Neuronal activation of nucleus accumbens by local methamphetamine administration induces cognitive impairment through microglial inflammation in mice.

More than half of methamphetamine (METH) users present with cognitive impairment, making it difficult for them to reintegrate into society. However, the mechanisms of METH-induced cognitive impairment remain unclear. METH causes neuronal hyperactivation in the nucleus accumbens (NAc) by aberrantly releasing dopamine, which triggers dependence. In this study, to clarify the involvement of hyperactivation of NAc in METH-induced cognitive impairment, mice were locally microinjected with METH into NAc (mice with METH (NAc)) and investigated their cognitive phenotype. Mice with METH (NAc) exhibited cognitive dysfunction in behavioral analyses and decreased long-term potentiation in the hippocampus, with NAc activation confirmed by expression of FosB, a neuronal activity marker. In the hippocampus of mice with METH (NAc), activated microglia, but not astroglia, and upregulated microglia-related genes, Il1b and C1qa were observed. Finally, administration of minocycline, a tetracycline antibiotic with suppressive effect on microglial activation, to mice with METH (NAc) ameliorated cognitive impairment and synaptic dysfunction by suppressing the increased expression of Il1b and C1qa in the hippocampus. In conclusion, activation of NAc by injection of METH into NAc elicited cognitive impairment by facilitating immune activation in mice. This study suggests that immunological intervention could be a therapeutic strategy for addiction-related cognitive disturbances.

Raman silicon nanocavity laser with efficient light emission from the edge of an adjacent waveguide.

A Raman nanocavity laser can emit light into free space and into a properly designed waveguide adjacent to the cavity by mode coupling. In common device designs, the emission from the edge of this waveguide is relatively weak. However, a Raman silicon nanocavity laser with strong emission from the waveguide edge would be advantageous for certain applications. Here we investigate the increase in the edge emission that can be achieved by adding photonic mirrors to the waveguides adjacent to the nanocavity. We experimentally compare devices with and without photonic mirrors: the edge emission for devices with mirrors is 4.3 times stronger on average. This increase is analyzed using coupled-mode theory. The results indicate that the control of the round-trip phase shift (between the nanocavity and the mirror) and an increase of the quality factors of the nanocavity are important for further enhancement.

Suppressing the sample-to-sample variation of photonic crystal nanocavity Q-factors by air-hole patterns with broken mirror symmetry.

It is known that the quality factors (Q) of photonic crystal nanocavities vary from sample to sample due to air-hole fabrication fluctuations. In other words, for the mass production of a cavity with a given design, we need to consider that the Q can vary significantly. So far, we have studied the sample-to-sample variation in Q for symmetric nanocavity designs, that is, nanocavity designs where the positions of the holes maintain mirror symmetry with respect to both symmetry axes of the nanocavity. Here we investigate the variation of Q for a nanocavity design in which the air-hole pattern has no mirror symmetry (a so-called asymmetric cavity design). First, an asymmetric cavity design with a Q of about 250,000 was developed by machine learning using neural networks, and then we fabricated fifty cavities with the same design. We also fabricated fifty symmetric cavities with a design Q of about 250,000 for comparison. The variation of the measured Q values of the asymmetric cavities was 39% smaller than that of the symmetric cavities. This result is consistent with simulations in which the air-hole positions and radii are randomly varied. Asymmetric nanocavity designs may be useful for mass production since the variation in Q is suppressed.

Silicon nanocavity with a quality factor of 6.7 million fabricated by a CMOS-compatible process.

