Structural colour using organized microfibrillation in glassy polymer films.

The formation of microscopic cavities and microfibrils at stress hotspots in polymers is typically undesirable and is a contributor to material failure. This type of stress crazing is accelerated by solvents that are typically weak enough not to dissolve the polymer substantially, but which permeate and plasticize the polymer to facilitate the cavity and microfibril formation process1-3. Here we show that microfibril and cavity formation in polymer films can be controlled and harnessed using standing-wave optics to design a periodic stress field within the film4. We can then develop the periodic stress field with a weak solvent to create alternating layers of cavity and microfibril-filled polymers, in a process that we call organized stress microfibrillation. These multi-layered porous structures show structural colour across the full visible spectrum, and the colour can be tuned by varying the temperature and solvent conditions under which the films are developed. By further use of standard lithographic and masking tools, the organized stress microfibrillation process becomes an inkless, large-scale colour printing process generating images at resolutions of up to 14,000 dots per inch on a number of flexible and transparent formats5,6.

Single-pass generation of widely-tunable frequency-domain entangled photon pairs.

We demonstrate a technique that generates frequency-entangled photon pairs with strong polarization correlation by using a single-period nonlinear crystal and single pass configuration. The technique is based on the simultaneous occurrence of two spontaneous parametric down-conversion processes satisfying independent type-II collinear quasi-phase matching conditions in periodically poled stoichiometric lithium tantalate. The generated photon pairs exhibit non-degenerate Hong-Ou-Mandel interference, indicating the presence of quantum entanglement in the frequency domain. This method provides a light source capable of wide-range quantum sensing and quantum imaging or high-dimensional quantum processing.

Contribution of traditional Japanese Kampo medicines, kakkonto with shosaikotokakikyosekko, in treating patients with mild-to-moderate coronavirus disease 2019: Further analysis of a multicenter, randomized controlled trial.

We previously reported the finding of symptom relief in a randomized controlled trial with the combined use of kakkonto and shosaikotokakikyosekko added to conventional treatment in patients with coronavirus disease 2019 (COVID-19). For further evaluation, we performed post hoc analysis focused on symptom disappearance without recurrence, to determine a clearer effect of Kampo medicine. Patients with mild and moderate COVID-19 were randomly allocated to a control group receiving symptomatic therapy or a Kampo group receiving kakkonto (2.5 g) with shosaikotokakikyosekko (2.5 g) three times daily in addition to symptomatic therapy. The data of 161 patients (Kampo group, n = 81; control group, n = 80) were analyzed post hoc for the time to symptom disappearance. Kaplan-Meier and Cox proportional hazard estimates of disappearance of symptoms showed that all and each symptom targeted in this study disappeared faster in the Kampo group than in the control group, although not statistically significant (all symptomatic cases; hazard ratio [HR] 3.73, 95% confidence interval [CI] 0.46-29.98, log-rank p = 0.1763). In a supplemental assessment using covariate adjustment and competing risk analysis, fever disappeared faster in the Kampo group than in the control group (all symptomatic cases, HR 1.62, 95% CI 0.99-2.64, p = 0.0557; unvaccinated cases, HR 1.68, 95% CI 1.00-2.83, p = 0.0498) and shortness of breath disappeared significantly faster in Kampo group than in control group (all symptomatic cases, HR 1.92, 95% CI 1.07-3.42, p = 0.0278; unvaccinated cases, HR 2.15, 95% CI 1.17-3.96, p = 0.0141). These results demonstrate the advantages of Kampo treatment for acute COVID-19.

Anomalous Temperature Dependence of High-Harmonic Generation in Mott Insulators.

We reveal the crucial effect of strong spin-charge coupling on high-harmonic generation (HHG) in Mott insulators. In a system with antiferromagnetic correlations, the HHG signal is drastically enhanced with decreasing temperature, even though the gap increases and the production of charge carriers is suppressed. This anomalous behavior, which has also been observed in recent HHG experiments on Ca_{2}RuO_{4}, originates from a cooperative effect between the spin-charge coupling and the thermal ensemble, as well as the strongly temperature-dependent coherence between charge carriers. We argue that the peculiar temperature dependence of HHG is a generic feature of Mott insulators, which can be controlled via the Coulomb interaction and dimensionality of the system. Our results demonstrate that correlations between different degrees of freedom, which are a characteristic feature of strongly correlated solids, have significant and nontrivial effects on nonlinear optical responses.

