Many pathogenic microorganisms are believed to stochastically switch into low metabolic states that display resistance to supra-lethal levels of antibiotics. These so-called “persister” cells have been associated with recurrent infections and the development of antibiotic resistance. Whilst a compound that eliminates Staphylococcus aureus persister cells has been described, it is not active against Gram-negative bacteria. The aim of my PhD project was to develop a high-throughput assay for compounds that eradicate persister cells in the -proteobacterium Burkholderia thailandensis. Further to this, I aimed to develop “hit” compounds from screening into lead series through investigation of structure activity relationships and, use a chemical genetics approach to elucidate potential mechanisms of action. I developed a phenotypic assay to identify compounds that eradicate persister cells. The assay was based on the reduction of the resazurin based dye PrestoBlue. Optimization of the assay gave a Z’ prime of 0.41 when screened in high throughput at the DDU. Screening of the library of 61,250 compounds identified 2,127 compounds that gave a statistically significant reduction in persister cell numbers. Follow-up assays highlighted 29 compounds with a pIC50 greater than five. Detailed investigation allowed me to down select to six “best in class” compounds, which included the licensed drug chloroxine. A time dependent killing assay showed that chloroxine reduced levels of persister cells by three orders of magnitude over 72 hours (P = 0.01). Hit expansion around chloroxine using commercially available compounds did not identify any more potent compounds, but did highlight key features of the molecule for activity. Assay protocols were provided to collaborators at DSTL who were able to iv show that chloroxine is also active against persister cells formed by the tropical pathogen and Tier 1 biological agent Burkholderia pseudomallei. Investigations into the mechanism of action of chloroxine used Next Generation Sequencing of an over expression library, identifying two putative genes involved in inhibition of persister cells by chloroxine. My findings demonstrate a phenotypic assay against persister cells in Gram-negative bacteria, which has the power to identify potent anti-persister agents to assist in chemotherapy. Structural activity relationship and mechanism of action investigations have indicated lead series and genetic starting points for future development of this research. My PhD project has concluded with sufficient data for continuation of research following a number of leads and is at an ideal stage for instigation of a medicinal chemistry program for development of chloroxine as a clinical option for treatment of persistent melioidosis.

Master of Science / Department of Computer Science / Eugene Vasserman / Since 2014 there have been over 120 million new malicious programs registered every year. Due to the amount of new malware appearing every year, analysts have automated large sections of the malware reverse engineering process. Many automated analysis systems are created by re-implementing analysis techniques rather than automating existing tools that utilize the same techniques. New implementations take longer to create and do not have the same proven quality as a tool that evolved alongside malware for many years. The goal of this study is to assess the efficiency and effectiveness of using existing tools for the application of automated malware analysis. This study focuses on the problem of discovering how malware persists on an infected system. Six tools are chosen based on their usefulness in manual analysis for revealing different persistence techniques employed by malware. The functions of these tools are automated in a fashion that emulates how they can be manually utilized, resulting in information about a tested sample. These six tools are tested against a collection of actual malware samples, pulled from malware families that are known for employing various persistence techniques. The findings are then scanned for indicators of persistence. The results of these tests are used to determine the smallest tool subset that discovers the largest range of persistence mechanisms. For each tool, implementation difficulty is compared to the number of indicators discovered to reveal the effectiveness of similar tools for future analysis applications. The conclusion is that while the tools covered a wide range of persistence mechanisms, the standalone tools that were designed with scripting in mind were more effective than those with multiple system requirements or those with only a graphical interface. It was also discovered that the automation process limits functionality of some tools, as they are designed for analyst interaction. Regaining the tools’ functionality lost from automation to use them for other reverse engineering applications could be cumbersome and could require necessary implementation overhauls. Finally, the more successful tools were able to detect a broader range of techniques, while some less successful tools could only detect a portion of the same techniques. This study concludes that while an analysis system can be created by automating existing tools, the characteristics of the tools chosen impact the workload required to automate them. A well-documented tool that is controllable through a command line interface that offers many configuration options will require less work for an analyst to automate than a tool with little documentation that can only be controlled through a graphical interface.

