同分异构物分子结构与性能间的定量关系 1.多环芳烃中直链结构长度的优势

本文研究了多环烃异构物的分子轨道能量与电子活动性能的关系,包括各种并苯、联苯类异构物的分子轨道能级以及电子光谱等有关性能。每组异构物中,与最高占有分子轨道能级E_1及直接相关的性能以最长直链物为最低级限,带有侧位环的异构物则依侧位环数目递增,与E_(-1)及其直接相关性能,则以最长直链物为最高极限,依直环数的缩减而递减。各组异构物之间,性能～环数图线上形成的同系列曲线和等直环线都表明分子中直链的长度是主要因素。     

Intelligent Choice of the Number of Clusters in K-Means Clustering: An Experimental Study with Different Cluster Spreads

The issue of determining “the right number of clusters” in K-Means has attracted considerable interest, especially in the recent years. Cluster intermix appears to be a factor most affecting the clustering results. This paper proposes an experimental setting for comparison of different approaches at data generated from Gaussian clusters with the controlled parameters of between- and within-cluster spread to model cluster intermix. The setting allows for evaluating the centroid recovery on par with conventional evaluation of the cluster recovery. The subjects of our interest are two versions of the “intelligent” K-Means method, ik-Means, that find the “right” number of clusters by extracting “anomalous patterns” from the data one-by-one. We compare them with seven other methods, including Hartigan’s rule, averaged Silhouette width and Gap statistic, under different between- and within-cluster spread-shape conditions. There are several consistent patterns in the results of our experiments, such as that the right K is reproduced best by Hartigan’s rule – but not clusters or their centroids. This leads us to propose an adjusted version of iK-Means, which performs well in the current experiment setting.     

Complex reorganization and predominant non-homologous repair following chromosomal breakage in karyotypically balanced germline rearrangements and transgenic integration

We defined the genetic landscape of balanced chromosomal rearrangements at nucleotide resolution by sequencing 141 breakpoints from cytogenetically interpreted translocations and inversions. We confirm that the recently described phenomenon of 'chromothripsis' (massive chromosomal shattering and reorganization) is not unique to cancer cells but also occurs in the germline, where it can resolve to a relatively balanced state with frequent inversions. We detected a high incidence of complex rearrangements (19.2%) and substantially less reliance on microhomology (31%) than previously observed in benign copy-number variants (CNVs). We compared these results to experimentally generated DNA breakage-repair by sequencing seven transgenic animals, revealing extensive rearrangement of the transgene and host genome with similar complexity to human germline alterations. Inversion was the most common rearrangement, suggesting that a combined mechanism involving template switching and non-homologous repair mediates the formation of balanced complex rearrangements that are viable, stably replicated and transmitted unaltered to subsequent generations.     

Regulated import and degradation of a cytosolic protein in the yeast vacuole.

The key regulatory enzyme in gluconeogenesis, fructose 1,6-bisphosphatase (FBPase) is subject to glucose-stimulated proteolytic degradation in Saccharomyces cerevisiae. This process involves the regulated transfer of FBPase directly from the cytosol into the vacuole or a vacuole-related organelle. Glucose may regulate the production of an FBPase receptor or import factor that is transported to the vacuole through the secretory pathway.     

Ferroelectric polarization,domains structures and magnetic property of Y1-xInxMnO3

The vortex domains, structural properties and ferroelectric polarization in Y1-xInxMn O3 with 0 B x B 0.6have been extensively investigated in well-characterized samples. X-ray diffraction measurements demonstrated that the lattice parameters change continuously following the substitution of In for Y. Measurements of magnetic susceptibilities revealed that In substitution could visibly affect the magnetic transition and low-temperature magnetic properties. Transmission electron microscopy study showed that In substitution could result in notable decrease of the size of ferroelectric vortex domains. Cs-corrected scanning transmission electron microscopy observations and our careful analysis on atomic-poling configurations demonstrate that the ferroelectric polarizations of Y1-xInxMn O3 are suppressed with the increase of In content.     

