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The ‘trophic level enrichment’ between diet and body results in an overall increase in nitrogen isotopic values as the food chain is ascended. Quantifying the diet–body Δ15N spacing has proved difficult, particularly for humans. The value is usually assumed to be +3-5‰ in the archaeological literature. We report here the first (to our knowledge) data from humans on isotopically known diets, comparing dietary intake and a body tissue sample, that of red blood cells. Samples were taken from 11 subjects on controlled diets for a 30-d period, where the controlled diets were designed to match each individual’s habitual diet, thus reducing problems with short-term changes in diet causing isotopic changes in the body pool. The Δ15Ndiet-RBC was measured as +3.5‰. Using measured offsets from other studies, we estimate the human Δ15Ndiet-keratin as +5.0-5.3‰, which is in good agreement with values derived from the two other studies using individual diet records. We also estimate a value for Δ15Ndiet-collagen of ≈6‰, again in combination with measured offsets from other studies. This value is larger than usually assumed in palaeodietary studies, which suggests that the proportion of animal protein in prehistoric human diet may have often been overestimated in isotopic studies of palaeodiet.

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Steady state and dynamic models have been developed and applied to the River Kennet system. Annual nitrogen exports from the land surface to the river have been estimated based on land use from the 1930s and the 1990s. Long term modelled trends indicate that there has been a large increase in nitrogen transport into the river system driven by increased fertiliser application associated with increased cereal production, increased population and increased livestock levels. The dynamic model INCA Integrated Nitrogen in Catchments. has been applied to simulate the day-to-day transport of N from the terrestrial ecosystem to the riverine environment. This process-based model generates spatial and temporal data and reproduces the observed instream concentrations. Applying the model to current land use and 1930s land use indicates that there has been a major shift in the short term dynamics since the 1930s, with increased river and groundwater concentrations caused by both non-point source pollution from agriculture and point source discharges. �

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In the first part of this paper (Ulbrich et al. 2003), we gave a description of the August 2002 rainfall events and the resultant floods, in particular of the flood wave of the River Elbe. The extreme precipitation sums observed in the first half of the month were primarily associated with two rainfall episodes. The first episode occurred on 6/7 August 2002. The main rainfall area was situated over Lower Austria, the south-western part of the Czech Republic and south-eastern Germany. A severe flash flood was produced in the Lower Austrian Waldviertel (`forest quarter’ ). The second episode on 11± 13 August 2002 most severely affected the Erz Mountains and western parts of the Czech Republic. During this second episode 312mm of rain was recorded between 0600GMT on 12 August and 0600GMT on 13 August at the Zinnwald weather station in the ErzMountains, which is a new 24-hour record for Germany. The flash floods resulting from this rainfall episode and the subsequent Elbe flood produced the most expensive weatherrelated catastrophe in Europe in recent decades. In this part of the paper we discuss the meteorological conditions and physical mechanisms leading to the two main events. Similarities to the conditions that led to the recent summer floods of the River Oder in 1997 and the River Vistula in 2001 will be shown. This will lead us to a consideration of trends in extreme rainfall over Europe which are found in numerical simulations of anthropogenic climate change.

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OBJECTIVE: The goal of this study was to investigate the potential crosstalk between Rap1 and Rac1, 2 small GTPases central to platelet activation, particularly downstream of the collagen receptor GPVI. METHODS AND RESULTS: We compared the activation response of platelets with impaired Rap signaling (double knock-out; deficient in both the guanine nucleotide exchange factor, CalDAG-GEFI, and the Gi-coupled receptor for ADP, P2Y12), to that of wild-type platelets treated with a small-molecule Rac inhibitor, EHT 1864 (wild-type /EHT). We found that Rac1 is sequentially activated downstream of Rap1 on stimulation via GPVI. In return, Rac1 provides important feedback for both CalDAG-GEFI- and P2Y12-dependent activation of Rap1. When analyzing platelet responses controlled by Rac1, we observed (1) impaired lamellipodia formation, clot retraction, and granule release in both double knock-out and EHT 1864-treated wild-type platelets; and (2) reduced calcium store release in EHT 1864-treated wild-type but not double knock-out platelets. Consistent with the latter finding, we identified 2 pools of Rac1, one activated immediately downstream of GPVI and 1 activated downstream of Rap1. CONCLUSIONS: We demonstrate important crosstalk between Rap1 and Rac1 downstream of GPVI. Whereas Rap1 signaling directly controls sustained Rac1 activation, Rac1 affects CalDAG-GEFI- and P2Y12-dependent Rap1 activation via its role in calcium mobilization and granule/ADP release, respectively.

