Privacy and Truthful Equilibrium Selection for Aggregative Games

We study a very general class of games --- multi-dimensional aggregative games --- which in particular generalize both anonymous games and weighted congestion games. For any such game that is also large, we solve the equilibrium selection problem in a strong sense. In particular, we give an efficient weak mediator: a mechanism which has only the power to listen to reported types and provide non-binding suggested actions, such that (a) it is an asymptotic Nash equilibrium for every player to truthfully report their type to the mediator, and then follow its suggested action; and (b) that when players do so, they end up coordinating on a particular asymptotic pure strategy Nash equilibrium of the induced complete information game. In fact, truthful reporting is an ex-post Nash equilibrium of the mediated game, so our solution applies even in settings of incomplete information, and even when player types are arbitrary or worst-case (i.e. not drawn from a common prior). We achieve this by giving an efficient differentially private algorithm for computing a Nash equilibrium in such games. The rates of convergence to equilibrium in all of our results are inverse polynomial in the number of players $n$. We also apply our main results to a multi-dimensional market game. Our results can be viewed as giving, for a rich class of games, a more robust version of the Revelation Principle, in that we work with weaker informational assumptions (no common prior), yet provide a stronger solution concept (ex-post Nash versus Bayes Nash equilibrium). In comparison to previous work, our main conceptual contribution is showing that weak mediators are a game theoretic object that exist in a wide variety of games -- previously, they were only known to exist in traffic routing games

Study protocol: Evaluation of the ‘Flavour School’ sensory food education programme: a cluster-randomised controlled trial in UK primary school children, aged 4-7 years, to determine impact on confidence and curiosity in tasting vegetables and fruit

Background Many children would benefit from a diet richer in vegetables and fruit. ‘Flavour School’ is a programme of ‘sensory food education’, which aims to increase children’s confidence and curiosity in exploring foods and flavours, especially vegetables and fruit. This study will conduct a cluster-randomised controlled trial to assess the outcomes of the Flavour School programme in primary school children aged 4–7 years. Methods Four hundred plus children from 4+ schools will either complete the Flavour School programme (experimental group) or have no intervention with normal school teaching (control group), cluster-randomised within-schools, by school class. Baseline data collection will consist of video recorded behavioural observation during a tasting activity, and post-intervention data collection will repeat this activity after the experimental group have completed the intervention. Process measures will be assessed using a teacher engagement feedback questionnaire. Discussion This study will provide causal data on the efficacy of a sensory food education intervention for increasing children’s confidence and curiosity in exploring foods and flavours, especially vegetables and fruit. This new knowledge will help educators and policy makers to make evidence based decisions on uptake of sensory food education

PCB pollution continues to impact populations of orcas and other dolphins in European waters

Organochlorine (OC) pesticides and the more persistent polychlorinated biphenyls (PCBs) have well-established dose-dependent toxicities to birds, fish and mammals in experimental studies, but the actual impact of OC pollutants on European marine top predators remains unknown. Here we show that several cetacean species have very high mean blubber PCB concentrations likely to cause population declines and suppress population recovery. In a large pan-European meta-analysis of stranded (n = 929) or biopsied (n = 152) cetaceans, three out of four species:- striped dolphins (SDs), bottlenose dolphins (BNDs) and killer whales (KWs) had mean PCB levels that markedly exceeded all known marine mammal PCB toxicity thresholds. Some locations (e.g. western Mediterranean Sea, south-west Iberian Peninsula) are global PCB "hotspots" for marine mammals. Blubber PCB concentrations initially declined following a mid-1980s EU ban, but have since stabilised in UK harbour porpoises and SDs in the western Mediterranean Sea. Some small or declining populations of BNDs and KWs in the NE Atlantic were associated with low recruitment, consistent with PCB-induced reproductive toxicity. Despite regulations and mitigation measures to reduce PCB pollution, their biomagnification in marine food webs continues to cause severe impacts among cetacean top predators in European seas

The Critical Role of N- and C-Terminal Contact in Protein Stability and Folding of a Family 10 Xylanase under Extreme Conditions

