Upon activation by the platelet-derived growth factor receptor (PDGFR), phosphatidylinositol 3'-kinase (PI3K) converts phosphatidylinositol 4,5-bisphosphate to phosphatidylinositol 3,4,5-trisphosphate to activate the PI3K/Akt cellular survival signalling pathway within cells. The p85 subunit of PI3K has also been shown to have GTPase activating protein (GAP) activity towards Rab proteins involved in receptor endocytosis and trafficking, specifically Rab5 and Rab4. Rab5 is responsible for regulating the fusion of vesicles containing activated receptors to traffic them to intracellular early/sorting endosomes. Rab4 is responsible for regulating the exit of receptors to a recycling pathway back to the plasma membrane. The p85 RabGAP activity is responsible for deactivating Rab5 and Rab4 function by accelerating their GTPase activity, resulting in the inactive conformation of Rab5 and Rab4, and decreased vesicle fusion events during receptor trafficking. The work in this thesis was performed to understand how p85 interacts with, and regulates, Rab5 and Rab4. Glutathione S-transferase pulldown experiments showed the p85 protein was able to interact with Rab5 through its BH domain and another unidentified domain. Cells expressing a p85-R274A mutant defective for RabGAP activity displayed increased PDGFR activation and decreased degradation. To understand the mechanism of decreased PDGFR degradation, PDGFR immunoprecipitation experiments showed the PDGFR was ubiquitinated, a signal needed for multi-vesicular body sorting. Biotinylation experiments showed the PDGFR was being more rapidly endocytosed and then sequestered within the cell. Immunofluorescence experiments showed cells expressing the p85-R274A mutant clearly altered PDGFR trafficking during receptor endocytosis. These results suggest the PDGFR was not spending longer periods of time on the cell surface to continue signalling and was not lacking the modification needed to be sorted to a degradative pathway. The defective trafficking observed in p85-R274A expressing cells, over time, may block PDGFR trafficking, which prevents normal PDGFR dephosphorylation and degradation, and could be attributed to a lack of sufficient cytosolic Rab5-GDP and Rab4-GDP required to associate with new membranes and facilitate additional vesicle fusion events. The lack of lysosomal targeting allows the receptor to be sequestered in cells, but still have the ability to signal as the receptor would not be targeted to multi-vesicular bodies where signalling is abolished.

This thesis describes a novel device, the Virtual Air Gap Variable Reactor (VAG-VR), which is capable of producing a continuously variable reactance by locally saturating a small section of the reactor core via an embedded dc control winding. Variable Reactors have many applications in the power industry such as control of line power flow, voltage regulation, reactive line compensation and limiting inrush currents. A variable reactor is most commonly implemented as a thyristor controlled reactor (TCR) by switching in and out a constant reactance to achieve an averaged variable reactance. By using a virtual air gap, a continuously variable reactance is possible. The VAG-VR offers a better dynamic response, without introducing the harmonics created by the thyristor switching of a TCR. The VAG-VR gives low triplen harmonics and therefore allows control of reactive power in single phase or unbalanced three phase systems as would be required in the distribution system. An experimental prototype VAG-VR was developed to investigate three main performance measures: steady state performance, dynamic response and harmonic performance. Over the operating range of the VAG-VR inductance was varied from 100% to 9% of its original value. The dynamic response of the VAG-VR is approximately one tenth of a cycle. This compares favorably to a TCR which responds in approximately half a cycle. Harmonics are also shown to be significantly reduced in the VAG-VR compared to the TCR. A dynamic model of the VAG-VR, suitable for incorporation into power system simulations, was developed and validated. Parameters were determined both experimentally and through finite element method (FEM) simulations. Both experimental and simulation results indicate that the VAG-VR offers a technically viable alternative to the TCR.

Studien syftar till att undersöka forskares upprätthållande av säkerhetiseringen av Irans kärnkraftprogram och hur detta påverkar deras roll som potentiella policyskapare. Studien ämnar vara teoriutvecklande genom att definiera Köpenhamnsskolans aktörsroll inom säkerhetiseringsteorin på ett mer nyanserat och precist sätt. Studien går igenom olika perspektiv inom debatten kring ”bridging the gap” mellan teori och praktik och använder Köpenhamnsskolans säkerhetiseringsteori som analytiskt ramverk vid analysen av det empiriska materialet. Studien analyserar artiklar skrivna av amerikanska forskare i amerikanska tidskrifter och undersöker hur och om dessa upprätthåller säkerhetiseringen av Irans kärnkraftprogram. Studien sätter därmed forskarna i rollen som säkerhetiserande aktörer för att se hur detta kan påverka forskarnas roll i att ”bridge the gap”. Studien menar att forskare genom att ha ”dubbla roller” som både ”forskare” och ”aktörer” kan använda sig av säkerhetisering för att ”bridge the gap” mellan forskning och policyskapande.

A modified Split Hopkinson Pressure Bar (SHPB) system is used to determine the mechanical properties of soft and ultra-soft materials. An aluminum bar is introduced to reduce the impedance mismatch between the test system and sample. The small signal of the forces was measured by a quartz crystal gauge system. The high precision Laser gap gauge (LGG) system was used to measure the deformation of samples. The compressive tests of Cemented Paste Backfill (CPB), fresh CPB and Polymethylmethacrylate (PMMA) and the fracture toughness tests of PMMA were conducted to approve the legitimacy of our modified SHPB system. From these experiments, the efficiency and economy of the modified SHPB system were attested.

