Whispering-gallery mode InGaN microdisks on GaN substrates.

Microdisks fabricated with III-nitride materials grown on GaN substrates are demonstrated, taking advantage of the high material quality of homoepitaxial films and advanced micro-fabrication processes. The epitaxial structure consists of InGaN/GaN multi-quantum wells (MQWs) sandwiched between AlGaN/GaN and InAlN/GaN superlattices as cladding layers for optical confinement. Due to lattice-matched growth with low dislocations, an internal quantum efficiency of ∼40% is attained, while the sidewalls of the etched 8 µm-diameter microdisks patterned by microsphere lithography are optically smooth to promote the formation of whispering-gallery modes (WGMs) within the circular optical cavities. Optically pumped lasing with low threshold of ∼5.2 mJ/cm2 and quality (Q) factor of ∼3000 at the dominant lasing wavelength of 436.8 nm has been observed. The microdisks also support electroluminescent operation, demonstrating WGMs consistent with the photoluminescence spectra and with finite-difference time-domain (FDTD) simulations.

Packaging of InGaN stripe-shaped light-emitting diodes.

We demonstrate the fabrication of InGaN/GaN stripe-shaped light-emitting diodes (LEDs) in flip-chip packaging (FC-LED) and vertically mounted packaging (VM-LED). Compared to conventionally packaged LEDs, these packaging schemes enhance light output and emission divergence in ways favorable for general lighting applications. The FC-LED can sustain efficiency at high current operations due to effective heat sinking, while the VM-LED excels at light extraction efficiency due to the exposure of two large emission surfaces. Together with the properties of low luminous exitance and emission uniformity, the stripe-shaped LEDs are ideal for the assembly of luminaires. An LED light tube comprising a continuous linear array of 10 stripe-shaped LED chips has been assembled. The optical performance of the light tube is compared to another light tube assembled with conventional square-shaped LED chips (with and without external diffuser) by confocal microscopy. It is found that emission uniformity of the stripe-shaped LED tube is significantly improved, with a threefold increase in illumination area, without efficiency loss associated with diffusers.

The atomic structure of polar and non-polar InGaN quantum wells and the green gap problem.

We have used high resolution transmission electron microscopy (HRTEM), aberration-corrected quantitative scanning transmission electron microscopy (Q-STEM), atom probe tomography (APT) and X-ray diffraction (XRD) to study the atomic structure of (0001) polar and (11-20) non-polar InGaN quantum wells (QWs). This paper provides an overview of the results. Polar (0001) InGaN in QWs is a random alloy, with In replacing Ga randomly. The InGaN QWs have atomic height interface steps, resulting in QW width fluctuations. The electrons are localised at the top QW interface by the built-in electric field and the well-width fluctuations, with a localisation energy of typically 20meV. The holes are localised near the bottom QW interface, by indium fluctuations in the random alloy, with a localisation energy of typically 60meV. On the other hand, the non-polar (11-20) InGaN QWs contain nanometre-scale indium-rich clusters which we suggest localise the carriers and produce longer wavelength (lower energy) emission than from random alloy non-polar InGaN QWs of the same average composition. The reason for the indium-rich clusters in non-polar (11-20) InGaN QWs is not yet clear, but may be connected to the lower QW growth temperature for the (11-20) InGaN QWs compared to the (0001) polar InGaN QWs.

NRC-interacting factor directs neurite outgrowth in an activity-dependent manner.

Nuclear hormone receptor coregulator-interacting factor 1 (NIF-1) is a zinc finger nuclear protein that was initially identified to enhance nuclear hormone receptor transcription via its interaction with nuclear hormone receptor coregulator (NRC). NIF-1 may regulate gene transcription either by modulating general transcriptional machinery or remodeling chromatin structure through interactions with specific protein partners. We previously reported that the cytoplasmic/nuclear localization of NIF-1 is regulated by the neuronal Cdk5 activator p35, suggesting potential neuronal functions for NIF-1. The present study reveals that NIF-1 plays critical roles in regulating neuronal morphogenesis at early stages. NIF-1 was prominently expressed in the nuclei of developing rat cortical neurons. Knockdown of NIF-1 expression attenuated both neurite outgrowth in cultured cortical neurons and retinoic acid (RA)-treated Neuro-2a neuroblastoma cells. Furthermore, activity-induced Ca(2+) influx, which is critical for neuronal morphogenesis, stimulated the nuclear localization of NIF-1 in cortical neurons. Suppression of NIF-1 expression reduced the up-regulation of neuronal activity-dependent gene transcription. These findings collectively suggest that NIF-1 directs neuronal morphogenesis during early developmental stages through modulating activity-dependent gene transcription.

