Fruit polyphenols and CVD risk: a review of human intervention studies.

Epidemiological evidence suggests that polyphenols may, in part, explain the cardioprotective properties of fruits. This review aims to summarise the evidence for the effects of fruit polyphenols on four risk factors of CVD: platelet function, blood pressure, vascular function and blood lipids. This review includes human dietary intervention studies investigating fruits and their polyphenols. There was some evidence to suggest that fruits containing relatively high concentrations of flavonols, anthocyanins and procyanindins, such as pomegranate, purple grapes and berries, were effective at reducing CVD risk factors, particularly with respect to anti-hypertensive effects, inhibition of platelet aggregation and increasing endothelial-dependent vasodilation than other fruits investigated. Flavanone-rich fruits, such as oranges and grapefruits, were reported to have hypocholesterolaemic effects, with little impact on other risk factors being examined. However, the evidence was limited, inconsistent and often inconclusive. This is in part due to the heterogeneity in the design of studies, the lack of controls, the relatively short intervention periods and low power in several studies. Details of the polyphenol content of the fruits investigated were also omitted in some studies, negating comparison of data. It is recommended that large, well-powered, long-term human dietary intervention studies investigating a wider range of fruits are required to confirm these observations. Investigations into the potential synergistic effects of polyphenols on a combination of CVD risk markers, dose–response relationships and standardisation in methodology would facilitate the comparison of studies and also provide valuable information on the types of fruits which could confer protection against CVD.

Conceptualizing change in the Portuguese footwear industry: regional voices and cognitive spaces of agency

Expanding national services sectors and global competition aggravate current and perceived future market pressures on traditional manufacturing industries. These perceptions of change have provoked a growing intensification of geo-political discourses on technological innovation and ‘learning’, and calls for competency in design among other professional skills. However, these political discourses on innovation and learning have paralleled public concerns with the apparent ‘growth pains’ from factory closures and subsequent increases in unemployment, and its debilitating social and economic implications for local and regional development. In this respect the following investigation sets out to conceptualize change through the complementary and differing perceptions of industry and regional actors’ experiences or narratives, linking these perceptions to their structure-determined spheres of agent-environment interactivity. It aims to determine whether agents’ differing perceptions of industry transformation can have a role in the legitimization of their interests in, and in sustaining their organizational influence over the process of industry-regional transformation. It argues that industry and regional agent perceptions are among the cognitive aspects of agent-environment interactivity that permeate agency. It stresses agents’ ability to reason and manipulate their work environments to preserve their self-regulating interests in, and task representative influence over the multi-jurisdictional space of industry-regional transformation. The contributions of this investigation suggest that agents’ varied perceptions of industry and regional change inform or compete for influence over the redirection of regional, industry and business strategies. This claim offers a greater appreciation for the reflexive and complex institutional dimensions of industry planning and development, and the political responsibility to socially just forms of regional development. It positions the outcomes of this investigation at the nexus of intensifying geo-political discourses on the efficiency and equity of territorial development in Europe.

The Glu298Asp single nucleotide polymorphism in the endothelial nitric oxide synthase gene differentially effects the vascular response to acute consumption of fruit and vegetable puree-based drinks

