In situ signatures of interchange reconnection between magnetic clouds and open magnetic fields: a mechanism for the erosion of polar coronal holes?

We outline a method to determine the direction of solar open flux transport that results from the opening of magnetic clouds (MCs) by interchange reconnection at the Sun based solely on in-situ observations. This method uses established findings about i) the locations and magnetic polarities of emerging MC footpoints, ii) the hemispheric dependence of the helicity of MCs, and iii) the occurrence of interchange reconnection at the Sun being signaled by uni-directional suprathermal electrons inside MCs. Combining those observational facts in a statistical analysis of MCs during solar cycle 23 (period 1995 – 2007), we show that the time of disappearance of the northern polar coronal hole (1998 – 1999), permeated by an outward-pointing magnetic field, is associated with a peak in the number of MCs originating from the northern hemisphere and connected to the Sun by outward-pointing magnetic field lines. A similar peak is observed in the number of MCs originating from the southern hemisphere and connected to the Sun by inward-pointing magnetic field lines. This pattern is interpreted as the result of interchange reconnection occurring between MCs and the open field lines of nearby polar coronal holes. This reconnection process closes down polar coronal hole open field lines and transports these open field lines equatorward, thus contributing to the global coronal magnetic field reversal process. These results will be further constrainable with the rising phase of solar cycle 24.

Fulvalene titanium and zirconium complexes: synthesis and NMR study of phosphanido-, alkyl-, and alkynyl-derivatives. X-ray crystal structures of [{Ti(η5−C5H5)(μ−PPH2)}2{μ−(η5−C5H4−η5−C5H4)}] and [{Zr(η5−C5H5)(μ−C≡CSiMe3)}2{μ−(η5−C5H4−η5−C5H4)}]

Reaction of with one or two equivalents of LiPPh2 afforded the new phosphanidometal(III) complexes . Reaction of 2 with LiC≡CSiMe3 led to the diamagnetic zirconium(III) alkynyl derivative [{Zr(C5H5)(μ−C≡CSiMe3)}2(μ−η5−C5H4−η5−C5H4], 7. Alkylation of 6 with LiCH2CMe2Ph gave [{Zr(η5−C5H5)(CH2CMe2Ph)2}2{μ−(η5−C5H4)}], 8. A detailed NMR study of complexes 3 and 4 allowed the observation of the spectral behaviour of the eight different fulvalene protons through their coupling to the 31P nucleus. The fluxional behaviour of complex 7 was studied by dynamic DNMR, and kinetic parameters for the σ-π-conversion of the alkynyl ligand were determined. The molecular structures of complexes 3 and 7 were determined by X-ray diffraction methods.

Frequency of fruit and vegetable consumption and blood antioxidants in the Caerphilly cohort of older men

Objective: To assess the number of portions of fruit and vegetables consumed daily by a large representative sample of older men, and to determine how blood antioxidant (vitamins E, A and carotenoids) concentrations vary with fruit and vegetable consumption. Design: Cross-sectional study of free-living men. Subjects: Men aged 55-69 y (dietary data, n=1957; blood data, n=1874) participating in Phase III (1989-1993) of the Caerphilly and Speedwell Collaborative Heart Disease Studies. Methods: Dietary data were obtained by semi-quantitative food-frequency questionnaire and blood samples were analysed for antioxidant vitamins. Men were subdivided into groups on the basis of portions per day of fruit and vegetables. Within these sub-groups, mean and 95% ranges of intakes and of blood antioxidant levels were obtained. Log transformations were performed where appropriate. Results: Only 4.3% of the men met the recommended target of five portions, while 33.3% of the men consumed one or fewer portions of fruit and vegetables per day. Those men who consumed the poorest diets with respect to fruit and vegetable intakes were more likely to be from lower socio-economic classes, drink more alcohol and be current smokers. Fruit and vegetable intake reflected plasma concentrations of antioxidants, which showed a dose-response relationship to frequency of consumption. Conclusions: Older men in the UK consume much less fruit and vegetables than current recommendations. Major difficulties are likely to be encountered in trying to meet a dietary target that is clearly much higher than the fruit and vegetable consumption of large sections of the older population in the UK.

