139 research outputs found
Repositioning Architecture in the Digital: Proceedings of the 7th annual conference of the Jaap Bakema Study Centre
No full textPublication at the occasion of the 7th annual conference of the Jaap Bakema Study Centre with contributions by Georg Vrachliotis, Armin Linke, Marina Otero Verzier, Ludo Groen, Martin Kuijpers, Dirk van den Heuvel and Soscha Monteiro de Jesus.Space & Typ
Metadata for: ‘Long-read sequencing identifies copy-specific markers of SMN gene conversion in spinal muscular atrophy’
No full textDescription
This DataverseNL item contains the metadata of the Nanopore sequencing dataset and limited clinical data used in ‘Long-read sequencing identifies copy-specific markers of SMN gene conversion in spinal muscular atrophy’. Access to this data is restricted due to privacy regulations; conditions and instructions for access are listed below.
Abstract
Background: The complex 2 Mb survival motor neuron (SMN) locus on chromosome 5q13, including the spinal muscular atrophy (SMA)-causing gene SMN1 and modifier SMN2, remains incompletely resolved due to numerous segmental duplications. Variation in SMN2 copy number, presumably influenced by SMN1 to SMN2 gene conversion, affects disease severity, though SMN2 copy number alone has insufficient prognostic value due to limited genotype-phenotype correlations. With advancements in newborn screening and SMN-targeted therapies, identifying genetic markers to predict disease progression and treatment response is crucial. Progress has thus far been limited by methodological constraints.
Methods: To address this, we developed HapSMA, a method to perform polyploid phasing of the SMN locus to enable copy-specific analysis of SMN and its surrounding genes. We used HapSMA on publicly available Oxford Nanopore Technologies (ONT) sequencing data of 29 healthy controls and performed long-read, targeted ONT sequencing of the SMN locus of 31 patients with SMA.
Results: In healthy controls, we identified single nucleotide variants (SNVs) specific to SMN1 and SMN2 haplotypes that could serve as gene conversion markers. Broad phasing including the NAIP gene allowed for a more complete view of SMN locus variation. Genetic variation in SMN2 haplotypes was larger in SMA patients. 42% of SMN2 haplotypes of SMA patients showed varying SMN1 to SMN2 gene conversion breakpoints, serving as direct evidence of gene conversion as a common genetic characteristic in SMA and highlighting the importance of inclusion of SMA patients when investigating the SMN locus.
Conclusions: Our findings illustrate that both methodological advances and the analysis of patient samples are required to advance our understanding of complex genetic loci and address critical clinical challenges.
Github
The code for HapSMA is available at: https://github.com/UMCUGenetics/HapSMA (v1.0.0 was used for analyses in this study, v1.1.0 contains extra support for different types of data input). The code for analyses subsequent to HapSMA and input files used in these analyses are available at: https://github.com/UMCUGenetics/ManuscriptSMNGeneConversion.
IRB approval
The study protocol (09307/NL29692.041.09) was approved by the Medical Ethical Committee of the University Medical Center Utrecht and registered at the Dutch registry for clinical studies and trials (https://www.ccmo.nl/). Written informed consent was obtained from all adult patients, and from patients and/or parents additionally in case of children younger than 18 years old.
Contact information
Requests for data can be made by contacting the principal investigators of this study, Ludo van der Pol ([email protected]), Gijs van Haaften ([email protected]) or Ewout Groen ([email protected]) at
University Medical Center Utrecht
UMC Utrecht Brain Center
Heidelberglaan 100
3584 CX Utrecht
The Netherlands
Expected response time for processing a data sharing agreement is 4 to 6 weeks. <br/
Was Henri de Man an early Post-Keynesian Neo-Marxist?
No full textHenri de Man is the author of the dissenting “Au-delà du Marxisme” (1926) and of the Belgian
Plan du Travail (Labor Plan) of 1933. Later he became a Belgian social-democratic leader. He
published between 1931 and 1935 18 economic articles in the Bulletin d’Information et de
Documentation of the National Bank of Belgium. It is shown that the articles, partly inspired by
Keynes’s writings up to 1931, are rather reflecting early Keynesian economic ideas relating to
government intervention and public works, and do not contain any reference to the multiplier
mechanism. A number of arguments in the articles are, however, advocating a Marxist inspired
underconsumption theory. Based on further analysis of these articles, it is concluded that they
contain also other important characteristics in common with the post-Keynesian neo-Marxist
economic theories developed after the Second World War, such as the importance attached
to the external markets of capitalism and a rejection of the labor theory of value, as well as
a neglect of the Marxian law of the falling rate of profits. Their economic ideas are rooted in
Marxism and the analysis of new economic phenomena, including the early Keynesianism of John
Maynard Keynes. Therefore, they should be considered as an early version of these theories
Some Comments on the Question Whether Co-Occurrence Data Should Be Normalized
Full text linkIn a recent article in JASIST, L. Leydesdorff and L. Vaughan (2006) asserted that raw cocitation data should be analyzed directly, without first applying a normalization such as the Pearson correlation. In this communication, it is argued that there is nothing wrong with the widely adopted practice of normalizing cocitation data. One of the arguments put forward by Leydesdorff and Vaughan turns out to depend crucially on incorrect multidimensional scaling maps that are due to an error in the PROXSCAL program in SPSS.multidimensional scaling;PROXSCAL;Pearson correlation;author cocitation analysis;co-occurrence data;normalization
The mental lexicon as a mediator on the effects of speech skills on phonological awareness in Turkish kindergarteners
No full textThe current study focuses on underlying cognitive-linguistic precursors of phonological
awareness which is important for learning to read. The lexical restructuring hypothesis relates a
higher speech perception and higher vocabulary to a higher phonological awareness. A missing
link between these is the phonological specificity of the mental lexicon that is a logical result of
higher vocabulary and speech perception. This “lexical specificity” was found to mediate the
relation between speech perception and vocabulary on the one hand, and phonological awareness
on the other hand. Although phonological representations are both perceptual and articulatory,
role of speech production was highly neglected. This study investigated whether lexical
specificity and vocabulary mediate the effects of speech perception and speech production on
phonological awareness in 57 Turkish kindergartners. Speech perception and production were
significantly correlated. Speech perception significantly predicted vocabulary, lexical specificity
and phonological awareness, while speech production did not. Results did not support the
mediation of mental lexicon on the effects of speech skills on phonological awareness. We
conclude that speech perception is an important precursor of language skills and that
development of certain skills may differ for languages with different orthographies.