Scope Diets low in fruits and vegetables (FV) are responsible for 2.7 million deaths from cardiovascular diseases (CVD) and certain cancers annually. Many FV and their juices contain flavonoids, some of which increase endothelial nitric oxide synthase (eNOS) activity. A single nucleotide polymorphism in the eNOS gene, where thymine (T) replaces guanine (G) at position 894 predicting substitution of glutamate for aspartate at codon 298 (Glu298Asp), has been associated with increased CVD risk due to effects on nitric oxide synthesis and subsequently vascular reactivity. Individuals can be homozygous for guanine (GG), thymine (TT) or heterozygous (GT). Methods and results We investigated the effects of acute ingestion of a FV-puree-based-drink (FVPD) on vasodilation and antioxidant status in subjects retrospectively genotyped for this polymorphism. Healthy volunteers (n = 24; 11 GG, 11 GT, 2 TT) aged 30–70 were recruited to a randomized, controlled, crossover, acute study. We showed that acute consumption of 400 mL FVPD differentially affected individuals depending on their genotype. There was a significant genotype interaction for endothelium-dependent vasodilation measured by laser Doppler imaging with iontophoresis (P < 0.05) and ex vivo low-density lipoproteins (LDL) oxidation (P = 0.002). GG subjects had increased endothelium-dependent vasodilation 180 min (P = 0.028) and reduced ex vivo LDL oxidation (P = 0.013) after 60 min after FVPD compared with control, no differences were observed in GT subjects. Conclusion eNOS Glu298Asp genotype differentially affects vasodilation and ex vivo LDL oxidation after consumption of FV in the form of a puree-based drink.

Endosomal proteolysis regulates calcitonin gene-related peptide responses in mesenteric arteries

Background and Purpose: Calcitonin gene‐related peptide (CGRP) is a potent vasodilator, implicated in the pathogenesis of migraine. CGRP activates a receptor complex comprising, calcitonin receptor‐like receptor (CLR) and receptor activity‐modifying protein 1 (RAMP1). In vitro studies indicate recycling of CLR•RAMP1 is regulated by degradation of CGRP in early endosomes by endothelin‐converting enzyme‐1 (ECE‐1). However, it is not known if ECE‐1 regulates the resensitization of CGRP‐induced responses in functional arterial tissue. Experimental Approach: CLR, ECE‐1a‐d and RAMP1 expression in rat mesenteric artery smooth muscle cells (RMA‐SMCs) and mesenteric arteries was analyzed by RT‐PCR and by immunofluorescence and confocal microscopy. CGRP‐induced signaling in cells was examined by measuring cAMP production and ERK activation. CGRP‐induced relaxation of arteries was measured by isometric wire myography. ECE‐1 was inhibited using the specific inhibitor, SM‐19712. Key Results: RMA‐SMCs and arteries contained mRNA for CLR, ECE‐1a‐d and RAMP1. ECE‐1 was present in early endosomes of RMA‐SMCs and in the smooth muscle layer of arteries. CGRP induced endothelium‐independent relaxation of arteries. ECE‐1 inhibition had no effect on initial CGRP‐induced responses but reduced cAMP generation in RMA‐SMCs and vasodilation in mesenteric arteries responses to subsequent CGRP challenges. Conclusions and Implications: ECE‐1 regulates the resensitization of responses to CGRP in RMA‐SMCs and mesenteric arteries. CGRP‐induced relaxation does not involve endothelium‐derived pathways. This is the first report of ECE‐1 regulating CGRP responses in SMCs and arteries. ECE‐1 inhibitors may attenuate an important vasodilatory pathway, implicated in primary headaches and may represent a new therapeutic approach for the treatment of migraine.

Glu298Asp polymorphism influences the beneficial effects of fish oil fatty acids on postprandial vascular function

Our objective was to determine whether the endothelial nitric oxide synthase (eNOS) Glu298Asp polymorphism influences vascular response to raised NEFA enriched with saturated fatty acids (SFA) or long-chain (LC) n-3 polyunsaturated fatty acids (PUFA). Subjects were prospectively recruited for genotype (Glu298, n = 30 and Asp298, n = 29; balanced for age and gender) consumed SFA on two occasions, with and without the substitution of 0.07 g fat/kg body weight with LC n-3 PUFA, and with heparin infusion to elevate NEFA. Endothelial function was measured before and after NEFA elevation (240 min), with blood samples taken every 30 min. Flow-mediated dilation (FMD) decreased following SFA alone and increased following SFA+LC n-3 PUFA. There were 2-fold differences in the change in FMD response to the different fat loads between the Asp298 and Glu298 genotypes (P = 0.002) and between genders (P < 0.02). Sodium nitroprusside-induced reactivity, measured by laser Doppler imaging with iontophoresis, was significantly greater with SFA+LC n-3 PUFA in all female subjects (P < 0.001) but not in males. Elevated NEFA influences both endothelial-dependent and endothelial-independent vasodilation during the postprandial phase. Effects of fat composition appear to be genotype and gender dependent, with the greatest difference in vasodilatory response to the two fat loads seen in the Asp298 females.

