Leaving and Coming Back to Canada : Evidence from Longitudinal Data (Working Paper 32)

The paper exploits the unique strengths of Statistics Canada's Longitudinal Administrative Database ("LAD"), constructed from individuals' tax records, to shed new light on the extent and nature of the emigration of Canadians to other countries and their patterns of return over the period 1982-1999. The empirical evidence begins with some simple graphs of the overall rates of leaving over time, and follows with the presentation of the estimation results of a model that essentially addresses the question: "who moves?" The paper then analyses the rates of return for those observed to leave the country - something for which there is virtually no existing evidence. Simple return rates are reported first, followed by the results of a hazard model of the probability of returning which takes into account individuals' characteristics and the number of years they have already been out of the country. Taken together, these results provide a new empirical basis for discussions of emigration in general, and the brain drain in particular. Of particular interest are the ebb and flow of emigration rates observed over the last two decades, including a perhaps surprising turndown in the most recent years after climbing through the earlier part of the 1990s; the data on the number who return after leaving, the associated patterns by income level, and the increases observed over the last decade.

Structural and Functional Characterization of the Human Tribbles Homologue 2 Pseudokinase

The Tribbles Homologues are a family of three eukaryotic pseudokinases (Trb1, Trb2, Trb3) that act as allosteric inhibitors and regulatory scaffold sites in pathways governing adipogenesis, cell proliferation and insulin signaling. The Tribbles Homologues have the same overall tertiary structure of the eukaryotic protein kinase domain, but lack multiple residues necessary to catalysis in the nucleotide-binding P-loop and the Mg2+-coordinating DFG motif. Trb1 has been shown conclusively to be incapable of binding ATP, whereas a recent study presents evidence that Trb2 autophosphorylates independently of Mg2+ in vitro. This finding is surprising given the high degree of sequence similarity between the two proteins (71%), and suggests unique nucleotide binding and phosphotransfer mechanisms. The goal of this project was to investigate whether Trb2 possesses kinase activity or not and determine its structural basis. A method for the high-yield recombinant expression and purification of stable Trb2 was developed. Trb2 nucleotide binding and autophosphorylation could not be detected across multiple experimental approaches, including thermal shift assays, MANT-ATP fluorescence, radiolabeled phosphate incorporation, and nonspecific ATPase activity assays. Further characterization also revealed that Trb2 forms homomultimers with possible functional consequences, and extensive crystallization screening has yielded multiple promising conditions that could produce diffraction-quality crystals with further optimization. This project explores the difficulties in functionally characterizing putatively active pseudokinases, and proposes a structural basis for the conserved pseudokinase features of the Tribbles homologues.