Metallo-organic domino reactions: C-H versus C-C bond breaking

HL and MeL are prepared by condensing benzil dihydrazone with 2-formylpyridine and 2-acetylpyridine, respectively, in 1:2 molar proportions. While in a reaction with [Ru-(C6H6)Cl-2](2), HL yields the cation [Ru(C6H6){5,6-diphenyl-3-(pyridin-2-yl)- 1,2,4-triazine}Cl](+), MeL gives the cation [Ru(C6H6)(MeL)Cl](+). Both the cations are isolated as their hexafluorophosphate salts and characterised by X-ray crystallography. In the case of HL, double domino electrocyclic/elimination reactions are found to occur. The electrocyclic reaction occurs in a C=N-N=C-C=N fragment of HL and the elimination reaction involves breaking of a C-H bond of HL. Density functional calculations on model complexes indicate that the identified electrocyclic reaction is thermochemically as well as kinetically feasible for both HL and MeL in the gas phase. For a double domino reaction, similar to that operative in HL, to occur for MeL, breaking of a C-C bond would be required in the elimination step. Our model calculations show the energy barrier for this elimination step to be much higher (329.1 kJ mol(-1)) for MeL than that for HL (96.3 kJ mol(-1)). Thus, the domino reaction takes place for HL and not for MeL. This accounts for the observed stability of [Ru(C6H6)-(MeL)Cl](+) under the reaction conditions employed.

Stress relaxation behaviour of frozen sucrose solutions

The stress relaxation behaviour of two frozen sucrose solutions (7% and 19%) during indentation in the temperature range of -20C to -40C were investigated. The stress relaxation is similar to that of pure polycrystalline ice, which is controlled by steady-state creep. The steady state creep rate exponent, m, of 7% and 19% sucrose solutions lies between 2.3 and 3.6. The steady state creep rate constant, B, of 19% sucrose solution is greater than that of 7% sucrose solution. It is suggested that the steady-state creep rate exponent m depends on contributions from the proportions of favourably oriented grains, unfavourably oriented grains and grain boundaries to creep and that these components depend on the value of internal stress which is related to the hardness of samples at the different testing temperatures. The steady-state creep rate constant B depends on the mobility of dislocations in sucrose solutions which, in turn, depends on the temperature and the concentration of sucrose.

Fecal microbiota in patients receiving enteral feeding are highly variable and may be altered in those who develop diarrhea

Background: The pathogenesis of diarrhea in patients receiving enteral feeding includes colonic water secretion, antibiotic prescription, and enteropathogenic colonization, each of which involves an interaction with the gastrointestinal microbiota. Objective: The objective was to investigate temporal changes in the concentrations of fecal microbiota and short-chain fatty acids (SCFAs) in patients starting 14-d of enteral feeding and to compare these changes between patients who do and do not develop diarrhea. Design: Twenty patients starting exclusive nasogastric enteral feeding were monitored for 14 d. Fecal samples were collected at the start, middle, and end of this period and were analyzed for major bacterial groups by using culture independent fluorescence in situ hybridization and for SCFAs by using gas-liquid chromatography. Results: Although no significant changes in fecal microbiota or SCFAs were observed during enteral feeding, stark alterations occurred within individual patients. Ten patients (50%) developed diarrhea, and these patients had significantly higher concentrations of clostridia (P = 0.026) and lower concentrations (P = 0.069) and proportions (P = 0.029) of bifidobacteria. Patients with and without diarrhea had differences in the proportion of bifidobacteria (median: 0.4% and 3.7%; interquartile range: 0.8 compared with 4.3; P = 0.035) and clostridia (median: 10.4% and 3.7%; interquartile range: 14.7 compared with 7.0; P = 0.063), respectively, even at the start of enteral feeding. Patients who developed diarrhea had higher concentrations of total fecal SCFAs (P = 0.044), acetate (P = 0.029), and butyrate (P = 0.055). Conclusion: Intestinal dysbiosis occurs in patients who develop diarrhea during enteral feeding and may be involved in its pathogenesis. Am J Clin Nutr 2009; 89: 240-7.