Genome-wide association scan identifies a colorectal cancer susceptibility locus on chromosome 8q24

Using a multistage genetic association approach comprising 7,480 affected individuals and 7,779 controls, we identified markers in chromosomal region 8q24 associated with colorectal cancer. In stage 1, we genotyped 99,632 SNPs in 1,257 affected individuals and 1,336 controls from Ontario. In stages 2-4, we performed serial replication studies using 4,024 affected individuals and 4,042 controls from Seattle, Newfoundland and Scotland. We identified one locus on chromosome 8q24 and another on 9p24 having combined odds ratios (OR) for stages 1-4 of 1.18 (trend; P = 1.41 x 10(-8)) and 1.14 (trend; P = 1.32 x 10(-5)), respectively. Additional analyses in 2,199 affected individuals and 2,401 controls from France and Europe supported the association at the 8q24 locus (OR = 1.16, trend; 95% confidence interval (c.i.): 1.07-1.26; P = 5.05 x 10(-4)). A summary across all seven studies at the 8q24 locus was highly significant (OR = 1.17, c.i.: 1.12-1.23; P = 3.16 x 10(-11)). This locus has also been implicated in prostate cancer.     

Multiple apical plasma membrane constituents are associated with susceptibility to meconium ileus in individuals with cystic fibrosis

Variants associated with meconium ileus in cystic fibrosis were identified in 3,763 affected individuals by genome-wide association study (GWAS). Five SNPs at two loci near SLC6A14 at Xq23-24 (minimum P = 1.28 × 10(-12) at rs3788766) and SLC26A9 at 1q32.1 (minimum P = 9.88 × 10(-9) at rs4077468) accounted for ~5% of phenotypic variability and were replicated in an independent sample of affected individuals (n = 2,372; P = 0.001 and 0.0001, respectively). By incorporating the knowledge that disease-causing mutations in CFTR alter electrolyte and fluid flux across surface epithelium into a hypothesis-driven GWAS (GWAS-HD), we identified associations with the same SNPs in SLC6A14 and SLC26A9 and established evidence for the involvement of SNPs in a third solute carrier gene, SLC9A3. In addition, GWAS-HD provided evidence of association between meconium ileus and multiple genes encoding constituents of the apical plasma membrane where CFTR resides (P = 0.0002; testing of 155 apical membrane genes jointly and in replication, P = 0.022). These findings suggest that modulating activities of apical membrane constituents could complement current therapeutic paradigms for cystic fibrosis.     

Exome sequencing identifies NMNAT1 mutations as a cause of Leber congenital amaurosis

Leber congenital amaurosis (LCA) is an autosomal recessive retinal dystrophy that manifests with genetic heterogeneity. We sequenced the exome of an individual with LCA and identified nonsense (c.507G>A, p.Trp169*) and missense (c.769G>A, p.Glu257Lys) mutations in NMNAT1, which encodes an enzyme in the nicotinamide adenine dinucleotide (NAD) biosynthesis pathway implicated in protection against axonal degeneration. We also found NMNAT1 mutations in ten other individuals with LCA, all of whom carry the p.Glu257Lys variant.     

Genomic sequencing of colorectal adenocarcinomas identifies a recurrent VTI1A-TCF7L2 fusion

Prior studies have identified recurrent oncogenic mutations in colorectal adenocarcinoma and have surveyed exons of protein-coding genes for mutations in 11 affected individuals. Here we report whole-genome sequencing from nine individuals with colorectal cancer, including primary colorectal tumors and matched adjacent non-tumor tissues, at an average of 30.7× and 31.9× coverage, respectively. We identify an average of 75 somatic rearrangements per tumor, including complex networks of translocations between pairs of chromosomes. Eleven rearrangements encode predicted in-frame fusion proteins, including a fusion of VTI1A and TCF7L2 found in 3 out of 97 colorectal cancers. Although TCF7L2 encodes TCF4, which cooperates with β-catenin in colorectal carcinogenesis, the fusion lacks the TCF4 β-catenin-binding domain. We found a colorectal carcinoma cell line harboring the fusion gene to be dependent on VTI1A-TCF7L2 for anchorage-independent growth using RNA interference-mediated knockdown. This study shows previously unidentified levels of genomic rearrangements in colorectal carcinoma that can lead to essential gene fusions and other oncogenic events.