Cyclin-dependent kinase 5-dependent phosphorylation of Pctaire1 regulates dendrite development.

Pctaire1, a Cdk-related protein kinase, is prominently expressed in terminally differentiated tissues, including the brain and the testis. We have previously shown that Pctaire1 regulates neurotransmitter release through phosphorylation of NSF, and its kinase activity is regulated by the Cdk5-dependent phosphorylation at Serine-95 (Ser95). Nonetheless, the functional roles of Pctaire1 in neurons during development remained poorly understood. In this study, we found that Pctaire1 is expressed along neurites and is concentrated at the growth cones of early differentiating hippocampal neurons. Upon maturation of these neurons, Pctiare1 is expressed as puncta and co-localized with synaptic marker in dendrites. Phosphorylation of Pctaire1 at Ser95 increases upon neuronal differentiation, concurrent with the elevation in Cdk5 activity. Knockdown of Pctaire1 abolishes dendrite development, and more importantly, expression of Ser95 phosphorylation-deficient mutant of Pctaire1 also reduces dendrite complexity, suggesting that Cdk5 regulates Pctaire1 functions in differentiating neurons. Together, our findings demonstrate that Cdk5-dependent phosphorylation of Pctaire1 at Ser95 plays an important role in dendrite development.

Two-bit ferroelectric field-effect transistor memories assembled on individual nanotubes.

Carbon nanotube (CNT) ferroelectric field-effect transistors (FeFETs) with well-defined memory switch behaviors are promising for nonvolatile, nondestructive read-out (NDRO) memory operation and ultralow power consumption. Here, we report two-bit CNT-FeFET memories by assembling two top gates on individual nanotubes coated with ferroelectric thin films. Each bit of the nanotube transistor memory exhibits a controllable memory switching behavior induced by the reversible remnant polarization of the ferroelectric films, and its NDRO operation is demonstrated. The low driving voltage of 2 V, high carrier mobility over 1000 cm2 V(-1) s(-1), and potential ultrahigh integration density over 200 Gbit inch(-2) of the two-bit FeFET memory are highlighted in this paper.

Evaluation of InGaN/GaN light-emitting diodes of circular geometry.

Blue GaN light emitting diodes (LEDs) in the shape of cuboids and circular disks have been fabricated by laser micromachining. The proposed circular geometry serves to enhance overall light extraction on a macro-scale and to improve uniformity of the emission pattern due to the rotational symmetry of the chip. Analysis of the chip shaping effect is carried out by ray-tracing simulations and further supported with mathematical modeling using ideal LED models, and subsequently verified with fabricated devices. In comparison, a 10% improvement in overall emission was observed for circular LEDs over the regular cuboids, consistent with simulations and calculations. The measured emission pattern from the circular LED confirms the axial symmetry of the emission beam.

Polychromatic light-emitting diodes with a fluorescent nanosphere opal coating.

A hexagonally close-packed array consisting of fluorescent nanospheres was coated onto short-wavelength GaN light-emitting diodes to demonstrate polychromatic white light emission. The spherical particles self-assemble into ordered three-dimensional opal structures, performing the role of color conversion to generate a polychromatic spectrum with smooth and uniform emission patterns. Different ratios of green and orange-red fluorescent nanospheres were mixed and coated onto high-extraction-efficiency micro-LEDs. Four devices with different shades of white emission were demonstrated. Device A, with a high content of orange-red nanospheres, offers the highest CRI value of 80, whereas device C with a well-balanced ratio of green and orange-red nanospheres exhibits color characteristics closest to ideal white with CIE coordinate at (0.34, 0.34). At 20 mA driving current, the luminous efficacy of the devices A, B, C, and D are 40.5 lm W(-1), 57.7 lm W(-1), 63.1 lm W(-1), and 67.2 lm W(-1) respectively, while the correlated color temperatures (CCTs) of the corresponding devices are 3587, 4778, 5271, and 13 000 K.

The function of interdomain interactions in controlling nucleotide exchange rates in transducin.

