Lobbying Legislation and Cumulative Abnormal Returns

The Honest Leadership and Open Government Act of 2007 (Pub.L. 110-81, 121 Stat. 735, enacted September 14, 2007) was passed by the U.S. Congress in order “to strengthen public disclosure requirements concerning lobbying activity and funding. It placed more restrictions on gifts for members of Congress and their staff, and provides for mandatory disclosure of earmarks in expenditure bills.” Treating this event as a natural experiment, we examine how this legislation affected the Cumulative Abnormal Returns (CARs) of firms that lobbied in the year(s) leading up to the passing of the legislation. We find that companies that lobbied in the years leading up to the legislation significantly underperformed the market in the days surrounding the passage of the legislation

Elucidating the role of YAP in directing mesenchymal stem cell fate

Mesenchymal stem cells (MSCs) are a type of multipotent stem cell capable of differentiating into several cell types, including fat and bone cells. The Hippo pathway effectors TAZ and YAP have been implicated as important regulators of MSC fate, but their roles in this process are poorly understood. The goal of my thesis work was to illuminate the roles of YAP and TAZ in MSC differentiation. I examined how depleting YAP and/or TAZ, or expressing YAP mutants affect the differentiation of C3H10T1/2 cells, which are a multipotent mouse embryo fibroblast cell line capable of forming bone, fat and cartilage. Interestingly, knocking down either YAP or TAZ had different effects on C3H10T1/2 differentiation. YAP knockdown cells that underwent a brown/beige adipogenic protocol showed a significant increase in the amount of lipids produced as compared to control, suggesting that YAP has a role in inhibiting adipogenesis in these cells. YAP knockdown also increased alkaline phosphatase activity in cells subjected to an osteogenic protocol, while simultaneously producing lipid droplets. In contrast, knockdown of TAZ resulted in a decrease in both lipogenesis (in adipogenic differentiation) and alkaline phosphatase activity (in osteogenic differentiation). These observations indicate that depletion of YAP or TAZ leads to defective MSC differentiation, and that without proper YAP and TAZ signaling MSC cells may arrest in an immature state. Bone Morphogenic Proteins (BMPs) are known to play important roles in MSC differentiation, and YAP/TAZ have been implicated in BMP regulation in other systems. I therefore hypothesized that YAP/TAZ may affect MSC differentiation in part by altering BMP signaling. Analysis of activated phosphorylated Smad1 (p-Smad1), a key transcriptional effector of BMP signaling, showed that TAZ and YAP are required to promote p-Smad1 levels. Depletion of TAZ and YAP showed an increase in the expression of Gremlin1 (GREM1), an inhibitor of BMP signaling, and an increase in the expression of BMP4. These observations suggest that TAZ and YAP promote BMP signaling by controlling BMP ligand activity. Given that BMP signaling has important roles early in MSC differentiation, I hypothesized that YAP and TAZ may direct these early processes. To test this, I generated dox-inducible C3H10T1/2 cells capable of expressing wild type YAP or two mutant forms of YAP: a nuclear localized YAP mutant (YAP-5SA), and a transcriptionally inactive YAP mutant (YAP-5SA,S94A). Adipogenic differentiation with these cells showed a reduced level of lipogenesis in the constitutively active nuclear YAP mutant. Analysis of adipogenic markers by qPCR showed a reduction in both PPARγ and UCP1. Osteogenic differentiation experiments in these cells showed that transient expression of all forms of YAP increased the amount of alkaline phosphatase activity, with the 5SA form showing the greatest activity. RNA expression analysis showed that the early marker Runx 2 was highly upregulated in cells overexpressing wild type YAP, while the late markers osteocalcin and osteopontin were greatly reduced in comparison to control. As alkaline phosphatase activity is a mid-stage marker for bone differentiation, the staining results and qPCR data indicate that overexpression of YAP may result in arrest of the differentiation process. A microarray was performed using isolates from 10T1/2 cells transduced with TAZ, YAP or TAZ/YAP siRNA to further evaluate the mechanism through which TAZ and YAP may be acting. The TAZ and YAP double knockdown showed a large change in global gene expression as compared to both the control and the single knockdowns. Among the genes that showed a large change from control was BMP4, the expression of which was reduced more than two-fold over control. Additionally, GREM1 was up-regulated almost two-fold by the double knockdown. Also upregulated was the gene periostin which encodes a protein that enhances BMP incorporation into connective tissues, and may play a role in the mineralization of the extracellular matrix of bone. Based on my observations, along with those of others, I propose that TAZ and YAP are major factors in controlling early cell fate determination of MSCs. There appear to be multiple levels of regulation, and thus the next steps should include clarifying the roles of YAP and TAZ in vivo, and placing their activity chronologically in the differentiation timeline. Such studies will offer insight into stem cell differentiation and may eventually allow for therapeutic opportunities

Cold Warrior Abroad : The Foreign Missions of Vice President Richard Nixon

From 1953-1961, Richard Nixon served as Dwight Eisenhower’s vice president. As vice president, Nixon represented the United States and the Eisenhower administration on several foreign missions. Cold Warrior Abroad studies four of these missions in order to discern Nixon’s development as a statesman, and his understanding of, and impact on Eisenhower’s foreign policies. Through careful examination of archival sources, this thesis will reveal the significant role Nixon came to play in the alteration, execution, and sometimes formation of Eisenhower’s foreign policies in the regions the vice president visited

