Several native species of Lauraceae (e.g. sassafras) in the southeastern United States are being eradicated by laurel wilt disease. Laurel wilt is caused by a highly invasive and cryptic ambrosia beetle, Xyleborus glabratus, and its fungal symbiont. The symbiont pathogen is spread during colonization of native Lauraceae. Xyleborus glabratus and the pathogen are remarkably effective at colonizing and killing healthy populations of Lauraceae in a brief time period. Control methods have been unable to slow the spread of laurel wilt disease and X. glabratus populations have been spreading into northern latitudes. Presently, cold temperatures may be the only factor limiting establishment of the beetle in interior populations of sassafras. Empirically derived physiological data from this study were combined with climatic, microhabitat, and host data to model the invasive potential/hazard rate of X. glabratus and laurel wilt in sassafras forests of the United States. Sharing this model data will help land managers, forest health specialists, urban foresters, and landowners make informed proactive management decisions regarding laurel wilt disease.

Alternative reproductive tactics (ARTs), occur where members of one sex of a species have two or more strategies of obtaining fertilization. The tactics differ in behavioural approaches to reproduction, but also commonly differ in physiological and morphological traits. The round goby, Neogobius melanostomus, is a globally invasive species with male ARTs. How behaviour may influence invasiveness in round goby has been of recent interest, but researchers have not considered the role or impact that male ARTs may have. I compared guarder and sneaker male round goby, assessing differences in their boldness, activity, exploration, sociality, aggression, startle responses, and dispersal tendencies. Sneaker males were more bold, active, and explorative while guarder males were more aggressive. In addition, I studied whether more guarders or sneakers are caught in a population survey study and how variation in a common round goby trapping method, minnow traps, may create catch biases. Two commonly employed minnow trap models include a black vinyl plastic coated metal trap (black traps) and a galvanized metal steel trap (silver traps). I investigated whether these black and silver traps and baited (corn) and unbaited traps differ in terms of the numbers, ART ratios, and sizes of round goby captured. I found silver traps captured 1.7 times more round goby than black traps, while baited traps captured 3.4 times more round goby than unbaited traps. Baited traps captured larger round goby and tended to capture more guarders than unbaited traps. I also found black traps captured larger males, but there was no difference in the size of females captured. Taken together my results indicate that care needs to be applied when making estimates of round goby populations in terms of the types of individuals present and the trapping method used. / Thesis / Master of Science (MSc)

No description available.

Twenty-first-century globalization has led to an extraordinary rise in international trade and transit. Consequentially, invertebrates, plants, and mammals are displaced more frequently, which has catalyzed a historic rise in biological invasions. The Joro Spider (Araneae: Trichonephila clavata) recently established from Asia in a landlocked region of southern Appalachia. Its range continues to expand; its cold tolerance is expected to favor northward invasion. As a large-bodied orbweaver that forms extensive webs and aggregations, the Joro spider is likely capable of inducing fundamental change to community structure via spatial competition. A valuable first step in estimating any invader’s economic or biological impact is to hypothesize regions susceptible to invasion using species distribution models. Recent work also shows that comparing global and regional distribution models yields insight into different stages of invasion. To examine potential spread and niche utilization differences in the Joro spider, one global and two regional models were developed. Maximum Entropy models were trained using open-source citizen science occurrence data and six bioclimatic variables at 2.5-arcminute resolution. An AUC-weighted ensemble model was used to produce each of the 3 global suitability projections. To compare invasive stage differences, projections were then translated to presence-absence maps using a 50% suitability threshold. The Asia-regional model predicts widespread suitability in eastern North America. However, the US-regional model reflects local adaptation to a climate niche that does not occur in the spider’s historic Asian range. Permutation feature importance shows the US-regional model was driven mainly by precipitation seasonality (64%) and annual oscillations in daily temperature range (29.1%). The Asia-regional model was instead driven by mean temperature of the driest quarter (34.9%), maximum temperature of the warmest month (23.6%), and precipitation of the warmest quarter (20.1%). The introduced Joro spider has invaded a North American niche that it is naïve to, but which co-occurs spatially with a niche akin to its historic Asian niche. If the Asia-regional climatic niche is indeed exploitable in North America, then conservative estimates show the bounds of range suitability should approach the 95th meridian and the 28th and 50th parallels. A total of 1,231,711 km2 within North America was predicted above 50% suitability. Altogether, these findings suggest niche versatility and plentiful suitable habitat favors successful North American invasion by the Joro spider.