Commentary on 'Prebiotics, immune function, infection and inflammation: a review of the evidence'

There is a growing awareness that the gut microbiota and an appropriately functioning immune system play an important role in maintaining human health. Recent population statistics have highlighted some worrying trends, specifically that there is a growing burden of immunological disease in Western populations, that Western populations are ageing, and that obesity, with its strong inflammatory component, is reaching epidemic proportions.

Effects of cis-9,trans-11 and trans-1 0,cis-12 conjugated linoleic acid on immune cell function in healthy humans

Background: Animal studies have suggested that conjugated linoleic acid (CLA), a natural component of ruminant meat and dairy products, may confer beneficial effects on health. However, little information on the effects of CLA on immune function is available, especially in humans. Furthermore, the effects of individual isomers of CLA have not been adequately investigated. Objective: This study investigated the effects of supplementing the diet with 3 doses of highly enriched cis-9,trans-11 CLA (0.59, 1.19, and 2.38 g/d) or trans-10,cis-12 CLA (0.63, 1.26, and 2.52 g/d) on immune outcomes in healthy humans. Design: The study had a randomized, double-blind, crossover design. Healthy men consumed 1, 2, and 4 capsules sequentially that contained 80% of either cis-9,trans-11 CLA or trans-10,cis-12 CLA for consecutive 8-wk periods. This regimen was followed by a 6-wk washout and a crossover to the other isomer. Results: Both CLA isomers decreased mitogen-induced T lymphocyte activation in a dose-dependent manner. There was a significant negative correlation between mitogen-induced T lymphocyte activation and the proportions of both cis-9,trans-11 CLA and trans-10,cis-12 CLA in peripheral blood mononuclear cell lipids. However, CLA did not affect lymphocyte subpopulations or serum concentrations of C-reactive protein and did not have any consistent effects on ex vivo cytokine production. Conclusion: CLA supplementation results in a dose-dependent reduction in the mitogen-induced activation of T lymphocytes. The effects of cis-9,trans-l I CLA and trans-10,cis-12 CLA were similar, and there was a negative correlation between mitogen-induced T lymphocyte activation and the cis-9,trans-11 CLA and trans-10,cis-12 CLA contents of mononuclear cells.

Association of n-3 polyunsaturated fatty acids with stability of atherosclerotic plaques: a randomised controlled trial

Background N-3 polyunsaturated fatty acids (PUFAs) from oily fish protect against death from cardiovascular disease. We aimed to assess the hypothesis that incorporation of n-3 and n-6 PUFAs into advanced atherosclerotic plaques increases and decreases plaque stability, respectively. Methods We did a randomised controlled trial of patients awaiting carotid endarterectomy. We randomly allocated patients control, sunflower oil (n-6), or fish-oil (n-3) capsules until surgery. Primary outcome was plaque morphology indicative of stability or instability, and outcome measures were concentrations of EPA, DHA, and linoleic acid in carotid plaques; plaque morphology; and presence of macrophages in plaques. Analysis was per protocol. Findings 188 patients were enrolled and randomised; 18 withdrew and eight were excluded. Duration of oil treatment was 7-189 days (median 42) and did not differ between groups. The proportions of EPA and DHA were higher in carotid plaque fractions in patients receiving fish oil compared with those receiving control (absolute difference 0.5 [95% CI 0.3-0.7], 0.4 [0.1-0.6], and 0.2 [0.1-0.4] g/100 g total fatty acids for EPA; and 0.3 [0.0-0.8], 0.4 [0.1-0.7], and 0.3 [0.1-0.6] g/100 g total fatty acids for DHA; in plaque phospholipids, cholesteryl esters, and triacylglycerols, respectively). Sunflower oil had little effect on the fatty acid composition of lipid fractions. Fewer plaques from patients being treated with fish oil had thin fibrous caps and signs of inflammation and more plaques had thick fibrous caps and no signs of inflammation, compared with plaques in patients in the control and sunflower oil groups (odds ratio 0.52 [95% CI 0.24-0.89] and 1.19 [1.02-1.57] vs control; 0.49 [0.23-0.90] and 1.16 [1.01-1.53] vs sunflower oil). The number of macrophages in plaques from patients receiving fish oil was lower than in the other two groups. Carotid plaque morphology and infiltration by macrophages did not differ between control and sunflower oil groups. Interpretation Atherosclerotic plaques readily incorporate n-3 PUFAs from fish-oil supplementation, inducing changes that can enhance stability of atherosclerotic plaques. By contrast, increased consumption of n-6 PUFAs does not affect carotid plaque fatty-acid composition or stability over the time course studied here. Stability of plaques could explain reductions in non-fatal and fatal cardiovascular events associated with increased n-3 PUFA intake.

