Truncating mutations in the last exon of NOTCH2 cause a rare skeletal disorder with osteoporosis

Hajdu-Cheney syndrome is a rare autosomal dominant skeletal disorder with facial anomalies, osteoporosis and acro-osteolysis. We sequenced the exomes of six unrelated individuals with this syndrome and identified heterozygous nonsense and frameshift mutations in NOTCH2 in five of them. All mutations cluster to the last coding exon of the gene, suggesting that the mutant mRNA products escape nonsense-mediated decay and that the resulting truncated NOTCH2 proteins act in a gain-of-function manner.     

A New Adaptive Formant Vocoder

A new type of vocoder system based upon formant analysis is presented in this paper. The LMS adaptive algorithm is used for tracking formants of speech signals. The results of computer simulation show that the new vocoder has better synthesized speech quality.     

Lessons from common markers of tumor-initiating cells in solid cancers

Tumor-initiating cells (TICs) have emerged as the driving force of carcinomas, which appear as hierarchically structured. TICs as opposed to the tumor bulk display tumor forming potential, which is linked to a certain degree of self-renewal and differentiation, both major features of stem cells. Markers such as CD44, CD133, CD24, EpCAM, CD166, Lgr5, CD47, and ALDH have been described, which allow for the prospective enrichment of TICs. It is conspicuous that the same markers allow for an enrichment of TICs in various entities and, on the other hand, that different combinations of these markers were independently reported for the same tumor entity. Potential functions of these markers in the regulation of TIC phenotypes remained somewhat neglected although they might give insights in common molecular themes of TICs. The present review discusses major TIC markers with respect to their function and potential contributions to the tumorigenic phenotype of TICs.     

A New Discipline of Science-The Study of Open Complex Giant System and Its Methodology

This paper introduces the conception of open complex giant system and the methodology for dealing with the system, with stress on its profound significance in development of science and technology. The authors conclude that the reductionism underlying the exact science is not suitable to open complex giant system, and the only feasible alternative is the meta-synthetic engineering from the qualitative to the quantitative.     

Discussion on Electromagnetic Missile

This paper presents the principle of electromagnetic missile from the mathematical point of view, and verifies rigorously that the radiating power over whole space is limited.     

Simulation Modeling by Fuzzy Nets

Fuzzy technology is a newly developed discipline based on fuzzy mathematics. In the recent years, it has been successfully applied into many areas, such as process control, diagnosis,evaluation, decision making and scheduling, especially in simulation where accurate mathematical models can not or very hard be established. In this paper, to meet the demands of fuzzy simulation, two fuzzy nets will first be presented, which are quite suitable for modeling the parallel or concurrent systems with fuzzy behavior. Then, a concept of active simulation will be introduced, in which the simulation model not only can show its fuzzy behavior, but also has a certain ability which can actively perform many very useful actions, such as automatic warning, realtime monitoring, simulation re-sult checking, simulation model self-adapting, error recovery, simulating path tracing, system states inspecting and exception handling, by a unified approach while some specified events occur. The simulation model described by this     

更理想的生物质能

金融危机之后,能源和食品价格危机也是余震不断,其结果是,能源和农业成为了两个不可分割的问题。较低的石油价格使得来自农场和森林的燃料缺乏竞争力。事实虽然如此,但只从短期来看是这样的。金融危机促使人们产生了一种危机意识,必须以一切可能的手段避免依赖有限的资源;而最佳的对策是多样化的能源政策,其中。生物燃料将成为这一趋势的最大受益者。     

环太平洋地区的环境挑战

人类进入21世纪的同时,也进入了一个机会与挑战并存的崭新发展阶段。环境污染成了人类所面临的巨大挑战之一,需要引起我们所有人的关注。本书正是关于环太平洋地区环境问题的最新研究成果的专著,内容为环太平洋环境与健康科学协会第十二届国际会议上的会议论文。     

Loss-of-function mutations in LEMD3 result in osteopoikilosis, Buschke-Ollendorff syndrome and melorheostosis

Osteopoikilosis, Buschke-Ollendorff syndrome (BOS) and melorheostosis are disorders characterized by increased bone density. The occurrence of one or more of these phenotypes in the same individual or family suggests that these entities might be allelic. We collected data from three families in which affected individuals had osteopoikilosis with or without manifestations of BOS or melorheostosis. A genome-wide linkage analysis in these families, followed by the identification of a microdeletion in an unrelated individual with these diseases, allowed us to map the gene that is mutated in osteopoikilosis. All the affected individuals that we investigated were heterozygous with respect to a loss-of-function mutation in LEMD3 (also called MAN1), which encodes an inner nuclear membrane protein. A somatic mutation in the second allele of LEMD3 could not be identified in fibroblasts from affected skin of an individual with BOS and an individual with melorheostosis. XMAN1, the Xenopus laevis ortholog, antagonizes BMP signaling during embryogenesis. In this study, LEMD3 interacted with BMP and activin-TGFbeta receptor-activated Smads and antagonized both signaling pathways in human cells.