Nanomateriais manufaturados : avaliação de segurança através da caracterização dos seus efeitos genéticos

RESUMO - Os nanomateriais manufaturados (NMs), isto é, fabricados deliberadamente para fins específicos, apresentam propriedades físico-químicas únicas como a dimensão, área superficial ou funcionalização, que lhes conferem caraterísticas mecânicas, óticas, elétricas e magnéticas muito vantajosas para aplicações industriais e biomédicas. Efetivamente, a tecnologia baseada nos NMs, ou nanotecnologia, foi identificada como uma key enabling technology, impulsionadora do crescimento económico dos países industrializados, devido ao seu potencial para melhorar a qualidade e desempenho de muitos tipos de produtos e de processos. Contudo, a expansão da utilização de NMs contrasta com a insuficiente avaliação de risco para a saúde humana e para o ambiente, sendo considerados como um risco emergente para a saúde pública. As incertezas sobre a segurança dos NMs para a saúde pública advêm sobretudo de estudos epidemiológicos em humanos expostos a nanomateriais produzidos como consequência dos processos e atividades humanas e da poluição. Uma das principais preocupações relativamente aos efeitos adversos dos NMs na saúde humana é o seu potencial efeito carcinogénico, que é sugerido por alguns estudos experimentais, como no caso dos nanomateriais de dióxido de titânio ou dos nanotubos de carbono. Para avaliar em curto termo as propriedades carcinogénicas de um composto, utilizam-se frequentemente ensaios de genotoxicidade em linhas celulares de mamífero ou ensaios em modelos animais, em que se analisa uma variedade de lesões genéticas potencialmente relacionados com o processo de carcinogénese. No entanto, a investigação sobre as propriedades genotóxicas dos NMs não foi, até hoje, conclusiva. O presente estudo tem por objectivo principal caracterizar os efeitos genotóxicos associados à exposição a nanomateriais manufaturados, de forma a contribuir para a avaliação da sua segurança. Constituíram objectivos específicos deste estudo: i) avaliar a genotoxicidade dos NMs em três tipos de células humanas expostas in vitro: linfócitos humanos primários, linha celular de epitélio brônquico humano (BEAS-2B) e linha celular de adenocarcinoma epitelial de pulmão humano (A549); ii) avaliar a sua genotoxicidade num modelo de ratinho transgénico; iii) investigar alguns mecanismos de acção que poderão contribuir para a genotoxicidade dos nanomateriais, como a contribuição de lesões oxidativas para a genotoxicidade induzida pelos NMs in vitro, e a investigação da sua bioacumulação e localização celular in vivo. Foram analisados os efeitos genotóxicos associados à exposição a duas classes de NMs, dióxido de titânio e nanotubos de carbono de parede múltipla, bem como a um NM de óxido de zinco, candidato a ser utlilizado como controlo positivo de dimensão nanométrica. Os xx NMs utilizados foram previamente caracterizados com detalhe relativamente às suas características físico-químicas e também relativamente à sua dispersão em meio aquoso e no meio de cultura. A metodologia incluiu ensaios de citotoxicidade e de genotoxicidade in vitro, designadamente, ensaios