Have the GIPSI settled down? Breaks and multivariate stochastic volatility models for, and not against, the European financial integration

We investigate the integration of the European peripheral financial markets with Germany, France, and the UK using a combination of tests for structural breaks and return correlations derived from several multivariate stochastic volatility models. Our findings suggest that financial integration intensified in anticipation of the Euro, further strengthened by the EMU inception, and amplified in response to the 2007/2008 financial crisis. Hence, no evidence is found of decoupling of the equity markets in more troubled European countries from the core. Interestingly, the UK, despite staying outside the EMU, is not worse integrated with the GIPSI than Germany or France. © 2013 Elsevier B.V.

Stock market efficiency before and after a financial liberalisation reform:do breaks in volatility dynamics matter?

This article focuses on the deviations from normality of stock returns before and after a financial liberalisation reform, and shows the extent to which inference based on statistical measures of stock market efficiency can be affected by not controlling for breaks. Drawing from recent advances in the econometrics of structural change, it compares the distribution of the returns of five East Asian emerging markets when breaks in the mean and variance are either (i) imposed using certain official liberalisation dates or (ii) detected non-parametrically using a data-driven procedure. The results suggest that measuring deviations from normality of stock returns with no provision for potentially existing breaks incorporates substantial bias. This is likely to severely affect any inference based on the corresponding descriptive or test statistics.

Breaks in the UK household sector money demand function

We use non-parametric procedures to identify breaks in the underlying series of UK household sector money demand functions. Money demand functions are estimated using cointegration techniques and by employing both the Simple Sum and Divisia measures of money. P-star models are also estimated for out-of-sample inflation forecasting. Our findings suggest that the presence of breaks affects both the estimation of cointegrated money demand functions and the inflation forecasts. P-star forecast models based on Divisia measures appear more accurate at longer horizons and the majority of models with fundamentals perform better than a random walk model.

Long memory in log-range series:do structural breaks matter?

This paper examines whether the observed long memory behavior of log-range series is to some extent spurious and whether it can be explained by the presence of structural breaks. Utilizing stock market data we show that the characterization of log-range series as long memory processes can be a strong assumption. Moreover, we find that all examined series experience a large number of significant breaks. Once the breaks are accounted for, the volatility persistence is eliminated. Overall, the findings suggest that volatility can be adequately represented, at least in-sample, through a multiple breaks process and a short run component.

LSQ13fn: A type II-Plateau supernova with a possibly low metallicity progenitor that breaks the standardised candle relation∗

We present optical imaging and spectroscopy of supernova (SN) LSQ13fn, a type II supernova with several hitherto-unseen properties. Although it initially showed strong symmetric spectral emission features attributable to He ii, N iii, and C iii, reminiscent of some interacting SNe, it transitioned into an object that would fall more naturally under a type II-Plateau (IIP) classification. However, its spectral evolution revealed several unusual properties: metal lines appeared later than expected, were weak, and some species were conspicuous by their absence. Furthermore, the line velocities were found to be lower than expected given the plateau brightness, breaking the SN IIP standardised candle method for distance estimates. We found that, in combination with a short phase of early-time ejecta-circumstellar material interaction, metal-poor ejecta, and a large progenitor radius could reasonably account for the observed behaviour. Comparisons with synthetic model spectra of SNe IIP of a given progenitor mass would imply a progenitor star metallicity as low as 0.1 Z_⊙. LSQ13fn highlights the diversity of SNe II and the many competing physical effects that come into play towards the final stages of massive star evolution immediately preceding core-collapse.

APRIN(PDS5B) et PALB2, deux protéines impliquées dans la réparation de l’ADN par recombinaison homologue et l’apparition de cancers

Au Canada, en 2015, il était estimé que 78 000 personnes allaient mourir d’un cancer, représentant 30 % de tous les décès et faisant de celui-ci la première cause de mortalité. De plus, 196 900 nouveaux cas de cancers seraient découverts au cours de cette même année (Canadian Cancer Society’s Advisory Committee on Cancer Statistics. Canadian Cancer Statistics 2015. Toronto, ON : Canadian Cancer Society; 2015). L’intégrité du génome est chaque jour menacée par des conditions environnementales qui endommagent l’ADN (ultraviolets, produits chimiques divers, etc.). Parmi les différents types de lésions, l’un des plus délétères et pouvant mener au cancer est la cassure double-brin (CDB). Celle-ci peut être réparée suivant deux mécanismes majeurs : la jonction des extrémités non homologues (Non-Homologous End-Joining ou NHEJ) ou la Recombinaison Homologue (RH). Cette dernière, prépondérante pendant les phases S/G2, consiste en la réparation d’une CDB grâce à l’utilisation d’une chromatide soeur comme modèle, permettant une réparation fidèle du dommage. La RH est sous la dépendance de diverses protéines, dont RAD51, PALB2 et BRCA2. Ces deux dernières sont connues pour être mutées dans les cancers du sein et des ovaires. Ainsi, la compréhension de l’implication de chaque acteur dans la RH est un objectif fondamental dans la lutte contre le cancer et constitue l’objectif général de cette thèse. En 2012, une étude a montré qu’une nouvelle protéine, APRIN (Androgen-induced PRoliferation INhibitor), appartenant au complexe cohésine, interagissait avec BRCA2 et jouait un rôle dans la RH. Les rôles précis d’APRIN dans ce mécanisme restaient toutefois à être définis. Le projet principal de cette thèse repose sur la caractérisation fonctionnelle d’APRIN dans la réparation par RH. Nous révélons qu’APRIN aurait un rôle spécifique et indépendant de celui de la cohésine dans la RH, et pourrait agir à diverses étapes cruciales de ce mécanisme. De plus, nos données montrent que le niveau d’expression d’APRIN pourrait être un marqueur de prédiction dans le cancer ovarien. Étant donné qu’APRIN interagit aussi avec PALB2, autre partenaire essentiel de BRCA2, nous avons également étudié et caractérisé les fonctions de divers mutants de PALB2. Nous faisons ainsi la découverte inattendue d’un nouveau phénotype induit par une troncation de cette protéine associée à certains cancers agressifs. Ainsi, cette thèse apporte des informations supplémentaires et indispensables à la compréhension de la réparation de l’ADN par RH et de la survenue de certains cancers.

Exchange rate dynamics, structural breaks, and central bank interventions in Colombia

We evaluate the effectiveness of the Colombian Central Bank´s interventions in the foreign exchange market during the period 2000 to 2014 -- We examine the stochastic process that describes the exchange rate, with a focus on the detection of structural breaks or unit roots in the data to determine whether the Central Bank´s interventions were effective -- We find that the exchange rate can be described either by a random walk or by a trend-stationary model with multiple breaks -- In neither cases do we find any evidence that the exchange rate was affected by the Central Bank interventions

Hilbert Space Valued Signal Plus Noise Models: Analysis of Structural Breaks under High Dimensionality and Temporal Dependence

This thesis is concerned with change point analysis for time series, i.e. with detection of structural breaks in time-ordered, random data. This long-standing research field regained popularity over the last few years and is still undergoing, as statistical analysis in general, a transformation to high-dimensional problems. We focus on the fundamental »change in the mean« problem and provide extensions of the classical non-parametric Darling-Erdős-type cumulative sum (CUSUM) testing and estimation theory within highdimensional Hilbert space settings. In the first part we contribute to (long run) principal component based testing methods for Hilbert space valued time series under a rather broad (abrupt, epidemic, gradual, multiple) change setting and under dependence. For the dependence structure we consider either traditional m-dependence assumptions or more recently developed m-approximability conditions which cover, e.g., MA, AR and ARCH models. We derive Gumbel and Brownian bridge type approximations of the distribution of the test statistic under the null hypothesis of no change and consistency conditions under the alternative. A new formulation of the test statistic using projections on subspaces allows us to simplify the standard proof techniques and to weaken common assumptions on the covariance structure. Furthermore, we propose to adjust the principal components by an implicit estimation of a (possible) change direction. This approach adds flexibility to projection based methods, weakens typical technical conditions and provides better consistency properties under the alternative. In the second part we contribute to estimation methods for common changes in the means of panels of Hilbert space valued time series. We analyze weighted CUSUM estimates within a recently proposed »high-dimensional low sample size (HDLSS)« framework, where the sample size is fixed but the number of panels increases. We derive sharp conditions on »pointwise asymptotic accuracy« or »uniform asymptotic accuracy« of those estimates in terms of the weighting function. Particularly, we prove that a covariance-based correction of Darling-Erdős-type CUSUM estimates is required to guarantee uniform asymptotic accuracy under moderate dependence conditions within panels and that these conditions are fulfilled, e.g., by any MA(1) time series. As a counterexample we show that for AR(1) time series, close to the non-stationary case, the dependence is too strong and uniform asymptotic accuracy cannot be ensured. Finally, we conduct simulations to demonstrate that our results are practically applicable and that our methodological suggestions are advantageous.

