Self-Folded Three-Dimensional Graphene with a Tunable Shape and Conductivity.

Three-dimensional (3D) graphene architectures are of great interest as applications in flexible electronics and biointerfaces. In this study, we demonstrate the facile formation of predetermined 3D polymeric microstructures simply by transferring monolayer graphene. The graphene adheres to the surface of polymeric films via noncovalent π-π stacking bonding and induces a sloped internal strain, leading to the self-rolling of 3D microscale architectures. Micropatterns and varied thicknesses of the 2D films prior to the self-rolling allows for control over the resulting 3D geometries. The strain then present on the hexagonal unit cell of the graphene produces a nonlinear electrical conductivity across the device. The driving force behind the self-folding process arises from the reconfiguration of the molecules within the crystalline materials. We believe that this effective and versatile way of realizing a 3D graphene structure is potentially applicable to alternative 2D layered materials as well as other flexible polymeric templates.

Dopamine detection on activated reaction field consisting of graphene-integrated silicon photonic cavity.

Graphene is widely recognized as an outstanding and multi-functional material in various application fields such as electronics, photonics, mechanics, and life sciences. We propose a neurotransmitter sensor with ultra-small volume for detecting the photonic light-matter response. Such detection can be achieved using surface-activated monolayer graphene sheets and CMOS-compatible silicon-photonic circuits. Patterned pieces of CVD-grown graphene are integrated on the top of a silicon micro-ring resonator, which induce the adsorption of catecholamine molecules originated from the π-stacking effect. We used dopamine to demonstrate such detection and examine the sensitivity of graphene-dopamine coupling. To avoid high optical insertion loss and degradation of resonance characteristics caused by a graphene's extremely high optical absorption coefficient in the near infrared region, a ring resonator with adjusted coupling design is used to compensate for the drawbacks. Owing to the advanced nano-sensing platform and measurement system, an activated graphene-sensing surface of only ∼30 µm2/ch enables π coupling to dopamine with enough sensitivity to detect less than 10-µM solution concentration. The detection mechanism through the surface reaction is also verified by optical simulation and atomic force microscopy measurement, revealing that the flowing dopamine molecules can only occupy the outermost surface of graphene. We expect this sensor to contribute to the development of an innovative label-free and disposable bio-sensing platform with accurate, sensitive, and fast response.

Capturing the Freeze-Drying Dynamics of NaCl Nanoparticles Using THz Spectroscopy.

Sodium chloride (NaCl) aqueous solution becomes NaCl hydrate, NaCl·2H2O, at low temperature, which is different from potassium chloride and is a typical complex model for studying the freeze-drying process in foods and pharmaceuticals. Here, we detected unit-cell-sized NaCl particles in ice as precursor substances of NaCl·2H2O during freezing of NaCl solution by using terahertz (THz) spectroscopy. In the freezing process, Na+ and Cl- ions form two types of metastable unit-cell-sized NaCl particles on the pathway to the well-known NaCl·2H2O crystal production, which are not listed in the phase diagram of freezing of NaCl solution but have absorption peaks in THz spectra. This finding of single unit-cell-sized particles signifies the importance of studying the freeze-drying process in-depth and offers a new possibility for the development of freeze-drying technology for the manufacture of nanometer-sized particles such as ultrafine pharmaceutical powders, which more readily dissolve in water.

Chemical mapping of pharmaceutical cocrystals using terahertz spectroscopic imaging.

Terahertz (THz) spectroscopic imaging is a promising technique for distinguishing pharmaceuticals of similar molecular composition but differing crystal structures. Physicochemical properties, for instance bioavailability, are manipulated by altering a drug's crystal structure through methods such as cocrystallization. Cocrystals are molecular complexes having crystal structures different from those of their pure components. A technique for identifying the two-dimensional distribution of these alternate forms is required. Here we present the first demonstration of THz spectroscopic imaging of cocrystals. THz spectra of caffeine-oxalic acid cocrystal measured at low temperature exhibit sharp peaks, enabling us to visualize the cocrystal distribution in nonuniform tablets. The cocrystal distribution was clearly identified using THz spectroscopic data, and the cocrystal concentration was calculated with 0.3-1.3% w/w error from the known total concentration. From this result, THz spectroscopy allows quantitative chemical mapping of cocrystals and offers researchers and drug developers a new analytical tool.

