A novel tertiary amine series of potent muscarinic M(3) receptor antagonists are described that exhibit potential as inhaled long-acting bronchodilators for the treatment of chronic obstructive pulmonary disease. Geminal dimethyl functionality present in this series of compounds confers very long dissociative half-life (slow off-rate) from the M(3) receptor that mediates very long-lasting smooth muscle relaxation in guinea pig tracheal strips. Optimization of pharmacokinetic properties was achieved by combining rapid oxidative clearance with targeted introduction of a phenolic moiety to secure rapid glucuronidation. Together, these attributes minimize systemic exposure following inhalation, mitigate potential drug-drug interactions, and reduce systemically mediated adverse events. Compound 47 (PF-3635659) is identified as a Phase II clinical candidate from this series with in vivo duration of action studies confirming its potential for once-daily use in humans.

We discuss some of the interesting physics behind the design and operation of the Theremin electronic musical instrument. To complement the theory we present details of a parallel effort to construct two versions of this remarkable instrument. One of these designs remains fairly faithful to the traditional beat frequency oscillator approach that first inspired Theremin's invention, while the other contains more modern electronics that helps make more reliable the setting up and use of the instrument. The emphasis on the physical principles continues into a comparison of the two instruments. Following completion, the Theremins have been extensively used in public and schools science exhibitions and in lecture demonstrations.

A bacterium able to utilize sulfamate as N-source for growth was isolated from soil and identified as a Mycobacterium sp. An apparently previously unrecorded enzyme, sulfamate hydrolase (EC 3.10.1.-), converts sulfamate to equimolar amounts of ammonia and sulfate. This enzyme was purified to homogeneity and had a Km for sulfamate of 26.36 +/- 4.01 mM. Its Specificity Constant value, 74 M(-1) s(-1), was low, indicating that it was not a particularly good catalyst for this reaction and it may be a hydrolase recruited to this role from some other reaction sequence. However, under equivalent conditions it showed no detectable action on the other sulfamates, cyclamate and sulfamoylbenzoate, or on urea or methylamine.

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