Abstract platforms of computation

Computational formalisms have been pushing the boundaries of the field of computing for the last 80 years and much debate has surrounded what computing entails; what it is, and what it is not. This paper seeks to explore the boundaries of the ideas of computation and provide a framework for enabling a constructive discussion of computational ideas. First, a review of computing is given, ranging from Turing Machines to interactive computing. Then, a variety of natural physical systems are considered for their computational qualities. From this exploration, a framework is presented under which all dynamical systems can be considered as instances of the class of abstract computational platforms. An abstract computational platform is defined by both its intrinsic dynamics and how it allows computation that is meaningful to an external agent through the configuration of constraints upon those dynamics. It is asserted that a platform’s computational expressiveness is directly related to the freedom with which constraints can be placed. Finally, the requirements for a formal constraint description language are considered and it is proposed that Abstract State Machines may provide a reasonable basis for such a language.

Flavonoid-rich fruits and vegetables improve microvascular reactivity and inflammatory status in men at risk of cardiovascular disease – FLAVURS: a randomized controlled trial

BACKGROUND: Observed associations between increased fruit and vegetable (F&V) consumption, particularly those F&Vs that are rich in flavonoids, and vascular health improvements require confirmation in adequately powered randomized controlled trials. OBJECTIVE: This study was designed to measure the dose-response relation between high-flavonoid (HF), low-flavonoid (LF), and habitual F&V intakes and vascular function and other cardiovascular disease (CVD) risk indicators. DESIGN: A single-blind, dose-dependent, parallel randomized controlled dietary intervention study was conducted. Male and female low-F&V consumers who had a ≥1.5-fold increased risk of CVD (n = 174) were randomly assigned to receive an HF F&V, an LF F&V, or a habitual diet, with HF and LF F&V amounts sequentially increasing by 2, 4, and 6 (+2, +4, and +6) portions/d every 6 wk over habitual intakes. Microvascular reactivity (laser Doppler imaging with iontophoresis), arterial stiffness [pulse wave velocity, pulse wave analysis (PWA)], 24-h ambulatory blood pressure, and biomarkers of nitric oxide (NO), vascular function, and inflammation were determined at baseline and at 6, 12, and 18 wk. RESULTS: In men, the HF F&V diet increased endothelium-dependent microvascular reactivity (P = 0.017) with +2 portions/d (at 6 wk) and reduced C-reactive protein (P = 0.001), E-selectin (P = 0.0005), and vascular cell adhesion molecule (P = 0.0468) with +4 portions/d (at 12 wk). HF F&Vs increased plasma NO (P = 0.0243) with +4 portions/d (at 12 wk) in the group as a whole. An increase in F&Vs, regardless of flavonoid content in the groups as a whole, mitigated increases in vascular stiffness measured by PWA (P = 0.0065) and reductions in NO (P = 0.0299) in the control group. CONCLUSION: These data support recommendations to increase F&V intake to ≥6 portions daily, with additional benefit from F&Vs that are rich in flavonoids, particularly in men with an increased risk of CVD. This trial was registered at www.controlled-trials.com as ISRCTN47748735.

Criteria for validation and selection of cognitive tests for investigating the effects of foods and nutrients.

This review is an output of the International Life Sciences Institute (ILSI) Europe Marker Initiative, which aims to identify evidence-based criteria for selecting adequate measures of nutrient effects on health through comprehensive literature review. Experts in cognitive and nutrition sciences examined the applicability of these proposed criteria to the field of cognition with respect to the various cognitive domains usually assessed to reflect brain or neurological function. This review covers cognitive domains important in the assessment of neuronal integrity and function, commonly used tests and their state of validation, and the application of the measures to studies of nutrition and nutritional intervention trials. The aim is to identify domain-specific cognitive tests that are sensitive to nutrient interventions and from which guidance can be provided to aid the application of selection criteria for choosing the most suitable tests for proposed nutritional intervention studies using cognitive outcomes. The material in this review serves as a background and guidance document for nutritionists, neuropsychologists, psychiatrists, and neurologists interested in assessing mental health in terms of cognitive test performance and for scientists intending to test the effects of food or food components on cognitive function.

