Dual-wavelength spiral interferometry.

Spiral interferometry acquires the topography of the sample and determines the elevation or depression of the sample structure by a single measurement. The method has advantages in simple measurements and stable optical setup due to the coaxial interferometer. However, the measurable axial range was limited by the wavelength of the light. Here, we demonstrate dual-wavelength spiral interferometry without a significant modification to the original setup of the spiral interferometry. The retrieved phase profile using a synthesized wavelength of 3.33 µm enlarges the measurable axial range with a magnification factor of 6.2 compared with that measured by the light at 532 nm.

Development of novel potent ligands for GPR85, an orphan G protein-coupled receptor expressed in the brain.

GPR85 is a member of the G protein-coupled receptor and is a super-conserved receptor expressed in the brain sub-family (Super Conserved Receptor Expressed in Brain; SREB) with GPR27 and GPR173. These three receptors are "orphan receptors"; however, their endogenous ligands have not been identified. SREB has garnered the interest of many scientists because it is expressed in the central nervous system and is evolutionarily conserved. In particular, brain mass is reported to be increased and learning and memory are improved in GPR85 knockout mice (Matsumoto et al. 2008). In this study, we characterized newly synthesized compounds using a GPR85-Gsα fusion protein and the [35 S]GTPγS binding assay and identified novel GPR85 inverse-agonists with IC50 values of approximately 1 µM. To analyze the neurochemical character of the compounds and investigate the physiological significance of GPR85, we used cerebellar Purkinje cells expressing GPR85 and an electrophysiological technique. Based on the results, the inverse-agonist compound for GPR85 modulated potassium channel opening. Together with the results of previous gene analysis of GPR85, we expect that the development of the GPR85 ligand will provide new insights into a few types of neurological disorders.

Nanometer-precision surface metrology of millimeter-sized stepped objects using full-cascade-linked synthetic-wavelength digital holography using a line-by-line full-mode-extracted optical frequency comb.

Digital holography (DH) is a powerful tool for the surface profilometry of objects with sub-wavelength precision. In this article, we demonstrate full-cascade-linked synthetic-wavelength DH for nanometer-precision surface metrology of millimeter-sized stepped objects. 300 modes of optical frequency comb (OFC) with different wavelengths are sequentially extracted at a step of mode spacing from a 10GHz-spacing, 3.72THz-spanning electro-optic modulator OFC. The resulting 299 synthetic wavelengths and a single optical wavelength are used to generate a fine-step wide-range cascade link covering within a wavelength range of 1.54 µm to 29.7 mm. We determine the sub-millimeter and millimeter step differences with axial uncertainty of 6.1 nm within the maximum axial range of 14.85 mm.

Carrier conversion from terahertz wave to dual-wavelength near-infrared light for photonic terahertz detection in wireless communication.

THz waves are promising wireless carriers for next-generation wireless communications, where a seamless connection from wireless to optical communication is required. In this study, we demonstrate carrier conversion from THz waves to dual-wavelength NIR light injection-locking to an optical frequency comb using asynchronous nonpolarimetric electro-optic downconversion with an electro-optic polymer modulator. THz wave in the W band was detected as a stable photonic RF beat signal of 1 GHz with a signal-to-noise ratio of 20 dB via the proposed THz-to-NIR carrier conversion. In addition, the results imply the potential of the photonic detection of THz waves for wireless-to-optical seamless communication.

Oxidopyridinium Cycloadditions Revisited: A Combined Computational and Experimental Study on the Reactivity of 1-(2-Pyrimidyl)-3-oxidopyridinium Betaine.

To investigate the effect of N-substituents on their reactivity and selectivity of oxidopyridinium betaines, we performed density functional theory (DFT) calculations of model cycloadditions with N-methylmaleimide and acenaphthylene. The theoretically expected results were compared with the experimental results. Subsequently, we demonstrated that 1-(2-pyrimidyl)-3-oxidopyridinium can be used for (5 + 2) cycloadditions with various electron-deficient alkenes, dimethyl acetylenedicarboxylate, acenaphthylene, and styrene. In addition, a DFT analysis of the cycloaddition of 1-(2-pyrimidyl)-3-oxidopyridinium with 6,6-dimethylpentafulvene suggested the possibility of pathway bifurcations involving a (5 + 4)/(5 + 6) ambimodal transition state, although only (5 + 6) cycloadducts were experimentally observed. A related (5 + 4) cycloaddition was observed in the reaction of 1-(2-pyrimidyl)-3-oxidopyridinium with 2,3-dimethylbut-1,3-diene.

