Diffusion-Dominated Luminescence Dynamics of CsPbBr3 Studied Using Cathodoluminescence and Microphotoluminescence Spectroscopy.

Time-resolved or time-correlation measurements using cathodoluminescence (CL) reveal the electronic and optical properties of semiconductors, such as their carrier lifetimes, at the nanoscale. However, halide perovskites, which are promising optoelectronic materials, exhibit significantly different decay dynamics in their CL and photoluminescence (PL). We conducted time-correlation CL measurements of CsPbBr3 using Hanbury Brown-Twiss interferometry and compared them with time-resolved PL. The measured CL decay time was on the order of subnanoseconds and was faster than PL decay at an excited carrier density of 2.1 × 1018 cm-3. Our experiment and analytical model revealed the CL dynamics induced by individual electron incidences, which are characterized by highly localized carrier generation followed by a rapid decrease in carrier density due to diffusion. This carrier diffusion can play a dominant role in the CL decay time for undoped semiconductors, in general, when the diffusion dynamics are faster than the carrier recombination.

Damage protection from focused ion beam process toward nanocavity-implemented compound semiconductor nanowire lasers.

A focused ion beam (FIB) can precisely mill samples and freely form any nanostructure even on surfaces with curvature, like a nanowire surface, which are difficult to implement by using conventional fabrication techniques, e.g. electron beam lithography. Thus, this tool is promising for nanofabrication; however, fabrication damage and contamination are critical issues, which deteriorate optical properties. In this work, we investigated the protective performance of Al2O3against the FIB process (especially by a gallium ion). Nanowires were coated with Al2O3as a hard mask to protect them from damage during FIB nanofabrication. To estimate the protective performance, their emission properties by photoluminescence measurement and time-resolved spectroscopy were compared with and without Al2O3coating conditions. From the results, we confirmed that the Al2O3coating protects the nanowires. In addition, the nanowires also showed lasing behavior even after FIB processing had been carried out to implement nanostructures. This indicates that their optical properties are well maintained. Thus, our study proves the usefulness of FIBs for future nanofabrication.

Humanized UGT2 and CYP3A transchromosomic rats for improved prediction of human drug metabolism.

Although "genomically" humanized animals are invaluable tools for generating human disease models as well as for biomedical research, their development has been mainly restricted to mice via established transgenic-based and embryonic stem cell-based technologies. Since rats are widely used for studying human disease and for drug efficacy and toxicity testing, humanized rat models would be preferred over mice for several applications. However, the development of sophisticated humanized rat models has been hampered by the difficulty of complex genetic manipulations in rats. Additionally, several genes and gene clusters, which are megabase range in size, were difficult to introduce into rats with conventional technologies. As a proof of concept, we herein report the generation of genomically humanized rats expressing key human drug-metabolizing enzymes in the absence of their orthologous rat counterparts via the combination of chromosome transfer using mouse artificial chromosome (MAC) and genome editing technologies. About 1.5 Mb and 700 kb of the entire UDP glucuronosyltransferase family 2 and cytochrome P450 family 3 subfamily A genomic regions, respectively, were successfully introduced via the MACs into rats. The transchromosomic rats were combined with rats carrying deletions of the endogenous orthologous genes, achieved by genome editing. In the "transchromosomic humanized" rat strains, the gene expression, pharmacokinetics, and metabolism observed in humans were well reproduced. Thus, the combination of chromosome transfer and genome editing technologies can be used to generate fully humanized rats for improved prediction of the pharmacokinetics and drug-drug interactions in humans, and for basic research, drug discovery, and development.

Designs toward synchronization of optical limit cycles with coupled silicon photonic crystal microcavities.