Heterogeneous surface expression of EspA translocon filaments by Escherichia coli O157:H7 is controlled at the posttranscriptional level

Type III secretion systems of enteric bacteria enable translocation of effector proteins into host cells. Secreted proteins of verotoxigenic Escherichia coli O157 strains include components of a translocation apparatus, EspA, -B, and -D, as well as "effectors" such as the translocated intimin receptor (Tir) and the mitochondrion-associated protein (Map). This research has investigated the regulation of LEE4 translocon proteins, in particular EspA. EspA filaments could not be detected on the bacterial cell surface when E. coli O157:H7 was cultured in M9 minimal medium but were expressed from only a proportion of the bacterial population when cultured in minimal essential medium modified with 25 mM HEPES. The highest proportions of EspA-filamented bacteria were detected in late exponential phase, after which filaments were lost rapidly from the bacterial cell surface. Our previous research had shown that human and bovine E. coli O157:H7 strains exhibit marked differences in EspD secretion levels. Here it is demonstrated that the proportion of the bacterial population expressing EspA filaments was associated with the level of EspD secretion. The ability of individual bacteria to express EspA filaments was not controlled at the level of LEE1-4 operon transcription, as demonstrated by using both beta-galactosidase and green fluorescent protein (GFP) promoter fusions. All bacteria, whether expressing EspA filaments or not, showed equivalent levels of GFP expression when LEEI-4 translational fusions were used. Despite this, the LEE4-espADB mRNA was more abundant from populations with a high proportion of nonsecreting bacteria (low secretors) than from populations with a high proportion of secreting and therefore filamented bacteria (high secretors). This research demonstrates that while specific environmental conditions are required to induce LEEI-4 expression, a further checkpoint exists before EspA filaments are produced on the bacterial surface and secretion of effector proteins occurs. This checkpoint in E. coli O157:H7 translocon expression is controlled by a posttranscriptional mechanism acting on LEE4-espADB mRNA. The heterogeneity in EspA filamentation could arise from phase-variable expression of regulators that control this posttranscriptional mechanism.

Mutation of toxB and a truncated version of the efa-1 gene in Escherichia coli O157 : H7 influences the expression and secretion of locus of enterocyte effacement-encoded proteins but not intestinal colonization in calves or sheep

Enterohemorrhagic Escherichia coli (EHEC) strains comprise a broad group of bacteria, some of which cause attaching and effacing (AE) lesions and enteritis in humans and animals. Non-O157:H7 EHEC strains contain the gene efa-1 (referred to in previous publications as efa1), which influences adherence to cultured epithelial cells. An almost identical gene in enteropathogenic E. coli (lifA) mediates the inhibition of lymphocyte proliferation and proinflammatory cytokine synthesis. We have shown previously that significantly lower numbers of EHEC 05 and 0111 efa-1 mutants are shed in feces following experimental infection in calves and that these mutants exhibit reduced adherence to intestinal epithelia compared with isogenic wild-type strains. E. coli O157:H7 strains lack efa-1 but encode a homolog on the pO157 plasmid (toxB/l7095) and contain a truncated version of the efa-1 gene (efa-1'/z4332 in O island 122 of the EDL933 chromosome). Here we report that E. coli O157:H7 toxB and efa-1' single and double mutants exhibit reduced adherence to cultured epithelial cells and show reduced expression and secretion of proteins encoded by the locus of enterocyte effacement (LEE), which plays a key role in the host-cell interactions of EHEC. The activity of LEE1, LEE4, and LEE5 promoters was not significantly altered in E. coli O157:H7 strains harboring toxB or efa-1' mutations, indicating that the effect on the expression of LEE-encoded secreted proteins occurs at a posttranscriptional level. Despite affecting type III secretion, mutation of toxB and efa-1' did not significantly affect the course of fecal shedding of E. coli O157:H7 following experimental inoculation of 10- to 14-day-old calves or 6-week-old sheep. Mutation of tir caused a significant reduction in fecal shedding of E. coli O157:H7 in calves, indicating that the formation of AE lesions is important for colonization of the bovine intestine.

