Gibbs entropy and irreversible thermodynamics

Recently a number of approaches has been developed to connect the microscopic dynamics of particle systems to the macroscopic properties of systems in nonequilibrium stationary states, via the theory of dynamical systems. This way a direct connection between dynamics and Irreversible Thermodynamics has been claimed to have been found. However, the main quantity used in these studies is a (coarse-grained) Gibbs entropy, which to us does not seem suitable, in its present form, to characterize nonequilibrium states. Various simplified models have also been devised to give explicit examples of how the coarse-grained approach may succeed in giving a full description of the Irreversible Thermodynamics. We analyze some of these models pointing out a number of difficulties which, in our opinion, need to be overcome in order to establish a physically relevant connection between these models and Irreversible Thermodynamics.Comment: 19 pages, 4 eps figures, LaTeX2

The efficiency of CD4 recruitment to ligand-engaged TCR controls the agonist/partial agonist properties of peptide-MHC molecule ligands.

One hypothesis seeking to explain the signaling and biological properties of T cell receptor for antigen (TCR) partial agonists and antagonists is the coreceptor density/kinetic model, which proposes that the pharmacologic behavior of a TCR ligand is largely determined by the relative rates of (a) dissociation ofligand from an engaged TCR and (b) recruitment oflck-linked coreceptors to this ligand-engaged receptor. Using several approaches to prevent or reduce the association of CD4 with occupied TCR, we demonstrate that consistent with this hypothesis, the biological and biochemical consequence of limiting this interaction is to convert typical agonists into partial agonist stimuli. Thus, adding anti-CD4 antibody to T cells recognizing a wild-type peptide-MHC class II ligand leads to disproportionate inhibition of interleukin-2 (IL-2) relative to IL-3 production, the same pattern seen using a TCR partial agonist/antagonist. In addition, T cells exposed to wild-type ligand in the presence of anti-CD4 antibodies show a pattern of TCR signaling resembling that seen using partial agonists, with predominant accumulation of the p21 tyrosine-phosphorylated form of TCR-zeta, reduced tyrosine phosphorylation of CD3epsilon, and no detectable phosphorylation of ZAP-70. Similar results are obtained when the wild-type ligand is presented by mutant class II MHC molecules unable to bind CD4. Likewise, antibody coligation of CD3 and CD4 results in an agonist-like phosphorylation pattern, whereas bivalent engagement of CD3 alone gives a partial agonist-like pattern. Finally, in accord with data showing that partial agonists often induce T cell anergy, CD4 blockade during antigen exposure renders cloned T cells unable to produce IL-2 upon restimulation. These results demonstrate that the biochemical and functional responses to variant TCR ligands with partial agonist properties can be largely reproduced by inhibiting recruitment of CD4 to a TCR binding a wild-type ligand, consistent with the idea that the relative rates of TCR-ligand disengagement and of association of engaged TCR with CD4 may play a key role in determining the pharmacologic properties of peptide-MHC molecule ligands. Beyond this insight into signaling through the TCR, these results have implications for models of thymocyte selection and the use of anti-coreceptor antibodies in vivo for the establishment ofimmunological tolerance

The human salivary microbiome exhibits temporal stability in bacterial diversity

The temporal variability of the human microbiome may be an important factor in determining its relationship with health and disease. In this study, the saliva of 40 participants was collected every 2 months over a one-year period to determine the temporal variability of the human salivary microbiome. Salivary pH and 16S rRNA gene copy number were measured for all participants, with the microbiome of 10 participants assessed through 16S rRNA amplicon sequencing. In February 2013, 16S rRNA gene copy number was significantly (P < 0.001) higher, with individual changes between time points significant (P = 0.003). Salivary pH levels were significantly (P < 0.001) higher in December 2012 than in October 2012 and February 2013, with significant (P < 0.001) individual variations seen throughout. Bacterial α-diversity showed significant differences between participants (P < 0.001), but not sampling periods (P = 0.801), and a significant positive correlation with salivary pH (R(2) = 7.8%; P = 0.019). At the phylum level, significant differences were evident between participants in the Actinobacteria (P < 0.001), Bacteroidetes (P < 0.001), Firmicutes (P = 0.008), Fusobacteria (P < 0.001), Proteobacteria (P < 0.001), Synergistetes (P < 0.001) and Spirochaetes (P = 0.003) phyla. This study charted the temporal variability of the salivary microbiome, suggesting that bacterial diversity is stable, but that 16S rRNA gene copy number may be subject to seasonal flux

Energy density of foods and beverages in the Australian food supply: influence of macronutrients and comparison to dietary intake.

OBJECTIVES: The energy density (ED) of the diet is considered an important determinant of total energy intake and thus energy balance and weight change. We aimed to compare relationships between ED and macronutrient content in individual food and beverage items as well as population diet in a typical Western country. DESIGN: Nutrient data for 3673 food items and 247 beverage items came from the Australian Food and Nutrient database (AusNut). Food and beverage intake data came from the 1995 Australian National Nutrition Survey (a 24-h dietary recall survey in 13 858 people over the age of 2). Relationships between ED and macronutrient and water content were analysed by linear regression with 95% prediction bands. RESULTS: For both individual food items and population food intake, there was a positive relationship between ED and percent energy as fat and negative relationships between ED and percent energy as carbohydrate and percent water by weight. In all cases, there was close agreement between the slopes of the regression lines between food items and dietary intake. There were no clear relationships between ED and macronutrient content for beverage items. Carbohydrate (mostly sucrose) contributed 91, 47, and 25% of total energy for sugar-based, fat-based, and alcohol-based beverages respectively. CONCLUSIONS: The relationship between ED and fat content of foods holds true across both population diets and individual food items available in the food supply in a typical Western country such as Australia. As high-fat diets are associated with a high BMI, population measures with an overall aim of reducing the ED of diets may be effective in mediating the growing problem of overweight and obesity

Spectra of dynamical Dark Energy cosmologies from constant-w models

WMAP5 and related data have greatly restricted the range of acceptable cosmologies, by providing precise likelihood ellypses on the the w_0-w_a plane. We discuss first how such ellypses can be numerically rebuilt, and present then a map of constant-w models whose spectra, at various redshift, are expected to coincide with acceptable models within ~1%

National evaluation of the neighbourhood nurseries: integrated report

Report description: The NNI was launched in 2001 to provide high quality childcare in the most disadvantaged neighbourhoods of England, to help parents into employment, reduce child poverty and boost children’s development. By 2005 45,000 new childcare places had been created in approximately 1,400 neighbourhood nurseries. This report brings together the findings of the four individual strands of the National Evaluation of Neighbourhood Nurseries Initiative as shown above and makes a number of recommendations. The report shows the rationale for the government’s strategy in targeting disadvantaged neighbourhoods and in focusing on high quality childcare to provide the link between raising parental employment and income and improving children’s life chances