The cell wall is essential for fungal survival in natural environments. Galactofuranose (Galf) decorates certain carbohydrates and lipids of Aspergillus cell wall, is absent in humans and appears to play a role in fungal cell wall maturation. Previous studies in our lab showed that deletion of any of three sequential-acting genes (ugeA, ugmA, and ugtA) of Galf pathway caused substantially reduced growth and spore production. Two genes upstream of the Galf pathway, galD and galE are essential for galactose metabolism in many systems including the budding yeast, Saccharomyces cerevisiae. Interestingly, characterization of galD and galE in A. nidulans using cell and molecular techniques showed that unlike yeast, neither of these genes was essential for growth at physiological pH 7.5. Nevertheless for each case, their expressions were up-regulated by growth on galactose, revealing the relative complexity of galactose metabolism in A. nidulans. Our study also showed that repression of the three sequentially acting Galf pathway genes by conditional promoters phenocopied previously characterized deletion morphology. Using anti-Galf (L10) we also showed that deletion and repression of these genes caused no Galf in the hyphal wall. Gene deletion or repression also increased sensitivity to the wall-targeting drug, caspofungin. Related results from qPCR showed that deletion or repression of ugmA increased gene expression of α-glucan synthase agsB and decreased that of β-glucan synthase fksA. Therefore, Galf is non-essential but important for many aspects of Aspergillus growth, sporulation, and wall maturation. Aspergillosis, the most common airborne systemic fungal disease, is typically caused by Aspergillus fumigatus. Several A. fumigatus UgmA (AfUgmA) mutants with altered enzyme activity due to single amino acid changes were used to assess their effect on growth and wall composition in A. nidulans. Wild type AfugmA complemented the phenotypic defects in an A. nidulans ugmAΔ strain, consistent with these two genes being homologous. The AfUgmA crystal structure has been solved, and the in vitro enzymatic effects of specific mutations in the enzyme active site have been published. AfUgmA mutated strains with reduced activity in vitro impaired A. nidulans growth in a manner substantially similar to gene deletion and gene down-regulation. Site directed mutagenesis showed that AfUgmA residues R182 and R327 were critical for Galf generation both in vivo and in vitro. This supports previous results showing that UgmA is essential for Galf biosynthesis. Using fluorescent latex beads, we showed that reduction of wall Galf increased hyphal surface adhesion. Consistent with qPCR studies, immunofluorescence and ELISA results showed that loss or absence of Galf increased wall α-glucan but reduced wall β -glucan. Galf is important for wall surface integrity and for maintaining dynamic co-ordination with other pathways. To begin to assess this dynamic co-ordination, Tandem Affinity Purification (TAP) tagging combined with LC-MS/MS was used to identify the interacting partners of UgmA. Our results showed that UgmA interacted with proteins that are involved in cytoskeleton generation, osmotic adaptation, and cell signalling pathway. Further study will help us to understand the dynamic coordination of Galf biosynthesis pathway with other wall carbohydrate polymers for Aspergillus wall formation. In summary, my thesis results have clearly shown that Galf plays important roles in Aspergillus growth, and wall surface integrity. We also showed that Galf deficient strains are hypersensitive to wall-targeting drugs, indicating that Galf biosynthesis pathway could be potential target for combination therapy. The Galf pathway also maintained a dynamic co-ordination with alpha-glucan and beta-glucan carbohydrate pathways. Future study may include developing an inhibitor against UgmA and exploring the relationship of Galf pathway with alpha-glucan and beta-glucan carbohydrate pathways.

Salmonella causes gastrointestinal illness in humans. The purpose of the study was to determine the relative contribution of different food commodities to sporadic cases of salmonellosis (attribution analysis) caused by Salmonella Newport (SN) using Pulsed-Field Gel Electrophoresis (PFGE) patterns and antimicrobial sensitivity (AST) data submitted by public health laboratories and regulatory agencies from 2003 to 2006. The genetic relationship between isolates from non-human (348) and human (10,848) sources was studied by two unique clustering methods: UPGMA and Ward. Results show poultry was the highest contributor of human SN infections, followed by tomatoes and beef. Beef was the largest contributing food commodity of multi-drug resistant (MDR)-AmpC infection patterns. Results from this pilot study show that PFGE and AST can be useful tools in performing attribution analysis at the national level and that SN MDR-AmpC patterns are decreasing and seem to be restricted to isolates from animal sources.