Conditionally unbiased estimation in phase II/III clinical trials with early stopping for futility

Seamless phase II/III clinical trials combine traditional phases II and III into a single trial that is conducted in two stages, with stage 1 used to answer phase II objectives such as treatment selection and stage 2 used for the confirmatory analysis, which is a phase III objective. Although seamless phase II/III clinical trials are efficient because the confirmatory analysis includes phase II data from stage 1, inference can pose statistical challenges. In this paper, we consider point estimation following seamless phase II/III clinical trials in which stage 1 is used to select the most effective experimental treatment and to decide if, compared with a control, the trial should stop at stage 1 for futility. If the trial is not stopped, then the phase III confirmatory part of the trial involves evaluation of the selected most effective experimental treatment and the control. We have developed two new estimators for the treatment difference between these two treatments with the aim of reducing bias conditional on the treatment selection made and on the fact that the trial continues to stage 2. We have demonstrated the properties of these estimators using simulations

The 'ratione temporis' elements of self-defence

This article focuses on one particular factor that is of crucial importance to all self-defence actions. It is a factor that is almost always present in the application and appraisal of the right, but one that is not always explicitly engaged with: time. There are various ratione temporis elements underpinning the lawful exercise of the right of self-defence, and questions related to the timing of both an attack being responded to in self-defence and the response itself are notably controversial. The self-defence timeline is therefore charted, and the key legal debates encountered along its trajectory are identified. In particular, there is a focus on three temporal ‘stages’ of the right of self-defence: (i) the much-debated question of preventative forms of self-defence (the ‘before’); (ii) the timeliness of a state's defensive action, or what is sometimes called the need for the response to be ‘immediate’ (the ‘during’); and (iii) the duration of self-defence actions, including the crucial issue of when they must end (the ‘after’). The aim of this article is not to break new substantive ground with regard to these ‘stages’ as such, but is, rather, to draw together the temporal strands of self-defence in a more focused manner than is often the case in the literature.

Glacial-interglacial temperature change in the tropical West Pacific: a comparison of stalagmite-based paleo-thermometers

In the tropics, geochemical records from stalagmites have so far mainly been used to qualitatively reconstruct changes in precipitation, but several new methods to reconstruct past temperatures from stalagmite material have emerged recently: i) liquid–vapor homogenization of fluid inclusion water ii) noble gas concentrations in fluid inclusion water, iii) the partitioning of oxygen isotopes between fluid inclusion water and calcite, and iv) the abundance of the 13C18O16O (‘clumped’) isotopologue in calcite. We present, for the first time, a direct comparison of these four paleo-thermometers by applying them to a fossil stalagmite covering nearly two glacial–interglacial cycles (Marine Isotope Stages (MIS) 12–9) and to two modern stalagmites, all from northern Borneo. The temperature estimates from the different methods agree in most cases within errors for both the old and recent samples; reconstructed formation temperatures of the recent samples match within 2-sigma errors with measured cave temperatures. However, slight but systematic deviations are observed between noble gas and liquid–vapor homogenization temperatures. Whereas the temperature sensitivity of fluid inclusion δ18O and clumped isotopes is currently debated, we find that the calibration of Tremaine et al. (2011) for fluid inclusion δ18O and a synthetic calcite-based clumped isotope calibration (Ziegler et al., in prep.) yield temperature estimates consistent with the other methods. All methods (with the potential exception of clumped isotopes) show excellent agreement on the amplitude of glacial–interglacial temperature change, indicating temperature shifts of 4–5 °C. This amplitude is similar to the amplitude of Mg/Ca-based regional sea surface temperature records, when correcting for sea level driven changes in cave elevation. Our reconstruction of tropical temperature evolution over the time period from 440 to 320 thousand years ago (ka) adds support to the view that climate sensitivity to varying greenhouse forcing is substantial also in the deep tropics.

Supporting local diversity of habitats and species on farmland: a comparison of three wildlife-friendly schemes

