Perchlorate ion interferes with thyroid function by competitively inhibiting the sodium-iodide symporter, thus blocking iodide uptake into the thyroid gland. In this study, the effect of perchlorate exposure on thyroid function and thyroid-responsive gene expression were examined in (1) embryos from eggs laid by perchlorate-treated Japanese quail hens and (2) perchlorate-treated young Japanese quail. I hypothesized that perchlorate exposure would decrease thyroid function and that the consequent hypothyroidism would alter the expression of thyroid sensitive genes. Laying Japanese quail hens were treated with 2000 mg/l and 4000 mg/l ammonium perchlorate in drinking water. Eggs from these hens were incubated. Embryos, exposed to perchlorate in the egg, were sacrificed at day 14 of the 16.5 day incubation period. Japanese quail chicks, 4-5 days old, were treated with 2000 mg/l ammonium perchlorate in drinking water for 2 and 7.5 weeks. Thyroid status was evaluated by measuring plasma thyroid hormone concentrations, thyroid gland weight and thyroidal thyroid hormone storage. Expression of thyroid-responsive genes was evaluated by measuring the mRNA levels of Type 2 deiodinase (D2) in the brain and liver, RC3/neurogranin mRNA level in the brain and Spot 14 mRNA level in the liver. Maternal perchlorate exposure led to embryonic hypothyroidism, demonstrated by thyroid hypertrophy and very low embryonic thyroidal TH storage. Embryonic hypothyroidism decreased body growth and increased D2 mRNA level in the liver (a presumed compensatory response to hypothyroidism) but did not affect the mRNA levels of D2 and RC3 in the brain. Spot 14 mRNA was not detected in embryonic liver. In the second part of the study, quail chicks showed early signs of hypothyroidism after two weeks of 2000 mg/l ammonium perchlorate exposure; plasma concentration and thyroid gland stores of both T4 and T3 were significantly decreased. After 7.5 weeks of perchlorate exposure, all thyroid variables measured indicated that the chicks had become overtly hypothyroid. D2 mRNA level was increased, a compensatory response to hypothyroidism, and spot 14 mRNA level was decreased, a substrate-driven response in the liver of quail chicks after two weeks of perchlorate exposure. However, no difference was observed in the mRNA levels of D2 and spot 14 in the liver after 7.5 weeks of perchlorate exposure, suggesting there was some adaptation to the hypothyroid condition. The mRNA level of D2 and RC3 in the brain was not affected by perchlorate-induced hypothyroidism in quail chicks after either 2 or 7.5 weeks of perchlorate exposure. As in the embryos, this suggests the brain of chicks was "protected" from the hypothyroid body conditions. / Ph. D.

