Toxic level hypergolic vapor detection sensor development

Development of an electrochemical sensor technology capable of PPB level hypergolic vapor sensing is reported. A portable instrument capable of meeting the design goals is described

Molecular determinants of ginkgolide binding in the glycine receptor pore

Ginkgolides are potent blockers of the glycine receptor Cl- channel (GlyR) pore. We sought to identify their binding sites by comparing the effects of ginkgolides A, B and C and bilobalide on alpha1, alpha2, alpha1beta and alpha2beta GlyRs. Bilobalide sensitivity was drastically reduced by incorporation of the beta subunit. In contrast, the sensitivities to ginkgolides B and C were enhanced by beta subunit expression. However, ginkgolide A sensitivity was increased in the alpha2beta GlyR relative to the alpha2 GlyR but not in the alpha1beta GlyR relative to the alpha1 GlyR. We hypothesised that the subunit-specific differences were mediated by residue differences at the second transmembrane domain 2' and 6' pore-lining positions. The increased ginkgolide A sensitivity of the alpha2beta GlyR was transferred to the alpha1beta GlyR by the G2'A (alpha1 to alpha2 subunit) substitution. In addition, the alpha1 subunit T6'F mutation abolished inhibition by all ginkgolides. As the ginkgolides share closely related structures, their molecular interactions with pore-lining residues were amenable to mutant cycle analysis. This identified an interaction between the variable R2 position of the ginkgolides and the 2' residues of both alpha1 and beta subunits. These findings provide strong evidence for ginkgolides binding at the 2' pore-lining position

SeaWiFS Postlaunch Technical Report Series

The SeaWiFS Transfer Radiometer (SXR) was built for the Sea-viewing Wide Field-of-view Sensor (SeaWiFS) Project as part of an Interagency Agreement with the National Aeronautics and Space Administration (NASA). The SXR is a multichannel radiometer designed to verify and compare measurements of spectral radiance at six discrete wavelengths in the visible and near infrared for various calibration sources in the SeaWiFS Project. In addition, the SXR is used to compare these sources to standards of spectral radiance maintained at the National Institute of Standards and Technology (NIST). The SXR was designed, built, and thoroughly characterized in the Optical Technology Division at NIST. A unique optical design provides six independent optical paths, each equipped with a temperature stabilized interference filter and silicon photodiode. A separate beam path through the input lens is used to visually align the SXR. The entrance windows for each channel overlap at the source, with each channel sampling a unique solid angle within the field of view of the SXR; this allows for simultaneous sampling of all channels. The combined standard relative uncertainty of spectral radiance measurements with the SXR is estimated to be between 0.6% and 1.3%. This report describes the design and construction of the SXR in detail, and gives the results of the optical characterization and calibrations done at NIST. The SXR has been used for several intercomparisons which include several SeaWiFS Intercalibration Round-Robin Experiments (SIRREXs); those done at the Marine Optical Buoy (MOBY) laboratories in Honolulu, Hawaii; at the NEC Corporation in Yokohama, Japan; and Orbital Sciences Corporation (OSC) in Germantown, Maryland. Thorough optical characterization and calibration of the SXR was essential to the successful application of the radiometer for these measurements

An investigation of traumatic life events and obsessive-compulsive disorder.

Abstract Obsessive-compulsive disorder (OCD), like most other psychiatric disorders, is suspected of being influenced by an interaction between life events and genes, both with regard to onset and course of illness. To date, no specific genes have been identified as playing a frequent role, and only a relatively few empirical studies have assessed the association between stressful life events (SLEs) and OCD. The present study builds on past research by examining the potential contributions from traumatic life events (TLEs) on the severity and symptom features in 265 individuals with Structured Clinical Interview for DSM-IV (SCID)-diagnosed OCD. Of these participants 54% endorsed having experienced at least one TLE in their life time. The presence of one or more TLEs was associated with increased OCD symptom severity. This relationship remained significant despite controlling for key variables including age, OCD age-of-onset, comorbidity, and depressive symptoms. In addition, obsessions/checking and symmetry/ordering were two of four symptom factors that were specifically associated with the occurrence of TLEs. These results are generally supportive of a pathoplastic relationship between TLEs and OCD symptomatology and thus suggest the need for greater systematic consideration of life stresses in research focused on the nature and treatment of OCD.