Restoration and maintenance of habitat diversity have been suggested as conservation priorities in farmed landscapes, but how this should be achieved and at what scale are unclear. This study makes a novel comparison of the effectiveness of three wildlife-friendly farming schemes for supporting local habitat diversity and species richness on 12 farms in England. The schemes were: (i) Conservation Grade (Conservation Grade: a prescriptive, non-organic, biodiversity-focused scheme), (ii) organic agriculture and (iii) a baseline of Entry Level Stewardship (Entry Level Stewardship: a flexible widespread government scheme). Conservation Grade farms supported a quarter higher habitat diversity at the 100-m radius scale compared to Entry Level Stewardship farms. Conservation Grade and organic farms both supported a fifth higher habitat diversity at the 250-m radius scale compared to Entry Level Stewardship farms. Habitat diversity at the 100-m and 250-m scales significantly predicted species richness of butterflies and plants. Habitat diversity at the 100-m scale also significantly predicted species richness of birds in winter and solitary bees. There were no significant relationships between habitat diversity and species richness for bumblebees or birds in summer. Butterfly species richness was significantly higher on organic farms (50% higher) and marginally higher on Conservation Grade farms (20% higher), compared with farms in Entry Level Stewardship. Organic farms supported significantly more plant species than Entry Level Stewardship farms (70% higher) but Conservation Grade farms did not (10% higher). There were no significant differences between the three schemes for species richness of bumblebees, solitary bees or birds. Policy implications. The wildlife-friendly farming schemes which included compulsory changes in management, Conservation Grade and organic, were more effective at increasing local habitat diversity and species richness compared with the less prescriptive Entry Level Stewardship scheme. We recommend that wildlife-friendly farming schemes should aim to enhance and maintain high local habitat diversity, through mechanisms such as option packages, where farmers are required to deliver a combination of several habitats.

Using U0126 to dissect the role of the extracellular signal-regulated kinase 1/2 (ERK1/2) cascade in the regulation of gene expression by endothelin-1 in cardiac myocytes

The hypertrophic agonist endothelin-1 rapidly but transiently activates the extracellular signal-regulated kinase 1/2 (ERK1/2) cascade (and other signalling pathways) in cardiac myocytes, but the events linking this to hypertrophy are not understood. Using Affymetrix rat U34A microarrays, we identified the short-term (2-4 h) changes in gene expression induced in neonatal myocytes by endothelin-1 alone or in combination with the ERK1/2 cascade inhibitor, U0126. Expression of 15 genes was significantly changed by U0126 alone, and expression of an additional 78 genes was significantly changed by endothelin-1. Of the genes upregulated by U0126, four are classically induced through the aryl hydrocarbon receptor (AhR) by dioxins suggesting that U0126 activates the xenobiotic response element in cardiac myocytes potentially independently of effects on ERK1/2 signalling. The 78 genes showing altered expression with endothelin-1 formed five clusters: (i) three clusters showing upregulation by endothelin-1 according to time course (4 h > 2 h; 2 h > 4 h; 2 h approximately 4 h) with at least partial inhibition by U0126; (ii) a cluster of 11 genes upregulated by endothelin-1 but unaffected by U0126 suggesting regulation through signalling pathways other than ERK1/2; (iii) a cluster of six genes downregulated by endothelin-1 with attenuation by U0126. Thus, U0126 apparently activates the AhR in cardiac myocytes (which must be taken into account in protracted studies), but careful analysis allows identification of genes potentially regulated acutely via the ERK1/2 cascade. Our data suggest that the majority of changes in gene expression induced by endothelin-1 are mediated by the ERK1/2 cascade.

How well do we understand and evaluate climate change feedback processes?

Processes in the climate system that can either amplify or dampen the climate response to an external perturbation are referred to as climate feedbacks. Climate sensitivity estimates depend critically on radiative feedbacks associated with water vapor, lapse rate, clouds, snow, and sea ice, and global estimates of these feedbacks differ among general circulation models. By reviewing recent observational, numerical, and theoretical studies, this paper shows that there has been progress since the Third Assessment Report of the Intergovernmental Panel on Climate Change in (i) the understanding of the physical mechanisms involved in these feedbacks, (ii) the interpretation of intermodel differences in global estimates of these feedbacks, and (iii) the development of methodologies of evaluation of these feedbacks (or of some components) using observations. This suggests that continuing developments in climate feedback research will progressively help make it possible to constrain the GCMs’ range of climate feedbacks and climate sensitivity through an ensemble of diagnostics based on physical understanding and observations.

