Persistence of anticancer activity in berry extracts after simulated gastrointestinal digestion and colonic fermentation.

Fruit and vegetable consumption is associated at the population level with a protective effect against colorectal cancer. Phenolic compounds, especially abundant in berries, are of interest due to their putative anticancer activity. After consumption, however, phenolic compounds are subject to digestive conditions within the gastrointestinal tract that alter their structures and potentially their function. However, the majority of phenolic compounds are not efficiently absorbed in the small intestine and a substantial portion pass into the colon. We characterized berry extracts (raspberries, strawberries, blackcurrants) produced by in vitro-simulated upper intestinal tract digestion and subsequent fecal fermentation. These extracts and selected individual colonic metabolites were then evaluated for their putative anticancer activities using in vitro models of colorectal cancer, representing the key stages of initiation, promotion and invasion. Over a physiologically-relevant dose range (0-50 µg/ml gallic acid equivalents), the digested and fermented extracts demonstrated significant anti-genotoxic, anti-mutagenic and anti-invasive activity on colonocytes. This work indicates that phenolic compounds from berries undergo considerable structural modifications during their passage through the gastrointestinal tract but their breakdown products and metabolites retain biological activity and can modulate cellular processes associated with colon cancer.

A Monte Carlo study of solutions of oppositely charged polyelectrolytes

The formation of complexes appearing in solutions containing oppositely charged polyelectrolytes has been investigated by Monte Carlo simulations using two different models. The polyions are described as flexible chains of 20 connected charged hard spheres immersed in a homogenous dielectric background representing water. The small ions are either explicitly included or their effect described by using a screened Coulomb potential. The simulated solutions contained 10 positively charged polyions with 0, 2, or 5 negatively charged polyions and the respective counterions. Two different linear charge densities were considered, and structure factors, radial distribution functions, and polyion extensions were determined. A redistribution of positively charged polyions involving strong complexes formed between the oppositely charged polyions appeared as the number of negatively charged polyions was increased. The nature of the complexes was found to depend on the linear charge density of the chains. The simplified model involving the screened Coulomb potential gave qualitatively similar results as the model with explicit small ions. Finally, owing to the complex formation, the sampling in configurational space is nontrivial, and the efficiency of different trial moves was examined.

What is the climate system able to do ‘on its own’?

The climate of the Earth, like planetary climates in general, is broadly controlled by solar irradiation, planetary albedo and emissivity as well as its rotation rate and distribution of land (with its orography) and oceans. However, the majority of climate fluctuations that affect mankind are internal modes of the general circulation of the atmosphere and the oceans. Some of these modes, such as El Nino-Southern Oscillation (ENSO), are quasi-regular and have some longer-term predictive skill; others like the Arctic and Antarctic Oscillation are chaotic and generally unpredictable beyond a few weeks. Studies using general circulation models indicate that internal processes dominate the regional climate and that some like ENSO events have even distinct global signatures. This is one of the reasons why it is so difficult to separate internal climate processes from external ones caused, for example, by changes in greenhouse gases and solar irradiation. However, the accumulation of the warmest seasons during the latest two decades is lending strong support to the forcing of the greenhouse gases. As models are getting more comprehensive, they show a gradually broader range of internal processes including those on longer time scales, challenging the interpretation of the causes of past and present climate events further.

Recent Glacier Retreat Exceeds Internal Variability

Glacier fluctuations exclusively due to internal variations in the climate system are simulated using downscaled integrations of the ECHAM4/OPYC coupled general circulation model (GCM). A process-based modeling approach using a mass balance model of intermediate complexity and a dynamic ice flow model considering simple shearing flow and sliding are applied. Multimillennia records of glacier length fluctuations for Nigardsbreen (Norway) and Rhonegletscher (Switzerland) are simulated using autoregressive processes determined by statistically downscaled GCM experiments. Return periods and probabilities of specific glacier length changes using GCM integrations excluding external forcings such as solar irradiation changes, volcanic, or anthropogenic effects are analyzed and compared to historical glacier length records. Preindustrial fluctuations of the glaciers as far as observed or reconstructed, including their advance during the “Little Ice Age,” can be explained by internal variability in the climate system as represented by a GCM. However, fluctuations comparable to the present-day glacier retreat exceed any variation simulated by the GCM control experiments and must be caused by external forcing, with anthropogenic forcing being a likely candidate.

