Open solar flux estimates from near-Earth measurements of the interplanetary magnetic field: comparison of the first two perihelion passes of the Ulysses spacecraft

Results from all phases of the orbits of the Ulysses spacecraft have shown that the magnitude of the radial component of the heliospheric field is approximately independent of heliographic latitude. This result allows the use of near- Earth observations to compute the total open flux of the Sun. For example, using satellite observations of the interplanetary magnetic field, the average open solar flux was shown to have risen by 29% between 1963 and 1987 and using the aa geomagnetic index it was found to have doubled during the 20th century. It is therefore important to assess fully the accuracy of the result and to check that it applies to all phases of the solar cycle. The first perihelion pass of the Ulysses spacecraft was close to sunspot minimum, and recent data from the second perihelion pass show that the result also holds at solar maximum. The high level of correlation between the open flux derived from the various methods strongly supports the Ulysses discovery that the radial field component is independent of latitude. We show here that the errors introduced into open solar flux estimates by assuming that the heliospheric field’s radial component is independent of latitude are similar for the two passes and are of order 25% for daily values, falling to 5% for averaging timescales of 27 days or greater. We compare here the results of four methods for estimating the open solar flux with results from the first and second perehelion passes by Ulysses. We find that the errors are lowest (1–5% for averages over the entire perehelion passes lasting near 320 days), for near-Earth methods, based on either interplanetary magnetic field observations or the aa geomagnetic activity index. The corresponding errors for the Solanki et al. (2000) model are of the order of 9–15% and for the PFSS method, based on solar magnetograms, are of the order of 13–47%. The model of Solanki et al. is based on the continuity equation of open flux, and uses the sunspot number to quantify the rate of open flux emergence. It predicts that the average open solar flux has been decreasing since 1987, as Correspondence to: M. Lockwood (m.lockwood@rl.ac.uk) is observed in the variation of all the estimates of the open flux. This decline combines with the solar cycle variation to produce an open flux during the second (sunspot maximum) perihelion pass of Ulysses which is only slightly larger than that during the first (sunspot minimum) perihelion pass.

Short-term variability of solar wind number density, speed and dynamic pressure as a function of the interplanetary magnetic field components: A survey over two solar cycles

The variability of hourly values of solar wind number density, number density variation, speed, speed variation and dynamic pressure with IMF Bz and magnitude |B| has been examined for the period 1965–1986. We wish to draw attention to a strong correlation in number density and number density fluctuation with IMF Bz characterised by a symmetric increasing trend in these quantities away from Bz = 0 nT. The fluctuation level in solar wind speed is found to be relatively independent of Bz. We infer that number density and number density variability dominate in controlling solar wind dynamic pressure and dynamic pressure variability. It is also found that dynamic pressure is correlated with each component of IMF and that there is evidence of morphological differences between the variation with each component. Finally, we examine the variation of number density, speed, dynamic pressure and fluctuation level in number density and speed with IMF magnitude |B|. Again we find that number density variation dominates over solar wind speed in controlling dynamic pressure.

Targeting myocardial remodelling to develop novel therapies for heart failure: a position paper from the Working Group on Myocardial Function of the European Society of Cardiology

The failing heart is characterized by complex tissue remodelling involving increased cardiomyocyte death, and impairment of sarcomere function, metabolic activity, endothelial and vascular function, together with increased inflammation and interstitial fibrosis. For years, therapeutic approaches for heart failure (HF) relied on vasodilators and diuretics which relieve cardiac workload and HF symptoms. The introduction in the clinic of drugs interfering with beta-adrenergic and angiotensin signalling have ameliorated survival by interfering with the intimate mechanism of cardiac compensation. Current therapy, though, still has a limited capacity to restore muscle function fully, and the development of novel therapeutic targets is still an important medical need. Recent progress in understanding the molecular basis of myocardial dysfunction in HF is paving the way for development of new treatments capable of restoring muscle function and targeting specific pathological subsets of LV dysfunction. These include potentiating cardiomyocyte contractility, increasing cardiomyocyte survival and adaptive hypertrophy, increasing oxygen and nutrition supply by sustaining vessel formation, and reducing ventricular stiffness by favourable extracellular matrix remodelling. Here, we consider drugs such as omecamtiv mecarbil, nitroxyl donors, cyclosporin A, SERCA2a (sarcoplasmic/endoplasmic Ca(2 +) ATPase 2a), neuregulin, and bromocriptine, all of which are currently in clinical trials as potential HF therapies, and discuss novel molecular targets with potential therapeutic impact that are in the pre-clinical phases of investigation. Finally, we consider conceptual changes in basic science approaches to improve their translation into successful clinical applications.