Keywords: phonological awareness, lexical specificity, speech production, speech
perception, lexical restructuring hypothesi
Gioco, guerra e diritto nel De ludo scacchorum in legali methodo tractatus (1583) di Tommaso Azzi
No full textThe De ludo scacchorum in legale methodo tractatus (1583) of Tommaso Azzi, is not really a treatise on the game of chess, but a work that addresses various legal issues. In De ludo the theme of war is relevant. The aim of my essay is to show how the close connection between war, game of chess and law established by Azzi is functional to the idea of just war based on the game theory. According to Azzi the war has affinities to the game: strict rules, a limited and orderly space in which to take place, a position of equality between the parties. In this treaty the author underlines similarities between war and gaming and he represents war as a regulated phenomenon, within a path of “civilisation”.Il De ludo scacchorum in legali methodo tractatus (1583) del giurista Tommaso Azzi non è realmente un trattato sul gioco degli scacchi, ma un’opera che affronta varie questioni giuridiche. Tra i temi ricorrenti del De ludo troviamo il tema della guerra. La tesi di questo saggio è mostrare come la stretta connessione tra guerra, gioco degli scacchi e diritto stabilita da Azzi sia funzionale all’affermazione di una idea di guerra giusta ricalcata sul gioco. Tale guerra deve quindi possedere le caratteristiche proprie del gioco: regole severe, uno spazio limitato e ordinato in cui svolgersi, una posizione di uguaglianza tra le parti. Il trattato si inserisce così all’interno di una tradizione che, sottolineando le similitudini tra guerra e gioco, rappresenta la guerra come un fenomeno regolato, all’interno di un percorso di “civilizzazione”
Some Comments on the Question Whether Co-occurrence Data Should Be Normalized
Full text linkIn a recent paper in the Journal of the American Society for Information Science and Technology, Leydesdorff and Vaughan assert that raw cocitation data should be analyzed directly, without first applying a normalization like the Pearson correlation. In this report, it is argued that there is nothing wrong with the widely adopted practice of normalizing cocitation data. One of the arguments put forward by Leydesdorff and Vaughan turns out to depend crucially on incorrect multidimensional scaling maps that are due to an error in the PROXSCAL program in SPSS.Multidimensional scaling;Author cocitation analysis;Co-occurrence data;Normalization;PROXSCAL;Pearson correlation
José Eduardo Agualusa et sa Robinsonne Ludo
Full text linkFrom a cross-reading with Daniel Defoe’s Robinson Crusoe, we consider José Eduardo Agualusa’s novel, Teoria Geral do Esquecimento (2012), as a postmodern Robinsonade. Indeed, the author builds his character, Ludovica Fernandes Mano, as a castaway from Portuguese colonization in Angola, after the independence of the African country. She lived as a recluse for twenty-eight years in her apartment in Luanda, before getting out with the help of a young boy, Sabalu. From then on, a postcolonial reversal takes place, since this character, although he corresponds to the figure of Robinson’s Friday, is not in a subordinate position. The relationship that is established between Ludo and Sabalu is made up of mutual aid, care and reciprocal exchanges, a far cry from the unequivocal and ethnocentric relationship of Defoe’s novel.À partir d’une lecture croisée avec le Robinson Crusoe, de Daniel Defoe, nous envisageons le roman de José Eduardo Agualusa, Teoria Geral do Esquecimento (2012), comme une robinsonnade postmoderne. En effet, l’auteur construit son personnage, Ludovica Fernandes Mano, comme une naufragée de la colonisation portugaise en terres angolaises, au sortir de l’indépendance du pays africain. Elle vit recluse durant vingt-huit ans dans son appartement luandais, avant d’en sortir grâce à l’aide d’un jeune garçon, Sabalu. Dès lors, il s’opère un renversement postcolonial, puisque ce personnage, bien qu’il corresponde à la figure du Vendredi de Robinson, n’est pas dans une position subalterne. La relation qui s’établit entre Ludo et Sabalu est faite d’entraide, de sollicitude et d’échanges réciproques, bien loin donc de la relation univoque et ethnocentrée du roman de Defoe
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