Load research is the study of load characteristics on a power distribution system which helps planning engineer make decisions about equipment ratings and future expansion decisions. As it is expensive to collect and maintain data across the entire system, data is collected only for a sample of customers, where the sample is divided into groups based upon the customer class. These sample measurements are used to calculate the load research factors like kWHr-to-peak kW conversion factors, diversity factors and 24 hour average consumption as a function of class, month and day type. These factors are applied to the commonly available monthly billing kW data to estimate load on the system. Among various customers on a power system, industrial customers form an important group for study as their annual kWHr consumption is among the highest. Also the errors with which the estimates are calculated are also highest for this class. Hence we choose the industrial class to demonstrate the Lawson-Hanson Non-Negative Least Square (NNLS) optimization technique to minimize the residual squared error between the estimated loads and the SCADA currents on the system. Five feeders with industrial dominant customers are chosen to demonstrate the improvement provided by the NNLS model. The results showed significant improvement over the Nonlinear Load Research Estimation (NLRE) method. / Master of Science

Interleukin-33 (IL-33) is a multifunctional cytokine that mediates local inflammation upon tissue damage. IL-33 is known to act on multiple cell types including group 2 innate lymphoid cells (ILC2s), Th2 cells, and mast cells to drive production of Th2 cytokines including IL-5 and IL-13. IL-33 signaling activity through transmembrane ST2L can be inhibited by soluble ST2 (sST2), which acts as a decoy receptor. Previous findings suggested that modulation of IL-13 levels in mice lacking decoy IL-13Rα2, or mice lacking IL-13, impacted responsiveness to IL-33. In this study, we used Il13-/- mice to investigate whether IL-13 regulates IL-33 activity by modulating the transmembrane and soluble forms of ST2. In Il13-/- mice, the effects of IL-33 administration were exacerbated relative to wild type (WT). Il13-/- mice administered IL-33 i.p. had heightened splenomegaly, more immune cells in the peritoneum including an expanded ST2L+ ILC2 population, increased eosinophilia in the spleen and peritoneum, and reduced sST2 in the circulation and peritoneum. In the spleen, lung, and liver of mice given IL-33, gene expression of both isoforms of ST2 was increased in Il13-/- mice relative to WT. Because IL-13 and IL-4 signal through a shared receptor complex IL-13Rα1/IL-4Rα, we also studied the combined deficiency of IL-4 and IL-13 using Il4rα-/- mice which are defective in both IL-4 and IL-13 signaling. Responses of Il4rα-/- mice were indistinguishable from those of Il13-/- mice in our model system of IL-33-induced inflammation, suggesting that IL-4 does not play a distinct role separate from IL-13 in regulation of IL-33 activity. Through in vitro experiments, we confirmed fibroblasts to be an IL-13-responsive cell type that can regulate IL-33 activity through production of sST2. This study elucidates the important regulatory activity that IL-13 exerts on IL-33 through induction of IL-33 decoy receptor sST2 and through modulation of ST2L+ ILC2s.

<P> Type II Secretion (T2S) and type IV pilus (T4P) systems in Gram-negative bacteria share many features that suggest a common ancestral origin. This study examined the role of the minor pilins FimU, PilV, PilW, PilX and PilE, as well as the putative adhesin PilYl in both the T4P and T2S systems, and elucidated the role of these proteins in pilus assembly. Genetic analysis of the major pilin cluster and the minor pilin operon revealed that the major pilin alleles are associated with a specific set of minor pilins, and that unrelated strains of the same major pilin type have identical minor pilin genes, suggesting that the two gene clusters were horizontally acquired as a 'pilin island'. We observed that the minor pilins required a specific stoichiometric ratio for proper assembly, as overexpression either completely abolished, or significantly reduced twitching motility in mutant backgrounds. We demonstrated that the minor pilins were incorporated into the pilus fibre, and that they were dependent on PilA for surface localization. The T4P minor pilins were also shown to play a role in the secretion of effectors through the T2S system, as elastase and haemolytic phospholipase C secretion was reduced in minor pilin mutants, while overexpression of FimU or PilX significantly increased secretion of T2S exoproteins. Therefore, the minor pilins may participate in T2S substrate recognition. We found that PilYl was not essential for assembly in the absence of retraction, but that its absence caused changes in the levels of other T4P biogenesis proteins, namely FimU, PilW, PilF and PilQ secretin multimers. Finally we show that the minor pilin, PilX functions as a strain-specific factor, potentially through specific interactions with non-conserved residues of PilQ that are necessary to induce opening of the secretin. </p> / Thesis / Doctor of Philosophy (PhD)

Type IV pili (T4P) are protein filaments found on the surface of a variety of bacterial species and mediate biofilm formation, adhesion, and flagellum-independent twitching motility. The biogenesis of T4P is dependent on a cell envelope-spanning, multiprotein complex that localizes to the poles in rod-shaped cells. How these proteins localize and cross the peptidoglycan (PG) layer in the absence of dedicated PG-hydrolyzing enzymes is unknown. In P. aeruginosa, PilMNOP interact to form the alignment subcomplex, connected via PilP to PilQ, which forms the outer membrane secretin. We hypothesized that polar localization and integration of the T4P machinery was driven by ordered recruitment to future sites of cell division, placing assembly system components at division septa in the correct position before daughter-cell separation. To determine which T4P components are essential for localization of the complex, we fused the T4P inner membrane assembly protein PilO to the fluorescent protein mCherry to monitor its localization. mCherry-PilO localized to the cell poles and midcell in wild type bacteria. However, it was delocalized in a strain lacking PilQ. A PilQ-mCherry fusion localized to the cell poles, likely through its putative septal PG binding AmiN domains, suggesting that PilQ binds PG and thus localizes its partners to future sites of cell division. In the absence of the associated pilotin protein (PilF), which is required for PilQ multimerization in the OM, T4P components were polarly localized, implying that localization is not dependent on secretin formation. The results of this research support a pre-installation mechanism for integration of protein complexes in the gram negative cell envelope without PG hydrolysis, which may be applicable to other systems. / Thesis / Master of Science (MSc)

Background and Objectives: Mesothelin, identified as a tumor-associated biomarker, is more often overexpressed in triple receptor-negative breast cancer (TNBC) than in common luminal breast tumor subtype or normal tissues. The objective of this systematic review is to determine the association between the expressions of mesothelin with survival outcomes in patients with TNBC. Methods We searched the following electronic databases: MEDLINE, EMBASE, the Cochrane Central Register of Controlled Trials, PubMed, and Web of Science with no time or language restriction till May 19, 2016. Any prospective or retrospective longitudinal studies that investigate the prognosis of TNBC with mesothelin baseline measurement were selected. Two reviewers independently assessed every article for inclusion, extracted data, and assessed the methodological quality of every eligible trial. Pooled measures of associations were summarized with meta-analyses. Results and conclusions Among the 592 patients with TNBC included in the four eligible studies, 269 patients (45.4%) demonstrated mesothelin expression. For the primary outcome OS, we found the trend toward decreased survival for patients with mesothelin-positive TNBC than those without mesothelin expression. We also found that for long-term OS, the association was statistically significant (OR = 0.46; 95% CI= 0.30 to 0.73; P< 0.001). For the secondary outcomes, we found that mesothelin expression in patients with TNBC was associated with lower DFS and higher overall mortality than those without mesothelin expression. Despite the limitations of sample size, this present study shows a significant association between mesothelin expressions and survival outcomes in patients with TNBC. Patients with mesothelin-positive TNBC could benefit from mesothelin-targeted immunotherapies recently in the development. / Thesis / Master of Science (MSc) / It is unclear whether mesothelin expression in triple-negative breast cancer (TNBC) is an independent prognostic marker for survival. To the best of our knowledge, no systematic review or meta-analysis has ever been done on this topic. The present systematic review aims to evaluate the role of mesothelin as a prognostic marker for TNBC. The primary objective of this review is to synthesize available evidence on the association between the expression of mesothelin and overall survival (OS) of patients with TNBC. The secondary objectives include determining the relationship between the expression of mesothelin and disease-free survival (DFS), distant metastases, and mortality. Despite some limitations, this study shows a significant association between mesothelin expressions and long-term OS rate as well as DFS rate and mortality rate in patients with TNBC. Mesothelin has a prognostic significance for patients with mesothelin based on our findings. Patients with mesothelin-positive TNBC could benefit from mesothelin-targeted immunotherapies in development.

