Discovery of a potent glucokinase activator with a favorable liver and pancreas distribution pattern for the treatment of type 2 diabetes mellitus.

Glucokinase (GK) is an enzyme that plays an important role as a glucose sensor while maintaining whole body glucose homeostasis. Allosteric activators of GK (GKAs) have the potential to treat type 2 diabetes mellitus. To identify novel GKAs, a series of compounds based on a thiophenyl-pyrrolidine scaffold were designed and synthesized. In this series, compound 38 was found to inhibit glucose excursion in an oral glucose tolerance test (OGTT) in mice. Optimization of 38 using a zwitterion approach led to the identification of the novel GKA 59. GKA 59 exhibited potent blood glucose control in the OGTT test as well as a favorable safety profile. Owing to low pancreatic distribution, compound 59 primarily activates GK in the liver. This characteristic could overcome limitations of other GKAs, such as hypoglycemia, increased plasma triglycerides, and loss of efficacy.

Quantum key distribution over 120 km using ultrahigh purity single-photon source and superconducting single-photon detectors.

Advances in single-photon sources (SPSs) and single-photon detectors (SPDs) promise unique applications in the field of quantum information technology. In this paper, we report long-distance quantum key distribution (QKD) by using state-of-the-art devices: a quantum-dot SPS (QD SPS) emitting a photon in the telecom band of 1.5 µm and a superconducting nanowire SPD (SNSPD). At the distance of 100 km, we obtained the maximal secure key rate of 27.6 bps without using decoy states, which is at least threefold larger than the rate obtained in the previously reported 50-km-long QKD experiment. We also succeeded in transmitting secure keys at the rate of 0.307 bps over 120 km. This is the longest QKD distance yet reported by using known true SPSs. The ultralow multiphoton emissions of our SPS and ultralow dark count of the SNSPD contributed to this result. The experimental results demonstrate the potential applicability of QD SPSs to practical telecom QKD networks.

High quality-factor Si/SiO(2)-InP hybrid micropillar cavities with submicrometer diameter for 1.55-µm telecommunication band.

We theoretically demonstrate high quality(Q)-factor micropillar cavities at 1.55-µm wavelength based on Si/SiO(2)-InP hybrid structure. An adiabatic design in distributed Bragg reflectors (DBRs) improves Q-factor for upto 3 orders of magnitude, while reducing the diameter to sub-micrometer. A moderate Q-factor of ~3000 and a Purcell factor of ~200 are realized by only 2 taper segments and fewer conventional DBR pairs, enabling single photon generation at GHz rate. As the taper segment number is increased, Q-factor can be boosted to ~10(5)-10(6), enabling coherent exchange between the emitter and the optical mode at 1.55 µm, which is applicable in quantum information networks.

Design of Si/SiO2 micropillar cavities for Purcell-enhanced single photon emission at 1.55 µm from InAs/InP quantum dots.

Numerical simulations were carried out on micropillar cavities consisting of Si/SiO2 distributed Bragg reflectors (DBRs) with an InP spacer layer. Owing to a large refractive index contrast of ~2 in DBRs, cavities with just 4/6.5 top/bottom DBR pairs that give a low pillar height (~4.5 µm), have noticeable Purcell-enhancement effect in the 1.55-µm band. With careful designs on cavities with diameters of ~2.30 µm, a quality factor of up to 3300, a nominal Purcell factor of up to 110, and an output efficiency of ~60% are obtainable. These results ensure improvement of operation frequency and enhancement of photon indistinguishability for 1.55-µm single photon sources based on InAs/InP quantum dots.

Synthesis and pharmacological profile of a new selective G protein-coupled receptor 119 agonist; 6-((2-fluoro-3-(1-(3-isopropyl-1,2,4-oxadiazol-5-yl)piperidin-4-yl)propyl)amino)-2,3-dihydro-1H-inden-1-one.

6-((2-Fluoro-3-(1-(3-isopropyl-1,2,4-oxadiazol-5-yl)piperidin-4-yl)propyl)amino)-2,3-dihydro-1H-inden-1-one is a potent drug-like G protein-coupled receptor 119 (GPR119) agonist. It is hoped that this compound would be instrumental in probing the pharmacological potential of GPR119 agonists.

Synthesis and SAR studies of bicyclic amine series GPR119 agonists.

We disclosed a novel series of G-protein coupled receptor 119 (GPR119) agonists based on a bicyclic amine scaffold. Through the optimization of hit compound 1, we discovered that the basic nitrogen atom of bicyclic amine played an important role in GPR119 agonist activity expression and that an indanone in various bicyclic rings was suitable in this series of compounds. The indanone derivative 2 showed the effect of plasma glucose control in oGTT and scGTT in the rodent model.

Fabrication of a tubular FeCo bimetallic nanostructure using a cellulose-cobalt hexacyanoferrate composite as a precursor.

A tubular fibre structure with a ca. 9-11 microm outer diameter comprised of FeCo nanoparticle assemblies with an amorphous carbon core was fabricated via reductive thermal decomposition of a cellulose-cobalt hexacyanoferrate (Fe-CN-Co) composite material.

Aldehyde dehydrogenase inhibitors from the mushroom Clitocybe clavipes.

Five fatty acid derivatives including three novel compounds were isolated from the mushroom Clitocybe clavipe. Their structures were elucidated by spectral analyses. These compounds inhibited aldehyde dehydrogenase in vitro.