基于关系代数的遗传算法模型及其应用

运用选择、投影、广义笛卡尔积等关系代数运算 ,给出了遗传算法的搜索空间及个体、遗传算子和搜索最优解过程等关系代数形式的描述 ,建立了遗传算法的关系代数模型 ,给出了遗传算法的数学解释 .然后 ,给出建立遗传算法关系代数模型的意义 ,说明了数据挖掘和知识发现应用于遗传算法的可行性 .最后 ,用该模型描述了 2个常见用遗传算法解决的问题 ,即TSP问题和交互式遗传算法中的服装设计问题 ,结果表明该模型的可行性 .     

Alcohol dehydrogenase 2 is a major hepatic enzyme for human retinol metabolism

The metabolism of all-trans- and 9-cis-retinol/ retinaldehyde has been investigated with focus on the activities of human, mouse and rat alcohol dehydrogenase 2 (ADH2), an intriguing enzyme with apparently different functions in human and rodents. Kinetic constants were determined with an HPLC method and a structural approach was implemented by in silico substrate dockings. For human ADH2, the determined K_m values ranged from 0.05 to 0.3 μM and k_cat values from 2.3 to 17.6 min⁻¹, while the catalytic efficiency for 9-cis-retinol showed the highest value for any substrate. In contrast, poor activities were detected for the rodent enzymes. A mouse ADH2 mutant (ADH2Pro47His) was studied that resembles the human ADH2 setup. This mutation increased the retinoid activity up to 100-fold. The K_m values of human ADH2 are the lowest among all known human retinol dehydrogenases, which clearly support a role in hepatic retinol oxidation at physiological concentrations. Received 12 October 2006; received after revision 6 December 2006; accepted 8 January 2007     

Cellular internalization of proinsulin C-peptide

Proinsulin C-peptide is known to bind specifically to cell membranes and to exert intracellular effects, but whether it is internalized in target cells is unknown. In this study, using confocal microscopy and immunostained or rhodamine-labeled peptide, we show that C-peptide is internalized and localized to the cytosol of Swiss 3T3 and HEK-293 cells. In addition, transport into nuclei was found using the labeled peptide. The internalization was followed at 37°C for up to 1 h, and was reduced at 4°C and after preincubation with pertussis toxin. Hence, it is concluded to occur via an energy-dependent, pertussis toxin-sensitive mechanism and without detectable degradation within the experimental time course. Surface plasmon resonance measurements demonstrated binding of HEK-293 cell extract components to C-peptide, and subsequent elution of bound material revealed the components to be intracellular proteins. The identification of C-peptide cellular internalization, intracellular binding proteins, absence of rapid subsequent C-peptide degradation and apparent nuclear internalization support a maintained activity similar to that of an intracrine peptide hormone. Hence, the data suggest the possibility of one further C-peptide site of action. Received 31 October 2006; received after revision 27 December 2006; accepted 30 December 2006     

Tracings of the north of Europe: Robert Chambers in search of the Ice Age

Scottish publisher and naturalist Robert Chambers pursued an amateur interest in geology through much of his life. His early measurements of raised beaches in Scotland earned him membership in the Geological Society of London in 1844, a recognition much appreciated by the anonymous author of the ‘scandalous’ Vestiges published the same year. Although familiar with emerging ice age theories, Chambers remained with most British geologists a sceptic through the 1840s, even after a trip to the glaciers of the Alps in 1848, which nevertheless prepared him for the turning point, which came in 1849 during an extensive field trip in Norway and Sweden. Here a wealth of observations left him in no doubt that vast glaciers had formerly covered Scandinavia, polishing cliffs, scouring striations, depositing old moraines and erratic boulders. This also led him to a new glacial reading of the British landscape, and with the ardent conviction of a fresh convert he became one of the most vocal supporters of glacial theory in Britain in the 1850s at a time when the iceberg drift theory for boulder transport was still favoured by most prominent British geologists. While Chambers through his popular Chambers’s Edinburgh Journal communicated his travels and ice age vision to a wide audience, and also pointed out ice age evidence on guided excursions around Edinburgh, he did not enter this new vision into subsequent editions of Vestiges, probably in order not to reveal its author. This paper explores Chambers’s contributions to the ice age debate, his field trips and the genesis of his convictions, and evaluates his impact on the scientific debate.     

