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We performed a feasibility study on a high-strength Bi2-x Pb x Sr2Ca2Cu3O10-x (Bi-2223) tape conductor for high-field solenoid applications. The investigated conductor, DI-BSCCO Type HT-XX, is a pre-production version of Type HT-NX, which has recently become available from Sumitomo Electric Industries (SEI). It is based on their DI-BSCCO Type H tape, but laminated with a high-strength Ni-alloy. We used stress-strain characterizations, single- and double-bend tests, easy- and hard-way bent coil-turns at various radii, straight and helical samples in up to 31.2 T background field, and small 20-turn coils in up to 17 T background field to systematically determine the electro-mechanical limits in magnet-relevant conditions. In longitudinal tensile tests at 77 K, we found critical stress- and strain-levels of 516 MPa and 0.57%, respectively. In three decidedly different experiments we detected an amplification of the allowable strain with a combination of pure bending and Lorentz loading to ≥ 0.92% (calculated elastically at the outer tape edge). This significant strain level, and the fact that it is multi-filamentary conductor and available in the reacted and insulated state, makes DI-BSCCO HT-NX highly suitable for very high-field solenoids, for which high current densities and therefore high loads are required to retain manageable magnet dimensions.

Mummichogs prefer seawater (SW) but have wide ability to acclimate to extreme temperatures and salinities. In the field, minnow trapping revealed that mummichogs move progressively into low-salinity warmer water during early spring after ice melt and show significant aversion to colder temperatures and high salinity. First appearance in estuarine shallows occurred above 10°C, and catch increased to 21°C over 4 wk. Three-spine sticklebacks (Gasterosteus aculeatus) also preferred warmer low-salinity locations but preferred slowing streams, whereas mummichogs preferred tidal ponds. In the laboratory, artificial haloclines tested isothermal salinity preference, between 28‰ full-strength SW (below) and 10% SW (3.0‰; above). Mummichogs of both sexes acclimated to 5°C in SW strongly preferred SW. Freshwater (0% SW)-acclimated mummichogs at 21°C also preferred SW, but of sexually mature fish acclimated to 21°C SW, only the males preferred SW; the females showed no significant preference for SW, meaning they freely entered low salinity. SW preference was manifested by a stereotypic passive aversion to the dilute upper layer at the halocline. We conclude that the overall movement of mummichogs into summer breeding grounds of low salinity is driven by maturation of females and their preference for warmer water regardless of salinity.

Epithelia involved in vectorial salt transport respond to apical and basolateral changes in osmotic activity by moderating the transmural solute transport rate simultaneously with underlying volume regulatory mechanisms involved in regulatory volume increase (RVI) and decrease (RVD). This review examines rapid osmotic responses in salt secreting epithelia of marine and euryhaline teleost fish, with inclusion of recent results from other ion transporting epithelia that also respond rapidly to osmotic shock. Mitochondrion-rich chloride secreting cells of marine teleost fish gills and skin, when exposed to hypertonic shock, activate NaCl secretion via phosphorylation of Na(+), K(+), 2Cl(-) cotransporter (NKCC1) in the basolateral membrane and activation of anion channels in the apical membrane. Conversely, NaCl secretion is inhibited when chloride secreting cells are swollen osmotically. Mammalian airway epithelial cells also possess NKCC1 basally and apical anion channels [Cystic Fibrosis Transmembrane conductance Regulator (CFTR)]; with hypotonic shock, this epithelium releases ATP and NaCl secretion is stimulated via purinergic receptors, while hypertonic shock inhibits Na(+) uptake. In the eye, the ciliary epithelium activates Cl(-) channels in response to hypotonic shock as RVD, an effect that modulates transepithelial fluid transport rates. In the renal A6 cell line, K(+) and Cl(-) effluxes activate during RVD and RVI Na(+) transepithelial absorption. A common theme in these systems is ATP release in hypotonic shock with subsequent RVD-effective mechanisms such as NKCC1 inhibition and K(+) and Cl(-) efflux, but there are different effects of osmotic changes on transepithelial transport, apparently depending on the role of the epithelial system.

