The Full Strategy Minority Game

The Full Strategy Minority Game (FSMG) is an instance of the Minority Game (MG) which includes a single copy of every potential agent. In this work, we explicitly solve the FSMG thanks to certain symmetries of this game. Furthermore, by considering the MG as a statistical sample of the FSMG, we compute approximated values of the key variable {\sigma}2/N in the symmetric phase for different versions of the MG. As another application we prove that our results can be easily modified in order to handle certain kind of initial biased strategies scores, in particular when the bias is introduced at the agents' level. We also show that the FSMG verifies a strict period two dynamics (i.e., period two dynamics satisfied with probability 1) giving, to the best of our knowledge, the first example of an instance of the MG for which this feature can be analytically proved. Thanks to this property, it is possible to compute in a simple way the probability that a general instance of the MG breaks the period two dynamics for the first time in a given simulation.Comment: To appear in Physica

Self-tuning experience weighted attraction learning in games

Self-tuning experience weighted attraction (EWA) is a one-parameter theory of learning in games. It addresses a criticism that an earlier model (EWA) has too many parameters, by fixing some parameters at plausible values and replacing others with functions of experience so that they no longer need to be estimated. Consequently, it is econometrically simpler than the popular weighted fictitious play and reinforcement learning models. The functions of experience which replace free parameters “self-tune” over time, adjusting in a way that selects a sensible learning rule to capture subjects’ choice dynamics. For instance, the self-tuning EWA model can turn from a weighted fictitious play into an averaging reinforcement learning as subjects equilibrate and learn to ignore inferior foregone payoffs. The theory was tested on seven different games, and compared to the earlier parametric EWA model and a one-parameter stochastic equilibrium theory (QRE). Self-tuning EWA does as well as EWA in predicting behavior in new games, even though it has fewer parameters, and fits reliably better than the QRE equilibrium benchmark

Modelling proteins’ hidden conformations to predict antibiotic resistance

AbstractTEM β-lactamase confers bacteria with resistance to many antibiotics and rapidly evolves activity against new drugs. However, functional changes are not easily explained by differences in crystal structures. We employ Markov state models to identify hidden conformations and explore their role in determining TEM’s specificity. We integrate these models with existing drug-design tools to create a new technique, called Boltzmann docking, which better predicts TEM specificity by accounting for conformational heterogeneity. Using our MSMs, we identify hidden states whose populations correlate with activity against cefotaxime. To experimentally detect our predicted hidden states, we use rapid mass spectrometric footprinting and confirm our models’ prediction that increased cefotaxime activity correlates with reduced Ω-loop flexibility. Finally, we design novel variants to stabilize the hidden cefotaximase states, and find their populations predict activity against cefotaxime in vitro and in vivo. Therefore, we expect this framework to have numerous applications in drug and protein design.</jats:p

Designing Conducting Polymers Using Bioinspired Ant Algorithms

Ant algorithms are inspired in real ants and the main idea is to create virtual ants that travel into the space of possible solution depositing virtual pheromone proportional to how good a specific solution is. This creates a autocatalytic (positive feedback) process that can be used to generate automatic solutions to very difficult problems. In the present work we show that these algorithms can be used coupled to tight-binding hamiltonians to design conducting polymers with pre-specified properties. The methodology is completely general and can be used for a large number of optimization problems in materials science

Playing The Hypothesis Testing Minority Game In The Maximal Reduced Strategy Space

Hypothesis Testing Minority Game (HMG) is a variant of the standard Minority Game (MG) that models the inertial behavior of agents in the market. In the earlier study of our group, we find that agents cooperate better in HMG than in the standard MG when strategies are picked from the full strategy space. Here we continue to study the behavior of HMG when strategies are chosen from the maximal reduced strategy space. Surprisingly, we find that, unlike the standard MG, the level of cooperation in HMG depends strongly on the strategy space used. In addition, a novel intermittency dynamics is also observed in the minority choice time series in a certain parameter range in which the orderly phases are characterized by a variety of periodic dynamics. Remarkably, all these findings can be explained by the crowd-anticrowd theory.Comment: 12 pages, 7 figures, to appear in Physica

Landmark survival as an end-point for trials in critically ill patients – comparison of alternative durations of follow-up: an exploratory analysis

