A 45 K-gate HEMT array with 35-ps DCFL and 50-ps BDCFL gates

A 45 K-gate emitter-coupled-logic (ECL)-compatible array with unbuffered and buffered direct-coupled FET-logic (DCFL and BDCFL) gates has been developed using 0.6-μm-gate high-electron-mobility transistors (HEMTs) and four-level gold-based interconnects. The high-speed DCFL gates and more functional BDCFL gates are used to replace ECL macros efficiently. The basic cell, equivalent to four three-input NOR gates, consists of 12 enhancement-mode (E-mode) HEMTs, four depletion mode (D-mode) HEMTs, and two source-follower buffers. The basic gate delay times are 35 ps for 0.24-mW unbuffered DCFL gates and 50 ps for 0.38-mW BDCFL gates. The gate array chip is 9.8×9.8 mm and contains 45600 gates. The chip dissipates 11 W in 80% gate use. Silylated polymethyl silsequioxane (PMSS), which has a low dielectric constant of 3, is used for the interlayer dielectrics to reduce wiring delay     

Selective photochemical dry etching of GaAs/AlGaAs and InGaAs/InAlAs heterostructures

Selective photochemical dry etching of GaAs layers on AlGaAs using HCl gas and InGaAs layers on InAlAs using CH/sub 3/Br gas is studied. A low pressure mercury lamp was used as the deep UV light source. A selectivity of more than 150 for GaAs over AlGaAs and more than 60 for InGaAs over InAlAs was obtained.<>     

Computer Aided Analysis of Cell-Cycle Phase from Cytophotometric Histogram

A method for estimating, from cytophotometric data, the proportion of cells in three different phases of the cell cycle is proposed. Computation is done by means of determining seven parameters in the approximate function for the fluorescence intensity histogram. The proportion of cells in the GI, S, and G2-M phases, obtained by this method, was found to be reliable.     

Structure of the gene encoding the alpha subunit of the human interleukin 3 receptor

Interleukin 3 is a cytokine that stimulates proliferation and differentiation of hematopoietic progenitor cells. Its receptor consists of two subunits, an interleukin 3-specific alpha subunit and a beta subunit shared by garanulocyte-macrophage colony stimulating factor and interleukin 5 receptors. In this paper, we determined the genomic structure of the alpha subunit of the human interleukin 3 receptor, which spans approximately 40 kb and has 12 exons. We found that the genomic structures of the alpha subunits of the human interleukin 3 and granulocyte-macrophage colony stimulating factor receptors are very similar. They possess a unique additional intron in the 'C domain', which is absent in the alpha subunit of the interleukin 5 receptor. These results suggest a shared evolutionary pathway of these two genes.     

Constitutive activation of cyclic AMP but not phosphatidylinositol signaling caused by four mutations in the 6th transmembrane helix of the human thyrotropin receptor

Four different somatic mutations (F631C, T632I, D633E, and D633Y) in the putative 6th transmembrane helix of the human thyrotropin receptor (TSHR) were recently described in hyperfunctioning thyroid adenomas [Porcellini et al. (1994) J. Clin. Endocrinol. Metab. 79, 657-661]. We transiently expressed these mutant receptors in Cos-7 cells and measured [125I]TSH binding, basal and TSH-stimulated cAMP production, and phosphatidylinositol hydrolysis. The concentration of receptors expressed at the cell surface was lower for the mutants than for the wild type (WT) TSHR. Compared to the WT, all four mutant receptors caused a marked increase in basal cAMP levels, but did not increase basal production of inositol phosphates. This suggests that autonomous thyroid function and adenoma formation may be related to constitutive activation of the cAMP pathway alone. A cluster of conserved residues at the base of the 6th transmembrane helix of the TSHR and other glycoprotein hormone receptors appears important for maintaining an inactive receptor conformation.     