de quebras no DNA (ensaio do cometa) e nos cromossomas (ensaio do micronúcleo) em células humanas expostas a várias concentrações de NMs, por comparação com células não expostas. Também foram realizados ensaios in vivo de quebras no DNA, quebras cromossómicas e ainda um ensaio de mutações em vários órgãos de grupos de ratinhos transgénicos LacZ, expostos por via intravenosa a duas doses de dióxido de titânio. Foi investigada a existência de uma relação dose-resposta após exposição das células humanas ou dos animais a NMs. A contribuição de lesões oxidativas para a genotoxicidade após exposição das células aos NMs in vitro foi explorada através do ensaio do cometa modificado com enzima. Realizaram-se estudos histológicos e citológicos para deteção e localização celular dos NMs nos órgãos-alvo dos ratinhos expostos in vivo. Os resultados demonstraram efeitos genotóxicos em alguns dos NMs analisados em células humanas. No entanto, os efeitos genotóxicos, quando positivos, foram em níveis reduzidos, ainda que superiores aos valores dos controlos, e a sua reprodutibilidade era dependente do sistema experimental utilizado. Para outros NMs, a evidência de genotoxicidade revelou-se equívoca, conduzindo à necessidade de esclarecimento através de ensaios in vivo. Para esse fim, recorreu-se a uma análise integrada de múltiplos parâmetros num modelo animal, o ratinho transgénico baseado em plasmídeo contendo o gene LacZ exposto a um NM de dióxido de titânio, NM-102. Embora tenha sido demonstrada a exposição e a acumulação do NM no fígado, não se observaram efeitos genotóxicos nem no fígado, nem no baço nem no sangue dos ratinhos expostos a esse NM. Neste estudo concluiu-se que algumas formas de dióxido de titânio e nanotubos de carbono de parede múltipla produzem efeitos genotóxicos em células humanas, contribuindo para o conjunto de evidências sobre o efeito genotóxico desses NMs. As diferenças observadas relativamente à genotoxicidade entre NMs do mesmo tipo, mas distintos em algumas das suas características físico-quimicas, aparentemente não são negligenciáveis, pelo que os resultados obtidos para um NM não devem ser generalizados ao grupo correspondente. Para além disso, a genotoxicidade equívoca verificada para o NM-102 em células humanas expostas in vitro, não foi confirmada no modelo in vivo, pelo que o valor preditivo da utilização dos ensaios in vitro para a identificação de NMs com efeitos genotóxicos (e portanto potencialmente carcinogénicos) ainda tem de ser esclarecido antes de ser possível extrapolar as conclusões para a saúde humana. Por sua vez, como a informação aqui produzida pelas metodologias in vitro e in vivo não reflete os efeitos de exposição continua ou prolongada, que poderá conduzir a efeitos genotóxicos distintos, esta xxi deverá ser complementada com outras linhas de evidência relativamente à segurança dos NMs. Perante a incerteza dos níveis de exposição real do organismo humano e do ambiente, a segurança da utilização dos NMs não pode ser garantida a longo prazo e, tendo em conta a elevada produção e utilização destes NMs, são prementes futuros estudos de monitorização ambiental e humana.

