Medoidshift clustering applied to genomic bulk tumor data.

Despite the enormous medical impact of cancers and intensive study of their biology, detailed characterization of tumor growth and development remains elusive. This difficulty occurs in large part because of enormous heterogeneity in the molecular mechanisms of cancer progression, both tumor-to-tumor and cell-to-cell in single tumors. Advances in genomic technologies, especially at the single-cell level, are improving the situation, but these approaches are held back by limitations of the biotechnologies for gathering genomic data from heterogeneous cell populations and the computational methods for making sense of those data. One popular way to gain the advantages of whole-genome methods without the cost of single-cell genomics has been the use of computational deconvolution (unmixing) methods to reconstruct clonal heterogeneity from bulk genomic data. These methods, too, are limited by the difficulty of inferring genomic profiles of rare or subtly varying clonal subpopulations from bulk data, a problem that can be computationally reduced to that of reconstructing the geometry of point clouds of tumor samples in a genome space. Here, we present a new method to improve that reconstruction by better identifying subspaces corresponding to tumors produced from mixtures of distinct combinations of clonal subpopulations. We develop a nonparametric clustering method based on medoidshift clustering for identifying subgroups of tumors expected to correspond to distinct trajectories of evolutionary progression. We show on synthetic and real tumor copy-number data that this new method substantially improves our ability to resolve discrete tumor subgroups, a key step in the process of accurately deconvolving tumor genomic data and inferring clonal heterogeneity from bulk data

The GlueX DIRC Project

The GlueX experiment was designed to search for and study the pattern of gluonic excitations in the meson spectrum produced through photoproduction reactions at a new tagged photon beam facility in Hall D at Jefferson Laboratory. The particle identification capabilities of the GlueX experiment will be enhanced by constructing a DIRC (Detection of Internally Reflected Cherenkov light) detector, utilizing components of the decommissioned BaBar DIRC. The DIRC will allow systematic studies of kaon final states that are essential for inferring the quark flavor content of both hybrid and conventional mesons. The design for the GlueX DIRC is presented, including the new expansion volumes that are currently under development.Comment: 8 pages, 6 figure

Association of carotid atherosclerosis and left ventricular hypertrophy.

AbstractObjectives. This study was undertaken to determine the prevalence of carotid atherosclerosis in a large group of asymptomatic hypertensive and normotensive adults and to examine its relation to the presence of left ventricular hypertrophy.Background. Both electrocardiographic and echocardiographic left ventricular hypertrophy predict an increased risk of cardiovascular events and mortality, including cerebrovascular disease, but the mechanism of association is unknown.Methods. Four hundred eighty-six (277 normotensive and 209 untreated hypertensive) adults, free of clinical evidence of cardiovascular disease, were studied prospectively with echocardiography to determine left ventricular mass and carotid ultrasound to detect atherosclerosis and to measure common carotid artery dimensions.Results. Carotid atherosclerosis was present in 16% of normotensive and 23% of hypertensive participants (p < 0.05) and was associated with older age, higher systolic and pulse pressures and larger left ventricular mass index ([mean ± SD] 91 ± 19 vs. 82 ± 18 g/m2, p < 0.0001). The difference in mass persisted after adjustment for baseline differences in age and blood pressure. Subjects with left ventricular hypertrophy were twice as likely to have carotid atheromas (35% vs. 18%, p < 0.01). Logistic regression analyses, including standard risk factors, indicated that only age and left ventricular mass index independently predicted the presence of carotid plaque, both in the entire study group and when normotensive and hypertensive subjects were considered separately.Conclusions. We believe that the present study provides the first evidence that higher left ventricular mass as detected by echocardiography is associated with the presence of carotid plaque. The association between cardiac hypertrophy and systemic atherosclerosis may contribute to the pathogenesis of the high incidence of vascular events that is well documented in patients with left ventricular hypertrophy