Alternative first exon splicing regulates subcellular distribution of methionine sulfoxide reductases

BACKGROUND: Methionine sulfoxide reduction is an important protein repair pathway that protects against oxidative stress, controls protein function and has a role in regulation of aging. There are two enzymes that reduce stereospecifically oxidized methionine residues: MsrA (methionine-S-sulfoxide reductase) and MsrB (methionine-R-sulfoxide reductase). In many organisms, these enzymes are targeted to various cellular compartments. In mammals, a single MsrA gene is known, however, its product is present in cytosol, nucleus, and mitochondria. In contrast, three mammalian MsrB genes have been identified whose products are located in different cellular compartments. RESULTS: In the present study, we identified and characterized alternatively spliced forms of mammalian MsrA. In addition to the previously known variant containing an N-terminal mitochondrial signal peptide and distributed between mitochondria and cytosol, a second mouse and human form was detected in silico. This form, MsrA(S), was generated using an alternative first exon. MsrA(S) was enzymatically active and was present in cytosol and nucleus in transfected cells, but occurred below detection limits in tested mouse tissues. The third alternative form lacked the active site and could not be functional. In addition, we found that mitochondrial and cytosolic forms of both MsrA and MsrB in Drosophila could be generated by alternative first exon splicing. CONCLUSION: Our data suggest conservation of alternative splicing to regulate subcellular distribution of methionine sulfoxide reductases

Registering a Non-Rigid Multi-Sensor Ensemble of Images

Image registration is the task of aligning two or more images into the same reference frame to compare or distinguish the images. The majority of registration methods deal with registering only two images at a time. Recently, a clustering method that concurrently registers more than two multi-sensor images was proposed, dubbed ensemble clustering. In this thesis, we apply the ensemble clustering method to deformable registration scenario for the first time. Non-rigid deformation is implemented by a FFD model based on B-splines. A regularization term is added to the cost function of the method to limit the topology and degree of the allowable deformations. However, the increased degrees of freedom in the transformations caused the Newton-type optimization process to become ill-conditioned. This made the registration process unstable. We solved this problem by using the matrix approximation afforded by the singular value decomposition (SVD). Experiments showed that the method is successfully applied to non-rigid multi-sensor ensembles and overall yields better registration results than methods that register only 2 images at a time. In addition, we parallelized the ensemble clustering method to accelerate the performance of the method. The parallelization was implemented on GPUs using CUDA (Compute Unified Device Architecture) programming model. The GPU implementation greatly reduced the running time of the method

Career Barriers of College Women across Racial/Ethnic Groups: Examination of The Perception of Barriers Scale

The purpose of the study was to examine the factor structure, measurement invariance, and psychometric properties of a commonly used measure of perceived career barriers (The Perception of Barriers Scale; Luzzo & McWhirter, 2001) with a sample of racially diverse college women. The results supported a nine-factor structure of the Perception of Barriers Scale indicating different sources of barriers. In general, configural, metric, and scalar invariance of the Perception of Barriers subscales were found across Asian American, African American, Latina American, and White American college women for the nine-factor structure. All three groups of women of color reported higher career barriers due to racial discrimination, higher educational barriers due to finances concerns, and higher educational barriers due to lack of confidence and skills than White women. The results also demonstrated the potential difference in salient barriers across Asian American, African American, and Latina American women. The reliability estimates were satisfactory and construct validity was supported by negative associations among the scores on several Perception of Barriers subscales and a career-self-efficacy measure. The findings suggested that college women experience barriers from various sources when pursuing their career and educational goals

Politics and the Limits of Philosophy: Political Realism and the Limits of the Political Realist Critique

This thesis will argue that political theory is a diverse field with many questions that can be asked. Because of this, the disagreement between political realism and moralism is not as stark as it may seem. There are four main sections in this thesis. The first section (chapter 1-2) will discuss the idea of a distinctively political normativity. Political realists argue that there is a normativity internal to politics, and we should not apply external moral standards to the domain of politics. I discuss the main strategies that political realists have used to establish this distinctively political normativity and show that they fail to achieve the result political realists want. The second section (chapter 3-4) develops a version of political realism and the political realist critique that does not rely on a distinctively political normativity. I argue that political realists want political theorists to theorise about politics with an ethic of responsibility. Chapter 4 applies the political realist critique to three examples of political philosophy. The third section (chapter 5-6) develops the moralist response. It is here that I show that not all political philosophy has to guide real political agents engage in political struggle directly. Chapter 5 discusses the many roles that political theory can play, and the political realist attempt to limit political theory is unsuccessful. Chapter 6 shows how even political theorists who are interested in stability do not have to theorise about politics in the way that political realists want. Finally, the last section (chapter 7) discusses how the political realist position relies on several metaethical/metaphysical claims about how our moral convictions are the product of a particular history. I argue that this scepticism is implausible because it attempts to undermine the validity of moral justification through an explanation of how we obtained our convictions