A glycine-arginine domain in control of the human MRE11 DNA repair protein.

Human MRE11 is a key enzyme in DNA double-strand break repair and genome stability. Human MRE11 bears a glycine-arginine-rich (GAR) motif that is conserved among multicellular eukaryotic species. We investigated how this motif influences MRE11 function. Human MRE11 alone or a complex of MRE11, RAD50, and NBS1 (MRN) was methylated in insect cells, suggesting that this modification is conserved during evolution. We demonstrate that PRMT1 interacts with MRE11 but not with the MRN complex, suggesting that MRE11 arginine methylation occurs prior to the binding of NBS1 and RAD50. Moreover, the first six methylated arginines are essential for the regulation of MRE11 DNA binding and nuclease activity. The inhibition of arginine methylation leads to a reduction in MRE11 and RAD51 focus formation on a unique double-strand break in vivo. Furthermore, the MRE11-methylated GAR domain is sufficient for its targeting to DNA damage foci and colocalization with gamma-H2AX. These studies highlight an important role for the GAR domain in regulating MRE11 function at the biochemical and cellular levels during DNA double-strand break repair.

Effect of school based physical activity programme (KISS) on fitness and adiposity in primary schoolchildren: cluster randomised controlled trial.

To assess the effectiveness of a school based physical activity programme during one school year on physical and psychological health in young schoolchildren. Cluster randomised controlled trial. 28 classes from 15 elementary schools in Switzerland randomly selected and assigned in a 4:3 ratio to an intervention (n=16) or control arm (n=12) after stratification for grade (first and fifth grade), from August 2005 to June 2006. 540 children, of whom 502 consented and presented at baseline. Children in the intervention arm (n=297) received a multi-component physical activity programme that included structuring the three existing physical education lessons each week and adding two additional lessons a week, daily short activity breaks, and physical activity homework. Children (n=205) and parents in the control group were not informed of an intervention group. For most outcome measures, the assessors were blinded. Primary outcome measures included body fat (sum of four skinfolds), aerobic fitness (shuttle run test), physical activity (accelerometry), and quality of life (questionnaires). Secondary outcome measures included body mass index and cardiovascular risk score (average z score of waist circumference, mean blood pressure, blood glucose, inverted high density lipoprotein cholesterol, and triglycerides). 498 children completed the baseline and follow-up assessments (mean age 6.9 (SD 0.3) years for first grade, 11.1 (0.5) years for fifth grade). After adjustment for grade, sex, baseline values, and clustering within classes, children in the intervention arm compared with controls showed more negative changes in the z score of the sum of four skinfolds (-0.12, 95 % confidence interval -0.21 to -0.03; P=0.009). Likewise, their z scores for aerobic fitness increased more favourably (0.17, 0.01 to 0.32; P=0.04), as did those for moderate-vigorous physical activity in school (1.19, 0.78 to 1.60; P<0.001), all day moderate-vigorous physical activity (0.44, 0.05 to 0.82; P=0.03), and total physical activity in school (0.92, 0.35 to 1.50; P=0.003). Z scores for overall daily physical activity (0.21, -0.21 to 0.63) and physical quality of life (0.42, -1.23 to 2.06) as well as psychological quality of life (0.59, -0.85 to 2.03) did not change significantly. A school based multi-component physical activity intervention including compulsory elements improved physical activity and fitness and reduced adiposity in children. Trial registration Current Controlled Trials ISRCTN15360785.

Trigger and data link system for CMS Resistive Plate Chambers at the LHC accelerator

The purpose of the work was to realize a high-speed digital data transfer system for RPC muon chambers in the CMS experiment on CERN’s new LHC accelerator. This large scale system took many years and many stages of prototyping to develop, and required the participation of tens of people. The system interfaces to Frontend Boards (FEB) at the 200,000-channel detector and to the trigger and readout electronics in the control room of the experiment. The distance between these two is about 80 metres and the speed required for the optic links was pushing the limits of available technology when the project was started. Here, as in many other aspects of the design, it was assumed that the features of readily available commercial components would develop in the course of the design work, just as they did. By choosing a high speed it was possible to multiplex the data from some the chambers into the same fibres to reduce the number of links needed. Further reduction was achieved by employing zero suppression and data compression, and a total of only 660 optical links were needed. Another requirement, which conflicted somewhat with choosing the components a late as possible was that the design needed to be radiation tolerant to an ionizing dose of 100 Gy and to a have a moderate tolerance to Single Event Effects (SEEs). This required some radiation test campaigns, and eventually led to ASICs being chosen for some of the critical parts. The system was made to be as reconfigurable as possible. The reconfiguration needs to be done from a distance as the electronics is not accessible except for some short and rare service breaks once the accelerator starts running. Therefore reconfigurable logic is extensively used, and the firmware development for the FPGAs constituted a sizable part of the work. Some special techniques needed to be used there too, to achieve the required radiation tolerance. The system has been demonstrated to work in several laboratory and beam tests, and now we are waiting to see it in action when the LHC will start running in the autumn 2008.

Car Crash

A student crashes a car through the main entrance of Brock University and ransacks the office of the University President. The Buick La Sabre is driven through the glass doors of the Schmon Tower in the early morning, just as staff are beginning to report for work. The occupant of the vehicle proceeds to the tower's thirteenth floor, where he overturns furniture in the President's offices and breaks windows. University officials find him sitting in the President's chair, claiming he is God or Jesus.