Ultralow-frequency ultranarrow-bandwidth coherent terahertz imaging for nondestructive testing of mortar material.

Nondestructive testing of concrete materials is essential in civil engineering to maintain social infrastructure such as buildings or bridges. In this study, we constructed an ultralow-frequency, ultranarrow-bandwidth, coherent terahertz (THz) imaging system based on THz time-domain spectroscopy (THz-TDS). Based on its ultralow-frequency-localized THz wave and coherent detection, the present system achieved a wide dynamic range of THz power over 100 dB at 0.046 THz, which is appropriate to measure the mortar material. The achieved dynamic range of the THz power was 59 dB larger than that of a commercialized THz-TDS system and 49 dB larger than that of an ultralow-frequency noncoherent THz imaging system equipped with a high-power electric THz source. Ultimately, the proposed system could visualize the inner structure of a mortar sample with a thickness of 10 mm, and the present system can investigate a mortar sample with a thickness of over 130 mm. The proposed method is an attractive tool for non-destructive testing of thick concrete structures characterized by non-invasiveness and non-contact remoteness.

Thermal control of a Kerr microresonator soliton comb via an optical sideband.

We report the thermal control of a dissipative Kerr microresonator soliton comb via an optical sideband generated from an electro-optic modulator. Same as the previous reports using an independent auxiliary laser, our sideband-based (S-B) auxiliary light also enables access to a stable soliton comb and reduces the phase noise of the soliton comb, greatly simplifying the set-up with an auxiliary laser. More importantly, because of the intrinsically high frequency/phase correlation between the pump and S-B auxiliary light, the detuning between the pump and resonance frequency is automatically almost fixed, which allows an 18 times larger "effective" soliton existence range than the conventional method using an independent auxiliary laser, as well as a scanning of the soliton comb of more than 10 GHz without using microheaters.

Combined Computational and Experimental Study on [5 + 2] Cycloaddition of 2-Trifluoromethylated Oxidopyrylium Species Leading to 1-(Trifluoromethyl)-8-oxabicyclo[3.2.1]oct-3-en-2-ones.

Trifluoromethylation of furfural using the Ruppert-Prakash reagent (TMSCF3) and subsequent photo-Achmatowicz reaction afforded 6-hydroxy-2-(trifluoromethyl)-2H-pyran-3(6H)-one. After acetylation, the resultant 6-acetoxy-2-(trifluoromethyl)-2H-pyran-3(6H)-one was transformed into various 1-(trifluoromethyl)-8-oxabicyclo[3.2.1]oct-3-en-2-one derivatives through a base-mediated oxidopyrylium [5 + 2] cycloaddition. The reactivity and selectivity of the 2-trifluoromethylated oxidopyrylium species toward [5 + 2] cycloaddition were analyzed using density functional theory calculations.

Co-Catalyzed atom transfer radical addition of bromodifluoroacetamides, expanding the scope of radical difluoroalkylation.

The atom transfer radical addition (ATRA) of bromodifluoroacetamides to arylalkynes and terminal alkenes was conducted using von Wangelin's Co catalyst system (CoBr2/1,2-bis(diphenylphosphino)benzene/Zn) in acetone/H2O at 30 °C to afford the corresponding functionalized difluoroacetamides in 33-89% yields. Moreover, the Co catalyst was successfully applied to the tandem addition/cyclization of 1,6-diene and -enyne substrates and intramolecular ATRA of N-allyl and N-propargyl bromodifluoroacetamides, significantly expanding the scope of radical difluoroalkylation.

Assessment of Ultra-Early-Stage Liver Fibrosis in Human Non-Alcoholic Fatty Liver Disease by Second-Harmonic Generation Microscopy.

Non-alcoholic fatty liver disease (NAFLD) is associated with the chronic progression of fibrosis. In general, the progression of liver fibrosis is determined by a histopathological assessment with a collagen-stained section; however, the ultra-early stage of liver fibrosis is challenging to identify because of the low sensitivity in the collagen-selective staining method. In the present study, we demonstrate the feasibility of second-harmonic generation (SHG) microscopy in the histopathological diagnosis of the liver of NAFLD patients for the quantitative assessment of the ultra-early stage of fibrosis. We investigated four representative NAFLD patients with early stages of fibrosis. SHG microscopy visualised well-matured fibrotic structures and early fibrosis diffusely involving liver tissues, whereas early fibrosis is challenging to be identified by conventional histopathological methods. Furthermore, the SHG emission directionality analysis revealed the maturation of each collagen fibre of each patient. As a result, SHG microscopy is feasible for assessing liver fibrosis on NAFLD patients, including the ultra-early stage of liver fibrosis that is difficult to diagnose by the conventional histopathological method. The assessment method of the ultra-early fibrosis by using SHG microscopy may serve as a crucial means for pathological, clinical, and prognostic diagnosis of NAFLD patients.