Increasing the electron-transfer ability of Cyanidioschyzon merolae ferredoxin by a one-point mutation--a high resolution and Fe-SAD phasing crystal structure analysis of the Asp58Asn mutant.

Cyanidioschyzon merolae (Cm) is a single cell red algae that grows in rather thermophilic (40-50°C) and acidic (pH 1-3) conditions. Ferredoxin (Fd) was purified from this algae and characterized as a plant-type [2Fe-2S] Fd by physicochemical techniques. A high resolution (0.97Å) three-dimensional structure of the CmFd D58N mutant molecule has been determined using the Fe-SAD phasing method to clarify the precise position of the Asn58 amide, as this substitution increases the electron-transfer ability relative to wild-type CmFd by a factor of 1.5. The crystal structure reveals an electro-positive surface surrounding Asn58 that may interact with ferredoxin NADP(+) reductase or cytochrome c.

Graphene-Based FRET Aptasensors.

Graphene-based FRET aptasensors can be realized only by unique combinations of aptamer that can be freely functionalized by chemical modification, and graphene/graphene oxide that works as an excellent fluorescence acceptor at the same time as aptamer adsorbates. This review describes the principles of the sensor, several applications to microchannel devices, improvement of the sensing performance by molecular design of the aptamer and remarks on future prospects based on an introduction of recent works and achievements, including the author's paper. The sensor employs DNA modified with graphene/graphene oxide at the terminal as the molecular probe. This system is supported by the excellent property of DNA that does not lose the molecular recognition ability even due to a chemical modification at the terminal. I hope that this review will be useful for developing research on higher performance of graphene aptasensors in the future.

Complete Genome Sequences of Four Halophilic Thermus thermophilus Strains Isolated from Arima Hot Spring in Japan.

We isolated four Thermus thermophilus strains from Arima Hot Spring in Japan. Complete genome sequencing revealed that they showed average nucleotide identities of ≥99.21% to each other and to strains previously isolated from the same spot, but of ≤97.86% to strains from geographically different spots in Japan, reflecting habitat-specific genomic conservation.

Tough, permeable and biocompatible microfluidic devices formed through the buckling delamination of soft hydrogel films.

Microchannels in soft materials play an important role in developing movable, deformable, and biocompatible fluidic systems for applications in various fields. Intensively investigated approaches to create microscale channel architectures use mechanical instability in soft materials, which can provide intricate yet ordered architectures with low cost and high throughput. Here, for microchannel fabrication, we demonstrate the use of swelling-driven buckle delamination of hydrogels, which is a mechanical instability pattern found in compressed film/substrate layer composites. By spatially controlling interfacial bonding between a thin polyacrylamide (PAAm) gel film and glass substrate, swelling-driven compressive stress induces buckle delamination at programmed positions, resulting in the formation of continuous hollow paths as microchannels. Connecting flow tubes with a 3D-printed connecter provides a deformable microfluidic device, enabling pressure-driven flows without leakage from the connecter and rupture of the channels. Furthermore, by stacking less-swellable bulk gels on the device, we obtained a tough, permeable, and biocompatible microfluidic device. Finally, we performed a cell culture on the device and chemical stimulation to cells through the diffusion of molecules from the microchannels. The results of this work shed light on designing pressure sensitive/resistant microfluidic systems based on diverse hydrogels with intricate 3D morphologies and will be useful for applications in the fields of bioanalysis, biomimetics, tissue engineering, and cell biology.

Novel benzoylpiperidine-based stearoyl-CoA desaturase-1 inhibitors: Identification of 6-[4-(2-methylbenzoyl)piperidin-1-yl]pyridazine-3-carboxylic acid (2-hydroxy-2-pyridin-3-ylethyl)amide and its plasma triglyceride-lowering effects in Zucker fatty rats.

