BackgroundDuring early stages of brain development, secreted molecules, components of intracellular signaling pathways and transcriptional regulators act in positive and negative feed-back or feed-forward loops at the mid-hindbrain boundary. These genetic interactions are of central importance for the specification and subsequent development of the adjacent mid- and hindbrain. Much less, however, is known about the regulatory relationship and functional interaction of molecules that are expressed in the tectal anlage after tectal fate specification has taken place and tectal development has commenced.ResultsHere, we provide experimental evidence for reciprocal regulation and subsequent cooperation of the paired-type transcription factors Pax3, Pax7 and the TALE-homeodomain protein Meis2 in the tectal anlage. Using in ovo electroporation of the mesencephalic vesicle of chick embryos we show that (i) Pax3 and Pax7 mutually regulate each other's expression in the mesencephalic vesicle, (ii) Meis2 acts downstream of Pax3/7 and requires balanced expression levels of both proteins, and (iii) Meis2 physically interacts with Pax3 and Pax7. These results extend our previous observation that Meis2 cooperates with Otx2 in tectal development to include Pax3 and Pax7 as Meis2 interacting proteins in the tectal anlage.ConclusionThe results described here suggest a model in which interdependent regulatory loops involving Pax3 and Pax7 in the dorsal mesencephalic vesicle modulate Meis2 expression. Physical interaction with Meis2 may then confer tectal specificity to a wide range of otherwise broadly expressed transcriptional regulators, including Otx2, Pax3 and Pax7.

Acyl phosph(on)ates are shown to inhibit serine -lactamases and provide a new source of relatively stable complexes. Thus, benzoyl phenyl phosphate, benzoyl phenylphosphonate, and dibenzoyl phosphate react with the class C -lactamase of Enterobacter cloacae P99 at micromolar concentrations to form an acyl enzyme of half-life about 40 s. The phosphonate reacts further more slowly to produce a much more inert complex. Dibenzoyl phosphate reacts with the class A TEM -lactamase to form an acyl enzyme of half-life about 8 s and, more slowly, reaching completion after an average of about 80 turnovers, a more inert complex, of half-life about 2 h. The acyl phosphonates thus represent a new starting point for the design of -lactamase inhibitors and perhaps of antibacterial agents.

In this paper, we model the relation between testing e ort, coverage and reliability. W e present a logarithmic model that relates testing e ort to test coverage block, branch, c-use or p-use. The model is based on the hypothesis that the enumerables like branches or blocks for any c o v erage measure have di erent detectability, just like defects have di erent detectability. This model allows us to relate a test coverage measure directly with defect coverage. Data sets for programs with real defects are used to validate the model. The results are consistent with the known inclusion relationships among block, branch and p-use coverage measures. We show h o w defect density controls time to next failure.The model can eliminate the variables like test application strategy from consideration. It is suitable for high reliability applications where automatic or manual test generation is used to cover enumerables which h a v e not yet been tested.

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