The geometry of the double-pulsar system J0737-3039 from systematic intensity variations

The recent discovery of J0737-3039A & B-two pulsars in a highly relativistic orbit around one another - offers an unprecedented opportunity to study the elusive physics of pulsar radio emission. The system contains a rapidly rotating pulsar with a spin period of 22.7 ms and a slow companion with a spin period of 2.77 s, hereafter referred to as 'A' and 'B', respectively. A unique property of the system is that the pulsed radio flux from B increases systematically by almost two orders-of-magnitude during two short portions of each orbit. Here, we describe a geometrical model of the system that simultaneously explains the intensity variations of B and makes definitive and testable predictions for the future evolution of the emission properties of both stars. Our model assumes that B's pulsed radio flux increases when illuminated by emission from A. This model provides constraints on the spin axis orientation and emission geometry of A and predicts that its pulse profile will evolve considerably over the next several years due to geodetic precession until it disappears entirely in 15-20 years

Liver Transplantation for Alagille's Syndrome

Twenty-three children with Alagille's syndrome and end-stage liver disease underwent liver transplantation with cyclosporine and low-dose steroid immunosuppression. Two to 9 years (mean, 4.4 years) after surgery, 13 (57%) of the children were still alive, with normal liver function. Three of the fatalities were due to cardiovascular failure secondary to associated cardiopulmonary disease. Mortality was higher among patients who had more severe cardiac disease and patients who had previously undergone a Kasai procedure. Although it has a higher than average risk, liver transplantation can be efficacious in patients with Alagille's syndrome and end-stage liver disease. (Arch Surg. 1993;128:337-339). © 1993, American Medical Association. All rights reserved

Quantum anti-Zeno effect without wave function reduction

We study the measurement-induced enhancement of the spontaneous decay (called quantum anti-Zeno effect) for a two-level subsystem, where measurements are treated as couplings between the excited state and an auxiliary state rather than the von Neumann's wave function reduction. The photon radiated in a fast decay of the atom, from the auxiliary state to the excited state, triggers a quasi-measurement, as opposed to a projection measurement. Our use of the term "quasi-measurement" refers to a "coupling-based measurement". Such frequent quasi-measurements result in an exponential decay of the survival probability of atomic initial state with a photon emission following each quasi-measurement. Our calculations show that the effective decay rate is of the same form as the one based on projection measurements. What is more important, the survival probability of the atomic initial state which is obtained by tracing over all the photon states is equivalent to the survival probability of the atomic initial state with a photon emission following each quasi-measurement to the order under consideration. That is because the contributions from those states with photon number less than the number of quasi-measurements originate from higher-order processes.Comment: 7 pages, 3 figure

Use of approximations of Hamilton-Jacobi-Bellman inequality for solving periodic optimization problems

We show that necessary and sufficient conditions of optimality in periodic optimization problems can be stated in terms of a solution of the corresponding HJB inequality, the latter being equivalent to a max-min type variational problem considered on the space of continuously differentiable functions. We approximate the latter with a maximin problem on a finite dimensional subspace of the space of continuously differentiable functions and show that a solution of this problem (existing under natural controllability conditions) can be used for construction of near optimal controls. We illustrate the construction with a numerical example.Comment: 29 pages, 2 figure

Resistance to novel drug classes

Understanding the mechanisms that underlie resistance development to novel drugs is essential to a better clinical management of resistant viruses and to prevent further resistance development and spread. RECENT FINDINGS: Integrase inhibitors and CCR5 antagonists are the more recent antiretroviral classes developed. The HIV-1 integrase, responsible for the chromosomal integration of the newly synthesized double-stranded viral DNA into the host genomic DNA, represents a new and important target; and two integrase inhibitors (INIs), raltegravir and elvitegravir, have been shown promising results in clinical trials. Viral entry is also an attractive step for the development of new drugs against HIV variants resistant to current antiretroviral drugs, and two CCR5 antagonists have been designed to inhibit HIV-1 binding to R5 co-receptor and are under clinical investigation. SUMMARY: Drug resistance to INIs occurs through the selection of mutations within HIV integrase. The kinetic of selection seems rapid and one mutation alone is able to confer resistance to integrase inhibitor, suggesting that this class of drug has a low genetic barrier. Two ways could explain the failure of the CCR5 antagonist class: a rapid outgrowth of pre-existing archived X4 virus or the selection of a resistance to CCR5 antagonists through amino acid changes in V

Distributed Change Detection via Average Consensus over Networks

Distributed change-point detection has been a fundamental problem when performing real-time monitoring using sensor-networks. We propose a distributed detection algorithm, where each sensor only exchanges CUSUM statistic with their neighbors based on the average consensus scheme, and an alarm is raised when local consensus statistic exceeds a pre-specified global threshold. We provide theoretical performance bounds showing that the performance of the fully distributed scheme can match the centralized algorithms under some mild conditions. Numerical experiments demonstrate the good performance of the algorithm especially in detecting asynchronous changes.Comment: 15 pages, 8 figure

Rodents and humans are able to detect the odour of L-Lactate.

This is the final version of the article. Available from PLoS via the DOI in this record.L-Lactate (LL) is an essential cellular metabolite which can be used to generate energy. In addition, accumulating evidence suggests that LL is used for inter-cellular signalling. Some LL-sensitive receptors have been identified but we recently proposed that there may be yet another unknown G-protein coupled receptor (GPCR) sensitive to LL in the brain. Olfactory receptors (ORs) represent the largest family of GPCRs and some of them are expressed outside the olfactory system, including brain, making them interesting candidates for non-olfactory LL signalling. One of the "ectopically" expressed ORs, Olfr78 in mice (Olr59 in rats and OR51E2 in humans), reportedly can be activated by LL. This implies that both rodents and humans should be able to detect the LL odour. Surprisingly, this has never been demonstrated. Here we show that mice can detect the odour of LL in odour detection and habituation-dishabituation tasks, and discriminate it from peppermint and vanilla odours. Behaviour of the Olfr78 null mice and wildtype mice in odour detection task was not different, indicating that rodents are equipped with more than one LL-sensitive OR. Rats were also able to use the smell of LL as a cue in an odour-reward associative learning task. When presented to humans, more than 90% of participants detected a smell of LL in solution. Interestingly, LL was perceived differently than acetate or propionate-LL was preferentially reported as a pleasant sweet scent while acetate and propionate were perceived as repulsive sour/acid smells. Subjective perception of LL smell was different in men and women. Taken together, our data demonstrate that both rodents and humans are able to detect the odour of LL. Moreover, in mice, LL perception is not purely mediated by Olfr78. Discovery of further LL-sensitive OR might shed the light on their contribution to LL signalling in the body.This work was supported by BBSRC: BB/L019396/1, BB/K009192/1; and MRC MR/L020661/1. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript