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Tumors may contain billions of cells, including distinct malignant clones and nonmalignant cell types. Clarifying the evolutionary histories, prevalence, and defining molecular features of these cells is essential for improving clinical outcomes, since intratumoral heterogeneity provides fuel for acquired resistance to targeted therapies. Here we present a statistically motivated strategy for deconstructing intratumoral heterogeneity through multiomic and multiscale analysis of serial tumor sections (MOMA). By combining deep sampling of IDH-mutant astrocytomas with integrative analysis of single-nucleotide variants, copy-number variants, and gene expression, we reconstruct and validate the phylogenies, spatial distributions, and transcriptional profiles of distinct malignant clones. By genotyping nuclei analyzed by single-nucleus RNA-seq for truncal mutations, we further show that commonly used algorithms for identifying cancer cells from single-cell transcriptomes may be inaccurate. We also demonstrate that correlating gene expression with tumor purity in bulk samples can reveal optimal markers of malignant cells and use this approach to identify a core set of genes that are consistently expressed by astrocytoma truncal clones, including AKR1C3, whose expression is associated with poor outcomes in several types of cancer. In summary, MOMA provides a robust and flexible strategy for precisely deconstructing intratumoral heterogeneity and clarifying the core molecular properties of distinct cellular populations in solid tumors.

An efficient and practical synthesis of bridged diarylacetylenes in multigram quantities is carried out using high-yielding synthetic methods and readily available starting materials. The structural analysis has indicated that conformations, bending of the linear triple bond and the angle between the mean planes of aromatic rings of various bridged diarylacetylenes are governed by the p-pi conjugation among the aromatic rings and the ethereal groups.

An efficient and practical synthesis of bridged diarylacetylenes in multigram quantities has been successfully carried out using high-yielding (classical) synthetic methods and readily available starting materials. The structural analysis of the representative bridged diarylacetylenes by X-ray crystallography strongly suggests that conformations, bending of the linear triple bond, and the angle between the mean planes of aromatic rings in various bridged diarylacetylenes are governed by the p-π conjugation among the aromatic rings and the ethereal groups. Furthermore, the synthetic scheme also allows the preparation of (appropriately) bromo-substituted bridged diarylacetylenes which hold potential for their future usage for the preparation of polymeric analogues as well as the hexaarylbenzene derivatives for potential applications in the emerging area of molecular electronics and nanotechnology. [ABSTRACT FROM AUTHOR]

Strength, orientation, and location of the moving equivalent dipole of isolated, perfused rabbit hearts were determined throughout ventricular activation before and after right bundle branch block. The intervention did not appreciably modify early activation, but delayed late forces and caused them to migrate into the basilar free right ventricular wall. [ABSTRACT FROM PUBLISHER]