Axon initial segment dysfunction in a mouse model of human genetic epilepsy with febrile seizures plus

Febrile seizures are a common childhood seizure disorder and a defining feature of genetic epilepsy with febrile seizures plus (GEFS+), a syndrome frequently associated with Na+ channel mutations. Here, we describe the creation of a knockin mouse heterozygous for the C121W mutation of the ß1 Na+ channel accessory subunit seen in patients with GEFS+. Heterozygous mice with increased core temperature displayed behavioral arrest and were more susceptible to thermal challenge than wild-type mice. Wild-type ß1 was most concentrated in the membrane of axon initial segments (AIS) of pyramidal neurons, while the ß1(C121W) mutant subunit was excluded from AIS membranes. In addition, AIS function, an indicator of neuronal excitability, was substantially enhanced in hippocampal pyramidal neurons of the heterozygous mouse specifically at higher temperatures. Computational modeling predicted that this enhanced excitability was caused by hyperpolarized voltage activation of AIS Na+ channels. This heat-sensitive increased neuronal excitability presumably contributed to the heightened thermal seizure susceptibility and epileptiform discharges seen in patients and mice with ß1(C121W) subunits. We therefore conclude that Na+ channel ß1 subunits modulate AIS excitability and that epilepsy can arise if this modulation is impaired

The Keck Low-Resolution Imaging Spectrometer

The Low Resolution Imaging Spectrometer (LRIS) for the Cassegrain focus of the Keck 10-m telescope on Mauna Kea is described. It has an imaging mode so it can also be used for taking direct images. The field of view in both spectrographic and imaging modes is 6 by 7.8 arcmin. It can be used with both conventional slits and custom-punched slit masks. The optical quality of the spectrograph is good enough to take full advantage of the excellent imaging properties of the telescope itself. The detector is a cooled back-illuminated Tektronics Inc. 2048 X 2048 CCD which gives a sampling rate of 4.685 pixels per arcsec. In the spectrographic mode the spectrograph has a maximum efficiency at the peak of the grating blaze of 32%-34% for the two lowest resolution gratings and 28% for the 1200 g mm^(-1) grating. This efficiency includes the detector but not the telescope or the atmosphere

SeaWiFs Technical Report Series. Volume 34: The Third SeaWiFS Intercalibration Round-Robin Experiment (SIRREX-3), 19-30 September 1994

This report presents results of the third Sea-viewing Wide Field-of-view Sensor (SeaWiFS) Intercalibration Round- Robin Experiment (SIRREX-3), which was held at the San Diego State University (SDSU) Center for Hydro-Optics and Remote Sensing (CHORS) on 19-30 September 1994. Spectral irradiances of FEL lamps belonging to each participant were intercompared by reference to the National Institute of Standards and Technology (NIST) scale of spectral irradiance using secondary standard lamps F268, F269, and F182, with a Type A uncertainty between 1.1-1.5%. This level of uncertainty was achieved despite difficulties with lamp F269. The average spectral irradiances of FEL lamps, compared in both SIRREX-2 and SIRREX-3, differed between the two experiments by 1.5%, which probably indicates that the values assigned to the secondary standard lamp at the time of SIRREX-2 were in error. With two exceptions, spectral radiance values of integrating sphere sources were measured during SIRREX-3 with uncertainties in temporal stability of less than 0.3% and absolute uncertainties of 1.5-2.0%. This is a significant improvement over similar intercomparisons in SIRREX- I and SIRREX-2. Plaque reflectances were intercompared with an uncertainty of about 1-2%, but the absolute uncertainty is undefined. Although this is an improvement over results of previous SIRREXS, the sources and magnitude of uncertainty associated with transfers of spectral radiance using plaques requires further evaluation in future experiments

Regulation of insulin-regulated membrane aminopeptidase activity by its C-terminal domain

The development of inhibitors of insulin-regulated aminopeptidase (TRAP), a membrane-bound zinc metallopeptidase, is a promising approach for the discovery of drugs for the treatment of memory loss such as that associated with Alzheimer's disease. There is, however, no consensus in the literature about the mechanism by which inhibition occurs. Sequence alignments, secondary structure predictions, and homology models based on the structures of recently determined related metallopeptidases suggest that the extracellular region consists of four domains. Partial proteolysis and mass spectrometry reported here confirm some of the domain boundaries. We have produced purified recombinant fragments of human IRAP on the basis of these data and examined their kinetic and biochemical properties. Full-length extracellular constructs assemble as dimers with different nonoverlapping fragments dimerizing as well, suggesting an extended dimer interface. Only recombinant fragments containing domains 1 and 2 possess aminopeptidase activity and bind the radiolabeled hexapeptide inhibitor, angiotensin IV (Ang IV). However, fragments lacking domains 3 and 4 possess reduced activity, although they still bind a range of inhibitors with the same affinity as longer fragments. In the presence of Ang IV, IRAP is resistant to proteolysis, suggesting significant conformational changes occur upon binding of the inhibitor. We show that TRAP has a second Zn(2+) binding site, not associated with the catalytic region, which is lost upon binding Ang IV. Modulation of activity caused by domains 3 and 4 is consistent with a conformational change regulating access to the active site of IRAP