Genetic modifiers of Huntington disease differentially influence motor and cognitive domains.

Genome-wide association studies (GWASs) of Huntington disease (HD) have identified six DNA maintenance gene loci (among others) as modifiers and implicated a two step-mechanism of pathogenesis: somatic instability of the causative HTT CAG repeat with subsequent triggering of neuronal damage. The largest studies have been limited to HD individuals with a rater-estimated age at motor onset. To capitalize on the wealth of phenotypic data in several large HD natural history studies, we have performed algorithmic prediction by using common motor and cognitive measures to predict age at other disease landmarks as additional phenotypes for GWASs. Combined with imputation with the Trans-Omics for Precision Medicine reference panel, predictions using integrated measures provided objective landmark phenotypes with greater power to detect most modifier loci. Importantly, substantial differences in the relative modifier signal across loci, highlighted by comparing common modifiers at MSH3 and FAN1, revealed that individual modifier effects can act preferentially in the motor or cognitive domains. Individual components of the DNA maintenance modifier mechanisms may therefore act differentially on the neuronal circuits underlying the corresponding clinical measures. In addition, we identified additional modifier effects at the PMS1 and PMS2 loci and implicated a potential second locus on chromosome 7. These findings indicate that broadened discovery and characterization of HD genetic modifiers based on additional quantitative or qualitative phenotypes offers not only the promise of in-human validated therapeutic targets but also a route to dissecting the mechanisms and cell types involved in both the somatic instability and toxicity components of HD pathogenesis.

Evaluating the performance of a turbulent wet scrubber for scrubbing particulate matter.

UNLABELLED: A turbulent wet scrubber was designed and developed to scrub particulate matter (PM) at micrometer and submicrometer levels from the effluent gas stream of an industrial coal furnace. Experiments were conducted to estimate the particle removal efficiency of the turbulent scrubber with different gas flow rates and liquid heads above the nozzle. Particles larger than 1 microm were removed very efficiently, at nearly 100%, depending upon the flow rate, the concentration of the dust-laden air stream, and the water level in the reservoir Particles smaller than 1 microm were also removed to a greater extent at higher gas flow rates and for greater liquid heads. Pressure-drop studies were also carried out to estimate the energy consumed by the scrubber for the entire range of particle sizes distributed in the carrier gas. A maximum pressure drop of 217 mm H2O was observed for a liquid head of 36 cm and a gas flow rate of 7 m3/min. The number of transfer units (NTU) analysis for the efficiencies achieved by the turbulent scrubber over the range of particles also reveals that the contacting power achieved by the scrubber is better except for smaller particles. The turbulent scrubber is more competent for scrubbing particulate matter, in particular PM2.5, than other higher energy or conventional scrubbers, and is comparable to other wet scrubbers of its kind for the amount of energy spent. IMPLICATIONS: The evaluation of the turbulent scrubber is done to add a novel scrubber in the list of wet scrubbers for industrial applications, yet simple in design, easy to operate, with better compactness, and with high efficiencies at lower energy consumption. Hence the turbulent scrubber can be used to combat particulate from industrial gaseous effluents and also has a scope to absorb gaseous pollutants if the gases are soluble in the medium used for particles capture.

Lattice Distortion, Amorphization and Wear Resistance of Carbon-Doped SUS304 by Laser Ablation.

Lattice distortion and amorphization of carbon-doped SUS304 by variation of the laser output were investigated in terms of phase formation and the bonding state. The laser output was changed by 10% in the range of 60% to 100% after covering the SUS304 with carbon paste. A graphite peak and expanded austenite (S-phase) peak were observed in the carbon-doped SUS304, and Rietveld refinement was performed to identify the lattice distortion. The lattice constant of SUS304 was initially 3.612 Å, but expansion lattice distortion occurred in the carbon-doped SUS304 as a result of the S phase formation and carbon doping, and the lattice constant increased to 3.964 Å (100% laser output). X-ray photoelectron spectroscopy analysis for the bonding state of the carbon-doped SUS304 showed that the sp2/sp3 ratio decreased from 3.21 (70% laser output) to 2.52 (100% laser output). The residual stress in the lattice was accumulated due to carbon doping by high thermal energy, which resulted in the formation of amorphous carbon. The bonding environment was represented by the ID/IG ratio using Raman analysis, and it increased from 0.55 (70% laser output) to 1.68 (100% laser output). During microstructure analysis of the carbon-doped SUS304, disordered structures by amorphization were observed in the carbon-doped SUS304 by the greater than 90% laser output. The amorphous carbon filled the lattice grains or voids to lubricate the surface, which improved the friction coefficient and wear rate from 0.23 and 7.63 mm3(Nm)-110-6 to 0.09 and 1.43 mm3(Nm)-110-6, respectively.