A driven high-Q Si microcavity is known to exhibit limit cycle oscillation originating from carrier-induced and thermo-optic nonlinearities. We propose a novel nanophotonic device to realize synchronized optical limit cycle oscillations with coupled silicon (Si) photonic crystal (PhC) microcavities. Here, coupled limit cycle oscillators are realized by using coherently coupled Si PhC microcavities. By simulating coupled-mode equations, we theoretically demonstrate mutual synchronization (entrainment) of two limit cycles induced by coherent coupling. Furthermore, we interpret the numerically simulated synchronization in the framework of phase description. Since our proposed design is perfectly compatible with current silicon photonics fabrication processes, the synchronization of optical limit cycle oscillations will be implemented in future silicon photonic circuits.

Designs toward synchronization of optical limit cycles with coupled silicon photonic crystal microcavities: erratum.

Correction for the citation of a reference.

Mid-Infrared Lasing of Single Wurtzite InAs Nanowire.

Mid-infrared (MIR) photonics is a developing technology for sensing materials by their characteristic MIR absorptions. Since silicon (Si) is a low-loss material in most of the MIR region, Si photonic structures have been fabricated to guide and confine MIR light, and they allow us to achieve sensitive and integrated sensing devices. However, since the implementation of MIR light sources on Si is still challenging, we propose a thick indium arsenide (InAs) nanowire as an MIR laser that can couple to Si photonic structures with material manipulation. In this study, thick InAs nanowires are grown on an indium phosphide substrate with a self-catalyst vapor-liquid-solid method and transferred to gold-deposited SiO2/Si substrates. Low-temperature microphotoluminescence (PL) spectroscopy shows that InAs nanowires exhibit broad PL peaking at a wavelength of around 2.6 µm (3850 cm-1 in frequency), which corresponds to the bandgap energy of wurtzite InAs. At high optical pump fluences, single InAs nanowire exhibits sharp emission peaks, while their integrated intensity and polarization degree increase abruptly at the threshold pump fluence. These nonlinear behaviors indicate that the MIR lasing action takes place in the InAs nanowire in its cavity mode. Our demonstration of the MIR nanowire laser expands the wavelength coverage and potential application of semiconductor nanowires.

Room temperature continuous-wave nanolaser diode utilized by ultrahigh-Q few-cell photonic crystal nanocavities.

Few-cell point-defect photonic crystal (PhC) nanocavities (such as LX and H1 type cavities), have several unique characteristics including an ultra-small mode volume (Vm), a small device footprint advantageous for dense integration, and a large mode spacing advantageous for high spontaneous-emission coupling coefficient (ß), which are promising for energy-efficient densely-integratable on-chip laser light sources enhanced by the cavity QED effect. To achieve this goal, a high quality factor (Q) is essential, but conventional few-cell point-defect cavities do not have a sufficiently high Q. Here we adopt a series of modified designs of LX cavities with a buried heterostructure (BH) multi-quantum-well (MQW) active region that can achieve a high Q while maintaining their original advantages and fabricate current-injection laser devices. We have successfully observed continuous-wave (CW) lasing in InP-based L1, L2, L3 and L5 PhC nanocavities at 23°C with a DC current injection lower than 10 µA and a bias voltage lower than 0.9 V. The active volume is ultra-small while maintaining a sufficiently high confinement factor, which is as low as ~10-15 cm3 for a single-cell (L1) nanocavity. This is the first room-temperature current-injection CW lasing from any types of few-cell point-defect PhC nanocavities (LX or H1 types). Our report marks an important step towards realizing a nanolaser diode with a high cavity-QED effect, which is promising for use with on-chip densely integrated laser sources in photonic networks-on-chip combined with CMOS processors.

Design of nanowire-induced nanocavities in grooved 1D and 2D SiN photonic crystals for the ultra-violet and visible ranges.