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This review summarises the history of transgenic (GM) cereals, principally maize, and then focuses on the scientific literature published in the last two years. It describes the production of GM cereals with modified traits, divided into input traits and output traits. The first category includes herbicide tolerance and insect resistance, and resistance to abiotic and biotic stresses; the second includes altered grains for starch, protein or nutrient quality, the use of cereals for the production of high value medical or other products, and the generation of plants with improved efficiency of biofuel production. Using data from field trial and patent databases the review considers the diversity of GM lines being tested for possible future development. It also summarises the dichotomy of response to GM products in various countries, describes the basis for the varied public acceptability of such products, and assesses the development of novel breeding techniques in the light of current GM regulatory procedures.

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Neural differentiation of embryonic stem cells (ESCs) requires coordinated repression of the pluripotency regulatory program and reciprocal activation of the neurogenic regulatory program. Upon neural induction, ESCs rapidly repress expression of pluripotency genes followed by staged activation of neural progenitor and differentiated neuronal and glial genes. The transcriptional factors that underlie maintenance of pluripotency are partially characterized whereas those underlying neural induction are much less explored, and the factors that coordinate these two developmental programs are completely unknown. One transcription factor, REST (repressor element 1 silencing transcription factor), has been linked with terminal differentiation of neural progenitors and more recently, and controversially, with control of pluripotency. Here, we show that in the absence of REST, coordination of pluripotency and neural induction is lost and there is a resultant delay in repression of pluripotency genes and a precocious activation of both neural progenitor and differentiated neuronal and glial genes. Furthermore, we show that REST is not required for production of radial glia-like progenitors but is required for their subsequent maintenance and differentiation into neurons, oligodendrocytes, and astrocytes. We propose that REST acts as a regulatory hub that coordinates timely repression of pluripotency with neural induction and neural differentiation.

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Proteolytic enzymes comprise approximately 2 percent of the human genome [1]. Given their abundance, it is not surprising that proteases have diverse biological functions, ranging from the degradation of proteins in lysosomes to the control of physiological processes such as the coagulation cascade. However, a subset of serine proteases (possessing serine residues within their catalytic sites), which may be soluble in the extracellular fluid or tethered to the plasma membrane, are signaling molecules that can specifically regulate cells by cleaving protease-activated receptors (PARs), a family of four G-protein-coupled receptors (GPCRs). These serine proteases include members of the coagulation cascade (e.g., thrombin, factor VIIa, and factor Xa), proteases from inflammatory cells (e.g., mast cell tryptase, neutrophil cathepsin G), and proteases from epithelial tissues and neurons (e.g., trypsins). They are often generated or released during injury and inflammation, and they cleave PARs on multiple cell types, including platelets, endothelial and epithelial cells, myocytes, fibroblasts, and cells of the nervous system. Activated PARs regulate many essential physiological processes, such as hemostasis, inflammation, pain, and healing. These proteases and their receptors have been implicated in human disease and are potentially important targets for therapy. Proteases and PARs participate in regulating most organ systems and are the subject of several comprehensive reviews [2, 3]. Within the central and peripheral nervous systems, proteases and PARs can control neuronal and astrocyte survival, proliferation and morphology, release of neurotransmitters, and the function and activity of ion channels, topics that have also been comprehensively reviewed [4, 5]. This chapter specifically concerns the ability of PARs to regulate TRPV channels of sensory neurons and thereby affect neurogenic inflammation and pain transmission [6, 7].

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We study the behavior and emotional arousal of the participants in an experimental auction, leading to an asymmetric social dilemma involving an auctioneer and two bidders. An antisocial transfer (bribe) which is beneficial for the auctioneer (official) is paid, if promised, by the winner of the auction. Some pro-social behavior on both the auctioneers' and the bidders' sides is observed even in the absence of any punishment mechanism (Baseline, Treatment 0). However, pro-social behavior is adopted by the vast majority of subjects when the loser of the auction can inspect the transaction between the winner and the auctioneer (Inspection, Treatment 1). The inspection and punishment mechanism is such that, if a bribe is (not) revealed, both corrupt agents (the denouncing bidder) lose(s) this period's payoffs. This renders the inspection option unprofitable for the loser and is rarely used, especially towards the end of the session, when pro-social behavior becomes pervasive. Subjects' emotional arousal was obtained through skin conductance responses. Generally speaking, our findings suggest that stronger emotions are associated with decisions deviating from pure monetary reward maximization, rather than with (un)ethical behavior per se. In fact, using response times as a measure of the subject's reflection during the decision-making process, we can associate emotional arousal with the conflict between primary or instinctive and secondary or contemplative motivations and, more specifically, with deviations from the subject's pure monetary interest.