Imatinib induces diastolic dysfunction and ventricular early-repolarization delay in the halothane-anesthetized dogs: Class effects of tyrosine kinase inhibitors.

Imatinib has been reported to induce heart failure and/or QTc prolongation. To better understand their underlying mechanisms, we assessed its effects on cardiohemodynamic, electrocardiographic and echocardiographic variables along with biomarkers of myocardial damage. Imatinib mesylate in doses of 1 and 10 mg/kg was intravenously administered to the halothane-anesthetized beagle dogs (n = 4). Effects of imatinib on each phase of isovolumetric contraction, ejection, isovolumetric relaxation and filling were studied, whereas its electrophysiological effects on early and late repolarization were analyzed by measuring J-Tpeak and Tpeak-Tend, respectively. The low and high doses of imatinib provided peak plasma concentrations of 3.23 and 17.39 µg/mL, reflecting clinically-relevant and supratherapeutic concentrations, respectively. Neither lethal ventricular tachyarrhythmia nor cardiohemodynamic collapse was observed. Imatinib decreased amplitude of peak -dP/dt, indicating suppression of isovolumetric relaxation, whereas no significant change was detected in the other phases. Imatinib prolonged QTc and J-Tpeakc without altering Tpeak-Tend, indicating increase of net inward current, which leads to intracellular Ca2+ overload. Thus, imatinib suppressed ventricular active relaxation and early repolarization, which may suggest the association of mitochondrial dysfunction-associated inhibition of ATP production. Since those findings were also reported for dasatinib, sunitinib and lapatinib, they could be common cardiac phenotype of tyrosine kinase inhibitors in vivo.

Real-Time Megapixel Electro-Optical Imaging of THz Beams with Probe Power Normalization.

In this work, we present a simple method to improve the spatial uniformity of two-dimensional electro-optical imaging of terahertz (THz) beams. In this system, near-field THz images are captured by fully illuminating a sample using conventional optical microscope objectives. Unfortunately, due to the linear relationship between the optical probe power and the measured THz electric field, any spatial variation in probe intensity translates directly into a variation of the recorded THz electric field. Using a single normalized background frame information map as a calibration tool prior to recording a sequence of THz images, we show a full recovery of a two-dimensional flat field for various combinations of magnification factors. Our results suggest that the implementation of dynamic intensity profile correction is a promising avenue for real-time electro-optical imaging of THz beams.

Broadband sum frequency generation spectroscopy of dark exciton states in hBN-encapsulated monolayer WSe2.

We demonstrate that broadband sum frequency generation (SFG) spectroscopy based on a partially incoherent supercontinuum light source can elucidate dark p-series excitons in monolayer WSe2 encapsulated between hexagonal boron nitride (hBN) slabs. The observed 2p exciton peak energy is a few meV higher than that predicted by the Rytova-Keldysh potential model, which is originated from the Berry phase effect. Interestingly, although the radiative relaxation of the 2p exciton is weaker, the 2p exciton peak is broader than the 1s and 2s peaks, which indicates its faster dephasing than the 1s and 2s excitons. Measuring the excitation intensity and temperature dependence, we clarified that this broader linewidth is not caused by excitation- or phonon-induced dephasing, but rather by exciton-electron scattering.

Control of High-Harmonic Generation by Tuning the Electronic Structure and Carrier Injection.

High-harmonic generation (HHG), which is the generation of light with multiple optical harmonics, is an unconventional nonlinear optical phenomenon beyond the perturbation regime. HHG, which was initially observed in gaseous media, has recently been demonstrated in solid-state materials. Determining how to control such extreme nonlinear optical phenomena is a challenging subject. Here, we demonstrate the control of HHG through tuning the electronic structure and carrier injection using single-walled carbon nanotubes (SWCNTs). We reveal systematic changes in the high-harmonic spectra of SWCNTs with a series of electronic structures ranging from a metal structure to a semiconductor structure. We demonstrate enhancement or reduction of harmonic generation by more than 1 order of magnitude by tuning the electron and hole injection into the semiconductor SWCNTs through electrolyte gating. These results open a path toward the control of HHG in the context of field-effect transistor devices.

