Direct observation of spinodal decomposition phenomena in InAlN alloys during in-situ STEM heating.

The spinodal decomposition and thermal stability of thin In0.72Al0.28N layers and In0.72Al0.28N/AlN superlattices with AlN(0001) templates on Al2O3(0001) substrates was investigated by in-situ heating up to 900 °C. The thermally activated structural and chemical evolution was investigated in both plan-view and cross-sectional geometries by scanning transmission electron microscopy in combination with valence electron energy loss spectroscopy. The plan-view observations demonstrate evidence for spinodal decomposition of metastable In0.72Al0.28N after heating at 600 °C for 1 h. During heating compositional modulations in the range of 2-3 nm-size domains are formed, which coarsen with applied thermal budgets. Cross-sectional observations reveal that spinodal decomposition begin at interfaces and column boundaries, indicating that the spinodal decomposition has a surface-directed component.

Core-shell formation in self-induced InAlN nanorods.

We have examined the early stages of self-induced InAlN core-shell nanorod (NR) formation processes on amorphous carbon substrates in plan-view geometry by means of transmission electron microscopy methods. The results show that the grown structure phase separates during the initial moments of deposition into a majority of Al-rich InAlN and a minority of In-enriched InAlN islands. The islands possess polygonal shapes and are mainly oriented along a crystallographic c-axis. The growth proceeds with densification and coalescence of the In-enriched islands, resulting in a base for the In-enriched NR cores with shape transformation to hexagonal. The Al-rich shell formation around such early cores is observed at this stage. The matured core-shell structure grows axially and radially, eventually reaching a steady growth state which is dominated by the axial NR growth. We discuss the NR formation mechanism by considering the adatom surface kinetics, island surface energy, phase separation of InAlN alloys, and incoming flux directions during dual magnetron sputter epitaxy.

Stacking fault related luminescence in GaN nanorods.

Optical and structural properties are presented for GaN nanorods (NRs) grown in the [0001] direction on Si(111) substrates by direct-current reactive magnetron sputter epitaxy. Transmission electron microscopy (TEM) reveals clusters of dense stacking faults (SFs) regularly distributed along the c-axis. A strong emission line at ∼3.42 eV associated with the basal-plane SFs has been observed in luminescence spectra. The optical signature of SFs is stable up to room temperatures with the activation energy of ∼20 meV. Temperature-dependent time-resolved photoluminescence properties suggest that the recombination mechanism of the 3.42 eV emission can be understood in terms of multiple quantum wells self-organized along the growth axis of NRs.

Excitons and biexcitons in InGaN quantum dot like localization centers.

Indium segregation in a narrow InGaN single quantum well creates quantum dot (QD) like exciton localization centers. Cross-section transmission electron microscopy reveals varying shapes and lateral sizes in the range ∼1-5 nm of the QD-like features, while scanning near field optical microscopy demonstrates a highly inhomogeneous spatial distribution of optically active individual localization centers. Microphotoluminescence spectroscopy confirms the spectrally inhomogeneous distribution of localization centers, in which the exciton and the biexciton related emissions from single centers of varying geometry could be identified by means of excitation power dependencies. Interestingly, the biexciton binding energy (E(b)xx) was found to vary from center to center, between 3 to -22 meV, in correlation with the exciton emission energy. Negative binding energies are only justified by a three-dimensional quantum confinement, which confirms QD-like properties of the localization centers. The observed energy correlation is proposed to be understood as variations of the lateral extension of the confinement potential, which would yield smaller values of E(b)xx for reduced lateral extension and higher exciton emission energy. The proposed relation between lateral extension and E(b)xx is further supported by the exciton and the biexciton recombination lifetimes of a single QD, which suggest a lateral extension of merely ∼3 nm for a QD with strongly negative E(b)xx = -15.5 meV.

Built-in surface electric field, piezoelectricity and photoelastic effect in GaN nanorods for nanophotonic devices.