Introdução: O aprendizado intencional/incidental pode influenciar a memória. A persistência deste efeito avaliado ao longo do tempo foi pouco estudada até o momento. Objetivos: Avaliar a persistência da memória comparando as aprendizagens intencional e incidental. Métodos: A amostra (120 sujeitos funcionalmente independentes, com idade variando de 18 a 81 anos), foi subdividida em dois grupos (experimental - condição ‘intenção de aprender’ - e controle). Uma abordagem ecológica foi utilizada para a avaliação do aprendizado incidental. As avaliações foram realizadas dois e sete dias após a codificação. Resultados: A intenção de aprender e a aquisição incidental (a partir de experiências de vida diária) melhoraram a recuperação da memória no dia dois, mas não sete dias após a codificação. Conclusão: Estes achados sugerem que o estado motivacional (espontâneo ou induzido) que modula o sistema da atenção deve ser importante para a melhora na recuperação das informações aprendidas. / Background: The intentional/incidental learning can influence memory. The persistence of this effect assessed over time has been little studied up to date. Objectives: To evaluate the persistence of memory comparing intentional and incidental learning conditions. Method: The sample (120 functionally independent subjects, age ranging from 18 to 81 years old), was subdivided into two groups (experimental - intention to learn condition - and control). An ecological approach was applied for the incidental learning condition. The assessments were performed two and seven days after the encoding. Results: The intention to learn and the incidental acquisition (from daily life experiences) improved performance two but not seven days after the encoding. Conclusions: These findings suggest that motivational state (spontaneous or induced) which module the system of attention may be important for the improvement in the retrieval of the information learned.

abstract: Disparities exist among minorities in educational a ttainment. The gap widens when examining access to higher education and persi stence rates among minority males as compared to their white counterparts and minorit y females. The purpose of this action research study was to explore the impact of a recip rocal mentoring model between faculty and minority male students in an effort to examine the effects on student persistence and the students' academic experience. The researcher attempted to examine mentoring relationships, the process of reciprocal mentoring, and the effects on persistence and the students' academic experience f or the purpose of learning about one another's perspectives. This study investigated min ority male persistence within Chandler-Gilbert Community College (CGCC). Persiste nce was defined as a student who enrolled during the fall 2013 academic semester and continued at the same institution or transferred to another two-year or four-year instit ution working on degree completion. The author used a mixed methods design and used Cri tical Race Theory (CRT) as the theoretical framework by which to examine issues pe rtaining to minority male student perspectives and experiences. The results yielded e ight assertions related to minority male retention and persistence. / Dissertation/Thesis / Ed.D. Educational Leadership and Policy Studies 2014

Researchers have turned their attention to the use of learning analytics and dashboard systems in education. Schools are using knowledge gained in this area to address the issue of persistence to increase graduation rates. While dashboard systems have been developed and are starting to be implemented, it is not yet clear how activity and performance data from dashboards influences student behavior. In addition, much of the research has been focused on instructor-facing dashboards rather than student-facing dashboards. The current study implemented a student-facing dashboard in the learning management system and measured how information on the dashboard may have influenced participation in discussions, student performance on graded items, and persistence in future courses. A dashboard tool was developed for this study. Activity, performance, and persistence data was collected from all participating students. The study followed an experimental design approach that involved assigning a random group of students from multiple courses to a dashboard tool which showed the individual student’s activity and performance compared with that of their peers. Activity indicators included frequency of posting, average length of posts, percent of posts made to peers, and percent of posts made to instructor. The current score for the student, as a measure of performance, was also shown on the dashboard along with the current class average. Multivariate analysis of variance (MANOVA) was used to determine whether there were statistically significant differences in participation as measured by number of posts, word count of posts, and percent of posts to peers or performance as measured by final grade. Chi Squared analysis was used to determine whether there were significant differences in persistence as a measure of whether students registered for and attended the following session. The analysis of results indicated no significant differences in participation or performance between the experimental and control groups (f(4, 59) = .947, p = .443). Similarly, no significant differences were found in persistence between the two groups (χ2(2) = .960, p = .619). Further research is needed to more fully understand the use of student dashboard interfaces and their impact on student behavior. Future studies using a similar methodology should incorporate larger sample sizes and include all students in the class, rather than using self-selected samples. A better understanding of how the use of dashboards influences participation, performance, and persistence is needed in order to develop effective strategies for supporting students.

