Simulation-based model checking approach to cell fate specification during Caenorhabditis elegans vulval development by hybrid functional Petri net with extension

<p>Abstract</p> <p>Background</p> <p>Model checking approaches were applied to biological pathway validations around 2003. Recently, Fisher <it>et al</it>. have proved the importance of model checking approach by inferring new regulation of signaling crosstalk in <it>C. elegans </it>and confirming the regulation with biological experiments. They took a discrete and state-based approach to explore all possible states of the system underlying vulval precursor cell (VPC) fate specification for desired properties. However, since both discrete and continuous features appear to be an indispensable part of biological processes, it is more appropriate to use quantitative models to capture the dynamics of biological systems. Our key motivation of this paper is to establish a quantitative methodology to model and analyze <it>in silico </it>models incorporating the use of model checking approach.</p> <p>Results</p> <p>A novel method of modeling and simulating biological systems with the use of model checking approach is proposed based on hybrid functional Petri net with extension (HFPNe) as the framework dealing with both discrete and continuous events. Firstly, we construct a quantitative VPC fate model with 1761 components by using HFPNe. Secondly, we employ two major biological fate determination rules – Rule I and Rule II – to VPC fate model. We then conduct 10,000 simulations for each of 48 sets of different genotypes, investigate variations of cell fate patterns under each genotype, and validate the two rules by comparing three simulation targets consisting of fate patterns obtained from <it>in silico </it>and <it>in vivo </it>experiments. In particular, an evaluation was successfully done by using our VPC fate model to investigate one target derived from biological experiments involving hybrid lineage observations. However, the understandings of hybrid lineages are hard to make on a discrete model because the hybrid lineage occurs when the system comes close to certain thresholds as discussed by Sternberg and Horvitz in 1986. Our simulation results suggest that: Rule I that cannot be applied with qualitative based model checking, is more reasonable than Rule II owing to the high coverage of predicted fate patterns (except for the genotype of <it>lin-15ko; lin-12ko </it>double mutants). More insights are also suggested.</p> <p>Conclusion</p> <p>The quantitative simulation-based model checking approach is a useful means to provide us valuable biological insights and better understandings of biological systems and observation data that may be hard to capture with the qualitative one.</p

Ontology-based instance data validation for high-quality curated biological pathways

<p>Abstract</p> <p>Background</p> <p>Modeling in systems biology is vital for understanding the complexity of biological systems across scales and predicting system-level behaviors. To obtain high-quality pathway databases, it is essential to improve the efficiency of model validation and model update based on appropriate feedback.</p> <p>Results</p> <p>We have developed a new method to guide creating novel high-quality biological pathways, using a rule-based validation. Rules are defined to correct models against biological semantics and improve models for dynamic simulation. In this work, we have defined 40 rules which constrain event-specific participants and the related features and adding missing processes based on biological events. This approach is applied to data in Cell System Ontology which is a comprehensive ontology that represents complex biological pathways with dynamics and visualization. The experimental results show that the relatively simple rules can efficiently detect errors made during curation, such as misassignment and misuse of ontology concepts and terms in curated models.</p> <p>Conclusions</p> <p>A new rule-based approach has been developed to facilitate model validation and model complementation. Our rule-based validation embedding biological semantics enables us to provide high-quality curated biological pathways. This approach can serve as a preprocessing step for model integration, exchange and extraction data, and simulation.</p

リディア・M・チャイルド『共和国ロマンス』論 -ゴシック・ロマンス,その皮膚とその血と-

Abstract This paper describes reading A Romance of the Republic as a Gothic romance, revealing the slavery system as a cruel means of repressing human beings to a level below animals and of sexually exploiting black women. One of the leading members of the abolitionist movement, Lydia Maria Child, wrote this novel in 1869 not only to open the road toward admitting the miscegenation of the times but also to underscore the social value of giving educational and vocational training to black people. Child sets the beautiful octroon sisters, being as very light-skinned as white women and gifted in music and art, as the heroines of this narrative. Brought up in a secluded mansion in the suburbs of New Orleans, the sudden realization that they had become slaves on the death of their father befalls them. The narrative begins with their struggle to escape from the bonds of slavery to gain their freedom. The stark realism of the story works to subdue the high spirit of Child\u27s ideal for the Republic. Yet the narrative illuminates for us the superb gothic literary entertainment of escape and pursuit, white-skinned black beauties pitted against a white villain, their encounter as an opera singer and as an audience member, and the exchange of black and white babies, all set in such international cities as Boston, New York and Rome