Nanowire-induced SiN photonic crystal (PhC) nanocavities specifically designed for the ultra-violet and visible range are investigated by three-dimensional finite-difference time-domain calculations. As opposed to their silicon PhC counterpart, we find that the formation of nanowire-induced two-dimensional (2D) SiN PhC nanocavities is more challenging because of the low refractive index of SiN. We thus discuss optimization strategies to circumvent such difficulties and we investigate the influence of critical design parameters such as PhC geometry, as well as nanowire geometry and position. We also propose a novel nanowire-induced cavity design based on one-dimensional (1D) nanobeam PhCs. We finally report on nanowire-induced nanocavity designs in 1D (resp. 2D) PhCs presenting quality factors as high as Qc = 5.1 x 104 (resp. Qc = 2.5 x 104 with a mode volume Vm=1.8(λ/nrNW)3 (resp. Vm=5.1(λ/nrNW)3), which show good prospects for light-matter interaction in the near-ultraviolet and visible ranges.

Optomechanical oscillator pumped and probed by optically two isolated photonic crystal cavity systems.

Optomechanical control of on-chip emitters is an important topic related to integrated all-optical circuits. However, there is neither a realization nor a suitable optomechanical structure for this control. The biggest obstacle is that the emission signal can hardly be distinguished from the pump light because of the several orders' power difference. In this study, we designed and experimentally verified an optomechanical oscillation system, in which a lumped mechanical oscillator connected two optically isolated pairs of coupled one-dimensional photonic crystal cavities. As a functional device, the two pairs of coupled cavities were respectively used as an optomechanical pump for the lumped oscillator (cavity pair II, wavelengths were designed to be within a 1.5 µm band) and a modulation target of the lumped oscillator (cavity pair I, wavelengths were designed to be within a 1.2 µm band). By conducting finite element method simulations, we found that the lumped-oscillator-supported configurations of both cavity pairs enhance the optomechanical interactions, especially for higher order optical modes, compared with their respective conventional side-clamped configurations. Besides the desired first-order in-plane antiphase mechanical mode, other mechanical modes of the lumped oscillator were investigated and found to possibly have optomechanical applications with a versatile degree of freedom. In experiments, the oscillator's RF spectra were probed using both cavity pairs I and II, and the results matched those of the simulations. Dynamic detuning of the optical spectrum of cavity pair I was then implemented with a pumped lumped oscillator. This was the first demonstration of an optomechanical lumped oscillator connecting two optically isolated pairs of coupled cavities, whose biggest advantage is that one cavity pair can be modulated with an lumped oscillator without interference from the pump light in the other cavity pair. Thus, the oscillator is a suitable platform for optomechanical control of integrated lasers, cavity quantum electrodynamics, and spontaneous emission. Furthermore, this device may open the door on the study of interactions between photons, phonons, and excitons in the quantum regime.

Systematic study of thresholdless oscillation in high-ß buried multiple-quantum-well photonic crystal nanocavity lasers.

Buried multiple-quantum-well (MQW) 2D photonic crystal cavities (PhC) achieve low non-radiative recombination and high carrier confinement thus making them highly efficient emitters. In this study, we have investigated the lasing characteristics of high-ß(spontaneous emission coupling factor) buried MQW photonic crystal nanocavity lasers to clarify the theoretically-predicted thresholdless operation in high-ß nanolasers. The strong light and carrier confinement and low non-radiative recombination in our nanolasers have enabled us to clearly demonstrate very smooth lasing transition in terms of the light-in vs light-out curve and cavity linewidth. To clarify the thresholdless lasing behavior, we carried out a lifetime measurement and a photon correlation measurement, which also confirmed the predicted behavior. In addition, we systematically investigated the dependence of ß on the detuning frequency, which was in good agreement with a numerical simulation based on the finite-difference time-domain method. This is the first convincing systematic study of nanolasers based on an MQW close to the thresholdless regime.

Trans-chromosomic mice containing a human CYP3A cluster for prediction of xenobiotic metabolism in humans.

