采用网格再划分技术的网格推延造型

提出了一种对自由多边形物体直观高效的三维网格推延造型方法,采用这种造型方法,用户可以在已有的三维物体上勾勒两笔二维轮廓,从而推延了新的空间网格曲面,阐述了两种网格再划分技术,网格优化和网格细分,在此基础上,详细介绍了网格推延造型的方法,该方法能广泛地应用于多边形物体的自由造型。     

Episodic fresh surface waters in the Eocene Arctic Ocean

It has been suggested, on the basis of modern hydrology and fully coupled palaeoclimate simulations, that the warm greenhouse conditions that characterized the early Palaeogene period (55-45 Myr ago) probably induced an intensified hydrological cycle with precipitation exceeding evaporation at high latitudes. Little field evidence, however, has been available to constrain oceanic conditions in the Arctic during this period. Here we analyse Palaeogene sediments obtained during the Arctic Coring Expedition, showing that large quantities of the free-floating fern Azolla grew and reproduced in the Arctic Ocean by the onset of the middle Eocene epoch (approximately 50 Myr ago). The Azolla and accompanying abundant freshwater organic and siliceous microfossils indicate an episodic freshening of Arctic surface waters during an approximately 800,000-year interval. The abundant remains of Azolla that characterize basal middle Eocene marine deposits of all Nordic seas probably represent transported assemblages resulting from freshwater spills from the Arctic Ocean that reached as far south as the North Sea. The termination of the Azolla phase in the Arctic coincides with a local sea surface temperature rise from approximately 10 degrees C to 13 degrees C, pointing to simultaneous increases in salt and heat supply owing to the influx of waters from adjacent oceans. We suggest that onset and termination of the Azolla phase depended on the degree of oceanic exchange between Arctic Ocean and adjacent seas.     

Evolutionary genomics: codon bias and selection on single genomes

The idea that natural selection on genes might be detected using only a single genome has been put forward by Plotkin and colleagues, who present a method that they claim can detect selection without the need for comparative data and which, if correct, would confer greater power of analysis with less information. Here we argue that their method depends on assumptions that confound their conclusions and that, even if these assumptions were valid, the authors' inferences about adaptive natural selection are unjustified.     

Activating mutations in ALK provide a therapeutic target in neuroblastoma

Neuroblastoma, an embryonal tumour of the peripheral sympathetic nervous system, accounts for approximately 15% of all deaths due to childhood cancer. High-risk neuroblastomas are rapidly progressive; even with intensive myeloablative chemotherapy, relapse is common and almost uniformly fatal. Here we report the detection of previously unknown mutations in the ALK gene, which encodes a receptor tyrosine kinase, in 8% of primary neuroblastomas. Five non-synonymous sequence variations were identified in the kinase domain of ALK, of which three were somatic and two were germ line. The most frequent mutation, F1174L, was also identified in three different neuroblastoma cell lines. ALK complementary DNAs encoding the F1174L and R1275Q variants, but not the wild-type ALK cDNA, transformed interleukin-3-dependent murine haematopoietic Ba/F3 cells to cytokine-independent growth. Ba/F3 cells expressing these mutations were sensitive to the small-molecule inhibitor of ALK, TAE684 (ref. 4). Furthermore, two human neuroblastoma cell lines harbouring the F1174L mutation were also sensitive to the inhibitor. Cytotoxicity was associated with increased amounts of apoptosis as measured by TdT-mediated dUTP nick end labelling (TUNEL). Short hairpin RNA (shRNA)-mediated knockdown of ALK expression in neuroblastoma cell lines with the F1174L mutation also resulted in apoptosis and impaired cell proliferation. Thus, activating alleles of the ALK receptor tyrosine kinase are present in primary neuroblastoma tumours and in established neuroblastoma cell lines, and confer sensitivity to ALK inhibition with small molecules, providing a molecular rationale for targeted therapy of this disease.     

Structural basis of RNA recognition and activation by innate immune receptor RIG-I

Retinoic-acid-inducible gene-I (RIG-I; also known as DDX58) is a cytoplasmic pathogen recognition receptor that recognizes pathogen-associated molecular pattern (PAMP) motifs to differentiate between viral and cellular RNAs. RIG-I is activated by blunt-ended double-stranded (ds)RNA with or without a 5'-triphosphate (ppp), by single-stranded RNA marked by a 5'-ppp and by polyuridine sequences. Upon binding to such PAMP motifs, RIG-I initiates a signalling cascade that induces innate immune defences and inflammatory cytokines to establish an antiviral state. The RIG-I pathway is highly regulated and aberrant signalling leads to apoptosis, altered cell differentiation, inflammation, autoimmune diseases and cancer. The helicase and repressor domains (RD) of RIG-I recognize dsRNA and 5'-ppp RNA to activate the two amino-terminal caspase recruitment domains (CARDs) for signalling. Here, to understand the synergy between the helicase and the RD for RNA binding, and the contribution of ATP hydrolysis to RIG-I activation, we determined the structure of human RIG-I helicase-RD in complex with dsRNA and an ATP analogue. The helicase-RD organizes into a ring around dsRNA, capping one end, while contacting both strands using previously uncharacterized motifs to recognize dsRNA. Small-angle X-ray scattering, limited proteolysis and differential scanning fluorimetry indicate that RIG-I is in an extended and flexible conformation that compacts upon binding RNA. These results provide a detailed view of the role of helicase in dsRNA recognition, the synergy between the RD and the helicase for RNA binding and the organization of full-length RIG-I bound to dsRNA, and provide evidence of a conformational change upon RNA binding. The RIG-I helicase-RD structure is consistent with dsRNA translocation without unwinding and cooperative binding to RNA. The structure yields unprecedented insight into innate immunity and has a broader impact on other areas of biology, including RNA interference and DNA repair, which utilize homologous helicase domains within DICER and FANCM.     

