Computational Evolutionary Embryogeny

Evolutionary and developmental processes are used to evolve the configurations of 3-D structures in silico to achieve desired performances. Natural systems utilize the combination of both evolution and development processes to produce remarkable performance and diversity. However, this approach has not yet been applied extensively to the design of continuous 3-D load-supporting structures. Beginning with a single artificial cell containing information analogous to a DNA sequence, a structure is grown according to the rules encoded in the sequence. Each artificial cell in the structure contains the same sequence of growth and development rules, and each artificial cell is an element in a finite element mesh representing the structure of the mature individual. Rule sequences are evolved over many generations through selection and survival of individuals in a population. Modularity and symmetry are visible in nearly every natural and engineered structure. An understanding of the evolution and expression of symmetry and modularity is emerging from recent biological research. Initial evidence of these attributes is present in the phenotypes that are developed from the artificial evolution, although neither characteristic is imposed nor selected-for directly. The computational evolutionary development approach presented here shows promise for synthesizing novel configurations of high-performance systems. The approach may advance the system design to a new paradigm, where current design strategies have difficulty producing useful solutions

Engineering by fundamental elements of evolution

The method presented in this note mimics two fundamental mechanisms from nature, growth, and development, for the synthesis of new three-dimensional structures. The structures were synthesized to support a load generated by a wind. Every structure grows from a single artificial cell following a set of genes, encoded in an artificial genome shared by all cells. Genes are a set of commands that control the growth process. Genes are regulated by interaction with the environment. The environment is both external and internal to the structure. The performance each structure is measured by its ability to hold the load and other additional engineering criteria. A population of structures is evolved using a genetic algorithm, which alters the genome of two mating individuals. We will present evolved phenotypes with high degrees of modularity and symmetry which evolved according to engineering criteria. Neither one of these two characteristics has been directly imposed as the fitness evaluation, but rather spontaneously emerge as a consequence of natural selection. We will argue that the types of rules we are using in this model are not biased toward any of these characteristics, but rather basic rules for growth and development

Tolerance without clonal expansion: Self-antigen-expressing B cells program self-reactive T cells for future deletion

B cells have been shown in various animal models to induce immunological tolerance leading to reduced immune responses and protection from autoimmunity. We show that interaction of B cells with naive T cells results in T cell triggering accompanied by the expression of negative costimulatory molecules such as PD-1, CTLA-4, B and T lymphocyte attenuator, and CD5. Following interaction with B cells, T cells were not induced to proliferate, in a process that was dependent on their expression of PD-1 and CTLA-4, but not CD5. In contrast, the T cells became sensitive to Ag-induced cell death. Our results demonstrate that B cells participate in the homeostasis of the immune system by ablation of conventional self-reactive T cells

Multisite Evaluation of the BD Max Extended Enteric Bacterial Panel for Detection of Yersinia enterocolitica, Enterotoxigenic Escherichia coli, Vibrio, and Plesiomonas shigelloides from Stool Specimens.

The purpose of this study was to perform a multisite evaluation to establish the performance characteristics of the BD Max extended enteric bacterial panel (xEBP) assay directly from unpreserved or Cary-Blair-preserved stool specimens for the detection of Yersinia enterocolitica, enterotoxigenic Escherichia coli (ETEC), Vibrio, and Plesiomonas shigelloides The study included prospective, retrospective, and prepared contrived specimens from 6 clinical sites. BD Max xEBP results were compared to the reference method, which included standard culture techniques coupled with alternate PCR and sequencing, except for ETEC, for which the reference method was two alternate PCRs and sequencing. Alternate PCR was also used to confirm the historical results for the retrospective specimens and for discrepant result analysis. A total of 2,410 unformed, deidentified stool specimens were collected. The prevalence in the prospective samples as defined by the reference method was 1.2% ETEC, 0.1% Vibrio, 0% Y. enterocolitica, and 0% P. shigelloides Compared to the reference method, the positive percent agreement (PPA) (95% confidence interval [CI]), negative percent agreement (NPA) (95% CI), and kappa coefficient (95% CI) for the BD Max xEBP assay for all specimens combined were as follows: ETEC, 97.6% (87.4 to 99.6), 99.8% (99.5 to 99.9), and 0.93 (0.87 to 0.99); Vibrio, 100% (96.4 to 100), 99.7% (99.4 to 99.8), and 0.96 (0.93 to 0.99); Y. enterocolitica, 99.0% (94.8 to 99.8), 99.9% (99.8 to 99.9), and 0.99 (0.98 to 1); P. shigelloides, 100% (96.4 to 100), 99.8% (99.5 to 99.9), and 0.98 (0.95 to 1), respectively. In this multicenter study, the BD Max xEBP showed a high correlation (kappa, 0.97; 95% CI, 0.95 to 0.98) with the conventional methods for the detection of ETEC, Vibrio, Y. enterocolitica, and P. shigelloides in stool specimens from patients suspected of acute gastroenteritis, enteritis, or colitis

