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The inbuilt 2-N-hydroxy-1-oxo-3-carboxylic acid of isoquinolone was designed as pyrophosphate mimic for hepatitis C NS5B polymerase. Various 2-hydroxy-1-oxo-1,2-dihydroisoquinoline-3-carboxylic acid derivatives 11a-p were synthesized and evaluated as HCV NS5B polymerase inhibitors. Compound 11c exhibited moderate inhibitory potency based on the inorganic pyrophosphate generation (IC50 = 9.5 μM) and based on NTP incorporation by NS5B enzyme (IC50 = 5.9 μM). Compound 11c demonstrated antiviral activity (EC50 = 15.7 μM) and good selectivity in HCV genotype 1b replicon Ava.5 cells. Compound 11c reduced the interaction of NTP to NS5B polymerase. Docking model showed that 11c situated in similar orientation to the bound uridine triphosphate in the active site of NS5B polymerase. As a result, 2-hydroxy-1-oxo-1,2-dihydroisoquinoline-3-carboxylic acid was disclosed as a novel inbuilt γ-keto-acid pharmacophore for HCV NS5B polymerase inhibitors.

A synchronous optical code-division multiple access system with balanced encoder instead of on-off-keying (OOK) encoder is proposed. In the system, the multi-user interference is maintained constant during a frame, and the receiver estimates the interference frame by frame instead of bit by bit. The data rate of the proposed system is no longer severely limited by the electronic processing time in estimating the interference, and the structure of the proposed receiver is simpler than those in OOK systems. In the receiver, both linear and non-linear threshold estimators are introduced. Numerical results show that the proposed system has smaller bit error rate than OOK systems, especially when the number of training bits is increased.

Electrodeposition of a metallic Al layer on a Mg alloy from a Lewis acidic Al chloride–1-ethyl-3-methylimidazolium chloride (EMIC) ionic liquid has been carried out at room temperature. The effects of the AlCl3 to EMIC molar ratio, in the range from 50%–50% to 60%–40%, on the electrodeposition characteristics were investigated. Scanning electron microscopy, X-ray energy dispersive spectroscopy, and X-ray diffractometry were used to examine the surface morphology, the chemical composition, and the crystal structure of the deposited layers prepared in the ionic liquids with different AlCl3 to EMIC ratios. The improvement of corrosion resistance of a Mg alloy to the Al surface coating was also evaluated by means of various electrochemical methods. The electrochemical impedance spectroscopic data indicated that while a bare Mg alloy had a polarisation resistance of only 470 Ω cm2 in 3˙5 wt-% NaCl solution, the Al coated sample deposited in the ionic liquid with 60%AlCl3 showed a resistance as high as ...

To better predict risk of progression of low-grade squamous intraepithelial lesions (LSILs) of the uterine cervix in women with human papillomavirus (HPV) infections, 294 baseline cervical specimens from women with LSILs were evaluated. Specimens were tested for HPV DNA using hybrid capture 2 (HC2) and PCR-reverse line blotting. 65 LSILs with HPV DNA types 16, 18, 52, or 58 were examined for physical status, E2/E6 ratio and viral load at two time points, along with patient age. Women with LSILs whose viral loads increased between baseline and 6 month follow-up had a 45% risk of developing HSIL (OR=7.6, 95% CI=1.9–29.4, P

The present study was undertaken to explore factors associated with observance of prescribed antihypertensive medications. Secondary data analysis utilising ambulatory claims of the Taiwan National Health Insurance involved all initially treated hypertensive patients (n=565,048) from June 1, 1997 to June 30, 1998. The main outcome measure was the statistical analysis of factors prompting medication switch and dropout rates. The overall continuity rate was 51%. Specific continuity rates were 40% for calcium antagonists, 36% for angiotensin-converting enzyme inhibitors, 35% for beta-blockers and 29% for diuretics. Less than 30% of patients changed medications and more than 20% of patients changed clinics. The change increased the likelihood of switching medications sevenfold. Switch was minimal for calcium antagonists. Patients taking calcium antagonists were the least likely to switch medications and had the lowest dropout rate. Changing clinics was the most influential medication switch factor.

The inbuilt 2-N-hydroxy-1-oxo-3-carboxylic acid of isoquinolone was designed as pyrophosphate mimic for hepatitis C NS5B polymerase. Various 2-hydroxy-1-oxo-1,2-dihydroisoquinoline-3-carboxylic acid derivatives 11a-p were synthesized and evaluated as HCV NS5B polymerase inhibitors. Compound 11c exhibited moderate inhibitory potency based on the inorganic pyrophosphate generation (IC₅₀ = 9.5 μM) and based on NTP incorporation by NS5B enzyme (IC₅₀ = 5.9 μM). Compound 11c demonstrated antiviral activity (EC₅₀ = 15.7 μM) and good selectivity in HCV genotype 1b replicon Ava.5 cells. Compound 11c reduced the interaction of NTP to NS5B polymerase. Docking model showed that 11c situated in similar orientation to the bound uridine triphosphate in the active site of NS5B polymerase. As a result, 2-hydroxy-1-oxo-1,2-dihydroisoquinoline-3-carboxylic acid was disclosed as a novel inbuilt β-N-Hydroxy-γ-keto-acid pharmacophore for HCV NS5B polymerase inhibitors.