Multicascade-linked synthetic-wavelength digital holography using a line-by-line spectral-shaped optical frequency comb.

Phase imaging without a phase wrapping ambiguity is required for wide-axial-range 3D imaging in the fields of surface topography measurement and biomedical imaging. Although multicascade-linked synthetic-wavelength digital holography (MCL-SW-DH) using an optical frequency synthesizer (OFS) is a promising method to meet this requirement, the slow switching of multiple optical wavelengths in the OFS prevents rapid imaging. In the work described in this article, a line-by-line spectral-shaped electro-optics-modulator-based optical frequency comb (EOM-OFC) is used as a light source in MCL-SW-DH to achieve rapid image acquisition. While MCL-SW-DH enables surface topography measurement with millimeter-order axial range and micrometer-order axial resolution, the line-by-line spectral-shaped EOM-OFC extracts a single narrow-linewidth OFC mode from the 10 GHz-spacing EOM-OFC at a center wavelength of 1545 nm within a spectral range of 30 nm at an interval of 500 ms. The effectiveness of the proposed MCL-SW-DH was highlighted by performing surface topography measurement with four step differences of sub-millimeter to millimeter size with an axial uncertainty of 2.08 µm in the image acquisition time of several seconds. The proposed MCL-SW-DH will be a powerful tool for 3D imaging with a wide axial range and high axial resolution.

Computationally image-corrected dual-comb microscopy with a free-running single-cavity dual-comb fiber laser.

Dual-comb microscopy (DCM), an interesting imaging modality based on the optical-frequency-comb (OFC) mode and image pixel one-to-one correspondence, benefits from scan-less full-field imaging and simultaneous confocal amplitude and phase imaging. However, the two fully frequency-stabilized OFC sources requirement hampers DCM practicality due to the complexity and costs. Here, a bidirectional single-cavity dual-comb fiber laser (SCDCFL) is adopted as a DCM low-complexity OFC source. Although the residual timing jitter in the SCDCFL blurs the image of a static object acquired by DCM, computational image correction significantly suppresses the image blur. Nanometer-order step surface profilometry with a 14.0 nm uncertainty highlights the computationally image-corrected DCM effectiveness. We further discuss a possibility to expand the computational image correction to a dynamic object and demonstrate its preliminary experiment. The proposed method enhances the DCM generality and practicality due to low-complexity OFC source.

Frequency-scanned microresonator soliton comb with tracking of the frequency of all comb modes.

Rapid and large scanning of a dissipative Kerr-microresonator soliton comb with characterization of all comb modes along with the separation of the comb modes is imperative for the emerging applications of frequency-scanned soliton combs. However, the scan speed is limited by the gain of feedback systems, and measurement of the frequency shift of all comb modes has not been demonstrated. To overcome the limitation of the feedback, we incorporate feedback with feedforward. With an additional gain of >40dB by a feedforward signal, a dissipative Kerr-microresonator soliton comb is scanned by 70 GHz in 500µs, 50 GHz in 125µs, and 25 GHz in 50µs (= 500 THz/s). Furthermore, we propose and demonstrate a method to measure the frequency shift of all comb modes, in which an imbalanced Mach-Zehnder interferometer with two outputs with different wavelengths is used. Because of the two degrees of freedom of optical frequency combs, the measurement at two different wavelengths enables estimation of the frequency shift of all comb modes.

Synthesis of 1-(Difluoromethyl)alk-1-enes via Palladium-Catalyzed SN2'-Type Substitution Reaction of Difluoromethylated Allylic Phosphates with 1,3-Dicarbonyl Compounds and Imides.

