The take-up of Neighbourhood Planning in England 2011-2015

Exploration of how neighbourhoods and others have responded to the UK government���s localism agenda in England, and specifically towards Neighbourhood Planning (NP), is important given that NP is a prominent part of that policy agenda. It is also of interest as the ramifications emerge for planning practice in the formal introduction of statutory plans which are ostensibly led by communities (Parker et al, 2015; Gallent, 2013). There is a necessary task to provide critical commentary on the socio-economic impact of localist policy. The paper explores the issues arising from experience thus far and highlights the take-up of Neighbourhood Planning since 2011. This assessment shows how a vast majority of those active have been in parished areas and in less-deprived areas. This indicates that government needs to do more to ensure that NP is accessible and worthwhile for a wider range of communities.

Phosphorothioate backbone modifications of nucleotide-based drugs are potent platelet activators

Nucleotide-based drug candidates such as antisense oligonucleotides, aptamers, immunoreceptor-activating nucleotides, or (anti)microRNAs hold great therapeutic promise for many human diseases. Phosphorothioate (PS) backbone modification of nucleotide-based drugs is common practice to protect these promising drug candidates from rapid degradation by plasma and intracellular nucleases. Effects of the changes in physicochemical properties associated with PS modification on platelets have not been elucidated so far. Here we report the unexpected binding of PS-modified oligonucleotides to platelets eliciting strong platelet activation, signaling, reactive oxygen species generation, adhesion, spreading, aggregation, and thrombus formation in vitro and in vivo. Mechanistically, the platelet-specific receptor glycoprotein VI (GPVI) mediates these platelet-activating effects. Notably, platelets from GPVI function-deficient patients do not exhibit binding of PS-modified oligonucleotides, and platelet activation is fully abolished. Our data demonstrate a novel, unexpected, PS backbone-dependent, platelet-activating effect of nucleotide-based drug candidates mediated by GPVI. This unforeseen effect should be considered in the ongoing development programs for the broad range of upcoming and promising DNA/RNA therapeutics.

The role of Planning Aid England in supporting communities��� engagement in planning

In considering the position of community engagement within planning in a time of neo-liberalism and a context of ���neo-communitarian localism��� (cf. Jessop, 2002; DeFilippis, 2004), this paper reviews the role and relevance of Planning Aid in terms of its performance and aspirations in guiding and transforming planning practice (Friedmann, 1973; 1987; 2011) since its inception in 1973. In doing this we reflect on the critiques of Planning Aid performance provided by Allmendinger (2004) and bring the account up-to-date following on from past considerations (e.g. Bidwell and Edgar, 1982; Thomas, 1992; Brownill and Carpenter, 2007a,b; Carpenter and Brownill, 2008) and prompted by the 35 years since the University of Reading produced the first published work reviewing Planning Aid (Curtis and Edwards, 1980). Our paper is timely given renewed attacks on planning, the implementation of a form of localism and reductions in funding for planning in a time of austerity. Our view is that the need for forms of ���neo-advocacy��� planning and community development are perhaps even more necessary now, given the continuing under-representation of lower income groups, minority groups and to allow for the expression of alternative planning futures. Thus further consideration of how to ensure that Planning Aid functions are sustained and understood requires the attention of policymakers and the planning profession more widely.

Understanding inter-satellite biases of microwave humidity sounders using global simultaneous nadir overpasses

Simultaneous nadir overpasses (SNOs) of polar-orbiting satellites are most frequent in polar areas but can occur at any latitude when the equatorial crossing times of the satellites become close owing to orbital drift. We use global SNOs of polar orbiting satellites to evaluate the intercalibration of microwave humidity sounders from the more frequent high-latitude SNOs. We have found based on sensitivity analyses that optimal distance and time thresholds for defining collocations are pixel centers less than 5 km apart and time differences less than 300 s. These stringent collocation criteria reduce the impact of highly variable surface or atmospheric conditions on the estimated biases. Uncertainties in the estimated biases are dominated by the combined radiometric noise of the instrument pair. The effects of frequency changes between different versions of the humidity sounders depend on the amount of water vapor in the atmosphere. There are significant scene radiance and thus latitude dependencies in the estimated biases and this has to taken into account while intercalibrating microwave humidity sounders. Therefore the results obtained using polar SNOs will not be representative for moist regions, necessitating the use of global collocations for reliable intercalibration.

Endothelin-1 and fibroblast growth factors stimulate the mitogen-activated protein kinase signaling cascade in cardiac myocytes. The potential role of the cascade in the integration of two signaling pathways leading to myocyte hypertrophy.