Here, we report on the increase of the quality-factors of photonic crystal nanocavities fabricated by a CMOS-compatible process. We fabricated nanocavities with the same cavity design but used either a binary photomask or a phase-shift photomask in the photolithography step to assess the impact of the photomask-type on the fabrication accuracy of the air holes. We characterized 62 cavities using time-resolved measurements and the best cavity had a quality-factor of 6.65 × 106. All cavities exhibited a quality-factor larger than 2 million and the overall average was 3.25 × 106. While the estimated magnitude of the scattering loss due to the air hole variations in the 33 cavities fabricated with the phase-shift photomask was slightly lower than that in the 29 cavities fabricated with binary photomask, the phase-shift photomask did not provide a significant improvement in the fabrication accuracy. On average, the scattering loss in these samples is more than 3 times larger than that of nanocavities fabricated using electron-beam lithography, which indicates room for further improvement.

Involvement of the Restoration of Cerebral Blood Flow and Maintenance of eNOS Expression in the Prophylactic Protective Effect of the Novel Ferulic Acid Derivative FAD012 against Ischemia/Reperfusion Injuries in Rats.

Tissue plasminogen activator, aiming to restore cerebral blood flow (CBF), has been used for acute ischemic strokes in clinics; however, its narrow therapeutic time window remains a serious concern. To develop novel prophylactic drugs to alleviate cerebral ischemia/reperfusion injuries, ferulic acid derivative 012 (FAD012) was synthesized and showed comparable antioxidant properties to ferulic acid (FA) and probably possesses the potent ability to cross the blood-brain barrier. A more potent cytoprotective effect of FAD012 against H2O2-induced cytotoxicity in PC12 cells was also observed. In vivo toxicity was not observed in rats given a long-term oral administration of FAD012, indicating its good tolerability. A one-week-course oral administration of FAD012 significantly alleviated middle cerebral artery occlusion (MCAO)-induced cerebral ischemia/reperfusion injuries in rats, accompanied by the restoration of CBF and endothelial nitrogen oxide synthetase (eNOS) expression. Treatment with FAD012 significantly restored the cell viability and eNOS expression damaged by H2O2, used to mimic MCAO-triggered oxidative stress, in rat brain microvascular endothelial cells. Our findings suggested that FAD012 protected the viability of vascular endothelium and maintained eNOS expression, ultimately contributing to the restoration of CBF, and may provide a rationale for the development of FAD012 into an effective prophylactic drug for patients at high risk of stroke.

Cannabinoid Type 1 Receptors in the Basolateral Amygdala Regulate ACPA-Induced Place Preference and Anxiolytic-Like Behaviors.

The number of cannabis users is increasing in the world. However, the mechanisms involved in the psychiatric effects and addiction formation remain unclear. Medical treatments against cannabis addiction have not yet been established. Δ9-Tetrahydrocannabinol (THC), the main active substance in cannabis, binds and affects cannabinoid type 1 receptors (CB1R) in the brain. The mice were intraperitoneally (i.p.) administered arachidonylcyclopropylamide (ACPA), a CB1R-selective agonist, and then two behavioral experiments on anxiety and addiction were performed. Administration of ACPA caused anxiolytic-like behavior in the elevated plus maze test. In addition, ACPA increased place preference in a conditioned place preference (CPP) test. The basolateral amygdala (BLA), which is the focus of this study, is involved in anxiety-like behavior and reward and is reported to express high levels of CB1R. We aimed to reveal the role of CB1R in BLA for ACPA-induced behavior. AM251, a CB1R selective antagonist, was administered intra-BLA before i.p. administration of ACPA. Intra-BLA administration of AM251 inhibited ACPA-induced anxiolytic-like behavior and place preference. These results suggest that CB1R in the BLA contributes to behavior disorders caused by the acute or chronic use of cannabis.

Sub-100-nW-threshold Raman silicon laser designed by a machine-learning method that optimizes the product of the cavity Q-factors.

Raman silicon lasers based on photonic crystal nanocavities with a threshold of several hundred microwatts for continuous-wave lasing have been realized. In particular, the threshold depends on the degree of confinement of the excitation light and the Raman scattering light in the two nanocavity modes. Here, we report lower threshold values for Raman silicon nanocavity lasers achieved by increasing the quality (Q) factors of the two cavity modes. By using an optimization method based on machine learning, we first increase the product of the two theoretical Q values by a factor of 17.0 compared to the conventional cavity. The experimental evaluation demonstrates that, on average, the actually achieved product is more than 2.5 times larger than that of the conventional cavity. The input-output characteristic of a Raman laser with a threshold of 90 nW is presented and the lowest threshold obtained in our experiments is 40 nW.