Kierkegaard : the temporality of becoming a self

Introduction In Difference and Repetition, Deleuze compares and contrasts Kierkegaard's and Nietzsche's ideas of repetition. He argues that neither of them really give a representation of repetition. Repetition for them is a sort of selective task: the way in which they determine what is ethical and eternal. With Nietzsche, it is a theater of un belie f. ..... Nietzsche's leading idea is to found the repetition in the etemal return at once on the death of God and the dissolution of the self But it is a quite different alliance in the theater of faith: Kierkegaard dreams of alliance between a God and a self rediscovered. I Repetition plays a theatrical role in their thinking. It allows them to dramatically stage the interplay of various personnae. Deleuze does give a positive account ofKierkegaard's "repetition"; however, he does not think that Kierkegaard works out a philosophical model, or a representation of what repetition is. It is true that in the book Repetition, Constantin Constantius does not clearly and fully work out the concept of repetition, but in Sickness Unto Death, Kierkegaard gives a full explanation of the self and its temporality which can be connected with repetition. When Sickness Unto Death is interpreted according to key passages from Repetition and The Concept of Anxiety, a clear philosophical concept of repetition can be established. In my opinion, Kierkegaard's philosophy is about the task of becoming a self, and I will be attempting to show that he does have a model of the temporality of self-becoming. In Sickness Unto Death, Kierkegaard explains his notions of despair with reference to sin, self, self-becoming, faith, and repetition. Despair is a sickness of the spirit, of the self, and accordingly can take three forms: in despair not to be conscious of having a self (not despair in the strict sense); in despair not to will to be oneself; in despair to will to be oneself2 In relation to this definition, he defines a self as "a relation that relates itself to itself and in relating itself to itself relates to another.''3 Thus, a person is a threefold relationship, and any break in that relationship is despair. Despair takes three forms corresponding to the three aspects of a self s relation to itself Kierkegaard says that a selfis like a house with a basement, a first floor, and a second floor.4 This model of the house, and the concept of the stages on life's way that it illustrates, is central to Kierkegaard's philosophy. This thesis will show how he unpacks this model in many of his writings with different concepts being developed in different texts. His method is to work with the same model in different ways throughout his authorship. He assigns many of the texts to different pseudonyms, but in this thesis we will treat the model and the related concepts as being Kierkegaard's and not only the pseudonyms. This is justified as our thesis will show this modelremains the same throughout Kierkegaard's work, though it is treated in different ways by different pseudonyms. According to Kierkegaard, many people live in only the basement for their entire lives, that is, as aesthetes ("in despair not to be conscious of having a self'). They live in despair of not being conscious of having a self They live in a merely horizontal relation. They want to get what they desire. When they go to the first floor, so to speak, they reflect on themselves and only then do they begin to get a self In this stage, one acquires an ideology of the required and overcomes the strict commands of the desired. The ethical is primarily an obedience to the required whereas the aesthetic is an obedience to desire. In his work Fear and Trembling (Copenhagen: 1843), Johannes de Silentio makes several observations concerning this point. In this book, the author several times allows the desired ideality of esthetics to be shipwrecked on the required ideality of ethics, in order through these collisions to bring to light the religious ideality as the ideality that precisely is the ideality of actuality, and therefore just as desirable as that of esthetics and not as impossible as the ideality of ethics. This is accomplished in such a way that the religious ideality breaks forth in the dialectical leap and in the positive mood - "Behold all things have become new" as well as in the negative mood that is the passion of the absurd to which the concept "repetition" corresponds.s Here one begins to become responsible because one seeks the required ideality; however, the required ideality and the desired ideality become inadequate to the ethical individual. Neither of them satisfy him ("in despair not to will to be oneself'). Then he moves up to the second floor: that is, the mystical region, or the sphere of religiousness (A) ("despair to will to be oneself). Kiericegaard's model of a house, which is connected with the above definition ofdespair, shows us how the self arises through these various stages, and shows the stages of despair as well. On the second floor, we become mystics, or Knights of Infinite Resignation. We are still in despair because we despair ofthe basement and the first floor, however, we can be fiill, free persons only ifwe live on all the floors at the same time. This is a sort of paradoxical fourth stage consisting of all three floors; this is the sphere of true religiousness (religiousness (B)). It is distinguished from religiousness (A) because we can go back and live on all the floors. It is not that there are four floors, but in the fourth stage, we live paradoxically on three at once. Kierkegaard uses this house analogy in order to explain how we become a self through these stages, and to show the various stages of despair. Consequently, I will be explaining self-becoming in relation to despair. It will also be necessary to explain it in relation to faith, for faith is precisely the overcoming of despair. After explaining the becoming of the self in relation to despair and faith, I will then explain its temporality and thereby its repetition. What Kierkegaard calls a formula, Deleuze calls a representation. Unfortunately, Deleuze does not acknowledge Kierkegaard's formula for repetition. As we shall see, Kierkegaard clearly gives a formula for despair, faith, and selfbecoming. When viewed properly, these formulae yield a formula for repetition because when one hasfaith, the basement, firstfloor, and secondfloor become new as one becomes oneself The self is not bound in the eternity ofthe first floor (ethical) or the temporality of the basement (aesthete). I shall now examine the two forms of conscious despair in such a way as to point out also a rise in the consciousness of the nature of despair and in the consciousness that one's state is despair, or, what amounts to the same thing and is the salient point, a rise in the consciousness of the self The opposite to being in despair is to have faith. Therefore, the formula set forth above, which describes a state in which there is not despair at all, is entirely correct, and this formula is also the formula for faMi in ^elating itself to itself and in willing to be itself, the self rests transparently in the power that established it.

