Financial constraints on research and development

This dissertation examines whether-there exists financial constraints and, if so, their implications for investment in research and development expenditures. It develops a theoretical model of credit rationing and research and development in which both are determined simultaneously and endogenously. The model provides a useful tool to examine different policies that may help alleviate the negative the effect of financial constraints faced by firms.^ The empirical evidence presented deals with two different cases, namely, the motor vehicle industry in Germany (1970-1990) and the electrical machinery industry In Spain (1975-1990).^ The innovation in the empirical analysis is that it follows a novel approach to identify events that allow us to isolate the effect of financial constraints in the determination of research and development.^ Further, empirical evidence is presented to show that in the above two cases financial constraints affect investment in physical capital as well.^ The empirical evidence presented supports the results of the theoretical model developed in this dissertation, showing that financial constraints negatively affect the rate of growth of innovation by reducing the intensity of research and development activity. ^

Role of Pseudomonas aeruginosa PA4157in Quorum Sensing and Iron Transport Regulation

Pseudomonas aeruginosa, a Gram-negative opportunistic pathogen, is a pnmary contributing factor responsible for the morbidity and mortality in patients with cystic fibrosis. One of the trademarks of P. aeruginosa is its ability to resist antibiotics. P. aeruginosa does so in part through the LysR-type transcription factor, AmpR. To identify additional members of the AmpR regulon, a new algorithm called iterative enhancement of motifs was used to identify putative AmpR binding sites upstream of open reading frames in the P. aeruginosa genome. The surprising primary hit of this analysis was the promoter of an uncharacterized open reading frame, P A 415 7. P A 415 7 is located upstream ofthefep operon, which is known to be involved in iron acquisition. PA4157 shares high homology to the IclR family of transcriptional regulators which are known to regulate quorum sensing (QS), an elaborate cell-cell communication signaling system that uses quoromones. We postulated two hypotheses: 1) AmpR regulation of QS genes is mediated by PA4157, and 2) PA4157 may be involved in iron acquisition. To address the role of P A 415 7 we generated an in-frame chromosomal deletion of P A 415 7 in P. aeruginosa PA01 (PA0 PA4157). We compared PA0 PA4157 with its parent strain P A0 1 for its ability to produce quoromones using Chromobacterium violaceum as an indicator strain and LasA proteases using Staphylococcus aureus. We also tested its role in virulence using a Caenorhabditis elegans killing assay. Growth in iron-deficient media was also examined to determine if P A4157 has a potential role in iron uptake regulation. Our preliminary results suggest that P A 415 7 is not involved in quorum sensing regulation but does seem to exert a negative regulatory effect on iron uptake in P. aeruginosa P A0 1.