Impact of long-range correlations on trend detection in total ozone

Total ozone trends are typically studied using linear regression models that assume a first-order autoregression of the residuals [so-called AR(1) models]. We consider total ozone time series over 60°S–60°N from 1979 to 2005 and show that most latitude bands exhibit long-range correlated (LRC) behavior, meaning that ozone autocorrelation functions decay by a power law rather than exponentially as in AR(1). At such latitudes the uncertainties of total ozone trends are greater than those obtained from AR(1) models and the expected time required to detect ozone recovery correspondingly longer. We find no evidence of LRC behavior in southern middle-and high-subpolar latitudes (45°–60°S), where the long-term ozone decline attributable to anthropogenic chlorine is the greatest. We thus confirm an earlier prediction based on an AR(1) analysis that this region (especially the highest latitudes, and especially the South Atlantic) is the optimal location for the detection of ozone recovery, with a statistically significant ozone increase attributable to chlorine likely to be detectable by the end of the next decade. In northern middle and high latitudes, on the other hand, there is clear evidence of LRC behavior. This increases the uncertainties on the long-term trend attributable to anthropogenic chlorine by about a factor of 1.5 and lengthens the expected time to detect ozone recovery by a similar amount (from ∼2030 to ∼2045). If the long-term changes in ozone are instead fit by a piecewise-linear trend rather than by stratospheric chlorine loading, then the strong decrease of northern middle- and high-latitude ozone during the first half of the 1990s and its subsequent increase in the second half of the 1990s projects more strongly on the trend and makes a smaller contribution to the noise. This both increases the trend and weakens the LRC behavior at these latitudes, to the extent that ozone recovery (according to this model, and in the sense of a statistically significant ozone increase) is already on the verge of being detected. The implications of this rather controversial interpretation are discussed.

On the need for a new playing die

We model the rolling of a standard die, using a Markov matrix. Though a die may be called ‘fair’, its initial position influences a roll’s outcome. This being undesirable, a simple solution is proposed.

Response of the Atlantic meridional overturning circulation to a reversal of greenhouse gas increases

The reversibility of the Atlantic meridional overturning circulation (AMOC) is investigated in multi-model experiments using global climate models (GCMs) where CO2 concentrations are increased by 1 or 2 % per annum to 2× or 4× preindustrial conditions. After a period of stabilisation the CO2 is decreased back to preindustrial conditions. In most experiments when the CO2 decreases, the AMOC recovers before becoming anomalously strong. This "overshoot" is up to an extra 18.2Sv or 104 % of its preindustrial strength, and the period with an anomalously strong AMOC can last for several hundred years. The magnitude of this overshoot is shown to be related to the build up of salinity in the subtropical Atlantic during the previous period of high CO2 levels. The magnitude of this build up is partly related to anthropogenic changes in the hydrological cycle. The mechanisms linking the subtropical salinity increase to the subsequent overshoot are analysed, supporting the relationship found. This understanding is used to explain differences seen in some models and scenarios. In one experiment there is no overshoot because there is little salinity build up, partly as a result of model differences in the hydrological cycle response to increased CO2 levels and partly because of a less aggressive scenario. Another experiment has a delayed overshoot, possibly as a result of a very weak AMOC in that GCM when CO2 is high. This study identifies aspects of overshoot behaviour that are robust across a multi-model and multi-scenario ensemble, and those that differ between experiments. These results could inform an assessment of the real-world AMOC response to decreasing CO2.

