28 research outputs found
The Rule of Law is Dead! Long Live the Rule of Law!
Polls show that a significant proportion of the public considers judges to be political. This result holds whether Americans are asked about Supreme Court justices, federal judges, state judges, or judges in general. At the same time, a large majority of the public also believes that judges are fair and impartial arbiters, and this belief also applies across the board. In this paper, I consider what this half-law-half-politics understanding of the courts means for judicial legitimacy and the public confidence on which that legitimacy rests. Drawing on the Legal Realists, and particularly on the work of Thurman Arnold, I argue against the notion that the contradictory views must be resolved in order for judicial legitimacy to remain intact. A rule of law built on contending legal and political beliefs is not necessarily fair or just. But it can be stable. At least in the context of law and courts, a house divided may stand
Prioritization of genes driving congenital phenotypes of patients with de novo genomic structural variants
Background:Genomic structural variants (SVs) can affect many genes and regulatory elements. Therefore, the molecular mechanisms driving the phenotypes of patients carrying de novo SVs are frequently unknown.
Methods:We applied a combination of systematic experimental and bioinformatic methods to improve the molecular diagnosis of 39 patients with multiple congenital abnormalities and/or intellectual disability harboring apparent de novo SVs, most with an inconclusive diagnosis after regular genetic testing.
Results: In 7 of these cases (18%), whole-genome sequencing analysis revealed disease-relevant complexities of the SVs missed in routine microarray-based analyses. We developed a computational tool to predict the effects on genes directly affected by SVs and on genes indirectly affected likely due to the changes in chromatin organization and impact on regulatory mechanisms. By combining these functional predictions with extensive phenotype information, candidate driver genes were identified in 16/39 (41%) patients. In 8 cases, evidence was found for the involvement of multiple candidate drivers contributing to different parts of the phenotypes. Subsequently, we applied this computational method to two cohorts containing a total of 379 patients with previously detected and classified de novo SVs and identified candidate driver genes in 189 cases (50%), including 40 cases whose SVs were previously not classified as pathogenic. Pathogenic position effects were predicted in 28% of all studied cases with balanced SVs and in 11% of the cases with copy number variants.
Conclusions:These results demonstrate an integrated computational and experimental approach to predict driver genes based on analyses of WGS data with phenotype association and chromatin organization datasets. These analyses nominate new pathogenic loci and have strong potential to improve the molecular diagnosis of patients with de novo SVs
La solitaire dans la foule
L’ironie de cette expression si tendrement possessive, « Notre Colette », n’aurait pas, je crois, échappé à la femme si contradictoire qu’on fête ces jours-ci – une femme qui a lutté toute sa vie pour échapper aux entraves de la possession sans jamais avoir renoncé au désir d’être possédée. Chacun peut avoir « sa » Colette, mais « Notre Colette » est plutôt « Colette parmi nous » ; et parmi nous, comme la solitaire dans la foule qu’elle décrit dans un recueil de vingt trois nouvelles écrites ..
Notre Colette
« Notre » Colette… Des regards croisés se posent dans ces pages sur une œuvre décidément inclassable. Si la vie de l’écrivain – particulièrement dans son rapport à l’histoire – pique la curiosité au moins autant que ses livres, ceux-ci fournissent matière à de nouvelles réflexions : ils nous concernent, ici et maintenant, parce qu’ils évoquent une jouissance et des amours sans frontières, parce qu’ils chantent le culte de l’instant dilaté et maîtrisé, parce qu’ils osent présenter – et parfois préférer – les monstres. Ils laissent entrevoir la « femme cachée », les forces clandestines qui ouvrent la voie à l’écriture, suscitent d’étonnants personnages, et tracent un alphabet du monde. Cheminement très maîtrisé d’ailleurs, comme le montrent la mise en scène soignée des multiples images de l’écrivain, ou les étincelants paradoxes de son portrait inattendu en moraliste. Cette Colette-là est nôtre, parce qu’elle est autre