Novel KCND3 Variant Underlying Nonprogressive Congenital Ataxia or SCA19/22 Disrupt KV4.3 Protein Expression and K+ Currents with Variable Effects on Channel Properties

KCND3 encodes the voltage-gated potassium channel K_V4.3 that is highly expressed in the cerebellum, where it regulates dendritic excitability and calcium influx. Loss-of-function K_V4.3 mutations have been associated with dominant spinocerebellar ataxia (SCA19/22). By targeted NGS sequencing, we identified two novel KCND3 missense variants of the K_V4.3 channel: p.S347W identified in a patient with adult-onset pure cerebellar syndrome and p.W359G detected in a child with congenital nonprogressive ataxia. Neuroimaging showed mild cerebellar atrophy in both patients. We performed a two-electrode voltage-clamp recording of K_V4.3 currents in Xenopus oocytes: both the p.G345V (previously reported in a SCA19/22 family) and p.S347W mutants exhibited reduced peak currents by 50%, while no K+ current was detectable for the p.W359G mutant. We assessed the effect of the mutations on channel gating by measuring steady-state voltage-dependent activation and inactivation properties: no significant alterations were detected in p.G345V and p.S347W disease-associated variants, compared to controls. K_V4.3 expression studies in HEK293T cells showed 53% (p.G345V), 45% (p.S347W) and 75% (p.W359G) reductions in mutant protein levels compared with the wildtype. The present study broadens the spectrum of the known phenotypes and identifies additional variants for KCND3-related disorders, outlining the importance of SCA gene screening in early-onset and congenital ataxia.     

Review on development of metal/ceramic interpenetrating phase composites and critical analysis of their properties

Metal/ceramic composites are in high demand in several industries because of their superior thermo-mechanical properties. Among various composite types, the interpenetrating phase composites (IPCs) with percolating metallic and ceramic phases offer manifold benefits, such as a good combination of strength, toughness, and stiffness, very good thermal properties, excellent wear resistance, as well as the flexibility of microstructure and processing route selection, etc. The fabrication of metal/ceramic IPCs typically involves two steps - i) processing of an open porous ceramic body, and ii) infiltration of metallic melt in the pores to fabricate the IPC. Although significant progress has been made in recent years for developing both porous ceramics and melt infiltration methods, to the best of the knowledge of the authors, no review article summarizing all the aspects of processing and properties of IPCs has been published till date. This review article is aimed at filling this gap. Starting with a brief introduction about the current status and applications of IPCs, the various processing routes for fabricating open porous ceramic preforms and melt infiltration techniques have been discussed. Subsequently, the data available for various important physical, mechanical, and thermal properties for IPCs have been critically analyzed to thoroughly understand their dependence on various structural and processing parameters. To compare the properties of IPCs with other relevant materials, seven different Ashby material property maps have been used, and the domains for IPCs have been created in them. For each map, the concept of material indices has been employed to critically discuss how IPCs perform in relation to other material classes for various optimum design conditions. Finally, a detailed future outlook for further research on IPCs has been provided.     

Wet-oxygen corrosion resistance and mechanism of bi-layer Mullite/SiC coating for Cf/SiC composites

A bi-layer oxidation-resistant coating consisting of a mullite outer coating, and a SiC inner coating on the surface of C_f/SiC composites was prepared by the chemical vapour deposition and an air spray sol-gel process, and its corrosion behavior was evaluated in a wet-oxygen coupling environment. Results show that the formation of SiO₂ glass layer and its reaction with mullite particles to form aluminosilicate glass layer, leading to an increase in the density of the mullite outer coating, so that the weight loss of bi-layer Mullite/SiC coating coated C/SiC sample was only 1.11 × 10^?3 g·cm^?2 in the first 100 h of oxidation. However, the weight loss of the coated sample reached 26.82 × 10^?3 g·cm^?2 after 200 h of oxidation due to a part of the mullite outer coating was detached. The SiO₂ glass phase reacted with water vapour to generate gaseous Si(OH)_x, which created distinct holes on the surface of the SiO₂ glass layer or inside the molten aluminosilicate glass layer. Eventually, the mullite outer coating was blistered and detached from the surface of the sample due to the combination and growth of holes.     

The toughening design of multi-layer antioxidation coating on C/C matrix via SiC-SiCw transition layer grown in-situ

Poor antioxidant and thermal-shock capacities of C/C composites thermal barrier coating (TBC) caused by cracking and shedding of coatings has been a major obstacle blocking the development of C/C composites. Herein, in-situ growth of whisker reinforced silicon carbide transition layer and inter-embedding mechanism of multi-gradient coatings were brought into the design of TBC to enhance the antioxidant and thermal-shock capacities. A three-layer gradient coating SiC-SiC_w/ZrB₂-SiC/ZrSiO₄-aluminosilicate glass (ZAG) from inside to outside, in which ZrB₂-SiC/ZAG serve as oxygen barrier layers with self-healing ability and SiC-SiC_w provides thermal stress buffering and bonding against cracking and shedding of coatings, is designed. The ZAG mainly forms a dense oxygen blocking frontier with self-healing ability through fluidized glass, while the ZrB₂-SiC can react actively with infiltrated oxygen in a way of self-sacrifice, preventing oxygen erosion to C/C matrix and SiC-SiC_w transition layer. As a result, the collaborative work among layers endows this coating with excellent high temperature service performance. This work provides a new insight for the design of excellent TBC.     

