Protein tyrosine phosphatase 1B deficiency or inhibition delays ErbB2-induced mammary tumorigenesis and protects from lung metastasis

We investigated the role of protein tyrosine phosphatase 1B (PTP1B) in mammary tumorigenesis using both genetic and pharmacological approaches. It has been previously shown that transgenic mice with a deletion mutation in the region of Erbb2 encoding its extracellular domain (referred to as NDL2 mice, for 'Neu deletion in extracellular domain 2') develop mammary tumors that progress to lung metastasis. However, deletion of PTP1B activity in the NDL2 transgenic mice either by breeding with Ptpn1-deficient mice or by treatment with a specific PTP1B inhibitor results in significant mammary tumor latency and resistance to lung metastasis. In contrast, specific overexpression of PTP1B in the mammary gland leads to spontaneous breast cancer development. The regulation of ErbB2-induced mammary tumorigenesis by PTB1B occurs through the attenuation of both the MAP kinase (MAPK) and Akt pathways. This report provides a rationale for the development of PTP1B as a new therapeutic target in breast cancer.     

Genome-wide meta-analysis increases to 71 the number of confirmed Crohn's disease susceptibility loci

We undertook a meta-analysis of six Crohn's disease genome-wide association studies (GWAS) comprising 6,333 affected individuals (cases) and 15,056 controls and followed up the top association signals in 15,694 cases, 14,026 controls and 414 parent-offspring trios. We identified 30 new susceptibility loci meeting genome-wide significance (P < 5 × 10??). A series of in silico analyses highlighted particular genes within these loci and, together with manual curation, implicated functionally interesting candidate genes including SMAD3, ERAP2, IL10, IL2RA, TYK2, FUT2, DNMT3A, DENND1B, BACH2 and TAGAP. Combined with previously confirmed loci, these results identify 71 distinct loci with genome-wide significant evidence for association with Crohn's disease.     

Wavelet Neural Networks for Adaptive Equalization by Using the Orthogonal Least Square Algorithm

Equalizers are widely used in digital communication systems for corrupted or time varying channels. To overcome performance decline for noisy and nonlinear channels, many kinds of neural network models have been used in nonlinear equalization. In this paper, we propose a new nonlinear channel equalization, which is structured by wavelet neural networks. The orthogonal least square algorithm is applied to update the weighting matrix of wavelet networks to form a more compact wavelet basis unit, thus obtaining good equalization performance. The experimental results show that performance of the proposed equalizer based on wavelet networks can significantly improve the neural modeling accuracy and outperform conventional neural network equalization in signal to noise ratio and channel non-linearity.     

A Non-confrontational Art of Living in the Technosphere and Infosphere

Several trends in contemporary philosophy have revived the question of the good life. This article addresses the more elaborate notion of an “art of living” in the specific context of the technosphere on the basis of recent works in philosophy of technology. It also brings ideas from Asian philosophy and from Buddhism in particular into the discussion. The focus is on the notion of non-confrontation, which could lead to a decisive change in the methods and scope of technology assessment within the humanities. The art of living in the technosphere emerges as an existential virtuosity that pertains to practical wisdom.     

Chromosomal rearrangements maintain a polymorphic supergene controlling butterfly mimicry

Supergenes are tight clusters of loci that facilitate the co-segregation of adaptive variation, providing integrated control of complex adaptive phenotypes. Polymorphic supergenes, in which specific combinations of traits are maintained within a single population, were first described for 'pin' and 'thrum' floral types in Primula and Fagopyrum, but classic examples are also found in insect mimicry and snail morphology. Understanding the evolutionary mechanisms that generate these co-adapted gene sets, as well as the mode of limiting the production of unfit recombinant forms, remains a substantial challenge. Here we show that individual wing-pattern morphs in the polymorphic mimetic butterfly Heliconius numata are associated with different genomic rearrangements at the supergene locus P. These rearrangements tighten the genetic linkage between at least two colour-pattern loci that are known to recombine in closely related species, with complete suppression of recombination being observed in experimental crosses across a 400-kilobase interval containing at least 18 genes. In natural populations, notable patterns of linkage disequilibrium (LD) are observed across the entire P region. The resulting divergent haplotype clades and inversion breakpoints are found in complete association with wing-pattern morphs. Our results indicate that allelic combinations at known wing-patterning loci have become locked together in a polymorphic rearrangement at the P locus, forming a supergene that acts as a simple switch between complex adaptive phenotypes found in sympatry. These findings highlight how genomic rearrangements can have a central role in the coexistence of adaptive phenotypes involving several genes acting in concert, by locally limiting recombination and gene flow.     

Effects of aging on the microstructures and mechanical properties of extruded AM50 ＋ xCa magnesium alloys

The effects of aging treatment on the microstructures and mechanical properties of extruded AM50 ＋ xCa alloys （x = 0. 1%, 2% in mass fraction） were studied. The results indicated the secondary phase Mg17Al12 precipitated from the saturated a-Mg solid solution while Al2Ca changed slightly when the aging time was increased. The hardness of extruded AM50 ＋ xCa alloys increased initially to its peak, and then dropped to reach its original hardness with the increase in aging time.