Starting from a known piperazine-based SCD-1 inhibitor, we obtained more potent benzoylpiperidine analogs. Optimization of the structure of the benzoylpiperidine-based SCD-1 inhibitors resulted in the identification of 6-[4-(2-methylbenzoyl)piperidin-1-yl]pyridazine-3-carboxylic acid (2-hydroxy-2-pyridin-3-yl-ethyl)amide (24) which showed strong inhibitory activity against both human and murine SCD-1. In addition, this compound exhibited good oral bioavailability and demonstrated plasma triglyceride lowering effects in Zucker fatty rats in a dose-dependent manner after a 7-day oral administration (qd).

Novel spiropiperidine-based stearoyl-CoA desaturase-1 inhibitors: Identification of 1'-{6-[5-(pyridin-3-ylmethyl)-1,3,4-oxadiazol-2-yl]pyridazin-3-yl}-5-(trifluoromethyl)-3,4-dihydrospiro[chromene-2,4'-piperidine].

Cyclization of the benzoylpiperidine in lead compound 2 generated a series of novel and highly potent spiropiperidine-based stearoyl-CoA desaturase (SCD)-1 inhibitors. Among them, 1'-{6-[5-(pyridin-3-ylmethyl)-1,3,4-oxadiazol-2-yl]pyridazin-3-yl}-5-(trifluoromethyl)-3,4-dihydrospiro[chromene-2,4'-piperidine] (19) demonstrated the most powerful inhibitory activity against SCD-1, not only in vitro but also in vivo (C57BL/6J mice). With regard to the pharmacological evaluation, 19 showed powerful reduction of the desaturation index in the plasma of C57BL/6J mice on a non-fat diet after a 7-day oral administration (q.d.) without causing notable abnormalities in the eyes or skin up to the highest dose (3mg/kg) in our preliminary analysis.

Novel and potent inhibitors of stearoyl-CoA desaturase-1. Part II: Identification of 4-ethylamino-3-(2-hydroxyethoxy)-N-[5-(3-trifluoromethylbenzyl)thiazol-2-yl]benzamide and its biological evaluation.

The continuing investigation of SAR studies of 3-(2-hydroxyethoxy)-N-(5-benzylthiazol-2-yl)-benzamides as stearoyl-CoA desaturase-1 (SCD-1) inhibitors is reported. Our prior hit-to-lead effort resulted in the identification of 1a as a potent and orally efficacious SCD-1 inhibitor. Further optimization of the structural motif resulted in the identification of 4-ethylamino-3-(2-hydroxyethoxy)-N-[5-(3-trifluoromethylbenzyl)thiazol-2-yl]benzamide (37c) with sub nano molar IC(50) in both murine and human SCD-1 inhibitory assays. This compound demonstrated a dose-dependent decrease in the plasma desaturation index in C57BL/6J mice on a non-fat diet after 7 days of oral administration.

Novel and potent inhibitors of stearoyl-CoA desaturase-1. Part I: Discovery of 3-(2-hydroxyethoxy)-4-methoxy-N-[5-(3-trifluoromethylbenzyl)thiazol-2-yl]benzamide.

A series of structurally novel stearoyl-CoA desaturase-1 (SCD-1) inhibitors has been identified by optimizing a hit from our corporate library. Preliminary structure-activity relationship (SAR) studies led to the discovery of the highly potent and orally bioavailable thiazole-based SCD-1 inhibitor, 3-(2-hydroxyethoxy)-4-methoxy-N-[5-(3-trifluoromethylbenzyl)thiazol-2-yl]benzamide (23a).

Chirality emergence in thin solid films of amino acids by polarized light from synchrotron radiation and free electron laser.

One of the most attractive hypothesis for the origin of homochirality in terrestrial bioorganic compounds is that a kind of "chiral impulse" as an asymmetric excitation source induced asymmetric reactions on the surfaces of such materials such as meteorites or interstellar dusts prior to the existence of terrestrial life (Cosmic Scenario). To experimentally introduce chiral structure into racemic films of amino acids (alanine, phenylalanine, isovaline, etc.), we irradiated them with linearly polarized light (LPL) from synchrotron radiation and circularly polarized light (CPL) from a free electron laser. After the irradiation, we evaluated optical anisotropy by measuring the circular dichroism (CD) spectra and verified that new Cotton peaks appeared at almost the same peak position as those of the corresponding non-racemic amino acid films. With LPL irradiation, two-dimensional anisotropic structure expressed as linear dichroism and/or linear birefringence was introduced into the racemic films. With CPL irradiation, the signs of the Cotton peaks exhibit symmetrical structure corresponding to the direction of CPL rotation. This indicates that some kinds of chiral structure were introduced into the racemic film. The CD spectra after CPL irradiation suggest the chiral structure should be derived from not only preferential photolysis but also from photolysis-induced molecular structural change. These results suggest that circularly polarized light sources in space could be associated with the origin of terrestrial homochirality; that is, they would be effective asymmetric exciting sources introducing chiral structures into bio-organic molecules or complex organic compounds.

