Indiana University-Purdue University Indianapolis (IUPUI) / Indoleamine 2,3-dioxygenase (IDO) is a rate limiting enzyme in tryptophan catabolism that has been implicated in the pathogenesis of a number of diseases. Large interindividual variability in IDO activity in the absence of stimuli and as the result of therapy induced changes has been reported. This variability has the potential to contribute to susceptibility to disease and to interindividual variability in therapeutic response. To identify genetic variations that might contribute to interindividual variability in IDO activity, we resequenced the exons, intron/exon borders and 1.3 kb of the 5’-flanking region of the INDO gene in 48 African-American (AA) and 48 Caucasian-American (CA) subjects from the Coriell DNA Repository. A total of 24 INDO variants were identified. Seventeen of these were in exons, introns, or exon/intron boundries, while seven were within 1.3 kb upstream of the translation start site. Seventeen are novel and 7 were previously identified. When transiently expressed in COS-7 or HEK293 cells the amino acid sequence change in Arg77His resulted in significant decrease in activity, and it reduced the Vmax of IDO. The Arg77His variant and the 9 bp deletion resulted in nearly complete loss of enzyme activity and a lack of detectable protein expression. The function of the Arg77His variant IDO was restored in a dose dependent manner by the heme analog hemin; but there was no associated increase in IDO protein. Cellular heme concentration was higher in cells transfected with the wild type and Ala4Thr variant constructs, but not in cells transfected with the Arg77His variant. The heme synthesis inhibitor, succinylacetone (SA), blocked IDO activity in cells transfected with Arg77His. We identified 22 putative transcription binding sites within the 1.3 kb upstream of the translation start site. Two of the SNPs were located in GATA3 and FOXC1 sites. A specific 3-SNP haplotype reduced promoter activity when transiently transfected into 2 different cell lines. We conclude that there are naturally occurring genetic variants in the INDO gene which affect both expression and activity. These results make clear that interindividual variability in IDO activity at baseline or in response to therapy may be in part due to inherited genetic variability.

No description available.

Syftet med detta arbete är att ta reda på om läxor ger fördjupad kunskap inom ett ämne.Vidare vill vi veta vad syftet med läxor är. Vi har genomfört femton intervjuer, jämtfördelade mellan lärare, elever och föräldrar. Resultatet pekar på att läxor behövs, men atteleverna vill ha en annan typ av hemuppgifter än de i nuläget har. Vi genomförde ävenmindre studie på sex av våra egna barn för att få veta hur mycket tid de trodde sig läggapå sina läxor och hur lång tid de i verkligheten ägnade åt läxläsning. Vår slutsats är attom läxor ges, ska de vara väl genomtänkta och att det kan skapas utrymme för att göraläxorna under skoldagen.Nyckelord: läxor, kreativitet, individ, variation

Mémoire numérisé par la Direction des bibliothèques de l'Université de Montréal.

This thesis contributes to the discussion of register variation within Egyptian Arabic by focusing on the usage of verbs in blogs and transcripts of movies and television. Register variation has been extensively researched for English as well as several other languages; yet, the lexical and grammatical features that distinguish registers of Egyptian Arabic have not been analyzed. Several challenges have prevented such an analysis, among them the perceived lack of an automatic annotator and the uncertainty of results. In order to overcome these challenges, two corpora were compiled: one containing texts from blogs and the other transcripts of movies and television shows. With each corpus representing a potential register of the dialect, the verbs in each corpus were lemmatized and semi-automatically annotated for either aspect or mood. The verbs were then counted according to lemma, aspect, and mood in order to determine the extent of variance between the two corpora. The effectiveness of the state-of-the-art automatic annotator was also evaluated by comparing the counts it provided to those produced from corrections of its output. This thesis found that verbs are in fact used differently in the two corpora suggesting register variation and identified potential verbal features characteristic of each register. It also found that the automatic tagger produced counts that lead to the same conclusions as the corrected annotation.

Ecosystems and their components (e.g., organisms, physicochemical variables) are dynamic in space and time. This dynamism makes ecological change notoriously difficult to study and manage. This thesis therefore aims to develop new ways of using spatiotemporal information for inference and prediction. Applying theoretical and statistical concepts to patterns of spatiotemporal variation in aquatic ecosystems led to three discoveries that show promise as ecological applications. First, I show that temporal variability of an ecosystem process can be inferred from its spatial variability. This application may be the first quantitative form of the widely-used method, space-for-time substitution. Its use is supported by an analytical framework giving the conditions under which space is a good surrogate for time. Second, I demonstrate the use of spatiotemporal patterns to predict responses of variables when ecosystem fragments are connected. Connection leads to large shifts in spatiotemporal pattern and other response metrics (e.g., temporal variability) for variables showing asynchrony and concentration gradients among sites (e.g., populations). Meanwhile, these changes are minimal if variables exhibit synchrony and homogeneity across space (e.g., energetic variables). A final discovery is that temporal attributes like stability are strong predictors of persistent spatial variation – a pattern that reflects how reliably resource concentrations occur in the same locations. This finding suggests the potential of time-for-space substitution, where one or few well-resolved time series could be used to infer landscape patterns. All but one of the tested approaches were data efficient and broadly-applicable across ecosystems and ecological processes. They thus contribute new possibilities for prediction when data are scarce, as well as new perspectives on dynamics in multi-variable landscapes. Research here shows that work at the intersection of spatial and temporal pattern can strengthen the interpretation of ecosystem dynamics and, more generally, foster synthesis from populations to landscapes. / Thesis / Doctor of Philosophy (PhD) / The physical and biological components of ecosystems are constantly in flux, varying in value among locations (spatially) and over time (temporally). This dynamism makes it difficult to predict current or future behaviours of ecological variables (e.g., population size). This thesis tests the potential of using spatial and temporal patterns to make inferences and predictions about changes in ecological systems. I tested three new theory-based tools in aquatic ecosystems, finding that: The size of temporal fluctuations in an ecosystem variable can be predicted from the size of value-differences among locations; spatial and temporal patterns can predict how a variable responds when isolated fragments of ecosystems are connected; and attributes of ecosystem variables (e.g., their stability) can indicate the likelihood of resources recurring in the same location. Findings show that new insight into spatial and temporal patterns can help prediction and management in complex landscapes.

<p> This paper is an exploratory study of the intermetropolitan mortality variations in Canada for the years 1971 and 1976. A characterization of the mortality variations based on life expectancies is first performed. Through the use of BACKWARD regression, these variations are then explained by marital status and income variables. Major findings are as follows: (1) There is an east-west spatial pattern for mortality variation with the eastern Census Metropolitan Areas (C~~'s) and northern Ontario CMA's experiencing below average life expectancies and the western CMA's having the highest life expectancies. (2) Victoria B. C. has the longest life expectancy of all of the CMA's for both 1971 and 1976. (3) For females, the MARRIED and LOW INCOME (under $1,000) variables are statistically significant, with MARRIED negatively related and LOW INCOME positively related to mortality. (4) For males, the MARRIED and DIVORCED variables are statistically significant. MARRIED is negatively related to mortality, while a negative relationship was found for DIVORCED although this finding is doubted to be a true relationship. (5) The levels of explanation are not very high. To know whether the unexplained variation is mostly due to chance variation, future research should add more cities to the sample. </p> / Thesis / Bachelor of Arts (BA)

The aim of this study is to examine the linguistic features in teachers’ spoken language, how they adapt their language to their recipient, as well as how the teachers go about building positive studentteacher relationships. The data was collected by observing the teachers’ language usage through audio recordings in the classroom as well as short interviews. The results show that there are some differences in the teachers’ spoken language where some correlations can be made to the age and the gender of the teacher. Moreover, the results show that none of the teachers adapt their spoken language to their recipient in any meaningful capacity. Finally, all the teachers show an awareness of the benefits of positive student-teacher relationships, however, the methods used to achieve them differ.

To achieve expressive musical results in violin bowing, performers access wide ranges of combined musical tone loudness and duration variables. By comparison, allowable mechanical variability in bow stroke execution may be limited. Such constraints on string bowing variability similarly might limit variability of bowing limb movement. Constrained variability may carry risk of upper extremity musculoskeletal disorders. Therefore if musical and/or bowing-execution variables influence bowing limb movement variability, they may in turn influence risk of cumulative injury in the player. In two experimental studies we examined the influence of the musical variables of duration and sound intensity (loudness) on variability in both string bowing mechanical variables and bowing limb joint moments (i.e. rotational forces) and joint angle trajectories. Five violinists performed playing tasks in which bow strokes varied across four levels of duration and three levels of loudness. Given a constant-amplitude bow stroke, quiet, brief strokes and loud, long strokes had to be executed close to the lower and upper limits of permissible bow-on-string force (bow force). In Study #1, we computed one- and three-dimensional bow movement variance measures, in both kinematic (bow velocity across violin string, distance from bow-to-bridge) and kinetic (bow force) variables. In Study #2 we computed the cycle-to-cycle standard deviation of joint moments and angles for each moment and angular degree of freedom in the bowing limb. In each study, these variability measures were compared across the 12 experimental conditions. We hypothesized that variability would be lowest when executing quiet/brief and loud/long strokes, compared to strokes that could be executed further from bow force limits. However, it was also anticipated that variability instead could be influenced most strongly by bow and/or limb velocity, magnitude of bow force, and/or bowed-string loudness response properties. Results from both studies indicated that variability in both bow-on-string and limb movement was conditioned on these latter properties: tone duration and loudness exerted consistent effects on variances and standard deviations. Contradicting the main hypothesis, variability was not influenced by proximity to bow force limits. We conclude that bowing variability is constrained mainly by factors not specific to variability tolerance at the bow-violin string interface.

No description available.