An endoribonuclease-prepared siRNA screen in human cells identifies genes essential for cell division

RNA interference (RNAi) is an evolutionarily conserved defence mechanism whereby genes are specifically silenced through degradation of messenger RNAs; this process is mediated by homologous double-stranded (ds)RNA molecules. In invertebrates, long dsRNAs have been used for genome-wide screens and have provided insights into gene functions. Because long dsRNA triggers a nonspecific interferon response in many vertebrates, short interfering (si)RNA or short hairpin (sh)RNAs must be used for these organisms to ensure specific gene silencing. Here we report the generation of a genome-scale library of endoribonuclease-prepared short interfering (esi)RNAs from a sequence-verified complementary DNA collection representing 15,497 human genes. We used 5,305 esiRNAs from this library to screen for genes required for cell division in HeLa cells. Using a primary high-throughput cell viability screen followed by a secondary high content videomicroscopy assay, we identified 37 genes required for cell division. These include several splicing factors for which knockdown generates mitotic spindle defects. In addition, a putative nuclear-export terminator was found to speed up cell proliferation and mitotic progression after knockdown. Thus, our study uncovers new aspects of cell division and establishes esiRNA as a versatile approach for genomic RNAi screens in mammalian cells.     

Hierarchical trees can be perfectly scaled in one dimension

Holman (1972) proved theorems which led him to suggest that there was a fundamental opposition between hierarchical clustering and non-metric Euclidean multidimensional scaling. Empirical experience has shown this to be untrue. Explanations of this apparent contradiction have been offered previously by Kruskal (1977) and Critchley (1986). In this paper we point out the feasibility of perfectly scaling a hierarchical tree in one dimension when the primary approach to ties (Kruskal 1964) is taken. Indeed, there is a whole polyhedral convex cone of solutions for which we obtain an explicit expression.     

Cloned neuronal IK(A) channels reopen during recovery from inactivation

The kinetic behaviour and functional role of potassium ion (K+) channels mediating a fast-inactivating K+ current (IK(A)) has been widely discussed. Activating in the subthreshold range of excitation, IK(A) channels are assumed to reduce the excitatory effect of depolarizing membrane currents in a time-dependent manner. Here we report that IK(A) channels not only open in response to a depolarization but open again after repolarization of the membrane. Although the current in response to the depolarization is rapidly inactivating, the current elicited by repolarization declines slowly and produces long-lasting afterhyperpolarizations under current-clamp conditions. This implies an additional physiological role for IK(A) channels, particularly those that activate positive to the threshold of excitation. The underlying biophysical mechanism was studied by fast-application of peptides corresponding to the N-terminal end of the IK(A) channel proteins. It was found to be a voltage-dependent release of the inactivation gate.     

射频集成电路与技术

射频集成电路是所有无线通信系统中不可或缺的部分，因此具有巨大的市场背景；射频技术是整个无线系统中的技术难点，具有重要的研究意义。该书针对射频集成电路与技术进行了全面而概括的论述，使得读者可以对整个射频系统具有全面的认识。     

Adsorption-induced scission of carbon-carbon bonds

Covalent carbon-carbon bonds are hard to break. Their strength is evident in the hardness of diamonds and tensile strength of polymeric fibres; on the single-molecule level, it manifests itself in the need for forces of several nanonewtons to extend and mechanically rupture one bond. Such forces have been generated using extensional flow, ultrasonic irradiation, receding meniscus and by directly stretching a single molecule with nanoprobes. Here we show that simple adsorption of brush-like macromolecules with long side chains on a substrate can induce not only conformational deformations, but also spontaneous rupture of covalent bonds in the macromolecular backbone. We attribute this behaviour to the fact that the attractive interaction between the side chains and the substrate is maximized by the spreading of the side chains, which in turn induces tension along the polymer backbone. Provided the side-chain densities and substrate interaction are sufficiently high, the tension generated will be strong enough to rupture covalent carbon-carbon bonds. We expect similar adsorption-induced backbone scission to occur for all macromolecules with highly branched architectures, such as brushes and dendrimers. This behaviour needs to be considered when designing surface-targeted macromolecules of this type-either to avoid undesired degradation, or to ensure rupture at predetermined macromolecular sites.     

Superhydrophobicity: drying transition of confined water

Long-range hydrophobic interactions operating underwater are important in the mediation of many natural and synthetic phenomena, such as protein folding, adhesion and colloid stability. Here we show that rough hydrophobic surfaces can experience attractive forces over distances more than 30 times greater than any reported previously, owing to the spontaneous evaporation of the intervening, confined water. Our finding highlights the importance of surface roughness in the interaction of extended structures in water, which has so far been largely overlooked.     

The twentieth century was the wettest period in northern Pakistan over the past millennium

Twentieth-century warming could lead to increases in the moisture-holding capacity of the atmosphere, altering the hydrological cycle and the characteristics of precipitation. Such changes in the global rate and distribution of precipitation may have a greater direct effect on human well-being and ecosystem dynamics than changes in temperature itself. Despite the co-variability of both of these climate variables, attention in long-term climate reconstruction has mainly concentrated on temperature changes. Here we present an annually resolved oxygen isotope record from tree-rings, providing a millennial-scale reconstruction of precipitation variability in the high mountains of northern Pakistan. The climatic signal originates mainly from winter precipitation, and is robust over ecologically different sites. Centennial-scale variations reveal dry conditions at the beginning of the past millennium and through the eighteenth and early nineteenth centuries, with precipitation increasing during the late nineteenth and the twentieth centuries to yield the wettest conditions of the past 1,000 years. Comparison with other long-term precipitation reconstructions indicates a large-scale intensification of the hydrological cycle coincident with the onset of industrialization and global warming, and the unprecedented amplitude argues for a human role.     

A large population of 'Lyman-break' galaxies in a protocluster at redshift z approximately 4.1

The most massive galaxies and the richest clusters are believed to have emerged from regions with the largest enhancements of mass density relative to the surrounding space. Distant radio galaxies may pinpoint the locations of the ancestors of rich clusters, because they are massive systems associated with 'overdensities' of galaxies that are bright in the Lyman-alpha line of hydrogen. A powerful technique for detecting high-redshift galaxies is to search for the characteristic 'Lyman break' feature in the galaxy colour, at wavelengths just shortwards of Lyalpha, which is due to absorption of radiation from the galaxy by the intervening intergalactic medium. Here we report multicolour imaging of the most distant candidate protocluster, TN J1338-1942 at a redshift z approximately 4.1. We find a large number of objects with the characteristic colours of galaxies at that redshift, and we show that this excess is concentrated around the targeted dominant radio galaxy. Our data therefore indicate that TN J1338-1942 is indeed the most distant cluster progenitor of a rich local cluster, and that galaxy clusters began forming when the Universe was only ten per cent of its present age.