Dissertations / Theses on the topic 'Evidence accumulation'

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Using firm-level data from an administrative Brazilian dataset, I document a few stylized facts regarding capital stock accumulation patterns and investment decisions. Finding evidence largely in favor of micro-level lumpiness of investment as it was found for American firms, I document that there are a few particularities in the behavior of Brazilian firms. First, I document that the distribution of the growth rate of capital is more dispersed, with “fatter” tails. Second, I also show that, as economic activity, the volume of investment and capital stock are more concentrated on a small number of firms, micro-level lumpiness might have a bigger role in understanding aggregate movements. Third, I show that the observable characteristics of Brazilian firms explain a lot more of sudden movements in capital growth when compared to the U.S., after controlling for industry specific characteristics and other variables. Fourth and last, I compute statistical measures related to the investment rate distribution, which show that investment at the firm-level seems to be even “lumpier” in Brazil, with firms investing less on average, while experiencing more episodes of investment spikes and periods of inaction.

Cortical circuits combine new inputs with ongoing activity during a variety of behaviors, including evidence accumulation during decision-making. However, the neural circuit mechanisms underlying how populations of neurons perform the computations necessary for this process and the dynamics which govern how neuronal populations change from moment-to-moment during evidence accumulation remain unclear. Here, we trained mice to perform several novel virtual-navigation decision tasks, including one which requires the accumulation of multiple, discrete evidence cues. As mice accumulated evidence, the posterior parietal cortex (PPC) transitioned between distinguishable and largely uncorrelated activity patterns, often involving mostly different sets of active neurons from moment-to-moment. These activity patterns contained task-relevant information distributed across the neuronal population. Because animals make decisions on single trials, we chose to analyze these activity patterns on a trial-by-trial basis. As single trials unfolded, each event — whether a new evidence cue or a behavioral choice — modified the dynamics of the PPC for seconds, even across trials. These events did not change the tonic activity of a specific set of neurons; rather, each event altered the probabilities that govern how one activity pattern transitions to the next, constraining the possible future patterns of activity. Thus, representations of ongoing events were influenced both by the sequence of previous evidence cues within the current trial and by the outcome of the previous trial, thereby generating multiple distinguishable activity patterns for the same level of accumulated evidence. These observations suggest that evidence accumulation does not rely upon the explicit competition between groups of neurons (as would be predicted by winner-take-all models), but instead reflects dynamical properties of the PPC that may instantiate a form of short-term memory consistent with reservoir computing.
Medical Sciences

Kyoto University (京都大学)
0048
新制・課程博士
博士(経済学)
甲第11126号
経博第196号
新制||経||194(附属図書館)
22695
UT51-2004-R2
京都大学大学院経済学研究科経済システム分析専攻
(主査)教授 藤田 昌久, 助教授 森 知也, 助教授 文 世一
学位規則第4条第1項該当

Reconstructed snow accumulation rate observations from five new firn cores show a statistically significant negative trend in accumulation rates over the past four decades across the central West Antarctic ice sheet. A negative temporal trend in accumulation is unexpected in light of rising surface temperatures and simulations run by GCMs. Both the magnitude of the mean accumulation rates and the range of interannual variability observed in the new records compares favorably to older records, suggesting that the new accumulation rate records may serve as a regional proxy for recent temporal trends in West Antarctic accumulation rates. The observed negative trend is likely the result of Southern Hemisphere high-latitude internal atmospheric dynamics, dominated by changes in the austral fall season. The well-documented positive trend in the Southern Annular Mode causes a low pressure center to form over the Amundsen Sea, which in turn produces lower accumulation rates across the western portion of the West Antarctic ice sheet. The new accumulation rate records are compared to several models/reanalyses to test the skill of simulated accumulation rate predictions. While the models/reanalyses and the new observations agree well in both mean and variability, the simulated records do not capture the full negative trend observed in the reconstructed records.