Human CYP3A is the most abundant P450 isozyme present in the human liver and small intestine, and metabolizes around 50% of medical drugs on the market. The human CYP3A subfamily comprises four members (CYP3A4, CYP3A5, CYP3A7, CYP3A43) encoded on human chromosome 7. However, transgenic mouse lines carrying the entire human CYP3A cluster have not been constructed because of limitations in conventional cloning techniques. Here, we show that the introduction of a human artificial chromosome (HAC) containing the entire genomic human CYP3A locus recapitulates tissue- and stage-specific expression of human CYP3A genes and xenobiotic metabolism in mice. About 700 kb of the entire CYP3A genomic segment was cloned into a HAC (CYP3A-HAC), and trans-chromosomic (Tc) mice carrying a single copy of germline-transmittable CYP3A-HAC were generated via a chromosome-engineering technique. The tissue- and stage-specific expression profiles of CYP3A genes were consistent with those seen in humans. We further generated mice carrying the CYP3A-HAC in the background homozygous for targeted deletion of most endogenous Cyp3a genes. In this mouse strain with 'fully humanized' CYP3A genes, the kinetics of triazolam metabolism, CYP3A-mediated mechanism-based inactivation effects and formation of fetal-specific metabolites of dehydroepiandrosterone observed in humans were well reproduced. Thus, these mice are likely to be valuable in evaluating novel drugs metabolized by CYP3A enzymes and in studying the regulation of human CYP3A gene expression. Furthermore, this system can also be used for generating Tc mice carrying other human metabolic genes.

Movable high-Q nanoresonators realized by semiconductor nanowires on a Si photonic crystal platform.

Subwavelength semiconductor nanowires have recently attracted interest for photonic applications because they possess various unique optical properties and offer great potential for miniaturizing devices. However, realizing tight light confinement or efficient coupling with photonic circuits is not straightforward and remains a challenge. Here we show that a high-Q nanocavity can be created by placing a single III­V semiconductor nanowire with a diameter of under 100 nm in a grooved waveguide in a Si photonic crystal, by means of nanoprobe manipulation. We observe very fast spontaneous emission (91 ps) from nanowires accelerated by the strong Purcell enhancement in nanocavities, which proves that very strong light confinement can be achieved. Furthermore, this system enables us to move the nanocavity anywhere along the waveguide. This configuration provides a significant degree of flexibility in integrated photonics and permits the addition and displacement of various functionalities of III­V nanocavity devices in Si photonic circuits.

A novel transchromosomic system: stable maintenance of an engineered Mb-sized human genomic fragment translocated to a mouse chromosome terminal region.

Transchromosomic (Tc) technology using human chromosome fragments (hCFs), or human artificial chromosomes (HACs), has been used for generating mice containing Mb-sized segments of the human genome. The most significant problem with freely segregating chromosomes with human centromeres has been mosaicism, possibly due to the instability of hCFs or HACs in mice. We report a system for the stable maintenance of Mb-sized human chromosomal fragments following translocation to mouse chromosome 10 (mChr.10). The approach utilizes microcell-mediated chromosome transfer and a combination of site-specific loxP insertion, telomere-directed chromosome truncation, and precise reciprocal translocation for the generation of Tc mice. Human chromosome 21 (hChr.21) was modified with a loxP site and truncated in homologous recombination-proficient chicken DT40 cells. Following transfer to mouse embryonic stem cells harboring a loxP site at the distal region of mChr.10, a ~4 Mb segment of hChr.21 was translocated to the distal region of mChr.10 by transient expression of Cre recombinase. The residual hChr.21/mChr.10ter fragment was reduced by antibiotic negative selection. Tc mice harboring the translocated ~4 Mb fragment were generated by chimera formation and germ line transmission. The hChr.21-derived Mb fragment was maintained stably in tissues in vivo and expression profiles of genes on hChr.21 were consistent with those seen in humans. Thus, Tc technology that enables translocation of human chromosomal regions onto host mouse chromosomes will be useful for studying in vivo functions of the human genome, and generating humanized model mice.

Highly stable maintenance of a mouse artificial chromosome in human cells and mice.

