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Traditional Chinese Medicine (TCM) is becoming more and more popular all over the world. Novel analytical tools for quality control are highly demanded enabling analysis starting at breeding and ending at biological fluids including urine or serum. Compared to analytical separation methods (chromatography, electrophoresis) near-infrared spectroscopy (NIRS) allows analyzing matter of interest non-invasively, fast and physical/chemical parameters simultaneously. It can be used for the quantitative control of certain (active) ingredients. In many cases identification can only be achieved by pattern recognition. Therefore, NIRS combined with cluster analysis offers huge potential to identify e.g. species, geographic origin, special medicinal formula etc. In the present contribution the fundamentals, possibilities of NIR applied in quality control of TCM are pointed out and its ad- and disadvantages are discussed in detail by several practical examples.

Poly(α-methylstyrene)- block-poly(4-hydroxystyrene) acts as both a lithographic deep UV photoresist and a self-assembling material, making it ideal for patterning simultaneously by both top-down and bottom-up fabrication methods. Solvent vapor annealing improves the quality of the self-assembled patterns in this material without compromising its ability to function as a photoresist. The choice of solvent used for annealing allows for control of the self-assembled pattern morphology. Annealing in a nonselective solvent (tetrahydrofuran) results in parallel orientation of cylindrical domains, while a selective solvent (acetone) leads to formation of a trapped spherical morphology. Finally, we have self-assembled both cylindrical and spherical phases within lithographically patterned features, demonstrating the ability to precisely control ordering. Observing the time evolution of switching from cylindrical to spherical morphology within these features provides clues to the mechanism of ordering by selective solvent.

Pentylenetetrazole (PTZ) is a central nervous system convulsant that is thought, based on binding studies, to act at the picrotoxin (PTX) site of the gamma-aminobutyric acid type A (GABA(A)) receptor. In the present study, we have investigated the mechanism and site of action of PTZ in recombinant GABA(A) receptors. In rat alpha 1 beta 2 gamma 2 receptors, PTZ inhibited GABA-activated Cl(-) current in a concentration-dependent, voltage-independent manner, with an IC(50) of 0.62 +/- 0.13 mM. The mechanism of inhibition appeared competitive with respect to GABA in both rat and human alpha 1 beta 2 gamma 2 receptors. Varying subunit configuration (change or lack of alpha subunit isoform or lack of gamma 2 subunit) had modest effects on PTZ-induced inhibition, as evidenced by comparable IC(50) values (0.6-2.2 mM) in all receptor configurations tested. This contrasts with PTX and other PTX-site ligands, which have greater affinity in receptors lacking an alpha subunit. Using a one-site model for PTZ interaction with alpha 1 beta 2 gamma 2 receptors, the association rate (k(+1)) was found to be 1.14 x 10(3) M(-1) s(-1) and the dissociation rate (k(-1)) was 0.476 s(-1), producing a functional k(d) of 0.418 mM. PTZ could only gain access to its binding site extracellularly. Single-channel recordings demonstrated that PTZ decreased open probability by increasing the duration of closed states but had no effect on single-channel conductance or open state duration. alpha-Isopropyl-alpha-methyl-gamma-butyrolactone, a compound known to antagonize effects of PTX, also diminished the effects of PTZ. Taken together, our results indicate that pentylenetetrazole and picrotoxin interact with overlapping but distinct domains of the GABA(A) receptor.

The radiochemical synthesis and pharmacological properties are described of [3H]RY 80 (ethyl-8-acetylene-5, 6-dihydro-5-methyl-6-oxo-4H-imidazo[1,5a][1, 4]benzodiazepine-3-carboxylate, [ethyl-3H]). This compound is one of a series of 8-substituted imidazobenzodiazepines that exhibits both high affinity and selectivity for gamma-aminobutyric acid (GABA)A receptors containing alpha-5 subunits. Saturable, high-affinity (Kd approximately 0.7 nM) binding of [3H]RY 80 was observed in hippocampal membranes. The maximum number (Bmax) of [3H]RY 80 binding sites was approximately 18% of that obtained with [3H]flunitrazepam, a radioligand that labels all "diazepam-sensitive" GABAA receptors. This value is consistent with previous estimates (10-20%) of the proportion of rat hippocampal GABAA receptors containing alpha-5 subunits determined by immunoprecipitation with selective antibodies and competition experiments using an alpha-5-selective ligand. In recombinant GABAA receptors composed of alpha-5 beta-3 gamma-2 subunits, the Kd of [3H]RY 80 (approximately 0.5 nM) was consistent with the value obtained in hippocampus, whereas the Bmax value was not significantly different from that obtained with [3H]flunitrazepam. The potencies of several benzodiazepine site ligands to inhibit [3H]RY 80 binding to hippocampal membranes were in agreement with the values obtained in recombinant (alpha-5 beta-3 gamma-2) GABAA receptors. [3H]RY 80 was used both in a "GABA shift" assay to correctly predict the in vivo actions of a novel, alpha-5-selective ligand and to characterize a population of GABAA receptors containing alpha-5 subunits in neonatal rat cortex. These findings demonstrate that [3H]RY 80 can be used as a radioligand to examine the properties of GABAA receptors containing alpha-5 subunits.