PONTIFÍCIA UNIVERSIDADE CATÓLICA DO RIO DE JANEIRO
COORDENAÇÃO DE APERFEIÇOAMENTO DO PESSOAL DE ENSINO SUPERIOR
PROGRAMA DE SUPORTE À PÓS-GRADUAÇÃO DE INSTS. DE ENSINO
Esta dissertação estuda se existem heterogeneidades no processo de acumulação de capital humano durante o trabalho. Utilizando microdados em painel da RAIS e a descrição de ocupações com base em suas tarefas, nós propomos o conceito de experiência em tarefas em equações de salário. Primeiro, apresentamos um modelo no qual retorno a experiência é heterogêneo entre trabalhadores. Depois, nós estimamos a equação de salário interpretando o retorno a experiência como a taxa média na qual trabalhadores transformam o tempo em trabalhos passados em produtividade no trabalho corrente. Os resultados mostram, de forma robusta, que o parâmetro associado à experiência analítica é maior que os parâmetros associados à experiência rotineira, por exemplo. Nosso modelo ajuda a compreender a importância e limitações deste resultado.
This dissertation studies if there are heterogeneities in the human capital accumulation process while on the job. Using unique Brazilian employer-employee panel data and task description of fourdigit occupations, we propose the concept of task experience in log wage equations. We first present a model in which returns to experience are heterogeneous across workers. Then, we estimate the log-wage equations interpreting the returns to experience as the average rate in which workers have their time at past work transformed into productivity in the current job. The results robustly show that the parameter related to analytical experience is greater than the parameters related to routine or other task experiences. Our model helps understanding the importance and limitations of these findings.

This is an analysis of the investment behaviour of Turkish firms at the aggregate and sectoral levels. Despite the growing literature of empirical private investment studies, a theory-based approach to modelling investment is rare both for developing countries in general and for Turkey in particular. One of the most commonly used modelling strategies is to adapt the main elements of the neoclassical accelerator model subject to additional structural modifications for a developing country. However, many of these studies are eclectic in the sense that they are not based on any specification of the microeconomic optimisation problem of firms. The central purpose of the thesis is to develop econometrically estimateable investment functions based on a sound microeconomic framework. This study theoretically examines both the investment behaviour of firms and the role of financial decisions in investment behaviour in earlier chapters. Subsequent empirical chapters are built upon the main findings of the theoretical chapters, and accommodate three empirical models, all of which originate from an explicit optimisation problem of a representative firm. The first empirical model is derived from the cost minimisation of the firm subject to a given level of demand in the output market and two alternative production technology assumptions (namely putty-putty and putty-clay assumptions). The second model recognises the presence of adjustment costs of the capital stock, and develops an error-correction representation of an investment model from an quadratic cost function minimisation. These first two models analyse the roles of the neoclassical determinants of investment (the accelerator and the relative cost of capital) and credit constraints resulting from imperfections in capital markets in Turkey. However, the inclusion of the financial variable is less sound in these two models. The significance of capital market imperfections in the forms of a rising cost schedule of borrowing and quantitative constraints is the subjects of the third model. A dynamic model is developed through a maximisation of the intertemporal discounted cash flow of a representative firm subject to capital market imperfections, borrowing constraints and capital adjustment costs. An Euler equation for the rate of capital accumulation is derived by re-arranging the first-order condition for capital, which is influenced by the binding borrowing constraint through an unobservable shadow price. These three models are applied to annual aggregate and sectoral data from Turkey. The empirical findings of this thesis suggest that fiscal and monetary policies influence investment behaviour both via the relative cost of capital and via credit availability to the private sector in Turkey. In particular, the empirical results imply that a high interest rate policy in an imperfect capital market imposing extra cost on the market rate through the risk premium may have discouraging effects on investment decisions either through its impact on the user cost of capital or through the risk premium component of cost of borrowing as in the third model. However, high interest rate policies may also affect credit availability as postulated in the McKinnon-Shaw hypothesis.