Discovering biomarkers for antidepressant response: protocol from the Canadian biomarker integration network in depression (CAN-BIND) and clinical characteristics of the first patient cohort

Background Major Depressive Disorder (MDD) is among the most prevalent and disabling medical conditions worldwide. Identification of clinical and biological markers (“biomarkers”) of treatment response could personalize clinical decisions and lead to better outcomes. This paper describes the aims, design, and methods of a discovery study of biomarkers in antidepressant treatment response, conducted by the Canadian Biomarker Integration Network in Depression (CAN-BIND). The CAN-BIND research program investigates and identifies biomarkers that help to predict outcomes in patients with MDD treated with antidepressant medication. The primary objective of this initial study (known as CAN-BIND-1) is to identify individual and integrated neuroimaging, electrophysiological, molecular, and clinical predictors of response to sequential antidepressant monotherapy and adjunctive therapy in MDD. Methods CAN-BIND-1 is a multisite initiative involving 6 academic health centres working collaboratively with other universities and research centres. In the 16-week protocol, patients with MDD are treated with a first-line antidepressant (escitalopram 10–20 mg/d) that, if clinically warranted after eight weeks, is augmented with an evidence-based, add-on medication (aripiprazole 2–10 mg/d). Comprehensive datasets are obtained using clinical rating scales; behavioural, dimensional, and functioning/quality of life measures; neurocognitive testing; genomic, genetic, and proteomic profiling from blood samples; combined structural and functional magnetic resonance imaging; and electroencephalography. De-identified data from all sites are aggregated within a secure neuroinformatics platform for data integration, management, storage, and analyses. Statistical analyses will include multivariate and machine-learning techniques to identify predictors, moderators, and mediators of treatment response. Discussion From June 2013 to February 2015, a cohort of 134 participants (85 outpatients with MDD and 49 healthy participants) has been evaluated at baseline. The clinical characteristics of this cohort are similar to other studies of MDD. Recruitment at all sites is ongoing to a target sample of 290 participants. CAN-BIND will identify biomarkers of treatment response in MDD through extensive clinical, molecular, and imaging assessments, in order to improve treatment practice and clinical outcomes. It will also create an innovative, robust platform and database for future research.

Characterisation of the intracellular-glutamate decarboxylase system (GAD): analysis of its function, transcription and role in the acid resistance of various strains of Listeria monocytogenes

The glutamate decarboxylase (GAD) system is important for the acid resistance of Listeria monocytogenes. We previously showed that under acidic conditions, glutamate (Glt)/γ-aminobutyrate (GABA) antiport is impaired in minimal media but not in rich ones, like brain heart infusion. Here we demonstrate that this behavior is more complex and it is subject to strain and medium variation. Despite the impaired Glt/GABA antiport, cells accumulate intracellular GABA (GABA(i)) as a standard response against acid in any medium, and this occurs in all strains tested. Since these systems can occur independently of one another, we refer to them as the extracellular (GAD(e)) and intracellular (GAD(i)) systems. We show here that GAD(i) contributes to acid resistance since in a ΔgadD1D2 mutant, reduced GABA(i) accumulation coincided with a 3.2-log-unit reduction in survival at pH 3.0 compared to that of wild-type strain LO28. Among 20 different strains, the GAD(i) system was found to remove 23.11% ± 18.87% of the protons removed by the overall GAD system. Furthermore, the GAD(i) system is activated at milder pH values (4.5 to 5.0) than the GAD(e) system (pH 4.0 to 4.5), suggesting that GAD(i) is the more responsive of the two and the first line of defense against acid. Through functional genomics, we found a major role for GadD2 in the function of GAD(i), while that of GadD1 was minor. Furthermore, the transcription of the gad genes in three common reference strains (10403S, LO28, and EGD-e) during an acid challenge correlated well with their relative acid sensitivity. No transcriptional upregulation of the gadT2D2 operon, which is the most important component of the GAD system, was observed, while gadD3 transcription was the highest among all gad genes in all strains. In this study, we present a revised model for the function of the GAD system and highlight the important role of GAD(i) in the acid resistance of L. monocytogenes.

6,6 '-bis-(5,6-diethyl-[1,2,4]triazin-3-yl)-2,2 '-bipyridyl the first example of a new class of quadridentate hetercyclic extraction reagents for the separation of americium(III) and europium(III)

The synthesis of the first example of a new class of tetradentate reagents for the efficient separation of americium(Ill) and europium(111) is reported together with the structure of the complex formed with europium(III), (C) 2004 Elsevier B.V. All rights reserved.