A role for hippocampal PSA-NCAM and NMDA-NR2B receptor function in flavonoid-induced spatial memory improvements in young rats

The increase in incidence and prevalence of neurodegenerative diseases highlights the need for a more comprehensive understanding of how food components may affect neural systems. In particular, flavonoids have been recognized as promising agents capable of influencing different aspects of synaptic plasticity resulting in improvements in memory and learning in both animals and humans. Our previous studies highlight the efficacy of flavonoids in reversing memory impairments in aged rats, yet little is known about the effects of these compounds in healthy animals, particularly with respect to the molecular mechanisms by which flavonoids might alter the underlying synaptic modifications responsible for behavioral changes. We demonstrate that a 3-week intervention with two dietary doses of flavonoids (Dose I: 8.7 mg/day and Dose II: 17.4 mg/day) facilitates spatial memory acquisition and consolidation (24 recall) (p < 0.05) in young healthy rats. We show for the first time that these behavioral improvements are linked to increased levels in the polysialylated form of the neural adhesion molecule (PSA-NCAM) in the dentate gyrus (DG) of the hippocampus, which is known to be required for the establishment of durable memories. We observed parallel increases in hippocampal NMDA receptors containing the NR2B subunit for both 8.7 mg/day (p < 0.05) and 17.4 mg/day (p < 0.001) doses, suggesting an enhancement of glutamate signaling following flavonoid intervention. This is further strengthened by the simultaneous modulation of hippocampal ERK/CREB/BDNF signaling and the activation of the Akt/mTOR/Arc pathway, which are crucial in inducing changes in the strength of hippocampal synaptic connections that underlie learning. Collectively, the present data supports a new role for PSA-NCAM and NMDA-NR2B receptor on flavonoid-induced improvements in learning and memory, contributing further to the growing body of evidence suggesting beneficial effects of flavonoids in cognition and brain health.

Prebiotic feeding elevates central brain derived neurotrophic factor, N-methyl-D-aspartate receptor subunits and D-serine

The influence of the gut microbiota on brain chemistry has been convincingly demonstrated in rodents. In the absence of gut bacteria, the central expression of brain derived neurotropic factor, (BDNF), and N-methyl-d-aspartate receptor (NMDAR) subunits are reduced, whereas, oral probiotics increase brain BDNF, and impart significant anxiolytic effects. We tested whether prebiotic compounds, which increase intrinsic enteric microbiota, also affected brain BDNF and NMDARs. In addition, we examined whether plasma from prebiotic treated rats released BDNF from human SH-SY5Y neuroblastoma cells, to provide an initial indication of mechanism of action. Rats were gavaged with fructo-oligosaccharides (FOS), galacto-oligosaccharides (GOS) or water for five weeks, prior to measurements of brain BDNF, NMDAR subunits and amino acids associated with glutamate neurotransmission (glutamate, glutamine, and serine and alanine enantiomers). Prebiotics increased hippocampal BDNF and NR1 subunit expression relative to controls. The intake of GOS also increased hippocampal NR2A subunits, and frontal cortex NR1 and d-serine. Prebiotics did not alter glutamate, glutamine, l-serine, l-alanine or d-alanine concentrations in the brain, though GOSfeeding raised plasma d-alanine. Elevated levels of plasma peptide YY (PYY) after GOS intake was observed. Plasma from GOS rats increased the release of BDNF from SH-SY5Y cells, but not in the presence of PYY antisera. The addition of synthetic PYY to SH-SY5Y cell cultures, also elevated BDNF secretion. We conclude that prebiotic-mediated proliferation of gut microbiota in rats, like probiotics, increases brain BDNF expression, possibly through the involvement of gut hormones. The effect of GOS on components of central NMDAR signalling was greater than FOS, and may reflect the proliferative potency of GOS on microbiota. Our data therefore, provide a sound basis to further investigate the utility of prebiotics in the maintenance of brain health and adjunctive treatment of neuropsychiatric disorders.

