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By fixing charged colloidal crystals in a poly(acrylamide) hydrogel matrix, we fabricated photonic crystals whose diffraction peak wavelengths were tunable by applying mechanical stress. The reflection spectrum for a single crystal grain was measured by applying microspectroscopy under compression. The photonic band gap wavelength shifted linearly and reversibly over almost the entire visible light wavelength region (460−810 nm).

Measurements of (p, ρ,T) at given temperatures and pressures in the compressed liquid phase for {xC2H5OH + (1−x)H2O} withx= (0.1002, 0.2503, 0.4999, 0.7459 and 0.8904) were carried out with a metal-bellows variable volumometer along six isotherms betweenT= 320 K andT= 420 K at pressures from the bubble pressure to 200 MPa. The results cover the high-density region from ρ = 863 kg·m−3to ρ = 1019 kg·m−3forx= 0.1002, from ρ = 798 kg·m−3to ρ = 976 kg·m−3forx= 0.2503, from ρ = 727 kg·m−3to ρ = 929 kg·m−3forx= 0.4999, from ρ = 684 kg·m−3to ρ = 899 kg·m−3forx= 0.7495, and from ρ = 665 kg·m−3to ρ = 885 kg·m−3forx= 0.8904. The experimental uncertainties of temperatureT, pressureP, density ρ, and mole fractionxwere estimated to be ± 3 mK, ± 1.0−10−3·ρ, 1.0·10−3·ρ, and ± 6·10−4·x, respectively. Measurements of saturated liquid density and bubble pressure at temperatures from 320 K to 420 K are also reported. The bubble pressure indicate positive deviations from Raoult's law at all temperatures measured. The excess molar volumes indicate negative values in the temperature and pressure range of the present measurements and approach zero with increasing pressure.

Ethyl N-[3-(2-fluoro-4-(thiazolidin-3-yl(imino)methyl)benzoyl)amino-2,2-dimethylpentanoyl]piperidine-4-acetate 40 (NSL-96184) is a highly potent and orally active fibrinogen receptor antagonist, which is characterized by the presence of the trisubstituted β-amino acid residue, 3-ethyl-2,2-dimethyl-β-alanine. This compound was developed on the basis of the SAR study of N-[3-(N-4-amidinobenzoyl)amino-2,2-dimethyl-3-phenylpropionyl]piperidine-4-acetic acid 1 (NSL-95301) with the derivatization focused on the central trisubstituted β-amino acid unit as well as the basic amidinobenzoyl unit, and the esterification of the carboxyl group for prodrug composition. Compound 1, which was reported in our previous study, was discovered by the application of combinatorial chemistry. The molecular modeling study suggests that the trisubstituted β-amino acid unit is responsible for fixing the molecule to its active conformation. Compound 40 showed an excellent profile in the in vitro and in vivo studies for its human platelet aggregation inhibitory activity and oral availability in guinea pigs. This oral availability largely depends on the modification of the amidino group with a cyclic secondary amine, i.e., thiazolidine in 40. In in vivo studies, the onset of the antiplatelet action of 40 is very fast after oral administration, whereas its duration of action is relatively short. These results suggest that 40 has an excellent therapeutic potential, especially for antithrombotic treatment in the acute phase. 3-Substituted-2,2-dimethyl-β-amino acid residues would serve as new and useful linear templates to restrict the conformational flexibility of peptidomimetics.

By using porcine elastase I cDNA as a probe, we have isolated two different but closely related cDNAs encoding elastase-like proteases from a human pancreatic cDNA library. The amino acid sequences deduced from the cloned cDNA sequences showed 56-61% identity with those of both pancreatic elastases I and II, similar to the homology between elastases I and II. The active form of the elastase-like proteases appeared to be composed of 242 amino acids and preceded by a signal peptide and propeptide of 28 amino acids. Dot blot analysis of various tissue mRNAs demonstrated that the genes for the cloned cDNAs are expressed at a high level only in the pancreas. In addition, sequence analysis of the cloned genomic genes corresponding to one of the cDNAs showed that they are members of the elastase gene family. These results indicate that the two enzymes encoded by the cDNAs should be classified into a third class of elastase isozyme. Therefore, we designated them as human pancreatic elastases IIIA and IIIB. They strongly resembled cholesterol-binding pancreatic protease, suggesting that they may possess not only a digestive function but also function(s) related to cholesterol metabolism or transport in the intestine.

