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

Anatomical Pathways Involved in Generating and Sensing Rhythmic Whisker Movements

The rodent whisker system is widely used as a model system for investigating sensorimotor integration, neural mechanisms of complex cognitive tasks, neural development, and robotics. The whisker pathways to the barrel cortex have received considerable attention. However, many subcortical structures are paramount to the whisker system. They contribute to important processes, like filtering out salient features, integration with other senses, and adaptation of the whisker system to the general behavioral state of the animal. We present here an overview of the brain regions and their connections involved in the whisker system. We do not only describe the anatomy and functional roles of the cerebral cortex, but also those of subcortical structures like the striatum, superior colliculus, cerebellum, pontomedullary reticular formation, zona incerta, and anterior pretectal nucleus as well as those of level setting systems like the cholinergic, histaminergic, serotonergic, and noradrenergic pathways. We conclude by discussing how these brain regions may affect each other and how they together may control the precise timing of whisker movements and coordinate whisker perception

Cues and knowledge structures used by mental-health professionals when making risk assessments

Background: Research into mental-health risks has tended to focus on epidemiological approaches and to consider pieces of evidence in isolation. Less is known about the particular factors and their patterns of occurrence that influence clinicians’ risk judgements in practice. Aims: To identify the cues used by clinicians to make risk judgements and to explore how these combine within clinicians’ psychological representations of suicide, self-harm, self-neglect, and harm to others. Method: Content analysis was applied to semi-structured interviews conducted with 46 practitioners from various mental-health disciplines, using mind maps to represent the hierarchical relationships of data and concepts. Results: Strong consensus between experts meant their knowledge could be integrated into a single hierarchical structure for each risk. This revealed contrasting emphases between data and concepts underpinning risks, including: reflection and forethought for suicide; motivation for self-harm; situation and context for harm to others; and current presentation for self-neglect. Conclusions: Analysis of experts’ risk-assessment knowledge identified influential cues and their relationships to risks. It can inform development of valid risk-screening decision support systems that combine actuarial evidence with clinical expertise

The development of a space climatology: 1. solar-wind magnetosphere coupling as a function of timescale and the effect of data gaps

Different terrestrial space weather indicators (such as geomagnetic indices, transpolar voltage, and ring current particle content) depend on different “coupling functions” (combinations of near-Earth solar wind parameters) and previous studies also reported a dependence on the averaging timescale, {\tau}. We study the relationships of the am and SME geomagnetic indices to the power input into the magnetosphere P_{\alpha}, estimated using the optimum coupling exponent {\alpha} for a range of {\tau} between 1 min and 1 year. The effect of missing data is investigated by introducing synthetic gaps into near-continuous data and the best method for dealing with them when deriving the coupling function, is formally defined. Using P_{\alpha}, we show that gaps in data recorded before 1995 have introduced considerable errors into coupling functions. From the near-continuous solar wind data for 1996-2016, we find {\alpha} = 0.44 plus/minus 0.02 and no significant evidence that {\alpha} depends on {\tau}, yielding P_{\alpha} = B^0.88 Vsw^1.90 (mswNsw)^0.23 sin4({\theta}/2), where B is the Interplanetary Magnetic Field (IMF), Nsw the solar wind number density, msw its mean ion mass, Vsw its velocity and {\theta} is the IMF clock angle in the Geocentric Solar Magnetospheric reference frame. Values of P_{\alpha} that are accurate to within plus/minus 5% for 1996-2016 have an availability of 83.8% and the correlation between P_{\alpha} and am for these data is shown to be 0.990 (between 0.972 and 0.997 at the 2{\sigma} uncertainty level), 0.897 plus/minus 0.004, and 0.790 plus/minus 0.03, for {\tau} of 1 year, 1 day and 3 hours, respectively, and that between P_{alpha} and SME at {\tau} of 1 min. is 0.7046 plus/minus 0.0004

Conceptualising sustainability in UK urban Regeneration: a discursive Formation

Despite the wide usage and popular appeal of the concept of sustainability in UK policy, it does not appear to have challenged the status quo in urban regeneration because policy is not leading in its conceptualisation and therefore implementation. This paper investigates how sustainability has been conceptualised in a case-based research study of the regeneration of Eastside in Birmingham, UK, through policy and other documents, and finds that conceptualisations of sustainability are fundamentally limited. The conceptualisation of sustainability operating within urban regeneration schemes should powerfully shape how they make manifest (or do not) the principles of sustainable development. Documents guide, but people implement regeneration—and the disparate conceptualisations of stakeholders demonstrate even less coherence than policy. The actions towards achieving sustainability have become a policy ‘fix’ in Eastside: a necessary feature of urban policy discourse that is limited to solutions within market-based constraints

Heme oxygenase-1 regulates cell proliferation via carbon monoxide-mediated inhibition of T-type Ca2+ channels

Induction of the antioxidant enzyme heme oxygenase-1 (HO-1) affords cellular protection and suppresses proliferation of vascular smooth muscle cells (VSMCs) associated with a variety of pathological cardiovascular conditions including myocardial infarction and vascular injury. However, the underlying mechanisms are not fully understood. Over-expression of Cav3.2 T-type Ca2+ channels in HEK293 cells raised basal [Ca2+]i and increased proliferation as compared with non-transfected cells. Proliferation and [Ca2+]i levels were reduced to levels seen in non-transfected cells either by induction of HO-1 or exposure of cells to the HO-1 product, carbon monoxide (CO) (applied as the CO releasing molecule, CORM-3). In the aortic VSMC line A7r5, proliferation was also inhibited by induction of HO-1 or by exposure of cells to CO, and patch-clamp recordings indicated that CO inhibited T-type (as well as L-type) Ca2+ currents in these cells. Finally, in human saphenous vein smooth muscle cells, proliferation was reduced by T-type channel inhibition or by HO-1 induction or CO exposure. The effects of T-type channel blockade and HO-1 induction were non-additive. Collectively, these data indicate that HO-1 regulates proliferation via CO-mediated inhibition of T-type Ca2+ channels. This signalling pathway provides a novel means by which proliferation of VSMCs (and other cells) may be regulated therapeutically