Tourism Destination Preferences: A Longitudinal Analysis of Consumer Decision Sets

There have only been a small number of applications of consumer decision set theory to holiday destination choice, and these studies have tended to rely on a single cross sectional snapshot of research participants’ stated preferences. Very little has been reported on the relationship between stated destination preferences and actual travel, or changes in decision set composition over time. The paper presents a rare longitudinal examination of destination decision sets, in the context of short break holidays by car in Queensland, Australia. Two questionnaires were administered, three months apart. The first identified destination preferences while the second examined actual travel and revisited destination preferences. In relation to the conference theme, there was very little change in consumer preferences towards the competitive set of destinations over the three month period. A key implication for the destination of interest, which, in an attempt to change market perceptions, launched a new brand campaign during the period of the project, is that a long term investment in a consistent brand message will be required to change market perceptions. The results go some way to support the proposition that the positioning of a destination into a consumer’s decision set represents a source of competitive advantage.

Biochemical characterization of Aprataxin, the protein deficient in Ataxia with Oculomotor Apraxia type 1

Neurodegenerative disorders are heterogenous in nature and include a range of ataxias with oculomotor apraxia, which are characterised by a wide variety of neurological and ophthalmological features. This family includes recessive and dominant disorders. A subfamily of autosomal recessive cerebellar ataxias are characterised by defects in the cellular response to DNA damage. These include the well characterised disorders Ataxia-Telangiectasia (A-T) and Ataxia-Telangiectasia Like Disorder (A-TLD) as well as the recently identified diseases Spinocerebellar ataxia with axonal neuropathy Type 1 (SCAN1), Ataxia with Oculomotor Apraxia Type 2 (AOA2), as well as the subject of this thesis, Ataxia with Oculomotor Apraxia Type 1 (AOA1). AOA1 is caused by mutations in the APTX gene, which is located at chromosomal locus 9p13. This gene codes for the 342 amino acid protein Aprataxin. Mutations in APTX cause destabilization of Aprataxin, thus AOA1 is a result of Aprataxin deficiency. Aprataxin has three functional domains, an N-terminal Forkhead Associated (FHA) phosphoprotein interaction domain, a central Histidine Triad (HIT) nucleotide hydrolase domain and a C-terminal C2H2 zinc finger. Aprataxins FHA domain has homology to FHA domain of the DNA repair protein 5’ polynucleotide kinase 3’ phosphatase (PNKP). PNKP interacts with a range of DNA repair proteins via its FHA domain and plays a critical role in processing damaged DNA termini. The presence of this domain with a nucleotide hydrolase domain and a DNA binding motif implicated that Aprataxin may be involved in DNA repair and that AOA1 may be caused by a DNA repair deficit. This was substantiated by the interaction of Aprataxin with proteins involved in the repair of both single and double strand DNA breaks (XRay Cross-Complementing 1, XRCC4 and Poly-ADP Ribose Polymerase-1) and the hypersensitivity of AOA1 patient cell lines to single and double strand break inducing agents. At the commencement of this study little was known about the in vitro and in vivo properties of Aprataxin. Initially this study focused on generation of recombinant Aprataxin proteins to facilitate examination of the in vitro properties of Aprataxin. Using recombinant Aprataxin proteins I found that Aprataxin binds to double stranded DNA. Consistent with a role for Aprataxin as a DNA repair enzyme, this binding is not sequence specific. I also report that the HIT domain of Aprataxin hydrolyses adenosine derivatives and interestingly found that this activity is competitively inhibited by DNA. This provided initial evidence that DNA binds to the HIT domain of Aprataxin. The interaction of DNA with the nucleotide hydrolase domain of Aprataxin provided initial evidence that Aprataxin may be a DNA-processing factor. Following these studies, Aprataxin was found to hydrolyse 5’adenylated DNA, which can be generated by unscheduled ligation at DNA breaks with non-standard termini. I found that cell extracts from AOA1 patients do not have DNA-adenylate hydrolase activity indicating that Aprataxin is the only DNA-adenylate hydrolase in mammalian cells. I further characterised this activity by examining the contribution of the zinc finger and FHA domains to DNA-adenylate hydrolysis by the HIT domain. I found that deletion of the zinc finger ablated the activity of the HIT domain against adenylated DNA, indicating that the zinc finger may be required for the formation of a stable enzyme-substrate complex. Deletion of the FHA domain stimulated DNA-adenylate hydrolysis, which indicated that the activity of the HIT domain may be regulated by the FHA domain. Given that the FHA domain is involved in protein-protein interactions I propose that the activity of Aprataxins HIT domain may be regulated by proteins which interact with its FHA domain. We examined this possibility by measuring the DNA-adenylate hydrolase activity of extracts from cells deficient for the Aprataxin-interacting DNA repair proteins XRCC1 and PARP-1. XRCC1 deficiency did not affect Aprataxin activity but I found that Aprataxin is destabilized in the absence of PARP-1, resulting in a deficiency of DNA-adenylate hydrolase activity in PARP-1 knockout cells. This implies a critical role for PARP-1 in the stabilization of Aprataxin. Conversely I found that PARP-1 is destabilized in the absence of Aprataxin. PARP-1 is a central player in a number of DNA repair mechanisms and this implies that not only do AOA1 cells lack Aprataxin, they may also have defects in PARP-1 dependant cellular functions. Based on this I identified a defect in a PARP-1 dependant DNA repair mechanism in AOA1 cells. Additionally, I identified elevated levels of oxidized DNA in AOA1 cells, which is indicative of a defect in Base Excision Repair (BER). I attribute this to the reduced level of the BER protein Apurinic Endonuclease 1 (APE1) I identified in Aprataxin deficient cells. This study has identified and characterised multiple DNA repair defects in AOA1 cells, indicating that Aprataxin deficiency has far-reaching cellular consequences. Consistent with the literature, I show that Aprataxin is a nuclear protein with nucleoplasmic and nucleolar distribution. Previous studies have shown that Aprataxin interacts with the nucleolar rRNA processing factor nucleolin and that AOA1 cells appear to have a mild defect in rRNA synthesis. Given the nucleolar localization of Aprataxin I examined the protein-protein interactions of Aprataxin and found that Aprataxin interacts with a number of rRNA transcription and processing factors. Based on this and the nucleolar localization of Aprataxin I proposed that Aprataxin may have an alternative role in the nucleolus. I therefore examined the transcriptional activity of Aprataxin deficient cells using nucleotide analogue incorporation. I found that AOA1 cells do not display a defect in basal levels of RNA synthesis, however they display defective transcriptional responses to DNA damage. In summary, this thesis demonstrates that Aprataxin is a DNA repair enzyme responsible for the repair of adenylated DNA termini and that it is required for stabilization of at least two other DNA repair proteins. Thus not only do AOA1 cells have no Aprataxin protein or activity, they have additional deficiencies in PolyADP Ribose Polymerase-1 and Apurinic Endonuclease 1 dependant DNA repair mechanisms. I additionally demonstrate DNA-damage inducible transcriptional defects in AOA1 cells, indicating that Aprataxin deficiency confers a broad range of cellular defects and highlighting the complexity of the cellular response to DNA damage and the multiple defects which result from Aprataxin deficiency. My detailed characterization of the cellular consequences of Aprataxin deficiency provides an important contribution to our understanding of interlinking DNA repair processes.