Tracing troposphere-to-stratosphere transport above a mid-latitude deep convective system

Within the project SPURT (trace gas measurements in the tropopause region) a variety of trace gases have been measured in situ in order to investigate the role of dynamical and chemical processes in the extra-tropical tropopause region. In this paper we report on a flight on 10 November 2001 leading from Hohn, Germany (52�N) to Faro, Portugal (37�N) through a strongly developed deep stratospheric intrusion. This streamer was associated with a large convective system over the western Mediterranean with potentially significant troposphere-to-stratosphere transport. Along major parts of the flight we measured unexpectedly high NOy mixing ratios. Also H2O mixing ratios were significantly higher than stratospheric background levels confirming the extraordinary chemical signature of the probed air masses in the interior of the streamer. Backward trajectories encompassing the streamer enable to analyze the origin and physical characteristics of the air masses and to trace troposphere-to-stratosphere transport. Near the western flank of the streamer features caused by long range transport, such as tropospheric filaments characterized by sudden drops in the O3 and NOy mixing ratios and enhanced CO and H2O can be reconstructed in great detail using the reverse domain filling technique. These filaments indicate a high potential for subsequent mixing with the stratospheric air. At the south-western edge of the streamer a strong gradient in the NOy and the O3 mixing ratios coincides very well with a sharp gradient in potential vorticity in the ECMWF fields. In contrast, in the interior of the streamer the observed highly elevated NOy and H2O mixing ratios up to a potential temperature level of 365K and potential vorticity values of maximum 10 PVU cannot be explained in terms of resolved troposphere-to-stratosphere transport along the backward trajectories. Also mesoscale simulations with a High Resolution Model reveal no direct evidence for convective H2O injection up to this level. Elevated H2O mixing ratios in the ECMWF and HRM are seen only up to about tropopause height at 340 hPa and 270 hPa, respectively, well below flight altitude of about 200 hPa. However, forward tracing of the convective influence as identified by satellite brightness temperature measurements and counts of lightning strokes shows that during this part of the flight the aircraft was closely following the border of an air mass which was heavily impacted by convective activity over Spain and Algeria. This is evidence that deep convection at mid-latitudes may have a large impact on the tracer distribution of the lowermost stratosphere reaching well above the thunderstorms anvils as claimed by recent studies using cloud-resolving models.

The dichotomous structure of the warm conveyor belt

The warm conveyor belt (WCB) of an extratropical cyclone generally splits into two branches. One branch (WCB1) turns anticyclonically into the downstream upper-level tropospheric ridge, while the second branch (WCB2) wraps cyclonically around the cyclone centre. Here, the WCB split in a typical North Atlantic cold-season cyclone is analysed using two numerical models: the Met Office Unified Model and the COSMO model. The WCB flow is defined using off-line trajectory analysis. The two models represent the WCB split consistently. The split occurs early in the evolution of the WCB with WCB1 experiencing maximum ascent at lower latitudes and with higher moisture content than WCB2. WCB1 ascends abruptly along the cold front where the resolved ascent rates are greatest and there is also line convection. In contrast, WCB2 remains at lower levels for longer before undergoing saturated large-scale ascent over the system's warm front. The greater moisture in WCB1 inflow results in greater net potential temperature change from latent heat release, which determines the final isentropic level of each branch. WCB1 also exhibits lower outflow potential vorticity values than WCB2. Complementary diagnostics in the two models are utilised to study the influence of individual diabatic processes on the WCB. Total diabatic heating rates along the WCB branches are comparable in the two models with microphysical processes in the large-scale cloud schemes being the major contributor to this heating. However, the different convective parameterisation schemes used by the models cause significantly different contributions to the total heating. These results have implications for studies on the influence of the WCB outflow in Rossby wave evolution and breaking. Key aspects are the net potential temperature change and the isentropic level of the outflow which together will influence the relative mass going into each WCB branch and the associated negative PV anomalies at the tropopause-level flow.