Herein, we report the synthesis of 1-(difluoromethyl)alkenes via a palladium-catalyzed reaction of difluoromethyl-substituted allylic phosphates with 1,3-dicarbonyl compounds using PdCl2(PPh3)2 as a precatalyst. 1,3-Dicarbonyl compounds attacked the γ-carbon with respect to the difluoromethyl group to afford their corresponding SN2'-type substitution products irrespective of the substitution pattern in the allylic phosphates. This regioselectivity has been ascribed to the electronic environment of the unsymmetrical π-allylpalladium intermediate using density functional theory (DFT) calculations. The reaction of difluoromethyl-substituted allylic phosphates with imides was also carried out using a different catalyst system composed of [PdCl(η3-allyl)]2 and di(diphenylphosphino)butane (dppb).

Synthesis of D-π-A type benzothiazole-pyridinium salt composite and its application as photo-degradation agent for amyloid fibrils.

We have synthesized a cyan fluorescent benzothiazole-pyridinium salt composite based on D-π-A architecture. This salt was found to work as not only a two- and three-photon excitable fluorophore but also a degradation agent against amyloid fibrils under LED irradiation conditions.

Hybrid optical imaging with near-infrared, mid-infrared, and terahertz wavelengths for nondestructive inspection [Invited].

Optical imaging is a powerful tool for nondestructive inspection, with high spatial resolution and low invasiveness. As light-material interactions vary a great deal depending on the wavelength, it is difficult to select the best imaging wavelength without prior knowledge of the optical properties of the material. To overcome this difficulty, we constructed a hybrid optical imaging system using three different wavelengths: near-infrared (NIR), mid-infrared (MIR), and terahertz (THz) regions. The same imaging optics were integrated with different light sources and detectors. Depending on the light-material interaction and detection sensitivity, NIR and THz imaging indicated some potential for nondestructive inspection, but MIR imaging showed difficulty. A combination of NIR and THz imaging will be a powerful tool for optical nondestructive inspection.

Investigation of the phase noise of a microresonator soliton comb.

Optical frequency combs generated from microresonators (especially microresonator soliton combs) have been attracting significant attentions because of the potential to be fully chip-scale. Among various promising applications of soliton combs, coherent optical communications and mm/THz wireless communications require low phase noise of the comb modes and low relative phase noise between the comb modes, respectively. Here, we measure the phase noise of a soliton comb, investigating how the thermorefractive noise of a microresonator influences on the phase noise. We observe the quadratic increase of the phase noise of the comb modes, as the comb mode number, counted from the wavelength of a pump cw laser, increases. In addition, we measure the relative phase noise between the comb modes, showing less influence of the phase noise of pump cw lasers by comparing soliton combs generated from pump cw lasers with low and large phase noise.

Dynamic characterization of polarization property in liquid-crystal-on-silicon spatial light modulator using dual-comb spectroscopic polarimetry.

Spectroscopic polarimetry (SP) is a powerful tool for characterization of thin film, polarization optics, semiconductor, and others. However, mechanical polarization modulation of broadband light hampers its application for dynamic monitoring of a sample. In this article, we demonstrate the dynamic SP with features of polarization-modulation-free polarimetry and spectrometer-free spectroscopy benefiting from dual-comb spectroscopy (DCS) using a pair of optical frequency combs (OFCs). DCS enables the direct determination of polarization without the need for polarization modulation by using mode-resolved OFC spectra of amplitude and phase for two orthogonally linear-polarized lights while securing rapid, high-precision, broadband spectroscopy without the need for spectrometer. Effectiveness of the proposed system is highlighted by visualizing the hysteresis property of dynamic response in a liquid-crystal-on-silicon spatial light modulator at a sampling rate of 105 Hz.

Palladium-Catalyzed [3+2] and [2+2+2] Annulations of 4-Iodo-2-quinolones with Activated Alkynes through Selective C-H Activation.

The palladium-catalyzed reaction of 4-iodo-2-quinolones with activated alkynes was investigated. Cyclopenta[de]quinoline-2(1 H)-ones and/or phenanthridine-6(5 H)-ones were obtained through [3+2] annulation involving aromatic C-H activation or [2+2+2] annulation involving vinylic C-H activation, respectively. Reasonable mechanisms for the formation of these annulation products have been proposed based on density functional theory calculations.

Two- and three-photon excitable quaternized imidazo[1,2-a]pyridines as mitochondrial imaging and potent cancer therapy agents.

We have synthesized a series of quaternized imidazo[1,2-a]pyridines in three steps from commercially available reagents. These compounds exhibit blue fluorescence emission at around 425 nm with good quantum yields. In addition, one specific compound was found to work as not only a two- and three-photon excitable mitochondria imaging agent, but also a therapeutic agent upon continuous irradiation conditions.