The intramolecular contacts in heterotrimeric G proteins that determine the rates of basal and receptor-stimulated nucleotide exchange are not fully understood. The alpha subunit of heterotrimeric G proteins consists of two domains: a Ras-like domain with structural homology to the monomeric G protein Ras and a helical domain comprised of six alpha-helices. The bound nucleotide lies in a deep cleft between the two domains. Exchange of the bound nucleotide may involve opening of this cleft. Thus interactions between the domains may affect the rate of nucleotide exchange in G proteins. We have tested this hypothesis in the alpha subunit of the rod cell G protein transducin (Galpha(t)). Site-directed mutations were prepared in a series of residues located at the interdomain interface. The proteins were expressed in vitro in a reticulocyte lysate system. The rates of basal and rhodopsin-catalyzed nucleotide exchange were determined using a trypsin digestion assay specifically adapted for kinetic measurements. Charge-altering substitutions of two residues at the interdomain interface, Lys(273) and Lys(276), increased basal nucleotide exchange rates modestly (5-10-fold). However, we found no evidence that interactions spanning the two domains in Galpha(t) significantly affected either basal or rhodopsin-catalyzed nucleotide exchange rates. These results suggest that opening of the interdomain cleft is not an energetic barrier to nucleotide exchange in Galpha(t). Experiments with Galpha(i1) suggest by comparison that the organization and function of the interdomain region differ among various G protein subtypes.

Cdk5 is involved in neuregulin-induced AChR expression at the neuromuscular junction.

Here we describe an important involvement of Cdk5/p35 in regulating the gene expression of acetylcholine receptor (AChR) at the neuromuscular synapse. Cdk5 and p35 were prominently expressed in embryonic muscle, and concentrated at the neuromuscular junction in adulthood. Neuregulin increased the p35-associated Cdk5 kinase activity in the membrane fraction of cultured C2C12 myotubes. Co-immunoprecipitation studies revealed the association between Cdk5, p35 and ErbB receptors in muscle and cultured myotubes. Inhibition of Cdk5 activity not only blocked the NRG-induced AChR transcription, but also attenuated ErbB activation in cultured myotubes. In light of our finding that overexpression of p35 alone led to an increase in AChR promoter activity in muscle, Cdk5 activation is sufficient to mediate the up-regulation of AChR gene expression. Taken together, these results reveal the unexpected involvement of Cdk5/p35 in neuregulin signaling at the neuromuscular synapse.

Altered expression of tissue-type plasminogen activator and type 1 inhibitor in astrocytes of mouse cortex following scratch injury in culture.

The expression of plasminogen and plasminogen activators (PG/PAs) in reactive astrocytes was examined following scratch injury. In response to injury, casein-degrading activity could be observed around astrocytes. The protein expression of tissue-type plasminogen activator (tPA) was up-regulated, while the free form of urokinase-type plasminogen activator (uPA) was not detected. Consistent with these findings, results obtained with zymograph assay also revealed that tPA activity, but not uPA activity, was up-regulated. Moreover, the addition of 6-amino-caproitic acid (EACA) to casein-covered astrocytes significantly prevented the recovery of the injured astrocytes in a dose-dependent manner. Taken together, our data demonstrate that the expression of PG/PAs in cultured astrocytes is regulated following injury, suggesting that caseinolytic activity is an essential component during the process of astrocyte recovery.

Developmental and tissue-specific expression of DEAD box protein p72.

Retinoic acid (RA) is a vitamin A derivative that has been well documented to be involved in cell differentiation. Using RNA fingerprinting by arbitrarily primed PCR, we have previously identified a number of transcripts that are regulated during RA-induced neuronal differentiation of embryonal carcinoma NT2/D1 cells. DEAD box protein p72 is one of the clones found to be down-regulated following treatment with RA. To further investigate the regulation of p72, the mRNA expression of p72 in various neuronal cell lines and primary neuronal cultures was examined. Transcripts of p72 were reduced in differentiated PC12 and IMR-32 cells but not in SH-SYSY cells. Partial cDNA fragments of p72 were isolated from rat and chick for the systematic analysis of p72 expression in different adult tissues and developmental stages. While prominent expression of p72 was observed in brain and testis, the expression was down-regulated in brain, muscle and liver during development. Taken together, our findings provide the first demonstration on the spatial and temporal expression profile of p72 in rat and chick tissues which is consistent with a role of p72 during early development.

pH dependence of photolysis intermediates in the photoactivation of rhodopsin mutant E113Q.

