Insertion/deletion-related polymorphisms in the human T cell receptor beta gene complex.

Insertion/deletion related polymorphisms (IDRP) involving stretches of 15-30 kb within the human TCR-beta gene complex were revealed by pulse-field gel electrophoresis. Two independent IDRP systems were detected by analysis of Sfi I- and Sal I-digested human DNA samples using probes for TCR C and V region gene segments. The allelic nature of these systems was verified in family studies, and mapping data allowed localization of one area of insertion/deletion among the V gene segments and the other near the C region genes. All but one of 50 individuals tested could be typed for the two allelic systems, and gene frequencies for the two allelic forms were 0.37/0.61 and 0.46/0.54, indicating that these polymorphisms are widespread

Heterogeneity in background fitness acts as a suppressor of selection

This is the author accepted manuscript. The final version is available from Elsevier via the DOI in this record.We introduce the concept of heterogeneity in background fitness to evolutionary dynamics in finite populations. Background fitness is specific to an individual but not linked to its strategy. It can be thought of as a property that is related to the physical or societal position of an individual, but is not dependent on the strategy that is adopted in the evolutionary process under consideration. In our model, an individual's total fitness is the sum of its background fitness and the fitness derived from using a specific strategy. This approach has important implications for the imitation of behavioural strategies: if we imitate others for their success, but can only adopt their behaviour and not their social and economic ties, we may imitate in vain. We study the effect of heterogeneity in background fitness on the fixation of a mutant strategy with constant fitness. We find that heterogeneity suppresses selection, but also decreases the time until a novel strategy either takes over the population or is lost again. We derive analytical solutions of the fixation probability in small populations. In the case of large total background fitness in a population with maximum inequality, we find a particularly simple approximation of the fixation probability. Numerical simulations suggest that this simple approximation also holds for larger population sizes. Previous article in issueO.P.H. is grateful for fellowship support from Harvard's Department of Organismic and Evolutionary Biology. O.P.H. and M.A.N. are thankful for support from the Templeton Foundation. A.T. thanks the Max-Planck-Gesellschaft for generous funding

SUSY Contributions to RbR_b and Top Decay

I report on a systematic analysis of the MSSM parameter space to obtain the best SUSY solution to the $R_b$ anomaly within the constraint of top quark decay. Phenomenological implications for top decay and direct stop production at the Tevatron collider are discussed.Comment: Latex file (3 pages)+ 2 ps files containing figures. Invited talk at SUSY96, Maryland, May 199

Punishment does not promote cooperation under exploration dynamics when anti-social punishment is possible

This is the author accepted manuscript. The final version is available from Elsevier via the DOI in this record.It has been argued that punishment promotes the evolution of cooperation when mutation rates are high (i.e. when agents engage in ‘exploration dynamics’). Mutations maintain a steady supply of agents that punish free-riders, and thus free-riders are at a disadvantage. Recent experiments, however, have demonstrated that free-riders sometimes also pay to punish cooperators. Inspired by these empirical results, theoretical work has explored evolutionary dynamics where mutants are rare, and found that punishment does not promote the evolution of cooperation when this ‘anti-social punishment’ is allowed. Here we extend previous theory by studying the effect of anti-social punishment on the evolution of cooperation across higher mutation rates, and by studying voluntary as well as compulsory Public Goods Games. We find that for intermediate and high mutation rates, adding punishment does not promote cooperation in either compulsory or voluntary public goods games if anti-social punishment is possible. This is because mutations generate agents that punish cooperators just as frequently as agents that punish defectors, and these two effects cancel each other out. These results raise questions about the effectiveness of punishment for promoting cooperation when mutations are common, and highlight how decisions about which strategies to include in the strategy set can have profound effects on the resulting dynamics.O.P.H. is grateful to the department of Organismic and Evolutionary Biology at Harvard for fellowship support. Funding from the John Templeton Foundation is gratefully acknowledged