Development of hypogene and supergene alteration and copper mineralization patterns, Sar Cheshmeh porphyry copper deposits, Iran /

The formation of the Sar Cheshmeh porphyry Cu-Mo deposit is related to the culmination of calc-alkaline igneous activity in the Kerman region. The deposit comprises a suite of Late Cenozoic intrusive sub-volcanic and extrusive rocks emplaced into a folded series of Eocene andesitic lavas and pyroclastic sediments. The earliest stage of magmatism was emplacement of a large granodiorite stock about 29 m.y.b.p. This was followed by intrusion of two separate porphyritic bodies at 15 (Sar Cheshrneh porphyry) and 12 m.y.b.p. (Late porphyry) and a series of sub-volcanic dikes between 12 and 9 m.y.b.p. Magmatic activity terminated with multi-phase extrusion of a Pelean dacitic dome complex between 10 and 2.8 m.y.b.p. The country rocks and the earlier porphyritic intrusions are pervasively altered to biotite-rich potassium silicate (metasomatic and hydrothermal) sericite-clay, phyllic and chlorite-clay, argillic assemblages. These grade outwards to an extensive propylitic zone. Within the ore body, the later intra-. and post-mineral dikes only reach the propylitic grade. At least three different sets of quartz veins are present, including a sericite-chlorite-quartz set which locally retrogrades pervasive secondary biotite to sericite. In the hypogene zone, metasomatic and hydrothermal alteration is related to all stages of magmatism but copper mineralization and veining are restricted to a period of 15 to 9 m.y.b.p.related to the early intrusive phases. The copper mineralization and silicate alteration do not fit a simple annular ring model but have been greatly modified by, 1. The existence of an ititial, outer ring, of metasomatic alteration overprinted by an inner.ring of hydrothermal alteration and, 2. later extensive dilating effects of intra- and post-mineral dikes. The hydrothermal clay mineral assemblage in the hypogene zone is illite-chlorite-kaolinite-smectite (beidellite). Preliminary studies indicate that the amount of each of these clays varies vertically and that hydrothermal zonation of clay minerals is possible. However, these minerals alter to illite-kaolinite assemblages in the supergene sulfide zone and to more kaolinite-rich assemblages in the supergene leached zone. Hydrothermal biotite breaks down readily in the supergene zone and is not well preserved in surface outcrops. The distribution of copper minerals in the supergene sulfide enrichment zone is only partly related to rock type being more dependent on topography and the availability of fractures.

The determination of sinigrin in Brassica, and investigations into the use of allyl-isothiocyanate as a nematicide

