High-yielding 18F radiosynthesis of a novel oxytocin receptor tracer, a probe for nose-to-brain oxytocin uptake in vivo

A novel Al18F labelled peptide tracer for PET imaging of oxytocin receptor has been accessed through a high radiochemical yield approach. This tracer showed comparable affinity and higher selectivity and stability compared to oxytocin, and was used to demonstrate direct nose-to-brain uptake following intranasal administration, a common yet controversial delivery route for oxytocin-based therapeutics

Complete quantization of a diffeomorphism invariant field theory

In order to test the canonical quantization programme for general relativity we introduce a reduced model for a real sector of complexified Ashtekar gravity which captures important properties of the full theory. While it does not correspond to a subset of Einstein's gravity it has the advantage that the programme of canonical quantization can be carried out completely and explicitly, both, via the reduced phase space approach or along the lines of the algebraic quantization programme. This model stands in close correspondence to the frequently treated cylindrically symmetric waves. In contrast to other models that have been looked at up to now in terms of the new variables the reduced phase space is infinite dimensional while the scalar constraint is genuinely bilinear in the momenta. The infinite number of Dirac observables can be expressed in compact and explicit form in terms of the original phase space variables. They turn out, as expected, to be non-local and form naturally a set of countable cardinality.Comment: 32p, LATE

Development of photocrosslinking probes based on Huwentoxin-IV to map the site of interaction on Nav1.7

Voltage-gated sodium (Nav) channels respond to changes in the membrane potential of excitable cells through the concerted action of four voltage-sensor domains (VSDs). Subtype Nav1.7 plays an important role in the propagation of signals in pain-sensing neurons and is a target for the clinical development of novel analgesics. Certain inhibitory cystine knot (ICK) peptides produced by venomous animals potently modulate Nav1.7, however the molecular mechanisms underlying their selective binding and activity remain elusive. This study reports on the design of a library of photoprobes based on the potent spider toxin Huwentoxin-IV and the determination of the toxin binding interface on VSD2 of Nav1.7 through a photocrosslinking and tandem mass spectrometry approach. Our Huwentoxin-IV probes selectively crosslink to extracellular loop S1-2 and helix S3 of VSD2 in a chimeric channel system. Our results provide a strategy that will enable mapping of sites of interaction of other ICK peptides on Nav channels

Effects of the Selective Serotonin Reuptake Inhibitor Fluoxetine on Counterregulatory Responses to Hypoglycemia in Individuals With Type 1 Diabetes

OBJECTIVE—Previous work has demonstrated that chronic administration of the serotonin reuptake inhibitor (SSRI) fluoxetine augments counterregulatory responses to hypoglycemia in healthy humans. However, virtually no information exists regarding the effects of fluoxetine on integrated physiological counterregulatory responses during hypoglycemia in type 1 diabetes. Therefore, the specific aim of this study was to test the hypothesis that 6-week use of the SSRI fluoxetine would amplify autonomic nervous system (ANS) counterregulatory responses to hypoglycemia in individuals with type 1 diabetes

Protein multi-scale organization through graph partitioning and robustness analysis: Application to the myosin-myosin light chain interaction

Despite the recognized importance of the multi-scale spatio-temporal organization of proteins, most computational tools can only access a limited spectrum of time and spatial scales, thereby ignoring the effects on protein behavior of the intricate coupling between the different scales. Starting from a physico-chemical atomistic network of interactions that encodes the structure of the protein, we introduce a methodology based on multi-scale graph partitioning that can uncover partitions and levels of organization of proteins that span the whole range of scales, revealing biological features occurring at different levels of organization and tracking their effect across scales. Additionally, we introduce a measure of robustness to quantify the relevance of the partitions through the generation of biochemically-motivated surrogate random graph models. We apply the method to four distinct conformations of myosin tail interacting protein, a protein from the molecular motor of the malaria parasite, and study properties that have been experimentally addressed such as the closing mechanism, the presence of conserved clusters, and the identification through computational mutational analysis of key residues for binding.Comment: 13 pages, 7 Postscript figure

The Anatomy of Memory Politics: A Formalist Analysis of Tate Britain’s ‘Artist and Empire’ and the Struggle over Britain’s Imperial Past

In this paper, I propose a new approach for understanding the meaning of memory politics, which draws upon the archetypal literary criticism of Northrop Frye. I suggest that the four archetypes elaborated by Frye—comedy, romance, tragedy, and satire—can be used as a heuristic device for interpreting the contested historical narratives that are associated with the politics of memory. I illustrate this approach through a case-study of Artists and Empire: Facing Britain’s Imperial Past, an exhibition held at Tate Britain in 2016, amidst increasing contestation over the meaning of the British Empire. In sum, I find that the exhibit narrated Britain’s imperial past as a comedy, in which a key theme was the progressive cultural mixing of the British and the people they colonized. To conclude, I discuss the implications of such a narrative for constructing an inclusive, postcolonial British identity. As an alternative, I draw on Aristotle to suggest that a tragic narrative would have been more propitious

Some closure operations in Zariski-Riemann spaces of valuation domains: a survey

In this survey we present several results concerning various topologies that were introduced in recent years on spaces of valuation domains

Conformal blocks and generalized theta functions

Let M(r) be the moduli space of rank r vector bundles with trivial determinant on a Riemann surface X . This space carries a natural line bundle, the determinant line bundle L . We describe a canonical isomorphism of the space of global sections of L^k with a space known in conformal field theory as the ``space of conformal blocks", which is defined in terms of representations of the Lie algebra sl(r, C((z))).Comment: 43 pages, Plain Te