Cooperating with the future

This is the author accepted manuscript. The final version is available from Nature Publishing Group via the DOI in this record.Overexploitation of renewable resources today has a high cost on the welfare of future generations1,2,3,4,5. Unlike in other public goods games6,7,8,9, however, future generations cannot reciprocate actions made today. What mechanisms can maintain cooperation with the future? To answer this question, we devise a new experimental paradigm, the ‘Intergenerational Goods Game’. A line-up of successive groups (generations) can each either extract a resource to exhaustion or leave something for the next group. Exhausting the resource maximizes the payoff for the present generation, but leaves all future generations empty-handed. Here we show that the resource is almost always destroyed if extraction decisions are made individually. This failure to cooperate with the future is driven primarily by a minority of individuals who extract far more than what is sustainable. In contrast, when extractions are democratically decided by vote, the resource is consistently sustained. Voting10,11,12,13,14,15 is effective for two reasons. First, it allows a majority of cooperators to restrain defectors. Second, it reassures conditional cooperators16 that their efforts are not futile. Voting, however, only promotes sustainability if it is binding for all involved. Our results have implications for policy interventions designed to sustain intergenerational public goods.Financial support from the Department of Organismic and Evolutionary Biology at Harvard, the Harvard Office for Sustainability and the John Templeton Foundation is gratefully acknowledged

Think global, act local: Preserving the global commons

This is the author accepted manuscript. The final version is available from Springer Nature via the DOI in this recordPreserving global public goods, such as the planet’s ecosystem, depends on large-scale cooperation, which is difficult to achieve because the standard reciprocity mechanisms weaken in large groups. Here we demonstrate a method by which reciprocity can maintain cooperation in a large-scale public goods game (PGG). In a first experiment, participants in groups of on average 39 people play one round of a Prisoner’s Dilemma (PD) with their two nearest neighbours on a cyclic network after each PGG round. We observe that people engage in “local-to-global” reciprocity, leveraging local interactions to enforce global cooperation: Participants reduce PD cooperation with neighbours who contribute little in the PGG. In response, low PGG contributors increase their contributions if both neighbours defect in the PD. In a control condition, participants do not know their neighbours’ PGG contribution and thus cannot link play in the PD to the PGG. In the control we observe a sharp decline of cooperation in the PGG, while in the treatment condition global cooperation is maintained. In a second experiment, we demonstrate the scalability of this effect: in a 1,000-person PGG, participants in the treatment condition successfully sustain public contributions. Our findings suggest that this simple “local-to-global” intervention facilitates large-scale cooperation.This work was supported by Office of Naval Research grant N00014-16-1-2914 and by the John Templeton Foundation. The Program for Evolutionary Dynamics is supported in part by a gift from B Wu and Eric Larson

Follow-up examination of linkage and association to chromosome 1q43 in multiple sclerosis.

Multiple sclerosis (MS) is a debilitating neuroimmunological and neurodegenerative disease affecting >4,00,000 individuals in the United States. Population and family-based studies have suggested that there is a strong genetic component. Numerous genomic linkage screens have identified regions of interest for MS loci. Our own second-generation genome-wide linkage study identified a handful of non-major histocompatibility complex regions with suggestive linkage. Several of these regions were further examined using single-nucleotide polymorphisms (SNPs) with average spacing between SNPs of approximately 1.0 Mb in a dataset of 173 multiplex families. The results of that study provided further evidence for the involvement of the chromosome 1q43 region. This region is of particular interest given linkage evidence in studies of other autoimmune and inflammatory diseases including rheumatoid arthritis and systemic lupus erythematosus. In this follow-up study, we saturated the region with approximately 700 SNPs (average spacing of 10 kb per SNP) in search of disease-associated variation within this region. We found preliminary evidence to suggest that common variation within the RGS7 locus may be involved in disease susceptibility