Thèse réalisée en cotutelle avec l'Université Européenne de Bretagne - Rennes 2
Alors que plusieurs auteurs ont souligné l’existence d’un contexte social relativement permissif pour expliquer l’ampleur de la coercition sexuelle dont sont victimes les femmes, cette thèse a privilégié un niveau d’analyse individuel. De concert avec une perspective interactionniste somme toute classique, il a alors été proposé que des facteurs situationnels puissent contribuer à actualiser des facteurs de risque individuels et, par ce biais, précipiter le passage à l’acte. L'objectif général de cette thèse était ainsi d'étudier expérimentalement les effets de l'alcool et de l'excitation sexuelle sur la perception du consentement et les intentions comportementales d'utiliser des stratégies coercitives pour avoir une relation sexuelle. Plus exactement, et afin d’étudier les effets de l’alcool sur la perception des intentions comportementales exprimées par une femme, un plan expérimental inter-participants a permis de répartir aléatoirement 150 participants, issus de la population générale, dans une condition Avec alcool ou dans une condition Sans alcool. La concentration d’alcool dans le sang visée était de 0,8 g/L (2,22 ml de vodka à 40 % par kg). Par la suite, les participants étaient à nouveau répartis aléatoirement dans l'une des deux modalités du facteur Excitation sexuelle, soit Avec excitation sexuelle et Sans excitation sexuelle. Un plan factoriel inter-participants 2x2 a alors permis d'étudier les effets de l'alcool et de l'excitation sexuelle sur le temps de latence pour indiquer qu'une femme n'est plus intéressée par avoir une relation sexuelle, ainsi que sur les intentions comportementales d’utiliser des stratégies coercitives non-violentes et de commettre un viol. Pour ce qui est de la perception des intentions comportementales, les résultats, obtenus à l’aide d’analyses de variance mixte, indiquent qu’il existe une difficulté à percevoir correctement une absence de consentement lorsqu’elle n’est pas exprimée avec suffisamment d’intensité. Toutefois, cette difficulté est indépendante des effets de l’alcool, dans la mesure où elle se manifeste aussi bien chez les hommes qui ont consommé de l’alcool que chez ceux qui n’ont pas consommé d’alcool. Pour ce qui est de l’identification d’une absence de consentement sexuel, les résultats, obtenus à l’aide de modèles de régression linaire multiple et de régression de Cox, indiquent qu’il existe un effet de l’alcool, mais que cet effet est modéré par les distorsions cognitives. Toutefois, si la consommation d’alcool contribue, chez les individus présentant des distorsions cognitives au-delà d’un certain niveau, à différer l’identification d’une absence de consentement sexuel, elle ne l’empêche pas. Enfin, les résultats, issus de modèles de régression linéaire multiple et logistique multiple, indiquent que l’effet de l’alcool sur les intentions comportementales d’utiliser des stratégies coercitives est également modéré (et conditionné) par le niveau de distorsions cognitives. Plus exactement, malgré la perception d’une absence de consentement sexuel, notamment lorsqu’elle est exprimée avec suffisamment d’intensité, les individus qui présentent un niveau particulièrement élevé de distorsions cognitives sont plus à risque d’utiliser des stratégies coercitives non-violentes en l’absence d’alcool, mais sont également plus à risque de commettre un viol lorsqu’ils ont consommé de l’alcool. Par ailleurs, les résultats indiquent que notre manipulation de l’excitation sexuelle pourrait avoir, au moins partiellement, échoué. De nouvelles études apparaissent ainsi nécessaires afin de comprendre le rôle éventuel de l’excitation sexuelle dans la perception du consentement et les intentions comportementales d’utiliser des stratégies coercitives pour avoir une relation sexuelle. Alors que ces résultats ouvrent la voie à de nouvelles recherches afin de mieux comprendre les processus et mécanismes par lesquels l’alcool peut, chez certains individus, contribuer à expliquer la coercition sexuelle, des implications pratiques peuvent également être proposées. Ainsi, si les résultats relatifs à la perception du consentement soutiennent l’importance de programmes de prévention primaire, voire situationnelle, les résultats relatifs aux intentions comportementales d’utiliser des stratégies coercitives soulignent que des programmes de prévention secondaire apparaissent également comme un élément indispensable d’une politique efficace de prévention de la coercition sexuelle.
