Mutations in the ligand-binding domain of the kit receptor: an uncommon site in human piebaldism

Heterozygous mutations in the gene for the Kit transmembrane receptor have been identified recently in human piebaldism and mouse "dominant spotting." Interestingly, all of the 14 known missense mutations that cause depigmentation in these species map to the tyrosine kinase domain of the receptor, whereas none have involved the extracellular ligand-binding domain. In an attempt to detect these uncommon mutations, we screened the nine exons encoding the extracellular portion of Kit for single-strand conformation polymorphisms (SSCP) in eight piebald subjects previously reported to be negative for kinase mutations. Four of these eight kindreds proved to carry novel mutations. The first mutation, found in two apparently unrelated probands with mild piebaldism and English ancestry, substitutes an arginine for a highly conserved cysteine at codon 136. This substitution disrupts a putative disulfide bond required for formation of the second Ig-like (D2) loop of the Kit ligand-binding domain. The second mutation, detected in a piebald kindred characterized by unusually limited depigmentation, substitutes a threonine for an alanine at codon 178, a site just proximal to conserved cysteines at codons 183 and 186. The third mutation, occurring in a kindred with more extensive depigmentation, is a novel four-base insertion in exon 2 that results in a proximal frameshift and premature termination. The data strongly suggest that piebaldism can result from missense mutations in the Kit ligand-binding domain, although the resulting phenotype may be milder than that observed for null or kinase mutations. The apparent clustering of these uncommon mutations at or near the conserved cysteines for the D2 Ig-like loop further suggests a critical role for this region in Kit receptor function.     

The effect of the aspect ratio on the hydrophobicity of microstructured polydimethylsiloxane (PDMS) robust surfaces

In this study, we have designed and fabricated robust hydrophobic surfaces that are composed of various micropillar arrays and investigated the effect of the aspect ratio (feature height/feature size) of the micropillar on the wettability of the fabricated surfaces. The robust, micropillar-arrayed surfaces were designed to yield the same Wenzel and Cassie water contact angles (CAs). According to our design rule, one can achieve an enhanced hydrophobic surface by increasing the height of the micropillars. The designed hydrophobic surfaces were fabricated by polydimethylsiloxane (PDMS) replica molding with photolithographically micropatterned SU-8 masters. The hydrophobicity properties of the fabricated PDMS surfaces were fully characterized theoretically and experimentally. From the theoretical and experimental results, it was found that the micropillars of an intrinsically hydrophobic material with a high aspect ratio enhance the hydrophobicity of the surface by increasing the surface roughness (in view of the Wenzel state) and the opportunities for the entrapment of air beneath a water droplet (the Cassie state).     

Synthesis and characterization of novel blue azo‐dye derivatives containing acrylate group for dye‐based color filters

Abstract— Even though dyes have a fine resolution and good chromaticities, they are not widely used as coloring materials for color filters (CFs) due to their low thermal stability and chemical resistance. A series of azo‐dye derivatives, which consist of two cross‐linkable acrylate or methacrylate groups to improve thermal and chemical properties, have been synthesized and used to fabricate color filters. The spectral properties and chemical/thermal stabilities of the fabricated CFs were investigated by comparing dye‐based CFs, without a complicated dispersion process, but with pigment‐based CFs using dispersed pigment. Also, more properties including the development test and surface morphologies lithographic properties were studied. The synthesized azo dyes were characterized by elemental analysis, UV‐visible spectra, IR, mass, and ¹H‐NMR spectra.     

Using jump-diffusion modeling for valuing real options in infrastructure projects

In infrastructure financed projects, in order to attract private investors, host governments often provide some guarantees. This paper develops a value model of minimum revenue guarantee with multiple-exercise real options under the impact of the emergency incident. The model is applied to infrastructure financed projects using the minimum revenue guarantee under simulation. The simulation results indicate that, before quantifying the value of the minimum revenue guarantee, it is necessary to forecast the jump degree and intensity of the emergency incident, as well as prevent and control risks arising from such emergencies. Otherwise, underestimation of the guarantee value will occur and the government will have to bear huge debt in this condition. We also analyze the dependence of the guaranteed value on the minimum guaranteed revenue level, initial revenue and number of exercise rights. For various conditions, the diagrams of the guaranteed value are also presented.     

Development of a sequential robust–tolerance design model for a destructive quality characteristic

Robust design (RD) and tolerance design (TD) have received much attention from researchers and practitioners for more than two decades, and a number of methodologies for modeling and optimizing the RD and TD processes have been studied. However, there is ample room for improvement. Because most existing research considers RD and TD as separate research fields, the primary objective of this paper is to develop a sequential robust–tolerance design method to jointly determine the best factor settings and the closed-form solutions for the optimal specification limits. We then apply the proposed method to a destructive quality characteristic. Finally, a case study and sensitivity analyses are performed for verification purposes, and further studies are discussed.     

The election problem in asynchronous distributed systems with bounded faulty processes

Determining the “weakest” failure detectors is a central topic in solving many agreement problems such as Consensus, Non-Blocking Atomic Commit and Election in asynchronous distributed systems. So far, this has been studied extensively for several such fundamental problems. It is stated that Perfect Failure Detector P is the weakest failure detector to solve the Election problem with any number of faulty processes. In this paper, we introduce Modal failure detector M and show that to solve Election, M is the weakest failure detector to solve election when the number of faulty processes is less than ⌈n/2⌉. We also show that it is strictly weaker than P.

Neuroproteomics and its applications in research on nicotine and other drugs of abuse

The rapidly growing field of neuroproteomics is able to track changes in protein expression and protein modifications underlying various physiological conditions, including the neural diseases related to drug addiction. Thus, it presents great promise in characterizing protein function, biochemical pathways, and networks to understand the mechanisms underlying drug dependence. In this article, we first provide an overview of proteomics technologies and bioinformatics tools available to analyze proteomics data. Then we summarize the recent applications of proteomics to profile the protein expression pattern in animal or human brain tissues after the administration of nicotine, alcohol, amphetamine, butorphanol, cocaine, and morphine. By comparing the protein expression profiles in response to chronic nicotine exposure with those appearing in response to treatment with other drugs of abuse, we identified three biological processes that appears to be regulated by multiple drugs of abuse: energy metabolism, oxidative stress response, and protein degradation and modification. Such similarity indicates that despite the obvious differences among their chemical properties and the receptors with which they interact, different substances of abuse may cause some similar changes in cellular activities and biological processes in neurons.     

高放废物地质处置性能评价

为建立我国高放废物地质处置性能评价方法而系统地介绍了性能评价的研究目的、研究内容、研究方法、国内外研究现状；以此为基础，提出了关于开展我国性能评价的若干建议。性能评价方法的建立将有利于我国高放废物地质处置事业的协调发展。