地下圆形衬砌洞室对SV及Rayleigh波的动应力集中(II):数值结果

为了解决在入射平面SV波和Rayleigh波作用下地下圆形衬砌洞室的动应力集中问题,利用文献[5]的级数解,分析了衬砌刚度、入射波长、入射角度诸因素对动应力集中系数(DSCF)的影响。数值结果表明:(1)衬砌刚度对DSCF有重要影响,柔性衬砌情况DSCF最小,刚性衬砌情况的最大;环向与轴向DSCF最大可分别达到32.31与16.12;(2)入射频率和入射角度对DSCF也有很大影响。     

A nuclear-receptor-dependent phosphatidylcholine pathway with antidiabetic effects

Nuclear hormone receptors regulate diverse metabolic pathways and the orphan nuclear receptor LRH-1 (also known as NR5A2) regulates bile acid biosynthesis. Structural studies have identified phospholipids as potential LRH-1 ligands, but their functional relevance is unclear. Here we show that an unusual phosphatidylcholine species with two saturated 12 carbon fatty acid acyl side chains (dilauroyl phosphatidylcholine (DLPC)) is an LRH-1 agonist ligand in vitro. DLPC treatment induces bile acid biosynthetic enzymes in mouse liver, increases bile acid levels, and lowers hepatic triglycerides and serum glucose. DLPC treatment also decreases hepatic steatosis and improves glucose homeostasis in two mouse models of insulin resistance. Both the antidiabetic and lipotropic effects are lost in liver-specific Lrh-1 knockouts. These findings identify an LRH-1 dependent phosphatidylcholine signalling pathway that regulates bile acid metabolism and glucose homeostasis.     

TERRA and hnRNPA1 orchestrate an RPA-to-POT1 switch on telomeric single-stranded DNA

Maintenance of telomeres requires both DNA replication and telomere 'capping' by shelterin. These two processes use two single-stranded DNA (ssDNA)-binding proteins, replication protein A (RPA) and protection of telomeres 1 (POT1). Although RPA and POT1 each have a critical role at telomeres, how they function in concert is not clear. POT1 ablation leads to activation of the ataxia telangiectasia and Rad3-related (ATR) checkpoint kinase at telomeres, suggesting that POT1 antagonizes RPA binding to telomeric ssDNA. Unexpectedly, we found that purified POT1 and its functional partner TPP1 are unable to prevent RPA binding to telomeric ssDNA efficiently. In cell extracts, we identified a novel activity that specifically displaces RPA, but not POT1, from telomeric ssDNA. Using purified protein, here we show that the heterogeneous nuclear ribonucleoprotein A1 (hnRNPA1) recapitulates the RPA displacing activity. The RPA displacing activity is inhibited by the telomeric repeat-containing RNA (TERRA) in early S phase, but is then unleashed in late S phase when TERRA levels decline at telomeres. Interestingly, TERRA also promotes POT1 binding to telomeric ssDNA by removing hnRNPA1, suggesting that the re-accumulation of TERRA after S phase helps to complete the RPA-to-POT1 switch on telomeric ssDNA. Together, our data suggest that hnRNPA1, TERRA and POT1 act in concert to displace RPA from telomeric ssDNA after DNA replication, and promote telomere capping to preserve genomic integrity.     

How Cooper pairs vanish approaching the Mott insulator in Bi2Sr2CaCu2O8+delta

The antiferromagnetic ground state of copper oxide Mott insulators is achieved by localizing an electron at each copper atom in real space (r-space). Removing a small fraction of these electrons (hole doping) transforms this system into a superconducting fluid of delocalized Cooper pairs in momentum space (k-space). During this transformation, two distinctive classes of electronic excitations appear. At high energies, the mysterious 'pseudogap' excitations are found, whereas, at lower energies, Bogoliubov quasi-particles-the excitations resulting from the breaking of Cooper pairs-should exist. To explore this transformation, and to identify the two excitation types, we have imaged the electronic structure of Bi(2)Sr(2)CaCu(2)O(8+delta) in r-space and k-space simultaneously. We find that although the low-energy excitations are indeed Bogoliubov quasi-particles, they occupy only a restricted region of k-space that shrinks rapidly with diminishing hole density. Concomitantly, spectral weight is transferred to higher energy r-space states that lack the characteristics of excitations from delocalized Cooper pairs. Instead, these states break translational and rotational symmetries locally at the atomic scale in an energy-independent way. We demonstrate that these unusual r-space excitations are, in fact, the pseudogap states. Thus, as the Mott insulating state is approached by decreasing the hole density, the delocalized Cooper pairs vanish from k-space, to be replaced by locally translational- and rotational-symmetry-breaking pseudogap states in r-space.     

Probing the penicillin sidechain selectivity of recombinant deacetoxycephalosporin C synthase

Deacetoxycephalosporin C synthase from Streptomyces clavuligerus catalyses the conversion of the five-membered penicillin ring to the unsaturated six-membered cephem ring of deacetoxycephalosporin C. The effects on enzyme activity of the penicillin substrate sidechain and various cofactors were investigated using a continuous spectrophotometric assay. The conversion of penicillin G to phenylacetyl-7-aminodeacetoxycephalo sporanic acid (G-7-ADCA) was confirmed, and further details of the reaction were elucidated. The conversion of ampicillin to cephalexin was faster than that of acetyl-6-APA to acetyl-7-ADCA kcat = 0.120 +/- 0.001 s(-1) versus 0.035 +/- 0.001 s(-1), but they had similar Km values: 4.86 +/- 0.12 and 3.28 +/- 0.26 mM, respectively. Amoxycillin and penicillin V were also converted at low levels. Conversion was not detected for penicillanate, 6-aminopenicillanate, carbenicillin, temocillin, ticarcillin or benzylpenicilloic acid, suggesting that the enzyme has a relatively strict selectivity for the sidechain of the penicillin substrate.     