Stabilization strategies adopted by proteins under extreme conditions are very complex and involve various kinds of interactions. Recent studies have shown that a large proportion of proteins have their N- and C-terminal elements in close contact and suggested they play a role in protein folding and stability. However, the biological significance of this contact remains elusive.In the present study, we investigate the role of N- and C-terminal residue interaction using a family 10 xylanase (BSX) with a TIM-barrel structure that shows stability under high temperature, alkali pH, and protease and SDS treatment. Based on crystal structure, an aromatic cluster was identified that involves Phe4, Trp6 and Tyr343 holding the N- and C-terminus together; this is a unique and important feature of this protein that might be crucial for folding and stability under poly-extreme conditions. folding and activity. Alanine substitution with Phe4, Trp6 and Tyr343 drastically decreased stability under all parameters studied. Importantly, substitution of Phe4 with Trp increased stability in SDS treatment. Mass spectrometry results of limited proteolysis further demonstrated that the Arg344 residue is highly susceptible to trypsin digestion in sensitive mutants such as ΔF4, W6A and Y343A, suggesting again that disruption of the Phe4-Trp6-Tyr343 (F-W-Y) cluster destabilizes the N- and C-terminal interaction. Our results underscore the importance of N- and C-terminal contact through aromatic interactions in protein folding and stability under extreme conditions, and these results may be useful to improve the stability of other proteins under suboptimal conditions

Induction of SCEs and DNA fragmentation in bovine peripheral lymphocytes by in vitro exposure to tolylfluanid-based fungicide

The potential for genotoxic and cytotoxic effects of tolylfluanid-based fungicide (50% active agent) was evaluated using sister chromatid exchange (SCE) and proliferation indices (PI) in cultured bovine peripheral lymphocytes. For the detection of possible genetic damage, DNA fragmentation assay was also applied. Bovine lymphocytes cultured for 72 h were treated with the fungicide at the final concentrations of 1.75, 3.5, 8.75, and 17.5 μg/mL for the last 24 and 48 h of culture without S9 metabolic activation, and during the last 2 h of culture with S9 metabolic activation. In the SCE assays no evidence for genotoxic activity of the fungicide was found in treatments of 24 h without and 2 h with S9. After the 24 h exposure to tolylfluanid, a weak decrease in the PI was observed. With the prolonged exposure time (48 h), dose dependence in the increase of SCE frequencies was observed. Moreover, after 48 h exposure slight fragmentation of DNA at the concentrations of 3.5 and 8.75 μg/mL was demonstrated. SCE quantification is the most widely used approach for the assessment of genotoxic/cytogenetic effects of chemical compounds. Positive results in the assay at 48 h exposure indicated a potential of the fungicide to increase frequency of chromosomal damage (replication injuries) that is the confirmation of early effect of exposure

Integrating Multiple Biomarkers of Fish Health: A Case Study of Fish Health in Ports

Biomarkers of fish health are recognised as valuable biomonitoring tools that inform on the impact of pollution on biota. The integration of a suite of biomarkers in a statistical analysis that better illustrates the effects of exposure to xenobiotics on living organisms is most informative; however, most published ecotoxicological studies base the interpretation of results on individual biomarkers rather than on the information they carry as a set. To compare the interpretation of results from individual biomarkers with an interpretation based on multivariate analysis, a case study was selected where fish health was examined in two species of fish captured in two ports located in Western Australia. The suite of variables selected included chemical analysis of white muscle, body condition index, liver somatic index (LSI), hepatic ethoxyresorufin-O-deethylase activity, serum sorbitol dehydrogenase activity, biliary polycyclic aromatic hydrocarbon metabolites, oxidative DNA damage as measured by serum 8-oxo-dG, and stress protein HSP70 measured on gill tissue. Statistical analysis of individual biomarkers suggested little consistent evidence of the effects of contaminants on fish health. However, when biomarkers were integrated as a set by principal component analysis, there was evidence that the health status of fish in Fremantle port was compromised mainly due to increased LSI and greater oxidative DNA damage in fish captured within the port area relative to fish captured at a remote site. The conclusions achieved using the integrated set of biomarkers show the importance of viewing biomarkers of fish health as a set of variables rather than as isolated biomarkers of fish health

Polychlorinated Biphenyls and Biotransformation Enzymes in Three Species of Sea Turtles from the Baja California Peninsula of Mexico