Novel behaviors arising from the coupling between the built-in surface electric field, piezoelectricity, electron-hole pairs and external light beam were observed in GaN nanorods. An increase in the optical excitation density resulted in a blueshift in the photoluminescence spectra and a redshift in the frequency of the GaN A(1)(LO) phonon. The underlying mechanism was attributed to the screening of the built-in surface electric field by photoexcited carriers and, through the converse piezoelectric effect, a reduction in the internal strain. The existence of the built-in surface electric field in GaN nanorods was confirmed by scanning Kelvin probe microscopy. Our results firmly establish the existence of the photoelastic effect in GaN nanorods. In addition to underpinning the principle for applications in nanophotonic devices, this discovery also draws attention to the novel effects arising from the inherent large surface-to-volume ratio of nanostructures, which is possibly applicable to many other nanomaterials.

Epitaxial growth of InN films by molecular-beam epitaxy using hydrazoic acid (HN3) as an efficient nitrogen source.

Epitaxial InN films have been successfully grown on c-plane GaN template by gas-source molecular-beam epitaxy with hydrazoic acid (HN3) as an efficient nitrogen source. Results in residual-gas analyzer show that the HN3 is highly dissociated to produce nitrogen radicals and can be controlled in the amounts of active nitrogen species by tuning HN3 pressure. A flat and high-purity InN epifilm has been realized at the temperature near 550 degrees C, and a growth rate of 200 nm/hr is also achieved. Moreover, the epitaxial relationship of the InN(002) on the GaN(002) is reflected in the X-ray diffraction, and the full-width at half-maximum of the InN(002) peak as narrow as 0.05 degrees is related to a high-quality crystallinity. An infrared photoluminescence (PL) emission peak at 0.705 eV and the integrated intensity increasing linearly with excitation power suggest that the observed PL can be attributed to a free-to-bound recombination.

Effect of hydroxyzine on the transport of etoposide in rat small intestine.

Etoposide, an anti-neoplastic agent and a substrate of P-glycoprotein (P-gp), exhibits variable oral bioavailability. P-gp, the multidrug resistance gene (mdr1) product, has been considered as an absorption barrier against intestinal drug absorption. Terfenadine, an antihistamine, has been shown to be a P-gp inhibitor. The current study was designed to assess the effect of hydroxyzine, an antihistamine, on the transport of etoposide in the small intestine. Everted rat gut sacs were used to determine the absorption and exsorption of etoposide under different conditions, as rhodamine 123 was chosen to evaluate the role of P-gp in the drug interaction. The results showed that the transport of etoposide was significantly increased from the luminal site to the serosal site in the jejunum by 2- and 4-fold after 90 min in the presence of hydroxyzine and quinidine, respectively. A similar trend was observed in the ileal sacs. This in vitro exsorption study also demonstrated that hydroxyzine could reduce the efflux of etoposide to the luminal site in either jejunum or ileum. The effect of hydroxyzine on the pharmacokinetics of etoposide differed by the in vivo route of administration, thus assuming clinical importance for chemotherapeutic treatment.

Heteroaryl and cycloalkyl sulfonamide hydroxamic acid inhibitors of matrix metalloproteinases.

Heteroaryl and cycloalkyl sulfonamide-hydroxamic acid MMP inhibitors were investigated. Of these, the pyridyl analogue 2 is the most potent and selective inhibitor of MMP-9 and MMP-13 in vitro.

Effects of pravastatin on left ventricular mass in patients with hyperlipidemia and essential hypertension.