Technological and methodological advances of the past few decades have provided hydrologists with advanced and increasingly complex hydrological models. These models improve our ability to simulate hydrological systems, but they also require a lot of detailed input data and, therefore, have a limited applicability in locations with poor data availability. From a case study of Big Creek watershed, a 186.4 km2 urbanizing watershed in Atlanta, GA, for which continuous flow data are available since 1960, this project investigates the relationship between model complexity, data availability and predictive performance in order to provide reliability factors for the use of reduced complexity models in areas with limited data availability, such as small ungaged watersheds in similar environments. My hope is to identify ways to increase model efficiency without sacrificing significant model reliability that will be transferable to ungaged watersheds.

In diagnostic test studies, one crucial task is to evaluate the diagnostic accuracy of a test. Currently, most studies focus on the Receiver Operating Characteristics Curve and the Area Under the Curve. On the other hand, the Youden index, widely applied in practice, is another comprehensive measurement for the performance of a diagnostic test. For a continuous-scale test classifying diseased and non-diseased groups, finding the Youden index of the test is equivalent to maximize the sum of sensitivity and specificity for all the possible values of the cut-point. This dissertation concentrates on statistical inferences for the Youden index. First, an auxiliary tool for the Youden index, called the diagnostic curve, is defined and used to evaluate the diagnostic test. Second, in the paired-design study to assess the diagnostic accuracy of two biomarkers, the difference in paired Youden indices frequently acts as an evaluation standard. We propose an exact confidence interval for the difference in paired Youden indices based on generalized pivotal quantities. A maximum likelihood estimate-based interval and a bootstrap-based interval are also included in the study. Third, for certain diseases, an intermediate level exists between diseased and non-diseased status. With such concern, we define the Youden index for three ordinal groups, propose the empirical estimate of the Youden index, study the asymptotic properties of the empirical Youden index estimate, and construct parametric and nonparametric confidence intervals for the Youden index. Finally, since covariates often affect the accuracy of a diagnostic test, therefore, we propose estimates for the Youden index with a covariate adjustment under heteroscedastic regression models for the test results. Asymptotic properties of the covariate-adjusted Youden index estimators are investigated under normal error and non-normal error assumptions.

Diagnostic testing is essential to distinguish non-diseased individuals from diseased individuals. More accurate tests lead to improved treatment and thus reduce medical mistakes. The sensitivity and specificity are two important measurements for the diagnostic accuracy of a diagnostic test. When the test results are continuous, it is of interest to construct a confidence interval for the sensitivity at a fixed level of specificity for the test. In this thesis, we propose three empirical likelihood intervals for the sensitivity. Simulation studies are conducted to compare the empirical likelihood based confidence intervals with the existing normal approximation based confidence interval. Our studies show that the new intervals had better coverage probability than the normal approximation based interval in most simulation settings.

Cervical Cancer is the second most common type of cancer in women worldwide (500,000 cases/year) and one of the leading causes of cancer-related mortality in women in developing countries (230,000 cases/year). The Spectrx LightTouch™ device uses light to detect chemical and structural changes in cervical tissue. Light responds differently when exposed to normal cells and cancerous cells. The purpose of this research is to find the best model that can be used to diagnose the early cervical cancerous conditions. To achieve this goal, we first tried to reduce the number of variables. We use statistical and non-statistical methods to search for useful explanatory variables. Partial Least Square, Logistic Regression, CART, MARS, SVM have been used to build models. Bootstrap was adopted to estimate the threshold of PLS model. Comparison of the results indicates that PLS produces relatively better model in terms of the performances and to control over model threshold.

