Multiway vortex valve system Patent

Multiple vortex amplifier system as fluid valv

A Novel Alcohol-Sensitive Site in the M3 Domain of the NMDA Receptor GluN2A Subunit

Accumulating studies have demonstrated that the N-methyl-D-aspartate receptor is one of the most important targets of ethanol in the central nervous system. Previous studies from this laboratory have found that one position in the third (F637) and two positions in the fourth (M823 and A825) membrane-associated (M) domains of the N-methyl-D-aspartate receptor GluN2A subunit modulate alcohol action and ion channel gating. Using site-directed mutagenesis and whole-cell patch-clamp recording, we have found an additional position in M3 of the GluN2A subunit, F636, which significantly influences ethanol sensitivity and functionally interacts with F637. Tryptophan substitution at F636 significantly decreased the ethanol IC50, decreased both peak and steady-state glutamate EC50, and altered agonist deactivation and apparent desensitization. There was a significant correlation between steadystate: peak current ratio, a measure of desensitization, and ethanol IC50 values for a series of mutants at this site, raising the possibility that changes in ethanol sensitivity may be secondary to changes in desensitization. Mutant cycle analysis revealed a significant interaction between F636 and F637 in regulating ethanol sensitivity. Our results suggest that F636 in the M3 domain of the GluN2A subunit not only influences channel gating and agonist potency, but also plays an important role in mediating the action of ethanol. These studies were supported by grants R01 AA015203-01A1 and AA015203-06A1 from the NIAAA to R.W.P

Single-node orbit analsyis with radiation heat transfer only

The steady-state temperature of a single node which dissipates energy by radiation only is discussed for a nontime varying thermal environment. Relationships are developed to illustrate how shields can be utilized to represent a louver system. A computer program is presented which can assess periodic temperature characteristics of a single node in a time varying thermal environment having energy dissipation by radiation only. The computer program performs thermal orbital analysis for five combinations of plate, shields, and louvers

The influence of privatization on occupational wages

This paper uses individual worker and municipal information to examine privatization's influence on the wages of thirteen occupations. Findings reveal that the group of relatively low-skill content occupations comprising bus drivers and construction laborers receive a wage premium in the absence of privatization, and privatization is associated with an erosion of this premium. In contrast, the group of relatively high-skill content occupations comprising physicians and lawyers receive a non-trivial public sector discount in the absence of privatization and only the wage differential of physicians erodes with increased privatization. However, physician's public sector discount does not erode when estimating privatization's influence on this occupation's weekly earnings.privatization, occupational wage, wage differential

A Site of Alcohol Action at the NMDA Receptor M3-M4 Domain Interface

The N-methyl-D-aspartate (NMDA) glutamate receptor is a major target of ethanol in the brain. Previous studies have identified positions in the third and fourth membrane-associated (M) domains of the NMDA receptor GluN1 and GluN2A subunits that influence alcohol sensitivity. The structural model of the NMDA receptor, predicted from the structure of the related GluA2 subunit, indicates a close apposition of the alcohol-sensitive positions in M3 and M4 between the two subunit types. We investigated possible interactions between the M3 and M4 domain positions of the two subunit types affecting the ethanol sensitivity of the receptor by using dual substitution mutants. In an initial screen of single-substitution mutants, we found that a position in both subunits adjacent to one previously identified, GluN1(G638) and GluN2A(F636), can strongly regulate ethanol sensitivity. Significant interactions affecting ethanol inhibition were observed at four pairs of positions in GluN1/GluN2A: G638/M823, F639/L824, M818/F636, and L819/F637. Two of these interactions involve a position in M4 of both subunits, GluN1(M818) and GluN2A(L824), that does not by itself alter ethanol sensitivity, and one of the previously identified positions affecting ethanol sensitivity, GluN2A(A825), did not appear to interact with any other position tested. These results also indicate a shift by one position of the predicted alignment of the GluN1 M4 domain. These findings have allowed for the refinement of the NMDA receptor M domain structure, and support the existence of four sites of alcohol action on the NMDA receptor at the M3-M4 domain intersubunit interfaces. These studies were supported by grants R01 AA015203-01A1 and AA015203-06A1 from the NIAAA to R.W.P

Interactions Among Positions in the Third and Fourth Membrane-Associated Domains at the Intersubunit Interface of the N-Methyl-D-Aspartate Receptor Forming Sites of Alcohol Action

The N-methyl-d-aspartate (NMDA) glutamate receptor is a major target of ethanol in the brain. Previous studies have identified positions in the third and fourth membrane-associated (M) domains of the NMDA receptor GluN1 and GluN2A subunits that influence alcohol sensitivity. The predicted structure of the NMDA receptor, based on that of the related GluA2 subunit, indicates a close apposition of the alcohol-sensitive positions in M3 and M4 between the two subunit types. We tested the hypothesis that these positions interact to regulate receptor kinetics and ethanol sensitivity by using dual substitution mutants. In single-substitution mutants, we found that a position in both subunits adjacent to one previously identified, GluN1(Gly-638) and GluN2A(Phe-636), can strongly regulate ethanol sensitivity. Significant interactions affecting ethanol inhibition and receptor deactivation were observed at four pairs of positions in GluN1/GluN2A: Gly-638/Met-823, Phe-639/Leu-824, Met-818/Phe-636, and Leu-819/Phe-637; the latter pair also interacted with respect to desensitization. Two interactions involved a position in M4 of both subunits, GluN1(Met-818) and GluN2A(Leu-824), that does not by itself alter ethanol sensitivity, whereas a previously identified ethanol-sensitive position, GluN2A(Ala-825), did not unequivocally interact with any other position tested. These results also indicate a shift by one position of the predicted alignment of the GluN1 M4 domain. These findings have allowed for the refinement of the NMDA receptor M domain structure, demonstrate that this region can influence apparent agonist affinity, and support the existence of four sites of alcohol action on the NMDA receptor, each consisting of five amino acids at the M3-M4 domain intersubunit interfaces