Doctor of Philosophy

dissertationTraditional associative plasticity theories have previously been shown to be incompatible with experimental data. For this reason, a nonassociative plasticity theory is commonly adopted. Nonassociative plasticity theories are prone to several forms of instability that result in the governing equations becoming ill-posed. Two of these instabilities are discussed: the localization instability and the Sandler-Rubin instability, which is a nonphysical instability that may occur with any degree of nonassociativity. The primary purpose of this dissertation is to describe how traditional nonassociative plasticity theory can be reformulated to eliminate the Sandler-Rubin instability while maintaining agreement with experimental data. Numerical and analytical techniques are used to investigate the effects of three nontraditional plasticity models on the existence of the Sandler-Rubin instability: viscoplasticity, incrementally non-linear plasticity, and nonlocal plasticity. Of these, it is shown that only incremental nonlinearity eliminates the instability while maintaining agreement with existing experimental data. Standard laboratory tests cannot detect nonlinearity in a material's incremental response. For this reason a new experimental method and a new data analysis technique are presented and used to validate incrementally nonlinear plasticity theory. The new technique uses a cyclic load path and an interpolation scheme to infer the material response to several loading directions at the same material state. This new technique was used to study the incremental response of aluminum 6061-T0. The new technique suggests that there is significant nonlinearity in the incremental response of this material. Though it will be demonstrated that the Sandler-Rubin instability is not eliminated with nonlocal theory, this theory is nevertheless well established at regularizing otherwise ill-posed localization problems. Few efficient numerical schemes exist for solving the equations of nonlocal plasticity. Schemes have previously been developed for solving these equations as part of a finite-element or element-free Galerkin method, but no general convergence criterion had been developed for these methods. A new numerical scheme for solving these equations using the material point method (MPM) is presented. The new scheme uses the MPM background grid for particle-to-particle communication, and results in a simple, matrix-free algorithm. A convergence crite- rion derived for the new method is furthermore shown to be applicable to some of the methods developed by other researchers

Toward a Theory of the Evolution of Fair Play

Juvenile animals of many species engage in social play, but its functional significance is not well understood. This is especially true for a type of social play called fair play (Fp). Social play often involves behavioral patterns similar to adult behaviors (e.g., fighting, mating, and predatory activities), but young animals often engage in Fp behaviors such as role-reversals and self-handicapping, which raises the evolutionary problem of why Fp exists. A long-held working hypothesis, tracing back to the 19th century, is that social play provides contexts in which adult social skills needed for adulthood can be learned or, at least, refined. On this hypothesis, Fp may have evolved for adults to acquire skills for behaving fairly in the sense of equitable distribution of resources or treatment of others. We investigated the evolution of Fp using an evolutionary agent-based model of populations of social agents that learn adult fair behavior (Fb) by engaging in Fp as juveniles. In our model, adults produce offspring by accumulating resources over time through foraging. Adults can either behave selfishly by keeping the resources they forage or they can pool them, subsequently dividing the pooled resources after each round of foraging. We found that fairness as equitability was beneficial especially when resources were large but difficult to obtain and led to the evolution of Fp. We conclude by discussing the implications of this model, for developing more rigorous theory on the evolution of social play, and future directions for theory development by modeling the evolution of play

Experimental assessment of unvalidated assumptions in classical plasticity theory.

This report investigates the validity of several key assumptions in classical plasticity theory regarding material response to changes in the loading direction. Three metals, two rock types, and one ceramic were subjected to non-standard loading directions, and the resulting strain response increments were displayed in Gudehus diagrams to illustrate the approximation error of classical plasticity theories. A rigorous mathematical framework for fitting classical theories to the data, thus quantifying the error, is provided. Further data analysis techniques are presented that allow testing for the effect of changes in loading direction without having to use a new sample and for inferring the yield normal and flow directions without having to measure the yield surface. Though the data are inconclusive, there is indication that classical, incrementally linear, plasticity theory may be inadequate over a certain range of loading directions. This range of loading directions also coincides with loading directions that are known to produce a physically inadmissible instability for any nonassociative plasticity model