A study of anticipatory non-autonomous systems

Rhythms are manifested ubiquitously in dynamical biological processes. These fundamental processes which are necessary for the survival of living organisms include metabolism, breathing, heart beat, and, above all, the circadian rhythm coupled to the diurnal cycle. Thus, in mathematical biology, biological processes are often represented as linear or nonlinear oscillators. In the framework of nonlinear and dissipative systems (ie. the flow of energy, substances, or sensory information), they generate stable internal oscillations as a response to environmental input and, in turn, utilise such output as a means of coupling with the environment.

Using standby generators in support of an electricity network: logistics and experience

Electricity load shifting is becoming a big topic in the world of ‘green’ retail. Marks & Spencer (M&S) aim to become the world’s most sustainable retailer (1) and part of that commitment means contributing to the future electricity network. While intelligent operation of fridges and Heating, Ventilation and Air Conditioning (HVAC) systems are a wide area of research, standby generators should be considered too, as they are the most widely adopted form of distributed generation. In this paper, the experience of using standby generators in Northern Ireland to support the grid is shared and the logistics of future projects are discussed. Interactions with maintenance schedules, electricity costs, grid code, staffing and store opening times are discussed as well as the financial implications associated with running generators for grid support.

Polyphenols, glucosinolates, dietary fibre and colon cancer: Understanding the potential of specific types of fruit and vegetables to reduce bowel cancer progression

Colorectal cancer is the third most prevalent cancer worldwide and the most common diet-related cancer, influenced by diets rich in red meat, low in plant foods and high in saturated fats. Observational studies have shown that fruit and vegetable intake may reduce colorectal cancer risks, although the precise bioactive components remain unclear. This review will outline the evidence for the role of polyphenols, glucosinolates and fibres against cancer progression in the gastrointestinal tract. Those bioactive compounds are considered protective agents against colon cancer, with evidence taken from epidemiological, human clinical, animal and in vitro studies. Various mechanisms of action have been postulated, such as the potential of polyphenols and glucosinolates to inhibit cancer cell growth and the actions of insoluble fibres as prebiotics and the evidence for these actions are detailed within. In addition, recent evidence suggests that polyphenols also have the potential to shift the gut ecology in a beneficial manner. Such actions of both fibre and polyphenols in the gastrointestinal tract and through interaction with gut epithelial cells may act in an additive manner to help explain why certain fruits and vegetables, but not all, act to differing extents to inhibit cancer incidence and progression. Indeed, a focus on the individual actions of such fruit and vegetable components, in particular polyphenols, glucosinolates and fibres is necessary to help explain which components are active in reducing gastrointestinal cancer risk.

Stencil dies: new tools for an old trade

Traces the invention and development of stencil dies in the USA in the middle decades of the nineteenth century, focussing on the work of M. J. Metcalf, A. J. Fullam, and S. M. Spencer.

Fruits, vegetables, 100% juice, and cognitive function

Although reviews of the association between polyphenol intake and cognition exist, research examining the cognitive effects of fruit, vegetable, and juice consumption across epidemiological and intervention studies has not been previously examined. Critical inclusion criteria were human participants, a measure of fruit, vegetable, or 100% juice consumption, an objective measure of cognitive function, and a clinical diagnosis of neuropsychological disease. Studies were excluded if consumption of fruit, vegetables, or juice was not assessed in isolation from other foods groups, or if there was no statistical control for education or IQ. Seventeen of 19 epidemiological studies and 3 of 6 intervention studies reported significant benefits of fruit, vegetable, or juice consumption for cognitive performance. The data suggest that chronic consumption of fruits, vegetables, and juices is beneficial for cognition in healthy older adults. The limited data from acute interventions indicate that consumption of fruit juices can have immediate benefits for memory function in adults with mild cognitive impairment; however, as of yet, acute benefits have not been observed in healthy adults. Conclusions regarding an optimum dietary intake for fruits, vegetables, and juices are difficult to quantify because of substantial heterogeneity in the categorization of consumption of these foods.