Maximally effective concentrations of endothelin-1 (ET-1), acidic FGF (aFGF), or 12-O-tetradecanoylphorbol-13-acetate (TPA) activated mitogen-activated protein kinase (MAPK) by 3-4-fold in crude extracts of myocytes cultured from neonatal rat heart ventricles. Maximal activation was achieved after 5 min. Thereafter, MAPK activity stimulated by ET-1 or aFGF declined to control values within 1-2 h, whereas activation by TPA was more sustained. Two peaks of MAPK activity (a 42- and a 44-kDa MAPK) were resolved in cells exposed to ET-1 or aFGF by fast protein liquid chromatography on a Mono Q column. One major and one minor peak of MAPK kinase (MAPKK) was stimulated by ET-1 or aFGF. Cardiac myocytes expressed protein kinase C (PKC)-alpha, -delta, -epsilon and -zeta as shown immunoblotting. Exposure to 1 microM TPA for 24 h down-regulated PKC-alpha, -delta, and -epsilon, but not PKC-zeta. This maneuver wholly abolished the activation of MAPK on re-exposure to TPA but did not affect the response to aFGF. The effect of ET-1 was partially down-regulated. ET-1 stimulated phospho[3H]inositide hydrolysis 18-fold, whereas aFGF stimulated by only 30%. Agonists which initially utilize dissimilar signaling pathways may therefore converge at the level of MAPKK/MAPK and this may be relevant to the hypertrophic response of the heart.

Expression of protein kinase C isoforms during cardiac ventricular development.

The expression of protein kinase C (PKC) isoforms (PKC-alpha, PKC-beta 1, PKC-delta, PKC-epsilon, and PKC-zeta) was studied by immunoblotting in whole ventricles of rat hearts during postnatal development (1-26 days) and in the adult. PKC-alpha, PKC-beta 1, PKC-delta, PKC-epsilon, and PKC-zeta were detected in ventricles of 1-day-old rats, although PKC-alpha and PKC-beta 1 were only barely detectable. All isoforms were rapidly downregulated during development, with abundances relative to total protein declining in the adult to < 25% of 1-day-old values. PKC-beta 1 was not detectable in adult ventricles. The specific activity of PKC was also downregulated. The rat ventricular myocyte becomes amitotic soon after birth but continues to grow, increasing its protein content 40- to 50-fold between the neonate and the 300-g adult. An important question is thus whether the amount of PKC per myocyte is downregulated. With the use of isolated cells, immunoblotting showed that the contents per myocyte of PKC-alpha and PKC-epsilon increased approximately 10-fold between the neonatal and adult stages. In rat ventricles, the rank of association with the particulate fraction was PKC-delta > PKC-epsilon > PKC-zeta. Association of these isoforms with the particulate fraction was less in the adult than in the neonate. In primary cultures of ventricular myocytes prepared from neonatal rat hearts, 1 microM 12-O-tetradecanoylphorbol-13-acetate (TPA) elicited translocation of PKC-alpha, PKC-delta, and PKC-epsilon from the soluble to the particulate fraction in < 1 min, after which time no further translocation was observed. Prolonged exposure (16 h) of myocytes to 1 microM TPA caused essentially complete downregulation of these isoforms, although downregulation of PKC-epsilon was slower than for PKC-delta. In contrast, PKC-zeta was neither translocated nor downregulated by 1 microM TPA. Immunoblotting of human ventricular samples also revealed downregulation of PKC relative to total protein during fetal/postnatal development.

Stakeholder perceptions of event attribution in the loss and damage debate

In 2013 the Warsaw International Mechanism (WIM) for loss and damage (L&D) associated with climate change impacts was established under the United Nations Framework Convention on Climate Change (UNFCCC). For scientists, L&D raises ques- tions around the extent that such impacts can be attributed to anthropogenic climate change, which may generate complex results and be controversial in the policy arena. This is particularly true in the case of probabilistic event attribution (PEA) science, a new and rapidly evolving field that assesses whether changes in the probabilities of extreme events are attributable to GHG emissions. If the potential applications of PEA are to be considered responsibly, dialogue between scientists and policy makers is fundamental. Two key questions are considered here through a literature review and key stakeholder interviews with representatives from the science and policy sectors underpinning L&D. These provided the opportunity for in-depth insights into stakeholders��� views on firstly, how much is known and understood about PEA by those associated with the L&D debate? Secondly, how might PEA inform L&D and wider climate policy? Results show debate within the climate science community, and limited understanding among other stakeholders, around the sense in which extreme events can be attributed to climate change. However, stake- holders do identify and discuss potential uses for PEA in the WIM and wider policy, but it remains difficult to explore precise applications given the ambiguity surrounding L&D. This implies a need for stakeholders to develop greater understandings of alternative conceptions of L&D and the role of science, and also identify how PEA can best be used to support policy, and address associated challenges.