Identification of common microRNA-mRNA regulatory biomodules in human epithelial cancer

The complex regulatory network between microRNAs and gene expression remains an unclear domain of active research. We proposed to address in part this complex regulation with a novel approach for the genome-wide identification of biomodules derived from paired microRNA and mRNA profiles, which could reveal correlations associated with a complex network of dys-regulation in human cancer. Two published expression datasets for 68 samples with 11 distinct types of epithelial cancers and 21 samples of normal tissues were used, containing microRNA expression and gene expression profiles, respectively. As results, the microRNA expression used jointly with mRNA expression can provide better classifiers of epithelial cancers against normal epithelial tissue than either dataset alone (P=1×10^–10, F test). We identified a combination of 6 microRNA-mRNA biomodules that optimally classified epithelial cancers from normal epithelial tissue (total accuracy = 93.3%; 95% confidence intervals: 86%–97%), using penalized logistic regression (PLR) algorithm and three-fold cross-validation. Three of these biomodules are individually sufficient to cluster epithelial cancers from normal tissue using mutual information distance. The biomodules contain 10 distinct microRNAs and 98 distinct genes, including well known tumor markers such as miR-15a, miR-30e, IRAK1, TGFBR2, DUSP16, CDC25B and PDCD2. In addition, there is a significant enrichment (Fisher’s exact test P=3×10^–10) between putative microRNA-target gene pairs reported in 5 microRNA target databases and the inversely correlated microRNA-mRNA pairs in the biomodules. Further, microRNAs and genes in the biomodules were found in abstracts mentioning epithelial cancers (Fisher’s Exact test, unadjusted P<0.05). Taken together, these results strongly suggest that the discovered microRNA-mRNA biomodules correspond to regulatory mechanisms common to human epithelial cancer samples. In conclusion, we developed and evaluated a novel comprehensive method to systematically identify, on a genome scale, microRNA-mRNA expression biomodules common to distinct cancers of the same tissue. These biomodules also comprise novel microRNA and genes as well as an imputed regulatory network, which may accelerate the work of cancer biologists as large regulatory maps of cancers can be drawn efficiently for hypothesis generation.     

Strong polarization enhancement in asymmetric three-component ferroelectric superlattices

Theoretical predictions--motivated by recent advances in epitaxial engineering--indicate a wealth of complex behaviour arising in superlattices of perovskite-type metal oxides. These include the enhancement of polarization by strain and the possibility of asymmetric properties in three-component superlattices. Here we fabricate superlattices consisting of barium titanate (BaTiO3), strontium titanate (SrTiO3) and calcium titanate (CaTiO3) with atomic-scale control by high-pressure pulsed laser deposition on conducting, atomically flat strontium ruthenate (SrRuO3) layers. The strain in BaTiO3 layers is fully maintained as long as the BaTiO3 thickness does not exceed the combined thicknesses of the CaTiO3 and SrTiO3 layers. By preserving full strain and combining heterointerfacial couplings, we find an overall 50% enhancement of the superlattice global polarization with respect to similarly grown pure BaTiO3, despite the fact that half the layers in the superlattice are nominally non-ferroelectric. We further show that even superlattices containing only single-unit-cell layers of BaTiO3 in a paraelectric matrix remain ferroelectric. Our data reveal that the specific interface structure and local asymmetries play an unexpected role in the polarization enhancement.     

Estimating nutrient budgets in a coastal lagoon

To estimate nutrient budgets,water samples were collected at 16 sites in Tapong lagoon from January 2004 through April 2005 and the parameters of water quality were analyzed immediately after collection.These data were used to build a box model for calculating nutrient budgets of the lagoon.We estimated the net amount of nutrient fluxes into (coming from creeks) and out (from tidal inlet) of the lagoon and calculated the total amount of nutrient that deposits into the sediment in a full tidal cycle.During J...     

Accurate whole-genome sequencing and haplotyping from 10 to 20 human cells

Recent advances in whole-genome sequencing have brought the vision of personal genomics and genomic medicine closer to reality. However, current methods lack clinical accuracy and the ability to describe the context (haplotypes) in which genome variants co-occur in a cost-effective manner. Here we describe a low-cost DNA sequencing and haplotyping process, long fragment read (LFR) technology, which is similar to sequencing long single DNA molecules without cloning or separation of metaphase chromosomes. In this study, ten LFR libraries were made using only ～100?picograms of human DNA per sample. Up to 97% of the heterozygous single nucleotide variants were assembled into long haplotype contigs. Removal of false positive single nucleotide variants not phased by multiple LFR haplotypes resulted in a final genome error rate of 1 in 10?megabases. Cost-effective and accurate genome sequencing and haplotyping from 10-20 human cells, as demonstrated here, will enable comprehensive genetic studies and diverse clinical applications.     

Extinction risk from climate change

Climate change over the past approximately 30 years has produced numerous shifts in the distributions and abundances of species and has been implicated in one species-level extinction. Using projections of species' distributions for future climate scenarios, we assess extinction risks for sample regions that cover some 20% of the Earth's terrestrial surface. Exploring three approaches in which the estimated probability of extinction shows a power-law relationship with geographical range size, we predict, on the basis of mid-range climate-warming scenarios for 2050, that 15-37% of species in our sample of regions and taxa will be 'committed to extinction'. When the average of the three methods and two dispersal scenarios is taken, minimal climate-warming scenarios produce lower projections of species committed to extinction ( approximately 18%) than mid-range ( approximately 24%) and maximum-change ( approximately 35%) scenarios. These estimates show the importance of rapid implementation of technologies to decrease greenhouse gas emissions and strategies for carbon sequestration.