Experimentally validated continuous-time repetitive control of non-minimum phase plants with a prescribed degree of stability

This paper considers the application of continuous-time repetitive control to non-minimum phase plants in a continuous-time model predictive control setting. In particular, it is shown how some critical performance problems associated with repetitive control of such plants can be avoided by use of predictive control with a prescribed degree of stability. The results developed are first illustrated by simulation studies and then through experimental tests on a non-minimum phase electro-mechanical system

Effects of Heparin and Enoxaparin on APP Processing and Aβ Production in Primary Cortical Neurons from Tg2576 Mice

BACKGROUND Alzheimer's disease (AD) is caused by accumulation of Aβ, which is produced through sequential cleavage of β-amyloid precursor protein (APP) by the β-site APP cleaving enzyme (BACE1) and γ-secretase. Enoxaparin, a low molecular weight form of the glycosaminoglycan (GAG) heparin, has been reported to lower Aβ plaque deposition and improve cognitive function in AD transgenic mice. METHODOLOGY/PRINCIPAL FINDINGS We examined whether heparin and enoxaparin influence APP processing and inhibit Aβ production in primary cortical cell cultures. Heparin and enoxaparin were incubated with primary cortical cells derived from Tg2576 mice, and the level of APP and proteolytic products of APP (sAPPα, C99, C83 and Aβ) was measured by western blotting. Treatment of the cells with heparin or enoxaparin had no significant effect on the level of total APP. However, both GAGs decreased the level of C99 and C83, and inhibited sAPPα and Aβ secretion. Heparin also decreased the level of β-secretase (BACE1) and α-secretase (ADAM10). In contrast, heparin had no effect on the level of ADAM17. CONCLUSIONS/SIGNIFICANCE The data indicate that heparin and enoxaparin decrease APP processing via both α- and β-secretase pathways. The possibility that GAGs may be beneficial for the treatment of AD needs further study.This work was funded by a project grant (490031) from the National Health and Medical Research Council of Australia (http://www.nhmrc.gov.au). The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript

Short-term genome stability of serial Clostridium difficile ribotype 027 isolates in an experimental gut model and recurrent human disease

Copyright: © 2013 Eyre et al. This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are creditedClostridium difficile whole genome sequencing has the potential to identify related isolates, even among otherwise indistinguishable strains, but interpretation depends on understanding genomic variation within isolates and individuals.Serial isolates from two scenarios were whole genome sequenced. Firstly, 62 isolates from 29 timepoints from three in vitro gut models, inoculated with a NAP1/027 strain. Secondly, 122 isolates from 44 patients (2–8 samples/patient) with mostly recurrent/on-going symptomatic NAP-1/027 C. difficile infection. Reference-based mapping was used to identify single nucleotide variants (SNVs).Across three gut model inductions, two with antibiotic treatment, total 137 days, only two new SNVs became established. Pre-existing minority SNVs became dominant in two models. Several SNVs were detected, only present in the minority of colonies at one/two timepoints. The median (inter-quartile range) [range] time between patients’ first and last samples was 60 (29.5–118.5) [0–561] days. Within-patient C. difficile evolution was 0.45 SNVs/called genome/year (95%CI 0.00–1.28) and within-host diversity was 0.28 SNVs/called genome (0.05–0.53). 26/28 gut model and patient SNVs were non-synonymous, affecting a range of gene targets.The consistency of whole genome sequencing data from gut model C. difficile isolates, and the high stability of genomic sequences in isolates from patients, supports the use of whole genome sequencing in detailed transmission investigations.Peer reviewe

Convergence Characteristics of the Cumulant Expansion for Fourier Path Integrals

The cumulant representation of the Fourier path integral method is examined to determine the asymptotic convergence characteristics of the imaginary-time density matrix with respect to the number of path variables $N$ included. It is proved that when the cumulant expansion is truncated at order $p$, the asymptotic convergence rate of the density matrix behaves like $N^{-(2p+1)}$. The complex algebra associated with the proof is simplified by introducing a diagrammatic representation of the contributing terms along with an associated linked-cluster theorem. The cumulant terms at each order are expanded in a series such that the the asymptotic convergence rate is maintained without the need to calculate the full cumulant at order $p$. Using this truncated expansion of each cumulant at order $p$, the numerical cost in developing Fourier path integral expressions having convergence order $N^{-(2p+1)}$ is shown to be approximately linear in the number of required potential energy evaluations making the method promising for actual numerical implementation.Comment: 47 pages, 2 figures, submitted to PR

The use of intraoperative nitrous oxide leads to postoperative increases in plasma homocysteine