Sustainability reports should provide a balanced picture of a company’s sustainability aspects, but because of its voluntary nature, overly positive aspects are often presented (Holder-Webb et al., 2009; Lougee &amp; Wallace, 2008). Though, negative disclosure may also be released as it could improve transparency, enhance trust, and decrease the risk of green or whitewashing tendencies (Hahn &amp; Lüfs, 2014, Hahn &amp; Reimsbach, 2013). However, when disclosing negative information, it is important for companies to legitimize the negative aspects, as the negative information could otherwise harm the company. As a result of this, different legitimacy strategies are used by companies when disclosing negative information (Hahn et al., 2021). Based on this, this thesis explores and analyses strategies for disclosing negative sustainability information. In particular, the study examines companies within the fast fashion industry, a heavily debated sector in regard to sustainability, which indicates that the companies within the business should try to legitimize themselves.    To fulfil the purpose of this study the choice was made to conduct a content analysis and semi-structured interviews, where four fast fashion companies’ (H&amp;M, SHEIN, Boohoo and American Eagle) sustainability reports were analysed to identify negative sustainability disclosure and assess how the companies’ tried to legitimize these negative aspects. Later, the disclosure strategies’ impacts on stakeholders were examined through 10 semi-structured interviews with concerned stakeholders. The results show that the companies subject to research did use the strategies corrective action, marginalization, abstraction, and preventive action to legitimize negative sustainability issues. The strategies were often not effective in enhancing legitimacy mainly because of too vague measures, but also because of the disbelief from stakeholders regarding the industry’s will and ability to change. However, the findings also indicated that the negative disclosure could enhance a bit of legitimacy as it signalled transparency and accountability, which is preferred compared to denial or compliance.    The study’s implications are important for scholars and practitioners. The theoretical contributions were added to the research field of negative disclosure and legitimacy strategies, and the implications are important for managers working within the fast fashion industry as well. This is because the results of this study will develop their knowledge of how certain negative disclosures strategies can play a both positive and negative role in enhancing the legitimacy towards stakeholders.

Dangerous things can happen in the name of good intentions and we, as teachers or parents, are unaware of the ways we hurt children. In the book Emile or on Education we see a fictional example of a pedagogical relationship between a teacher and a student, where the teacher -Jean Jacques- is eager to teach and raise his pupil, Emile, in certain ways, so as to make him independent and happy. Jean Jacques’ intentions are unquestionably good. His goal is to protect Emile and prevent his alienation by society, through the appropriate negative education. In trying to prevent Emile’s alienation, though, he creates another type of alienation, unknowingly and unintentionally. The aim of my thesis is to analyze the system of negative education and its negative consequences, focusing on the notion of alienation. Jean Jacques, while striving to prevent alienation, through negative education, created a new type of alienation, that is even more dangerous than the one he avoided. Thus, my thesis aims to raise awareness regarding the following: a) even when pedagogical processes are based on good intentions, they can still lead to negative consequences, b) upbringing and education are both a broadening and a narrowing process.