Left ventricular (LV) mass is a powerful predictor for future cardiovascular events. Epidemiologic studies have shown that hyperlipidemia is associated with higher LV mass. The effects of statin therapy for hyperlipidemia on LV mass have not been studied. To determine the effects of statin therapy on LV mass, we prospectively studied 3 groups of age and body surface area-matched patients: group 1 (n = 20), patients with systemic hypertension and hyperlipidemia treated with pravastatin plus anti-hypertensive drugs; group 2 (n = 20), patients with hypertension and hyperlipidemia treated with hypertensive agents and diet control alone; and group 3 (n = 20), hypertensive patients with normolipidemia treated with antihypertensive agents. A group of controls without hypertension or hyperlipidemia was used for comparison. Echocardiograms were recorded at baseline and after 6-month therapy. All hypertensive groups showed significant decreases in LV mass index after treatment. Group 1 had the greatest decrease in LV mass and it was significantly higher than in groups 2 and 3. Multivariate analysis revealed that regression of LV mass was significantly correlated only with the use of statins and sex (p = 0.005 and 0.01, respectively, R(2) = 0.47). Linear regression analysis in group 1 showed a significant correlation between changes in arterial compliance and LV mass regression (r = 0.57, p = 0.01). Thus, the addition of a statin may have an additional effect on reducing LV mass, independent of lipid-lowering effects.

A [35S]GTPgammaS binding assessment of metabotropic glutamate receptor standards in Chinese hamster ovary cell lines expressing the human metabotropic receptor subtypes 2 and 4.

The activities of metabotropic glutamate receptor (mGluR) standards were evaluated in the [35S]GTPgammaS binding assay and in the forskolin (FSK)-enhanced cyclic AMP assay using Chinese hamster ovary (CHO) cells or homogenates which expressed the human mGluR (hmGluR) subtypes 2 and 4. Though distinct rank orders of activities were determined for the agonists between the cell lines expressing individual hmGluRs, similar rank orders of agonist activities were determined for the standards between assays. O-phospho-L-serine (L-SOP) and (S)-2-amino-2-methyl-4-phosphonobutanoic acid (MAP4) antagonized agonist EC90 responses in the cell lines expressing the hmGluR 2 and 4 subtypes, respectively. In addition to its antagonist effect, L-SOP increased the baseline level of cAMP when tested in the absence of agonist. In spite of this anomalous effect, L-SOP was found to be a competitive antagonist in the cAMP assay as well as in the [35S]GTPgammaS binding assay with a pA2 value of 5.2 in both assays. MAP4 was a competitive antagonist of L(+)-2-amino-4-phosphonobutyric acid (L-AP4)-induced responses in the CHO cell line expressing hmGluR4 with pA2 values of 4.4 and 4.5 determined in the [35S]GTPgammaS binding and cAMP assays, respectively.

Etodolac selectively inhibits human prostaglandin G/H synthase 2 (PGHS-2) versus human PGHS-1.

The isozymes of prostaglandin G/H synthase (PGHS) are shown to be differentially inhibited in vitro by currently marketed nonsteroidal anti-inflammatory drugs (NSAIDs) using microsomal rhPGHS-1 and rhPGHS-2. Comparison of selectivity ratios (IC50 rhPGHS-1/IC50 rhPGHS-2) demonstrated a 10-fold selectivity of etodolac (Lodine) for rhPGHS-2, whereas the other NSAIDs evaluated demonstrated no preference or a slight preference for inhibition of rhPGHS-1. In vitro enzyme results were supported by a human whole blood assay where etodolac also demonstrated a 10-fold selectivity for inhibition of PGHS-2 mediated TxB2 production. Taken together, these data may be key to explaining the clinically observed gastrointestinal safety of etodolac versus other marketed NSAIDs.

A putative sirolimus (rapamycin) effector protein.

Sirolimus (rapamycin), a new immunosuppressive drug, inhibits proliferation of a wide spectrum of T and B cells. The immunosuppressive mechanism of sirolimus is still unclear. We recently isolated a membrane associated protein with an apparent molecular weight of 210 kDa, p210, from cultured Molt 4 cells and BJAB cells and from normal human T cells using an affinity matrix method. The p210 binds to sirolimus:FKBP12 complex, but only at background levels to FKBP12 alone, to FK506:FKBP12 complex, or sirolimus-biotin alone. Among the sirolimus analogs tested, the binding ability of p210 to drug:FKBP12 complexes correlates with the immunosuppressive activity of the drugs, suggesting that p210 is the sirolimus effector protein.

Immunogenicity of recombinant influenza virus haemagglutinin carrying peptides from the envelope protein of human immunodeficiency virus type 1.