Receptor cross-talk can optimize assays for autoantibodies to the thyrotropin receptor: effect of phenylisopropyladenosine on adenosine 3',5'-monophosphate and inositol phosphate levels in rat FRTL-5 thyroid cells

Immunoglobulins (IgG) from patients with Graves' disease increase inositol phosphate (IP) as well as cAMP production in rat thyroid FRTL-5 cells; IgGs from normal control subjects do not. Graves' IgG-and TSH-induced IP formation is inhibited by blocking TSH receptor (TSHR) antibodies from hypothyroid patients with primary myxedema, as is the cAMP response; this suggests that the Graves' IgG are acting through the TSHR to induce both the cAMP and phosphatidyl-inositol 4,5-biphosphate signal cascades in FRTL-5 thyroid cells as in cells with recombinant TSHR. Optimal conditions for measuring the Graves' IgG-induced IP increase include a NaCl-free Hanks' Balanced Salt Solution (HBSS) buffer system and a P1 purinergic receptor agonist; the action of each is additive. Optimization by NaCl-free HBSS is similar to that observed in cAMP assays and is specific for TSH or Graves' IgG; thus, NaCl-free HBSS did not affect ATP-induced, and actually inhibited norepinephrine-induced, IP production in FRTL-5 cells. The P1 purinergic receptor agonist acts via receptor cross-talk, which also allows further optimization of cAMP assays. Thus, adenosine deaminase improves Graves' IgG-induced cAMP production by removing adenosine from the medium. Although NaCl-free HBSS improved TSH- or Graves' IgG-induced IP and cAMP production in cells with recombinant TSHR; the modulatory action of phenylisopropyladenosine was lost.     

Protective effect of thromboxane synthetase inhibitor on hypertensive renal damage in Dahl salt-sensitive rats

1. The effects of OKY-046, a specific thromboxane (TX) synthetase inhibitor, on blood pressure, urinary excretion of TX and its release from blood platelets and renal papilla, and pathological change of glomeruli were evaluated in Dahl salt-sensitive rats. 2. Average daily intakes of OKY-046-treated rats were 0.93 mg/kg (low dose), 9.8 mg/kg (moderate dose), and 88 mg/kg (high dose). 3. Systolic blood pressure tended to decrease by 6.3, 11.4, and 10.9% in three OKY-treated groups. 4. OKY-046 suppressed the release of TX from platelets in a dose-dependent fashion. Both TX in urine and released from renal papilla decreased in OKY-treated groups with moderate and high dose. OKY-046 resulted no change in urinary excretion or release from renal papilla of prostaglandin E2 or 6-keto-prostaglandin F1alpha. 5. Glomerular sclerosis score decreased significantly in both groups treated with moderate and high doses of OKY-046. 6. An inhibition of renal TX synthesis by TX synthetase inhibitor has a protective effect on the development of hypertensive renal damage with minor antihypertensive effect in Dahl salt-sensitive rats.     

pH-independent fluorescent chemosensor for highly selective lithium ion sensing

Since lithium salts are used as pharmaceutically active compounds against manic-depressive psychosis, there is a demand to monitor the lithium concentration in blood in the narrow range of 0.6-1.2 mM effectively and safely. Here we report on an optical sensor approach for the determination of Li+, based on the design and synthesis of a novel lithium fluoroionophore KLI-1 and its polymer immobilizable derivative KLI-2, and the application to an optode. The novel lithium fluoroionophores rely on a tetramethyl "blocking subunit" bearing 14-crown-4 as a Li+-selective binding site and 4-methylcoumarin as a fluorophore, intramolecularly connected to show ICT-type wavelength shift for ratiometric fluorescence measurements. The fluoroionophores showed high selectivity for Li+ with binding-induced blue shift in the fluorescence spectra, no response to major biological interfering cations (K+, Ca2+, Mg2+), a selectivity of log kLi+,Na+ = -2.4 over Na+ in solution, and no response to pH in the range of pH 3-10. A hydrophilic optode membrane with KLI-2 immobilized also showed good selectivity for Li+, pH independence in the physiological range (pH 6-8), and fully reversible signal changes. KLI-1 and KLI-2 are excellent Li+ fluorescent chemosensors that can be applied to quantitative measurements of lithium in clinical samples, although possible interference from Na+ has to be considered at the lower therapeutic level of Li+.