Les trois études traitent du processus de croissance des entreprises, sa persistance, ainsi que du rôle de l’innovation dans la performance des entreprises. Dans la première étude, nous nous concentrons sur la persistance de la forte croissance des entreprises et examinons si ce modèle de croissance spécifique est associé à de meilleures capacités d’exploitation. La deuxième étude vise à explorer la relation entre la croissance et l’innovation, en tenant compte de la nature multidimensionnelle du processus d’innovation. Nous observons un large ensemble de variables d’innovation qui saisissent des sources différentes, des modes et types d’activités innovantes mises en œuvre au sein des entreprises. Dans le troisième essai, nous examinons le rôle de la persistance de l’innovation sur la persistance des performances en terme de croissance. / The three essays focus on the process of firm growth, its persistence, and on the role of innovation in affecting firm performance. In the first essay we concentrate on persistence of high-growth and investigate whether this peculiar growth pattern is associated with better operating capabilities. The second essay aims to explore the relationship between growth and innovation, taking into accountthe multidimensional nature of the innovation process. We provide a broad picture of the relationship between growth and innovation, by looking at a wide set of innovation variables that capture the different sources, modes and types of innovative activity undertaken within firms. In the third essay we examine the role of persistence of innovation on persistence of growth performance, assessing whether a systematic, rather than sporadic, engagement in innovation activities induces more structure in the process of firm growth.

Many organic compounds, although beneficial, are associated with negative health and ecological impacts. It is therefore imperative to understand the environmental fates of these contaminants. Whereas the fates and health impacts of many persistent organic pollutants have been extensively examined, there is limited research characterizing the fates of these and the less persistent organic compounds in tropical multi-use watersheds. This study therefore aimed to evaluate the roles of forests and climate change on the environmental fates and health impacts of select organic chemicals in the Rio Cobre watershed, a tropical river basin in Jamaica. A total of 16 organic compounds were selected for this assessment, including some polybrominated diphenyl ethers (PBDEs), dioxins, furans and current-use pesticides. In the first portion of the assessment, field measurements of the concentrations of select PBDEs (PBDE-28, -47, -99, -100, -153, -154, -183 and -209) in the deposition, soil, litterfall and atmosphere of a forest and nearby clearing in the aforementioned watershed were evaluated. The mean air and litterfall concentrations of the PBDEs were lower in the forest than in the clearing, whereas the deposition flux rate and soil concentrations were higher in the forest. It was therefore concluded that the tropical forest filtered the PBDEs by transferring them from the atmosphere to the soil. In the next segment of the assessment, a multimedia environmental model of contaminant fate and transport, reflective of a region with three vegetative covers – urban, agricultural/grassland and forests – was developed to assist with the evaluations. This model, RioShed, was used to compute and compare fate metrics, including persistence and long range transport potential, for the aforementioned 16 organic compounds given varying forest parameters and climatic conditions. The atmospheric long range transport potentials and overall persistence of the organics were generally lower in the forested tropical watershed than in the un-forested tropical watershed, especially when the forests were fully evergreen. In this tropical watershed, the fate metrics were particularly responsive to precipitation rates. The atmospheric long range transport potentials and overall persistence of the evaluated organics increased and decreased, respectively, under the climate change condition of decreased precipitation rates. However, the effects of precipitation on the atmospheric long range transport potentials and overall persistence were more varied for the current-use pesticides. It was therefore concluded that the fates of the evaluated chemicals differed in forested versus un-forested tropical watersheds and that such differences were influenced by forest parameters, climate drivers and the chemical properties of the organics. The results and methods described in this dissertation are applicable in environmental multi-media model development and can be used to inform land management practices, as well as assist in decision-making for environmental sustainability in tropical developing countries.