Individuals with abdominal obesity are at higher risk for developing type 2 diabetes, predisposing cardiovascular events and insulin resistance. Low glycemic index (GI) diets may be beneficial in the management of insulin resistance. Insulin resistance is associated with increased intramyocellular lipid (IMCL) content as measured by proton nuclear magnetic resonance spectroscopy (1H-MRS). The primary objective of this thesis was to determine whether a low GI diet can improve insulin sensitivity by reducing IMCL of skeletal muscle. One hundred and twenty-one male and female participants aged 30 to 70 years (mean+SD, 53+10)) with abdominal obesity, entered a 4 to 6 week weight-maintaining, low-fat dietary advice run-in phase. Of the 121 eligible participants, 95 completed the run-in phase and were randomly assigned to either a low-GI (LGID, n=48) or high-GI diet (HGID, n=47) for 24 weeks. Participants underwent a 75g oral glucose tolerance test (OGTT) and had soleus-muscle IMCL measured by 1H-MRS at the beginning and end of the intervention period. Insulin sensitivity was assessed by the homeostatic model assessment index (HOMA) and the insulinogenic index (ISI) was calculated for insulin secretion. At the end of the run-in phase, there were significant reductions in serum total-, LDL-, and HDL-cholesterol (all, p<0.0001) and an increase in fasting plasma glucose (p<0.05). In 57 participants who wore a continuous glucose monitoring system for 24 hours during the run-in period, a total of 30% (p<0.001) of the variation in the incremental area under the blood glucose curve after self-selected breakfast meals was explained by GI. After 24 weeks, diet GI was significantly lower in the LGID than HGID group (55.5+3.1 vs 63.9+3.1, p<0.0001). Plasma glucose 60 minutes after the OGTT was significantly lower on the LGID than at baseline (p<0.05) and there was a non-significant trend towards an increase in ISI (p=0.07). On the HGID, ISI increased significantly from baseline (p<0.01). It is concluded that the LGID reduced 60 minute plasma glucose but did not significantly affect IMCL or insulin sensitivity in individuals with abdominal obesity.

Verslo mokymų rinka išgyvena dinamišką laikotarpį, kuris pasižymi mokymų apimčių didėjimu, naujų įmonių teikiančių tokias paslaugas atsiradimu. Augimo laikotarpiu daugelis tradicinių verslo problemų nėra aštrios, tačiau rinkai pasiekus brandos stadiją, situacija keičiasi. Kainodaros sprendimai – vieni sudėtingiausių ir turinčių didelį poveikį verslo stabilumui bei plėtrai. Šio darbo tikslas – padėti mokymus teikiančioms bendrovėms tvirčiau jaustis ieškant atsakymų į klausimus – kokie yra klientų segmentai pagal jautrumą kainai, radus šiuos atsakymus, didesnė tikimybė priimti teisingus plėtros sprendimus. Baigiamojo darbo tema: Lietuvos verslo mokymų rinkos segmentavimo galimybės taikant jautrumo kainai kriterijų. Darbo tikslas - nustatyti, kokios yra mokymų rinkos segmentavimo galimybės pagal jautrumą mokymo kainai. Darbo uždaviniai: 1. Išanalizuoti Lietuvos mokymo paslaugų rinką. 2. Surinkti duomenis apie šiuo metu Lietuvos mokymo paslaugų rinkoje taikomas kainas. 3. Atlikti kiekybinę apklausą, nustatant kainos jautrumo parametrus skirtingiems Lietuvos mokymo paslaugų klientams. 4. Pasiūlyti prioritetus, kaip Lietuvos mokymų rinka gali būti segmentuojama pagal jautrumą mokymo kainai ir kokie kainodaros metodai taikytini skirtingiems segmentams. Tyrimo metodika. Darbe buvo panaudotas kiekybinis tyrimo metodas - Westendorp „Price Sensitivity Meter“ („Kainos jautrumo nustatymo“) klausimynas. / The market of business training experiences dynamic time, which is characterized by an increasing scope of training and discovery of new enterprises providing such services. At the stage of development a lot of traditional business problems are not severe, however, when the market reaches the maturity stage the situation changes. Pricing solutions are one of the most complex and having a huge impact on business stability and expansion. The aim of the research is to help training providers to feel more confident while looking for an answer to the question – what are the client segments according to the price sensitivity. After having answered it, there is greater likelihood to take the right decisions in expansion. Theme: Application of Price Sensitivity Criterion in the Market of Business Training in Lithuania and its Segmentation Position Objectives: to determine the segmentation position of executive training market in applying the price sensitivity criterion. Aims of the research: 1. To analyze the market in the Training service sector of Lithuania. 2. To carry out analysis in price rates in the training sector in Lithuania. 3. To conduct a survey in order to set rice sensitivity parameters on different Lithuanian clients in the training service sector. To propose a method of how the training sector in Lithuania can be segmented according to the price sensitivity in training and what pricing methods could be applied to different segments... [to full text]

