Geminorum-type dwarf nova CW Mon, taken during quiescence as part of our COS survey of accreting white dwarfs (WDs) in Cataclysmic Variables. We use a synthetic photosphere and optically thick accretion disk spectra to model the COS spectrum as well as archival IUE spectra obtained decades ago, when the system was in an even deeper quiescent state. Assuming a reddening of $E(B-V)$ = 0.06, an inclination of 60° (CW Mon has eclipses of the accretion disk), and a WD mass of $0.8\,{M}_{\odot }$, our results indicate the presence of a 22–27,000 K WD and a low mass accretion rate $\dot{M}\lesssim {10}^{-10}\,{M}_{\odot }\,{\mathrm{yr}}^{-1}$, for a derived distance of ~200 to ~300 pc.

This collection asks a direct but complex question: is the EU humane enough? The implementation of EU law and policy and its balance between economic and social values continues to provoke debate. Providing fresh insight, Nuno Ferreira and Dora Kostakopoulou present a novel analytical framework, centred on the notion of humaneness, for assessing EU law and policy. This innovative approach leads to recommendations for policy change towards a more humanistic philosophy for the EU. Broad in its scope, this remarkable volume draws together interdisciplinary perspectives from contributors who examine key EU law and policy fields, including economic integration, asylum and free movement, citizenship and development, and security. This book is essential reading for scholars, students and policy-makers seeking new ways of exploring the economic versus social values debate in EU law.

We sought to understand from a rhetorical perspective the sources of the runaway popularity of Steve Jobs' Stanford commencement speech. Our analysis shows the rhetorical sophistication of this speech in terms of mutually reinforcing use of established dynamics, canons, and devices of rhetoric. We find however that these aspects of classical rhetoric are imbued with and reinforced by Burkeian identification processes that permeate the speech. We contend that an important aspect of leaders' rhetorical competence, and an enabler for constructing evocative, impactful rhetoric is the skillful employment of processes of identification.