While a relatively permissive social context has been argued to explain the extent of sexual coercion against women, this dissertation has favored an individual level of analysis. In accordance with a classic interactionist perspective, situational factors have been proposed to contribute to trigger individual risk factors and, therefore, precipitate sexual coercion. The overall objective of this dissertation was to experimentally study the effects of acute alcohol intoxication and sexual arousal on the perception of consent and on behavioral intentions to use coercive strategies to have sex. More precisely, a between-subjects design was used to study the effects of acute alcohol intoxication in men on their perception of a woman’s behavioral intents. The 150 participants, recruited from the general population, were thus randomized either in a condition With alcohol or in a condition Without alcohol. The targeted blood alcohol content was 0,08 % (2,22 ml of 40% alcohol-by-volume Absolut vodka per kg of body weight). Then, participants were once again randomized in one of the two levels of “Sexual arousal” factor: a condition With sexual arousal and a condition Without sexual arousal. A 2x2 between-subjects factorial design was thereby used to study the effects of acute alcohol intoxication and sexual arousal on the latency to indicate that a woman is no longer interested in having sex as well as on the behavioral intentions to use non-violent coercive strategies and to commit rape. First, in regards to the perception of a woman’s behavioral intents, the results of mixed ANOVAs indicate that there exists a difficulty in correctly perceiving an absence of consent if it is not expressed with sufficient intensity. However, this difficulty is independent of the effects of alcohol consumption, as participants in both conditions express this difficulty. Secondly, for the identification of an absence of sexual consent, results of multiple linear regressions and Cox regression indicate that alcohol consumption does have an effect, but this effect is moderated by cognitive distortions. Moreover, if alcohol consumption contributes to postpone the identification of an absence of sexual consent in participants with a higher level of cognitive distortions, it does not ultimately hinder it. Finally, results of multiple linear and multiple logistic regressions indicate that the effect of alcohol consumption on behavioral intentions to use coercive strategies to have sex is also moderated (and conditioned) by the level of cognitive distortions. Despite the fact that participants ultimately correctly perceive an absence of sexual consent, those with a higher level of cognitive distortions are more likely to use non-violent coercive strategies to have sex if no alcohol is consumed and, are also more likely to commit rape when they consume alcohol. Moreover, results indicate that our experimental manipulation of sexual arousal may have partially failed. New studies appear necessary in order to better understand the potential role of sexual arousal on the perception of consent and on behavioral intentions to use coercive strategies. While these results pave the way for new research in order to better understand the processes and mechanisms by which acute alcohol intoxication may help to explain sexual coercion in some individuals, practical implications must also be considered. While results related to the perception of consent support the relevance of primary and situational prevention, results related to behavioral intentions to use coercive strategies to have sex highlight the need for secondary prevention in order to develop an effective policy for sexual coercion prevention.