Creation of the WATCH Forcing Data and Its Use to Assess Global and Regional Reference Crop Evaporation over Land during the Twentieth Century

The Water and Global Change (WATCH) project evaluation of the terrestrial water cycle involves using land surface models and general hydrological models to assess hydrologically important variables including evaporation, soil moisture, and runoff. Such models require meteorological forcing data, and this paper describes the creation of the WATCH Forcing Data for 1958–2001 based on the 40-yr ECMWF Re-Analysis (ERA-40) and for 1901–57 based on reordered reanalysis data. It also discusses and analyses modelindependent estimates of reference crop evaporation. Global average annual cumulative reference crop evaporation was selected as a widely adopted measure of potential evapotranspiration. It exhibits no significant trend from 1979 to 2001 although there are significant long-term increases in global average vapor pressure deficit and concurrent significant decreases in global average net radiation and wind speed. The near-constant global average of annual reference crop evaporation in the late twentieth century masks significant decreases in some regions (e.g., the Murray–Darling basin) with significant increases in others.

Analyses of single nucleotide polymorphisms in selected nutrient-sensitive genes in weight-regain prevention: the DIOGENES study

BACKGROUND: Differences in the interindividual response to dietary intervention could be modified by genetic variation in nutrient-sensitive genes. OBJECTIVE: This study examined single nucleotide polymorphisms (SNPs) in presumed nutrient-sensitive candidate genes for obesity and obesity-related diseases for main and dietary interaction effects on weight, waist circumference, and fat mass regain over 6 mo. DESIGN: In total, 742 participants who had lost ≥ 8% of their initial body weight were randomly assigned to follow 1 of 5 different ad libitum diets with different glycemic indexes and contents of dietary protein. The SNP main and SNP-diet interaction effects were analyzed by using linear regression models, corrected for multiple testing by using Bonferroni correction and evaluated by using quantile-quantile (Q-Q) plots. RESULTS: After correction for multiple testing, none of the SNPs were significantly associated with weight, waist circumference, or fat mass regain. Q-Q plots showed that ALOX5AP rs4769873 showed a higher observed than predicted P value for the association with less waist circumference regain over 6 mo (-3.1 cm/allele; 95% CI: -4.6, -1.6; P/Bonferroni-corrected P = 0.000039/0.076), independently of diet. Additional associations were identified by using Q-Q plots for SNPs in ALOX5AP, TNF, and KCNJ11 for main effects; in LPL and TUB for glycemic index interaction effects on waist circumference regain; in GHRL, CCK, MLXIPL, and LEPR on weight; in PPARC1A, PCK2, ALOX5AP, PYY, and ADRB3 on waist circumference; and in PPARD, FABP1, PLAUR, and LPIN1 on fat mass regain for dietary protein interaction. CONCLUSION: The observed effects of SNP-diet interactions on weight, waist, and fat mass regain suggest that genetic variation in nutrient-sensitive genes can modify the response to diet. This trial was registered at clinicaltrials.gov as NCT00390637.

A generalised Bayesian instrumental variable approach under student t-distributed errors with application

Bayesian analysis is given of an instrumental variable model that allows for heteroscedasticity in both the structural equation and the instrument equation. Specifically, the approach for dealing with heteroscedastic errors in Geweke (1993) is extended to the Bayesian instrumental variable estimator outlined in Rossi et al. (2005). Heteroscedasticity is treated by modelling the variance for each error using a hierarchical prior that is Gamma distributed. The computation is carried out by using a Markov chain Monte Carlo sampling algorithm with an augmented draw for the heteroscedastic case. An example using real data illustrates the approach and shows that ignoring heteroscedasticity in the instrument equation when it exists may lead to biased estimates.