Terahertz microscopy assisted by semiconductor nonlinearities.

Terahertz (THz) imaging is currently based on linear effects, but there is great interest on how nonlinear effects induced by terahertz radiation could be exploited to provide extra information that is unobtainable by conventional imaging schemes. In particular, at field strengths on the order of 100 kV cm-1 to 1 MV cm-1, transmission properties inside semiconductor materials are largely affected at the picosecond time-scale, which raise the prospect of interesting nonlinear imaging applications at THz frequencies. Here, we experimentally investigate a method to map the two-dimensional nonlinear near-field distribution of an intense THz pulse passing through a thin film-doped semiconductor. By inserting a metamaterial structure between the electro-optic sensor and the doped film, the nonlinear near-field dynamics shows a different and enhanced contrast of the sample when compared to its linear counterpart.

Superradiance-to-Polariton Crossover of Wannier Excitons with Multiple Resonances.

We demonstrated the superradiance-to-polariton crossover of the blue excitons in Cu_{2}O by varying the sample thicknesses instead of controlling the cavity quality factor. The crossover behavior was compared with unprecedented calculations based on the nonlocal optical response theory with the inclusion of three exciton resonances. The crossover thickness, found to be 177±2 nm, was smaller than the predicted value for a single resonance by a factor of 5. The fact that there was much larger longitudinal-transverse splitting (40±5 meV) than in the bulk implies a surprisingly fast radiative recombination even without a cavity structure.

Zener Tunneling Breakdown in Phase-Change Materials Revealed by Intense Terahertz Pulses.

We have systematically investigated the spatial and temporal dynamics of crystallization that occur in the phase-change material Ge_{2}Sb_{2}Te_{5} upon irradiation with an intense terahertz (THz) pulse. THz-pump-optical-probe spectroscopy revealed that Zener tunneling induces a nonlinear increase in the conductivity of the crystalline phase. This fact causes the large enhancement of electric field associated with the THz pulses only at the edge of the crystallized area. The electric field concentrating in this area causes a temperature increase via Joule heating, which in turn leads to nanometer-scale crystal growth parallel to the field and the formation of filamentary conductive domains across the sample.

Reconsideration of the relaxational and vibrational line shapes of liquid water based on ultrabroadband dielectric spectroscopy.

The Debye relaxation function is widely used to describe the large dielectric dispersion of ambient water around 20 GHz. However, from a theoretical point of view, this function is supposed to give incorrect predictions at high frequencies owing to the inappropriate assumption that inertial effects and intermolecular interactions do not affect the relaxation dynamics. Our ultrabroadband spectroscopy investigation of liquid water ranging from 500 MHz to 400 THz did demonstrate that the Debye function is inaccurate far above the microwave region. As an alternative, we tried a stochastic frequency modulation (SFM) model assuming instantaneous modification of the line shapes by the correlation with the surrounding system. The SFM relaxation model reproduced the experimental dielectric spectra up to 400 THz, showing that the hydrogen-bond dynamics are associated with the inertial effect that causes the non-exponential relaxation behaviour in a very short time (typically 25 fs). Within the framework of this relaxation model, the hindered translation modes are able to be approximated as fast modulation (homogeneous) line shapes because the interaction time with frequency modulation is too short. Compared with them, the libation mode is found to have a relatively slow modulation (inhomogeneous) origin, where disturbance of water hydrogen bonds induced by the hindered translations leads to fluctuations in the libration frequency.

Focusing light with orbital angular momentum by circular array antenna.

We experimentally demonstrated focusing of light with orbital angular momentum (OAM) using an 8-element circular array of linear antennas. A spiral phase plate was used to generate a vortex beam with an OAM of h in the terahertz (THz) frequency region. We used THz near-field microscope to directly measure the phase vortex. A beam profile with a center dark spot and 2π phase rotation was observed in the small center gap region of the circular array antenna after the vortex beam excitation. The beam size is reduced by a factor of 3.4 ± 0.2. Half-wave resonance of the antenna element is responsible for the focusing function, indicating the scalability of this method to other frequency regions. This method will enable deep subwavelength focusing of light with OAM and eliminate the obstacle for the observation of the dipole forbidden transition with finite OAM of the vortex beam.