To clarify the role of hypothyroidism in diabetes-induced sympathetic neuropathy, we examined the responsiveness to sympathetic nerve stimulation and to agonists of the left atria of streptozotocin-induced diabetic rats, and compared it with those in hypothyroid, thyroxine(T4)-treated diabetic or T4-treated hypothyroid rats. Positive inotropic response of isolated left atria to transmural nerve stimulation (TNS) was examined in the presence of atropine. In diabetic rats, plasma triiodothyronine and T4 levels decreased markedly. The responses to TNS and norepinephrine (NE) also decreased. The decrease was greater in response to TNS, which may be due to the reduction of presynaptic NE release. As to the postsynaptic response, the maximal response to NE decreased without any significant change in ED50 value, and a similar decrease in the maximal response to Ca++ was also observed in spite of a slight decrease in the beta receptor density. Therefore, in diabetic rats the decreased response to TNS may result mainly from a decreased NE release from nerve endings and a decreased contractility beyond the adrenoceptor level. In hypothyroid rats, the response to TNS and NE decreased, and the decrease was again greater in response to TNS. The decrease in the NE response was due to the increased ED50 value without any change in the maximal response. Similarly, the maximal response to Ca++ did not change. Thus in the hypothyroid rats, the decreased response to TNS probably results from a decreased NE release from nerve endings as well as a decreased sensitivity to NE.(ABSTRACT TRUNCATED AT 250 WORDS)

To develop a specific antagonist of platelet alphaIIbbeta3 using small linear peptides, we synthesized a series of hexapeptides that did not have an Arg-Gly-Asp (RGD) sequence and examined their anti-platelet activity and their specificity for alphaIIbbeta3. We found a novel motif sequence, Pro-X1-X2-X3-Asp-X4, where X1 to X4 were all L-form alpha-amino acids, which specifically inhibited aggregation of human platelets at submicromolar concentrations. The Pro residue at the N terminus was essential to the anti-platelet activity, and the acetylation of the imino group of this residue also resulted in the complete loss of the activity. The results of the binding assay using purified human platelet alphaIIbbeta3 and placental alphavbeta3 and those of the cell adhesion assay suggest that this motif peptide is highly specific for platelet alphaIIbbeta3 among other integrins. Flow cytometric studies using an fluorescein isothiocyanate-labeled RGD peptide showed that this motif peptide inhibited the binding of an RGD peptide to activated platelets, suggesting that it has the same inhibitory mode as RGD peptides. Conformational analysis of this motif peptide and an RGD-containing peptide suggests that the imino group of the Pro residue may substitute for the role of the guanidino group of the Arg residue of the RGD sequence.

The effects of a large external uniaxial stress (s`) along [100] on the optical features associated with biaxially strained bulk GaAs and two GaAs/Ga1-xAlxAs single quantum wells (SQWs), with widths of 52 and 200 Å, grown on Si(001) have been studied using photoreflectance at 77 and 300 K. Measurements were made with incident light polarized parallel and perpendicular to s`. This stress configuration makes it possible to externally alter the light-hole (LH) and heavy-hole (HH) splitting in both the bulk material and the SQWs. In the SQW of width 200 Å, the ground-state valence band was continually tuned from HLs to HHs. In the bulk material, a stress-induced anticrossing of the LH and HH features of the fundamental gap was observed with an interesting polarization effect.

To determine the effects of an aldose reductase inhibitor (ARI) on diabetes-induced cardiac autonomic nerves disturbance, we examined the effects of ONO-2235, an ARI, as well as insulin on the responsiveness to the nerve stimulation and agonists of the isolated atria of the streptozotocin-induced diabetic rats. Insulin, 4 U/animal/day, was administered s.c. for 4 weeks before the experiment and ARI (ONO-2235), 40 mg/kg/day, was administered p.o. 3 weeks before the experiment. The transmural nerve stimulation (TNS) of sympathetic nerves and parasympathetic nerve was performed in the presence of atropine and metoprolol plus prazocin, respectively. The positive chronotropic and the inotropic responses of the atria to sympathetic TNS and to norepinephrine decreased in the rats diabetic for 8 and 12 weeks. In the rats diabetic for 8 weeks, the insulin treatment restored completely both the positive chronotropic and the inotropic responses to sympathetic TNS, whereas the ARI treatment partially improved the positive chronotropic response and did not improve the positive inotropic response. In the rats diabetic for 12 weeks, the insulin treatment partially improved the positive chronotropic and the inotropic responses to sympathetic TNS, whereas the ARI treatment only slightly improved the positive chronotropic response and did not improve the positive inotropic response to TNS. The combination treatment with insulin and ARI restored completely both the positive chronotropic and the inotropic responses in the rats diabetic for 12 weeks. In rats diabetic for both 8 and 12 weeks, the decreased positive chronotropic and the inotropic responses to norepinephrine recovered completely with the insulin treatment, but did not with the ARI treatment.(ABSTRACT TRUNCATED AT 250 WORDS)