108 research outputs found
Avoiding or restricting defectors in public goods games?
When creating a public good, strategies or mechanisms are required to handle defectors. We first show mathematically and numerically that prior agreements with posterior compensations provide a strategic solution that leads to substantial levels of cooperation in the context of public goods games, results that are corroborated by available experimental data. Notwithstanding this success, one cannot, as with other approaches, fully exclude the presence of defectors, raising the question of how they can be dealt with to avoid the demise of the common good. We show that both avoiding creation of the common good, whenever full agreement is not reached, and limiting the benefit that disagreeing defectors can acquire, using costly restriction mechanisms, are relevant choices. Nonetheless, restriction mechanisms are found the more favourable, especially in larger group interactions. Given decreasing restriction costs, introducing restraining measures to cope with public goods free-riding issues is the ultimate advantageous solution for all participants, rather than avoiding its creation.SCOPUS: ar.jinfo:eu-repo/semantics/publishe
Extending conceptual DFT to include external variables: the influence of magnetic fields
An extension of conceptual DFT to include the influence of an external magnetic field is proposed in the context of a program set up to cope with the ever increasing variability of reaction conditions and concomitant reactivity. The two simplest global reactivity descriptors, the electronic chemical potential (μ) and the hardness (η), are considered for the main group atoms H-Kr using current density-functional theory. The magnetic field strength, |B|, is varied between 0.0 and 1.0 B0 = ħe−1a0−2 ≈ 2.3505 × 105 T, encompassing the Coulomb and intermediate regimes. The carbon atom is studied as an exemplar system to gain insight into the behaviour of the neutral, cationic and anionic species under these conditions. Their electronic configurations change with increasing |B|, leading to a piecewise behaviour of the ionization energy (I) and electron affinity (A) values as a function of |B|. This results in complex behaviour of properties such as the electronegativity χ = −1/2(I + A) = −μ and hardness η = 1/2(I − A). This raises an interesting question: to what extent are atomic properties periodic in the presence of a magnetic field? In the Coulomb regime, close to |B| = 0, we find the familiar periodicity of the atomic properties, and make the connections to response functions central to conceptual DFT. However, as the field increases in the intermediate regime configurational changes of the atomic species lead to discontinuous changes in their properties; fundamentally changing their behaviour, which is illustrated by constructing a periodic table of χ and η values at |B| = 0.5 B0. These values tend to increase for groups 1-2 and decrease for groups 16-18, leading to a narrower range overall and suggesting substantial changes in the chemistry of the main group elements. Changes within each group are also examined as a function of |B|. These are more complex to interpret due to the larger number of configurations accessible to heavier elements at high field. This is illustrated for group 17 where Cl and Br have qualitatively different configurations to their lighter cogener at |B| = 0.5 B0. The insight into periodic trends in strong magnetic fields may provide a crucial starting point for predicting chemical reactivity under these exotic conditions
Molecular charge distributions in strong magnetic fields: a conceptual and current DFT study
The effect of strong magnetic fields on the charge distribution of the hydrogen halides, H2O and NH3 is studied in the context of recent extensions of conceptual density functional theory to include additional variables such as external magnetic fields. From conceptual DFT studies on atoms in strong magnetic fields, changes in electronegativity and hardness suggest a reversal in polarity for all three diatomic molecules under these conditions. This is confirmed by current DFT calculations on these molecules in the presence of strong magnetic fields parallel and perpendicular to the internuclear axis; in the former case the electric dipole moment only undergoes small changes whereas in the latter case it changes significantly and also reverses in direction, doing so at lower field strength if the geometry is relaxed. The absence of a dipole moment induced perpendicular to the bond when a magnetic field is applied in this direction is understood by consideration of time reversal symmetry. Similar results are obtained for H2O and NH3; this may be an important point to consider in future studies focused on the unresolved question on the behaviour of hydrogen bonding in applied magnetic fields
Intergenerational Wealth Transmission and the Dynamics of Inequality in Small-Scale Societies
Small-scale human societies range from foraging bands with a strong egalitarian ethos to more economically stratified agrarian and pastoral societies. We explain this variation in inequality using a dynamic model in which a population’s long-run steady-state level of inequality depends on the extent to which its most important forms of wealth are transmitted within families across generations. We estimate the degree of intergenerational transmission of three different types of wealth (material, embodied, and relational), as well as the extent of wealth inequality in 21 historical and contemporary populations. We show that intergenerational transmission of wealth and wealth inequality are substantial among pastoral and small-scale agricultural societies (on a par with or even exceeding the most unequal modern industrial economies) but are limited among horticultural and foraging peoples (equivalent to the most egalitarian of modern industrial populations). Differences in the technology by which a people derive their livelihood and in the institutions and norms making up the economic system jointly contribute to this pattern
Which humans behave adaptively, and why does it matter?