Objectives: Adherence to multiple sclerosis (MS) treatment is essential to optimize the likelihood of full treatment effect. This prospective, observational, single-center cohort study investigated adherence to fingolimod over the 2 years following treatment initiation. Two facets of adherence - implementation and persistence - were examined and compared between new and experienced users of disease-modifying treatments (DMTs). Materials and methods: Implementation rates were based on the proportion of days covered and calculated as percentages per half-yearly visits and over 2 years, captured through refill data, pill count, and self-report. Nonadherence was defined as taking less than 85.8% of prescribed pills. Implementation rates were classified as nonadherent (< 85.8%), suboptimally adherent (>= 85.8% but. 96.2%), and optimally adherent (>= 96.2%), including perfectly adherent (100%). Persistence, ie, time until discontinuation, was analyzed by Kaplan-Meier analysis. Reasons for discontinuation were recorded. Results: The cohort included 98 patients with relapsing MS, all of whom received a dedicated education session about their medication. Of these 80% were women, 31.6% had fingolimod as first DMT, and 68.4% had switched from other DMTs. The mean implementation rate over 2 years was 98.6% (IQR(1-3) 98.51%-98.7%) and did not change significantly over time; 89% of measurements were in the optimally adherent category, 45.6% in the perfectly adherent category. There was one single occurrence of nonadherence. New users of DMTs were 1.29 times more likely to be adherent than experienced users (OR 1.29, 95% CI 1.11-1.51; P < 0.001), but not more persistent. Nineteen of 98 patients discontinued fingolimod. Conclusion: The very high implementation rates displayed in this sample of MS patients suggest that facilitation by health care professionals in preserving adherence behavior may be sufficient for the majority of patients. Targeted interventions should focus on patients who are nonadherent or who stop treatment without intention to reinitiate.

The main objective of this research was to determine the seed bank longevity of Melinis repens at two Southern Florida sites. Seeds were divided among different exposure levels (shade versus sun) and depths (surface versus buried) and tested for baseline viability using 2,3,5-Triphenyl-tetrazolium chloride. Statistical analysis determined that at the pine rockland site there was a significant interaction between time, exposure, and depth. The initial mean viability at this site declined from 49.71% to 11.26% and 13.06% for sun/buried seeds and sun/surface seeds, respectively, by month 8. The mean viability of shade/surface seeds and shade/buried seeds declined to 24.56% and 22.06% after 8 months. There were no significant effects in the Florida scrub. In order for land managers to completely remove this species from a site, treatment with herbicide will need to continue for a minimum of one year to effectively kill all viable seeds in the seed bank.

This dissertation was undertaken to answer the following research question: What is the relationship between parental involvement and college generation status with the persistence of Hispanic Millennial college students? Social capital theory (Coleman, 1988) was used as a theoretical framework to analyze and gain a greater understanding of the factors that correlated with the persistence of first-generation Hispanic Millennial college students. This dissertation used an ex post facto with hypothesis research design. The research hypothesis was that parental involvement would be positively related with the second-year persistence of first-generation Hispanic Millennial college students. This dissertation used the data collected from 1179 Hispanic students who participated in the ELS: 2002 and enrolled in college. Logistic regression analysis of data from 972 of the students with completed surveys were used to examine the relationship between the dependent variable, which was student persistence to the second year, and the following independent variables: socio-economic status, family income, high school grade point average, gender, financial aid, highest degree ever expected, academic engagement, social engagement, college generation, and parental involvement. This dissertation’s findings show that parental involvement was not statistically associated with persistence to the second year of college, but that high school grade point average, highest degree expected, academic engagement, and the interaction between parental involvement and college generation were. While the findings do not support the hypothesis, they provide some evidence that may be supportive of the argument that recommendations that may affect degree expectations, high school GPA, and academic engagement of first generation Hispanic Millennial college students may be positively related to their college persistence.