An Investigation of Factors Influencing the Association between Top Management Ownership and Earnings Management

This study conjectures and shows that the level of stock ownership by top management is non-monotonically associated with managers’ propensity to manage earnings. Increasing ownership from low levels decreases earnings management while ownership at high levels increases earnings management. Further, this study attempts to discern when the effects of management ownership are more salient for the firm. The results of this exploratory analysis of 15,945 firm observations over a six-year period show that the non-monotonic association between top management ownership and earnings management is significant, and hence more important, for the firm characteristics of low growth opportunities, high operating volatility, small size, frequent losses, high-technology, and low institutional ownership

Generation of robust CD8+ T-cell responses against subdominant epitopes in conserved regions of HIV-1 by repertoire mining with mimotopes

HLA-A*0201-restricted virus-specific CD8(+) cytotoxic T lymphocytes (CTLs) do not appear to control HIV effectively in vivo. To enhance the immunogenicity of a highly conserved subdominant epitope, TV9 (TLNAWVKVV, p24 Gag(19–27)), mimotopes were designed by screening a large combinatorial nonapeptide library with TV9-specific CTLs primed in vitro from healthy donors. A mimic peptide with a low binding affinity to HLA-A*0201, TV9p6 (KINAWIKVV), was studied further. Parallel cultures of in vitro-primed CTLs showed that TV9p6 consistently activated crossreactive and equally functional CTLs as measured by cytotoxicity, cytokine production and suppression of HIV replication in vitro. Comparison of TCRB gene usage between CTLs primed from the same donors with TV9 or TV9p6 revealed a degree of clonal overlap in some cases and an example of a conserved TCRB sequence encoded distinctly at the nucleotide level between individuals (a “public” TCR); however, in the main, distinct clonotypes were recruited by each peptide antigen. These findings indicate that mimotopes can mobilize functional crossreactive clonotypes that are less readily recruited from the naïve T cell pool by the corresponding wildtype epitope. Mimotope-induced repertoire diversification could potentially override subdominance under certain circumstances and enhance vaccine-induced responses to conserved but poorly immunogenic determinants within the HIV proteome