The body in the library: adventures in realism

This essay looks at two aspects of the virtual ‘material world’ of realist fiction: objects encountered by the protagonist and the latter’s body. Taking from Sartre two angles on the realist pact by which readers agree to lend their bodies, feelings, and experiences to the otherwise ‘languishing signs’ of the text, it goes on to examine two sets of first-person fictions published between 1902 and 1956 — first, four modernist texts in which banal objects defy and then gratify the protagonist, who ends up ready and almost able to write; and, second, three novels in which the body of the protagonist is indeterminate in its sex, gender, or sexuality. In each of these cases, how do we as readers make texts work for us as ‘an adventure of the body’

Practical, ethical and regulatory considerations for the evolving medical and research genomics landscape.

We are entering a fascinating and uncertain period of medical history, as today’s DNA sequencing technology has the potential to help each of us direct our care and predict our future based on knowledge of our own individual inherited and acquired genetics. However, from a global and local economic perspective, these are lean years, and this adds a significant degree of uncertainty to the immediate future of this enterprise. It is therefore incumbent upon us as a community to show that personalized genomic medicine will not just be a luxury or a burdensome cost center, but that it truly has the potential to save both lives and health care expenses via data-driven management, early disease detection/screening and more efficacious pharmaceutical delivery. To do this, we need to determine how to move forward towards expanded clinical use of this technology in a manner both rapid and economical, while ensuring the integrity of the process and the safety and well-being of patients and research participants. Here, we discuss some of the ethical, regulatory and practical considerations that are emerging in the field of genomic medicine. We also propose that many of the cost and safety issues we are facing can be mitigated through expanded reliance on existing clinical regulatory frameworks and the implementation of worksharing strategies designed to leverage the strengths of our genomics centers and clinical interpretive teams

Prevention of hormone action by local application of actinomycin D

This article does not have an abstract

Operations on integral lifts of K(n)

This very rough sketch is a sequel to arXiv:1808.08587; it presents evidence that operations on lifts of the functors K(n) to cohomology theories with values in modules over valuation rings of local number fields, indexed by Lubin-Tate groups of such fields, are extensions of the groups of automorphisms of the indexing group laws, by the exterior algebras on the normal bundle to the orbits of the group laws in the space of lifts.Comment: \S 2.0 hopefully less cryptic. To appear in the proceedings of the 2015 Nagoya conference honoring T Ohkawa. Comments very welcome

Type I D-branes in an H-flux and twisted KO-theory

Witten has argued that charges of Type I D-branes in the presence of an H-flux, take values in twisted KO-theory. We begin with the study of real bundle gerbes and their holonomy. We then introduce the notion of real bundle gerbe KO-theory which we establish is a geometric realization of twisted KO-theory. We examine the relation with twisted K-theory, the Chern character and provide some examples. We conclude with some open problems.Comment: 23 pages, Latex2e, 2 new references adde

dCas9-based epigenome editing suggests acquisition of histone methylation is not sufficient for target gene repression.

Distinct epigenomic profiles of histone marks have been associated with gene expression, but questions regarding the causal relationship remain. Here we investigated the activity of a broad collection of genomically targeted epigenetic regulators that could write epigenetic marks associated with a repressed chromatin state (G9A, SUV39H1, Krüppel-associated box (KRAB), DNMT3A as well as the first targetable versions of Ezh2 and Friend of GATA-1 (FOG1)). dCas9 fusions produced target gene repression over a range of 0- to 10-fold that varied by locus and cell type. dCpf1 fusions were unable to repress gene expression. The most persistent gene repression required the action of several effector domains; however, KRAB-dCas9 did not contribute to persistence in contrast to previous reports. A 'direct tethering' strategy attaching the Ezh2 methyltransferase enzyme to dCas9, as well as a 'recruitment' strategy attaching the N-terminal 45 residues of FOG1 to dCas9 to recruit the endogenous nucleosome remodeling and deacetylase complex, were both successful in targeted deposition of H3K27me3. Surprisingly, however, repression was not correlated with deposition of either H3K9me3 or H3K27me3. Our results suggest that so-called repressive histone modifications are not sufficient for gene repression. The easily programmable dCas9 toolkit allowed precise control of epigenetic information and dissection of the relationship between the epigenome and gene regulation