There has long been debate about the relevance of evolutionary theory to the study of humans. To many of us, however, the debate has shifted from whether to proceed with an evolutionary approach to how to proceed. Increasingly, it has been argued that studies of the current reproductive function of human traits make little or no contribution to the understanding of the psyche (e.g., Symons 1989). Here, on the basis of arguments about the relationship between an adaptation and an adaptive outcome, and a review of studies that assess current adaptiveness, I argue to the contrary that knowledge of the contexts in which people do or do not behave adaptively provides important information about the nature of the mechanisms that comprise the human psyche. In particular, studies that indicate that people behave adaptively in at least some contemporary environments cast doubt on many nonevolutionary constructions of human nature, and can be used now to distinguish alternative evolutionary constructions that are at odds over many issues pentaining to the human psyche's ontogeny and evolutionary background, especially the extent to which the human psyche is general purpose.Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/28505/1/0000302.pd
Regulatory T Cell Responses in Participants with Type 1 Diabetes after a Single Dose of Interleukin-2: A Non-Randomised, Open Label, Adaptive Dose-Finding Trial
BACKGROUND: Interleukin-2 (IL-2) has an essential role in the expansion and function of CD4+ regulatory T cells (Tregs). Tregs reduce tissue damage by limiting the immune response following infection and regulate autoreactive CD4+ effector T cells (Teffs) to prevent autoimmune diseases, such as type 1 diabetes (T1D). Genetic susceptibility to T1D causes alterations in the IL-2 pathway, a finding that supports Tregs as a cellular therapeutic target. Aldesleukin (Proleukin; recombinant human IL-2), which is administered at high doses to activate the immune system in cancer immunotherapy, is now being repositioned to treat inflammatory and autoimmune disorders at lower doses by targeting Tregs. METHODS AND FINDINGS: To define the aldesleukin dose response for Tregs and to find doses that increase Tregs physiologically for treatment of T1D, a statistical and systematic approach was taken by analysing the pharmacokinetics and pharmacodynamics of single doses of subcutaneous aldesleukin in the Adaptive Study of IL-2 Dose on Regulatory T Cells in Type 1 Diabetes (DILT1D), a single centre, non-randomised, open label, adaptive dose-finding trial with 40 adult participants with recently diagnosed T1D. The primary endpoint was the maximum percentage increase in Tregs (defined as CD3+CD4+CD25highCD127low) from the baseline frequency in each participant measured over the 7 d following treatment. There was an initial learning phase with five pairs of participants, each pair receiving one of five pre-assigned single doses from 0.04 × 106 to 1.5 × 106 IU/m2, in order to model the dose-response curve. Results from each participant were then incorporated into interim statistical modelling to target the two doses most likely to induce 10% and 20% increases in Treg frequencies. Primary analysis of the evaluable population (n = 39) found that the optimal doses of aldesleukin to induce 10% and 20% increases in Tregs were 0.101 × 106 IU/m2 (standard error [SE] = 0.078, 95% CI = -0.052, 0.254) and 0.497 × 106 IU/m2 (SE = 0.092, 95% CI = 0.316, 0.678), respectively. On analysis of secondary outcomes, using a highly sensitive IL-2 assay, the observed plasma concentrations of the drug at 90 min exceeded the hypothetical Treg-specific therapeutic window determined in vitro (0.015-0.24 IU/ml), even at the lowest doses (0.040 × 106 and 0.045 × 106 IU/m2) administered. A rapid decrease in Treg frequency in the circulation was observed at 90 min and at day 1, which was dose dependent (mean decrease 11.6%, SE = 2.3%, range 10.0%-48.2%, n = 37), rebounding at day 2 and increasing to frequencies above baseline over 7 d. Teffs, natural killer cells, and eosinophils also responded, with their frequencies rapidly and dose-dependently decreased in the blood, then returning to, or exceeding, pretreatment levels. Furthermore, there was a dose-dependent down modulation of one of the two signalling subunits of the IL-2 receptor, the β chain (CD122) (mean decrease = 58.0%, SE = 2.8%, range 9.8%-85.5%, n = 33), on Tregs and a reduction in their sensitivity to aldesleukin at 90 min and day 1 and 2 post-treatment. Due to blood volume requirements as well as ethical and practical considerations, the study was limited to adults and to analysis of peripheral blood only. CONCLUSIONS: The DILT1D trial results, most notably the early altered trafficking and desensitisation of Tregs induced by a single ultra-low dose of aldesleukin that resolves within 2-3 d, inform the design of the next trial to determine a repeat dosing regimen aimed at establishing a steady-state Treg frequency increase of 20%-50%, with the eventual goal of preventing T1D. TRIAL REGISTRATION: ISRCTN Registry ISRCTN27852285; ClinicalTrials.gov NCT01827735.This is the final version of the article. It first appeared from the Public Library of Science via http://dx.doi.org/10.1371/journal.pmed.100213
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