A statistical mechanical approach for the computation of the climatic response to general forcings

The climate belongs to the class of non-equilibrium forced and dissipative systems, for which most results of quasi-equilibrium statistical mechanics, including the fluctuation-dissipation theorem, do not apply. In this paper we show for the first time how the Ruelle linear response theory, developed for studying rigorously the impact of perturbations on general observables of non-equilibrium statistical mechanical systems, can be applied with great success to analyze the climatic response to general forcings. The crucial value of the Ruelle theory lies in the fact that it allows to compute the response of the system in terms of expectation values of explicit and computable functions of the phase space averaged over the invariant measure of the unperturbed state. We choose as test bed a classical version of the Lorenz 96 model, which, in spite of its simplicity, has a well-recognized prototypical value as it is a spatially extended one-dimensional model and presents the basic ingredients, such as dissipation, advection and the presence of an external forcing, of the actual atmosphere. We recapitulate the main aspects of the general response theory and propose some new general results. We then analyze the frequency dependence of the response of both local and global observables to perturbations having localized as well as global spatial patterns. We derive analytically several properties of the corresponding susceptibilities, such as asymptotic behavior, validity of Kramers-Kronig relations, and sum rules, whose main ingredient is the causality principle. We show that all the coefficients of the leading asymptotic expansions as well as the integral constraints can be written as linear function of parameters that describe the unperturbed properties of the system, such as its average energy. Some newly obtained empirical closure equations for such parameters allow to define such properties as an explicit function of the unperturbed forcing parameter alone for a general class of chaotic Lorenz 96 models. We then verify the theoretical predictions from the outputs of the simulations up to a high degree of precision. The theory is used to explain differences in the response of local and global observables, to define the intensive properties of the system, which do not depend on the spatial resolution of the Lorenz 96 model, and to generalize the concept of climate sensitivity to all time scales. We also show how to reconstruct the linear Green function, which maps perturbations of general time patterns into changes in the expectation value of the considered observable for finite as well as infinite time. Finally, we propose a simple yet general methodology to study general Climate Change problems on virtually any time scale by resorting to only well selected simulations, and by taking full advantage of ensemble methods. The specific case of globally averaged surface temperature response to a general pattern of change of the CO2 concentration is discussed. We believe that the proposed approach may constitute a mathematically rigorous and practically very effective way to approach the problem of climate sensitivity, climate prediction, and climate change from a radically new perspective.

Investigation of the faecal microbiota of geriatric cats

Aims: To investigate the faecal microbiota of geriatric cats, as aging affects the nutrient digestibility and metabolic function of the feline intestine. Methods and results: 20 geriatric cats were randomly assigned to two groups that were fed different foods. Coriobacteriaceae, Clostridium cluster XIV, bifidobacteria, and lactic acid bacteria were the dominant faecal bacterial groups, accounting for ∼40% of total bacteria. Clostridium cluster IX was less predominant (0.5% of total bacteria), while the remaining bacterial populations enumerated only accounted for 0.2% of total bacteria. Highly diverse microbial profiles were demonstrated for geriatric cats with denaturing gradient gel electrophoresis, although a few common bands were evident. Some differences were seen in the feline faecal microbiota between animal groups at the same time or over time for individual animals. However, no obvious clustering based on animal group or sample time was indicated. Conclusions: geriatric cats harboured a complex faecal microbiota and ∼41% of total bacteria have been detected with the probes employed. Significance and impact of study: First molecular-based study examining faecal microbiota of geriatric felines. Knowledge of the microbiota associated with ageing in cats may allow improved development of foods specific for the needs of senior cats.

The first five years of the EU Impact Assessment system: a risk economics perspective on gaps between rationale and practice

In 2003 the European Commission started using Impact Assessment (IA) as the main empirical basis for its major policy proposals. The aim was to systematically assess ex ante the economic, social and environmental impacts of EU policy proposals. In parallel, research proliferated in search for theoretical grounds for IAs and in an attempt to evaluate empirically the performance of the first sets of IAs produced by the European Commission. This paper combines conceptual and evaluative studies carried out in the first five years of EU IAs. It concludes that the great discrepancy between rationale and practice calls for a different theoretical focus and a higher emphasis on evaluating empirically crucial risk economics aspects of IAs, such as the value of statistical life, price of carbon, the integration of macroeconomic modelling and scenario analysis.