The goal of this thesis was to study factors related to the development of Brassica juncea as a sustainable nematicide. Brassica juncea is characterized by the glycoside (glucosinolate) sinigrin. Various methods were developed for the determination of sinigrin in Brassica juncea tissue extracts. Sinigrin concentrations in plant tissues at various stages of growth were monitored. Sinigrin enzymatically breaks down into allylisothiocyanate (AITC). AITC is unstable in aqueous solution and degradation was studied in water and in soil. Finally, the toxicity of AITC against the root-lesion nematode (Pratylenchus penetrans) was determined. A method was developed to extract sinigrin from whole Brassica j uncea tissues. The optimal time of extraction wi th boiling phosphate buffer (0.7mM, pH=6.38) and methanol/water (70:30 v/v) solutions were both 25 minutes. Methanol/water extracted 13% greater amount of sinigrin than phosphate buffer solution. Degradation of sinigrin in boiling phosphate buffer solution (0.13%/minute) was similar to the loss of sinigrin during the extraction procedure. The loss of sinigrin from boiling methanol/water was estimated to be O.Ol%/minute. Brassica juncea extract clean up was accomplished by an ion-pair solid phase extraction (SPE) method. The recovery of sinigrin was 92.6% and coextractive impurities were not detected in the cleaned up extract. Several high performance liquid chromatography (HPLC) methods were developed for the determination of sinigrin. All the developed methods employed an isocratic mobile phase system wi th a low concentration of phosphate buffer solution, ammonium acetate solution or an ion-pair reagent solution. A step gradient system was also developed. The method involved preconditioning the analytical column with phosphate buffer solution and then switching the mobile phase to 100% water after sample injection.Sinigrin and benzyl-glucosinolate were both studied by HPLC particle beam negative chemical ionization mass spectrometry (HPLCPB- NCI-MS). Comparison of the mass spectra revealed the presence of fragments arising from the ~hioglucose moiety and glucosinolate side-chain. Variation in the slnlgrin concentration within Brassica juncea plants was studied (Domo and Cutlass cuItivars). The sinigrin concentration in the top three leaves was studied during growth of each cultivar. For Cutlass, the minimum (200~100~g/g) and maximum (1300~200~g/g) concentrations were observed at the third and seventh week after planting, respectively. For Domo, the minimum (190~70~g/g) and maximum (1100~400~g/g) concentrations were observed at the fourth and eighth week after planting, respectively. The highest sinigrin concentration was observed in flower tissues 2050±90~g/g and 2300±100~g/g for Cutlass and Domo cultivars, respectively. Physical properties of AITC were studied. The solubility of AITC in water was determined to be approximately 1290~g/ml at 24°C. An HPLC method was developed for the separation of degradation compounds from aqueous AITC sample solutions. Some of the degradation compounds identified have not been reported in the literature: allyl-thiourea, allyl-thiocyanate and diallyl-sulfide. In water, AITC degradation to' diallyl-thiourea was favored at basic pH (9.07) and degradation to diallyl-sulfide was favored at acidic pH (4 . 97). It wap necessary to amend the aqueous AITC sample solution with acetonitrile ?efore injection into the HPLC system. The acetonitrile amendment considerably improved AITC recovery and the reproducibility of the results. The half-life of aqueous AITC degradation at room temperature did not follow first-order kinetics. Beginning with a 1084~g/ml solution, the half-life was 633 hours. Wi th an ini tial AITC concentration of 335~g/ml the half-life was 865 hours. At 35°C the half-life AITC was 76+4 hours essentially independent of the iiisolution pH over the range of pH=4.97 to 9.07 (1000~g/ml). AITC degradation was also studied in soil at 35°C; after 24 hours approximately 75% of the initial AITC addition was unrecoverable by water extraction. The ECso of aqueous AITC against the root-lesion nematode (Pratylenchus penetrans) was determined to be approximately 20~g/ml at one hour exposure of the nematode to the test solution. The toxicological study was also performed with a myrosinase treated Brassica juncea extract. Myrosinase treatment of the Brassica juncea extract gave nearly quantitative conversion of sinigrin into AITC. The myrosinase treated extract was of the same efficacy as an aqueous AITC solution of equivalent concentration. The work of this thesis was focused upon understanding parameters relevant to the development of Brassica juncea as a sustainable nematicide. The broad range of experiments were undertaken in support of a research priority at Agriculture and Agri-Food Canada.

Dr. Stuart D. Scott Papers, 1837-2010 (non-inclusive)

