Synthesis and Initial Characterization of a Selective,Pseudo-irreversible Inhibitor of Human Butyrylcholinesterase as PET Tracer

The enzyme butyrylcholinesterase (BChE) represents a promising target for imaging probes to potentially enable early diagnosis of neurodegenerative diseases like Alzheimer's disease (AD) and to monitor disease progression in some forms of cancer. In this study, we present the design, facile synthesis, in vitro and preliminary ex vivo and in vivo evaluation of a morpholine-based, selective inhibitor of human BChE as a positron emission tomography (PET) tracer with a pseudo-irreversible binding mode. We demonstrate a novel protecting group strategy for ¹⁸F radiolabeling of carbamate precursors and show that the inhibitory potency as well as kinetic properties of our unlabeled reference compound were retained in comparison to the parent compound. In particular, the prolonged duration of enzyme inhibition of such a morpholinocarbamate motivated us to design a PET tracer, possibly enabling a precise mapping of BChE distribution.     

Identification of factors that accelerate hydrogen production by Clostridium butyricum RAK25832 using casamino acids as a nitrogen source

The ability of Clostridium butyricum RAK25832 to use casamino acids as a nitrogen source was investigated. Strain RAK25832 showed the capacity to utilize different types of carbon sources. With glucose as a carbon source (10 g/L), the preferred final concentration of casamino acids was 26.67 g/L, with a cumulative hydrogen production, production rate, and yield of 2505 mL H₂/L, 160 mL/h, and 1.81 mol H₂/mol glucose, respectively. Eighteen metal elements were screened to identify the most important metals for biohydrogen production, and four elements were optimized. The optimal medium composition was MgCl₂·6H₂O (0.1 g/L), K₂HPO₄·3H₂O (6.67 g/L), NaHCO₃ (2.6 g/L), and FeCl₂·4H₂O (0.002 g/L). Vitamin supplementation of the medium showed no significant effect on hydrogen production. Under the optimized conditions, cumulative hydrogen production reached 3074 mL H₂/L. This is the first study to demonstrate the use of casamino acids as a nitrogen source by C. butyricum.     

External stimulus-responsive biomaterials designed for the culture and differentiation of ES,iPS, and adult stem cells

The physical and chemical characteristics of biomaterial surface and hydrogels can be altered by external stimuli, such as light irradiation, temperature changes, pH shifts, shear stress forces, electrical forces, and the addition of small chemical molecules. Such external stimulus-responsive biomaterials represent promising candidates that have been developed for the culture and differentiation of embryonic stem (ES) cells, induced pluripotent stem (iPS) cells, and adult stem cells. Biomaterials that are designed to respond in a reversible manner to specific external signals can be formed on micropatterned or non-micropatterned surface, in hydrogels, or on microcarriers. Stem cells and the cells differentiated from them into specific tissue lineages can be cultured and/or differentiated on dishes with immobilized external stimulus-responsive polymers. Cells can be detached from these dishes without using an enzymatic digestion method or a mechanical method when the appropriate external stimulus is generated on the surface. This review discusses the polymers and polymeric designs employed to produce surface and hydrogels for stem cell culture, differentiation, and/or cell detachment using various external stimuli.     

Molecular Mechanisms for the Regulation of Insulin-Stimulated Glucose Uptake by Small Guanosine Triphosphatases in Skeletal Muscle and Adipocytes

Insulin is a hormone that regulates the blood glucose level by stimulating various physiological responses in its target tissues. In skeletal muscle and adipose tissue, insulin promotes membrane trafficking of the glucose transporter GLUT4 from GLUT4 storage vesicles to the plasma membrane, thereby facilitating the uptake of glucose from the circulation. Detailed mechanisms underlying insulin-dependent intracellular signal transduction for glucose uptake remain largely unknown. In this article, I give an overview on the recently identified signaling network involving Rab, Ras, and Rho family small guanosine triphosphatases (GTPases) that regulates glucose uptake in insulin-responsive tissues. In particular, the regulatory mechanisms for these small GTPases and the cross-talk between protein kinase and small GTPase cascades are highlighted.     