Dynamic Creation of 3D Hydrogel Architectures via Selective Swelling Programmed by Interfacial Bonding.

The topological features of material surfaces are crucial to the emergence of functions based on characteristic architectures. Among them, the combination of surface architectures and soft materials, which are highly deformable and flexible, has great potential as regards developing functional materials toward providing/enhancing advanced functions such as switchability and variability. Therefore, a simple yet versatile method for creating three-dimensional (3D) architectures based on soft materials is strongly required. In this study, hydrogels are selected as the soft materials and hydrogel film/rigid substrate layer composites are fabricated to obtain a 3D hydrogel architecture based on swelling instability. When a hydrogel film weakly attached to a rigid substrate is exposed to water, swelling-driven compressive stress induces buckle-delamination of the film from the substrate. Utilizing the chemical modification of a rigid substrate and a conventional photolithography technique, the delamination location is successfully controlled, resulting in a high-aspect-ratio folding architecture at an arbitrary position. In addition, we systematically designed the delamination geometry and chemically tuned the swelling ratio of the hydrogel, leading to the discovery of several new morphology transitions and relationships between the morphologies and the controllable parameters. This work provides a new approach to fabricating highly programmable 3D architectures of soft materials.

Graphene-based neuron encapsulation with controlled axonal outgrowth.

Neuronal constructs with tuneable 3D geometry can contribute greatly to the construction of brain-like functional tissues for transplantable grafts and robust experimental models. In this study, we propose a self-folding graphene/polymer bilayer film that forms a micro-roll for neuron encapsulation, and highlight the importance of employing pores on the micro-roll to allow neurons to interact with their surroundings. The micro-patterns and varied thicknesses of the bilayer provide control over the 3D geometries of the micro-roll. The pores facilitate the diffusion of reagents, resulting in the adequate loading of probes for imaging and the successful stimulation of the encapsulated neurons. Moreover, the encapsulated neurons inside the micro-roll are functionally integrated into surrounding neuronal networks by extending their axons through the pores. Thus, our method for encapsulating neurons with a porous graphene-laden film allows the construction of precisely shaped neuronal tissues that interact with their surroundings. We believe that the method will open a new avenue for the reconstruction of functional neuronal tissues and is potentially applicable to other self-folding bilayers.

Analytical terahertz spectroscopy.

Recent progress in analytical terahertz (THz) spectroscopy is reviewed with illustrative examples showing that it is an effective method for detecting and identifying intermolecular interactions in chemical compounds, such as hydrogen bonds. The unique and characteristic properties of THz waves, their significance to both science and industry, and the bases of one of the successful fields of analytical THz spectroscopy, namely THz time-domain spectroscopy and THz imaging for chemical analysis, are described. Preliminary quantitative studies are presented to show the potential of THz spectroscopy for the detection and identification of intermolecular hydrogen bonds in unknown mixture samples. The selective detection of intramolecular hydrogen bonds and the detection of intramolecular interactions in ice are also introduced. Some brief remarks are provided on future developments, the main issues, and the prospects for analytical THz spectroscopy.

Terahertz time-domain spectra of aromatic carboxylic acids incorporated in nano-sized pores of mesoporous silicate.