Invisible Inequality Leads to Punishing the Poor and Rewarding the Rich

This is the author accepted manuscript. The final version is available from Cambridge University Press via the DOI in this record.Four experiments examine how lack of awareness of inequality affect behaviour towards the rich and poor. In experiment 1, participants who became aware that wealthy individuals donated a smaller percentage of their income switched from rewarding the wealthy to rewarding the poor. In experiments 2 and 3, participants who played a public goods game— and were assigned incomes reflective of the U.S. income distribution either at random or on merit—punished the poor (for small absolute contributions) and rewarded the rich (for large absolute contributions) when incomes were unknown; when incomes were revealed, participants punished the rich (for the low percentage of income contributed) and rewarded the poor (for their high percentage). In experiment 4, participants provided with public education contributions for five New York school districts levied additional taxes on mostly poorer school districts when incomes were unknown, but targeted wealthier districts when incomes were revealed. These results shed light on how income transparency shapes preferences for equity and redistribution. We discuss implications for policy-makers

A bi-dimensional finite mixture model for longitudinal data subject to dropout

In longitudinal studies, subjects may be lost to follow-up, or miss some of the planned visits, leading to incomplete response sequences. When the probability of non-response, conditional on the available covariates and the observed responses, still depends on unobserved outcomes, the dropout mechanism is said to be non ignorable. A common objective is to build a reliable association structure to account for dependence between the longitudinal and the dropout processes. Starting from the existing literature, we introduce a random coefficient based dropout model where the association between outcomes is modeled through discrete latent effects. These effects are outcome-specific and account for heterogeneity in the univariate profiles. Dependence between profiles is introduced by using a bi-dimensional representation for the corresponding distribution. In this way, we define a flexible latent class structure which allows to efficiently describe both dependence within the two margins of interest and dependence between them. By using this representation we show that, unlike standard (unidimensional) finite mixture models, the non ignorable dropout model properly nests its ignorable counterpart. We detail the proposed modeling approach by analyzing data from a longitudinal study on the dynamics of cognitive functioning in the elderly. Further, the effects of assumptions about non ignorability of the dropout process on model parameter estimates are (locally) investigated using the index of (local) sensitivity to non-ignorability

Trinitrophenol Reactive T-Cell Hybridomas Recognize Antigens That Require Antigen Processing

Protein antigens must be taken up, processed, and displayed on the surface of antigen-presenting cells in association with major histocompatibility complex molecules before they can be recognized by T cells. Whether recognition of the haptens used to study allergic contact hypersensitivity in murine models similarly requires processing has not been determined. We analyzed whether presentation of trinitrophenol to trinitrophenol reactive T-cell hybridomas requires antigen processing by studying the effects of inhibitors of antigen processing and presentation on tile ability of a syngeneic B-cell tumor (A20) to present trinitrophenol to a series of interleukin-2 producing, trinitrophenol specific, major histocompatibility complex class II-restricted T-cell hybridomas.The ability of trinitrophenol modified A20 cells to stimulate the hybridomas was completely inhibited by rnonoclonal, anti-trinitrophenol, or anti-Ia antibodies and was significantly reduced by paraformaldehyde fixation immediately after trinitrophenol modification. Trinitrophenol-modified A20 cultured at 37°C for 2h prior to fixation was significantly more effective at stimulating the hybridomas than trinitrophenol-modified A20 to present trinitrophenol was inhibited by chloroquine. Paraformaldehyde fixation and chloroquine treatment had similar effects on the ability of trinitrophenol modified lymph node dendritic cells to stimulate the trinitrophenol specific hybridomas. Paraformaldehyde fixation and chloroquine treatment had similar effects on the ability of A20 cells to present ovalbumin to ovalbumin-specific hybridomas as they had on the ability of trinitrophenol modified A20 cells to present trinitrophenol to the trinitrophenol specific hybridomas. One of seven T-cell hybridomas responded to trinitrophenol modified ovalbumin but not other trinitrophenol modified proteins. These results suggest that, at least in part, T cells in the contact hypersensitivity response to trinitrophenol recognize antigens that require processing and that trinitrophenol modified proteins can be recognized