Si vous voulez prendre votre train à l'heure, vous devez estimer à quelle distance se trouve la gare et combien de temps vous allez mettre pour y aller. Plusieurs études ont montré qu'il existe des interactions dans la perception de différentes dimensions. En 2003, Walsh a suggéré que le Temps, l'Espace et les Nombres faisaient partie d'un système de magnitudes commun qui serait localisé dans le cortex pariétal. Dans cette thèse nous avons étudié l'existence d'un tel système. La manipulation de la magnitude de dimensions non-temporelles n'a pas interféré avec les jugements de durée. En revanche, l'estimation du nombre et de l'espace a été biaisée par le taux d'accumulation d'évidence sensorielle. Dans une première expérience nous avons cherché à savoir si un système de magnitudes basé sur des probabilités Bayesiennes nécessitait l'utilisation d'un " prior " unique, amodal, ou alors nécessitait plusieurs " priors ". D'un point de vue Bayesien, nos résultats indiquent que l'estimation de différentes dimensions requiert plusieurs " priors ", ce qui ne supporte pas l'existence d'un système de magnitude commun. Pour étudier l'effet du nombre sur l'estimation de la durée, nous avons effectué une seconde étude dans laquelle les participants devaient reproduire des intervalles de temps et également juger la valeur numérique du stimulus visuel. Les résultats ont montré que l'interaction temps-nombre dépend essentiellement du format numérique utilisé (symbolique ou non symbolique). Ces résultats suggèrent que la magnitude numérique est automatiquement traitée alors que des ressources attentionnelles sont requises lorsque l'information numérique est présentée symboliquement
If you want to catch your train on time you have to estimate how far the station is from your current position and how long it will take you to go there. A growing body of evidence suggests that interferences may exist in the perception of different magnitude dimensions. These relationships fascinate researchers for decades and led Walsh (2003) to hypothesize that Time, Space and Number were part of a generalized magnitude system which may be located in the parietal cortex. In this thesis, we first investigated the possible existence of such system. Manipulating non-temporal magnitude dimensions did not interfere with duration judgments. Instead, numerical and spatial estimates were biased when we manipulated the rate of accumulation of sensory evidence. In this first experiment we asked whether a generalized Bayesian magnitude estimation system would sample evidence using a common, amodal prior, as expected by a generalized magnitude system. Our results suggested that from a Bayesian perspective, computations would necessitate multiple priors. This work provides substantial evidence against the existence of a generalized magnitude system. To further investigate interferences of numerical magnitude on perceived duration, we built a second experiment in which participants were required to reproduce intervals of time and also judge the numerical magnitude of the stimulus. Our results revealed that the number-time interaction depended on the numerical format that was used. Our work suggests that the numerical magnitude is automatically processed at a non-symbolic level whereas it requires attentional resources when numerical information is symbolically conveyed

Le carcinome hepatocellulaire est l'un des cancers les plus mortels dans le monde, en raison notamment de l'inefficacite des traitements classiques et de la tumeur qui est rarement operable. En outre, il n'existe pas de marqueur fiable pour detecter de facon precoce les tumeurs chez des patients a risque atteints de cirrhose ou d'hepatite chronique. Dans le but d'identifier de nouveaux marqueurs du cancer du foie, nous avons etudie l'activite des glycosyltransferases et l'expression des proteines seriques dans un modele de carcinome hepatocellulaire chez des souris transgeniques exprimant specifiquement un oncogene viral dans les hepatocytes. Nous avons mis en evidence 3 marqueurs precoces du cancer du foie chez la souris : - une augmentation de l'activite de l'6 sialyltransferase (st6gal i) dans le foie et le serum des souris transgeniques. Cette augmentation est visible des le debut du developpement du carcinome et s'accentue au cours de la tumorisation. Elle est due a la surexpression du gene st6gal i au niveau de l'arnm dans le foie tumoral. - un enrichissement des structures 6-sialylees sur les glycoproteines du foie et du serum des souris malades, du a l'augmentation d'activite de la st6gal i ainsi qu'a une diminution de l'3 sialytransferase. - l'accumulation de la ceruloplasmine dans le serum des souris transgeniques. Cette glycoproteine, presente en faible quantite dans le sang des souris normales, est decelable par electrophorese en gel de polyacrylamide des le debut du developpement du cancer et sa concentration serique augmente au cours de la tumorisation. La quantite d'arnm de la ceruloplasmine n'est pas differente entre souris normales et transgeniques. L'accumulation de la ceruloplasmine dans le serum des souris malades est probablement due a une modification de la stabilite de son arnm. Nous avons donc identifie des marqueurs precoces du carcinome hepatocellulaire murin qui peuvent etre utiles a la comprehension des mecanismes de tumorisation du foie.