A team comprised of the Tai-Yang Research Company, Creare, Inc., and the Advanced Space Propulsion Laboratory at NASA has designed, fabricated and tested a high-temperature superconducting magnet and flow cooling system for a space propulsion application. The magnet bore is 16 cm dia., 5.5 cm long, and generates 0.5 T, with a design operating current of 126 A. The magnet is wound with brass laminated 1 G BSCCO conductor, epoxy impregnated, then thermally connected to a flow cooling loop with a compressor, recuperator and GM cryocooler. Flow conditions are selected to simulate operation with a space proven turbo-Brayton cryocooler. This test demonstrates that design and integration of an HTS magnet with flow cooling is feasible, and offers the advantages of compactness, low weight, high efficiency and high reliability. Design details of the magnet and cooling system and results of successful system qualification tests are reported.

The development and testing of a flow cooling system for high-temperature superconducting (HTS) magnets is described. The system includes a turbo-Brayton cryocooler, a magnet thermal interface, and a magnet thermal isolation and support system. The target application is the Variable Specific Impulse Magnetoplasma Rocket (VASIMR). Turbo-Brayton coolers are well suited to such spacecraft applications, as they are compact, modular, lightweight, and efficient, with long maintenance-free lifetimes. Furthermore, the technology scales well to high-cooling capacities. The feasibility of using turbo-Brayton coolers in this application was proven in a design exercise in which existing cooler designs were scaled to provide cooling for the magnet sets required by 200 kW and 1 MW VASIMR engines. The performance of the concepts for the thermal interface and the thermal isolation and support system were measured in separate laboratory tests with a demonstration system built about a representative HTS magnet. Cooling for these tests was provided by a flow cooling loop comprising a compressor, recuperator and GM cryocooler, with the flow pressure, temperature, and mass flow rate selected to effectively simulate the turbo-Brayton operating condition. During system testing, the magnet was cooled below its design operating temperature of 35 K, and good thermal uniformity (

One of the earliest events in bone morphogenesis is the condensation of embryonic mesenchymal cells into chondroblasts and their subsequent proliferation and differentiation into chondrocytes. During this time, certain signaling cascades operate to establish proper patterning and differentiation of the cartilaginous skeleton. Characterization of the signaling pathways involved in these processes remains to be accomplished. We have identified a novel murine cytosolic tyrosine phosphatase termed PTPPBS gamma (+/-) which is a member of the PTP PC12,Br7,Sl (PTPPBS) family. Spatio-temporal expression analysis of the members of this tyrosine phosphatase family demonstrates significant expression of the gamma (-) splice variant in the cartilaginous skeleton. Using an embryonic mandibular explant culture system to serve as a model for cartilage formation, we examined the potential roles of the PTPPBS gamma phosphatase by loss-of-function studies achieved with antisense oligodeoxynucleotides. These studies demonstrated that loss of expression of the PTPPBS gamma (-) isoform resulted in abnormal patterning of Meckel's cartilage and an increase in the size of the chondrogenic regions. In gamma antisense-treated explants, bromodeoxyuridine-pulse labeling studies revealed increased proliferation of chondroblasts bordering along precartilaginous condensations and bordering populations of maturing chondrocytes. These studies provide evidence that in early skeletal development, PTPPBS gamma may regulate the rate of chondroblast proliferation in the cartilaginous skeleton.

A combinatorial tripeptide library having the general form D-Glu-Xxx-Xxx-CONH2 has been synthesized using a standard mix and split synthetic protocol that is expected to produce 676 components. All components of the mixture were analyzed using a new high-resolution ion mobility/time-of-flight mass spectrometer coupled with an electrospray ionization source. In this approach ions are separated by differences in their gas-phase mobilities prior to being introduced into the mass spectrometer for mass-to-charge analysis. The peptide library includes a wide range of different sequence, structural, and stereo isomers; trends in the number of expected and resolved isomers that are observed at each m/z ratio allow specific synthetic steps that have failed to be identified, even in the presence of other isomers. Information about the relative abundances of different isomers should dramatically improve the reliability of binding affinity studies from direct analysis of mixtures.