The most common and aggressive malignant brain tumor, glioblastoma (GBM), demonstrates on average a 5-year survival rate of only 6.8%. Difficulties arising in the treatment of GBM include the inability of large molecular agents to permeate through the blood-brain barrier (BBB); migration of highly invasive GBM cells beyond the solid tumor margin; and gross, macroscopic intratumor heterogeneity. These characteristics complicate treatment of GBM with standard of care, resulting in abysmal prognosis. Electroporation-based therapies have emerged as attractive alternates to standard of care, demonstrating favorable outcomes in a variety of tumors. Notably, irreversible electroporation (IRE) has been used for BBB disruption and nonthermal ablation of intracranial tumor tissues. Despite promising results, IRE can cause unintended muscle contractions and is susceptible to electrical heterogeneities. Second generation High-frequency IRE (H-FIRE) utilizes bursts of bipolar pulsed electric fields on the order of the cell charging time constant (~1 μs) to ablate tissue while reducing nerve excitation, muscle contraction, and is far less prone to differences in electrical heterogeneities. Throughout my dissertation, I discuss investigations of H-FIRE for the treatment of malignant gliomas and other intracranial disorders. To advance the versatility, usability, and understanding of H-FIRE for intracranial applications, my PhD thesis focuses on: (1) characterizing H-FIRE-mediated BBB disruption effects in an in vivo healthy rodent model; (2) the creation of a novel, real-time impedance spectroscopy technique (Fourier Analysis SpecTroscopy, FAST) using waveforms compatible with existing H-FIRE pulse generators; (3) development of FAST as an in situ technique to monitor ablation growth and to determine patient-specific ablation endpoints; (4) conducting a preliminary efficacy study of H-FIRE ablation in an orthotopic F98 rodent glioma model; and (5) establishing the feasibility of MRI-guided H-FIRE for the ablation malignant gliomas in a spontaneous canine glioma model. The culmination of this thesis advances our understanding of H-FIRE in intracranial tissues, as well as develops a novel, intraoperative impedance spectroscopy technique towards determining patient-specific ablation endpoints for intracranial H-FIRE procedures. / Doctor of Philosophy / The most aggressive malignant brain tumor, glioblastoma (GBM), demonstrates on average a 5-year survival rate of only 6.8%. Difficulties arising in the treatment of GBM include the inability of chemotherapy agents to diffuse into brain tumor tissue as these molecular are unable to pass the so-called blood-brain barrier (BBB). This tumor tissue also presents with cells with the propensity to invade healthy tissue, to the point where diagnostic scans are unable to capture this migration. These characteristics complicate treatment of GBM with standard of care, resulting in abysmal prognosis. Electroporation-based therapies have emerged as attractive alternates to standard of care, demonstrating favorable outcomes in a variety of tumors. For instance, irreversible electroporation (IRE) has been used to successfully treat tumors in the prostate, liver, kidney, and pancreas. Second generation High-frequency IRE (H-FIRE) may possess even greater antitumor qualities and this is the focus of my dissertation. Throughout my dissertation, I discuss investigations of H-FIRE with applications to treat malignant gliomas and other intracranial disorders. My PhD thesis focuses on: (1) characterizing H-FIRE effects for enhanced drug delivery to the brain; (2) the creation of a new, real-time electrical impedance spectroscopy technique (Fourier Analysis SpecTroscopy, FAST) using waveforms compatible with existing H-FIRE pulse generators; (3) development of FAST as a technique to determine H-FIRE treatment endpoints; (4) conducting a preliminary efficacy study of H-FIRE to ablate rodent glioma tumors; and (5) establishing the feasibility of MRI-guided H-FIRE for the ablation malignant gliomas in a spontaneous canine glioma model. The culmination of this thesis advances our understanding of H-FIRE in intracranial tissues, as well as develops a new impedance spectroscopy technique to be used in determining patient-specific ablation endpoints for intracranial H-FIRE procedures.

This dissertation consists of three essays studying three closely related aspects of supply chain resilience. The first essay is "Value of Supply Disruption Information and Information Accuracy", in which we examine the factors that influence the value of supply disruption information, investigate how information accuracy influences this value, and provide managerial suggestions to practitioners. The study is motivated by the fact that fully accurate disruption information may be difficult and costly to obtain and inaccurate disruption information can decrease the financial benefit of prior knowledge and even lead to negative performance. We perform the analysis by adopting a newsvendor model. The results show that information accuracy, specifically information bias and information variance, plays an important role in determining the value of disruption information. However, this influence varies at different levels of disruption severity and resilience capacity. The second essay is "Quantifying Supply Chain Resilience: A Dynamic Approach", in which we provide a new type of quantitative framework for assessing network resilience. This framework includes three basic elements: robustness, recoverability and resilience, which can be assessed with respect to different performance measures. Then we present a comprehensive analysis on how network structure and other parameters influence these different elements. The results of this analysis clearly show that both researchers and practitioners should be aware of the possible tradeoffs among different aspects of supply chain resilience. The ability of the framework to support better decision making is then illustrated through a systemic analysis based on a real supply chain network. The third essay is "Network Characteristics and Supply Chain Disruption Resilience", in which we investigate the relationships between network characteristics and supply chain resilience. In this work, we first prove that investigating network characteristics can lead to a better understanding of supply chain resilience behaviors. Later we select key characteristics that play a critical role in determining network resilience. We then construct the regression and decision tree models of different supply chain resilience measures, which can be used to estimate supply chain network resilience given the key influential characteristics. Finally, we conduct a case study to examine the estimation accuracy. / Ph. D.