Near-field thermophotovotaic devices with surrounding non-contact reflectors for efficient photon recycling.

Near-field thermophotovoltaic (TPV) power generation has been attracting increasing attention as a promising approach for efficient conversion of heat into electricity with high output power density. Here, we numerically investigate near-field TPV devices with surrounding reflectors for efficient recycling of low-energy photons, which do not contribute to the power generation. We reveal that the conversion efficiency of a near-field TPV system can be drastically increased by introducing a pair of reflectors above and below the system, especially when the two mirrors are not in contact with the emitter and absorber. In addition, we investigate the influence of non-perfect photon recycling on the TPV efficiency and reveal that near-field TPV systems are more robust against the decrease of the reflectivity of the reflectors than the far-field TPV systems.

Detection of negatively ionized air by using a Raman silicon nanocavity laser.

The performance of a Raman silicon laser based on a high quality-factor nanocavity depends on the degree of free-carrier absorption, and this characteristic may be useful for certain applications. Here we demonstrate that laser oscillation in a Raman silicon nanocavity laser stops abruptly after an exposure to a weak flux of negatively ionized air for a few seconds. Spectral measurements reveal that the laser interruption is mainly caused by the transfer of extra electrons from the negatively ionized air molecules to the silicon nanocavity. These electrons affect the efficiency of the Raman laser by free carrier absorption. We find that the laser output gradually recovers as the extra electrons escape from the nanocavity and confirm that such a detection of ionized air is repeatable. These results show that a Raman silicon nanocavity laser can be used for the detection of ionized air with a high spatial resolution.

1.2-µm-band ultrahigh-Q photonic crystal nanocavities and their potential for Raman silicon lasers.

Nanocavity devices based on silicon that can operate in the 1.2-µm band would be beneficial for several applications. We fabricate fifteen cavities with resonance wavelengths between 1.20 and 1.23 µm. Experimental quality (Q) factors larger than one million are obtained and the average Q values are lower for shorter wavelengths. Furthermore, we observe continuous-wave operation of a Raman silicon laser with an excitation wavelength of 1.20 µm and a Raman laser wavelength of 1.28 µm. The Q values of the nanocavity modes used to confine the excitation light and the Raman scattered light are about half of those for our Raman silicon laser operating in the 1.55-µm band. Nevertheless, this device exhibits an input-output characteristic with a clear laser threshold. Finally, we consider the effect of the higher scattering probability at shorter wavelengths on the Raman laser performance in the 1.2-µm band.

One-Chip Near-Field Thermophotovoltaic Device Integrating a Thin-Film Thermal Emitter and Photovoltaic Cell.

Thermal radiation transfer between two objects separated by a subwavelength gap (near-field thermal radiation transfer) can be orders of magnitude larger than that in free space, which is attracting increasing attention with respect to both fundamental nanoscience and its potential for high-power-density and high-efficiency conversion of heat to electricity in thermophotovoltaic (TPV) systems. However, the realization of near-field thermal radiation transfer in TPV systems involves significant challenges because it requires a subwavelength gap and large temperature difference between the emitter and the PV cell while minimizing the heat transfer that does not contribute to the photocurrent generation. To overcome these challenges, here we demonstrate a one-chip near-field TPV device consisting of a thin-film Si emitter and InGaAs PV cell with an intermediate Si substrate, which enables the suppression of the heat transfer due to sub-bandgap radiation by free carriers and surface modes. Through the one-chip integration and thermal isolation using Si process technologies, we realize a deep subwavelength gap (<150 nm) between the emitter and the intermediate substrate without using any external positioners while maintaining a large temperature difference (>700 K). Compared to the equivalent device operating in the far-field regime, we achieve 10-fold enhancement of the photocurrent in the PV cell without degrading the open-circuit voltage and fill factor, demonstrating the potential of our one-chip device for the future applications of near-field thermal radiation transfer.

