Shock Profiles for the Asymmetric Simple Exclusion Process in One Dimension

The asymmetric simple exclusion process (ASEP) on a one-dimensional lattice is a system of particles which jump at rates $p$ and $1-p$ (here $p>1/2$) to adjacent empty sites on their right and left respectively. The system is described on suitable macroscopic spatial and temporal scales by the inviscid Burgers' equation; the latter has shock solutions with a discontinuous jump from left density $\rho_-$ to right density $\rho_+$, $\rho_-<\rho_+$, which travel with velocity $(2p-1)(1-\rho_+-\rho_-)$. In the microscopic system we may track the shock position by introducing a second class particle, which is attracted to and travels with the shock. In this paper we obtain the time invariant measure for this shock solution in the ASEP, as seen from such a particle. The mean density at lattice site $n$, measured from this particle, approaches $\rho_{\pm}$ at an exponential rate as $n\to\pm\infty$, with a characteristic length which becomes independent of $p$ when $p/(1-p)>\sqrt{\rho_+(1-\rho_-)/\rho_-(1-\rho_+)}$. For a special value of the asymmetry, given by $p/(1-p)=\rho_+(1-\rho_-)/\rho_-(1-\rho_+)$, the measure is Bernoulli, with density $\rho_-$ on the left and $\rho_+$ on the right. In the weakly asymmetric limit, $2p-1\to0$, the microscopic width of the shock diverges as $(2p-1)^{-1}$. The stationary measure is then essentially a superposition of Bernoulli measures, corresponding to a convolution of a density profile described by the viscous Burgers equation with a well-defined distribution for the location of the second class particle.Comment: 34 pages, LaTeX, 2 figures are included in the LaTeX file. Email: [email protected], [email protected], [email protected]

High-protein/high red meat and high-carbohydrate weight-loss diets do not differ in their effect on faecal water genotoxicity tested by use of the WIL2-NS cell line and with other biomarkers of bowel health

The impact of popular weight-loss diets with different macronutrient profiles on bowel health in humans has not been previously assessed. The aim of this study was to investigate whether a high-protein/high red meat (HP) diet influences faecal water genotoxicity and other standard biomarkers of bowel health differently compared with a high-carbohydrate (HC) diet. Thirty-three male subjects were randomly assigned to a HP (35% protein, 40% carbohydrate) or HC (17% protein, 58% carbohydrate) isocaloric energy-restricted dietary intervention consisting of 12 weeks intensive weight loss followed by weight maintenance for up to 52 weeks. Faecal samples were collected at 0, 12 and 52 weeks. Faecal water genotoxicity was assessed in the WIL2-NS human B lymphoblastoid cell line by means of the cytokinesis-block micronucleus cytome assay. Average weight loss after 12 weeks was 9.3 ± 0.7kg for both diets, with no further change in weight at 52 weeks. Two-way ANOVA showed a significant effect with time (P<0.001) but not diet for total DNA damage, with a reduction in genotoxicity after 12 weeks intensive weight loss, and a subsequent increase after 9 months weight maintenance to levels not significantly different from baseline. There was no significant effect for time or diet on faecal pH, short-chain fatty acid excretion, phenol or p-cresol. Results suggest that HP and HC weight-loss diets may modify the carcinogenic profile of the bowel contents such that weight loss may exert a beneficial effect by reducing genotoxic load in the short term; however, these results require verification against a non-weight-loss control.Bianca Benassi-Evans, Peter Clifton, Manny Noakes, Michael Fenec

High protein-high red meat versus high carbohydrate weight loss diets do not differ in effect on genome stability and cell death in lymphocytes of overweight men

© The Author 2009. Published by Oxford University Press on behalf of the UK Environmental Mutagen Society. All rights reserved.The importance of diet in DNA damage prevention is well established; however, the comparison of weight loss diets with different micronutrient and macronutrient profiles on genome stability in peripheral blood lymphocytes (PBLs) has not been studied. This study tested the hypothesis that genome stability in PBLs of overweight men who consume a high protein–high red meat (HP) weight loss diet is different from that of overweight men who consume a high carbohydrate (HC) weight loss diet. Thirty-three male subjects were randomly assigned to an HP or HC isocaloric energy-restricted dietary intervention for 12 weeks intensive weight loss and weight maintenance up to 52 weeks. Blood samples were collected at 0, 12 and 52 weeks. DNA damage in PBLs was assessed using the cytokinesis-block micronucleus cytome (CBMN-Cyt) assay. Average weight loss after 12 weeks was 9.3 ± 0.7 kg for both diets, with no further change at 52 weeks. Two-way analysis of variance showed no time or diet effect on micronucleus frequency (chromosome loss/breaks). There was a significant trend with time (P = 0.03) but not diet, for reduction of nuclear buds (gene amplification). There was a positive trend with time for increased nucleoplasmic bridges (chromosome rearrangement) (P = 0.051). Necrosis and apoptosis both significantly decreased with time (P = 0.037 and P = 0.007, respectively) with no diet effect. There was no significant effect of time or diet for nuclear division index, a biomarker of immune response. The results suggest that the effect of the HP weight loss diet on DNA damage measured using the CBMN-Cyt assay in PBLs was not different from that observed for the HC weight loss diet.Bianca Benassi-Evans, Peter M. Clifton, Manny Noakes, Jennifer B. Keogh and Michael Fenec