In vitro colonic metabolism of coffee and chlorogenic acid results in selective changes in human faecal microbiota growth

Coffee is a relatively rich source of chlorogenic acids (CGA), which, like other polyphenols are postulated to exert preventative effects against cardiovascular disease and type-2 diabetes. As a considerable proportion of ingested CGA reaches the large intestine, CGA may be capable of exerting beneficial effects in the large gut. Here we utilise a stirred, anaerobic, pH controlled, batch culture fermentation model of the distal region of the colon in order to investigate the impact of coffee and CGA on the growth of the human faecal microbiota. Incubation of the coffee with the human faecal microbiota led to the rapid metabolism of CGA (4h) and the production of dihydrocaffeic acid and dihydroferulic acid, whilst caffeine remained un-metabolised. The coffee with the highest levels of CGA (p<0.05, relative to the other coffees) induced a significant increase in Bifidobacterium spp. relative to the control at 10 hours post exposure (p<0.05). Similarly, an equivalent quantity of CGA (80.8mg; matched with that in high CGA coffee) induced a significant increase in Bifidobacterium spp. (p<0.05). CGA alone also induced a significant increase in the Clostridium coccoides-Eubacterium rectale group (p<0.05). This selective metabolism and subsequent amplification of specific bacterial populations could be beneficial to host health.

A novel combined biomarker including plasma carotenoids, vitamin C, and ferric reducing antioxidant power is more strongly associated with fruit and vegetable intake than the individual components

BACKGROUND: Monitoring of fruit and vegetable (F&V) intake is fraught with difficulties. Available dietary assessment methods are associated with considerable error, and the use of biomarkers offers an attractive alternative. Few studies to date have examined the use of plasma biomarkers to monitor or predict the F&V intake of volunteers consuming a wide range of intakes from both habitual F&V and manipulated diets. OBJECTIVE: This study tested the hypothesis that an integrated biomarker calculated from a combination of plasma vitamin C, cholesterol-adjusted carotenoid concentration and Ferric Reducing Antioxidant Power (FRAP) had more power to predict F&V intake than each individual biomarker. METHODS: Data from a randomized controlled dietary intervention study [FLAVURS (Flavonoids University of Reading Study); n = 154] in which the test groups observed sequential increases of 2.3, 3.2, and 4.2 portions of F&Vs every 6 wk across an 18-wk period were used in this study. RESULTS: An integrated plasma biomarker was devised that included plasma vitamin C, total cholesterol-adjusted carotenoids, and FRAP values, which better correlated with F&V intake (r = 0.47, P < 0.001) than the individual biomarkers (r = 0.33, P < 0.01; r = 0.37, P < 0.001; and r = 0.14, respectively; P = 0.099). Inclusion of urinary potassium concentration did not significantly improve the correlation. The integrated plasma biomarker predicted F&V intake more accurately than did plasma total cholesterol-adjusted carotenoid concentration, with the difference being significant at visit 2 (P < 0.001) and with a tendency to be significant at visit 1 (P = 0.07). CONCLUSION: Either plasma total cholesterol-adjusted carotenoid concentration or the integrated biomarker could be used to distinguish between high- and moderate-F&V consumers. This trial was registered at www.controlled-trials.com as ISRCTN47748735.

