Games on graphs with a public signal monitoring

We study pure Nash equilibria in games on graphs with an imperfect monitoring based on a public signal. In such games, deviations and players responsible for those deviations can be hard to detect and track. We propose a generic epistemic game abstraction, which conveniently allows to represent the knowledge of the players about these deviations, and give a characterization of Nash equilibria in terms of winning strategies in the abstraction. We then use the abstraction to develop algorithms for some payoff functions.Comment: 28 page

Effects of divalent dopants on the microstructure and conversion efficiency of Cr4+ ions in Cr,Me:YAG (Me – Ca, Mg, Ca/Mg) transparent ceramics

The efficiency of Cr4+:YAG is directly proportional to the transparency and concentration of Cr4+ which can be tuned by changing the divalent dopant. The aim of this study was to investigate the influence of different kinds of divalent dopants on the properties of Cr,Me:YAG (Me = Ca, Mg or Ca/Mg) ceramics made by solid-state sintering in vacuum. Pure YAG phases with an in-line transmittance of 80% at 1064nm were prepared. It was revealed that the Cr4+ concentration is directly proportional to the concentration of divalent dopants and it does not depend on the type of dopant. Our experiment proves that the efficiency of high optical quality Cr4+:YAG ceramics preparedby sintering does not change when different kinds of divalent additives are used

Optical, Dielectric and Magnetic Properties of La1−xNdxFeO3 Powders and Ceramics

Nanocrystalline La1−xNdxFeO3 powders with different concentrations of Nd3+ have been synthesized using a modified Pechini method. Their structures were studied by X-ray powder diffraction (XRD). Furthermore, La1−xNdxFeO3 nanoceramics were prepared using a high pressure sintering technique. The luminescence spectra of the powders were investigated as a function of concentration of active dopant to check the possible energy transfers observed due to Nd3+ concentration changes. The electrical and magnetic properties of the powders and ceramics were investigated to determine the effect of Nd3+ doping on the dielectric permittivity and magnetization in the wide frequency range. © 2018 by the authors. Licensee MDPI, Basel, Switzerland.Funding: This project has received funding from the European Union’s Horizon 2020 research and innovation programme under the Marie Skłodowska-Curie grant agreement No 778070—TransFerr—H2020-MSCA-RISE-2017. Part of the work was developed within the scope of the project CICECO-Aveiro Institute of Materials, POCI-01-0145-FEDER-007679 (FCT Ref. UID/CTM/50011/2013), financed by national funds through the FCT/MEC and when appropriate co-financed by FEDER under the PT2020 Partnership Agreement

Magnetic Phase Diagram of GdNi2B2C: Two-ion Magnetoelasticity and Anisotropic Exchange Couplings

Extensive magnetization and magnetostriction measurements were carried out on a single crystal of GdNi2B2C along the main tetragonal axes. Within the paramagnetic phase, the magnetic and strain susceptibilities revealed a weak anisotropy in the exchange couplings and two-ion tetragonal-preserving alpha-strain modes. Within the ordered phase, magnetization and magnetostriction revealed a relatively strong orthorhombic distortion mode and rich field-temperature phase diagrams. For H//(100) phase diagram, three field-induced transformations were observed, namely, at: Hd(T), related to the domain alignment; Hr(T), associated with reorientation of the moment towards the c-axis; and Hs(T), defining the saturation process wherein the exchange field is completely counterbalanced. On the other hand, For H//(001) phase diagram, only two field-induced transformations were observed, namely at: Hr(T) and Hs(T). For both phase diagrams, Hs(T) follows the relation Hs[1-(T/Tn)^2]^(1/2)kOe with Hs(T-->0)=128.5(5) kOe and Tn(H=0)=19.5 K. In contrast, the thermal evolution of Hr(T) along the c-axis (much simpler than along the a-axis) follows the relation Hr[1-T/Tr]^(1/3) kOe where Hr(T-->0)=33.5(5) kOe and Tr(H=0)=13.5 K. It is emphasized that the magnetoelastic interaction and the anisotropic exchange coupling are important perturbations and therefore should be explicitly considered if a complete analysis of the magnetic properties of the borocarbides is desired

Impact of Alkali Ions Codoping on Magnetic Properties of La(0.9)A(0.1)Mn(0.9)Co(0.1)O(3) (A: Li, K, Na) Powders and Ceramics