Cytokinesis-block micronucleus cytome assays for the determination of genotoxicity and cytotoxicity of cecal water in rats and fecal water in humans

© 2007 American Association for Cancer ResearchWe tested the cytokinesis-block micronucleus cytome assay using the WIL2-NS human B lymphoblastoid cell line as a biomarker of genotoxicity and cytotoxicity of cecal water from rats and fecal water from humans. Cecal water was assessed in rats fed either a diet rich in fat, low in calcium and fiber, and barbecued red meat as the protein source (high colorectal cancer risk diet) or a diet high in fiber and calcium, low in fat, and casein as the protein source (low colorectal cancer risk diet) for 2 weeks. There was a significant 7.6-, 1.8-, and 4.0-fold increase in binucleated (BN) cells with micronuclei (Mn-BN), BN cells with nucleoplasmic bridges (Npb-BN), and necrotic cells (P < 0.001) with 1-h incubation with a 10% dilution of the cecal water isolated from rats fed the high colorectal cancer risk diet compared with rats fed the low colorectal cancer risk diet. In humans, fecal water samples collected from feces of free-living volunteers showed that 24-h exposure to 1% dilution of fecal water produced a significant 2.6-, 6.5-, 7.5-, and 2.2-fold increase in Mn-BN, Npb-BN, BN cells with nuclear buds, and necrotic cells compared with controls (P < 0.05). The coefficients of variations for interindividual differences for Mn-BN, Npb-BN, BN cells with nuclear buds, and necrosis biomarkers were greater than corresponding coefficients of variations for intraindividual variation. These results indicate that the cytokinesis-block micronucleus cytome assay can be used successfully to determine the interindividual variation in genotoxicity and cytotoxicity of cecal or fecal water and to identify dietary patterns that are likely to increase carcinogenic events in the colon

Application and adaptation of the in vitro micronucleus assay for the assessment of nutritional requirements of cells for DNA damage prevention

DNA damage is a fundamental cause of developmental and degenerative diseases. The in vitro cytokinesis-block micronucleus cytome (CBMN-Cyt) assay is an established comprehensive method for assessing cytostasis and chromosome stability in cells. Originally developed to study the acute effects of single environmental genotoxicants, creative applications and adaptations to the basic protocol have allowed its use in evaluating the impacts of dietary micronutrients and micronutrient combinations (nutriomes) on DNA damage. In this review, we examine some of these studies and the important findings they have generated with respect to nutrient/nutrient, nutrient/genotype and nutrient/genotoxicant interactions, as well as assessment of the carcinogenic (or protective) potential of whole dietary patterns. In addition, we outline current knowledge gaps and technical limitations and propose future adaptations to enhance the applicability of the CBMN-Cyt method for in vivo predictions.Caroline F. Bull, Sasja Beetstra-Hill, Bianca J. Benassi-Evans, Jimmy W. Crott, Michiyo Kimura, Theodora Teo, Jing Wu and Michael F. Fenec

BRACAVENIR - impact of a psychoeducational intervention on expectations and coping in young women (aged 18–30 years) exposed to a high familial breast/ovarian cancer risk: study protocol for a randomized controlled trial

International audienceBackground: Young women exposed to a high hereditary breast and ovarian cancer (HBOC) risk are particularly vulnerable. They are ignored by health prevention measures but exposed to a stream of contradictory information (medicine, media, Internet). They may feel concerned about surgical prevention issues at a key moment of their identity construction (self, relationship, sexuality). We designed a special psychoeducational intervention to help these women cope better with these difficulties.Methods/design: The BRACAVENIR study consists of a prospective, randomized superiority phase II trial with a wait list control group. Participants are childless young female counselees (aged 18–30 years) seen at the oncogenetics department of the Centre Jean Perrin and belonging to HBOC families either with or without BRCA mutations. They will be invited to attend a weekend group session at a spa resort and to participate in short expert conferences and focus group activities (group sharing, Moreno role game) supervised by a psychotherapist. Two sessions separated by a 6-month delay (wait list) will enable us to evaluate the intervention’s effect by comparing questionnaire scores between the 6-month time points. The main endpoint is an increase of the Herth Hope Index by at least 1 SD. Secondary endpoints are self-esteem, anxiety trait, anxiety state, coping, and quality of life. With a one-sided α = 0.05 and β = 0.20, 12 participants will be needed by group, plus an additional 2 in anticipation of dropouts. Participants will be randomized 1:1 to the first or the second session so that the groups will be comparable.Discussion: The intent of this trial is to bridge the gap on a psychosocial level in these young women with HBOC. A particularity of the design is the use of a waiting list, which should allow for avoiding major bias. The intervention consists of a short session that could be proposed to other young counselees if successful. The results may bring complementary information to facilitate the intervention and also influence the contents of the oncogenetic consultation.Trial registration: Ethics committee CPP SUD-EST-6: IRB00008526. Registered on 18 March 2016.ClinicalTrials.gov identifier: NCT02705924. Registered on 2 March 2016