A Novel LRRK2 Variant p.G2294R in the WD40 Domain Identified in Familial Parkinson’s Disease Affects LRRK2 Protein Levels

Leucine-rich repeat kinase 2 (LRRK2) is a major causative gene of late-onset familial Parkinson’s disease (PD). The suppression of kinase activity is believed to confer neuroprotection, as most pathogenic variants of LRRK2 associated with PD exhibit increased kinase activity. We herein report a novel LRRK2 variant—p.G2294R—located in the WD40 domain, detected through targeted gene-panel screening in a patient with familial PD. The proband showed late-onset Parkinsonism with dysautonomia and a good response to levodopa, without cognitive decline or psychosis. Cultured cell experiments revealed that p.G2294R is highly destabilized at the protein level. The LRRK2 p.G2294R protein expression was upregulated in the patient’s peripheral blood lymphocytes. However, macrophages differentiated from the same peripheral blood showed decreased LRRK2 protein levels. Moreover, our experiment indicated reduced phagocytic activity in the pathogenic yeasts and α-synuclein fibrils. This PD case presents an example wherein the decrease in LRRK2 activity did not act in a neuroprotective manner. Further investigations are needed in order to elucidate the relationship between LRRK2 expression in the central nervous system and the pathogenesis caused by altered LRRK2 activity.     

Hydrogen production through dry reforming of biogas using a porous electrochemical cell: Effects of a cobalt catalyst in the electrode and mixing of air with biogas

This paper reports the performance of porous Gd-doped ceria (GDC) electrochemical cells with Co metal in both electrodes (cell No. 1) and with Ni metal in the cathode and Co metal in the anode (cell No. 2) for CO₂ decomposition, CH₄ decomposition, and the dry reforming reaction of a biogas with CO₂ gas (CH₄ + CO₂ → 2H₂ + 2CO) or with O₂ gas in air (3CH₄ +?1.875CO₂ +?1.314O₂ → 6H₂ +?4.875CO +?0.7515O₂). GDC cell No. 1 produced H₂ gas at formation rates of 0.055 and 0.33?mL-H₂/(min?m²-electrode) per 1?mL-supplied gas/(min?m²-electrode) at 600?°C and 800?°C, respectively, by the reforming of the biogas with CO₂ gas. Similarly, cell No. 2 produced H₂ gas at formation rates of 0.40?mL-H₂/(min?m²) per 1?mL-supplied gas/(min?m²) at 800?°C from a mixture of biogas and CO₂ gas. The dry reforming of a real biogas with CO₂ or O₂ gas at 800?°C proceeded thermodynamically over the Co or Ni metal catalyst in the cathode of the porous GDC cell. Faraday's law controlled the dry reforming rate of the biogas at 600?°C in cell No. 2. This paper also clarifies the influence of carbon deposition, which originates from CH₄ pyrolysis (CH₄ → C + 2H₂) and disproportionation of CO gas (2CO → C + CO₂), on the cell performance during dry reforming. The dry reforming of a biogas with O₂ molecules from air exhibits high durability because of the oxidation of the deposited carbon by supplied air.     

Elastic, anelastic, and piezoelectric coefficients of langasite: resonance ultrasound spectroscopy with laser-Doppler interferometry

This paper presents advanced techniques to determine all independent elastic-stiffness coefficients C/sub ij/, the associated internal friction Q/sub ij//sup -1/, and piezoelectric coefficients e/sub ij/ of monocrystal langasite (La/sub 3/Ga/sub 5/SiO/sub 14/) using a single rectangular parallelepiped specimen. Langasite's crystal structure belongs to the trigonal system with point group 32, and thus possesses six independent C/sub ij/, two e/sub ij/, and two dielectric coefficients /spl epsiv//sub ij/. All of the elastic and piezoelectric coefficients affect the mechanical resonance frequencies of the solid specimen, and measuring them very accurately permits one to determine the C/sub ij/ and e/sub ij/ with known density, dimensions, and e/sub ij/. We developed a piezoelectric tripod to support the specimen upward and measured the free-vibration resonance frequencies with minimum load from its own weight. This weak and stable acoustic coupling ensures accuracy of the frequency measurement better than 10/sup -5/, enough to determine the coefficients reliably. Our C/sub ij/ fall in the range of results measured with previous (conventional) methods. Our e/sub 11/ is smaller than the reported values by 1.2-13%, and e/sub 14/ is larger by 44-97%. For the internal friction measurement, we used a solenoid coil to vibrate the specimen without any contact. The longitudinal-wave internal friction considerably exceeds the shear-wave internal friction, which can be explained by phonon-phonon interactions.     