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In 2006 the UK government announced a move to zero carbon homes by 2016. The demand posed a major challenge to policy makers and construction professionals entailing a protracted process of policy design. The task of giving content to this target is used to explore the role of evidence in the policy process. Whereas much literature on policy and evidence treats evidence as an external input, independent of politics, this paper explores the ongoing mutual constitution of both. Drawing on theories of policy framing and the sociology of classification, the account follows the story of a policy for Zero Carbon Homes from the parameters and values used to specify the target. Particular attention is given to the role of Regulatory Impact Assessments (RIAs) and to the creation of a new policy venue, the Zero Carbon Hub. The analysis underlines the way in which the choices about how to model and measure the aims potentially transforms them, the importance of policy venues for transparency and the role of RIAs in the authorization of particular definitions. A more transparent, open approach to policy formulation is needed in which the framing of evidence is recognized as an integral part of the policy process.

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Historical, artefactual and place-name evidence indicates that Scandinavian migrants moved to eastern England in the ninth century AD, settling in the Danelaw. However, only a handful of characteristically Scandinavian burials have been found in the region. One, widely held, explanation is that most of these Scandinavian settlers quickly adopted local Christian burial customs, thus leaving Scandinavians indistinguishable from the Anglo-Saxon population. We undertook osteological and isotopic analysis to investigate the presence of first-generation Scandinavian migrants. Burials from Masham were typical of the later Anglo-Saxon period and included men, women and children. The location and positioning of the four adult burials from Coppergate, however, are unusual for Anglo-Scandinavian York. None of the skeletons revealed interpersonal violence. Isotopic evidence did not suggest a marine component in the diet of either group, but revealed migration on a regional, and possibly an international, scale. Combined strontium and oxygen isotope analysis should be used to investigate further both regional and Scandinavian migration in the later Anglo-Saxon period.

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Adenosine and mitogen-activated protein kinases (MAPKs) have been separately implicated in cardiac ischaemic preconditioning. We investigated the activation of MAPK subfamilies by adenosine in perfused rat hearts. p38-MAPK was rapidly phosphorylated and activated (10-fold activation, maximal at 5 min) by 10 mM adenosine, as was the p38-MAPK substrate, MAPKAPK2 (4.5-fold). SAPKs/JNKs were activated (5-fold) and ERKs were phosphorylated (both maximal at 5 min). The concentration dependences of activation of p38-MAPK and ERKs were biphasic with a 'high affinity' component (maximal at 10-100 microM adenosine) and a 'low affinity' component that had not saturated at 10 mM. SAPKs/JNKs were activated only by 10 mM adenosine. These results are consistent with MAPK involvement in adenosine-mediated ischaemic preconditioning.

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Iso-score curves graph (iSCG) and mathematical relationships between Scoring Parameters (SP) and Forecasting Parameters (FP) can be used in Economic Scoring Formulas (ESF) used in tendering to distribute the score among bidders in the economic part of a proposal. Each contracting authority must set an ESF when publishing tender specifications and the strategy of each bidder will differ depending on the ESF selected and the weight of the overall proposal scoring. The various mathematical relationships and density distributions that describe the main SPs and FPs, and the representation of tendering data by means of iSCGs, enable the generation of two new types of graphs that can be very useful for bidders who want to be more competitive: the scoring and position probability graphs.

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Following previous studies, the aim of this work is to further investigate the application of colloidal gas aphrons (CGA) to the recovery of polyphenols from a grape marc ethanolic extract with particular focus on exploring the use of a non-ionic food grade surfactant (Tween 20) as an alternative to the more toxic cationic surfactant CTAB. Different batch separation trials in a flotation column were carried out to evaluate the influence of surfactant type and concentration and processing parameters (such as pH, drainage time, CGA/extract volumetric and molar ratio) on the recovery of total and specific phenolic compounds. The possibility of achieving selective separation and concentration of different classes of phenolic compounds and non-phenolic compounds was also assessed, together with the influence of the process on the antioxidant capacity of the recovered compounds. The process led to good recovery, limited loss of antioxidant capacity, but low selectivity under the tested conditions. Results showed the possibility of using Tween 20 with a separation mechanism mainly driven by hydrophobic interactions. Volumetric ratio rather than the molar ratio was the key operating parameter in the recovery of polyphenols by CGA.