Chronic consumption of flavanone-rich orange juice is associated with cognitive benefits: an 8-wk randomised, double-blind, placebo-controlled trial in healthy older adults

Background: Research indicates that chronic consumption of flavonoids is associated with cognitive benefits in adults with mild cognitive impairment and neurodegenerative disease, although, there has been no such studies in healthy older adults. Furthermore, the effects of commonly consumed orange juice flavanones on cognitive function remain unexplored. Objective: To investigate whether eight weeks of daily flavanone-rich orange juice consumption was beneficial for cognitive function in healthy older adults. Design: High flavanone (HF: 305mg) 100% orange juice and equicaloric low flavanone (LF: 37mg) orange flavored cordial (500ml) were consumed daily for eight weeks by thirty seven healthy older adults (mean age 67 years) according to a crossover, double blind, randomized design separated by a four week washout. Cognitive function, mood and blood pressure were assessed at baseline and follow up with standardized validated tests. Results: Global cognitive function was significantly better following eight week consumption of flavanone-rich juice relative to eight week consumption of the low flavanone control. No significant effects on mood or blood pressure were observed. Conclusions: Chronic daily consumption of flavanone-rich 100% orange juice over eight weeks is beneficial for cognitive function in healthy older adults. The potential for flavanone-rich foods and drinks to attenuate cognitive decline in ageing and the mechanisms which underlie these effects should be investigated.

Associations between flavan-3-ol intake and CVD risk in the Norfolk cohort of the European Prospective Investigation into Cancer (EPIC-Norfolk)

Background: Dietary intervention studies suggest that flavan-3-ol intake can improve vascular function and reduce the risk of cardiovascular diseases (CVD). However, results from prospective studies failed to show a consistent beneficial effect. Objective: To investigate associations between flavan-3-ol intake and CVD risk in the Norfolk arm of the European Prospective Investigation into Cancer and Nutrition (EPIC-Norfolk). Design: Data was available from 24,885 (11,252 men; 13,633 women) participants, recruited between 1993 and 1997 into the EPIC-Norfolk study. Flavan-3-ol intake was assessed using 7-day food diaries and the FLAVIOLA Flavanol Food Composition database. Missing data for plasma cholesterol and vitamin C were imputed using multiple imputation. Associations between flavan-3-ol intake and blood pressure at baseline were determined using linear regression models. Associations with CVD risk were estimated using Cox regression analyses. Results: Median intake of total flavan-3-ols was 1034 mg/d (range: 0 – 8531 mg/d) for men and 970 mg/d (0 – 6695 mg/d) for women, median intake of flavan-3-ol monomers was 233 mg/d (0 – 3248 mg/d) for men and 217 (0 – 2712 mg/d) for women. There were no consistent associations between flavan-3-ol monomer intake and baseline systolic and diastolic blood pressure (BP). After 286,147 person-years of follow up, there were 8463 cardio-vascular events and 1987 CVD related deaths; no consistent association between flavan-3-ol intake and CVD risk (HR 0.93, 95% CI:0.87; 1.00; Q1 vs Q5) or mortality was observed (HR 0.93, 95% CI: 0.84; 1.04). Conclusions: Flavan-3-ol intake in EPIC-Norfolk is not sufficient to achieve a statistically significant reduction in CVD risk.

Zombie mouse in a Chinese Room

John Searle’s Chinese Room Argument (CRA) purports to demonstrate that syntax is not sufficient for semantics, and, hence, because computation cannot yield understanding, the computational theory of mind, which equates the mind to an information processing system based on formal computations, fails. In this paper, we use the CRA, and the debate that emerged from it, to develop a philosophical critique of recent advances in robotics and neuroscience. We describe results from a body of work that contributes to blurring the divide between biological and artificial systems; so-called animats, autonomous robots that are controlled by biological neural tissue and what may be described as remote-controlled rodents, living animals endowed with augmented abilities provided by external controllers. We argue that, even though at first sight, these chimeric systems may seem to escape the CRA, on closer analysis, they do not. We conclude by discussing the role of the body–brain dynamics in the processes that give rise to genuine understanding of the world, in line with recent proposals from enactive cognitive science.