Improving the photovoltaic performance of co‐evaporated Cu2ZnSnS4 thin‐film solar cells by incorporation of sodium from NaF layers

We have investigated the influence of sodium (Na) on the properties of co‐evaporated Cu₂ZnSnS₄ (CZTS) layer microstructures and solar cells. The photovoltaic performance and diode properties were improved by incorporating Na from NaF layers into the CZTS layers, while Na had a negligible effect on the microstructural properties of the layer. The best cell fabricated by using an optimal CZTS layer (Cu/(Zn + Sn) = 0.70, Zn/Sn = 1.8) yielded an active area efficiency of 5.23%. The analysis of device properties suggests that charge‐carrier recombination at CZTS/CdS interface is suppressed by intentional Na incorporation from NaF layers. Copyright © 2016 John Wiley & Sons, Ltd.     

Research and Development of the Coprecipitation Process for Lanthanum Germanate Oxyapatite

Although lanthanum germanate oxyapatite (La–Ge–O) has shown good potential for use as a solid electrolyte in energy storage applications, its synthesis has been challenging by either solid‐ or solution‐state methods. In this study, a new synthesis of La–Ge–O was developed through a coprecipitation technique, in which a highly concentrated homogeneous aqueous solution of La and Ge was prepared from aqueous ammonium germanate and lanthanum nitrate solutions with the addition of dilute nitric acid. Several precipitates were formed by pH manipulation, including an amorphous material obtained at pH > 3. Compared to the individual precipitation behaviors of the parent compounds, the amorphous precipitate was formed only from the aqueous two‐component mixture, and appeared to contain both metals. This material was transformed into crystalline mixtures upon heating at 1273 K. The crystalline phases were La₂Ge₃O₉ and hexagonal‐type GeO₂ when the precipitate was formed below pH 8, and the La–Ge–O and La₂Ge₂O₇ phases when the precipitate was formed around pH 8. Product formation from the coprecipitate was discussed based on X‐ray diffraction and thermal analyses. The improved availability of La–Ge–O will allow more extensive investigations of its useful properties.     

Structurally Diverse Polyamines: Solid‐Phase Synthesis and Interaction with DNA

A versatile solid‐phase approach based on peptide chemistry was used to construct four classes of structurally diverse polyamines with modified backbones: linear, partially constrained, branched, and cyclic. Their effects on DNA duplex stability and structure were examined. The polyamines showed distinct activities, thus highlighting the importance of polyamine backbone structure. Interestingly, the rank order of polyamine ability for DNA compaction was different to that for their effects on circular dichroism and melting temperature, thus indicating that these polyamines have distinct effects on secondary and higher‐order structures of DNA.     

Current Control Method of Achieving Wide‐Range Power Driving for Linear Synchronous Motor with Half‐Wave‐Rectified Self‐Excitation

In a previous paper, we proposed a novel linear synchronous motor with half‐wave‐rectified self‐excitation. A long‐stator‐type linear synchronous motor was built and its performance was verified by experiments. This paper presents a new current control method for the linear synchronous motor in order to achieve a wide range of speeds and high‐power operations. First, we propose a current control method for high‐thrust operation in the constant‐thrust region. This operation is realized by using the reluctance thrust resulting from the saliency of the linear synchronous motor. We also propose a control method that maximizes the ratio of the thrust to the voltage; this method can be used to expand the operating range. Wide‐range‐speed operation can be achieved by applying this new control method along with field‐weakening control. The thrust and operating characteristics of the proposed control methods are estimated by performing experiments and coupled electric and magnetic analysis.     

Catalytic cycle of cytochrome-c3 hydrogenase,a [NiFe]-enzyme,deduced from the structures of the enzyme and the enzyme mimic

Hydrogenases catalyze uptake and production of H₂. Heterolytic cleavage of H₂ bound on [NiFe]-hydrogenase (E) produces two unequal H species to form E:H_aH_b, where H_a and H_b behave differently. The structures of various states of the enzyme established by crystallography and spectroscopy were used to construct a catalytic cycle of the enzyme. The Ni–Fe center of the active enzyme has the Ni–Fe bridging site vacant. The enzyme is suggested to bind H₂ either at Ni or Fe atom. In E:H_aH_b, H_a is considered to be a protein-bound hydron (proton or deuteron) at the entrance to the hydrophobic gas tunnel. The structure of a synthetic hydrogenase-mimic suggests H_b to be the 6th ligand to Fe. Two successive one-electron processes from E:H_aH_b complete the catalytic cycle of H₂ uptake. The reverse of the cycle operates in the H₂ production. The proposed catalytic cycle is consistent with the kinetic, crystallographic and spectroscopic studies.