Glutamic acid at position 113 in bovine rhodopsin ionizes to form the counterion to the protonated Schiff base (PSB), which links the 11-cis-retinylidene chromophore to opsin. Photoactivation of rhodopsin requires both Schiff base deprotonation and neutralization of Glu-113. To better understand the role of electrostatic interactions in receptor photoactivation, absorbance difference spectra were collected at time delays from 30 ns to 690 ms after photolysis of rhodopsin mutant E113Q solubilized in dodecyl maltoside at different pH values at 20 degrees C. The PSB form (pH 5. 5, lambda(max) = 496 nm) and the unprotonated Schiff base form (pH 8. 2, lambda(max) = 384 nm) of E113Q rhodopsin were excited using 477 nm or 355 nm light, respectively. Early photointermediates of both forms of E113Q were qualitatively similar to those of wild-type rhodopsin. In particular, early photoproducts with spectral shifts to longer wavelengths analogous to wild-type bathorhodopsin were seen. In the case of the basic form of E113Q, the absorption maximum of this intermediate was at 408 nm. These results suggest that steric interaction between the retinylidene chromophore and opsin, rather than charge separation, plays the dominant role in energy storage in bathorhodopsin. After lumirhodopsin, instead of deprotonating to form metarhodopsin I(380) on the submillisecond time scale as is the case for wild type, the acidic form of E113Q produced metarhodopsin I(480), which decayed very slowly (exponential lifetime = 12 ms). These results show that Glu-113 must be present for efficient deprotonation of the Schiff base and rapid visual transduction in vertebrate visual pigments.

Mutation of the fourth cytoplasmic loop of rhodopsin affects binding of transducin and peptides derived from the carboxyl-terminal sequences of transducin alpha and gamma subunits.

The role of the putative fourth cytoplasmic loop of rhodopsin in the binding and catalytic activation of the heterotrimeric G protein, transducin (G(t)), is not well defined. We developed a novel assay to measure the ability of G(t), or G(t)-derived peptides, to inhibit the photoregeneration of rhodopsin from its active metarhodopsin II state. We show that a peptide corresponding to residues 340-350 of the alpha subunit of G(t), or a cysteinyl-thioetherfarnesyl peptide corresponding to residues 50-71 of the gamma subunit of G(t), are able to interact with metarhodopsin II and inhibit its photoconversion to rhodopsin. Alteration of the amino acid sequence of either peptide, or removal of the farnesyl group from the gamma-derived peptide, prevents inhibition. Mutation of the amino-terminal region of the fourth cytoplasmic loop of rhodopsin affects interaction with G(t) (Marin, E. P., Krishna, A. G., Zvyaga T. A., Isele, J., Siebert, F., and Sakmar, T. P. (2000) J. Biol. Chem. 275, 1930-1936). Here, we provide evidence that this segment of rhodopsin interacts with the carboxyl-terminal peptide of the alpha subunit of G(t). We propose that the amino-terminal region of the fourth cytoplasmic loop of rhodopsin is part of the binding site for the carboxyl terminus of the alpha subunit of G(t) and plays a role in the regulation of betagamma subunit binding.

Production of human CNS neurons from embryonal carcinoma cells using a cell aggregation method.

When treated with retinoic acid (RA), a human embryonal carcinoma (EC) cell line, NTera2 cl.D/1 (NT2), differentiates into several morphologically distinct cell types, which include terminally differentiated postmitotic central nervous system (CNS) neurons. Accumulating evidence has demonstrated the significant potential of NT2 cells in studies related to cancer therapy and neurodegenerative diseases. However, preparation of enriched NT2 neurons often requires a lengthy period (ca. five weeks) and depends largely on tedious techniques similar to those used for primary neuronal cultures. Here, we report a rapid protocol for the preparation of these human CNS neurons. Using the method of cell aggregation, enriched NT2 neurons can be obtained in approximately two weeks. We also demonstrated that cell aggregation reduced the time normally required for the induction of neuronal differentiation, as revealed by the early expression of neuronal markers. The period of RA treatment could also be reduced if NT2 cells were maintained as aggregates for a sufficient period of time. Taken together, our findings demonstrated that cell aggregation promoted RA-induced neuronal differentiation of NT2 cells and provided a rapid protocol for the efficient production of NT2 neurons. The ability to produce large quantities of human CNS neurons should facilitate future use of these neurons for basic research and applications in cell therapy.

Cloning and expression of a novel neurotrophin, NT-7, from carp.