Terahertz time-domain spectroscopy (THz-TDS) is used to study the intra- and intermolecular vibrational modes of aromatic carboxylic acids, for example, o-phthalic acid, benzoic acid, and salicylic acid, which form either intra- or intermolecular hydrogen bond(s) in different ways. Incorporating the target molecules in nano-sized spaces in mesoporous silicate (SBA-16) is found to be effective for the separate detection of intramolecular hydrogen bonding modes and intermolecular modes. The results are supported by an analysis of the differences in the peak shifts, which depend on temperature, caused by the different nature of the THz absorption. Raman spectra revealed that incorporating the molecules in the nano-sized pores of SBA-16 slightly changes the molecular structures. In the future, THz-TDS using nanoporous materials will be used to analyze the intra- and intermolecular vibrational modes of molecules with larger hydrogen bonding networks such as proteins or DNA.

Detecting a sodium chloride ion pair in ice using terahertz time-domain spectroscopy.

The hydrogen bond resonance of a sodium chloride (NaCl) ion pair trapped in aqueous ice has been observed by transmission terahertz time-domain spectroscopy. The absorption peak of a sodium chloride ion pair in ice is 1.65 THz at 83 K. By investigating the interaction of the cation and anion with other chemical compounds, we deduce that the absorption peak originates from the hydrogen bond resonance of sodium chloride and water molecules. The charge redistribution that occurs when other ion pairs are added to aqueous salt solution changes the absorption spectrum. Furthermore, the results also indicate that simple molecules such as sodium halides have fingerprints in the terahertz region when the ions are trapped in ice. NaCl ion pairs in seawater and in Ringer's solution were examined.

Overexpression of LAMP3/TSC403/DC-LAMP promotes metastasis in uterine cervical cancer.

LAMP3 (DC-LAMP, TSC403, CD208) was originally isolated as a gene specifically expressed in lung tissues. LAMP3 is located on a chromosome 3q segment that is frequently amplified in some human cancers, including uterine cervical cancer. Because two other members of the LAMP family of lysosomal membrane glycoproteins, LAMP1 and LAMP2, were previously implicated in potentially modulating the interaction of vascular endothelial and cancer cells, we hypothesized that LAMP3 might also play an important part in metastasis. To clarify the metastatic potential of LAMP3 in cervical cancers, we transfected a LAMP3 expression vector into a human uterine cervical cancer cell line, TCS. In an in vitro invasion assay, the migration of LAMP3-overexpressing TCS cells was significantly higher than in control TCS cells. In an in vivo metastasis assay, distant metastasis was detected in 9 of 11 LAMP3-overexpressing TCS cell-injected mice and in only 1 of 11 control mice. Histologic study showed that LAMP3-overexpressing cells readily invaded into the lymph-vascular space. In clinical samples, quantitative real-time reverse transcription-PCR (RT-PCR) analyses showed that LAMP3 mRNA was significantly up-regulated in 47 of 47 (100%) cervical cancers and in 2 of 15 (13%) cervical intraepithelial neoplasias, compared with a low level of LAMP3 mRNA expressed in normal uterine cervixes. Interestingly, high LAMP3 expression was significantly correlated with the overall survival of patients with stage I/II cervical cancers. These findings indicate that LAMP3 overexpression is associated with an enhanced metastatic potential and may be a prognostic factor for cervical cancer.

Self-propelled ion gel at air-water interface.

We report on a self-propelled gel using ionic liquid as a new type of self-propellant that generates a powerful and durable motion at an air-water interface. The gel is composed of 1-ethyl-3-methylimidazolium-bis(trifluoromethylsulfonyl)imide (EMIM-TFSI) and poly(vinylidene fluoride-co-hexafluoropropylene) (P(VDF-co-HFP)). A long rectangular ion gel piece placed on the interface shows rapid rotation motion with maximum frequency close to 10 Hz, corresponding to the velocity over 300 mms-1 at an outmost end of the piece. The rotation continues for ca. 102 s, followed by a reciprocating motion (<~103 s) and a nonlinear motion in long-time observations (>~103 s). The behaviours can be explained by the model considering elution of EMIM-TFSI to the air-water interface, rapid dissolution into water, and slow diffusion in an inhomogeneous polymer gel network. Because the self-propellants are promptly removed from the interface by dissolution, durable self-propelled motions are observed also at limited interface areas close in size to the gel pieces. A variety of motions are induced in such systems where the degree of freedom in motion is limited. As the ion gel possesses formability and processability, it is also advantageous for practical applications. We demonstrate that the gel does work as an engine.