Introduction Interventional ICU trials have followed up patients for variable duration. However, the optimal duration of follow-up for the determination of mortality endpoint in such trials is uncertain. We aimed to determine the most logical and practical mortality end-point in clinical trials of critically ill patients. Methods We performed a retrospective analysis of prospectively collected data involving 369 patients with one of the three specific diagnoses (i) Sepsis (ii) Community acquired pneumonia (iii) Non operative trauma admitted to the Royal Perth Hospital ICU, a large teaching hospital in Western Australia (WA cohort). Their in-hospital and post discharge survival outcome was assessed by linkage to the WA Death Registry. A validation cohort involving 4609 patients admitted during same time period with identical diagnoses from 55 ICUs across Australia (CORE cohort) was used to compare the patient characteristics and in-hospital survival to look at the Australia-wide applicability of the long term survival data from the WA cohort. Results The long term outcome data of the WA cohort indicate that mortality reached a plateau at 90 days after ICU admission particularly for sepsis and pneumonia. Mortality after hospital discharge before 90 days was not uncommon in these two groups. Severity of acute illness as measured by the total number of organ failures or acute physiology score was the main predictor of 90-day mortality. The adjusted in-hospital survival for the WA cohort was not significantly different from that of the CORE cohort in all three diagnostic groups; sepsis (P = 0.19), community acquired pneumonia (P = 0.86), non-operative trauma (P = 0.47). Conclusions A minimum of 90 days follow-up is necessary to fully capture the mortality effect of sepsis and community acquired pneumonia. A shorter period of follow-up time may be sufficient for non-operative trauma

Forty-Year Analysis of Colonoscopic Surveillance Program for Neoplasia in Ulcerative Colitis: An Updated Overview

C.R.C. was funded by the Derek Willoughby Fund for Inflammatory Research. A.L.H. and T.A.G. were funded by Higher Education Funding Council of England

Lost therapeutic potential of monocyte-derived dendritic cells through lost tissue homing: Stable restoration of gut specificity with retinoic acid

© 2013 The Authors. Published by Wiley. This is an open access article available under a Creative Commons licence. The published version can be accessed at the following link on the publisher’s website: https://doi.org/10.1111/cei.12118Summary: Human monocyte-derived dendritic cells (DC) (MoDC) are utilized for immunotherapy. However, in-vitro immunological effects are often not mirrored in vivo. We studied the tissue-homing potential of MoDC. Circulating monocytes and DC expressed different tissue-homing markers and, during in-vitro development of MoDC, homing marker expression was lost resulting in a 'homeless' phenotype. Retinoic acid (RA) induced gut-homing markers (β7 and CCR9) and a regulatory phenotype and function [decreased human leucocyte antigen D-related (HLA-DR) and increased ILT3 and fluorescein isothiocyanate (FITC-dextran uptake) in MoDC]. RA-MoDC were less stimulatory and primed conditioned T cells with a gut-homing profile (β7+CLA-). Unlike the normal intestinal microenvironment, that from inflamed colon of ulcerative colitis (UC) patients did not induce regulatory properties in MoDC. However, RA-MoDC maintained their regulatory gut-specific properties even in the presence of UC microenvironment. Therefore, MoDC may be ineffectual for immunotherapy because they lack tissue-homing and tissue-imprinting specificity. However, MoDC rehabilitation with gut-homing potential by RA could be useful in promoting immunotherapy in pathologies such as UC. © 2013 The Authors. Clinical and Experimental Immunology published by John Wiley & Sons Ltd on behalf of British. Society for Immunology.This work was supported by Marie Curie Intra European Fellowship (FP7‐people‐IEF‐2008‐235993), St Mark's Hospital Foundation the Brigid Balfour Fund and the BBSRC (WMNI P33458).Published versio

Multiple myeloma causes clonal T-cell immunosenescence: Identification of potential novel targets for promoting tumour immunity and implications for checkpoint blockade

© 2016 Macmillan Publishers Limited. Tumour-induced dysfunction of cytotoxic T cells in patients with multiple myeloma (MM) may contribute to immune escape and be responsible for the lack of therapeutic efficacy of immune checkpoint blockade. We therefore investigated dysfunctional clonal T cells in MM and demonstrated immunosenescence but not exhaustion as a predominant feature. T-cell clones were detected in 75% of MM patients and their prognostic significance was revalidated in a new post-immunomodulatory drug cohort. The cells exhibited a senescent secretory effector phenotype: KLRG-1+/CD57+/CD160+/CD28-. Normal-for-age telomere lengths indicate that senescence is telomere independent and potentially reversible. p38-mitogen-activated protein kinase, p16 and p21 signalling pathways known to induce senescence were not elevated. Telomerase activity was found to be elevated and this may explain how normal telomere lengths are maintained in senescent cells. T-cell receptor signalling checkpoints were normal but elevated SMAD levels associated with T-cell inactivation were detected and may provide a potential target for the reversal of clonal T-cell dysfunction in MM. Low programmed death 1 and cytotoxic T-lymphocyte-associated antigen 4 expression detected on T-cell clones infers that these cells are not exhausted but suggests that there would be a suboptimal response to immune checkpoint blockade in MM. Our data suggest that other immunostimulatory strategies are required in MM