Neurotrophins have been demonstrated to play important roles in the development and functioning of the nervous system. This family of proteins consists of four homologous members in mammals: NGF, BDNF, NT-3, and NT-4/5. A new member, called NT-6, was recently cloned from the platyfish Xiphophorus maculatus. This protein shares closer structural relationship to NGF than the other neurotrophins, but contains a characteristic insertion of 22 amino acids that constituted the heparin-binding domain. Here we report the cloning of a novel neurotrophin from the fish Cyprinus carpio (carp), which shared about 66% amino acid identity to Xiphophorus NGF and NT-6. The neurotrophin, designated NT-7, possesses structural characteristics common to all known neurotrophins, such as the presence of six conserved cysteine residues and the flanking conserved sequences. In addition, there is an insertion of 15 amino acids at the position corresponding to that observed for NT-6. The neurotrophic activity of NT-7 was demonstrated by its ability to promote neurite outgrowth and neuronal survival of chick dorsal root ganglia. Phosphorylation assay of various Trk receptors overexpressed in fibroblasts suggested that NT-7 could activate TrkA but not TrkB or TrkC. Northern blot analysis revealed that NT-7 was predominantly expressed in peripheral tissues, though weak expression was also detected in the brain. Like NT-6, this novel neurotrophin might represent yet another NGF-like neurotrophin in lower vertebrates.

Gene expression in astrocytes during and after ischemia.

Involvement of the IEGs in brain injury and ischemia is under intensive investigation (Gubits et al., 1993). There are several families of the IEGs. They include the fos, jun, and zinc finger genes that encode transcription factors. Products of the fos family (c-fos, fra-1, fra-2, and fos B) bind to members of the jun family (c-jun, jun B, jun D) via leucine zippers, and this dimer then binds to the AP-1 site (consensus sequence -TGACTCA-) in the promoter of target genes, which in turn regulate the expression of late response genes that produce long-term changes in cells. For example, c-fos may regulate the long-term expression of preproenkephalin, nerve growth factor, dynorphin, vasoactive intestinal polypeptide, tyrosine hydroxylase and other genes with AP-1 sites in their promoters (Curran and Morgan, 1987; Sheng and Greenberg, 1990). It is likely that the c-fos gene up-regulation observed in ischemic astrocytes leads to the changes observed in the expressions of hsp and cytoskeleton protein genes in this experimental model. This is supported by the findings of Sarid (1991) and Pennypacker et al. (1994) who have shown that AP-1 DNA binding activity in hippocampus recognized an AP-1 sequence from the promoter region of the GFAP which is a potential target gene. van de Klundert et al. (1992) also suggested the involvement of AP-1 in transcriptional regulation of vimentin. IEGs can be induced within minutes by extracellular stimuli including transmitters, peptides, and growth factors. In this study, we have shown that c-fos induction by ischemia was rapid and transient.(ABSTRACT TRUNCATED AT 250 WORDS)

[Prevention of injurious effect of free radicals to island skin flap with mannitol and anisodamine--an experimental study].

Rat abdominal skin flaps were subjected to total venous occlusion for 8 hours. Prior to and immediately following release of the vascular occlusion, mannitol, anisodamine or placebos were administered. Mannitol and/or anisodamine significantly enhanced island flap survival. LPO or water content was significantly lower in drug groups than in placebo groups. However, XOD was not affected by the drugs. These findings indicated that oxygen free-radical played an important role in post-ischemic flap injury.

A study of molecular epidemiology of adenovirus of types 3 and 7 on infant pneumonia in northern China.

This paper analysed 102 strains of adenovirus types 3(Ad3) and 7(Ad7) causing infant pneumonia from 1976 to 1988 in northern China. Two genotypes of Ad7, 7b and 7d, were identified by using restriction endonucleases, BamHI, BcLI, BgLI, SmaI, XbaI and HindIII. 3 genotypes of Ad3, 3I, 3II and 3III, were identified by using BgLII and BamHI. Of 56 Ad7 strains, 34 were 7b (76.8%) spread over last 10 years; 13 7d(23.2%) occurred from 1982, together with 7b. Of 46 Ad3 strains, 42 3I(91.3%) spread over the past 12 years. 3II and 3III scattered all over these years. Ad3I and Ad7b were the dominant genotypes. The results indicated that Ad7d tended to increase with time from 1982. It is possible that Ad7d will become dominant genotype and replace Ad7b.

Identification of the types of adenovirus isolates with monoclonal antibodies.

The types of 59 isolates of adenovirus (Adv) which were isolated between winter, 1984 and spring, 1986 were identified by type-specific monoclonal antibodies (McAb) against Adv types 3 and 7. The results showed that the method could not only identify the types of Adv, but also discover the changes of their subtypes with time. The tedious neutralization test can be replaced by this simple method.