Regional heritability mapping identifies several novel loci (STAT4, ULK4, and KCNH5) for primary biliary cholangitis in the Japanese population

原発性胆汁性胆管炎の新たな遺伝要因を同定 --ヒト全ゲノム領域へのRHM法による世界初の成果--. 京都大学プレスリリース. 2021-04-09.While the advent of GWAS more than a decade ago has ushered in remarkable advances in our understanding of complex traits, the limitations of single-SNP analysis have also led to the development of several other approaches. Simulation studies have shown that the regional heritability mapping (RHM) method, which makes use of multiple adjacent SNPs jointly to estimate the genetic effect of a given region of the genome, generally has higher detection power than single-SNP GWAS. However, thus far its use has been mostly limited to agricultural settings, and its potential for the discovery of new genes in human diseases is yet to be fully exploited. In this study, by applying the RHM method to primary biliary cholangitis (PBC) in the Japanese population, we identified three novel loci (STAT4, ULK4, and KCNH5) at the genome-wide significance level, two of which (ULK4 and KCNH5) have not been found associated with PBC in any population previously. Notably, these genes could not be detected by using conventional single-SNP GWAS, highlighting the potential of the RHM method for the detection of new susceptibility loci in human diseases. These findings thereby provide strong empirical evidence that RHM is an effective and practical complementary approach to GWAS in this context. Also, liver tissue mRNA microarray analysis revealed higher gene expression levels in ULK4 in PBC patients (P < 0.01). Lastly, we estimated the common SNP heritability of PBC in the Japanese population (0.210 ± 0.026)

マーガレット・フラーの反カトリック思想 : イタリアの独立・統一と教皇ピウスIX世

Margaret Fuller, a leader of various movements toward liberalism, stayed in Rome from 1847 to 1850. Supporting the unification and independence of Italian princedoms, she strongly backed the revolutionary Roman Republic government and opposed the Jesuits in their conventional political system. Consequently she was to encourage the revolutionary campaign for exiles at home, offending Bishop Hughes of New York City Catholic diocese. Here I would like to clarify the process of her understanding of Italian affairs toward 1848-9 revolutionary movement and her negative attitude to both Pius IX and Italian Catholicism. This reveals that Fuller, being a member of the Transcendental Club, was a radically individualistic and staunch republican, though ethically Puritan. Observing the relationship between the pope and his people and the various rites and rituals of Catholic society, she became aware of what she called \u27the cancer of society\u27, the Jesuits. Having become despondent because of the failure of 1849 revolution in Italy, she earnestly hoped that a republican Italy would be born again

マーガレット フラー ノ イタリア ダヨリ ローマ キョウワコク ホウカイ ト ニューヨーク ジャーナリズム ノ タイトウ

This paper discusses the last series of Margaret Fuller\u27s dispatches from Rome as being both her finest literary achievement and a valuable historical document. As a correspondent of the New York Daily Tribune, she became radical in her politics as the wave of revolutions swept the Continent. When the French army attacked Rome to get the Pope back, she continued to send dispatches from barricaded Rome in support of the Italian Risorgimento. Through all of her dispatches, Fuller assured her position as a prominent journalist who established a new concept in 19th century American Journalism. Aside from yellow journalism, she set her own standard of having the political news be the most exacting and its commentary be of historical significance. She clearly exemplified her political standing as a republican. With the help of Giuseppe Mazzini and charge d\u27affaires Lewis Cass Jr. of the United States, she was able to put political documents in the paper. And in following the same European cultural trend, her romantic diction in her articles became stronger, more succinct, and more realistic