The present study was undertaken to explore factors associated with observance of prescribed antihypertensive medications. Secondary data analysis utilising ambulatory claims of the Taiwan National Health Insurance involved all initially treated hypertensive patients (n=565,048) from June 1, 1997 to June 30, 1998. The main outcome measure was the statistical analysis of factors prompting medication switch and dropout rates. The overall continuity rate was 51%. Specific continuity rates were 40% for calcium antagonists, 36% for angiotensin-converting enzyme inhibitors, 35% for beta-blockers and 29% for diuretics. Less than 30% of patients changed medications and more than 20% of patients changed clinics. The change increased the likelihood of switching medications sevenfold. Switch was minimal for calcium antagonists. Patients taking calcium antagonists were the least likely to switch medications and had the lowest dropout rate. Changing clinics was the most influential medication switch factor.

gamma S-Crystallin from shark eye lenses, formerly termed beta s crystallin in mammalian lenses, is structurally characterized in this study by cDNA cloning and sequencing. To facilitate sequence characterization of gamma S-crystallin possessing intermediate structural properties between beta- and gamma-crystallins, cDNA mixture was constructed from the poly(A)+ mRNA isolated from shark eye lenses, and amplification by polymerase chain reaction (PCR) was carried out to obtain nucleotide segments encoding multiple shark gamma S-crystallins. Sequencing several positive clones revealed that a multiplicity of isoforms exists in the gamma S-crystallin class of this cartilaginous fish, similar to authentic gamma-crystallin family characterized from the same shark species. Comparison of protein sequences encoded by two representative shark gamma S1 and gamma S2 cDNAs with those published sequences of beta-, gamma-, and gamma S crystallins from bovine, human, bullfrog and carp lenses indicated that there is about 35-64% sequence homology between shark gamma S crystallins and structurally related crystallins from different evolutionary classes, with a higher sequence similarity between shark gamma S and mammalian gamma-crystallins than that of shark gamma S and carp gamma S or bovine gamma S crystallins. A phylogenetic tree constructed on the basis of the sequence divergence among various beta-, gamma-, and gamma S crystallins corroborates the closer relatedness of shark gamma S to authentic gamma-crystallin than to mammalian and teleostean gamma S crystallins. It further strengthens the supposition that ancestral precursors of gamma S-crystallins were present in the shark lens long before the appearance of present-day teleostean and mammalian gamma S-crystallins.

Cardiotoxins, neurotoxins and phospholipase A2 (PLA2) are three major classes of toxic components present in the Taiwan cobra, Naja naja atra of the Elapidae family. Cardiotoxins (or called cytotoxins), a group of major polypeptides of around 60 amino-acid residues present abundantly in the elapid family of snakes, comprise about 45-55% of the crude venom of Taiwan cobra. In contrast to another prominent group of structurally similar neurotoxins with well-established acetylcholine receptors and modes of action, cardiotoxins showed no defined cellular targets and very diverse pharmacological functions. A systematic structure/function comparison of these toxins was made by their relative inhibitory effects on protein kinase C (PKC) isolated from mouse brains. Lethality and hemolysis of various cardiotoxin isoforms were also compared in order to shed some insight on the biological targets and mechanisms of these surface-active amphiphilic polypeptides. A structure comparison of these cardiotoxins based on computer model-building revealed that some defined and subtle differences can be detected upon the superposition of these three-dimensional polypeptide chains, which may reflect the intrinsic differences in the hydrophobic peptide segments present on the surface loops of toxin molecules. The differences seem to correlate with different inhibitory activities exhibited by cardiotoxins in contrast to the lack of activity by cobrotoxin and PLA2 on PKC.

This work investigates the thermal stability of chemically vapor deposited amorphous WSix layers used as a diffusion barrier between Cu and Si substrate, in which the WSix layers were deposited to a thickness of about 50 nm using the SiH4 reduction of WF6 at various SiH4/WF6 flow ratios. For 30 min annealing in nitrogen ambient, the effectiveness of the WSix layers as barriers between a copper overlayer and a p+–n junction diode decreases as the Si/W atomic ratio, x, increasing from 1 to 1.3. This composition change is obtained by raising the SiH4/WF6 flow ratio from 3 to 50. As deposited, all films are x-ray amorphous. Their resistivity increases roughly linearly with x. The barrier capability of WSix layers can be significantly improved by an in situ N2 plasma treatment. The N2 plasma treatment produces a very thin layer of WSiN (about 5 nm) on the surfaces of WSix layers. In particular, the Cu/WSiN/WSix/p+–n junction diodes with the WSix layers deposited with a SiH4/WF6 flow ratio of 3 were able to rem...