Localization of calcitonin receptor-like receptor (CLR) and receptor activity-modifying protein 1 (RAMP1) in human gastrointestinal tract

Calcitonin gene-related peptide (CGRP) exerts its diverse effects on vasodilation, nociception, secretion, and motor function through a heterodimeric receptor comprising of calcitonin receptor-like receptor (CLR) and receptor activity-modifying protein 1 (RAMP1). Despite the importance of CLR.RAMP1 in human disease, little is known about its distribution in the human gastrointestinal (GI) tract, where it participates in inflammation and pain. In this study, we determined that CLR and RAMP1 mRNAs are expressed in normal human stomach, ileum and colon by RT-PCR. We next characterized antibodies that we generated to rat CLR and RAMP1 in transfected HEK cells. Having characterized these antibodies in vitro, we then localized CLR-, RAMP1-, CGRP- and intermedin-immunoreactivity (IMD-IR) in various human GI segments. In the stomach, nerve bundles in the myenteric plexus and nerve fibers throughout the circular and longitudinal muscle had prominent CLR-IR. In the proximal colon and ileum, CLR was found in nerve varicosities of the myenteric plexus and surrounding submucosal neurons. Interestingly, CGRP expressing fibers did not co-localize, but were in close proximity to CLR. However, CLR and RAMP1, the two subunits of a functional CGRP receptor were clearly localized in myenteric plexus, where they may form functional cell-surface receptors. IMD, another member of calcitonin peptide family was also found in close proximity to CLR, and like CGRP, did not co-localize with either CLR or RAMP1 receptors. Thus, CGRP and IMD appear to be released locally, where they can mediate their effect on their receptors regulating diverse functions such as inflammation, pain and motility.

Film as literature, or the Truffaldian Malaise

This chapter looks at L’Homme qui aimait les femmes (1977) as a privileged instance of the self-effacing, obliquely disruptive, reflexive aesthetics that characterizes Truffaut’s cinema, by means of an intermedial approach. Although an original story, written by Truffaut in collaboration with Suzanne Schiffman and Michel Fermaud, the film’s subject is the writing of a book containing the protagonist’s story. More importantly, its mode of address presents this story as literature, through a complex network of flashbacks and voiceover narrations that comment on and make sense of the fragmentary present-tense action scenes. As well as a film, this method resulted in an actual novel, or cinéroman, this time authored exclusively by the director under the same title of L’Homme qui aimait les femmes, thus giving material form to the literary aim of the cinematic enterprise: a book.

Processing reflexives in a second language: the timing of structural and discourse-level information

We report the results from two eye-movement monitoring experiments examining the processing of reflexive pronouns by proficient German-speaking learners of second language (L2) English. Our results show that the nonnative speakers initially tried to link English argument reflexives to a discourse-prominent but structurally inaccessible antecedent, thereby violating binding condition A. Our native speaker controls, in contrast, showed evidence of applying condition A immediately during processing. Together, our findings show that L2 learners’ initial focusing on a structurally inaccessible antecedent cannot be due to first language influence and is also independent of whether the inaccessible antecedent c-commands the reflexive. This suggests that unlike native speakers, nonnative speakers of English initially attempt to interpret reflexives through discourse-based coreference assignment rather than syntactic binding.