This thesis aimed to answer how the European Union performed as a 'global actor' in the Russia and Ukraine war from 2014 until 2022 using theoretical approaches of international relations theories. Furthermore, realist scholars define the concept of actorness as an entity capable of military decisions. At the same time, the constructivist believes that actorness is defined by other capabilities that impact the global arena. The thesis discusses the realist thinking that the European Union is not a global actor yet due to its lack of military powers. Whereas constructivism states that the European Union is a global actor, placing other means of power forward such as normative, civilian, and economic capabilities through examples. The European Union's performance as a global actor in the Russia and Ukraine conflict has not effectively stopped the war, as it has escalated despite the gradual economic sanctions imposed in 2014. The sanctions imposed by the European Union have not been effective in the past as Russia managed to blow the economic pressures over due to each other's economic interdependence. Therefore, the European Union launched its sixth package of economic sanctions in 2022 and might see success as it decided a total ban Russia's natural resources in the upcoming year. However, that remains a matter of speculation as the European Union is a global actor in progress, and the practical growth of its foreign policy is under exercise and will be discussed better in the future.

Breast cancer is the major cause of cancer death among women worldwide. Understanding the mechanisms underlying breast cancer progression remains urgent for developing effective treatment strategies to eliminate breast cancer mortality. Our recent studies have demonstrated that Krüppel-like transcriptional factor 8 (KLF8) plays a critical role for breast cancer progression. Other studies have shown that Epithelial stromal interaction 1 (EPSTI1), a recently identified stromal fibroblast-induced gene in non-invasive breast cancer cells and epidermal growth factor receptor (EGFR) are highly overexpressed in aggressively invasive breast carcinomas including triple negative breast cancers. In this thesis project, we demonstrate high co-overexpression of KLF8 with EPSTI1 as well as EGFR in invasive breast cancer cells and patient tumors. We also show that KLF8 upregulates the expression of EPSTI1 by directly binding and activating the EPSTI1 gene promoter, and KLF8 upregulates the expression of EGFR not only by directly activating the EGFR gene promoter but also by preventing EGFR translation from microRNA141-dependent inhibition. Genetic, signaling and animal cancer model analyses indicate that downstream of KLF8, EPSTI1 promotes the tumor invasion and metastasis by activating NF-κB through binding valosin containing protein (VCP) and subsequent degradation of IκBα, whereas EGFR promotes tumor growth and metastasis via activation of ERK. Taken together, these data identify EPSTI1 and EGFR as novel iv KLF8 targets in breast cancer and suggest that KLF8 may be targeted for new effective treatment of breast cancer

Prostasin is expressed in normal prostate epithelial cells but down-regulated in prostate cancers, while prostasin re-expression in invasive prostate cancer cells reduced invasion. We examined prostasin expression and function in benign prostatic hyperplasia (BPH). We evaluated prostasin expression in 12 BPH specimens by immunohistochemistry, and evaluated the impact of prostasin silencing by siRNA on the expression of the inducible nitric oxide synthase (iNOS), intercellular adhesion molecule-1 (ICAM-1), and cyclin D1, as well as on cell proliferation and invasion, using the BPH-1 human prostate epithelial cell line model. Prostasin expression was localized in the glands of BPH tissues by immunohistochemistry, in either the tall columnar-shaped or the flattened epithelial cells. We silenced prostasin expression by >50% at both the mRNA and protein levels using siRNA in the BPH-1 human prostate epithelial cell line, and this silencing of prostasin expression was associated with an induction of iNOS and ICAM-1 expression and a down-regulation of cyclin D1 expression. The protein expression of EGFR, a putative prostasin substrate, was not affected by prostasin silencing in this cell line. The prostasin-silenced cells displayed a reduced cell proliferation rate and reduced invasiveness, cell behaviors regulated by cyclin D1, iNOS, and ICAM-1 in the BPH-1 cells. We believe that this down-regulation of cyclin D1 is due to prostasin's augmentative effect on iNOS. We also believe that the decrease in cell motility is due to an increase in iNOS and ICAM-1 as well as a decrease in cyclin D1, since all of these molecules can play a role in cell motility. In conclusion, Prostasin is somehow involved in the regulation of inflammatory gene expression (iNOS and ICAM-1) in prostate epithelial cells, as well as cyclin D1 expression, cell proliferation and invasion, involving molecular mechanisms different than those in the prostate cancer cells. These studies suggest that prostasin is a player in the glandular components of benign prostatic hyperplasia.

Community composition results from an integrated combination of random processes, regional habitat spatial structure, local environmental conditions, and species interactions. For example, the outcome of plant interactions can change depending on local environmental conditions such as nutrient availability, land management, or herbivory intensity. In particular, plant interactions may vary between facilitation and competition depending on ecological context, with facilitation expected to be prevalent under stressful conditions. I present the results of four studies that address different aspects of the community assemblage and dynamics emphasizing the synergistic effect of different processes. In the first, I investigated the importance of habitat isolation in determining species richness of wetlands with contrasting land use. The second describes an experiment to test the hypothesis that plant interactions with an unpalatable plant (Juncus effusus) would range from competition in ungrazed areas to facilitation in grazed areas and predicted that facilitative effects of Juncus would differ among functional groups of beneficiary species and be strongest when grazing was intense. In the third, I examine the community composition impacts of Juncus and predicted that Juncus would preserve functional diversity in grazed wetlands but that the effects of Juncus would vary along a grazing gradient. The fourth study investigated the relative importance of competition and nutrients in determining wetland invasion in two different land use types. Broadly, I demonstrate that the importance of different processes (habitat isolation, nutrient availability, competition/facilitation) to community composition is dependent on ecological conditions. This integrated view of community dynamics is interesting from a purely ecological perspective but also can be applied to understanding ecological problems such as exotic invasions and restoration of disturbed habitats.