How large is congressional dependence in agriculture. Bayesian inference about ‘scale’ and ‘scope’ in measuring a spatial externality

The political economy literature on agriculture emphasizes influence over political outcomes via lobbying conduits in general, political action committee contributions in particular and the pervasive view that political preferences with respect to agricultural issues are inherently geographic. In this context, ‘interdependence’ in Congressional vote behaviour manifests itself in two dimensions. One dimension is the intensity by which neighboring vote propensities influence one another and the second is the geographic extent of voter influence. We estimate these facets of dependence using data on a Congressional vote on the 2001 Farm Bill using routine Markov chain Monte Carlo procedures and Bayesian model averaging, in particular. In so doing, we develop a novel procedure to examine both the reliability and the consequences of different model representations for measuring both the ‘scale’ and the ‘scope’ of spatial (geographic) co-relations in voting behaviour.

Assessing the business risk of technology obsolescence through enterprise modelling

The problem of technology obsolescence in information intensive businesses (software and hardware no longer being supported and replaced by improved and different solutions) and a cost constrained market can severely increase costs and operational, and ultimately reputation risk. Although many businesses recognise technological obsolescence, the pervasive nature of technology often means they have little information to identify the risk and location of pending obsolescence and little money to apply to the solution. This paper presents a low cost structured method to identify obsolete software and the risk of their obsolescence where the structure of a business and its supporting IT resources can be captured, modelled, analysed and the risk to the business of technology obsolescence identified to enable remedial action using qualified obsolescence information. The technique is based on a structured modelling approach using enterprise architecture models and a heatmap algorithm to highlight high risk obsolescent elements. The method has been tested and applied in practice in two consulting studies carried out by Capgemini involving three UK police forces. However the generic technique could be applied to any industry based on plans to improve it using ontology framework methods. This paper contains details of enterprise architecture meta-models and related modelling.

Association between Mediterranean and Nordic diet scores and changes in weight and waist circumference: influence of FTO and TCF7L2 loci

BACKGROUND: Several studies have shown that adherence to the Mediterranean Diet measured by using the Mediterranean diet score (MDS) is associated with lower obesity risk. The newly proposed Nordic Diet could hold similar beneficial effects. Because of the increasing focus on the interaction between diet and genetic predisposition to adiposity, studies should consider both diet and genetics. OBJECTIVE: We investigated whether FTO rs9939609 and TCF7L2 rs7903146 modified the association between the MDS and Nordic diet score (NDS) and changes in weight (Δweight), waist circumference (ΔWC), and waist circumference adjusted for body mass index (BMI) (ΔWCBMI). DESIGN: We conducted a case-cohort study with a median follow-up of 6.8 y that included 11,048 participants from 5 European countries; 5552 of these subjects were cases defined as individuals with the greatest degree of unexplained weight gain during follow-up. A randomly selected subcohort included 6548 participants, including 5496 noncases. Cases and noncases were compared in analyses by using logistic regression. Continuous traits (ie, Δweight, ΔWC, and ΔWCBMI) were analyzed by using linear regression models in the random subcohort. Interactions were tested by including interaction terms in models. RESULTS: A higher MDS was significantly inversely associated with case status (OR: 0.98; 95% CI: 0.96, 1.00), ΔWC (β = -0.010 cm/y; 95% CI: -0.020, -0.001 cm/y), and ΔWCBMI (β = -0.008; 95% CI:-0.015, -0.001) per 1-point increment but not Δweight (P = 0.53). The NDS was not significantly associated with any outcome. There was a borderline significant interaction between the MDS and TCF7L2 rs7903146 on weight gain (P = 0.05), which suggested a beneficial effect of the MDS only in subjects who carried 1 or 2 risk alleles. FTO did not modify observed associations. CONCLUSIONS: A high MDS is associated with a lower ΔWC and ΔWCBMI, regardless of FTO and TCF7L2 risk alleles. For Δweight, findings were less clear, but the effect may depend on the TCF7L2 rs7903146 variant. The NDS was not associated with anthropometric changes during follow-up.