A synthetic phage-displayed antibody repertoire was constructed with equivalent chemical diversity in the third complementarity-determining regions of the heavy (CDR-H3) and light chains (CDR-L3), which contrasts with natural antibodies in which CDR-H3 is much more diverse than CDR-L3 due to the genetic mechanisms that generate antibody encoding genes. Surprisingly, the synthetic repertoire yielded numerous functional antibodies that contained mutated CDR-L3 sequences but a fixed CDR-H3 sequence. Alanine-scanning analysis of antibodies that recognized ten different antigens but contained a common CDR-H3 loop showed that, in most cases, the fixed CDR-H3 sequence was able to contribute favorably to antigen recognition, but in some cases, the loop was functionally inert. Structural analysis of one such antibody in complex with antigen showed that the inert CDR-H3 loop was nonetheless highly buried at the antibody-antigen interface. Taken together, these results show that CDR-H3 diversity is not necessarily required for the generation of antibodies that recognize diverse protein antigens with high affinity and specificity, and if given the chance, CDR-L3 readily assumes the dominant role for antigen recognition. These results contrast with the commonly accepted view of antigen recognition derived from the analysis of natural antibodies, in which CDR-H3 is presumed to be dominant and CDR-L3 is presumed to play an auxiliary role. Furthermore, the results show that natural antibody function is genetically constrained, and it should be possible to develop more functional synthetic antibody libraries by expanding the diversity of CDR-L3 beyond what is observed in nature.

Methods for detection of the spatial position and timing of diesel ignition with improved accuracy are demonstrated in an optically accessible constant-volume chamber at engine-like pressure and temperature conditions. High-speed pressure measurement using multiple transducers, followed by triangulation correction for the speed of the pressure wave, permits identification of the autoignition spatial location and timing. Simultaneously, high-speed schlieren and broadband chemiluminescence imaging provides validation of the pressure-based triangulation technique. The combined optical imaging and corrected pressure measurement techniques offer improved understanding of diesel ignition phenomenon. Schlieren imaging shows the onset of low-temperature (first-stage) heat release prior to high-temperature (second-stage) ignition. High-temperature ignition is marked by more rapid pressure rise and broadband chemiluminescence. The use of multiple pressure sensors also permits charge-amplifier gain optimization tailored to characterize spray behavior rather than the global combustion chamber, thereby providing significantly improved pressure-rise measurement and derived heat-release rate for the fuel spray. Based on pressure data only, this study provides ignition measurement accuracy with temporal resolution below 20 µs, and with spatial resolution below 5 mm, thereby fulfilling the need for better model validation data.

The aim of the study is to examine the survival of new establishments and to identify factors affecting their survival probability and their employment growth.This study uses a unique data set on all new establishments that were created in Sweden 1987 and 1988, with the exception of the construction industry. The results show among others that:(i) new establishments face a high risk of closing down, (ii) the probability of establishment survival increases with the age and size of the establishment,(iii) variables that are assumed to measure access to resources (being a part of a multi-unit firm,and being new due to merger or dispersal) have a positive effect on survival, (iv) the number of employees at the start- up year has a negative effect on the employment growth, and (v) demographic and educational factors are important in explaining survival and growth. Copyright Kluwer Academic Publishers 2004

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