Genome-wide association study identifies a new melanoma susceptibility locus at 1q21.3

We performed a genome-wide association study of melanoma in a discovery cohort of 2,168 Australian individuals with melanoma and 4,387 control individuals. In this discovery phase, we confirm several previously characterized melanoma-associated loci at MC1R, ASIP and MTAP-CDKN2A. We selected variants at nine loci for replication in three independent case-control studies (Europe: 2,804 subjects with melanoma, 7,618 control subjects; United States 1: 1,804 subjects with melanoma, 1,026 control subjects; United States 2: 585 subjects with melanoma, 6,500 control subjects). The combined meta-analysis of all case-control studies identified a new susceptibility locus at 1q21.3 (rs7412746, P = 9.0 × 10(-11), OR in combined replication cohorts of 0.89 (95% CI 0.85-0.95)). We also show evidence suggesting that melanoma associates with 1q42.12 (rs3219090, P = 9.3 × 10(-8)). The associated variants at the 1q21.3 locus span a region with ten genes, and plausible candidate genes for melanoma susceptibility include ARNT and SETDB1. Variants at the 1q21.3 locus do not seem to be associated with human pigmentation or measures of nevus density.     

Transforming growth factor-β-inducible early response gene 1 is a novel substrate for atypical protein kinase Cs

The protein kinase C (PKC) family of serine/threonine kinases consists of ten different isoforms grouped into three subfamilies, denoted classical, novel and atypical PKCs (aPKCs). The aPKCs, PKCι/λ and PKCζ serve important roles during development and in processes subverted in cancer such as cell and tissue polarity, cell proliferation, differentiation and apoptosis. In an effort to identify novel interaction partners for aPKCs, we performed a yeast two-hybrid screen with the regulatory domain of PKCι/λ as bait and identified the Krüppel-like factors family protein TIEG1 as a putative interaction partner for PKCι/λ. We confirmed the interaction of both aPKCs with TIEG1 in vitro and in cells, and found that both aPKCs phosphorylate the DNA-binding domain of TIEG1 on two critical residues. Interestingly, the aPKC-mediated phosphorylation of TIEG1 affected its DNA-binding activity, subnuclear localization and transactivation potential.     

从随机和到随机和过程

随机和的概念是早就有的,但利用随机和的形式构造随机过程尚未见先例。本文首先引进随机和过程的概念,对过程的一些性质进行了探讨,并举例说明了随机和过程的应用。我们利用本文的结论对布朗运动问题给出了简单的解法,得出的结果与求解朗之万随机微分方程的结果是相合的。本文提出了随机耗散系统的概念,这种系统是广泛存在的,发现随机和过程是描述这种系统机制的有效工具。     

新型木工螺旋刨刀设计方面注记

本文根据新型木工螺旋刨刀生产中提出的设计问题,给出了计算公式及其依据,为新型木工螺旋刨刀的实际制造提供了依据。     

Identification and characterisation of two allelic forms of human alcohol dehydrogenase 2

The human alcohol dehydrogenase system is comprised of multiple forms that catalyse the oxidation/reduction of a large variety of alcohols and aldehydes. A transition that results in an Ile308Val substitution was identified in the human ADH2 gene by single-strand conformation polymorphism analysis. Screening a Swedish population revealed that Val308 was the most frequent allele (73%), and site-directed mutagenesis was used to obtain both allelozymes, which were expressed in Escherichia coli for characterisation. Thermostability was assayed by activity measurements and circular dichroism spectroscopy. The results showed that the 308Val substitution decreases protein stability, as compared to the Ile308 variant, an effect also demonstrated during prolonged storage. Ethanol, octanol, 12-hydroxydodecanoic acid and all-trans retinol were used as model substrates and, generally, slightly higher Km values were observed with Val at position 308. Finally, homology modelling, from mouse ADH2, further supported the decreased stability of the Val308 variant and located position 308 in the subunit interface of the molecule and in the vicinity of the active-site pocket entrance. In conclusion, the Ile308Val substitution represents a novel functional polymorphism within the human alcohol dehydrogenase gene cluster that may affect the metabolism of ethanol and other substrates.