Insertional mutagenesis identifies multiple networks of cooperating genes driving intestinal tumorigenesis

The evolution of colorectal cancer suggests the involvement of many genes. To identify new drivers of intestinal cancer, we performed insertional mutagenesis using the Sleeping Beauty transposon system in mice carrying germline or somatic Apc mutations. By analyzing common insertion sites (CISs) isolated from 446 tumors, we identified many hundreds of candidate cancer drivers. Comparison to human data sets suggested that 234 CIS-targeted genes are also dysregulated in human colorectal cancers. In addition, we found 183 CIS-containing genes that are candidate Wnt targets and showed that 20 CISs-containing genes are newly discovered modifiers of canonical Wnt signaling. We also identified mutations associated with a subset of tumors containing an expanded number of Paneth cells, a hallmark of deregulated Wnt signaling, and genes associated with more severe dysplasia included those encoding members of the FGF signaling cascade. Some 70 genes had co-occurrence of CIS pairs, clustering into 38 sub-networks that may regulate tumor development.     

Functional metagenomic profiling of nine biomes

Microbial activities shape the biogeochemistry of the planet and macroorganism health. Determining the metabolic processes performed by microbes is important both for understanding and for manipulating ecosystems (for example, disruption of key processes that lead to disease, conservation of environmental services, and so on). Describing microbial function is hampered by the inability to culture most microbes and by high levels of genomic plasticity. Metagenomic approaches analyse microbial communities to determine the metabolic processes that are important for growth and survival in any given environment. Here we conduct a metagenomic comparison of almost 15 million sequences from 45 distinct microbiomes and, for the first time, 42 distinct viromes and show that there are strongly discriminatory metabolic profiles across environments. Most of the functional diversity was maintained in all of the communities, but the relative occurrence of metabolisms varied, and the differences between metagenomes predicted the biogeochemical conditions of each environment. The magnitude of the microbial metabolic capabilities encoded by the viromes was extensive, suggesting that they serve as a repository for storing and sharing genes among their microbial hosts and influence global evolutionary and metabolic processes.     

基于视点变化的徒手作图输入变形

提出了一种直观,高效地用于概念设计作用图的等手输入,进行几何变形的方法,采用此方法可以徒手输入两笔曲线（参考曲线和目标曲线）,并据此二曲线来移动多边形模型的顶点,从而达到变形三维模型的目的,解决了大曲率变形时产生的自相关问题,另外,还可用来定义变形影响区域。     

Subtropical Arctic Ocean temperatures during the Palaeocene/Eocene thermal maximum

The Palaeocene/Eocene thermal maximum, approximately 55 million years ago, was a brief period of widespread, extreme climatic warming, that was associated with massive atmospheric greenhouse gas input. Although aspects of the resulting environmental changes are well documented at low latitudes, no data were available to quantify simultaneous changes in the Arctic region. Here we identify the Palaeocene/Eocene thermal maximum in a marine sedimentary sequence obtained during the Arctic Coring Expedition. We show that sea surface temperatures near the North Pole increased from 18 degrees C to over 23 degrees C during this event. Such warm values imply the absence of ice and thus exclude the influence of ice-albedo feedbacks on this Arctic warming. At the same time, sea level rose while anoxic and euxinic conditions developed in the ocean's bottom waters and photic zone, respectively. Increasing temperature and sea level match expectations based on palaeoclimate model simulations, but the absolute polar temperatures that we derive before, during and after the event are more than 10 degrees C warmer than those model-predicted. This suggests that higher-than-modern greenhouse gas concentrations must have operated in conjunction with other feedback mechanisms--perhaps polar stratospheric clouds or hurricane-induced ocean mixing--to amplify early Palaeogene polar temperatures.     

Multistage interband cascade photovoltaic devices with a bandgapof 0.23 eV operating above room temperature

Interband cascade （IC） photovoltaic （PV）device structures, consisting of multiple discrete InAs/GaSb superlattice absorbers sandwiched between electronand hole barriers, were grown by molecular beam epitaxy.Details of the molecular beam epitaxy growth and materialcharacterization of the structures are presented. The dis-crete absorber architecture enables certain advantages, suchas high open-circuit voltage, high collection efficiency,high operating temperature, and smooth integration ofcascade stages with different bandgaps. The two- andthree-stage ICPV devices presented in this article operate atroom temperature with substantial open-circuit voltages ata cutoff wavelength of 5.3 μm （corresponding to a bandgapof 0.23 eV）, the longest ever reported for room temperaturePV devices. The device characteristics indicate a high levelof current matching and demonstrate the advantages of theinterband cascade approach in thermophotovoltaic celldesign.