To determine the utility of a new mechanically advantaged syringe in the performance of percutaneous coronary intervention.A new mechanically advantaged syringe has been developed to perform cardiovascular imaging. We wanted to assess the utility of this device in the performance of small catheter percutaneous coronary intervention. Data from coronary interventions performed with the standard technique at our institution, using a 10 ml manual syringe, were compared to the use of a new mechanically advantaged syringe. Contrast utilization during the standard technique was assessed by obtaining data from fifty consecutive successful single-vessel coronary interventions (angioplasty with or without stenting). After an initial learning experience with the mechanically advantaged syringe, fifty consecutive successful single-vessel coronary interventions were assessed. Most interventions performed using the mechanically advantaged syringe were with 6 French catheters. Detailed contrast utilization information was gathered.During the standard method of performing coronary intervention, 216 +/- 114 ml of contrast were used. Utilizing the mechanically advantaged OZ Power Syringe (Cardiovascular Innovations Inc., Athens, Texas), the contrast use was reduced to 66 +/- 39 ml (p0.0001) per case. The syringe also allowed excellent visualization despite using a smaller guide catheter system.The OZ Power Syringe can be utilized effectively in percutaneous coronary intervention. Our preliminary data suggest that there may be reduced contrast use without sacrificing image quality.

Pinhole leak or rupture of a stent delivery balloon is a well-recognized technical problem encountered in vascular interventions. This event leads to inadequate stent expansion. These stents cannot be fully deployed with the same balloon and frequently the balloon cannot be retrieved without dislodging the stent. We describe a technique for successful stent deployment in such situations using the Oz Power Syringe, a new manual power injector. Cathet. Cardiovasc. Intervent. 48:74-77, 1999.

The low-density lipoprotein receptor-related protein (LRP) is a multifunctional member of the low-density lipoprotein receptor family that has been implicated in a variety of physiologic and pathologic processes. However, little is known about LRP regulation at the molecular level, and the factors that might mediate LRP have not yet been characterized. This is particularly true of hepatocytes, an important site of LRP expression. Hepatocyte gene expression is known to be dependent on extracellular matrix composition, although the effect of extracellular matrix on lipoprotein receptor expression has not yet been investigated. Also, the mechanisms by which the extracellular matrix affects hepatocyte gene expression are not well understood. In this study, we show that hepatocyte LRP expression decreases rapidly at the mRNA, protein, and functional levels on collagen type I, but remains high on an Engelbreth-Holm-Swarm sarcoma matrix-preparation, Matrigel. LRP function was assessed with ligand binding studies and a novel cytotoxicity assay, using Pseudomonas exotoxin A. Investigation of the mechanism of LRP down-regulation revealed a two-fold longer LRP mRNA half-life in hepatocytes cultured on Matrigel relative to collagen. Taken together, these studies reveal that LRP expression in primary hepatocytes is dependent on the extracellular matrix, and that matrix-dependent differences in hepatocyte LRP mRNA expression are primarily due to changes in mRNA stability, indicating for the first time that the expression of LRP is subject to post-transcriptional regulation.

The use of automated sample preparation and data collection coupled with delayed ion extraction matrix-assisted laser desorption ionization with time-of-flight detection mass spectrometry (DE MALDI–TOF MS) enables the rapid mass analysis of oligonucleotide samples. We have incorporated a matrix-diluting and liquid-spotting automated work station and a DE MALDI mass spectrometer to provide high-throughput analysis of synthetic oligonucleotides. Automated sample preparation greatly speeds processing while the spotting function allows for precise sample placement on a 100-well sample plate. The DE MALDI MS typically determines the mass of each sample to within 0.13 ± 0.10% of the theoretically expected mass. This mass accuracy allows confirmation of identity and detection of low-level impurities present in synthetic oligonucleotide samples with an unprecedented degree of confidence. Using this automation suite, sample preparation, spotting, and analysis of 100 samples ranging from 12 to 70 bases in length can be routinely completed in less than 90 min.

