计算机在医学中的应用

本文主要介绍计算机与医学的关系及在医学各领域中的应用。     

Towards sound epistemological foundations of statistical methods for high-dimensional biology

A sound epistemological foundation for biological inquiry comes, in part, from application of valid statistical procedures. This tenet is widely appreciated by scientists studying the new realm of high-dimensional biology, or 'omic' research, which involves multiplicity at unprecedented scales. Many papers aimed at the high-dimensional biology community describe the development or application of statistical techniques. The validity of many of these is questionable, and a shared understanding about the epistemological foundations of the statistical methods themselves seems to be lacking. Here we offer a framework in which the epistemological foundation of proposed statistical methods can be evaluated.     

Alternative nucleotide incision repair pathway for oxidative DNA damage.

The DNA glycosylase pathway, which requires the sequential action of two enzymes for the incision of DNA, presents a serious problem for the efficient repair of oxidative DNA damage, because it generates genotoxic intermediates such as abasic sites and/or blocking 3'-end groups that must be eliminated by additional steps before DNA repair synthesis can be initiated. Besides the logistical problems, biological evidence hints at the existence of an alternative repair pathway. Mutants of Escherichia coli and mice (ref. 4 and M. Takao et al., personal communication) that are deficient in DNA glycosylases that remove oxidized bases are not sensitive to reactive oxygen species, and the E. coli triple mutant nei, nth, fpg is more radioresistant than the wild-type strain. Here we show that Nfo-like endonucleases nick DNA on the 5' side of various oxidatively damaged bases, generating 3'-hydroxyl and 5'-phosphate termini. Nfo-like endonucleases function next to each of the modified bases that we tested, including 5,6-dihydrothymine, 5,6-dihydrouracil, 5-hydroxyuracil and 2,6-diamino-4-hydroxy-5-N-methylformamidopyrimidine residues. The 3'-hydroxyl terminus provides the proper end for DNA repair synthesis; the dangling damaged nucleotide on the 5' side is then a good substrate for human flap-structure endonuclease and for DNA polymerase I of E. coli.     

Disposition of the portal vessels of the avian pituitary in relation to the median eminence and the pars distalis

Zusammenfassung Die ermittelte Gefässversorgung der Vogelhypophyse beweist die Existenz eines doppelten Portalsystems der Pars distalis, womit auf zwei hypothalamo-hypophysäre Mechanismen hingewiesen wird.     

Enhancement of cellular memory by reducing stochastic transitions

On induction of cell differentiation, distinct cell phenotypes are encoded by complex genetic networks. These networks can prevent the reversion of established phenotypes even in the presence of significant fluctuations. Here we explore the key parameters that determine the stability of cellular memory by using the yeast galactose-signalling network as a model system. This network contains multiple nested feedback loops. Of the two positive feedback loops, only the loop mediated by the cytoplasmic signal transducer Gal3p is able to generate two stable expression states with a persistent memory of previous galactose consumption states. The parallel loop mediated by the galactose transporter Gal2p only increases the expression difference between the two states. A negative feedback through the inhibitor Gal80p reduces the strength of the core positive feedback. Despite this, a constitutive increase in the Gal80p concentration tunes the system from having destabilized memory to having persistent memory. A model reveals that fluctuations are trapped more efficiently at higher Gal80p concentrations. Indeed, the rate at which single cells randomly switch back and forth between expression states was reduced. These observations provide a quantitative understanding of the stability and reversibility of cellular differentiation states.     

Étude de l'activité in vitro de la glycogène phosphorylase de la Carpe (Cyprinus carpio L.)

Summary In this paper we give some values of glycogen phosphorylase activity of heart, red muscle and white muscle from the Carp. We show that in vitro optimum temperature is 25°C for the fish, and not 30°C as in Mammalians. We also made measurements with rat and tench liver, but it has been impossible, under the same experimental conditions, to observe normal release of inorganic phosphorus from G-1-P with carp liver.     

De novo mutations revealed by whole-exome sequencing are strongly associated with autism

Multiple studies have confirmed the contribution of rare de novo copy number variations to the risk for autism spectrum disorders. But whereas de novo single nucleotide variants have been identified in affected individuals, their contribution to risk has yet to be clarified. Specifically, the frequency and distribution of these mutations have not been well characterized in matched unaffected controls, and such data are vital to the interpretation of de novo coding mutations observed in probands. Here we show, using whole-exome sequencing of 928 individuals, including 200 phenotypically discordant sibling pairs, that highly disruptive (nonsense and splice-site) de novo mutations in brain-expressed genes are associated with autism spectrum disorders and carry large effects. On the basis of mutation rates in unaffected individuals, we demonstrate that multiple independent de novo single nucleotide variants in the same gene among unrelated probands reliably identifies risk alleles, providing a clear path forward for gene discovery. Among a total of 279 identified de novo coding mutations, there is a single instance in probands, and none in siblings, in which two independent nonsense variants disrupt the same gene, SCN2A (sodium channel, voltage-gated, type II, α subunit), a result that is highly unlikely by chance.     

脉冲耦合神经网络对肝包虫图像分割

 在应用脉冲耦合神经网络模型分割图像的研究中,确定模型的参数是一个难点问题,其中连接系数β在脉冲耦合神经网络中起着重要的作用。本文使用最小交叉熵D(P, Q; t )和标准差,简化了脉冲耦合神经网络模型的连接系数β的估计公式,该方法可以自动确定并简化脉冲耦合神经网络模型的连接系数β。实验结果表明,该方法对肝包虫医学图像的分割效果显著,能获得较好的视觉结果并具有较强的普适性。     

Microstructure,mechanical properties and formability of friction stir welded dissimilar materials of IF-steel and 6061 Al alloy

AA 6061 alloy and interstitial-free(IF)steel plates were joined by the friction stir welding(FSW)method,and the microstructure,mechanical properties,and biaxial stretch formability of the friction stir welded(FSWed)parts were investigated.The results indicate that the FSWed parts showed optimum tensile strength during FSW with the 0.4-mm offset position of the tool.The Fe4Al13 intermetallic compound formed in the defect-free intersection of AA 6061 and IF-steel plates during FSW.The hardness of the IF-steel part of the FSWed region increased almost 90%relative to its initial hardness of HV0.2 105.The tensile and yield strengths of FSWed regions were approximately 170 MPa and 145 MPa,respectively.According to the formability tests,the Erichsen Index(EI)of the IF-steel,AA 6061,and the FSWed samples were determined to be 2.9 mm,1.9 mm,and 2.1 mm,respectively.The EI of the FSWed sample was almost the same as that of the AA 6061 alloy.However,it decreased compared with that of the IF-steel.The force at EI(FEI)was approximately 1180 N for the FSWed condition.This value is approximately 70%higher than that of AA 6061 alloy.