Dr. Stuart D. Scott has written extensively in the fields of prehistory and history. As an archaeologist, he has traveled to some of the most significant sites in the world, including Pompeii, Stonehenge, the Valley of the Kings, Egypt’s pyramids and the Taj Mahal. He spent nine months excavating with the Tikal Project in Guatemala before returning to the University of Arizona where he received a Ph.D. in 1963. He excavated in New Zealand as a Fulbright scholar in 1963-1964. In the fall of 1964, Dr. Scott started a long career in the Anthropology Department of the State University of New York. He taught graduate and undergraduate archaeology courses and continued his archaeological and historical research. In 1979, Scott established the Old Fort Niagara Archaeology in Progress Project at Old Fort Niagara in Youngstown, New York. For many years, he became involved with historical archaeology in western New York. It was during this work that he became interested in the Upper Canada Rebellion of 1837-1838 and its aftermath. Dr. Scott and his wife, Patricia Kay Scott, would use Christmas breaks, summer vacations, and sabbatical years to travel. They were repeatedly lured back to the South Pacific, conducting research in New Zealand, Australia and many of the Micronesian and Polynesian islands. To tell the whole story of the Rebellion and the prison exiles, they traveled extensively in Canada, the United States, England and Tasmania to collect archival research and to experience the scenes of this remarkable narrative. In 2004, Dr. Scott published To the Outskirts of Habitable Creation: Americans and Canadians Transported to Tasmania in the 1840s, which told the story of the men captured, tried, convicted, and exiled as a result of the Rebellion, also called the Patriot War. Other contributions include: • A collaboration with Dr. Charles Cazeau on the book Exploring the Unknown, Great Mysteries Reexamined published by Plenum Press in 1979 • The Patriot Game: New Yorkers and the Canadian Rebellion of 1837-1838, which appeared in New York History, Vol. 68, No.3. 1987 • A Frontier Spirit: The Life of James Gemmell published in Australiasian Canadian Studies, Vol. 25, No. 2 2007 • To the Outskirts of Habitable Creation which appeared in the Friends of the National Archives, Vol. 20, No. 1 2009 • Numerous academic journal publications • Service on conference panels • Various research papers and proposals Before retiring in 1997 and while still a resident of Buffalo, N.Y., Dr. Scott spent considerable time with Brock University President Emeritus James A. Gibson and History Professor Colin Duquemin. The three shared a love of Rebellion history. It was largely because of this connection that Brock University was chosen as the recipient of Dr. Scott’s research materials.

Elementary School Principals as Leaders of Inclusion for Students With Exceptionalities

Inclusion promotes equality, provides opportunities, breaks down barriers, and ensures accessibility for all members of a community. Consequently, elementary-school administrators should become inclusion leaders who introduce and maintain inclusive learning environments. This qualitative study profiled and discussed practices and beliefs of 4 elementary school principals in southern Ontario who are recognized leaders of inclusion for students with exceptionalities. The researcher used multiple instruments for triangulation, thematic qualitative data analysis (constant comparative method) of interview responses and reflective field notes, and data from the Principal and Inclusion Survey to interpret qualitative findings. Findings revealed distinct leadership profiles reflective of empathy and compassion among participants who all regard accommodation of students with exceptionalities as a moral obligation and view inclusion as a socially just pedagogical framework. The researcher recommends that senior school board administrators screen and secure principals who value inclusion to create and maintain school cultures that ensure students’ access to inclusive education.

We need to have a conversation about OpenURL, a close look at a corpus of error reports from the 2013 academic year. Or, How I learned to stop worrying and give up on clean metadata.

Presented at Access 2014, winner of poster contest.

Are Idiosyncratic Skewness and Idiosyncratic Kurtosis Priced?

This thesis investigates the pricing effects of idiosyncratic moments. We document that idiosyncratic moments, namely idiosyncratic skewness and idiosyncratic kurtosis vary over time. If a factor/characteristic is priced, it must show minimum variation to be correlated with stock returns. Moreover, we can identify two structural breaks in the time series of idiosyncratic kurtosis. Using a sample of US stocks traded on NYSE, AMEX and NASDAQ markets from January 1970 to December 2013, we run Fama-MacBeth test at the individual stock level. We document a negative and significant pricing effect of idiosyncratic skewness, consistent with the finding of Boyer et al. (2010). We also report that neither idiosyncratic volatility nor idiosyncratic kurtosis are consistently priced. We run robustness tests using different model specifications and period sub-samples. Our results are robust to the different factors and characteristics usually included in the Fama-MacBeth pricing tests. We also split first our sample using endogenously determined structural breaks. Second, we divide our sample into three equal sub-periods. The results are consistent with our main findings suggesting that expected returns of individual stocks are explained by idiosyncratic skewness. Both idiosyncratic volatility and idiosyncratic kurtosis are irrelevant to asset prices at the individual stock level. As an alternative method, we run Fama-MacBeth tests at the portfolio level. We find that idiosyncratic skewness is not significantly related to returns on idiosyncratic skewness-sorted portfolios. However, it is significant when tested against idiosyncratic kurtosis sorted portfolios.

Are Idiosyncratic Skewness and Idiosyncratic Kurtosis Priced?