PtdIns(5)P activates the host cell PI3-kinase/Akt pathway during Shigella flexneri infection

The virulence factor IpgD, delivered into nonphagocytic cells by the type III secretion system of the pathogen Shigella flexneri, is a phosphoinositide 4-phosphatase generating phosphatidylinositol 5 monophosphate (PtdIns(5) P). We show that PtdIns(5) P is rapidly produced and concentrated at the entry foci of the bacteria, where it colocalises with phosphorylated Akt during the first steps of infection. Moreover, S. flexneri-induced phosphorylation of host cell Akt and its targets specifically requires IpgD. Ectopic expression of IpgD in various cell types, but not of its inactive mutant, or addition of short-chain penetrating PtdIns(5) P is sufficient to induce Akt phosphorylation. Conversely, sequestration of PtdIns(5) P or reduction of its level strongly decreases Akt phosphorylation in infected cells or in IpgD-expressing cells. Accordingly, IpgD and PtdIns(5) P production specifically activates a class IA PI 3-kinase via a mechanism involving tyrosine phosphorylations. Thus, S. flexneri parasitism is shedding light onto a new mechanism of PI 3-kinase/Akt activation via PtdIns(5) P production that plays an important role in host cell responses such as survival.

Meal frequency; does it determine postprandial lipaemia?

OBJECTIVE: To determine the effect of altering meal frequency on postprandial lipaemia and associated parameters. DESIGN: A randomized open cross over study to examine the programming effects of altering meal frequency. A standard test meal was given on three occasions following: (i) the normal diet; (ii) a period of two weeks on a nibbling and (iii) a period of two weeks on a gorging diet. SETTING: Free living subjects associated with the University of Surrey. SUBJECTS: Eleven female volunteers (age 22 +/- 0.89 y) were recruited. INTERVENTIONS: The subjects were requested to consume the same foods on either a nibbling diet (12 meals per day) or a gorging diet (three meals per day) for a period of two weeks. The standard test meal containing 80 g fat, 63 g carbohydrate and 20 g protein was administered on the day prior to the dietary intervention and on the day following each period of intervention. MAJOR OUTCOME MEASURES: Fasting and postprandial blood samples were taken for the analysis of plasma triacylglycerol, non-esterified fatty acids, glucose, immunoreactive insulin, glucose-dependent insulinotropic polypeptide levels (GIP) and glucagon-like peptide (GLP-1), fasting total, low density lipoprotein (LDL)- and high density lipoprotein (HDL)-cholesterol concentrations and postheparin lipoprotein lipase (LPL) activity measurements. Plasma paracetamol was measured following administration of a 1.5 g paracetamol load with the meal as an index of gastric emptying. RESULTS: The compliance to the two dietary regimes was high and there were no significant differences between the nutrient intakes on the two intervention diets. There were no significant differences in fasting or postprandial plasma concentrations of triacylglycerol, non-esterified fatty acids, glucose, immunoreactive insulin, GIP and GLP-1 levels, in response to the standard test meal following the nibbling or gorging dietary regimes. There were no significant differences in fasting total or LDL-cholesterol concentrations, or in the 15 min postheparin lipoprotein lipase activity measurements. There was a significant increase in HDL-cholesterol in the subjects following the gorging diet compared to the nibbling diet. DISCUSSION: The results suggest that previous meal frequency for a period of two weeks in young healthy women does not alter the fasting or postprandial lipid or hormonal response to a standard high fat meal. CONCLUSIONS: The findings of this study did not confirm the previous studies which suggested that nibbling is beneficial in reducing the concentrations of lipid and hormones. The rigorous control of diet content and composition in the present study compared with others, suggest reported effects of meal frequency may be due to unintentional alteration in nutrient and energy intake in previous studies.

The compact city and the residential developer

Although the compact city is widely promoted as a sustainable form of urban development, little attention has been paid to the feasilibity of its implementation in practice. This paper addresses this isse by presenting the findings of a questionnaire study into the viability of the compact city from the perspective of the volume housebuilder. The study shows that, although well aware of the inherent problems witht the compact city, most were generally positive about the need to redirect more development back into urban areas. In addition, they suggested a large number of strategies for change, including i) a role for public sector agencies in overcoming the condstraints on urban sites; ii) the need for an upward reveision of acceptable densities in local plans and design guides; and iii) the creation of a separate, or revised, Use Class Order to enable mixed use development to compete on a level playing field. It is concluded that the residential developer could be engaged in the process of urban containment provided proposals for implementing the compact city of devised. The need for continuing research to test the actual effects of specific schemes is emphasised.