The specialized myocytes of the ventricular conduction system (VCS) coordinate ventricular contraction and are critical for efficient pumping by the heart. Impaired VCS conduction is characteristic of inherited forms of cardiac conduction disorders. Here we show that the Iroquois homeobox 3 (Irx3) transcription factor is preferentially expressed in the developing and mature VCS. Loss of Irx3 in mice results in slowed VCS conduction and prolonged QRS duration with right bundle branch block, caused by reduction (42%) in VCS-specific connexin 40 (Cx40) expression and VCS fiber hypoplasia, absent in littermate controls. Therefore, we show that the role of Irx3 in the heart is two-fold, whereby Irx3 (1) indirectly regulates Cx40 gene expression, by repressing a repressor of Cx40 transcript, and (2) controls VCS maturation, possibly in an Nkx2-5-dependent manner. To our knowledge, this is the first report of a role for Irx3 in regulating the development and function of the VCS.

The specialized myocytes of the ventricular conduction system (VCS) coordinate ventricular contraction and are critical for efficient pumping by the heart. Impaired VCS conduction is characteristic of inherited forms of cardiac conduction disorders. Here we show that the Iroquois homeobox 3 (Irx3) transcription factor is preferentially expressed in the developing and mature VCS. Loss of Irx3 in mice results in slowed VCS conduction and prolonged QRS duration with right bundle branch block, caused by reduction (42%) in VCS-specific connexin 40 (Cx40) expression and VCS fiber hypoplasia, absent in littermate controls. Therefore, we show that the role of Irx3 in the heart is two-fold, whereby Irx3 (1) indirectly regulates Cx40 gene expression, by repressing a repressor of Cx40 transcript, and (2) controls VCS maturation, possibly in an Nkx2-5-dependent manner. To our knowledge, this is the first report of a role for Irx3 in regulating the development and function of the VCS.

Upon activation by the platelet-derived growth factor receptor (PDGFR), phosphatidylinositol 3'-kinase (PI3K) converts phosphatidylinositol 4,5-bisphosphate to phosphatidylinositol 3,4,5-trisphosphate to activate the PI3K/Akt cellular survival signalling pathway within cells. The p85 subunit of PI3K has also been shown to have GTPase activating protein (GAP) activity towards Rab proteins involved in receptor endocytosis and trafficking, specifically Rab5 and Rab4. Rab5 is responsible for regulating the fusion of vesicles containing activated receptors to traffic them to intracellular early/sorting endosomes. Rab4 is responsible for regulating the exit of receptors to a recycling pathway back to the plasma membrane. The p85 RabGAP activity is responsible for deactivating Rab5 and Rab4 function by accelerating their GTPase activity, resulting in the inactive conformation of Rab5 and Rab4, and decreased vesicle fusion events during receptor trafficking. The work in this thesis was performed to understand how p85 interacts with, and regulates, Rab5 and Rab4. Glutathione S-transferase pulldown experiments showed the p85 protein was able to interact with Rab5 through its BH domain and another unidentified domain. Cells expressing a p85-R274A mutant defective for RabGAP activity displayed increased PDGFR activation and decreased degradation. To understand the mechanism of decreased PDGFR degradation, PDGFR immunoprecipitation experiments showed the PDGFR was ubiquitinated, a signal needed for multi-vesicular body sorting. Biotinylation experiments showed the PDGFR was being more rapidly endocytosed and then sequestered within the cell. Immunofluorescence experiments showed cells expressing the p85-R274A mutant clearly altered PDGFR trafficking during receptor endocytosis. These results suggest the PDGFR was not spending longer periods of time on the cell surface to continue signalling and was not lacking the modification needed to be sorted to a degradative pathway. The defective trafficking observed in p85-R274A expressing cells, over time, may block PDGFR trafficking, which prevents normal PDGFR dephosphorylation and degradation, and could be attributed to a lack of sufficient cytosolic Rab5-GDP and Rab4-GDP required to associate with new membranes and facilitate additional vesicle fusion events. The lack of lysosomal targeting allows the receptor to be sequestered in cells, but still have the ability to signal as the receptor would not be targeted to multi-vesicular bodies where signalling is abolished.

A modified Split Hopkinson Pressure Bar (SHPB) system is used to determine the mechanical properties of soft and ultra-soft materials. An aluminum bar is introduced to reduce the impedance mismatch between the test system and sample. The small signal of the forces was measured by a quartz crystal gauge system. The high precision Laser gap gauge (LGG) system was used to measure the deformation of samples. The compressive tests of Cemented Paste Backfill (CPB), fresh CPB and Polymethylmethacrylate (PMMA) and the fracture toughness tests of PMMA were conducted to approve the legitimacy of our modified SHPB system. From these experiments, the efficiency and economy of the modified SHPB system were attested.

This paper examines the effect of psychological traits on earnings and furthermore whether it helps explain the gender wage gap. Public-use data collected from The National Longitudinal Study of Adolescent Health is used to evaluate the impact on earnings on seven psychological factors: masculine traits, self esteem, analytical problem solving approach, willingness to work hard, impulsiveness, problem avoidance, and self-assessed intelligence. Findings show that gender differences in psychological traits are significant and returns to observable characteristics differ somewhat by gender as well. Among the young sample of U.S. employees evaluated in this study, I find that up to 21 percent of the gender wage gap can be explained, with psychological factors specifically explaining up to 1.5 percent of this gap.

This study aims to measure the wage gap between the white and Mexican population residing in the United States. It also looks at male and female first- and second-and-higher generations in both white and Mexican populations. Integrated Public Use Microdata Series (IPUMS) is used for the years 1980, 1990, 2000, and 2010. This study finds that first-generation white males are negatively affected by the wage gap, while second-and-higher-generation Mexican females have continuously benefited from the wage gap over the past thirty years.