This Ph.D. thesis comprises of two parts. Part I develops a framework to provide insights into the understanding of several political macro-economy issues related to fiscal policy making. This framework links the overall macroeconomic performance to the public spending and borrowing decisions. The key feature of this framework is that it makes a distinction between productive (e.g. public investment) and non-productive public spending (e.g. popular spending). It is shown that a high level of political instability may lead to myopic and populist policies and may be associated with less favorable macroeconomic performance in terms of not only future output and inflation but also future popular spending. Part I also suggests an alternative channel for expansionary or Non-Keynesian fiscal contractions based on the productivity enhancing role of productive public spending. It is shown that if the incumbent government reduces popular (productive) spending rather than productive (popular) spending, then Non-Keynesian (Keynesian) effects are achieved. Furthermore, it is shown that the favorable effects of public investment depends positively on its quality in this framework. Moreover, the net effect of productive spending financed by borrowing on the next period'
s macroeconomic performance depends on the benefits of productive spending relative to the costs of borrowing. Even under a capital borrowing rule higher public investment may yield unfavorable effects and also it may not necessarily prevent the strategic use of public investment, even though it prevents strategic debt accumulation. Part II investigates the effects of macroeconomic instability on capital accumulation and economic growth in the Turkish economy over the 1963-1999 period. Descriptive and econometric (time series) analyses suggest that macroeconomic instability not only deters capital accumulation and economic growth but it may also reverse the complementarity between public and private investment in the long-run.

Esta tesis doctoral se ha llevado a cabo con la finalidad de explorar la espacialidad de las evidencias materiales preservadas en la superficie del palafito del Villaggio delle Macine. El yacimiento, fechado entre Bronce Antiguo final y Bronce Medio inicial, se localiza en la Italia central. Un aproche geoestadístico, aplicado al análisis espacial intra-site, ha proporcionado las herramientas necesarias para poder discernir el patrón observado. El mismo, podría estar reflejando o bien la distribución espacial originaria de las actividades sociales llevadas a cabo durante la última fase de ocupación del yacimiento o bien, podría ser el resultado de potenciales procesos post-depositacionales (Capítulo 1). Diferentes perspectivas han sido analizadas para así, dar solución a la pregunta principal. En los Capítulos 2 y 3 un detallado resumen de los procesos de formación y deformación del depósito arqueológico ha mostrado como estos son indispensables para la interpretación de los patrones espaciales. Numerosos ejemplos, procedentes de contextos arqueológicos de distintas localizaciones, han recalcado la magnitud del aproche; el Capítulo 3 se centra en exclusiva en el análisis de los procesos de formación y deformación que interesan (y afectan) a los palafitos. El enfoque interdisciplinar planteado en ambos Capítulos 2 y 3 ha permitido a los arqueólogos “viajar en el tiempo”, diseccionando el palimpsesto preservado, objeto del análisis. En los Capítulos 5 y 6 se presenta y contextualiza el yacimiento en el marco del Bronce medio de la Italia Central. Se reconstruye el entorno natural que acogió el palafito y los procesos que formaron parte de su formación (y potencial deformación), a través de un análisis biográfico. En el Capítulo 6 se presentan los artefactos (y ecofactos) hallados en excavaciones y prospecciones, describiendo por cada categoría los problemas relativos de conservación y la información arqueológica aportada. El análisis se centra en los hallazgos de las prospecciones que constituyen la base de datos tratada para esta tesis. Además en el Capítulo 6 se presenta también, una reflexión teórica sobre las prospecciones superficiales en relación a sus puntos fuertes y debilidades considerando los estudios anteriormente realizados. De esa manera es posible resaltar las dificultades que estas técnicas de investigación conllevan y sus potenciales limitaciones. La tercera sección de esta tesis se focaliza en el análisis intra-site y en la geoestadística (Capítulos 4, 7, 8 y 9). El protocolo analítico propuesto y unas reflexiones iniciales caracterizan el Capítulo 4, mientras que en el 7, 8 y 9 presentan los análisis (y sus interpretaciones) realizados según la campaña de prospección. Finalmente, en el Capítulo 10 se discuten los resultados obtenidos que nos permiten contestar a la pregunta principal expresada en el Capítulo 1. La hipótesis que considera el patrón espacial observado como resultado de procesos post-depositacionales puede ser rechazada. Por consiguiente, aunque estos procesos puedan haber modificado, parcialmente, el patrón espacial original algunos rastros nos permiten inferir respecto la organización del espacio en el yacimiento durante su última fase de ocupación.