Human artificial chromosomes (HACs) and mouse artificial chromosomes (MACs) display several advantages as gene delivery vectors, such as stable episomal maintenance that avoids insertional mutations and the ability to carry large gene inserts including the regulatory elements. Previously, we showed that a MAC vector developed from a natural mouse chromosome by chromosome engineering was more stably maintained in adult tissues and hematopoietic cells in mice than HAC vectors. In this study, to expand the utility for a gene delivery vector in human cells and mice, we investigated the long-term stability of the MACs in cultured human cells and transchromosomic mice. We also investigated the chromosomal copy number-dependent expression of genes on the MACs in mice. The MAC was stably maintained in human HT1080 cells in vitro during long-term culture. The MAC was stably maintained at least to the F8 and F4 generations in ICR and C57BL/6 backgrounds, respectively. The MAC was also stably maintained in hematopoietic cells and tissues derived from old mice. Transchromosomic mice containing two or four copies of the MAC were generated by breeding. The DNA contents were comparable to the copy number of the MACs in each tissue examined, and the expression of the EGFP gene on the MAC was dependent on the chromosomal copy number. Therefore, the MAC vector may be useful not only for gene delivery in mammalian cells but also for animal transgenesis.

Carbon nanotube/polymer composite coated tapered fiber for four wave mixing based wavelength conversion.

In this paper, we demonstrate a nonlinear optical device based on a fiber taper coated with a carbon nanotube (CNT)/polymer composite. Using this device, four wave mixing (FWM) based wavelength conversion of 10 Gb/s Non-return-to-zero signal is achieved. In addition, we investigate wavelength tuning, two photon absorption and estimate the effective nonlinear coefficient of the CNTs embedded in the tapered fiber to be 1816.8 W(-1)km(-1).

Saturated absorption spectroscopy of acetylene molecules with an optical nanofiber.

We performed saturated absorption spectroscopy of acetylene (C2H2) ν1 + ν3 band transitions with an optical nanofiber (ONF). Owing to high-intensity light around the ONF, we observed a Lamb dip at relatively low-power laser (~10 mW) without a cavity. Our results showed that the simple ONF spectrometer is advantageous for performing saturation absorption spectroscopy and serves as a practical low-cost wavelength reference in the optical fiber communication band.

Complete genetic correction of ips cells from Duchenne muscular dystrophy.

Human artificial chromosome (HAC) has several advantages as a gene therapy vector, including stable episomal maintenance that avoids insertional mutations and the ability to carry large gene inserts including the regulatory elements. Induced pluripotent stem (iPS) cells have great potential for gene therapy, as such cells can be generated from the individual's own tissues, and when reintroduced can contribute to the specialized function of any tissue. As a proof of concept, we show herein the complete correction of a genetic deficiency in iPS cells derived from Duchenne muscular dystrophy (DMD) model (mdx) mice and a human DMD patient using a HAC with a complete genomic dystrophin sequence (DYS-HAC). Deletion or mutation of dystrophin in iPS cells was corrected by transferring the DYS-HAC via microcell-mediated chromosome transfer (MMCT). DMD patient- and mdx-specific iPS cells with the DYS-HAC gave rise to differentiation of three germ layers in the teratoma, and human dystrophin expression was detected in muscle-like tissues. Furthermore, chimeric mice from mdx-iPS (DYS-HAC) cells were produced and DYS-HAC was detected in all tissues examined, with tissue-specific expression of dystrophin. Therefore, the combination of patient-specific iPS cells and HAC-containing defective genes represents a powerful tool for gene and cell therapies.

Emulating the local Kuramoto model with an injection-locked photonic crystal laser array.