The role of working memory in the processing of reflexives

We report results from two eye-movement experiments that examined how differences in working memory (WM) capacity affect readers' application of structural constraints on reflexive anaphor resolution during sentence comprehension. We examined whether binding Principle A, a syntactic constraint on the interpretation of reflexives, is reducible to a memory friendly “recency” strategy, and whether WM capacity influences the degree to which readers create anaphoric dependencies ruled out by binding theory. Our results indicate that low and high WM span readers applied Principle A early during processing. However, contrary to previous findings, low span readers also showed immediate intrusion effects of a linearly closer but structurally inaccessible competitor antecedent. We interpret these findings as indicating that although the relative prominence of potential antecedents in WM can affect online anaphor resolution, Principle A is not reducible to a processing or linear distance based “least effort” constraint.

Habitual energy expenditure modifies the association between NOS3 gene polymorphisms and blood pressue

BACKGROUND: The endothelial nitric-oxide synthase (NOS3) gene encodes the enzyme (eNOS) that synthesizes the molecule nitric oxide, which facilitates endothelium-dependent vasodilation in response to physical activity. Thus, energy expenditure may modify the association between the genetic variation at NOS3 and blood pressure. METHODS: To test this hypothesis, we genotyped 11 NOS3 polymorphisms, capturing all common variations, in 726 men and women from the Medical Research Council (MRC) Ely Study (age (mean +/- s.d.): 55 +/- 10 years, body mass index: 26.4 +/- 4.1 kg/m(2)). Habitual/non-resting energy expenditure (NREE) was assessed via individually calibrated heart rate monitoring over 4 days. RESULTS: The intronic variant, IVS25+15 [G-->A], was significantly associated with blood pressure; GG homozygotes had significantly lower levels of diastolic blood pressure (DBP) (-2.8 mm Hg; P = 0.016) and systolic blood pressure (SBP) (-1.9 mm Hg; P = 0.018) than A-allele carriers. The interaction between NREE and IVS25+15 was also significant for both DBP (P = 0.006) and SBP (P = 0.026), in such a way that the effect of the GG-genotype on blood pressure was stronger in individuals with higher NREE (DBP: -4.9 mm Hg, P = 0.02. SBP: -3.8 mm Hg, P= 0.03 for the third tertile). Similar results were observed when the outcome was dichotomously defined as hypertension. CONCLUSIONS: In summary, the NOS3 IVS25+15 is directly associated with blood pressure and hypertension in white Europeans. However, the associations are most evident in the individuals with the highest NREE. These results need further replication and have to be ideally tested in a trial before being informative for targeted disease prevention. Eventually, the selection of individuals for lifestyle intervention programs could be guided by knowledge of genotype.

The effects of dietary nitrate on blood pressure and endothelial function: a review of human intervention studies.

Evidence has accumulated in recent years that suggests that nitrate from the diet, particularly vegetables, is capable of producing bioactive NO in the vasculature, following bioconversion to nitrite by oral bacteria. The aim of the present review was to consider the current body of evidence for potential beneficial effects of dietary nitrate on blood pressure and endothelial function, with emphasis on evidence from acute and chronic human intervention studies. The studies to date suggest that dietary nitrate acutely lowers blood pressure in healthy humans. An inverse relationship was seen between dose of nitrate consumed and corresponding systolic blood pressure reduction, with doses of nitrate as low as 3 mmol of nitrate reducing systolic blood pressure by 3 mmHg. Moreover, the current studies provide some promising evidence on the beneficial effects of dietary nitrate on endothelial function. In vitro studies suggest a number of potential mechanisms by which dietary nitrate and its sequential reduction to NO may reduce blood pressure and improve endothelial function, such as: acting as a substrate for endothelial NO synthase; increasing vasodilation; inhibiting mitochondrial reactive oxygen species production and platelet aggregation. In conclusion, the evidence for beneficial effects of dietary nitrate on blood pressure and endothelial function is promising. Further long-term randomised controlled human intervention studies assessing the potential effects of dietary nitrate on blood pressure and endothelial function are needed, particularly in individuals with hypertension and at risk of CVD.