Concentrations of polychlorinated biphenyls (PCBs) as well as the expression patterns of cytochrome P450 (CYP) enzymes and glutathione-S-transferase (GST) activities were measured in livers of loggerhead (Caretta caretta), green (Chelonia mydas), and olive ridley (Lepidocheyls olivacea) sea turtles from the Baja California peninsula of Mexico. The mean concentrations of total PCBs were 18.1, 10.5, and 15.2 ng/g wet weight (ww) respectively for the three species and PCB 153 was the dominant congener in all samples. Total PCB concentrations were dominated by penta- and hexa-chlorinated biphenyls. The mean estimated TEQs were 42.8, 22.9, and 10.4 pg/g (ww) for loggerhead, green, and olive ridley, respectively, and more than 70% was accounted for by non-ortho PCBs. Western blots revealed the presence of hepatic microsomal proteins that cross-reacted with anti-CYP2K1 and anti-CYP3A27 antibodies but not with anti-CYP1A antibody. There were no significant differences in GST activities between species. Grouping congeners based on structure–activity relationships for CYP isoenzymes suggested limited activity of CYP1A contribution to PCB biotransformation in sea turtles. These results suggest potential accumulation of PCBs that are CYP1A substrates and provide evidence for biotransformation capacity, which differs from known animal models, highlighting the need for further studies in reptiles, particularly those threatened with extinction

ARTEMIN Promotes De Novo Angiogenesis in ER Negative Mammary Carcinoma through Activation of TWIST1-VEGF-A Signalling

10.1371/journal.pone.0050098PLoS ONE711

Dibutyltin Disrupts Glucocorticoid Receptor Function and Impairs Glucocorticoid-Induced Suppression of Cytokine Production

BACKGROUND: Organotins are highly toxic and widely distributed environmental chemicals. Dibutyltin (DBT) is used as stabilizer in the production of polyvinyl chloride plastics, and it is also the major metabolite formed from tributyltin (TBT) in vivo. DBT is immunotoxic, however, the responsible targets remain to be defined. Due to the importance of glucocorticoids in immune-modulation, we investigated whether DBT could interfere with glucocorticoid receptor (GR) function. METHODOLOGY: We used HEK-293 cells transiently transfected with human GR as well as rat H4IIE hepatoma cells and native human macrophages and human THP-1 macrophages expressing endogenous receptor to study organotin effects on GR function. Docking of organotins was used to investigate the binding mechanism. PRINCIPAL FINDINGS: We found that nanomolar concentrations of DBT, but not other organotins tested, inhibit ligand binding to GR and its transcriptional activity. Docking analysis indicated that DBT inhibits GR activation allosterically by inserting into a site close to the steroid-binding pocket, which disrupts a key interaction between the A-ring of the glucocorticoid and the GR. DBT inhibited glucocorticoid-induced expression of phosphoenolpyruvate carboxykinase (PEPCK) and tyrosine-aminotransferase (TAT) and abolished the glucocorticoid-mediated transrepression of TNF-alpha-induced NF-kappaB activity. Moreover, DBT abrogated the glucocorticoid-mediated suppression of interleukin-6 (IL-6) and TNF-alpha production in lipopolysaccharide (LPS)-stimulated native human macrophages and human THP-1 macrophages. CONCLUSIONS: DBT inhibits ligand binding to GR and subsequent activation of the receptor. By blocking GR activation, DBT may disturb metabolic functions and modulation of the immune system, providing an explanation for some of the toxic effects of this organotin

From Isotropic to Anisotropic Side Chain Representations: Comparison of Three Models for Residue Contact Estimation

The criterion to determine residue contact is a fundamental problem in deriving knowledge-based mean-force potential energy calculations for protein structures. A frequently used criterion is to require the side chain center-to-center distance or the -to- atom distance to be within a pre-determined cutoff distance. However, the spatially anisotropic nature of the side chain determines that it is challenging to identify the contact pairs. This study compares three side chain contact models: the Atom Distance criteria (ADC) model, the Isotropic Sphere Side chain (ISS) model and the Anisotropic Ellipsoid Side chain (AES) model using 424 high resolution protein structures in the Protein Data Bank. The results indicate that the ADC model is the most accurate and ISS is the worst. The AES model eliminates about 95% of the incorrectly counted contact-pairs in the ISS model. Algorithm analysis shows that AES model is the most computational intensive while ADC model has moderate computational cost. We derived a dataset of the mis-estimated contact pairs by AES model. The most misjudged pairs are Arg-Glu, Arg-Asp and Arg-Tyr. Such a dataset can be useful for developing the improved AES model by incorporating the pair-specific information for the cutoff distance