Structural,electrical, and linear/nonlinear optical characteristics of thermally evaporated molybdenum oxide thin films

Homogeneous thin films of Molybdenum oxide (MoO₃) were grown on quartz and glass substrates using the thermal evaporation method. XRD results showed that the MoO₃ powder has a polycrystalline structure with an orthorhombic crystal system whereas the MoO₃ thin films have amorphous nature. SEM images showed that the MoO₃ thin films have a nearly uniform surfaces with worm-like shape grains. The film thickness influences on the linear and nonlinear optical characteristics of MoO₃ thin films that were examined using spectrophotometric measurements and from which, the linear optical constants of the MoO₃ thin films were estimated. The electronic transition type was determined as a direct allowed one. The values of the optical band gap were obtained to be in the range of 3.88–3.72 eV. The dispersion parameters, third-order nonlinear optical susceptibility, and the nonlinear refractive index of the MoO₃ thin films were determined and interpreted in the light of the single oscillator model. The temperature dependence of the DC electrical conductivity and the corresponding conduction mechanism for the MoO₃ films were investigated at temperatures ranging from 303 to 463 K.     

Status of Mysis diluviana in Lake Ontario in 2013: Lower abundance but higher fecundity than in the 1990s

Mysis diluviana is a major component of prey fish diets in the Great Lakes, so annual production of M. diluviana is important for understanding and modeling energy flow through Great Lakes food webs. However, only three lake-wide measurements of M. diluviana annual production in Lake Ontario are currently available (1971, 1990, 1995). During 2013, lake-wide coverage of Lake Ontario was achieved during four periods from April to November. Annual mean density and biomass of M. diluviana in 2013 were 99?#/m² (SE: 8) and 318?mg?dw/m² (SE: 28) – approximately half of values observed in 1990s. M. diluviana comprised 13–30% of offshore zooplankton biomass in each period. Reproduction peaked in fall, with mean brood size of 32 embryos (range: 11–49), at least 10% larger than in 1990s. Generation time was two years from embryo to initial reproduction. Growth rates were 0.052?mm/d for the age-0 cohort and 0.027?mm/d for the age-1 cohort. Age-0 growth rate was significantly higher than in 1980s–90s (0.035?mm/d). Annual production in 2013 was 0.85?g?dw/m²/yr (SE: 0.03) which was 30–40% of values observed in 1990 and 1995 (2.23 and 2.53?g/m²/yr). Annual production to biomass ratio (P/B) in 2013 was 2.65?/yr which was 80–85% of values observed in 1990 and 1995 (3.24 and 3.11?/yr), but this difference was not statistically significant. Our results suggest that changes in annual production over time can be estimated using changes in biomass over time and a mean P/B ratio.     

Methane bi-reforming over boron-doped Ni/SBA-15 catalyst: Longevity evaluation

A highly active and stable boron-promoted catalyst was successfully prepared by using the sequential incipient wetness impregnation technique and examined for methane bi-reforming reaction. The initial investigation found that the NiO and B₂O₃ particles were dispersed on the outer surface of the high surface area SBA-15 support. In addition, the catalytic activity was increased linearly with the tested reaction temperature due to the endothermic nature of the reaction. In fact, the catalyst achieved the CH₄ conversion and H₂/CO molar ratio of approximately 67.3% and 2.7, respectively at 1073 K. The resulting product ratio is highly suitable for downstream Fischer-Tropsch (FT) synthesis. The B-promoted catalyst showed the lowest degree of catalyst deactivation (4%) at 1023 K. Additionally, the XPS measurements unveiled that the boron facilitates the adsorption of CO₂ by donating electrons to the neighbouring Ni cluster and thus improved its catalytic performance. Furthermore, Raman and XRD analysis revealed that the boron promotion on 10%Ni/SBA-15 could prevent the reoxidation and deposition of carbonaceous species.     

A novel differential evolution mapping technique for generic combinatorial optimization problems

Differential evolution is primarily designed and used to solve continuous optimization problems. Therefore, it has not been widely considered as applicable for real-world problems that are characterized by permutation-based combinatorial domains. Many algorithms for solving discrete problems using differential evolution have been proposed, some of which have achieved promising results. However, to enhance their performance, they require improvements in many aspects, such as their convergence speeds, computational times and capabilities to solve large discrete problems. In this paper, we present a new mapping method that may be used with differential evolution to solve combinatorial optimization problems. This paper focuses specifically on the mapping component and its effect on the performance of differential evolution. Our method maps continuous variables to discrete ones, while at the same time, it directs the discrete solutions produced towards optimality, by using the best solution in each generation as a guide. To judge its performance, its solutions for instances of well-known discrete problems, namely: 0/1 knapsack, traveling salesman and traveling thief problems, are compared with those obtained by 8 other state-of-the-art mapping techniques. To do this, all mapping techniques are used with the same differential evolution settings. The results demonstrated that our technique significantly outperforms the other mapping methods in terms of the average error from the best-known solution for the traveling salesman problems, and achieves promising results for both the 0/1 knapsack and the traveling thief problems.