In-Orbit Performance of the GRACE Follow-on Laser Ranging Interferometer

The Laser Ranging Interferometer (LRI) instrument on the Gravity Recovery and Climate Experiment (GRACE) Follow-On mission has provided the first laser interferometric range measurements between remote spacecraft, separated by approximately 220 km. Autonomous controls that lock the laser frequency to a cavity reference and establish the 5 degrees of freedom two-way laser link between remote spacecraft succeeded on the first attempt. Active beam pointing based on differential wave front sensing compensates spacecraft attitude fluctuations. The LRI has operated continuously without breaks in phase tracking for more than 50 days, and has shown biased range measurements similar to the primary ranging instrument based on microwaves, but with much less noise at a level of 1 nm/Hz at Fourier frequencies above 100 mHz. © 2019 authors. Published by the American Physical Society

A genome-wide association study of anorexia nervosa.

Anorexia nervosa (AN) is a complex and heritable eating disorder characterized by dangerously low body weight. Neither candidate gene studies nor an initial genome-wide association study (GWAS) have yielded significant and replicated results. We performed a GWAS in 2907 cases with AN from 14 countries (15 sites) and 14 860 ancestrally matched controls as part of the Genetic Consortium for AN (GCAN) and the Wellcome Trust Case Control Consortium 3 (WTCCC3). Individual association analyses were conducted in each stratum and meta-analyzed across all 15 discovery data sets. Seventy-six (72 independent) single nucleotide polymorphisms were taken forward for in silico (two data sets) or de novo (13 data sets) replication genotyping in 2677 independent AN cases and 8629 European ancestry controls along with 458 AN cases and 421 controls from Japan. The final global meta-analysis across discovery and replication data sets comprised 5551 AN cases and 21 080 controls. AN subtype analyses (1606 AN restricting; 1445 AN binge-purge) were performed. No findings reached genome-wide significance. Two intronic variants were suggestively associated: rs9839776 (P=3.01 × 10(-7)) in SOX2OT and rs17030795 (P=5.84 × 10(-6)) in PPP3CA. Two additional signals were specific to Europeans: rs1523921 (P=5.76 × 10(-)(6)) between CUL3 and FAM124B and rs1886797 (P=8.05 × 10(-)(6)) near SPATA13. Comparing discovery with replication results, 76% of the effects were in the same direction, an observation highly unlikely to be due to chance (P=4 × 10(-6)), strongly suggesting that true findings exist but our sample, the largest yet reported, was underpowered for their detection. The accrual of large genotyped AN case-control samples should be an immediate priority for the field

A genome-wide association study of anorexia nervosa

Anorexia nervosa (AN) is a complex and heritable eating disorder characterized by dangerously low body weight. Neither candidate gene studies nor an initial genome wide association study (GWAS) have yielded significant and replicated results. We performed a GWAS in 2,907 cases with AN from 14 countries (15 sites) and 14,860 ancestrally matched controls as part of the Genetic Consortium for AN (GCAN) and the Wellcome Trust Case Control Consortium 3 (WTCCC3). Individual association analyses were conducted in each stratum and meta-analyzed across all 15 discovery datasets. Seventy-six (72 independent) SNPs were taken forward for in silico (two datasets) or de novo (13 datasets) replication genotyping in 2,677 independent AN cases and 8,629 European ancestry controls along with 458 AN cases and 421 controls from Japan. The final global meta-analysis across discovery and replication datasets comprised 5,551 AN cases and 21,080 controls. AN subtype analyses (1,606 AN restricting; 1,445 AN binge-purge) were performed. No findings reached genome-wide significance. Two intronic variants were suggestively associated: rs9839776 (P=3.01×10−7) in SOX2OT and rs17030795 (P=5.84×10−6) in PPP3CA. Two additional signals were specific to Europeans: rs1523921 (P=5.76×10−6) between CUL3 and FAM124B and rs1886797 (P=8.05×10−6) near SPATA13. Comparing discovery to replication results, 76% of the effects were in the same direction, an observation highly unlikely to be due to chance (P= 4×10−6), strongly suggesting that true findings exist but that our sample, the largest yet reported, was underpowered for their detection. The accrual of large genotyped AN case-control samples should be an immediate priority for the field