マーガレット・フラーとジュゼッペ・マッツィーニ : 人民とは誰か

This paper intends to clarify the idea of the People by Mazzini and Fuller\u27s criticism for his republicanism. Mazzini was an Italian revolutionary and exiled to London when Fuller met him at Thomas Carlyle\u27s house. Deeply moved by his cause, Fuller continued to give her support througout her life to the movement for a united republican Italy and the Roman Republic in 1849. Regardless of their shared sense of republicanism, however, Fuller began to discover Mazzini\u27s idea of the People a little different from her and to realize he would not want to admit the existence of class struggle. From Giovine Italia and his motto \u27God and People\u27, he developed his duty theory that a person\u27s right shall be given after one performs one\u27s duty, which seems morally Catholic. Though he acknowledged the benefit of industry and the progress of mankind as did Saint - Simon and Fourier, he exhibited a tendency to minimize class division. In developing his notion of the People, he appeared to include people of all classes, whereas, in fact, from his revolutionary plan he excluded the lower class and peasant folk, togethev comprising three fourth of population in Italy then. Fuller asserted natural rights of all people from Protestant individualism. Fuller not only realized the radical change of social structure under industrial revolution but also learned such new theories as Fourier - system, and communism. Moreoven she came to understand the class struggle underlying in 1848 revolution in Paris, strongly conscious of the cries of lower class under the potato-famine and economic recession. Basically a transcendentalists, idealistic and romantic, while also being a feminist very realistic, Fuller became a radical, insisting on the bestowal of the natural rights of laboring classes on both Italian and American people

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Olive Schreiner was the first \u27modern\u27 colonial writer from South Africa, and one of the most brilliant feminist writers in late-Victorian Britain. Born in 1855 to missionary parents in colonial South Africa, she passionately refused both Empire and God, as well as the gender roles of Victorian society. Her narrative, The Story of an African Farm, struck well with the hearts of the intellectuals who had concerns about. the great changes unfolding from the growing capitalistic society. This paper principally endeavors to analyze how Waldo\u27s tale in The Story of an African Farm expresses the traumatic discovery that there is no God on the African Farm and how Lyndall\u27s tale elaborates the New Woman dispute in the current allegory of oppressed womankind. Though represented in a farcical, rather sad and grim way, Waldo\u27s father Otto, Boer woman Tant\u27 Sannie, and the fraud Bonaparte Blenkins together illuminate the bleak image of fatherlessness of the farm and colony, the failure of patriarchy itself, and the decaying evangelical theology. Bonaparte symbolizes the oppressor of the colony and also the capriciously cruel Will under Schreiner\u27s social Darwinism. In London, Schreiner joined The Men and Women\u27s Club founded by Carl Pearson and expanded her concept of women\u27s sexuality and labor. Throughout her life she sought to vindicate the oppressed free of any differences in class, race, and sex

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クワイ脂質から苦味成分を分離し,その性状について検討した。(1)クワイの総脂質は生クワイの0.28%を占め総脂質中の中性脂質,糖脂質およびリン脂質の組成は38 : 24 : 39であった。このうち,中性脂質画分で強い苦味が認められた。(2)中性脂質画分からの苦味成分の分離法としては,展開溶媒にヘキサンーエチルエーテルー酢酸の溶媒系を用いるシリカゲル薄層クロマトグラフィーが有効であった。(3)クワイの中性脂質は,シリカゲル薄層クロマトグラフィーで10個の化合物に分離された。そのうち3化合物(苦味A,BおよびC)に苦味が認められ,最も苦味の強かった苦味Bがクワイの主たる苦味成分と考えられた。さらに,苦味Bは,本実験で用いた標品(トリグリセリド,ジグリセリド,モノグリセリドおよび遊離脂肪酸)とは異なる化合物であった。(4)シリカゲル薄層クロマトグラフィーで分離した苦味A,BおよびCは,温度および酸素の影響を強く受け,大気中・25℃の保存で1週間後にすでに苦味を消失していた