Microstructure Control of Thermally Sprayed Co-Based Self-Fluxing Alloy Coatings by Diffusion Treatment

This article describes microstructure control aimed for wear-resistance improvement of Co-based (Co-Cr-W-B-Si) self-fluxing alloy coating by diffusion treatment. The diffusion treatments of thermally sprayed Co-based self-fluxing alloy coating on steel substrate were carried out at 1370-1450 K for 600-6000 s under an Ar gas atmosphere. Microstructural variations of the coating and the interface between the substrate and the coating were investigated in detail. A proper diffusion treatment precipitates two kinds of fine compounds in Co-based matrix. X-ray diffractometer (XRD) and electron probe microanalyzer (EPMA) analysis revealed these precipitates to be a chromium boride dissolving cobalt and a tungsten boride containing cobalt and chromium. The size of each precipitate became larger with increasing treatment temperature and time. A coating with the proper size borides showed a superior wear-resistance. This article is an invited paper selected from presentations at the 2007 International Thermal Spray Conference and has been expanded from the original presentation. It is simultaneously published in Global Coating Solutions, Proceedings of the 2007 International Thermal Spray Conference, Beijing, China, May 14-16, 2007, Basil R. Marple, Margaret M. Hyland, Yuk-Chiu Lau, Chang-Jiu Li, Rogerio S. Lima, and Ghislain Montavon, Ed., ASM International, Materials Park, OH, 2007.     

Quantitative imaging of Young's modulus of solids: a contact-mechanics study

We developed equipment and methods for measuring quantitatively the local Young's modulus of solids. It consists of an electrodeless langasite oscillator and line antennas, and oscillator vibrations are generated and detected contactlessly. A constant biasing force results from oscillator mass and is independent of surface roughness. The effect of material anisotropy on the measured stiffness is theoretically discussed for studying the limitation of the quantitative measurement. The microscopy has been applied to polycrystalline copper, and the measured modulus is compared to calculations based on electron-backscatter-diffraction measurements. Also, we applied it to a duplex stainless steel and an embedded silicon-carbide fiber. The results reveal textured regions, defects with high sensitivity, and even stiffness distribution in a single grain.     

Gradient-index rod lens with a high acceptance angle for color use by Na(+) for Li(+) exchange

The relationship between the characteristics of gradient-index rod lenses obtained by ion exchange and their mother glass compositions is studied. It is observed that Li(2)O content, R(2)O (Li(2)O + Na(2)O) content, and the Li(2)O/Na(2)O ratio are important factors in attaining a high acceptance angle and a small field curvature. Thus the gradient-index lens array is fabricated by the use of a newly developed glass composition and its optical performance; the modulation transfer function, luminous intensity, and chromatic aberration are precisely evaluated. The array is found to have a sufficiently high performance to be applicable for color use.     

Synthesis of thermoresponsive block and graft copolymers via the combination of living cationic polymerization and RAFT polymerization using a vinyl ether-type RAFT agent

A novel vinyl ether-type RAFT agent, benzyl 2-(vinyloxy)ethyl carbonotrithioate (BVCT) was synthesized for various block copolymers via the combination of living cationic polymerization of vinyl ethers and reversible addition−fragmentation chain transfer (RAFT) polymerization. The novel BVCT–trifluoroacetic acid adduct play an important role to produce well-defined block copolymers, which is both as a cationogen under EtAlCl₂ initiation system in the presence of ethyl acetate for living cationic polymerization and a RAFT agent for blocks by RAFT polymerization. The resulting polymer, poly(vinyl ether)s, by living cationic polymerization had a high number average α-end functionality (≥0.9) as determined by both ¹H NMR and MALDI-TOF-MS spectrometry. In addition, this poly(vinyl ether)s worked well as a macromolecular chain transfer agent for RAFT polymerization. The RAFT polymerization of radically polymerizable monomers was conducted in toluene using 2,2′-azobis(isobutyronitrile) at 70 °C. For example, a double thermoresponsive block copolymer (MOVE₆₁-b-NIPAM₁₅₀) consisting of 2-methoxyethyl vinyl ether (MOVE) and N-isopropylacrylamide (NIPAM) was prepared via the combination of living cationic polymerization and RAFT polymerization. The block copolymer reversibly formed and deformed micellar assemblies above the phase separation temperature (T_ps) of poly(NIPAM) block in water. This BVCT is not only functioned as an initiator, but also acted as a monomer. When BVCT was copolymerized with MOVE by living cationic polymerization, followed by graft copolymerization with NIPAM via RAFT polymerization, well-defined graft copolymers (MOVE_n-co-BVCT_m)-g-NIPAM_x (n = 62–73, m = 1–9, x = 19–214) were successfully obtained. However, no micelle formed in water above T_ps of poly(NIPAM) graft chain unlike the case of block copolymers.     

Morphology‐dependent electrocatalytic activity of nanostructured Pt/C particles from hybrid aerosol–colloid process

An optimum nanostructure and pore size of catalyst supports is very important in achieving high catalytic performances. In this instance, we evaluated the effects of various carbon nanostructures on the catalytic performances of carbon‐supported platinum (Pt/C) electrocatalysts experimentally and numerically. The Pt/C catalysts were prepared using a hybrid method involving the preparation of dense, hollow, and porous nanostructured carbon particle via aerosol spray pyrolysis followed by microwave‐assisted Pt deposition. Electrochemical characterization of the catalysts showed that the porous Pt/C catalyst gave the best performance; its electrochemical surface area was much higher, more than twice than those of hollow or dense Pt/C. The effects of pore size on electrocatalysis were also studied. The results showed the importance of a balance between mesopores and macropores for effective catalysis with a high charge transfer rate. A fluid flow model showed that good oxygen transport contributed to the catalytic activity. © 2015 American Institute of Chemical Engineers AIChE J, 62: 440–450, 2016