The aim of the work was to check how the introduction of alkali and cobalt ions into a manganese structure can affect the structural disorder and, in consequence, lead to the changes (improvements) of magnetic properties. The high-pressure sintering technique was applied to check if the external factor can modify the magnetization of manganites. Nanocrystalline La0.9A0.1Mn0.9Co0.1O3 (where A is Li, K, Na) powders were synthesized by the combustion technique. The respective powders were used for nanoceramics preparation by the high-pressure sintering technique. The structure and morphology of the compounds were studied by X-ray powder diffraction, scanning electron microscopy and energy-dispersive X-ray spectroscopy. Magnetization studies for all compounds were performed in order to check the changes induced by either codoping or the sintering pressure. It was found that the type of the dopant ion and sintering pressure produced significant changes to the magnetic properties of the studied compounds. Alkali ions lead to the stabilization of Co ions in the +2 oxidation state and the formation of positive exchange interactions Mn3+–Mn4+ and Co2+–Mn4+ and the subsequent increase in remanent magnetization. High sintering pressure leads to a decrease in grain size and reduction of long-range ferromagnetic order and lower magnetization. © 2020 by the authors. Licensee MDPI, Basel, Switzerland.This project has received funding from the European Union’s Horizon 2020 research and innovation programme under the Marie Skłodowska‐Curie grant agreement No 778070–TransFerr–H2020‐MSCA‐RISE‐ 2017. Part of this work was developed within the scope of the project CICECO‐Aveiro Institute of Materials, UIDB/50011/2020 and UIDP/50011/2020, financed by national funds through the Portuguese Foundation for Science and Technology/MCTES. The equipment of the Ural Center for Shared Use “Modern nanotechnology” UrFU was used. The work has been supported in part by the Ministry of Science and Higher Education of the Russian Federation under Project № FEUZ‐2020‐0054

The Effect of Chaperonin Buffering on Protein Evolution

Molecular chaperones are highly conserved and ubiquitous proteins that help other proteins in the cell to fold. Pioneering work by Rutherford and Lindquist suggested that the chaperone Hsp90 could buffer (i.e., suppress) phenotypic variation in its client proteins and that alternate periods of buffering and expression of these variants might be important in adaptive evolution. More recently, Tokuriki and Tawfik presented an explicit mechanism for chaperone-dependent evolution, in which the Escherichia coli chaperonin GroEL facilitated the folding of clients that had accumulated structurally destabilizing but neofunctionalizing mutations in the protein core. But how important an evolutionary force is chaperonin-mediated buffering in nature? Here, we address this question by modeling the per-residue evolutionary rate of the crystallized E. coli proteome, evaluating the relative contributions of chaperonin buffering, functional importance, and structural features such as residue contact density. Previous findings suggest an interaction between codon bias and GroEL in limiting the effects of misfolding errors. Our results suggest that the buffering of deleterious mutations by GroEL increases the evolutionary rate of client proteins. We then examine the evolutionary fate of GroEL clients in the Mycoplasmas, a group of bacteria containing the only known organisms that lack chaperonins. We show that GroEL was lost once in the common ancestor of a monophyletic subgroup of Mycoplasmas, and we evaluate the effect of this loss on the subsequent evolution of client proteins, providing evidence that client homologs in 11 Mycoplasma species have lost their obligate dependency on GroEL for folding. Our analyses indicate that individual molecules such as chaperonins can have significant effects on proteome evolution through their modulation of protein folding

The effect of extrinsic mortality on genome size evolution in prokaryotes

Mortality has a significant role in prokaryotic ecology and evolution, yet the impact of variations in extrinsic mortality on prokaryotic genome evolution has received little attention. We used both mathematical and agent-based models to reveal how variations in extrinsic mortality affect prokaryotic genome evolution. Our results suggest that the genome size of bacteria increases with increased mortality. A high extrinsic mortality increases the pool of free resources and shortens life expectancy, which selects for faster reproduction, a phenotype we called ‘scramblers’. This phenotype is realised by the expansion of gene families involved in nutrient acquisition and metabolism. In contrast, a low mortality rate increases an individual’s life expectancy, which results in natural selection favouring tolerance to starvation when conditions are unfavourable. This leads to the evolution of small, streamlined genomes (‘stayers’). Our models predict that large genomes, gene family expansion and horizontal gene transfer should be observed in prokaryotes occupying ecosystems exposed to high abiotic stress, as well as those under strong predator- and/or pathogen-mediated selection. A comparison of genome size of cyanobacteria in relatively stable marine versus more turbulent freshwater environments corroborates our predictions, although other factors between these environments could also be responsible

Systematic, comprehensive, evidence-based approach to identify neuroprotective interventions for motor neuron disease: using systematic reviews to inform expert consensus

