Frequent mutations of chromatin remodeling genes in transitional cell carcinoma of the bladder

Transitional cell carcinoma (TCC) is the most common type of bladder cancer. Here we sequenced the exomes of nine individuals with TCC and screened all the somatically mutated genes in a prevalence set of 88 additional individuals with TCC with different tumor stages and grades. In our study, we discovered a variety of genes previously unknown to be mutated in TCC. Notably, we identified genetic aberrations of the chromatin remodeling genes (UTX, MLL-MLL3, CREBBP-EP300, NCOR1, ARID1A and CHD6) in 59% of our 97 subjects with TCC. Of these genes, we showed UTX to be altered substantially more frequently in tumors of low stages and grades, highlighting its potential role in the classification and diagnosis of bladder cancer. Our results provide an overview of the genetic basis of TCC and suggest that aberration of chromatin regulation might be a hallmark of bladder cancer.     

Effects of TiC on the microstructure and formation of acicular ferrite in ferritic stainless steel

The formation mechanism of acicular ferrite and its microstructural characteristics in 430 ferrite stainless steel with TiC additions were studied by theory and experiment. Using an edge-to-edge matching model, a 5.25 mismatch between TiC (FCC structure) and ferritic stainless steel (BCC structure) was identified, which met the mismatch requirement for the heterogeneous nucleation of 430 ferritic stainless steel. TiC was found to be an effective nucleation site for the formation of acicular ferrite in a smelting experiment, as analyzed by metallographic examination, Image-Pro Plus 6.0 analysis software, and SEM-EDS. Furthermore, small inclusions in the size of 2-4 μm increased the probability of acicular ferrite nucleation, and the secondary acicular ferrite would grow sympathetically from the initial acicular ferrite to produce multi-dimensional acicular ferrites. Moreover, the addition of TiC can increase the average microstrain and dislocation density of 430 ferrite stainless steel, as calculated by Williamson-Hall (WH) method, which could play some role in strengthening the dislocation.     

Taiga: Performance Optimization of the C4.5 Decision Tree Construction Algorithm

Classification is an important machine learning problem, and decision tree construction algorithms are an important class of solutions to this problem. Rain Forest is a scalable way to implement decision tree construction algorithms. It consists of several algorithms, of which the best one is a hybrid between a traditional recursive implementation and an iterative implementation which uses more memory but involves less write operations. We propose an optimized algorithm inspired by Rain Forest. By using a more sophisticated switching criterion between the two algorithms, we are able to get a performance gain even when all statistical information fits in memory. Evaluations show that our method can achieve a performance boost of 2.8 times in average than the traditional recursive implementation.     

随机变量列一类加权乘积和的强收敛性

讨论了任意r.v.列，两两NOD列和NA列的加权乘积和强收敛性，揭示了正则化因子，矩条件，权函数及r.v.列相关性之间的关系。     

THE INFLUENCE OF SO_3 IN C_2AF_(1-)-C_(11)A_7&CaF_2-C_2S SYSTEM ON FORMATION OF C_(11)A_7CaF_2

The paper reports investigation which have confirmed the relation between burningtemperature and formation of minerals,which exists in iron-rch fluornluminate cementIn order to burn iron-rich fluoraluminate cement at lower temperature,the SO_3 contentmust be controlled.     

A mouse model of human L1 retrotransposition

The L1 retrotransposon has had an immense impact on the size and structure of the human genome through a variety of mechanisms, including insertional mutagenesis. To study retrotransposition in a living organism, we created a mouse model of human L1 retrotransposition. Here we show that L1 elements can retrotranspose in male germ cells, and that expression of a human L1 element under the control of its endogenous promoter is restricted to testis and ovary. In the mouse line with the highest level of L1 expression, we found two de novo L1 insertions in 135 offspring. Both insertions were structurally indistinguishable from natural endogenous insertions. This suggests that an individual L1 element can have substantial mutagenic potential. In addition to providing a valuable in vivo model of retrotransposition in mammals, these mice are an important step in the development of a new random mutagenesis system.     

TNF-RII and c-IAP1 mediate ubiquitination and degradation of TRAF2

Tumour necrosis factor-alpha (TNF-alpha) is a proinflammatory mediator that exerts its biological functions by binding two TNF receptors (TNF-RI and TNF-RII), which initiate biological responses by interacting with adaptor and signalling proteins. Among the signalling components that associate with TNF receptors are members of the TNF-R-associated factor (TRAF) family. TRAF2 is required for TNF-alpha-mediated activation of c-Jun N-terminal kinase (JNK), contributes to activation of NF-kappaB, and mediates anti-apoptotic signals,. TNF-RI and TNF-RII signalling complexes also contain the anti-apoptotic ('inhibitor of apoptosis') molecules c-IAP1 and c-IAP2 (refs 5, 6), which also have RING domain-dependent ubiquitin protein ligase (E3) activity. The function of IAPs in TNF-R signalling is unknown. Here we show that binding of TNF-alpha to TNF-RII induces ubiquitination and proteasomal degradation of TRAF2. Although c-IAP1 bound TRAF2 and TRAF1 in vitro, it ubiquitinated only TRAF2. Expression of wild-type c-IAP1, but not an E3-defective mutant, resulted in TRAF2 ubiquitination and degradation. Moreover, E3-defective c-IAP1 prevented TNF-alpha-induced TRAF2 degradation and inhibited apoptosis. These findings identify a physiologic role for c-IAP1 and define a mechanism by which TNF-RII-regulated ubiquitin protein ligase activity can potentiate TNF-induced apoptosis.     

A 5-bp deletion in ELOVL4 is associated with two related forms of autosomal dominant macular dystrophy

Stargardt-like macular dystrophy (STGD3, MIM 600110) and autosomal dominant macular dystrophy (adMD) are inherited forms of macular degeneration characterized by decreased visual acuity, macular atrophy and extensive fundus flecks. Genetic mapping data suggest that mutations in a single gene may be responsible for both conditions, already known to bear clinical resemblance. Here we limit the minimum genetic region for STGD3 and adMD to a 0.6-cM interval by recombination breakpoint mapping and identify a single 5-bp deletion within the protein-coding region of a new retinal photoreceptor-specific gene, ELOVL4, in all affected members of STGD3 and adMD families. Bioinformatic analysis of ELOVL4 revealed that it has homology to a group of yeast proteins that function in the biosynthesis of very long chain fatty acids. Our results are therefore the first to implicate the biosynthesis of fatty acids in the pathogenesis of inherited macular degeneration.