This thesis investigates the pricing effects of idiosyncratic moments. We document that idiosyncratic moments, namely idiosyncratic skewness and idiosyncratic kurtosis vary over time. If a factor/characteristic is priced, it must show minimum variation to be correlated with stock returns. Moreover, we can identify two structural breaks in the time series of idiosyncratic kurtosis. Using a sample of US stocks traded on NYSE, AMEX and NASDAQ markets from January 1970 to December 2013, we run Fama-MacBeth test at the individual stock level. We document a negative and significant pricing effect of idiosyncratic skewness, consistent with the finding of Boyer et al. (2010). We also report that neither idiosyncratic volatility nor idiosyncratic kurtosis are consistently priced. We run robustness tests using different model specifications and period sub-samples. Our results are robust to the different factors and characteristics usually included in the Fama-MacBeth pricing tests. We also split first our sample using endogenously determined structural breaks. Second, we divide our sample into three equal sub-periods. The results are consistent with our main findings suggesting that expected returns of individual stocks are explained by idiosyncratic skewness. Both idiosyncratic volatility and idiosyncratic kurtosis are irrelevant to asset prices at the individual stock level. As an alternative method, we run Fama-MacBeth tests at the portfolio level. We find that idiosyncratic skewness is not significantly related to returns on idiosyncratic skewness-sorted portfolios. However, it is significant when tested against idiosyncratic kurtosis sorted portfolios.

Simulation-Based Finite-Sample Tests for Heteroskedasticity and ARCH Effects.

A wide range of tests for heteroskedasticity have been proposed in the econometric and statistics literature. Although a few exact homoskedasticity tests are available, the commonly employed procedures are quite generally based on asymptotic approximations which may not provide good size control in finite samples. There has been a number of recent studies that seek to improve the reliability of common heteroskedasticity tests using Edgeworth, Bartlett, jackknife and bootstrap methods. Yet the latter remain approximate. In this paper, we describe a solution to the problem of controlling the size of homoskedasticity tests in linear regression contexts. We study procedures based on the standard test statistics [e.g., the Goldfeld-Quandt, Glejser, Bartlett, Cochran, Hartley, Breusch-Pagan-Godfrey, White and Szroeter criteria] as well as tests for autoregressive conditional heteroskedasticity (ARCH-type models). We also suggest several extensions of the existing procedures (sup-type of combined test statistics) to allow for unknown breakpoints in the error variance. We exploit the technique of Monte Carlo tests to obtain provably exact p-values, for both the standard and the new tests suggested. We show that the MC test procedure conveniently solves the intractable null distribution problem, in particular those raised by the sup-type and combined test statistics as well as (when relevant) unidentified nuisance parameter problems under the null hypothesis. The method proposed works in exactly the same way with both Gaussian and non-Gaussian disturbance distributions [such as heavy-tailed or stable distributions]. The performance of the procedures is examined by simulation. The Monte Carlo experiments conducted focus on : (1) ARCH, GARCH, and ARCH-in-mean alternatives; (2) the case where the variance increases monotonically with : (i) one exogenous variable, and (ii) the mean of the dependent variable; (3) grouped heteroskedasticity; (4) breaks in variance at unknown points. We find that the proposed tests achieve perfect size control and have good power.

Computation and Analysis of Multiple Structural-Change Models

In a recent paper, Bai and Perron (1998) considered theoretical issues related to the limiting distribution of estimators and test statistics in the linear model with multiple structural changes. In this companion paper, we consider practical issues for the empirical applications of the procedures. We first address the problem of estimation of the break dates and present an efficient algorithm to obtain global minimizers of the sum of squared residuals. This algorithm is based on the principle of dynamic programming and requires at most least-squares operations of order O(T 2) for any number of breaks. Our method can be applied to both pure and partial structural-change models. Secondly, we consider the problem of forming confidence intervals for the break dates under various hypotheses about the structure of the data and the errors across segments. Third, we address the issue of testing for structural changes under very general conditions on the data and the errors. Fourth, we address the issue of estimating the number of breaks. We present simulation results pertaining to the behavior of the estimators and tests in finite samples. Finally, a few empirical applications are presented to illustrate the usefulness of the procedures. All methods discussed are implemented in a GAUSS program available upon request for non-profit academic use.