In vitro studies have shown LY203647 to be a selective antagonist of contractile responses to leukotriene (LT) D4 and LTE4 in guinea pig ileum, trachea and lung parenchyma. In pithed rat, i.v. injection of LTD4 produced pressor responses that were selectively antagonized by LY203647 in a dose-dependent manner [ED50 7.5 (6.0-9.5) mg/kg, i.v.]. In normal anesthetized rats and dogs, LTD4 reduced aortic blood flow and stroke volume in association with systemic vasoconstriction, variable blood pressure responses and no change in cardiac rate. LTD4 did not alter myocardial contractility corrected for alterations in afterload. Pretreatment of rats and dogs with LY203647 (1-10 mg/kg, i.v.) produced dose-related inhibition of the myocardial and systemic hemodynamic effects of LTD4, whereas coadministration of LY203647 reversed established myocardial depression and systemic and pulmonary vasoconstriction during continuous infusion of LTD4 in dogs. LY203647 (10 mg/kg over 90 min, i.v.) infusion in normal dogs abolished or greatly antagonized hemodynamic responses to LTD4 for 6 hr. In subsequent experiments, myocardial infarct size was measured after 1 hr of occlusion of the circumflex coronary artery and 5 hr of reperfusion. LY203647 (10 mg/kg over 90 min, i.v.) treatment did not alter cardiovascular parameters when compared to time-related alterations observed in control dogs. ST segment deviation and the intensity and duration of cardiac arrhythmias associated with coronary artery occlusion and reperfusion also were similar between groups. Resultant infarct sizes were 46 +/- 1 and 45 +/- 1% of the left ventricular mass placed at risk in control and LY203647-treated dogs, respectively. Present data illustrate the prominent cardiac and systemic hemodynamic effects of LTD4 and indicate that LY203647 produces selective and sustained antagonism of cardiovascular LTD4 receptors. Lack of containment of infarction by LY203647 suggests that endogenous cysteinyl-LT do not contribute to reperfusion injury of ischemic myocardium.

Chloride ion (Cl-) secretion by the rabbit corneal epithelium involves a catecholamine-stimulated Cl- conductance at the apical membrane, but the characteristics of the ion channel(s) responsible are unknown. A primary cell culture system was developed that induces stratified epithelial differentiation of rat and rabbit corneal epithelial cells, as detected by differential interference contrast light and transmission electron microscopy. In patch clamp studies, gigaOhm seal, were obtained easily during the first 1-4 days in vitro, and patches contained a voltage-dependent outwardly rectifying channel. Single-channel conductance at 24 degrees C was about 10, 29, and 72 pS in symmetric 150 mM NaCl at membrane potentials of -60, 0, and +60 mV, respectively. The current-voltage relationship measured with 75 mM NaCl and sucrose in the bath indicated anion selectivity. Increasing the temperature to 37 degrees C and replacing HEPES buffer with tricine, increased channel conductance and decreased rectification. Characteristics of this channel and a low conductance Cl- channel are compared with those of anion channels of other vertebrate epithelia.

Dithioate DNA was synthesized and used for various biochemical studies. Results from these studies indicate that dithioate DNA is a potent inhibitor of HIV Reverse Transcriptase, activates endogenous RNase H in HeLa cell nuclear extracts, and is a useful probe for studying protein-DNA interactions.

Brook trout (Salvelinus fontinalis) urinary bladder in vitro had a low serosa-positive transepithelial potential (6.7 +/- 1.2 mV), low transmural conductance (0.23 +/- 0.03 mS. cm-2), and net absorptive transport of Na+ and Cl-. The net flux of Na+ was equivalent to that of Cl- and much larger than the membrane current, indicating neutral NaCl uptake. Na+ uptake was not coupled to that of Cl-, since absorptive Na+ transport continued in (Cl-)-free media. In the absence of Cl-, the net absorption of Na+ was accompanied by net secretion of titratable acidity, suggestive of Na+-H+ exchange on the luminal surface. Active Cl- transport persisted in dilute (2.0 mM) tetraethylammonium chloride with zero K+ and zero Na+, indicating full independence of the Cl- transport from cation coupling and suggesting the presence of Cl(-)-HCO-3 exchange. The kinetics of Cl- uptake (K1/2 = 35-37 mM, maximal transport rate = 3.0-3.4 mu eq . cm-2 . h-1) were not significantly affected by removal of mucosal Na+ . Cl- uptake was inhibited partially by 10(-4) M amiloride but not by 10(-4) M bumetanide. The results strongly support a model for active NaCl transport involving paired ion exchangers, likely located at the luminal membrane.