In the present study, rundown of gamma-aminobutyric acid (GABA)-activated Cl- channels was studied in recombinant GABAA receptors stably expressed in human embryonic kidney cells (HEK 293), with conventional whole-cell and amphotericin B-perforated patch recording. When [ATP]i was lowered to 1 mM and resting [Ca++]i was buffered to a relatively high level, the response of alpha 3 beta 2 gamma 2 GABAA receptors to relatively low [GABA] (up to 50 microM) did not show rundown in the whole-cell configuration. However, high [GABA] (greater than 200 microM) induced significant rundown, which was observed by decreases in both the maximum GABA-induced current and GABA EC50. Rundown was prevented completely with a solution containing 4 mM Mg(++)-ATP and low resting [Ca++]i, or during perforated patch recording. The magnitude of rundown was comparable in alpha 1 beta 2 gamma 2 and beta 2 gamma 2 receptors. Neither stimulation nor inhibition of protein kinase A or protein kinase C had a significant effect on rundown. However, sodium metavanadate, an inhibitor of protein tyrosine phosphatase, significantly reduced rundown. In addition, inhibition of protein tyrosine kinase activity by either genistein or lavendustin A induced rundown of the GABA response. Inhibition of the Ca++/calmodulin-dependent phosphatase calcineurin with fenvalerate also prevented rundown of the response to GABA. Our results demonstrate that rundown of GABAA receptor function is concentration-dependent, due to depletion of ATP and/or unbuffered [Ca++]i, and does not depend on the presence or subtype of the alpha subunit. We propose that protein phosphorylation at a tyrosine kinase-dependent site, and a distinct unidentified site, which is dephosphorylated by calcineurin, maintains the function of GABAA receptors.

A novel MOS-controlled SiC thyristor device, the SiC emitter turn-off thyristor (ETO) is a promising technology for future high-voltage switching applications because it integrates the excellent current conduction capability of a SiC thyristor with a simple MOS-control interface. Through unity-gain turn-off, the SiC ETO also achieves excellent Safe Operation Area (SOA) and faster switching speeds than silicon ETOs. The world's first 4.5-kV SiC ETO prototype shows a forward voltage drop of 4.26 V at 26.5 A/cm2 current density at room and elevated temperatures. Tested in an inductive circuit with a 2.5 kV DC link voltage and a 9.56-A load current, the SiC ETO shows a fast turn-off time of 1.63 microseconds and a low 9.88 mJ turn-off energy. The low switching loss indicates that the SiC ETO could operate at about 4 kHz if 100 W/cm2 conduction and the 100 W/cm2 turn-off losses can be removed by the thermal management system. This frequency capability is about 4 times higher than 4.5-kV-class silicon power devices. The preliminary demonstration shows that the SiC ETO is a promising candidate for high-frequency, high-voltage power conversion applications, and additional developments to optimize the device for higher voltage (>5 kV) and higher frequency (10 kHz) are needed.

OBJECTIVE: To determine factors associated with the length of stay (LOS) for patients with suspected community-acquired pneumonia (CAP) who required hospitalization for treatment.STUDY DESIGN: The authors studied a population-based prospective cohort of 2757 adults with suspected CAP who were admitted over a two-year period. Logistic regression, multiple linear regression, and classification and regression trees were used to determine the factors associated with LOS.SETTING: The study was conducted in two community and tertiary care hospitals, two community and secondary care hospitals, and two community hospitals in the Capital Health Region of Edmonton, Alberta.RESULTS: Symptoms such as sweats, shaking chills and wheezing were associated with an LOS of seven days or shorter, whereas weight loss, functional impairment, heart, renal or neoplastic diseases and time to first dose of antibiotic were predictive of an LOS greater than seven days. Regression tree analysis indicated that rapid achievement of physiological stability was associated with a shorter LOS. The use of an indwelling urinary catheter was found to be an important determinant of LOS.CONCLUSIONS: The present study found several new associations with increased LOS in patients with CAP, including functional status, time to receipt of first dose of antibiotic therapy, use of certain antibiotics, presence of a urinary catheter and the importance of time to physiological stability. An intervention targeting avoidance of urinary catheters may be associated with a shorter LOS.

Patients aged 17 years and older who presented to seven emergency departments in Edmonton, Alberta over a two-year period with community-acquired pneumonia (n=8144) were studied. The admission rates were 271/100,00 and 296/100,000 persons for year 1 and year 2 of the study, respectively. The admission rate increased with increasing age, peaking at 4639/100,000/year for those 90 years of age and older. In contrast, the percentage of patients who were admitted to an intensive care unit was highest for those in the younger age groups between 17 and 59 years of age. From 59 years of age and older, there was a progressive decline in the percentage of patients admitted to an intensive care unit, with approximately 1% of those in the 90 years and older age group admitted. A pronounced seasonal effect on the number of patients presenting to emergency department was also noted. During the winter months, there was up to a 50% increase in the number of cases compared with the summer months.