This thesis is aimed to explore the spatiality of material evidence retrieved on the surface of the italian Bronze Age pile-dwelling of Villaggio delle Macine. A geostatistic approach, applied to intra-site spatial analysis, provides required tools to analyze the observed spatial pattern; this can mirror the original placement of social activities at the settlement during its last phase of occupation, or, conversely, it can be produced by potential post-depositional processes (Chapter 1). In an attempt to wondering such main question, different perspectives have been taken into account. Within Chapters 2 and 3 it is highlighted the importance of reconstruct the formation (and deformation) of the archaeological record, through a deepen analysis of the state of the art concerning this theme; supporting such assumption, several examples from different archaeological contexts scattered all over the world are introduced. In Chapter 3 this perspective is stressed focusing on lakeside settlement contexts. An interdisciplinary approach (Chapter 2 and 3) proved to allow archaeologists to “travel backward”, dissecting the preserved archaeological palimpsest under analysis. Chapters 5 and 6 are devoted to introduce and contextualize the site of Villaggio delle Macine in the framework of Middle Bronze Age in Central Italy, reconstructing the natural environment where the settlement has been hosted and the formation (and potential deformation) of the site itself, through a biographical approach (Chapter 5). Within Chapter 6, all categories of material evidence retrieved at the site during both excavations and surveys are described, highlighting, for each category, the issues related to their condition of preservation and the archaeological information derived from their analysis. Furthermore, a theoretical reflection concerning the surface surveys, in terms of their strengths and weakness, is introduced through a short summary of the state of the art. In this way further light is shed on the bias associated with archaeological surface surveys and their potential limitations. Finally, the dataset is extensively described in this chapter. The third section of this thesis is focused on the intra-site spatial analyses and geostatistics (Chapters 4, 7, 8 and 9). Theoretical reflections as well as the analytical procedure proposed there are described in Chapter 4, while Chapters 7, 8 and 9 are devoted to the detailed analyses performed for each survey campaigns. In Chapter 10 the discussion of all these results allows to wonder the main questions presented in Chapter 1; the starting null hypothesis which considered the observed spatial pattern as result of post-depositional processes can be rejected. Indeed, such disturbance could have provoked some spatial modification of the original pattern, but it is however preserved in such a way that allows reconstructing the organization of the space within the settlement during its last phase of occupation.

Thesis (Ph. D.)--University of Wisconsin--Madison, 1997.
Typescript. eContent provider-neutral record in process. Description based on print version record. Includes bibliographical references (leaves 177-186).

The major objectives of this research were to examine the bioaccumulation parameters [depuration rates (kd), half life (t1/2) and biomagnification factor (BMF)] of individual isomers of hexabromocyclododecane (HBCD, C12H18Br6) in fish and to test the hypothesis of in vivo bioisomerization. This was done by exposing three groups of juvenile rainbow trout (Oncorhynchus Mykiss) to food fortified with known concentrations of an individual diastereoisomer (α, β, γ) for 56 days (uptake phase) followed by 112 days (depuration phase) of unfortified food. A fourth group of fish were exposed to unfortified food for the duration of the experiment. Fish (n=4) from all four aquaria were sacrificed on days 0, 7, 14, 56, 63, 70, 112 and 168 and muscle tissue was extracted and analyzed for diastereoisomer concentrations by high performance liquid chromatography tandem mass spectrometry (LC/MS/MS). Bioaccumulation of the γ diastereoisomer was linear during the uptake phase while the α and β diastereoisomers were found to increase exponentially with respective doubling times of 14.1 and 20.5 days. Both the β and γ diastereoisomers followed first order depuration kinetics with calculated t1/2’s of 94 ± 25 and 84 ± 51 (± 1 × standard error) days, respectively. The BMF for the α diastereoisomer (BMF = 4.1) was one and a half times greater than the β-diastereoisomer (BMF = 2.6) and about one fifth larger than the γ-diastereoisomer (BMF = 3.6). The large BMF for the α diastereoisomer is consistent with this diastereoisomer dominating higher trophic level organisms in wildlife. Although the BMF of the β diastereoisomer suggests that it will biomagnify, because it is present in small quantities in commercial mixtures it is rarely detected in environmental samples. Results from these studies also provide evidence of bioisomerization of the β and γ diastereoisomers. Most importantly, the α diastereoisomer which was recalcitrant to bioisomerization by juvenile rainbow trout in this study and known to be the dominant diastereosiomer in fish, was bioformed from both the β and γ diastereoisomers. To our knowledge, this is the first report of bioisomerization of a halogenated organic pollutant in biota.