Dissecting the Shared Genetic Architecture of Suicide Attempt, Psychiatric Disorders, and Known Risk Factors

Background Suicide is a leading cause of death worldwide, and nonfatal suicide attempts, which occur far more frequently, are a major source of disability and social and economic burden. Both have substantial genetic etiology, which is partially shared and partially distinct from that of related psychiatric disorders. Methods We conducted a genome-wide association study (GWAS) of 29,782 suicide attempt (SA) cases and 519,961 controls in the International Suicide Genetics Consortium (ISGC). The GWAS of SA was conditioned on psychiatric disorders using GWAS summary statistics via multitrait-based conditional and joint analysis, to remove genetic effects on SA mediated by psychiatric disorders. We investigated the shared and divergent genetic architectures of SA, psychiatric disorders, and other known risk factors. Results Two loci reached genome-wide significance for SA: the major histocompatibility complex and an intergenic locus on chromosome 7, the latter of which remained associated with SA after conditioning on psychiatric disorders and replicated in an independent cohort from the Million Veteran Program. This locus has been implicated in risk-taking behavior, smoking, and insomnia. SA showed strong genetic correlation with psychiatric disorders, particularly major depression, and also with smoking, pain, risk-taking behavior, sleep disturbances, lower educational attainment, reproductive traits, lower socioeconomic status, and poorer general health. After conditioning on psychiatric disorders, the genetic correlations between SA and psychiatric disorders decreased, whereas those with nonpsychiatric traits remained largely unchanged. Conclusions Our results identify a risk locus that contributes more strongly to SA than other phenotypes and suggest a shared underlying biology between SA and known risk factors that is not mediated by psychiatric disorders.Peer reviewe

Associations between Attention-Deficit/Hyperactivity Disorder and various eating disorders: A Swedish nationwide population study using multiple genetically informative approaches

Background Although attention-deficit hyperactivity/impulsivity disorder (ADHD) and eating disorders (EDs) frequently co-occur, little is known about the shared etiology. In this study we comprehensively investigated the genetic association between ADHD and various EDs, including anorexia nervosa (AN) and other EDs (OED, including bulimia nervosa [BN]). Methods We applied different genetically informative designs to register-based information of a Swedish nationwide population (N=3,550,118). We first examined the familial co-aggregation of clinically diagnosed ADHD and EDs across multiple types of relatives. We then applied quantitative genetic modeling in full-sisters and maternal half-sisters to estimate the genetic correlations between ADHD and EDs. We further tested the associations between ADHD polygenic risk scores (PRS) and ED symptoms, and between AN PRS and ADHD symptoms, in a genotyped population-based sample (N=13,472). Results Increased risk of all types of EDs was found in individuals with ADHD (any ED: OR [95% CI]=3.97 [3.81-4.14], AN: 2.68 [2.15-2.86], OED: 4.66 [4.47-4.87], BN: 5.01 [4.63-5.41]) and their relatives compared to individuals without ADHD and their relatives. The magnitude of the associations reduced as the degree of relatedness decreased, suggesting shared familial liability between ADHD and EDs. Quantitative genetic models revealed stronger genetic correlation of ADHD with OED (0.37 [0.31-0.42]) than with AN (0.14 [0.05-0.22]). ADHD PRS correlated positively with ED symptom measures overall and sub-scales “drive for thinness” and “body dissatisfaction”, despite small effect sizes. Conclusions We observed stronger genetic association with ADHD for non-AN EDs than AN, highlighting specific genetic correlation beyond a general genetic factor across psychiatric disorders