Shimalactone Biosynthesis Involves Spontaneous Double Bicyclo-Ring Formation with 8π-6π Electrocyclization.

Shimalactones A and B are neuritogenic polyketides possessing characteristic oxabicyclo[2.2.1]heptane and bicyclo[4.2.0]octadiene ring systems that are produced by the marine fungus Emericella variecolor GF10. We identified a candidate biosynthetic gene cluster and conducted heterologous expression analysis. Expression of ShmA polyketide synthase in Aspergillus oryzae resulted in the production of preshimalactone. Aspergillus oryzae and Saccharomyces cerevisiae transformants expressing ShmA and ShmB produced shimalactones A and B, thus suggesting that the double bicyclo-ring formation reactions proceed non-enzymatically from preshimalactone epoxide. DFT calculations strongly support the idea that oxabicyclo-ring formation and 8π-6π electrocyclization proceed spontaneously after opening of the preshimalactone epoxide ring through protonation. We confirmed the formation of preshimalactone epoxide in vitro, followed by its non-enzymatic conversion to shimalactones in the dark.

A micrometre-scale Raman silicon laser with a microwatt threshold.

The application of novel technologies to silicon electronics has been intensively studied with a view to overcoming the physical limitations of Moore's law, that is, the observation that the number of components on integrated chips tends to double every two years. For example, silicon devices have enormous potential for photonic integrated circuits on chips compatible with complementary metal-oxide-semiconductor devices, with various key elements having been demonstrated in the past decade. In particular, a focus on the exploitation of the Raman effect has added active optical functionality to pure silicon, culminating in the realization of a continuous-wave all-silicon laser. This achievement is an important step towards silicon photonics, but the desired miniaturization to micrometre dimensions and the reduction of the threshold for laser action to microwatt powers have yet to be achieved: such lasers remain limited to centimetre-sized cavities with thresholds higher than 20 milliwatts, even with the assistance of reverse-biased p-i-n diodes. Here we demonstrate a continuous-wave Raman silicon laser using a photonic-crystal, high-quality-factor nanocavity without any p-i-n diodes, yielding a device with a cavity size of less than 10 micrometres and an unprecedentedly low lasing threshold of 1 microwatt. Our nanocavity design exploits the principle that the strength of light-matter interactions is proportional to the ratio of quality factor to the cavity volume and allows drastic enhancement of the Raman gain beyond that predicted theoretically. Such a device may make it possible to construct practical silicon lasers and amplifiers for large-scale integration in photonic circuits.

Optimization of photonic crystal nanocavities based on deep learning.

An approach to optimizing the Q factors of two-dimensional photonic crystal (2D-PC) nanocavities based on deep learning is hereby proposed and demonstrated. We prepare a data set consisting of 1000 nanocavities generated by randomly displacing the positions of many air holes in a base nanocavity and calculate their Q factors using a first-principles method. We train a four-layer neural network including a convolutional layer to recognize the relationship between the air holes' displacements and the Q factors using the prepared data set. After the training, the neural network is able to estimate the Q factors from the air holes' displacements with an error of 13% in standard deviation. Crucially, the trained neural network can estimate the gradient of the Q factor with respect to the air holes' displacements very quickly using back-propagation. A nanocavity structure with an extremely high Q factor of 1.58 × 109 was successfully obtained by optimizing the positions of 50 holes over ~106 iterations, taking advantage of the very fast evaluation of the gradient in high-dimensional parameter spaces. The obtained Q factor is more than one order of magnitude higher than that of the base cavity and more than twice that of the highest Q factors reported so far for cavities with similar modal volumes. This approach can optimize 2D-PC structures over a parameter space of a size unfeasibly large for previous optimization methods that were based solely on direct calculations. We believe that this approach is also useful for improving other optical characteristics.