An invasion percolation (IP) model was used to illustrate the effects of gravity on DNAPL migration into a horizontal water saturated fracture. While gravity is typically neglected in the conventional approach, this work demonstrated that gravity should often be included when modelling DNAPL invasion in water saturated fractures and provides an equation estimating the difference in invasion pattern between simulations including or neglecting gravity. The IP model was further utilized to examine the invasion of DNAPL saturated fractures by water. These simulated experiments focus on cases where covariance (COV), the ratio of the mean of the aperture field to the standard deviation of the aperture field) as well as when the fracture is inclined or declined from horizontal. Results show that when COV is greater than 0.1, then DNAPL will always remain in the fracture after waterflooding. Furthermore, fracture angles below -15 degrees permit the complete removal of DNAPL, while fractures oriented at higher angles do not. In order to study the transport of particles in water saturated fractures, physical experiments measuring the transport of 0.046 um and 0.55 um microspheres were undertaken on fractures where the geometry could be imported into a computer for comparative simulation analysis. Results demonstrated that during advection, particles generally travel at less than the velocity of the surrounding fluid. As well, hydrodynamic effects such as shear were shown to influence the effluent concentrations by increasing dispersion. Finally, the physical geometry of the fracture was shown to influence the particle pathway during transport and can limit the chances of particles adhering to a fracture wall, thus reducing dispersion and increasing peak concentration. The combined results of these studies show that fracture geometry has a significant effect on the mechanisms of transport in saturated fractures. / Thesis / Doctor of Philosophy (PhD) / This thesis describes the transport of contaminants in rock fractures in the environment. Specifically, the transport of denser than water liquids that are immiscible in water and particles are modelled and analysed. This work used experiments in order to calibrate these models for analysis. It was found that the local geometry of the fracture walls heavily influences the invasion pattern of immiscible dense fluids as well as the retention of the fluids after waterflooding (a first step in remediation). Particle transport was found to be heavily affected by the local geometry in the fracture, specifically lowering the likelihood of attachment to fracture walls limiting the filtration effects, and thus allowing greater contaminants to exit the fracture. Ultimately, these results lead to a greater understanding of the mechanisms of transport in fractured media.

Tumour dissemination is a major reason for failure of therapy for many tumour types therefore there is a requirement for novel targets & therapies. The αIIbβ3 and αvβ3 integrins have been demonstrated to have significant involvement at many stages of the tumour dissemination process including, tumour cell adhesion, migration, metastasis and angiogenesis, and thus the β3 integrins are a potential target for therapeutic antagonism with small molecules. Because of the clear interaction between the different integrin types, targeting integrins as a therapeutic strategy requires targeting more than one integrin type. Consequently, the ICT is developing a group of novel new αIIbβ3 and αvβ3 integrin dual antagonists. One of the main challenges is having a relevant, validated experimental model that expresses these integrins. The aim of the work presented here is to develop and validate an in vitro αIIbβ3 and αvβ3 integrin expressing assay of tumour cell invasion. The spheroid invasion assay has the advantage over standard monolayer transwell chamber invasion assays of being a 3-dimensional assay, and thus mimics better the cell-cell interactions and architecture that are present in a tumour compared to the monolayer-based assay. A panel of human cancer cell lines known to express one of the molecular targets of interest, αvβ3 integrin was evaluated for the ability to form spheroids and to invade through collagen matrices. One glioma cell line, U87-MG, demonstrated consistent spheroid formation and invasion and was thus selected for further studies. Optimum conditions were established for use of U87-MG in the invasion assay, and the assay was validated using a known inhibitor of invasion, LiCl and known β3 antagonist, cRGDfV. Subsequently a group of novel small molecule β3 antagonists were evaluated at nontoxic concentrations using the assay. Both LiCl and cRGDfV inhibited spheroid invasion through the gel in a dose-dependent manner, thus validating the assay. Furthermore, when the novel small molecule β3 antagonists were evaluated using the model, a dose and time dependent reduction in U87-MG spheroids invasion in collagen was observed. In further work initial steps were taken to construct a cell line which expresses both αIIbβ3 and αvβ3 integrin to use in the model to assess for dual integrin antagonism. In conclusion, this work has established a validated assay which has been utilised for some compounds to evaluate a group of novel small molecule β3 integrin antagonists with encouraging results.