Carnosine (␤-alanyl-L-histidine) and homocarnosine (␥-aminobutyric acid-L-histidine) are two naturally occurring dipeptides with potential neuroprotective and neurotransmitter functions in the brain. Peptidase activities degrading both carnosine and homocarnosine have been described previously, but the genes linked to these activities were unknown. Here we present the identification of two novel cDNAs named CN1 and CN2 coding for two proteins of 56.8 and 52.7 kDa and their classification as members of the M20 metalloprotease family. Whereas human CN1 mRNA and protein are brain-specific, CN2 codes for a ubiquitous protein. In contrast, expression of the mouse and rat CN1 orthologues was detectable only in kidney. The recombinant CN1 and CN2 proteins were expressed in Chinese hamster ovary cells and purified to homogeneity. CN1 was identified as a homodimeric dipeptidase with a narrow substrate specificity for Xaa-His dipeptides including those with Xaa ‫؍‬ ␤Ala (carnosine, K m 1.2 mM), N-methyl ␤Ala, Ala, Gly, and ␥-aminobutyric acid (homocarnosine, K m 200 M), an isoelectric point of pH 4.5, and maximal activity at pH 8.5. CN2 protein is a dipeptidase not limited to Xaa-His dipeptides, requires Mn 2؉ for full activity, and is sensitive to inhibition by bestatin (IC 50 7 nM). This enzyme does not degrade homocarnosine and hydrolyzes carnosine only at alkaline pH with an optimum at pH 9.5. Based on their substrate specificity and biophysical and biochemical properties CN1 was identified as human carnosinase (EC 3.4.13.20), whereas CN2 corresponds to the cytosolic nonspecific dipeptidase (EC 3.4.13.18).

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The Automated Planet Finder (APF) is a facility purpose-built for the discovery and characterization of extrasolar planets through high cadence Doppler velocimetry of the reflex barycentric accelerations of their host stars. Located atop Mt. Hamilton, the APF facility consists of a 2.4-m telescope and its Levy Spectrometer, an optical echelle spectrometer optimized for precision Doppler velocimetry. APF features a fixed format spectral range from 374 nm -970 nm, and delivers a "Throughput" (resolution * slit width product) of 114,000 arc-seconds, with spectral resolutions up to 150,000.Overall system efficiency (fraction of photons incident on the primary mirror that are detected by the science CCD) on blaze at 560 nm in planet-hunting mode is 15%. Firstlight tests on the RV standard stars HD 185144 and HD 9407 demonstrate sub-m s −1 precision (RMS per observation) held over a 3-month period. This paper reviews the basic features of the telescope, dome, and spectrometer, and gives a brief summary of first-light performance.

The structure of porcine neuropeptide Y in 0.05 M CD3COOD/D20 was determined by nuclear magnetic resonance spectroscopy. Nuclear Overhauser spectra yielded 377 distances which define a helical segment formed by residues 11 -36. An additional set of 24 distances were interpreted as intermolecular distances within a dimer. A combination of distance geometry calculations, energy minimization and molecular dynamics yielded a model of the dimer having antiparallel packing of two curved helical units whose hydrophobic sides form a well defined core. The N-terminus (residues 1-9) appears as an unstructured mobile segment.Large changes in the intrinsic fluorescence intensity of neuropeptide Y tyrosine residues allowed the determination of the dimer dissociation constant as 1.6 f 0.6 pM at pH 2 -8 in aqueous buffers and also indicated the enclosure of several tyrosine residues in the hydrophobic environment of the interface region in the dimeric species. Fluorescence anisotropy data reveals the slow rotation of such shielded residues.Neuropeptide Y is a 36-amino-acid peptide widely distributed throughout both the central and peripheral nervous systems. Co-located with noradrenaline in many neurons of the sympathetic nervous system, it is thought to be involved in the control of the cardiovascular system (Lundberg et al., 1982;Everitt et al., 1984). In vivo administration results in a potent vasoconstriction which is independent of adrenergic mechanisms.Neuropeptide Y is a member of the pancreatic polypeptide family and, based on sequence analogy with avian pancreatic polypeptide for which an X-ray crystal analysis exists (Blundell et al., 1981), a similar tertiary structure has been proposed (Allen et al., 1987). This model predicts an amphiphilic a-helix between residues 14 -32 with strong hydrophobic interactions between one face of the a-helix and the amino-terminal polyproline-like helix, that also has some amphiphilic character.Recently, an NMR study of the secondary structure of neuropeptide Y (Saudek and Pelton, 1990) showed that the ular dynamics calculations to generate a three-dimensional model for this peptide. The tyrosine fluorescence intensity and anisotropy data in aqueous buffers and in the presence of acetonitrile confirms some structural and dynamic features of the dimer model, and provides values for the dimer dissociation constant as a function of pH. MATERIALS AND METHODS Peptide synthesisPorcine neuropeptide Y was synthesized by standard solidphase peptide synthetic methods using the t-butyl benzyloxycarbonyl/benzyl protection strategy, purified by gel filtration (Sephadex C-10) and preparative CI8 reverse-phase HPLC, and identity and purity confirmed by amino acid analysis and fast-atom-bombardment mass spectroscopy, as reported previously (Saudek and Pelton. 1990).C-terminal segment from residues 11 -36 folds into an amphiphilic a-helix while the N-terminal segment, containing Spectra three prolines in both cis and tram conformations assumes no regular structure. Many NOES were detected also betw...

A large and homogeneous set of image quality data, obtained with HRCam at the prime focus of the CFHT, was correlated with thermal sensor data to identify and quantify "local seeing" effects. The main findings are as follows.1. Mirror seeing is an important source of image spread and amounts to FWHM = 0'.'40/°C 6/5 when the primary mirror is warmer than the air inside the dome.2. Dome seeing is marginally significant, at the rate of ~ 0'.'1/°C 6/5 of temperature difference between the air inside and outside the dome.3. Optical aberrations from the CFHT primary mirror and from HRCam currently impose a limit of FWHM = 0"38 to the image quality.4. The median natural atmospheric seeing at the CFHT site on Mauna Kea is FWHM = 0'.'43 ± 0'.'05, the 10th and 90th percentiles being ~ 0'.'25 and ~ 0'.'7, respectively.