Analysis of proarrhythmic potential of an atypical antipsychotic drug paliperidone in the halothane-anesthetized dogs.

Fatal cases with the use of atypical antipsychotic drug paliperidone have been reported; however, there was no clinical report describing paliperidone-induced torsade de pointes. In this study we assessed its electropharmacological effects together with its proarrhythmic potential in intravenous doses of 0.03, 0.3 and 3 mg/kg using the halothane-anesthetized dogs (n = 5), which could provide approximately 2, 20 and 200 times higher peak plasma drug concentrations than its therapeutic level, respectively. Paliperidone exerted potent vasodilator effect resulting in hypotension, which may be largely explained by its α1-adrenoceptor blocking action. In vivo electrophysiological results suggest that paliperidone may inhibit human ether-à-go-go-related gene K+ channel in a dose-related manner and modestly suppress Na+ channel in the in situ heart. The high dose of paliperidone may have some potential to induce early afterdepolarization that can trigger lethal ventricular arrhythmias, whereas the low and middle doses lack such proarrhythmic possibility, indicating that at least 20 times higher plasma concentration may be considered to be safe.

Ultrafast diffusion of a fluorescent cholesterol analog in compartmentalized plasma membranes.

Cholesterol distribution and dynamics in the plasma membrane (PM) are poorly understood. The recent development of Bodipy488-conjugated cholesterol molecule (Bdp-Chol) allowed us to study cholesterol behavior in the PM, using single fluorescent-molecule imaging. Surprisingly, in the intact PM, Bdp-Chol diffused at the fastest rate ever found for any molecules in the PM, with a median diffusion coefficient (D) of 3.4 µm²/second, which was ∼10 times greater than that of non-raft phospholipid molecules (0.33 µm²/second), despite Bdp-Chol's probable association with raft domains. Furthermore, Bdp-Chol exhibited no sign of entrapment in time scales longer than 0.5 milliseconds. In the blebbed PM, where actin filaments were largely depleted, Bdp-Chol and Cy3-conjugated dioleoylphosphatidylethanolamine (Cy3-DOPE) diffused at comparable Ds (medians = 5.8 and 6.2 µm²/second, respectively), indicating that the actin-based membrane skeleton reduces the D of Bdp-Chol only by a factor of ∼2 from that in the blebbed PM, whereas it reduces the D of Cy3-DOPE by a factor of ∼20. These results are consistent with the previously proposed model, in which the PM is compartmentalized by the actin-based membrane-skeleton fence and its associated transmembrane picket proteins for the macroscopic diffusion of all of the membrane molecules, and suggest that the probability of Bdp-Chol passing through the compartment boundaries, once it enters the boundary, is ∼10× greater than that of Cy3-DOPE. Since the compartment sizes are greater than those of the putative raft domains, we conclude that raft domains coexist with membrane-skeleton-induced compartments and are contained within them.

A Novel Peroxisome Proliferator-activated Receptor (PPAR)α Agonist and PPARγ Antagonist, Z-551, Ameliorates High-fat Diet-induced Obesity and Metabolic Disorders in Mice.

A novel peroxisome proliferator-activated receptor (PPAR) modulator, Z-551, having both PPARα agonistic and PPARγ antagonistic activities, has been developed for the treatment of obesity and obesity-related metabolic disorders. We examined the effects of Z-551 on obesity and the metabolic disorders in wild-type mice on the high-fat diet (HFD). In mice on the HFD, Z-551 significantly suppressed body weight gain and ameliorated insulin resistance and abnormal glucose and lipid metabolisms. Z-551 inhibited visceral fat mass gain and adipocyte hypertrophy, and reduced molecules involved in fatty acid uptake and synthesis, macrophage infiltration, and inflammation in adipose tissue. Z-551 increased molecules involved in fatty acid combustion, while reduced molecules associated with gluconeogenesis in the liver. Furthermore, Z-551 significantly reduced fasting plasma levels of glucose, triglyceride, free fatty acid, insulin, and leptin. To elucidate the significance of the PPAR combination, we examined the effects of Z-551 in PPARα-deficient mice and those of a synthetic PPARγ antagonist in wild-type mice on the HFD. Both drugs showed similar, but weaker effects on body weight, insulin resistance and specific events provoked in adipose tissue compared with those of Z-551 as described above, except for lack of effects on fasting plasma triglyceride and free fatty acid levels. These findings suggest that Z-551 ameliorates HFD-induced obesity, insulin resistance, and impairment of glucose and lipid metabolisms by PPARα agonistic and PPARγ antagonistic activities, and therefore, might be clinically useful for preventing or treating obesity and obesity-related metabolic disorders such as insulin resistance, type 2 diabetes, and dyslipidemia.