The development of a space climatology: 2. The distribution of power input into the magnetosphere on a 3‐hourly timescale

Paper 1 in this series (Lockwood et al., 2018a, https://doi.org/10.1029/2018SW001856) showed that the power input into the magnetosphere Pα is an ideal coupling function for predicting geomagnetic “range” indices that are strongly dependent on the substorm current wedge and that the optimum coupling exponent α is 0.44 for all averaging timescales, τ, between 1 min and 1 year. The present paper explores the implications of these results. It is shown that the form of the distribution of Pα at all averaging timescales τ is set by the interplanetary magnetic field orientation factor via the nature of solar wind‐magnetosphere coupling (due to magnetic reconnection in the dayside magnetopause) and that at τ = 3 hr (the timescale of geomagnetic range indices) the normalized Pα (divided by its annual mean, that is, τ=3hr/τ=1yr) follows a Weibull distribution with k of 1.0625 and λ of 1.0240. This applies to all years to a useful degree of accuracy. It is shown that exploiting the constancy of this distribution and using annual means to predict the full distribution gives the probability of space weather events in the largest 10% and 5% to within uncertainties of magnitude 10% and 12%, respectively, at the one sigma level

A global phylogeny of butterflies reveals their evolutionary history, ancestral hosts and biogeographic origins

Butterflies are a diverse and charismatic insect group that are thought to have evolved with plants and dispersed throughout the world in response to key geological events. However, these hypotheses have not been extensively tested because a comprehensive phylogenetic framework and datasets for butterfly larval hosts and global distributions are lacking. We sequenced 391 genes from nearly 2,300 butterfly species, sampled from 90 countries and 28 specimen collections, to reconstruct a new phylogenomic tree of butterflies representing 92% of all genera. Our phylogeny has strong support for nearly all nodes and demonstrates that at least 36 butterfly tribes require reclassification. Divergence time analyses imply an origin similar to 100 million years ago for butterflies and indicate that all but one family were present before the K/Pg extinction event. We aggregated larval host datasets and global distribution records and found that butterflies are likely to have first fed on Fabaceae and originated in what is now the Americas. Soon after the Cretaceous Thermal Maximum, butterflies crossed Beringia and diversified in the Palaeotropics. Our results also reveal that most butterfly species are specialists that feed on only one larval host plant family. However, generalist butterflies that consume two or more plant families usually feed on closely related plants

American Gut: an Open Platform for Citizen Science Microbiome Research

McDonald D, Hyde E, Debelius JW, et al. American Gut: an Open Platform for Citizen Science Microbiome Research. mSystems. 2018;3(3):e00031-18

Basic science232. Certolizumab pegol prevents pro-inflammatory alterations in endothelial cell function

Background: Cardiovascular disease is a major comorbidity of rheumatoid arthritis (RA) and a leading cause of death. Chronic systemic inflammation involving tumour necrosis factor alpha (TNF) could contribute to endothelial activation and atherogenesis. A number of anti-TNF therapies are in current use for the treatment of RA, including certolizumab pegol (CZP), (Cimzia ®; UCB, Belgium). Anti-TNF therapy has been associated with reduced clinical cardiovascular disease risk and ameliorated vascular function in RA patients. However, the specific effects of TNF inhibitors on endothelial cell function are largely unknown. Our aim was to investigate the mechanisms underpinning CZP effects on TNF-activated human endothelial cells. Methods: Human aortic endothelial cells (HAoECs) were cultured in vitro and exposed to a) TNF alone, b) TNF plus CZP, or c) neither agent. Microarray analysis was used to examine the transcriptional profile of cells treated for 6 hrs and quantitative polymerase chain reaction (qPCR) analysed gene expression at 1, 3, 6 and 24 hrs. NF-κB localization and IκB degradation were investigated using immunocytochemistry, high content analysis and western blotting. Flow cytometry was conducted to detect microparticle release from HAoECs. Results: Transcriptional profiling revealed that while TNF alone had strong effects on endothelial gene expression, TNF and CZP in combination produced a global gene expression pattern similar to untreated control. The two most highly up-regulated genes in response to TNF treatment were adhesion molecules E-selectin and VCAM-1 (q 0.2 compared to control; p > 0.05 compared to TNF alone). The NF-κB pathway was confirmed as a downstream target of TNF-induced HAoEC activation, via nuclear translocation of NF-κB and degradation of IκB, effects which were abolished by treatment with CZP. In addition, flow cytometry detected an increased production of endothelial microparticles in TNF-activated HAoECs, which was prevented by treatment with CZP. Conclusions: We have found at a cellular level that a clinically available TNF inhibitor, CZP reduces the expression of adhesion molecule expression, and prevents TNF-induced activation of the NF-κB pathway. Furthermore, CZP prevents the production of microparticles by activated endothelial cells. This could be central to the prevention of inflammatory environments underlying these conditions and measurement of microparticles has potential as a novel prognostic marker for future cardiovascular events in this patient group. Disclosure statement: Y.A. received a research grant from UCB. I.B. received a research grant from UCB. S.H. received a research grant from UCB. All other authors have declared no conflicts of interes