A novel evolutionary method for synthesis of 3D continuous structures

The design of complex structures which benefit the usage of inhomogeneous properties is a very difficult task. In this paper we present a novel approach in which we synthesize the design of structures by mimicking two fundamental processes from biology - Evolution and Development. We will show that by using these two processes in a computational model, we are able to evolve high performance structures. These structures contain a high degree of complexity from a topological aspect and from a materials distribution aspect. This degree of complexity is difficult or even impossible to achieve by ordinary design methods

Modularity and symmetry in computational embryogeny

Modularity and symmetry are two properties observed in almost every engineering and biological structure. The origin of these properties in nature is still unknown. Yet, as engineers we tend to generate designs which share these properties. In this paper we will report on the origin of these properties in three dimensional evolved structures (phenotypes). The phenotypes were evolved in an evolutionarydevelopmental model of biological structures. The phenotypes were grown under a high volatility stochastic environment. The phenotypes have evolved to function within the environment using the very basic requirements. Even though neither modularity nor symmetry have been directly imposed as part of the requirements, the phenotypes were able to generate these properties after only a few hundred generations. These results may suggest that modularity and symmetry are both very fundamental properties that develop during the early stages of evolution. This result may give insight to the origin of both modularity and symmetry in biological organisms

IL-23-mediated mononuclear phagocyte crosstalk protects mice from Citrobacter rodentium-induced colon immunopathology.

Gut homeostasis and mucosal immune defense rely on the differential contributions of dendritic cells (DC) and macrophages. Here we show that colonic CX3CR1(+) mononuclear phagocytes are critical inducers of the innate response to Citrobacter rodentium infection. Specifically, the absence of IL-23 expression in macrophages or CD11b(+) DC results in the impairment of IL-22 production and in acute lethality. Highlighting immunopathology as a death cause, infected animals are rescued by the neutralization of IL-12 or IFNγ. Moreover, mice are also protected when the CD103(+) CD11b(-) DC compartment is rendered deficient for IL-12 production. We show that IL-12 production by colonic CD103(+) CD11b(-) DC is repressed by IL-23. Collectively, in addition to its role in inducing IL-22 production, macrophage-derived or CD103(-) CD11b(+) DC-derived IL-23 is required to negatively control the otherwise deleterious production of IL-12 by CD103(+) CD11b(-) DC. Impairment of this critical mononuclear phagocyte crosstalk results in the generation of IFNγ-producing former TH17 cells and fatal immunopathology

Baseline resistance to nucleoside reverse transcriptase inhibitors fails to predict virologic response to combination therapy in children (PACTG 338)

BACKGROUND: The association between baseline drug resistance mutations and subsequent increase in viral failure has not been established for HIV-infected children. We evaluated drug resistance mutations at 39 codon sites (21 protease inhibitor (PI) resistant codons and 18 nucleoside reverse transcriptase inhibitor (NRTI) resistant codons) for 92 clinically stable NRTI-experienced, PI-naive HIV-infected children 2 to 17 years of age who were initiating new therapy with ritonavir plus zidovudine (ZDV) and lamivudine or plus stavudine. The association between baseline drug resistance mutations and subsequent viral failure after 12 and 24 weeks of highly active antiretroviral therapy (HAART) was studied. RESULTS: There were few primary PI associated mutations in this PI-naïve population, but 84% had NRTI mutations – codons 215 (66%), 41 (42%), 67 (37%), 210 (33%) and 70 (32%). None of the specific baseline drug resistance mutations were associated with a higher rate of virologic failure after 12 or 24 weeks of HAART. Median week 12 viral load decreased as the total number of NRTI mutations at baseline increased (P = 0.006). Specifically, a higher level of baseline ZDV resistance mutation was associated with a decrease in viral failure after 12 weeks on a ZDV-containing HAART regimen (P = 0.017). CONCLUSION: No increase was seen in the rate of viral failure after HAART associated with the presence of resistance mutations at baseline. This paradoxical result may be due to adherence, replicative capacity, or ZDV hypersusceptibility to the new regimen

ESDA2008-59036 A NOVEL EVOLUTIONARY METHOD FOR SYNTHESIS OF 3D CONTINUOUS STRUCTURES

ABSTRACT The design of complex structures which benefit the usage of inhomogeneous properties is a very difficult task. In this paper we present a novel approach in which we synthesize the design of structures by mimicking two fundamental processes from biology -Evolution and Development. We will show that by using these two processes in a computational model, we are able to evolve high performance structures. These structures contain a high degree of complexity from a topological aspect and from a materials distribution aspect. This degree of complexity is difficult or even impossible to achieve by ordinary design methods