Spectral control of near-field thermal radiation via photonic band engineering of two-dimensional photonic crystal slabs.

In this paper, we numerically investigate a method to obtain narrow-bandwidth near-field thermal radiation spectra by using two-dimensional (2D) photonic crystal (PC) slabs. Our examination reveals that near-field thermal radiation spectra can be artificially controlled via the photonic band engineering of 2D-PC slabs, where the radiation is enhanced in a range of frequencies of the flat bands and suppressed inside the photonic bandgap. By designing a thermal emitter with a 2D-PC slab of appropriate thickness, and by adjusting the gap between the emitter and the absorber, we can implement narrowband near-field thermal radiation that overcomes the far-field blackbody limit in the near-infrared range. Further, its linewidth is as small as Δλ = 0.14 µm.

Near-field thermophotovoltaic energy conversion using an intermediate transparent substrate.

We propose a scheme for near-field thermophotovoltaic (TPV) energy conversion, where thermal emission from an emitter is extracted by an intermediate transparent substrate attached to the top of a photovoltaic (PV) cell. The addition of an intermediate transparent substrate suppresses the unwanted heat transfer from the emitter to the PV cell due to the surface modes on the PV cell while maintaining the enhancement in the interband absorption. We confirm that our scheme is applicable for near-field TPV systems using a silicon (Si) or tungsten (W) emitter. As a specific example, we designed a near-field TPV system composed of a one-dimensional Si photonic crystal thermal emitter, an InGaAs PV cell, and an intermediate Si substrate, and displayed that our scheme could realize both high power density (>5 × 104 W/m2) and high power conversion efficiency (>40%) at a 50-nm gap between the emitter and the intermediate substrate.

Photonic crystal nanocavity with a Q factor exceeding eleven million.

Photonic crystal nanocavities that simultaneously possess small modal volumes and high quality (Q) factors have opened up novel research areas in photonics during this decade. Here, we present an important key for the increase of Q factors to ranges beyond ten million. A systematic investigation on photon lifetimes of air-bridge-type heterostructure nanocavities fabricated from silicon on insulator (SOI) substrates indicated the importance of cleaning the bottom side (buried oxide side) of the nanaocavites. Repeated thermal oxidation and an oxide removal process applied after the removal of the buried oxide layer underneath the nanocavities realized an experimental Q factor greater than eleven million, which is the highest experimental Q ever recorded. The results provide important information not only for Si PC nanocavities but also for general Si nanophotonic devices and photonic electronic convergence systems.

Analysis of high-Q photonic crystal L3 nanocavities designed by visualization of the leaky components.

We experimentally study photonic crystal L3 nanocavities whose design Q factors (Qdesign) have been improved with the visualization of leaky components design method. The experimental Q values (Qexp) are monotonically increased from 6,000 to 2,100,000 by iteratively modifying the positions of some of the air holes, as determined by the referred design method. We investigate the Qexp tolerance to imperfections in the fabricated samples, which reveals that the cavities improved by the visualization method tend to lose some tolerance to structural differences between the fabricated samples and the design values.

Ultrahigh-Q photonic crystal nanocavities fabricated by CMOS process technologies.

We fabricated photonic crystal high-quality factor (Q) nanocavities on a 300-mm-wide silicon-on-insulator wafer by using argon fluoride immersion photolithography. The heterostructure nanocavities showed an average experimental Q value of 1.5 million for 12 measured samples. The highest Q value was 2.3 million, which represents a record for a nanocavity fabricated by complementary metal-oxide-semiconductor (CMOS)-compatible machinery. We also demonstrated an eight-channel drop filter with 4 nm spacing consisting of arrayed nanocavities with three missing air holes. The standard deviation in the drop wavelength was less than 1 nm. These results will accelerate ultrahigh-Q nanocavity research in various areas.