Postmodernism, culture and feminism: the aesthetics of space and performance in Rock Follies and Rock Follies of '77

This article discusses the aesthetic and spatial representational strategies of the popular studio-based musical television drama serials Rock Follies and Rock Follies of ’77. It analyses how the texts’ themes relating to women and the entertainment industry are mediated through their postmodern ironic mode and representation of fantastic spaces. Rock Follies’ distinctive stylised aesthetic and mode of caricature are analysed with reference to the visual intentions and ‘voice’ of the writer, Howard Schuman. Through considering the programmes’ various spatial strategies, the article draws attention to the importance of visual and performance style in their postmodern discourse on culture, fantasy, gender and subjectivity. Analysis of the spaces of musical performance, characters’ domestic environments and simulated entertainment spaces reveals how a dialectic is established between the escapist imaginative pleasures of fantasy and the manipulative and exploitative practices of the culture industry. The shift from the optimism of the first series, when the LittleLadies first form, to the darker mood of the second series, in which they are increasingly divided by industry pressures, is traced through changes in the aesthetics of space and characterisation. As a space of artifice, performance and electronic visual manipulation that facilitates the texts’ reflexive representation of culture and feminised fantasy, the studio’s unique aesthetic strengths emerge through this case study.

Performing performers: embodiment and intertextuality in the contemporary biopic

The actor’s body is of critical importance to the biopic’s representation of ‘real’ lives, to issues of physical and gestural resemblance, and in its role as the dramatic vehicle; acting out significant moments, embodying transformations. Through detailed examination of Beyond the Sea (2004), De-Lovely (2004), Molière (2007), films which foreground the construction, and constructedness, of life through performance and spectacle, this chapter explores the self-reflexive and intertexual embodiment of life stories. It focuses on the material details of performance in relation to distinctly contemporary strategies of film style and tone, and how these connect to questions of expectation and agency.

Coargumenthood and the processing of reflexives

We report three eye-movement experiments and an antecedent choice task investigating the interpretation of reflexives in different syntactic contexts. This included contexts in which the reflexive and a local antecedent were coarguments of the same verbal predicate (John heard that the soldier had injured himself), and also so-called picture noun phrases, either with a possessor (John heard about the soldier’s picture of himself) or without (John heard that the soldier had a picture of himself). While results from the antecedent choice task indicated that comprehenders would choose a nonlocal antecedent (‘John’ above) for reflexives in either type of picture noun phrase, the eye-movement experiments suggested that participants preferred to initially interpret the reflexive in each context as referring to the local antecedent (‘the soldier’), as indexed by longer reading times when it mismatched in gender with the reflexive. We also observed a difference in the time-course of this effect. While it was observed during first-pass processing at the reflexive for coargument reflexives and those in picture noun phrases with a possessor, it was comparatively delayed for reflexives in possessorless picture noun phrases. These results suggest that locality constraints are more strongly weighted cues to retrieval than gender agreement for both coargument reflexives and those inside picture noun phrases. We interpret the observed time-course differences as indexing the relative ease of accessing the local antecedent in different syntactic contexts.

Trans-floating-point arithmetic removes nine quadrillion redundancies from 64-bit IEEE 754 floating-point arithmetic

IEEE 754 floating-point arithmetic is widely used in modern, general-purpose computers. It is based on real arithmetic and is made total by adding both a positive and a negative infinity, a negative zero, and many Not-a-Number (NaN) states. Transreal arithmetic is total. It also has a positive and a negative infinity but no negative zero, and it has a single, unordered number, nullity. Modifying the IEEE arithmetic so that it uses transreal arithmetic has a number of advantages. It removes one redundant binade from IEEE floating-point objects, doubling the numerical precision of the arithmetic. It removes eight redundant, relational,floating-point operations and removes the redundant total order operation. It replaces the non-reflexive, floating-point, equality operator with a reflexive equality operator and it indicates that some of the exceptions may be removed as redundant { subject to issues of backward compatibility and transient future compatibility as programmers migrate to the transreal paradigm.