Discretization schemes for constraint stabilization in nonlinear differential-algebraic systems

In this paper the problem of simulation of differential-algebraic systems is addressed. In modelling me- chanical systems the use of redundant coordinates and con- straints results in differential-algebraic equations, the integra- tion of which can lead to numerical instabilities, such as the so-called drift phenomenon. In [1] the authors have proposed a globally convergent conceptual continuous-time algorithm for the integration of constrained mechanical systems which ensures the existence of solutions and global attractivity of the solution manifold. The objective of this paper is to study the numerical implementation of the algorithm presented in [1]. In addition, the stability properties of the constrained system in the manifold are studied in both the continuous and discrete time cases. The proposed technique is illustrated by means of a simple example

A sequential regularization method for time-dependent incompressible Navier--Stokes equations

The objective of the paper is to present a method, called sequential regularization method (SRM), for the nonstationary incompressible Navier-Stokes equations from the viewpoint of regularization of differential-algebraic equations (DAEs) , and to provide a way to apply a DAE method to partial differential-algebraic equations (PDAEs). The SRM is a functional iterative procedure. It is proved that its convergence rate is O(ffl m ), where m is the number of the SRM iterations and ffl is the regularization parameter. The discretization and implementation issues of the method are considered. In particular, a simple explicit difference scheme is analyzed and its stability is proved under the usual step size condition of explicit schemes. It appears that the SRM formulation is new in the Navier-Stokes context. Unlike other regularizations or pseudo-compressibility methods in the Navier-Stokes context, the regularization parameter ffl in the SRM need not be very small, and the regularized..

Second Wave ERP Education

In the 1990s there was considerable growth in implementations of Enterprise Resource Planning (ERP) Systems. Companies expected these systems to support many of the day to day business transactions. The growth in ERP implementations had a resultant impact on the demand for ERP skills. Many universities recognised this demand and the potential of using ERP Systems software as a teaching tool, and endeavoured to incorporate ERP systems into their curriculum; however most universities have struggled in this task. ERP systems have now evolved to incorporate more strategic components and universities and ERP vendors are investigating ways in which curriculum can be developed to support these new solutions. This paper discusses the evolution of ERP systems and university curriculum. It identifies how one university is addressing this problem and how this approach can be adopted and expanded by other universities

Archaeology and memories on Birch Island

The site of Birch Island has been targeted by the non-profit Healthy Waters Labrador (HWL) and larger Labrador tourism initiative for conservation, environmental education, and commemoration of the former Birch Island settlement. The settlement existed from 1942 to 1969 when it was resettled under the Fisheries Household Resettlement Program. The goal of this project was to gather historical data to inform the information plaques that will be placed around the island. To fulfill this goal, an online survey was set up, 17 individuals were formally interviewed, and a map of surface debris from the former settlement was created. The analysis shows the changing landscape, the island’s traditions, and everyday interactions of life. The product of this research is an amalgamated body of knowledge including archival information, photos, interviews, and archaeological analysis of debris and artifacts that will assist in informing the information plaques planned for Birch Island by HWL

New oxidants for arylations with gold

Gold as an element, has been known for tens of thousands of years, though only recently has the chemistry of gold complexes emerged as an important field for synthetic organic chemistry research. One significant challenge when investigating the chemistry of gold complexes is the oxidation of gold(I) to gold(III), gold(I) having a very high oxidation potential. This thesis comprises an investigation of gold through a homogeneous oxidative arylation of arenes using arylsilanes. Chapter 2 examines the nature of ligands on gold through a gold catalysed arylation reaction and the application of this to synthesise chiral biaryls. The investigation realises that strongly coordinating L type ligands inhibit catalyst turnover and discovers that transient, enantiopure, chiral additives have no effect on the distribution of enantiomers of the chiral biaryl. Chapter 3 explores new, inorganic oxidants for the oxidation of gold(I) to gold(III) and investigates aryl iodide cocatalysts for gold catalysed arylation. It is discovered that periodic acid allows turnover of the gold catalyst and produces a biaryl product from an arylsilanes substrate. Through MALDI-MS, gold is also discovered to react with acetonitrile in the presence of periodic acid, in a novel oxidative reaction for gold, to form a gold(I) cyanide polymer. In Chapter 4, NMR kinetics and stoichiometric experiments are utilised in the investigation of mechanistic details of periodic acid as an oxidant for gold catalysed direct arylation. The six-electron reduction pathway for periodic acid to an iodonium species and the mechanism of formation of aryl iodide from the starting arylsilane is probed. Iodonium is proposed to be the intermediate that forms the aryl iodide byproduct. Further evidence for a reactive iodonium species is found using a chemospecific, nucleophilic trap that prevents the non-productive iodination of aryl silane. A substrate scope of the new arylation conditions using the trap is assessed and the reaction was found to tolerate substrates that generated 5 membered rings. This thesis aims to establish new conditions for gold catalysed arylation of arenes using arylsilanes and describes interactions of oxyiodine species with arylsilanes, nitrile solvents and gold