1. The effects of thiocyanate, ouabain, ion-substituted Ringer solution and electrochemical gradients on Na+ and Cl- transport were examined using the isolated skin of the marine teleost, Gillichthys mirabilis. 2. Bilateral replacement of Na+ with choline in the bathing solutions reduces net Cl- flux by 93%, indicating that active Cl- transport by the skin is Na-dependent. 3. Thiocyanate inhibits short-circuit current with an ED50 of 6.4 x 10(-4)M, and, at 10(-2)M, decreases Cl-efflux, influx, net flux and short-circuit current by 68, 33, 74 and 81%, respectively. 4. Ouabain (10(-5)M) reduces Cl- efflux and net flux by 56 and 86%, respectively, indicating that the Cl- transport requires Na,K-ATPase. 5. Subsequent addition of thiocyanate to ouabain-treated skin reduces Cl- efflux, net flux and short-circuit current, suggesting that the two agents operate at different sites involved in Cl- transport. 6. Unilateral substitution of gluconate for Cl- on the serosal side does not affect Cl- influx, indicating that Cl- passive transport is via Fickean diffusion, not Cl-Cl exchange diffusion. 7. The addition of NaCl to the mucosal side, which mimics the in vivo sea-water condition, increases Cl- influx and transepithelial potential and decreases tissue resistance. The net flux (secretion) of Cl- with hypertonic saline on the mucosal side (0.51 +/- 0.06 muequiv/cm2 . hr) demonstrates that the skin could secrete Cl- in vivo. 8. Na+ fluxes across the skin are passive, as the observed flux ration (efflux/influx) is similar to that predicted by the Ussing-Teorell equation under both closed- and open-circuit conditions. 9. The permeability ratio (PNa:PCl) in approximately 5.4:1.0, indicating that the skin is more permeable to Na+, and that at least part of the serosa-positive transepithelial potential may be a Na+ diffusion potential. 10. The results suggest that Cl- secretion by Gillichthys skin is secondary active transport involving Na,K-ATPase and serosal Na+.

LY83583 , a quinolinedione , and LY151364 , a quinoxalinedione , were developed as inhibitors of leukotriene (slow reacting substance of anaphylaxis) release. They preferentially inhibited the release of leukotrienes over histamine from fragmented guinea-pig lung and rat peritoneal cells in vitro, regardless of whether the mediators were released immunologically by antigen or chemically by the divalent cationic ionophore, A23187. Similar results were obtained with rat peritoneal cells in vivo. In that system, comparison of LY83583 with disodium cromoglycate showed the former to preferentially inhibit release of leukotrienes, whereas the latter favored inhibition of histamine release. LY83583 did not significantly decrease antigen-induced bronchospasm in guinea pigs after i.v. administration of doses that approached toxic levels. In addition, LY83583 did not antagonize contractions to carbachol or histamine on guinea-pig trachea, prostaglandin F2 alpha-elicited contraction on guinea-pig ileum or contractions produced by serotonin on guinea-pig aorta. This agent, at 1 X 10(-5) M, reduced the maximal responses to bradykinin on ileum and caused a rightward displacement with a reduction in the maximal response to norepinephrine on guinea-pig aorta. In summary, LY83583 and LY151364 have interesting pharmacologic profiles which make them useful as tools in understanding the role of the leukotrienes in isolated tissue systems.

The fluxes of 86Rb were measured across the isolated skin of the marine teleost Gillichthys. The efflux of 86Rb in Cl Ringer with 1.0 mM RbCl exceeded the influx by 8.0 +/- 1.2 neq . cm-2 . h-1 at closed circuit, indicating active transport of Rb+ in the secretory direction. However, the net Rb+ flux was not significantly different from zero in (Cl-free) gluconate Ringer, indicating that the active Rb+ transport was Cl dependent. The epithelium behaved as a single passive resistor to Rb+ in the absence of Cl-, and Rb+ movement under these conditions appeared to be by Fickean diffusion. Epinephrine (10(-5) M) inhibited partially the active Rb+ transport in Cl Ringer. These results suggest that there is active K+ transport across Gillichthys skin.

