PVC／NBR／PE反应性共混体系的研究

通过共交联反应使ＰＶＣ／ＮＢＲ－３１／Ｐ共混体系的相容性增加，机械性能得到改善，ＤＳＣ结果表明，交联使ＰＥ的结晶受到破坏，熔点下降。ＤＭＡ也证明交联增进了相应相互作用，使ＰＶＣ的Ｔｇ下降，ＰＥ的Ｔｇ上升，由于交联改变了共混体系的形态结构，使其冲击强度提高了一倍多。     

Recombination and linkage disequilibrium in Arabidopsis thaliana

Linkage disequilibrium (LD) is a major aspect of the organization of genetic variation in natural populations. Here we describe the genome-wide pattern of LD in a sample of 19 Arabidopsis thaliana accessions using 341,602 non-singleton SNPs. LD decays within 10 kb on average, considerably faster than previously estimated. Tag SNP selection algorithms and 'hide-the-SNP' simulations suggest that genome-wide association mapping will require only 40%-50% of the observed SNPs, a reduction similar to estimates in a sample of African Americans. An Affymetrix genotyping array containing 250,000 SNPs has been designed based on these results; we demonstrate that it should have more than adequate coverage for genome-wide association mapping. The extent of LD is highly variable, and we find clear evidence of recombination hotspots, which seem to occur preferentially in intergenic regions. LD also reflects the action of selection, and it is more extensive between nonsynonymous polymorphisms than between synonymous polymorphisms.     

Multispecies-compatible antitumor effects of a cross-species small-interfering RNA against mammalian target of rapamycin

Successful development of sequence-specific siRNA (small interfering RNA)-based drugs requires an siRNA design that functions consistently in different organisms. Utilizing the CAPSID program previously developed by our group, we here designed siRNAs against mammalian target of rapamycin (mTOR) that are entirely complementary among various species and investigated their multispecies-compatible gene-silencing properties. The mTOR siRNAs markedly reduced mTOR expression at both the mRNA and protein levels in human, mouse, and monkey cell lines. The reduction in mTOR expression resulted in inactivation of both mTOR complex I and II signaling pathways, as confirmed by reduced phosphorylation of p70S6K (70-kDa ribosomal protein S6 kinase), 4EBP1 (eIF4E-binding protein 1), and AKT, and nuclear accumulation of FOXO1 (forkhead box O1), with consequent cell-cycle arrest, proliferation inhibition, and autophagy activation. Moreover, interfering with mTOR activity in vivo using mTOR small-hairpin RNA-expressing recombinant adeno-associated virus led to significant antitumor effects in xenograft and allograft models. Thus, the present study demonstrates that cross-species siRNA successfully silences its target and readily produces multispecies-compatible phenotypic alterations-antitumor effects in the case of mTOR siRNA. Application of cross-species siRNA should greatly facilitate the development of siRNA-based therapeutic agents.     

Activation of the AXL kinase causes resistance to EGFR-targeted therapy in lung cancer

Human non-small cell lung cancers (NSCLCs) with activating mutations in EGFR frequently respond to treatment with EGFR-targeted tyrosine kinase inhibitors (TKIs), such as erlotinib, but responses are not durable, as tumors acquire resistance. Secondary mutations in EGFR (such as T790M) or upregulation of the MET kinase are found in over 50% of resistant tumors. Here, we report increased activation of AXL and evidence for epithelial-to-mesenchymal transition (EMT) in multiple in vitro and in vivo EGFR-mutant lung cancer models with acquired resistance to erlotinib in the absence of the EGFR p.Thr790Met alteration or MET activation. Genetic or pharmacological inhibition of AXL restored sensitivity to erlotinib in these tumor models. Increased expression of AXL and, in some cases, of its ligand GAS6 was found in EGFR-mutant lung cancers obtained from individuals with acquired resistance to TKIs. These data identify AXL as a promising therapeutic target whose inhibition could prevent or overcome acquired resistance to EGFR TKIs in individuals with EGFR-mutant lung cancer.     

PPAR γ partial agonist, KR-62776, inhibits adipocyte differentiation via activation of ERK

Indenone KR-62776 acts as an agonist of PPARγ without inducing obesity in animal models and cells. X-ray crystallography reveals that the indenone occupies the binding pocket in a different manner than rosiglitazone. 2-Dimensional gel-electrophoresis showed that the expression of 42 proteins was altered more than 2.0-fold between KR-62776- or rosiglitazone-treated adipocyte cells and control cells. Rosiglitazone down-regulated the expression of ERK1/2 and suppressed the phosphorylation of ERK1/2 in these cells. However, the expression of ERK1/2 was up-regulated in KR-62776-treated cells. Phosphorylated ERK1/2, activated by indenone, affects the localization of PPARγ, suggesting a mechanism for indenone-inhibition of adipogenesis in 3T3-L1 preadipocyte cells. The preadipocyte cells are treated with ERK1/2 inhibitor PD98059, a large amount of the cells are converted to adipocyte cells. These results support the conclusion that the localization of PPARγ is one of the key factors explaining the biological responses of the ligands. Received 04 March 2009; received after revision 13 March 2009; accepted 17 March 2009     

Differentiated cells are more efficient than adult stem cells for cloning by somatic cell nuclear transfer

Since the creation of Dolly via somatic cell nuclear transfer (SCNT), more than a dozen species of mammals have been cloned using this technology. One hypothesis for the limited success of cloning via SCNT (1%-5%) is that the clones are likely to be derived from adult stem cells. Support for this hypothesis comes from the findings that the reproductive cloning efficiency for embryonic stem cells is five to ten times higher than that for somatic cells as donors and that cloned pups cannot be produced directly from cloned embryos derived from differentiated B and T cells or neuronal cells. The question remains as to whether SCNT-derived animal clones can be derived from truly differentiated somatic cells. We tested this hypothesis with mouse hematopoietic cells at different differentiation stages: hematopoietic stem cells, progenitor cells and granulocytes. We found that cloning efficiency increases over the differentiation hierarchy, and terminally differentiated postmitotic granulocytes yield cloned pups with the greatest cloning efficiency.     

硬质合金可转位刀片周边仿形磨削方法的精度分析

本文根据仿磨原理,分别讨论了砂轮磨损和用一个标准仿形凸轮仿磨不同大小的同形非标准刀片时所产生的磨削误差及形状畸变,并导出了计算磨削误差及畸变的参数方程.     

Electroluminescence from single monolayers of nanocrystals in molecular organic devices

The integration of organic and inorganic materials at the nanometre scale into hybrid optoelectronic structures enables active devices that combine the diversity of organic materials with the high-performance electronic and optical properties of inorganic nanocrystals. The optimization of such hybrid devices ultimately depends upon the precise positioning of the functionally distinct materials. Previous studies have already emphasized that this is a challenge, owing to the lack of well-developed nanometre-scale fabrication techniques. Here we demonstrate a hybrid light-emitting diode (LED) that combines the ease of processability of organic materials with the narrow-band, efficient luminescence of colloidal quantum dots (QDs). To isolate the luminescence processes from charge conduction, we fabricate a quantum-dot LED (QD-LED) that contains only a single monolayer of QDs, sandwiched between two organic thin films. This is achieved by a method that uses material phase segregation between the QD aliphatic capping groups and the aromatic organic materials. In our devices, where QDs function exclusively as lumophores, we observe a 25-fold improvement in luminescence efficiency (1.6 cd A(-1) at 2,000 cd m(-2)) over the best previous QD-LED results. The reproducibility and precision of our phase-segregation approach suggests that this technique could be widely applicable to the fabrication of other hybrid organic/inorganic devices.