The obligate stem parasite Cuscuta pentagona is able to take up host plant mRNA through a specialized organ known as the haustorium. Direct cell-to-cell symplastic connections between two different organisms are rare, and the translocation mechanisms and fate of these RNAs in the parasite is not understood. To characterize this phenomenon, mobile Arabidopsis and tomato mRNAs were identified from microarray and transcriptome sequencing projects and quantified in the host-parasite system. Mobile RNAs were quantified using real time (qRT)-PCR and were found to vary substantially in their rate of uptake and distribution in the parasite. Transcripts of tomato Gibberellic Acid Insensitive (SlGAI) and Cathepsin D Protease Inhibitor (SlPI) can be traced over 30-cm of parasite stem. SlPI was abundant in the C. pentagona stem, but the number of copies decreased substantially within the first eight hours post detachment. Additional studies of mobile RNAs from Arabidopsis, Translationally Controlled Tumor Protein (AtTCTP), Auxin Response Factor (AtARF) and a Salt-inducible Zinc Finger Protein (AtSZFP) supported the idea that mRNA molecules differ in their mechanisms of uptake and mobility between host and parasite. Known phloem-mobile RNAs (SlGAI and AtTCTP) have uptake patterns that differ from each other as well as from other RNAs that are not reported to be phloem mobile (SlPI and AtSZF1). The function of RNAs in plants extend beyond protein translation to include post transcriptional gene silencing or long distance signaling, and mobile RNA in C. pentagona systems offers novel insights into this aspect of plant biology. Studies of cell-to-cell trafficking of RNAs and other macromolecules would be facilitated by the ability to manipulate individual cells. To this end, work was initiated to explore alternative approaches to understanding single cell biology using laser-mediated approaches. Optoperforation, or the use of multiphoton processes to form quasi-free electron plasmas to initiate transient pore formation in plasma membranes, has been demonstrated, but not in cells of an intact plant. This work details a protocol for optoperforation of Arabidopsis epidermal cells to allow for uptake of external dye-labeled dextrans and retention for up to 72 hours, and has the potential for transformation and molecular tagging applications. / Ph. D.

Gravimetric analysis was used to determine the release rates and longevities of several designs of pheromone dispensers for mating disruption of leafrollers and codling moth, Cydia pomonella (Linneaus). Release rates were described by linear equations for at least four months, but by the end of the season release rates tended to become erratic. Biocontrol’s red-brown codling moth dispenser lasted for up to four months, and one application of the dispenser in early May should control codling moth for the entire season in Virginia apple orchards. Ecogen and Hercon leafroller dispensers lasted for a shorter time than the codling moth dispensers and would require two applications per season to provide the best control of their target pests. In a commercial northern Virginia apple orchard, the effects of pheromone trap height and pheromone dispenser height on captures of the tufted apple bud moth, Platynota idaeusalis (Walker), were studied. Low traps (2.0 m) were more sensitive than high traps (4.5 m) for monitoring tufted apple bud moth. The number of moths caught in 1994 and 1995 in a two-hectare mating disruption plot with pheromone dispensers placed in the upper third of the tree was not significantly different from the number caught in a plot with pheromone dispensers placed at head height. Fruit damage was very high in both pheromone plots in 1994, but by 1995 it appeared that mating disruption was able to reduce fruit damage due to leafroller larvae. / Master of Science

The objective of this thesis is to assess and map the logistics chain of Kaunis Iron AB in order to find areas of optimisation opportunities. By focusing on the internal aspects of the logistics chain, this thesis aims to provide Kaunis Iron AB with quantified suggestions of how to increase the internal efficiency and effectiveness. With data provided by Kaunis Iron AB and workshops with key stakeholders, a comprehensive analysis of the logistics chain was established, from which different Key Perfomance Indicators could be identified. In addition to the data received from Kaunis Iron AB, other sources of secondary data was collected, further validating the findings and tying together the internal subjective perspective with a more objective ditto. With a ramp-up in production volume being imminent, evaluations both pertaining to the current state of operations and a future state were conducted coupled with comparisons between the two. Utilising the aforementioned Key Performance Indicators, several sensitivity analyses were presented, which showcased how different adjustments in the logistics chain affected the output, both at the current state conditions and in the ramped-up production state. From this, the thesis presents the adjustments that, we as authors, find most suitable for Kaunis Iron AB in order to optimise their logistics chain.

No / Supply chain resilience has been suggested to curb the impact of disruptions on supply chains. While this proposition seems coherent in theory, empirical evidence supporting this is limited, as existing literature has centred on exploring the impact of supply chain resilience on disruptions which are based on set time frames, non-supply chain specific as well as examining non-dynamic disruptive events. This study contends that resilience strategies are dynamic and as such their applications within supply chains differ. Therefore examining the impact of resilience will be appropriate on a dynamic disruption within a specific supply chain. In view of this, the paper examines through existing literature the applicability of agility within the pharmaceutical supply chain when dynamic disruptions like drug shortages occur. The study finds alertness, accessibility, connectivity and visibility as dimensions of supply chain agility that are capable of reducing the impact of drug shortages.