Analysis of 'APN' naphthenic acids by high temperature gas chromatoagraphy and high performance liquid chromatography

Examination by high temperature GC (HTGC) of the methyl esters of the so-called 'ARN' naphthenic acids from crude oils of North Sea UK, Norwegian Sea and West African oilfields revealed the distributions of resolved 4-8 ring C-80 tetra acids and trace amounts of other acids. Whilst all three oils contained apparently the same the proportions of each differed, possibly reflecting the growth tempe acids, ratures of the archaebacteria from which the acids are assumed to have originated. The structures of the 4, 5, 7 and 8 ring acids are tentatively assigned by comparison with the known 6 ring acid and related natural products and an HPLC method for the isolation of the individual acids is described. ESI-MS of individual acids isolated by preparative HPLC established the elution order of the 4-8 ring acids on the HPLC and HTGC systems and revealed the presence of previously unreported acids tentatively identified as C-81 and C-82 7 and 8 ring analogues.

Achievement of dietary fatty acid intakes in long-term controlled intervention studies: approach and methodology

Objective: To describe the calculations and approaches used to design experimental diets of differing saturated fatty acid (SFA) and monounsaturated fatty acid (MUFA) compositions for use in a long-term dietary intervention study, and to evaluate the degree to which the dietary targets were met. Design, setting and subjects: Fifty-one students living in a university hall of residence consumed a reference (SFA) diet for 8 weeks followed by either a moderate MUFA (MM) diet or a high MUFA (HM) diet for 16 weeks. The three diets were designed to differ only in their proportions of SFA and MUFA, while keeping total fat, polyunsaturated fatty acids (PUFA), trans-fatty acids, and the ratio of palmitic to stearic acid, and n-6 to n-3 PUFA, unchanged. Results: Using habitual diet records and a standardised database for food fatty acid compositions, a sequential process of theoretical fat substitutions enabled suitable fat sources for use in the three diets to be identified, and experimental margarines for baking, spreading and the manufacture of snack foods to be designed. The dietary intervention was largely successful in achieving the fatty acid targets of the three diets, although unintended differences between the original target and the analysed fatty acid composition of the experimental margarines resulted in a lower than anticipated MUFA intake on the HM diet, and a lower ratio of palmitic to stearic acid compared with the reference or MM diet. Conclusions: This study has revealed important theoretical considerations that should be taken into account when designing diets of specific fatty acid composition, as well as practical issues of implementation.

Mechanisms of alkylpyrazine formation in a potato model system containing added glycine

The use of glycine to limit acrylamide formation during the heating of a potato model system was also found to alter the relative proportions of alkylpyrazines. The addition of glycine increased the quantities of several alkylpyrazines, and labeling studies using [2-C-13]glycine showed that those alkylpyrazines which increased in the presence of glycine had at least one C-13-labeled methyl substituent derived from glycine. The distribution of C-13 within the pyrazines suggested two pathways by which glycine, and other amino acids, participate in alkylpyrazine formation, and showed the relative contribution of each pathway. Alkylpyrazines that involve glycine in both formation pathways displayed the largest relative increases with glycine addition. The study provided an insight into the sensitivity of alkylpyrazine formation to the amino acid composition in a heated food and demonstrated the importance of those amino acids that are able to contribute an alkyl substituent. This may aid in estimating the impact of amino acid addition on pyrazine formation, when amino acids are added to foods for acrylamide mitigation.