Haemagglutinin (HA), the major surface glycoprotein of influenza virus, is a potent immunogen against which viral neutralizing antibodies are directed. Studies of the three-dimensional structure of HA have identified major antigenic sites on the molecule. We have exploited HA as a carrier for small antigenic regions (epitopes) of the HIV-1 envelope (env) glycoprotein. Using recombinant DNA techniques, the epitopes were inserted in-frame into a known antigenic site of HA to produce HA-epitope chimeras. Guinea-pigs and mice immunized with these chimeras in combination with adjuvant generated significant immune responses against the carrier HA and also produced epitope-specific antibodies that recognized the native whole HIV-1 env. One of the chimeras which contained a V3-loop sequence of HIV-1 env elicited neutralizing antibodies against the homologous strain of HIV-1. The antibodies against HA and the inserted epitopes remained at high levels for up to 72 weeks. Remarkably, these responses were generated with low doses of immunogens containing only nanogram quantities of the inserted epitopes. These results suggest the utility of HA as a carrier to allow selective antibody induction against foreign epitopes, and offer a new approach for vaccine development as well as for the production of monospecific antibodies useful in diagnostics and research.

Aqueous acupuncture for postoperative pain--a matched controlled trial.

The analgesic effects of acupuncture are well-documented. Aqueous acupuncture, or point injection, is a conveniently modified modern acupuncture method. This matched controlled trial was carried out to evaluate the effects of aqueous acupuncture in postoperative pain control. A total of 12 patients were selected as age-, sex- and operative-style-matched controls. In treating group, 2 to 5 ml of 20% glucose solution was injected into Ho-Ku (LI 4) and Yang-Ling-Chuan (GB 34) when patients had regained conciousness from operation anesthesia. The pain intensity were recorded as score system included verbal, sleep disturbance and use of narcotics. In comparisons with the control group, the intensity of postoperative pain, and the amounts and frequency of narcotics used were significantly lower in the study group, especially for the first 12 postoperative hours. Aqueous acupuncture is a convenient and effective procedure in postoperative pain control.

Conservation of essential sequences in the major late promoter and tripartite leader of the simian adenovirus type 30.

We report here the cloning and sequencing of the major late promoter (MLP) and the tripartite leader (TPL) from simian adenovirus type 30 (sAd30) and the comparison of the sAd30 nucleotide (nt) sequence with that of human adenoviruses (hAd). The nt sequence homology between sAd30 and hAd2 is 75% from -66 to +190 relative to the cap site. This sAd30 MLP segment contains the upstream regulatory sequence element, TATA box, and downstream regulatory sequence elements that are homologous to hAd MLP. The sAd30 upstream regulatory sequence has a small palindromic DNA sequence GTCACGTGAC, and the TATA box contains the sequence of ATAAA instead of TATAAA. The sAd30 TPL was located on the sAd30 genome as identified by sequence homology with the hAd counterpart. The splice sites of TPL introns were confirmed by sequence analysis of cDNAs synthesized from sAd30-infected cells. There is a 74.2% nt sequence homology between the TPL of sAd30 and hAd2. The conservation of these sequence elements during evolution of Ad suggests that they are essential for the transcription and translation of Ad ML transcripts.

Elimination of antibiotic-resistant plasmids by quinolone antibiotics.

Of 7 plasmids we tested, the plasmid pORF2 was eliminated in vitro with the most efficiency by treatment with subinhibitory concentrations of novobiocin, coumermycin and 10 quinolones. It showed a cure rate of 43% by enoxacin; 12% by novobiocin, pefloxacin, ciprofloxacin and CI-934; 7% by coumermycin and ofloxacin; 9% by amifloxacin; and 4% by AM-833. On the other hand, pSC194, pBR322 and pMH612 were poorly cured in vitro by quinolones, except pSC194 which was cured 33% by enoxacin. R1, pP1603, and pUB110 were unaffected by the treatment. Mice were challenged intraperitoneally with a 2XLD50 of Escherichia coli carrying the ORF2 plasmid and were treated per os with 1 X or 1/2 X ED50 of either enoxacin or CI-934. The frequency of loss of ampicillin resistance determined 3 h after treatment shows curing effects of 92% for CI-934, 89% for enoxacin and 20% for untreated control.