May 2006

Neurodegeneration with Brain Iron Accumulation (NBIA) disorders, such as Phospholipase A2G6-Associated Neurodegeneration (PLAN) and Pantothenate Kinase-Associated Neurodegeneration (PKAN), are a group of rare early-onset, genetic disorders characterized by neurodegeneration and iron accumulation inside of the basal ganglia (BG), which is accompanied by progressive motor symptoms. In order to address the limitations in available models of NBIA, a B6.C3-Pla2g6m1J/CxRwb mouse model of PLAN was characterized. This model demonstrated key hallmarks of the disease presentation in NBIA, including a severe and early-onset motor deficit, neurodegeneration inside of the substantia nigra (SN) including a loss of dopaminergic function and the formation of abnormal spheroid inclusions as well as iron accumulation. The capture of these hallmarks of NBIA makes this an ideal animal research model for NBIA. Additionally, exploration of candidate systemic biomarkers of NBIA was performed in a case study of a patient with PLAN and in a cohort of 30 patients with PKAN. These investigations demonstrated reductions in transfer and slight, but not significant elevations in soluble transferrin receptor. No significant difference was seen in serum iron parameters. A systemic disease burden including chronic oxidative stress; elevated malondialdehyde, and inflammation; elevated C-reactive protein (CRP), IL-6 and TNFα was noted in both investigations. A number of candidate protein biomarkers including: fibrinogen, transthyretin, zinc alpha-2 glycoprotein and retinol binding protein were also identified. These markers correlated with measures of the severity of iron loading in the globus pallidus (GP); based on R2* magnetic resonance imaging (MRI) and the severity of motor symptoms (Barry-Albright Dystonia Rating Scale) making them potential candidates markers of dysfunction in NBIA. In the patient with PLAN, 37 weeks of therapy with the iron chelator deferiprone (DFP) as well as 20 months of therapy with the antioxidants alpha lipoic acid (ALA) and n-acetylcysteine (NAC) were efficacious in reducing the systemic oxidative and inflammatory disease burden, but it did not significantly alter the progression of the disease. In the antioxidant therapy, this efficacy was primarily due to ALA. When the cohort of patients with PKAN were treated with DFP for 18 months it was highly efficacious in lowering brain iron accumulation in the GP. No significant reduction in the speed of disease progression was seen in DFP treated patients compared to placebo based on initial analysis. Similar to the PLAN patient, DFP also mitigated the systemic disease burden in PKAN patients. In both cases DFP was well tolerated and had minimal impact on serum iron levels, TIBC and transferrin saturation. Collectively these investigations provide valuable insights into disease progression in NBIA. They also provide tools to aid further investigations in NBIA. These are provided in the form of a well-characterized B6.C3-Pla2g6m1J/CxRwb model of PLAN, which robustly captures the disease presentation seen in patients, as well as a panel of systemic blood-based markers of disease burden in NBIA and candidate markers of dysfunction in NBIA. These markers were used to assess two novel therapies in NBIA chelation with DFP and antioxidant therapy with ALA and NAC.
Graduate
2019-04-19