Near-infrared spectroscopic studies of human scalp hair in a forensic context

Human hair is a relatively inert biopolymer and can survive through natural disasters. It is also found as trace evidence at crime scenes. Previous studies by FTIRMicrospectroscopy and – Attenuated Total Reflectance (ATR) successfully showed that hairs can be matched and discriminated on the basis of gender, race and hair treatment, when interpreted by chemometrics. However, these spectroscopic techniques are difficult to operate at- or on-field. On the other hand, some near infrared spectroscopic (NIRS) instruments equipped with an optical probe, are portable and thus, facilitate the on- or at –field measurements for potential application directly at a crime or disaster scene. This thesis is focused on bulk hair samples, which are free of their roots, and thus, independent of potential DNA contribution for identification. It explores the building of a profile of an individual with the use of the NIRS technique on the basis of information on gender, race and treated hair, i.e. variables which can match and discriminate individuals. The complex spectra collected may be compared and interpreted with the use of chemometrics. These methods can then be used as protocol for further investigations. Water is a common substance present at forensic scenes e.g. at home in a bath, in the swimming pool; it is also common outdoors in the sea, river, dam, puddles and especially during DVI incidents at the seashore after a tsunami. For this reason, the matching and discrimination of bulk hair samples after the water immersion treatment was also explored. Through this research, it was found that Near Infrared Spectroscopy, with the use of an optical probe, has successfully matched and discriminated bulk hair samples to build a profile for the possible application to a crime or disaster scene. Through the interpretation of Chemometrics, such characteristics included Gender and Race. A novel approach was to measure the spectra not only in the usual NIR range (4000 – 7500 cm-1) but also in the Visible NIR (7500 – 12800 cm-1). This proved to be particularly useful in exploring the discrimination of differently coloured hair, e.g. naturally coloured, bleached or dyed. The NIR region is sensitive to molecular vibrations of the hair fibre structure as well as that of the dyes and damage from bleaching. But the Visible NIR region preferentially responds to the natural colourants, the melanin, which involves electronic transitions. This approach was shown to provide improved discrimination between dyed and untreated hair. This thesis is an extensive study of the application of NIRS with the aid of chemometrics, for matching and discrimination of bulk human scalp hair. The work not only indicates the strong potential of this technique in this field but also breaks new ground with the exploration of the use of the NIR and Visible NIR ranges for spectral sampling. It also develops methods for measuring spectra from hair which has been immersed in different water media (sea, river and dam)