Expression of hepatitis B surface antigen with a recombinant adenovirus.

Early region 1 of the adenovirus type 5 genome was replaced with a DNA sequence containing the gene coding for the hepatitis B surface antigen (HBsAg) flanked by the major late promoter from adenovirus 2 and processing and polyadenylylation signals from simian virus 40. In one type of hybrid virus only the adenovirus 2 major late promoter, including just 33 base pairs of the adenovirus type 2 tripartite leader, preceded the coding region of the HBsAg gene. In another, this region was preceded by both the adenovirus major late promoter and almost the entire tripartite leader. The structure of the substituted sequence in each of the recombinant viral DNAs was identical to that in the plasmids used to construct the viruses. Approximately equivalent amounts of HBsAg-specific mRNA were produced late in infection with each recombinant virus. Although HBsAg production was detected late in infection of the hybrid virus not containing the full tripartite leader sequence, its level was 1/70th of that obtained with the hybrid virus containing this sequence. One likely interpretation is that the presence of the tripartite leader at the 5' end of this mRNA is critical for the synthesis of HBsAg polypeptide in the late stage of infection. HBsAg produced upon infection with the hybrid adenoviruses was glycosylated and secreted into the culture medium as particles that were essentially indistinguishable from the 22-nm particles found in human serum.

Sequence of the serotype-specific glycoprotein of the human rotavirus Wa strain and comparison with other human rotavirus serotypes.

Complementary DNA was synthesized from the double-stranded RNA of the Wa strain of human rotavirus and inserted into the bacterial plasmid pBR322. Clones which contained the gene that codes for the viral glycoprotein (VP7) were identified and the nucleotide sequence was determined. The gene was 1062 base pairs in length with an open reading frame which coded for 326 amino acids. Two potential glycosylation sites were found as well as two hydrophobic regions at the N-terminus of the polypeptide. The untranslated regions at the 5' and 3' ends were 48 base pairs and 33 base pairs long, respectively. Only one nucleotide at position 493 differed from the sequence of the Wa VP7 gene described by Richardson et al. (1984, J. Virol. 51, 860-862). A strong prokaryotic promoter sequence was also found between residues 434 and 462. A comparison of the amino acid sequence of the Wa strain (serotype 1) to the Hu/5 strain of human rotavirus (serotype 2) and SA11, the simian rotavirus (serotype 3), revealed a high degree of homology (79.1% and 83.1%, respectively) between the serotypes, suggesting that rotavirus serotypes are stable. The hydrophilic regions of VP7 of the three serotypes were identified and compared for homology. Four of these regions showed variation between serotypes.

Characterization of a yeast replication origin (ars2) and construction of stable minichromosomes containing cloned yeast centromere DNA (CEN3).

A yeast DNA sequence (ars2), capable of supporting autonomous replication of plasmids, in yeast, has been characterized. The ars2 replicator occurs about 7 kb from the ARG4 gene on yeast chromosome VIII. Plasmids containing ars2 and the ARG4 gene transform yeast arg4 mutants to ARG4+ with high frequency (about 103 transformants/micrograms DNA) and replicate autonomously in the transformed cells. The ars2 plasmids are mitotically unstable and are readily lost from yeast cultures when grown under nonselective conditions. The addition of a DNA segment containing functional yeast centromere (CEN3) and an ars2 plasmid effectively stabilizes the plasmid against both mitotic and meiotic loss. The ars2-CEN3 minichromosomes replicate autonomously in controlled copy number while segregating in a typical Mendelian pattern (2+ :2-) during meiosis. The requirement for a separate replicator sequence for stable mitotic and meiotic maintenance of centromere-containing minichromosomes is equally satisfied by the presence of either ars1 or ars2. The centromere controls plasmid copy number to a low value (usually one) regardless of the type of replicator used.