Background: With an increasing population and volume in global trade, pressures on supply chains have escalated immensely. Over the past five years, multiple events have caused disruptions in supply chains, affecting economies and products not arriving on time. It is essential for managers to understand why a crisis might arise and how to handle it most efficiently to minimize the impact on the organization.  Purpose: Establish what managers in Sweden have learned from recent supply chain disruptions and how they are responding to the current disruption caused by Russia’s invasion of Ukraine. Method: The research was grounded on the interpretivism paradigm with convenience and purposeful sampling. Semi-structured interviews with seven participants were conducted and reviewed through thematic analysis with an inductive and deductive approach induced by exploratory research that led to qualitative data.  Conclusion: The findings in this report resulted in an understanding of the mechanisms used to handle recent disruptions. The focus was on securing the flow of materials through local and multiple suppliers, as well as warehouses with safety stock. Communication, transparency and other intangible competencies were also important. During the ongoing disruption, results showed that more emphasis was placed on local and multiple suppliers, mapping, and world assessment.

Why do we laugh at eight-year-old Butters Stotch when he sings about sodomy in South Park? How does the dominant audience understand Michael Scott to be heterosexual following his announcement that he would have sex with a male employee in the American version of The Office? What are the implications of laughing at Bobby Hill when his father expresses embarrassment over Bobby’s plus size modeling career in King of the Hill? I argue that the above characters are versions of the disruptive male character type common in sitcom satires. The sitcom satire is a hybrid genre that follows the sitcom format and contains satirical content. Using tools from queer theory and cultural studies, this thesis examines how particular examples of disruptive characters function in sitcom satires to reinforce cultural codes regarding gender and sexuality. In the first chapter, I suggest that when the male character disrupts normative gender and sexuality the audience laughs at the surprise and incongruity. I argue that the key feature of this character type is that he consistently disrupts cultural codes in ways that would normally mark him as homosexual yet he is not read as a gay character in the shows examined. I suggest that he is queer insofar as he does not fit neatly into the heterosexual/homosexual binary. Following this, in the second chapter, I explain how techniques used in the narrative; such as other characters' reactions, awkward silences, music selection, and scene changes, provide commentary on the disruption. I argue that characters that disrupt expectations of nonnative gender presentation and heterosexuality create anxiety for a dominant audience; the narrative commentary acknowledges that anxiety. Recognizing a character's disruption of cultural codes allows the dominant audience to relieve the anxiety and to reconcile the character's disruption with his heteronormative identity. Finally, in the third chapter I argue that the disruptive character often displays shame or pride in unexpected circumstances and is represented as ignorant I argue that by comparing normative behavior with disruptive or ignorant behavior, the narratives create the preferred or dominant meaning of the desirability of normative behavior. I conclude that the process of disruption, recuperation, and reinforcement reveals two perspectives. First, if disruptions confirm the desirability of the codes they attempt to subvert, then resisting these codes is difficult. Second. disruptions can reveal the construction of these codes; if these cultural codes were as natural as we are to believe, then our culture would not need to work as diligently to uphold them.

The introduction of the theoretical part is devoted to the analysis of threats, another part to the rescue of animals. In the next part, I focused on zoological gardens and evacuation of animals. The last chapter of the theoretical part deals with the evacuation of selected species of animals. When selecting individual species, I focused on those that are most represented in Dvorec Zoo. The aim of my thesis was to create an analysis of the preparedness of the selected zoo to selected crisis situations and to identify the risks of evacuation of the zoo. In order to achieve these goals, I have set research questions - how is the zoo prepared for selected crisis situations? And what are the possible risks associated with evacuating selected species? In the second part of my thesis I focused on the research itself, which included an interview with the director of Dvorec Zoo. Based on the interview and my own observation I processed the KARS method. The KARS method has identified 6 risks that could compromise the operation of Dvorec Zoo. These risks include extreme wind, large-scale gas supply disruption, large-scale electricity supply disruption, snow calamity, and extremely low temperatures. Based on the identified risks, I created a plan for MU solution for Dvorec Zoo. In the MU solution plan, I focused primarily on the impacts on operation, planned measures, procedures and responsible people. Dvorec Zoo will, of course, be provided with this plan.