A novel compound, LY83583 (6-anilino-5,8-quinolinedione), was found to lower basal levels of cyclic GMP (cGMP) in fragments of guinea-pig lung incubated in vitro. The lowering of cGMP was dose-related reaching a maximum of 72% at 5 X 10(-5) M. Basal levels of cyclic AMP (cAMP) were not lowered by LY83583. cGMP concentrations were also reduced in guinea-pig heart and cerebellum after incubation with LY83583. However, the drug did not alter the levels of this cyclic nucleotide in spleen. Exposure of lung fragments from sensitized guinea pigs to ovalbumin resulted in a marked increase in cGMP and cAMP. LY83583 prevented completely the accumulation of cGMP and attenuated the rise in cAMP. Similar results were obtained in rat cerebellum stimulated with kainic acid. The compound also blocked ovalbumin-induced release of slow reacting substance of anaphylaxis (leukotrienes) from guinea-pig lung. Subcutaneous administration of LY83583 to guinea pigs did not affect cGMP concentrations in vivo in lung, but the total amount of cGMP in spleen was reduced dramatically. This was accompanied by a marked splenomegaly. LY83585 did not inhibit lung guanylate cyclase. In fact, activity was increased in a cell-free preparation from guinea-pig lung. The mechanism by which LY83583 reduced concentrations of cGMP is presently unknown. Nevertheless, our studies suggest that LY83583 will be a valuable pharmacological tool to help elucidate the role of cGMP in biological events.

Evidence is presented that serotonin acts as a neurotransmitter in the cornea of the adult rabbit. Serotonin was localized to granules in a sparse population of subepithelial corneal nerves by an electron microscopic histochemical procedure. Significant endogenous levels of serotonin and its principal metabolite, 5-hydroxyindoleacetic acid, were detected in the central cornea by a fluorometric assay. Exogenous serotonin stimulated ion transport by corneal epithelium. This effect was potentiated by monoamine oxidase inhibition and was unaffected by an alpha-adrenergic receptor antagonist. Serotonin-stimulated ion transport was inhibited by the specific antagonist, methysergide, and by the replacement of Cl- with an impermeable anion. In tracer experiments, the serotonin-stimulated ion transport was shown to be caused by increased epithelial Cl- secretion. The serotonin response was partially inhibited by the beta-adrenergic antagonist, timolol. In a companion article, assay of corneal cyclic AMP showed stimulation of cyclic AMP synthesis by serotonin, inhibition by the specific antagonist, lysergic acid diethylamide, and potentiation by monoamine oxidase inhibition. We postulate that specific serotonergic receptors are present in the corneal epithelium and that activation of these receptors by serotonin released from serotonergic neurons increases the level of cyclic AMP, which stimulates active Cl- secretion by the corneal epithelium.

LY171883, 1-less than2-hydroxy-3-propyl-4-less than 4-(h-tetrazol-5-yl)butoxy greater than phenyl greater than ethanone, proved to be a potent antagonist of leukotriene (LT) D4 in guinea-pig ileum, trachea and lung parenchyma. The compound had little or no effect on contractions of isolated tissues to LTB4, prostaglandin F2 alpha, serotonin, histamine, bradykinin or carbamycholine. Responses of trachea to U46619, a thromboxane A2 mimetic, were antagonized by LY171883, but the doses required were approximately 10-fold higher than those necessary to produce the same degree of antagonism against LTD4. U46619 produced weak ileal contractions that were not blocked by LY171883. LY171883 antagonized both LTD4- and antigen-induced increases in total pulmonary resistance in anesthetized guinea pigs. LTD4 given intradermally to guinea pigs caused vascular leakage which was suppressed by prior administration of LY171883. LTC4-induced contractions of isolated ilea were only minimally antagonized by LY171883 whereas this agent reduced LTC4-evoked increases in total pulmonary resistance. Trachea contracted by LTD4 were relaxed by LY171883. Likewise, trachea contracted by either histamine or carbamylcholine were relaxed by LY171883 suggesting that this compound has airway smooth muscle relaxing properties. In vivo experiments supported these observations. In concert with these findings, biochemical studies showed LY171883 to be a potent inhibitor of phosphodiesterase obtained from human polymorphonuclear leukocytes and various guinea-pig tissues. This pharmacologic analysis indicates that LY171883, or a congener, may be of therapeutic value in asthma and in disease states characterized by an overproduction of LTD4.