Objectives: Motor neuron disease (MND) is an incurable progressive neurodegenerative disease with limited treatment options. There is a pressing need for innovation in identifying therapies to take to clinical trial. Here, we detail a systematic and structured evidence-based approach to inform consensus decision making to select the first two drugs for evaluation in Motor Neuron Disease-Systematic Multi-arm Adaptive Randomised Trial (MND-SMART: NCT04302870), an adaptive platform trial. We aim to identify and prioritise candidate drugs which have the best available evidence for efficacy, acceptable safety profiles and are feasible for evaluation within the trial protocol. Methods: We conducted a two-stage systematic review to identify potential neuroprotective interventions. First, we reviewed clinical studies in MND, Alzheimer’s disease, Huntington’s disease, Parkinson’s disease and multiple sclerosis, identifying drugs described in at least one MND publication or publications in two or more other diseases. We scored and ranked drugs using a metric evaluating safety, efficacy, study size and study quality. In stage two, we reviewed efficacy of drugs in MND animal models, multicellular eukaryotic models and human induced pluripotent stem cell (iPSC) studies. An expert panel reviewed candidate drugs over two shortlisting rounds and a final selection round, considering the systematic review findings, late breaking evidence, mechanistic plausibility, safety, tolerability and feasibility of evaluation in MND-SMART. Results: From the clinical review, we identified 595 interventions. 66 drugs met our drug/disease logic. Of these, 22 drugs with supportive clinical and preclinical evidence were shortlisted at round 1. Seven drugs proceeded to round 2. The panel reached a consensus to evaluate memantine and trazodone as the first two arms of MND-SMART. Discussion: For future drug selection, we will incorporate automation tools, text-mining and machine learning techniques to the systematic reviews and consider data generated from other domains, including high-throughput phenotypic screening of human iPSCs

Low-level regulatory T-cell activity is essential for functional type-2 effector immunity to expel gastrointestinal helminths

Helminth infection is frequently associated with the expansion of regulatory T cells (Tregs) and suppression of immune responses to bystander antigens. We show that infection of mice with the chronic gastrointestinal helminth Heligmosomoides polygyrus drives rapid polyclonal expansion of Foxp3(+)Helios(+)CD4(+) thymic (t)Tregs in the lamina propria and mesenteric lymph nodes while Foxp3(+)Helios(-)CD4(+) peripheral (p)Treg expand more slowly. Notably, in partially resistant BALB/c mice parasite survival positively correlates with Foxp3(+)Helios(+)CD4(+) tTreg numbers. Boosting of Foxp3(+)Helios(+)CD4(+) tTreg populations by administration of recombinant interleukin-2 (rIL-2):anti-IL-2 (IL-2C) complex increased worm persistence by diminishing type-2 responsiveness in vivo, including suppression of alternatively activated macrophage and granulomatous responses at the sites of infection. IL-2C also increased innate lymphoid cell (ILC) numbers, indicating that Treg functions dominate over ILC effects in this setting. Surprisingly, complete removal of Tregs in transgenic Foxp3-DTR mice also resulted in increased worm burdens, with "immunological chaos" evident in high levels of the pro-inflammatory cytokines IL-6 and interferon-γ. In contrast, worm clearance could be induced by anti-CD25 antibody-mediated partial depletion of early Treg, alongside increased T helper type 2 responses and without incurring pathology. These findings highlight the overarching importance of the early Treg response to infection and the non-linear association between inflammation and the prevailing Treg frequency

Membrane-Bound IL-21 Promotes Sustained Ex Vivo Proliferation of Human Natural Killer Cells

NK cells have therapeutic potential for a wide variety of human malignancies. However, because NK cells expand poorly in vitro, have limited life spans in vivo, and represent a small fraction of peripheral white blood cells, obtaining sufficient cell numbers is the major obstacle for NK-cell immunotherapy. Genetically-engineered artificial antigen-presenting cells (aAPCs) expressing membrane-bound IL-15 (mbIL15) have been used to propagate clinical-grade NK cells for human trials of adoptive immunotherapy, but ex vivo proliferation has been limited by telomere shortening. We developed K562-based aAPCs with membrane-bound IL-21 (mbIL21) and assessed their ability to support human NK-cell proliferation. In contrast to mbIL15, mbIL21-expressing aAPCs promoted log-phase NK cell expansion without evidence of senescence for up to 6 weeks of culture. By day 21, parallel expansion of NK cells from 22 donors demonstrated a mean 47,967-fold expansion (median 31,747) when co-cultured with aAPCs expressing mbIL21 compared to 825-fold expansion (median 325) with mbIL15. Despite the significant increase in proliferation, mbIL21-expanded NK cells also showed a significant increase in telomere length compared to freshly obtained NK cells, suggesting a possible mechanism for their sustained proliferation. NK cells expanded with mbIL21 were similar in phenotype and cytotoxicity to those expanded with mbIL15, with retained donor KIR repertoires and high expression of NCRs, CD16, and NKG2D, but had superior cytokine secretion. The mbIL21-expanded NK cells showed increased transcription of the activating receptor CD160, but otherwise had remarkably similar mRNA expression profiles of the 96 genes assessed. mbIL21-expanded NK cells had significant cytotoxicity against all tumor cell lines tested, retained responsiveness to inhibitory KIR ligands, and demonstrated enhanced killing via antibody-dependent cell cytotoxicity. Thus, aAPCs expressing mbIL21 promote improved proliferation of human NK cells with longer telomeres and less senescence, supporting their clinical use in propagating NK cells for adoptive immunotherapy