Relation between the fatty acid composition of peripheral blood mononuclear cells and measures of immune cell function in health free-living subjects aged 25-72 y

Background: There is little information about the relation between the fatty acid composition of human immune cells and the function of those cells over the habitual range of fatty acid intakes. Objective: The objective of the study was to determine the relation between the fatty acid composition of human peripheral blood mononuclear cell (PBMC) phospholipids and the functions of human immune cells. Design: One hundred fifty healthy adult subjects provided a fasting blood sample. The phagocytic and oxidative burst activities of monocytes and neutrophils were measured in whole blood. PBMCs were isolated and used to measure lymphocyte proliferation in response to the T cell mitogen concanavalin A and the production of cytokines in response to concanavalin A or bacterial lipopolysaccharide. The fatty acid composition of plasma and PBMC phospholipids was determined. Results: Wide variations in fatty acid composition of PBMC phospholipids and immune cell functions were identified among the subjects. The proportions of total Polyunsaturated fatty acids (PUFAs), of total n-6 and n-3 PUFAs, and of several individual PUFAs in PBMC phospholipids were positively correlated with phagocytosis by neutrophils and monocytes, neutrophil oxidative burst, lymphocyte proliferation, and interferon gamma production. The ratios of saturated fatty acids to PUFAs and of n-6 to n-3 PUFAs were negatively correlated with these same immune functions. The relation of PBMC fatty acid composition to monocyte oxidative burst was the reverse of its relation to monocyte phagocytosis and neutrophil oxidative burst. Conclusion: Variations in the fatty acid composition of PBMC phospholipids account for some of the variability in immune cell functions among healthy adults.

Protocol for the PINCER trial: a cluster randomised trial comparing the effectiveness of a pharmacist-led IT-based intervention with simple feedback in reducing rates of clinically important errors in medicines management in general practices

Background: Medication errors are an important cause of morbidity and mortality in primary care. The aims of this study are to determine the effectiveness, cost effectiveness and acceptability of a pharmacist-led information-technology-based complex intervention compared with simple feedback in reducing proportions of patients at risk from potentially hazardous prescribing and medicines management in general (family) practice. Methods: Research subject group: "At-risk" patients registered with computerised general practices in two geographical regions in England. Design: Parallel group pragmatic cluster randomised trial. Interventions: Practices will be randomised to either: (i) Computer-generated feedback; or (ii) Pharmacist-led intervention comprising of computer-generated feedback, educational outreach and dedicated support. Primary outcome measures: The proportion of patients in each practice at six and 12 months post intervention: - with a computer-recorded history of peptic ulcer being prescribed non-selective non-steroidal anti-inflammatory drugs - with a computer-recorded diagnosis of asthma being prescribed beta-blockers - aged 75 years and older receiving long-term prescriptions for angiotensin converting enzyme inhibitors or loop diuretics without a recorded assessment of renal function and electrolytes in the preceding 15 months. Secondary outcome measures; These relate to a number of other examples of potentially hazardous prescribing and medicines management. Economic analysis: An economic evaluation will be done of the cost per error avoided, from the perspective of the UK National Health Service (NHS), comparing the pharmacist-led intervention with simple feedback. Qualitative analysis: A qualitative study will be conducted to explore the views and experiences of health care professionals and NHS managers concerning the interventions, and investigate possible reasons why the interventions prove effective, or conversely prove ineffective. Sample size: 34 practices in each of the two treatment arms would provide at least 80% power (two-tailed alpha of 0.05) to demonstrate a 50% reduction in error rates for each of the three primary outcome measures in the pharmacist-led intervention arm compared with a 11% reduction in the simple feedback arm. Discussion: At the time of submission of this article, 72 general practices have been recruited (36 in each arm of the trial) and the interventions have been delivered. Analysis has not yet been undertaken.

