The landscape of cancer genes and mutational processes in breast cancer

All cancers carry somatic mutations in their genomes. A subset, known as driver mutations, confer clonal selective advantage on cancer cells and are causally implicated in oncogenesis, and the remainder are passenger mutations. The driver mutations and mutational processes operative in breast cancer have not yet been comprehensively explored. Here we examine the genomes of 100 tumours for somatic copy number changes and mutations in the coding exons of protein-coding genes. The number of somatic mutations varied markedly between individual tumours. We found strong correlations between mutation number, age at which cancer was diagnosed and cancer histological grade, and observed multiple mutational signatures, including one present in about ten per cent of tumours characterized by numerous mutations of cytosine at TpC dinucleotides. Driver mutations were identified in several new cancer genes including AKT2, ARID1B, CASP8, CDKN1B, MAP3K1, MAP3K13, NCOR1, SMARCD1 and TBX3. Among the 100 tumours, we found driver mutations in at least 40 cancer genes and 73 different combinations of mutated cancer genes. The results highlight the substantial genetic diversity underlying this common disease.     

A terahertz metamaterial with unnaturally high refractive index

Controlling the electromagnetic properties of materials, going beyond the limit that is attainable with naturally existing substances, has become a reality with the advent of metamaterials. The range of various structured artificial 'atoms' has promised a vast variety of otherwise unexpected physical phenomena, among which the experimental realization of a negative refractive index has been one of the main foci thus far. Expanding the refractive index into a high positive regime will complete the spectrum of achievable refractive index and provide more design flexibility for transformation optics. Naturally existing transparent materials possess small positive indices of refraction, except for a few semiconductors and insulators, such as lead sulphide or strontium titanate, that exhibit a rather high peak refractive index at mid- and far-infrared frequencies. Previous approaches using metamaterials were not successful in realizing broadband high refractive indices. A broadband high-refractive-index metamaterial structure was theoretically investigated only recently, but the proposed structure does not lend itself to easy implementation. Here we demonstrate that a broadband, extremely high index of refraction can be realized from large-area, free-standing, flexible terahertz metamaterials composed of strongly coupled unit cells. By drastically increasing the effective permittivity through strong capacitive coupling and decreasing the diamagnetic response with a thin metallic structure in the unit cell, a peak refractive index of 38.6 along with a low-frequency quasi-static value of over 20 were experimentally realized for a single-layer terahertz metamaterial, while maintaining low losses. As a natural extension of these single-layer metamaterials, we fabricated quasi-three-dimensional high-refractive-index metamaterials, and obtained a maximum bulk refractive index of 33.2 along with a value of around 8 at the quasi-static limit.     

北宋明州高丽使行馆

明州(即宁波)地处中国大陆东海之滨，航道四通八达，海外交通便利，是开展海外贸易较早的城市之一，和世界各国进行通商贸易已有一、二千年的历史．到了宋代，明州和世界各国(如：高丽、东南亚、阿拉伯等)的交往达到繁盛的阶段．特别是到了北宋时期，明州与高丽的交往有了显著的增加．北宋时，由于与高丽的交往日益频繁，高丽来明州的人日益增加，北宋政府为了接待高丽使者和商人，在明州兴建了“高丽使行馆”．为了了解北宋和高丽的交往情况，中韩两国历史学界和建筑学界提供了许多重要的线索，高丽使行馆作为两国交往的重要场所有很高的研究价值．本文尝试了解、研究有关高丽使行馆的情况．     

A high-resolution map of human chromosome 12

Our sequence-tagged site-content map of chromosome 12 is now integrated with the whole-genome fingerprinting effort. It provides accurate and nearly complete bacterial clone coverage of chromosome 12. We propose that this integrated mapping protocol serves as a model for constructing physical maps for entire genomes.     

Functional genomics in the rice blast fungus to unravel the fungal pathogenicity

A rapidly growing number of successful genome sequencing projects in plant pathogenic fungi greatly increase the demands for tools and methodologies to study fungal pathogenicity at genomic scale. Magnaporthe oryzae is an economically important plant pathogenic fungus whose genome is fully sequenced. Recently we have reported the development and application of functional genomics platform technologies in M. oryzae. This model approach would have many practical ramifications in design and implementation of upcoming functional genomics studies of filamentous fungi aimed at understanding fungal pathogenicity.     

Development of hyperphagia in male rats following placement of ventromedial hypothalamic lesions at four different ages

Zusammenfassung Im Gegensatz zu weiblichen Ratten zeigen männliche Tiere mit Läsionen des N. ventromedialis hypothalami im Alter von 26, 59, 75 und 140 Tagen kurz nach der Ablaktation keinen unmittelbaren Einfluss auf die Futteraufnahme, Erwachsene nie die in den gleichaltrigen weiblichen Ratten beobachtete Hyperphagie. Männliche Ratten erreichen das Kontrollniveau schon nach 5 Wochen, während die weiblichen Tiere noch ausgeprägte Hyperphagic zeigen.

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This investigation was supported by U.S.P.H.S. Grant No. HE 06975 of the National Heart Institute.     

HIV-1 superinfection despite broad CD8+ T-cell responses containing replication of the primary virus

Early treatment of acute HIV-1 infection followed by treatment interruptions has shown promise for enhancing immune control of infection. A subsequent loss of control, however, allows the correlates of protective immunity to be assessed. Here we show that sudden breakthrough of plasma viraemia occurred after prolonged immune containment in an individual infected with HIV-1 at a time when 25 distinct CD8+ T-cell epitopes in the viral proteins Gag, RT, Integrase, Env, Nef, Vpr, Vif and Rev were being targeted. Sequencing of the virus in plasma and cells showed that superinfection with a second clade-B virus was coincident with the loss of immune control. This sudden increase in viraemia was associated with a decline in half of the CD8+ T-cell responses. The declining CD8+ T-cell responses were coupled with sequence changes relative to the initial virus that resulted in impaired recognition. Our data show that HIV-1 superinfection can occur in the setting of a strong and broadly directed virus-specific CD8+ T-cell response. The lack of cross-protective immunity for closely related HIV-1 strains, despite persistent recognition of multiple CD8 epitopes, has important implications for public health and vaccine development.     

Countercurrent chromatography meets MS

Interfacing countercurrent chromatography with thermospray mass spectrometry provides a new analytical tool for detecting nonvolatile, hydrophilic or thermally unstable bioactive natural products.