The typological distinction between negative concord and double negation languages has received increasing attention over the past century beginning with Jespersen (1922). Multiple negation in Biblical Hebrew has been subject to mixed treatment in this regard. Some scholars have treated all multiple negation in Biblical Hebrew as emphatic (Gesenius, Kautzsch & Cowley 1910; Dahood 1975; Holmstedt 2016) while others have labeled these constructions as pleonastic (Jouon & Muraoka 2006). Snyman (2004) determines that Biblical Hebrew is neither a negative concord language nor a double negation language based upon his assessment that "BH does not exhibit multiple negation elements." In this thesis I explore a novel approach to evaluating the typological treatment of multiple negation in Biblical Hebrew. The criteria I use are derived from crosslinguistic observations made by Zeijlstra (2004a) and van der Auwera & van Alsenoy (2016), identifying the linguistic traits exclusive to negative concord languages (e.g. preverbal negative markers, paratactic negation, and banning true negative imperatives). I demonstrate the presence of these phenomena in Biblical Hebrew, determining it to be an NC language. I also discuss the implications these findings have on the current typology.

This thesis consists of two chapters, each of which is a unique research project. Chapter 1 is focused on the synthesis and biological evaluation of novel sideromycin antibiotics. Sideromycins are bifunctional “Trojan Horse” molecules that have an iron chelator “siderophore” moiety covalently bound to an antibiotic. Such molecules exploit existing bacterial mechanisms for obtaining iron from their environment. Antibiotics that would typically not pass Gram-negative membranes are allowed access via siderophore transporter proteins. This project utilized a siderophore that has not previously been used in this capacity. The synthesis and biological evaluation of multiple sideromycin conjugates is reported. Chapter 2 describes the chemical synthesis of coumarin natural products using a synthetic process recently developed in the Magolan laboratory that enables the efficient prenylation of phenols. These natural products are molecules of biological interest in various capacities but are rare and difficult to isolate from their plant sources. They have also previously been cumbersome to make via chemical synthesis. The chemistry described herein constitutes an inexpensive and efficient process to produce these compounds that is superior to previously known methods. / Thesis / Master of Science (MSc) / This thesis is divided into two chapters. The first chapter is focused on the development of new sideromycin antibiotics. Sideromycins are “Trojan Horse”-like antibiotics that exploit the mechanisms of Gram-negative bacteria for obtaining iron, an essential nutrient, to enable antibiotic entry. This chapter details the synthesis of molecules that attach functionalities called “siderophores” to antibiotics, enabling them to be “smuggled” into Gram-negative microbes. This project uses a siderophore not previously utilized in sideromycin research. The second chapter is focused on the chemical synthesis of rare natural products that are phenols with prenyl substituents. Many such compounds are plant-derived and have potential for biomedical use. However, difficulty in isolating them makes them prohibitively expensive in the purity and quantity required for research. They are also challenging to make synthetically. This chapter details the application of a recently discovered process in the Magolan laboratory to synthesize coumarin-containing prenylated phenolic natural products.

Obstacle detection and avoidance plays a crucial role in the autonomous navigation of unmanned ground vehicles (UGV). Information about the obstacles decreases as the distance between the UGV and obstacles increases. However, this information decreases much more rapidly for negative obstacles than for positive obstacles. UGV navigation becomes more challenging in off-road environments due to the higher probability of finding negative obstacles (e.g., potholes, ditches, trenches, etc.) compared with on-road environments. One approach to solve this problem is to avoid the candidate path with a negative obstacle, but in off-road environments avoiding negative obstacles in all situations is not possible. In such cases, the local path planner may need to choose a candidate path with a negative obstacle that causes the least amount of damage to the vehicle. To deal better with these types of scenarios, this research introduces a novel approach to perform 3D shape estimation of negative obstacles using LiDAR point cloud data. The dimensions (width, diameter, and depth), location (center), and curvature of negative obstacles were calculated based on an estimated shape. The presented approach can estimate the shape of different kinds of negative obstacles such as holes, trenches, in addition to large and complicated negative obstacles. This approach was tested on different terrain types using the Mississippi Autonomous Vehicle Simulation (MAVS).