Hyperhomocysteinemia is an independent risk factor for coronary artery and cerebrovascular disease, but its significance in the perioperative period is unknown. Nitrous oxide inhibits methionine synthase, which aids in the conversion of homocysteine to methionine. In this prospective, controlled, randomized study, we determined the effect of intraoperative nitrous oxide exposure on postoperative plasma homocysteine concentrations. Twenty ASA physical status I-III patients, aged \u3e18 yr, presenting for elective craniotomy, were randomized to receive general anesthesia with or without nitrous oxide (inspired nitrous oxide \u3e50%). Plasma was sampled before the induction of anesthesia, on arrival in the postanesthesia care unit (PACU) after discontinuation of nitrous oxide, and 24 h after induction. There was a significant increase (22.6 ± 11.4 vs 13.0 ± 4.7 μmol/L; P = 0.0038 for postoperative versus preinduction values) in plasma homocysteine concentrations in the nitrous oxide group on arrival in the PACU and for 24 h. In the nonnitrous oxide group, mean plasma homocysteine concentrations did not change (9.5 ± 1.9 vs 9.8 ± 1.6 μmol/L; P = 0.86 for postoperative versus preinduction values). The change in plasma homocysteine concentrations in the nitrous oxide group was significantly different from that in the nonnitrous group (P = 0.0031). We conclude that the use of intraoperative nitrous oxide leads to significant increases in perioperative plasma homocysteine concentrations. Implications: Short-term exposure to nitrous oxide led to significant increases in plasma homocysteine. Further investigations are required to determine the clinical significance of this change

Partial Averaging Approach to Fourier Coefficient Path Integration

The recently introduced method of partial averaging is developed in a general formalism for computing simple Cartesian path integrals. Examples of its application to both harmonic and anharmonic systems are given. For harmonic systems, where analytical results can be derived, both imaginary and complex time evolution is discussed. For two representative anharmonic systems, Monte Carlo path integral simulations of the imaginary time propagator (statistical density matrix) are presented. Connections with other Cartesian path integral techniques are stressed

When grassroots innovation movements encounter mainstream institutions: implications for models of inclusive innovation

Grassroots innovation movements (GIMs) can be regarded as initiators or advocates of alternative pathways of innovation. Sometimes these movements engage with more established science, technology and innovation (STI) institutions and development agencies in pursuit of their goals. In this paper, we argue that an important aspect to encounters between GIMs and mainstream STI institutions is the negotiation of different framings of grassroots innovation and development of policy models for inclusive innovation. These encounters can result in two different modes of engagement by GIMs; what we call insertion and mobilization. We illustrate and discuss these interrelated notions of framings and modes of engagement by drawing on three case studies of GIMs: the Social Technologies Network in Brazil, and the Honey Bee Network and People's Science Movements in India. The cases highlight that inclusion in the context of GIMs is not an unproblematic, smooth endeavour, and involves diverse interpretations and framings, which shape what and who gets included or excluded. Within the context of increasing policy interest, the analysis of encounters between GIMs and STI institutions can offer important lessons for the design of models of inclusive innovation and development

Re-colonizing spaces of memorializing: the case of the Chattri Indian Memorial, UK

This article inspects the ways that spaces of war memorialization are organized and reorganized through official and unofficial meaning-making activities. It aims to contribute to the discussion of the ‘value’ of memorializing by examining a multifaceted space of remembrance and commemoration: the Chattri Indian Memorial built near Brighton, UK. The article brings postcolonial perspectives to explore how memorializing has been organized here, focusing on the activities of once-colonized people and the affective, embodied aspects of organizing practices. Built in 1921 to honour Indian soldiers who fought in WWI, the Chattri evolved from a colonial instrument to symbol and space for ethnic-Indian group activities. The study employed historical, visual and ethnographic methods to study the tangible monument and the changing nature of the memorializing activities carried out around the monument. Memorializing is conceptualized within three inter-related processes: colonizing, de-colonizing and re-colonizing to examine how forms and practices of memorialization constitute a values-laden organizing system

Kinematic Evidence for an Old Stellar Halo in the Large Magellanic Cloud

The oldest and most metal-poor Milky Way stars form a kinematically hot halo, which motivates the two major formation scenarios for our galaxy: extended hierarchical accretion and rapid collapse. RR Lyrae stars are excellent tracers of old and metal-poor populations. We measure the kinematics of 43 RR Lyrae stars in the inner regions of the nearby Large Magellanic Cloud (LMC) galaxy. The velocity dispersion, \sigma_{true}=53\pm10 km/s, indicates that a kinematically hot metal-poor old halo also exists in the LMC. This suggests that our galaxy and smaller late-type galaxies like the LMC have similar early formation histories.Comment: 8 pages, 2 figures; to be published in Science on Sept. 12, 200