„Motinų jautrumo korekcijos analizė kūdikių prieraišumo kontekste“ SANTRAUKA Motinos jautrumo kūdikio signalams korekcija – palyginus naujas reiškinys, ypatingai Lietuvoje, tad šiuo tyrimu siekiama panagrinėti intervencijoje dalyvavusių motinų sąveikos su kūdikiais ypatumus, iškelti šiam procesui svarbius klausimus bei problemas, numatyti galimas ateities studijų kryptis. Pirmiausia siekiama panagrinėti motinų jautrumo pokyčius atliekant jautrumo korekciją. Kaip tyrimo problema keliamas klausimas – ar motinos jautrumas gali būti prognostinis kūdikio prieraišumo kokybės rodiklis. Taip pat norima aprašyti tyrime dalyvavusių motinų jautrumo, depresijos simptomų išreikštumo ir kasdienių rūpesčių vertinimo ypatumus bei palyginti jautrumo korekcijoje dalyvavusių ir nedalyvavusių motinų kūdikių prieraišumą. Šiame tyrime dalyvavo 35 motinų ir jų kūdikių poros. Dalis jų, t.y. 11 jautrių savo kūdikių signalams motinų sudarė vieną kontrolinę grupę; kitos – tai 24 mažai jautrios savo 6 mėnesių amžiaus kūdikių signalams motinos, atsitiktinai priskirtos vienai iš kitų dviejų - eksperimentei ar kontrolinei grupėms. Tad 10 iš jų dalyvavo vaizdo grįžtamuoju ryšiu paremtoje trumpalaikėje jautrumo korekcijos programoje, likusios (14) nedalyvavo. Po jautrumo korekcijos buvo įvertinti motinų jautrumo kūdikio signalams pokyčiai (Ainsworth motinos jautrumo skalė), depresijos simptomų išreikštumas (pagal Beck depresijos skalę), suvokiamo kasdienių rūpesčių vertinimo ypatumai (Kasdienių rūpesčių... [toliau žr. visą tekstą] / „Mothers' Sensitivity Correction Analysis in the Context of Infants' Attachment“ SUMMARY Maternal sensitivity correction is fairly novel and unexplored field, especially in Lithuania, therefore the aim of this study is to explore mother-infant interaction characteristics after participation in sensitivity correction programme, to highlight important questions and problems, to predict possible directions for future investigations. Also it is sought to analyze maternal sensitivity changes after the correction programme. The problem of this study is a question – can maternal sensitivity be a prognostic indicator of a child attachment security. This study is also ment to describe the peculiarities of maternal sensitivity, expresiveness of depression syptomes, estimation of daily hassles and to compare their child attachment security according to their participation in intervention programme. 35 mother-infant dyads participated in this study. Part of them, that is 11 sensitive mothers constituted one control group; others – 24 that were rated as inconsistently sensitive or insensitive to their infants‘ signals, formed two other – experimental and control groups. 10 of them participated in a short-term sensitivity correction programme with video feedback, while others (14) didn‘t. The changes in maternal sensitivity (Ainsworth Maternal Sensitivity Scale) to the infants‘ signals, as well as mothers‘ perceived daily hassles (Daily Hassles Questionaire) and depressiveness (according... [to full text]

Administrative data is one of the most commonly used data sources for diagnosed diabetes surveillance within Canada. Despite their widespread use, administrative case definitions have not been validated in many minority populations on which they are commonly used. Additionally, previous validation work has not evaluated the effect of conditional covariance between data sources, which has been widely shown to significantly bias parameter (sensitivity, specificity, and prevalence) estimation. Using administrative data and data sources which contained gold standard cases of diabetes, this thesis examined (1) the validity of commonly used administrative case definitions for identifying cases of diagnosed diabetes within an Aboriginal population at the sub-provincial level, and (2) the effect of conditional covariance on parameter estimates of an administrative case definition used to identify cases of diagnoses diabetes within the general population of Nova Scotia. We found significant differences in the sensitivity and specificity of a commonly used administrative case when applied to an Aboriginal population at the sub-provincial level. For the general population of Nova Scotia, we found that including a parameter to estimate conditional covariance between data sources resulted in significant variation in sensitivity, specificity, and prevalence estimates as compared to a study which did not consider this parameter. We conclude that work must continue to validate administrative case definitions both within minority populations and for the general population to enhance diabetes surveillance systems in Canada. / Validation study for administrative case definitions to identify cases of diagnosed diabetes in Canada