Scale interactions between the MJO and the western maritime continent

State-of-the-art regional climate model simulations that are able to resolve key mesoscale circulations are used, for the first time, to understand the interaction between the large-scale convective environment of the MJO and processes governing the strong diurnal cycle over the islands of the Maritime Continent (MC). Convection is sustained in the late afternoon just inland of the coasts due to sea breeze convergence. Previous work has shown that the variability in MC rainfall associated with the MJO is manifested in changes to this diurnal cycle; land-based rainfall peaks before the active convective envelope of the MJO reaches the MC, whereas oceanic rainfall rates peak whilst the active envelope resides over the region. The model simulations show that the main controls on oceanic MC rainfall in the early active MJO phases are the large-scale environment and atmospheric stability, followed by high oceanic latent heat flux forced by high near-surface winds in the later active MJO phases. Over land, rainfall peaks before the main convective envelope arrives (in agreement with observations), even though the large-scale convective environment is only moderately favourable for convection. The causes of this early rainfall peak are convective triggers from land-sea breeze circulations that are strong due to high surface insolation and surface heating. During the peak MJO phases cloud cover increases and surface insolation decreases, which weakens the strength of the mesoscale circulations and reduces land-based rainfall, even though the large-scale environment remains favourable for convection at this time. Hence, scale interactions are an essential part of the MJO transition across the MC.

Whey protein mouth drying influenced by thermal denaturation

Whey proteins are becoming an increasingly popular functional food ingredient. There are, however, sensory properties associated with whey protein beverages that may hinder the consumption of quantities sufficient to gain the desired nutritional benefits. One such property is mouth drying. The influence of protein structure on the mouthfeel properties of milk proteins has been previously reported. This paper investigates the effect of thermal denaturation of whey proteins on physicochemical properties (viscosity, particle size, zeta-potential, pH), and relates this to the observed sensory properties measured by qualitative descriptive analysis and sequential profiling. Mouthcoating, drying and chalky attributes built up over repeated consumption, with higher intensities for samples subjected to longer heating times (p < 0.05). Viscosity, pH, and zeta-potential were found to be similar for all samples, however particle size increased with longer heating times. As the pH of all samples was close to neutral, this implies that neither the precipitation of whey proteins at low pH, nor their acidity, as reported in previous literature, can be the drying mechanisms in this case. The increase in mouth drying with increased heating time suggests that protein denaturation is a contributing factor and a possible mucoadhesive mechanism is discussed.

Long-term positive effects of repeating a year in school: Six-year longitudinal study of self-beliefs, anxiety, social relations, school grades, and test scores

Consistently with a priori predictions, school retention (repeating a year in school) had largely positive effects for a diverse range of 10 outcomes (e.g., math self-concept, self-efficacy, anxiety, relations with teachers, parents and peers, school grades, and standardized achievement test scores). The design, based on a large, representative sample of German students (N = 1,325, M age = 11.75 years) measured each year during the first five years of secondary school, was particularly strong. It featured four independent retention groups (different groups of students, each repeating one of the four first years of secondary school, total N = 103), with multiple post-test waves to evaluate short- and long-term effects, controlling for covariates (gender, age, SES, primary school grades, IQ) and one or more sets of 10 outcomes realised prior to retention. Tests of developmental invariance demonstrated that the effects of retention (controlling for covariates and pre-retention outcomes) were highly consistent across this potentially volatile early-to-middle adolescent period; largely positive effects in the first year following retention were maintained in subsequent school years following retention. Particularly considering that these results are contrary to at least some of the accepted wisdom about school retention, the findings have important implications for educational researchers, policymakers and parents.

On the origins and timescales of geoeffective IMF

Southward Interplanetary Magnetic Field (IMF) in the Geocentric Solar Magnetospheric (GSM) reference frame is the key element that controls the level of space-weather disturbance in Earth���s magnetosphere, ionosphere and thermosphere. We discuss the relation of this geoeffective IMF component to the IMF in the Geocentric Solar Ecliptic (GSE) frame and, using the almost continuous interplanetary data for 1996-2015 (inclusive), we show that large geomagnetic storms are always associated with strong southward, out-of-ecliptic field in the GSE frame: dipole tilt effects, that cause the difference between the southward field in the GSM and GSE frames, generally make only a minor contribution to these strongest storms. The time-of-day/time-of-year response patterns of geomagnetic indices and the optimum solar wind coupling function are both influenced by the timescale of the index response. We also study the occurrence spectrum of large out-of-ecliptic field and show that for one-hour averages it is, surprisingly, almost identical in ICMEs (Interplanetary Coronal Mass Ejections), around CIRs/SIRs (Corotating and Stream Interaction Regions) and in the ���quiet��� solar wind (which is shown to be consistent with the effect of weak SIRs). However, differences emerge when the timescale over which the field remains southward is considered: for longer averaging timescales the spectrum is broader inside ICMEs, showing that these events generate longer intervals of strongly southward average IMF and consequently stronger geomagnetic storms. The behavior of out-of-ecliptic field with timescale is shown to be very similar to that of deviations from the predicted Parker spiral orientation, suggesting the two share common origins.