The Kuramoto model is a mathematical model for describing the collective synchronization phenomena of coupled oscillators. We theoretically demonstrate that an array of coupled photonic crystal lasers emulates the Kuramoto model with non-delayed nearest-neighbor coupling (the local Kuramoto model). Our novel strategy employs indirect coupling between lasers via additional cold cavities. By installing cold cavities between laser cavities, we avoid the strong coupling of lasers and realize ideal mutual injection-locking with effective non-delayed dissipative coupling. First, after discussing the limit cycle interpretation of laser oscillation, we demonstrate the synchronization of two indirectly coupled lasers by numerically simulating coupled-mode equations. Second, by performing a phase reduction analysis, we show that laser dynamics in the proposed device can be mapped to the local Kuramoto model. Finally, we briefly demonstrate that a chain of indirectly coupled photonic crystal lasers actually emulates the one-dimensional local Kuramoto chain. We also argue that our proposed structure, which consists of periodically aligned cold cavities and laser cavities, will best be realized by using state-of-the-art buried multiple quantum well photonic crystals.

Exploitation of the interaction of measles virus fusogenic envelope proteins with the surface receptor CD46 on human cells for microcell-mediated chromosome transfer.

BACKGROUND: Microcell-mediated chromosome transfer (MMCT) is a technique by which a chromosome(s) is moved from donor to recipient cells by microcell fusion. Polyethylene glycol (PEG) has conventionally been used as a fusogen, and has been very successful in various genetic studies. However, PEG is not applicable for all types of recipient cells, because of its cell type-dependent toxicity. The cytotoxicity of PEG limits the yield of microcell hybrids to low level (10-6 to 10-5 per recipient cells). To harness the full potential of MMCT, a less toxic and more efficient fusion protocol that can be easily manipulated needs to be developed. RESULTS: Microcell donor CHO cells carrying a human artificial chromosome (HAC) were transfected with genes encoding hemagglutinin (H) and fusion (F) proteins of an attenuated Measles Virus (MV) Edmonston strain. Mixed culture of the CHO transfectants and MV infection-competent human fibrosarcoma cells (HT1080) formed multinucleated syncytia, suggesting the functional expression of the MV-H/F in the CHO cells. Microcells were prepared and applied to HT1080 cells, human immortalized mesenchymal stem cells (hiMSC), and primary fibroblasts. Drug-resistant cells appeared after selection in culture with Blasticidin targeted against the tagged selection marker gene on the HAC. The fusion efficiency was determined by counting the total number of stable clones obtained in each experiment. Retention of the HAC in the microcell hybrids was confirmed by FISH analyses. The three recipient cell lines displayed distinct fusion efficiencies that depended on the cell-surface expression level of CD46, which acts as a receptor for MV. In HT1080 and hiMSC, the maximum efficiency observed was 50 and 100 times greater than that using conventional PEG fusion, respectively. However, the low efficiency of PEG-induced fusion with HFL1 was not improved by the MV fusogen. CONCLUSIONS: Ectopic expression of MV envelope proteins provides an efficient recipient cell-oriented MMCT protocol, facilitating extensive applications for studies of gene function and genetic corrections.

A highly stable and nonintegrated human artificial chromosome (HAC) containing the 2.4 Mb entire human dystrophin gene.

Episomal vector with the capacity to deliver a large gene containing all the critical regulatory elements is ideal for gene therapy. Human artificial chromosomes (HACs) have the capacity to deliver an extremely large genetic region to host cells without integration into the host genome, thus preventing possible insertional mutagenesis and genomic instability. Duchenne muscular dystrophy (DMD) is caused by mutation in the extremely large dystrophin gene (2.4 Mb). We herein report the development of a HAC vector containing the entire human dystrophin gene (DYS-HAC) that is stably maintained in mice and human immortalized mesenchymal stem cells (hiMSCs). The DYS-HAC was transferred to mouse embryonic stem (ES) cells, and isoforms of the DYS-HAC-derived human dystrophin in the chimeric mice generated from the ES cells were correctly expressed in tissue-specific manner. Thus, this HAC vector containing the entire dystrophin gene with its native regulatory elements is expected to be extremely useful for future gene and cell therapies of DMD.