A linear model for the structure of turbulence beneath surface water waves

The structure of turbulence in the ocean surface layer is investigated using a simplified semi-analytical model based on rapid-distortion theory. In this model, which is linear with respect to the turbulence, the flow comprises a mean Eulerian shear current, the Stokes drift of an irrotational surface wave, which accounts for the irreversible effect of the waves on the turbulence, and the turbulence itself, whose time evolution is calculated. By analysing the equations of motion used in the model, which are linearised versions of the Craik–Leibovich equations containing a ‘vortex force’, it is found that a flow including mean shear and a Stokes drift is formally equivalent to a flow including mean shear and rotation. In particular, Craik and Leibovich’s condition for the linear instability of the first kind of flow is equivalent to Bradshaw’s condition for the linear instability of the second. However, the present study goes beyond linear stability analyses by considering flow disturbances of finite amplitude, which allows calculating turbulence statistics and addressing cases where the linear stability is neutral. Results from the model show that the turbulence displays a structure with a continuous variation of the anisotropy and elongation, ranging from streaky structures, for distortion by shear only, to streamwise vortices resembling Langmuir circulations, for distortion by Stokes drift only. The TKE grows faster for distortion by a shear and a Stokes drift gradient with the same sign (a situation relevant to wind waves), but the turbulence is more isotropic in that case (which is linearly unstable to Langmuir circulations).

Local and average structure in zinc cyanide: towards an understanding of the atomistic origin of negative thermal expansion

Neutron diffraction at 11.4 and 295 K and solid-state 67Zn NMR are used to determine both the local and average structures in the disordered, negative thermal expansion (NTE) material, Zn(CN)2. Solid-state NMR not only confirms that there is head-to-tail disorder of the C≡N groups present in the solid, but yields information about the relative abundances of the different Zn(CN)4-n(NC)n tetrahedral species, which do not follow a simple binomial distribution. The Zn(CN)4 and Zn(NC)4 species occur with much lower probabilities than are predicted by binomial theory, supporting the conclusion that they are of higher energy than the other local arrangements. The lowest energy arrangement is Zn(CN)2(NC)2. The use of total neutron diffraction at 11.4 K, with analysis of both the Bragg diffraction and the derived total correlation function, yields the first experimental determination of the individual Zn−N and Zn−C bond lengths as 1.969(2) and 2.030(2) Å, respectively. The very small difference in bond lengths, of ~0.06 Å, means that it is impossible to obtain these bond lengths using Bragg diffraction in isolation. Total neutron diffraction also provides information on both the average and local atomic displacements responsible for NTE in Zn(CN)2. The principal motions giving rise to NTE are shown to be those in which the carbon and nitrogen atoms within individual Zn−C≡N−Zn linkages are displaced to the same side of the Zn···Zn axis. Displacements of the carbon and nitrogen atoms to opposite sides of the Zn···Zn axis, suggested previously in X-ray studies as being responsible for NTE behavior, in fact make negligible contribution at temperatures up to 295 K.

Finding the 'first voice' in rural England: the challenges of safeguarding intangible heritage in a national museum

This paper is an attempt to explore the challenges of defining intangible heritage and ‘community’ in England. It uses as its case study the Museum of English Rural Life, University of Reading: an urban museum with a rural theme. The paper examines current theoretical discourse around the concept of the ‘first voice’ and debate about the role of museums in the preservation of intangible heritage. It then examines the relevance of these concepts to the identification of ‘rural’ intangible heritage stake holders in England. In this way, it shows the potential for concepts of intangible heritage to influence national museums. However, by applying theory and practice which is designed to support work with well-defined ‘originating communities’ to a national museum, it also highlights the challenges of initiating community engagement in a multicultural society.

Towards a unified approach for the determination of the bioaccessibility of organic pollutants

Bioaccessibility studies have been widely used as a research tool to determine the potential human exposure to ingested contaminants. More recently they have been practically applied for soil borne toxic elements. This paper reviews the application of bioaccessibility tests across a range of organic pollutants and contaminated matrices. Important factors are reported to be: the physiological relevance of the test, the components in the gut media, the size fraction chosen for the test and whether it contains a sorptive sink. The bioaccessibility is also a function of the composition of the matrix (e.g. organic carbon content of soils) and the physico-chemical characteristics of the pollutant under test. Despite the widespread use of these tests, there are a large number of formats used and very few validation studies with animal models. We propose a unified format for a bioaccessibility test for organic pollutants. The robustness of this test should first be confirmed through inter laboratory comparison, then tested in-vivo.