Improving time and space resolution in electro-optic sampling for near-field terahertz imaging.

In this Letter, we present a significant improvement to time and space resolutions in electro-optic sampling (EO) for two-dimensional terahertz (THz) near-field imaging. Using a THz microscope, we readapt a recent EO sampling scheme based on optical probe spectrum filtering. Combined with an ultra-thin EO crystal, we achieve record broadband video-rate THz near-field imaging. Particularly, this new scheme improves the THz bandwidth, the imaging contrast, and the spatial resolution. To validate our method, we show THz near-field images ranging from 100 GHz to 4 THz with a spatial resolution up to λ/600 at 100 GHz. This demonstration positively affects the detection of intense THz pulses derived from the tilted-pulse-front excitation of lithium niobate and will accelerate our understanding of the interaction processes between electromagnetic waves and the conducting electrons of metallic interfaces.

Achieved Weight Gain and Return to Work After Intervention With Traditional Japanese Acupuncture for Avoidant Restrictive Food Intake Disorder: A Case Report.

Avoidant restrictive food intake disorder (ARFID) is newly established as a category of eating disorder (ED). Acupuncture is one treatment option for ED. However, no cases of acupuncture treatment of ARFID have been reported. A 28-year-old female presented with reduced food intake and weight, abdominal bloating, abnormal sense of taste, and tongue pain. Her body weight (BW) had been around 50 kg until four years previously. Three years before, her symptoms occurred, and her BW decreased to 36.5 kg after experiencing excessive mental stress at her workplace. She was diagnosed with ARFID by a psychosomatic physician and tended to refuse her prescribed antipsychotic drugs. She was treated weekly with the Hokushin-kai style, a traditional Japanese acupuncture, and the moxibustion method. After one month, the patient felt somewhat better and returned to work once a week for the first time in two years. Four months later, her BW started to increase. After 10 months, her BW had increased to 48 kg. Her acupuncture treatment continues. This case suggests acupuncture as an optional treatment for ARFID. Further studies, such as a combination of medications and acupuncture, would be desirable.

Phase-resolved measurement and control of ultrafast dynamics in terahertz electronic oscillators.

As a key component for next-generation wireless communications (6 G and beyond), terahertz (THz) electronic oscillators are being actively developed. Precise and dynamic phase control of ultrafast THz waveforms is essential for high-speed beam steering and high-capacity data transmission. However, measurement and control of such ultrafast dynamic process is beyond the scope of electronics due to the limited bandwidth of the electronic equipment. Here we surpass this limit by applying photonic technology. Using a femtosecond laser, we generate offset-free THz pulses to phase-lock the electronic oscillators based on resonant tunneling diode. This enables us to perform phase-resolved measurement of the emitted THz electric field waveform in time-domain with sub-cycle time resolution. Ultrafast dynamic response such as anti-phase locking behaviour is observed, which is distinct from in-phase stimulated emission observed in laser oscillators. We also show that the dynamics follows the universal synchronization theory for limit cycle oscillators. This provides a basic guideline for dynamic phase control of THz electronic oscillators, enabling many key performance indicators to be achieved in the new era of 6 G and beyond.

Dissipative structure in the photo-induced phase under steady light irradiation in the spin crossover complex.

We report the spatial and temporal dynamics of the photo-induced phase in the iron (II) spin crossover complex Fe(ptz)(6)(BF(4))(2) studied by image measurement under steady light irradiation and transient absorption measurement. The dynamic factors are derived from the spatial and temporal fluctuation of the image in the steady state under light irradiation between 65 and 100 K. The dynamic factors clearly indicate that the fluctuation has a resonant frequency that strongly depends on the temperature, and is proportional to the relaxation rate of the photo-induced phase. This oscillation of the speckle pattern under steady light irradiation is ascribed to the nonlinear interaction between the spin state and the lattice volume at the surface.