A climate change risk analysis for world ecosystems

We quantify the risks of climate-induced changes in key ecosystem processes during the 21st century by forcing a dynamic global vegetation model with multiple scenarios from 16 climate models and mapping the proportions of model runs showing forest/nonforest shifts or exceedance of natural variability in wildfire frequency and freshwater supply. Our analysis does not assign probabilities to scenarios or weights to models. Instead, we consider distribution of outcomes within three sets of model runs grouped by the amount of global warming they simulate: <2°C (including simulations in which atmospheric composition is held constant, i.e., in which the only climate change is due to greenhouse gases already emitted), 2–3°C, and >3°C. High risk of forest loss is shown for Eurasia, eastern China, Canada, Central America, and Amazonia, with forest extensions into the Arctic and semiarid savannas; more frequent wildfire in Amazonia, the far north, and many semiarid regions; more runoff north of 50°N and in tropical Africa and northwestern South America; and less runoff in West Africa, Central America, southern Europe, and the eastern U.S. Substantially larger areas are affected for global warming >3°C than for <2°C; some features appear only at higher warming levels. A land carbon sink of ≈1 Pg of C per yr is simulated for the late 20th century, but for >3°C this sink converts to a carbon source during the 21st century (implying a positive climate feedback) in 44% of cases. The risks continue increasing over the following 200 years, even with atmospheric composition held constant.

Sterically controlled recognition of macromolecular sequence information by molecular tweezers

Sequence-specific binding is demonstrated between pyrene-based tweezer molecules and soluble, high molar mass copolyimides. The binding involves complementary pi - pi stacking interactions, polymer chain-folding, and hydrogen bonding and is extremely sensitive to the steric environment around the pyromellitimide binding-site. A detailed picture of the intermolecular interactions involved has been obtained through single-crystal X-ray studies of tweezer complexes with model diimides. Ring-current magnetic shielding of polyimide protons by the pyrene '' arms '' of the tweezer molecule induces large complexation shifts of the corresponding H-1 NMR resonances, enabling specific triplet sequences to be identified by their complexation shifts. Extended comonomer sequences (triplets of triplets in which the monomer residues differ only by the presence or absence of a methyl group) can be '' read '' by a mechanism which involves multiple binding of tweezer molecules to adjacent diimide residues within the copolymer chain. The adjacent-binding model for sequence recognition has been validated by two conceptually different sets of tweezer binding experiments. One approach compares sequence-recognition events for copolyimides having either restricted or unrestricted triple-triplet sequences, and the other makes use of copolymers containing both strongly binding and completely nonbinding diimide residues. In all cases the nature and relative proportions of triple-triplet sequences predicted by the adjacent-binding model are fully consistent with the observed H-1 NMR data.

Part load operation coefficient of air-conditioning system of public building

IPLV overall coefficient, presented by Air-Conditioning and Refrigeration Institute (ARI) of America, shows running/operation status of air-conditioning system host only. For overall operation coefficient, logical solution has not been developed, to reflect the whole air-conditioning system under part load. In this research undertaking, the running time proportions of air-conditioning systems under part load have been obtained through analysis on energy consumption data during practical operation in all public buildings in Chongqing. This was achieved by using analysis methods, based on the statistical energy consumption data distribution of public buildings month-by-month. Comparing with the weight number of IPLV, part load operation coefficient of air-conditioning system, based on this research, does not only show the status of system refrigerating host, but also reflects and calculate energy efficiency of the whole air-conditioning system. The coefficient results from the processing and analyzing of practical running data, shows the practical running status of area and building type (actual and objective) – not clear. The method is different from model analysis which gets IPLV weight number, in the sense that this method of coefficient results in both four equal proportions and also part load operation coefficient of air-conditioning system under any load rate as necessary.

Associations between dairy consumption and body weight: a review of the evidence and underlying mechanisms

As the incidence of obesity is reaching 'epidemic' proportions, there is currently widespread interest in the impact of dietary components on body-weight and food intake regulation. The majority of data available from both epidemiological and intervention studies provide evidence of a negative but modest association between milk and dairy product consumption and BMI and other measures of adiposity, with indications that higher intakes result in increased weight loss and lean tissue maintenance during energy restriction. The purported physiological and molecular mechanisms underlying the impact of dairy constituents on adiposity are incompletely understood but may include effects on lipolysis, lipogeneis and fatty acid absorption. Furthermore, accumulating evidence indicates an impact of dairy constituents, in particular whey protein derivatives, on appetite regulation and food intake. The present review summarises available data and provides an insight into the likely contribution of dairy foods to strategies aimed at appetite regulation, weight loss or the prevention of weight gain.