Significance Theory predicts that chronic pathogens with vertical or familial transmission should become less virulent over time because of coevolution. Although transmitted in this way, Helicobacter pylori is the major causative agent of gastric cancer. In two distinct Colombian populations with similar levels of H. pylori infection but different incidences of gastric cancer, we examined human and pathogen ancestry in matched samples to assess whether their genomic variation affects the severity of premalignant lesions. Interaction between human Amerindian ancestry and H. pylori African ancestry accounted for the geographic disparity in clinical presentation. We conclude that coevolutionary relationships are important determinants of gastric disease risk and that the historical colonization of the Americas continues to influence health in modern American populations.

Legal reasoning requires identification through search of authoritative legal texts (such as statutes, constitutions, or prior judicial opinions) that apply to a given legal question. In this paper, using a network representation of US Supreme Court opinions that integrates citation connectivity and topical similarity, we model the activity of law search as an organizing principle in the evolution of the corpus of legal texts. The network model and (parametrized) probabilistic search behavior generates a Pagerank-style ranking of the texts that in turn gives rise to a natural geometry of the opinion corpus. This enables us to then measure the ways in which new judicial opinions affect the topography of the network and its future evolution. While we deploy it here on the US Supreme Court opinion corpus, there are obvious extensions to large evolving bodies of legal text (or text corpora in general). The model is a proxy for the way in which new opinions influence the search behavior of litigants and judges and thus affect the law. This type of ''legal search effect'' is a new legal consequence of research practice that has not been previously identified in jurisprudential thought and has never before been subject to empirical analysis. We quantitatively estimate the extent of this effect and find significant relationships between search-related network structures and propensity of future citation. This finding indicates that ''search influence'' is a pathway through which judicial opinions can affect future legal development.

The microstructural evolution of DAFA26, an alumina-forming austenitic (AFA) stainless steel, was investigated during aging. The effect of aging at 750°C and 800°C on the growth of spherical γ'-Ni 3 (Al, Ti) particles present in the as-processed state was studied extensively using X-ray diffraction, microhardness testing, scanning electron microscopy, transmission electron microscopy, and atom probe tomography. The γ' particles had a cube-on-cube orientation relationship with the matrix (i.e. (m // p , m // p)). The coarsening kinetics of γ'-Ni 3 Al particles were in agreement with the Lifshitz, Slyozof-Wagner theory. Coarse Laves phase particles were also present in the as-processed state, and during the aging process both smaller Laves phase precipitates and B2-NiAl precipitates formed on both the grain boundaries and in the matrix. The γ' precipitates were determined to have the most impact on the room temperature hardness.

Genomic alterations in the p53 tumour-suppressor gene

Plasminogen activator inhibitor 1 (PAI-1), a major modulator of the fibrinolytic system, is an important factor in cardiovascular disease (CVD) susceptibility and severity. PAI-1 is highly heritable, but the few genes associated with it explain only a small portion of its variation. Studies of PAI-1 typically employ linear regression to estimate the effects of genetic variants on PAI-1 levels, but PAI-1 is not normally distributed, even after transformation. Therefore, alternative statistical methods may provide greater power to identify important genetic variants. Additionally, most genetic studies of PAI-1 have been performed on populations of European descent, limiting the generalizability of their results. We analyzed >30,000 variants for association with PAI-1 in a Ghanaian population, using median regression, a non-parametric alternative to linear regression. Three variants associated with median PAI-1, the most significant of which was in the gene arylsulfatase B (ARSB) (p = 1.09 x 10−7). We also analyzed the upper quartile of PAI-1, the most clinically relevant part of the distribution, and found 19 SNPs significantly associated in this quartile. Of note an association was found in period circadian clock 3 (PER3). Our results reveal novel associations with median and elevated PAI-1 in an understudied population. The lack of overlap between the two analyses indicates that the genetic effects on PAI-1 are not uniform across its distribution. They also provide evidence of the generalizability of the circadian pathway’s effect on PAI-1, as a recent meta-analysis performed in Caucasian populations identified another circadian clock gene (ARNTL).