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A major unanswered question in neuroscience is whether there exists genomic variability between individual neurons of the brain, contributing to functional diversity or to an unexplained burden of neurological disease. To address this question, we developed a method to amplify genomes of single neurons from human brains. Because recent reports suggest(More)
The basic idea of image registration is to find a reasonable transformation of an image so that the resulting difference between it and another image is made small. We derive an optimal control method for determining such a transformation; the approach is based on the grid deformation method and seeks to minimize an objective functional that measures the(More)
Plant cell and organ cultures have emerged as potential sources of secondary metabolites, which are used as pharmaceuticals, agrochemicals, flavors, fragrances, coloring agents, biopesticides, and food additives. In recent years, various strategies have been developed to assess biomass accumulation and synthesis of secondary compounds in cultures. Biomass(More)
Somatic mutations occur during brain development and are increasingly implicated as a cause of neurogenetic disease. However, the patterns in which somatic mutations distribute in the human brain are unknown. We used high-coverage whole-genome sequencing of single neurons from a normal individual to identify spontaneous somatic mutations as clonal marks to(More)
Whether somatic mutations contribute functional diversity to brain cells is a long-standing question. Single-neuron genomics enables direct measurement of somatic mutation rates in human brain and promises to answer this question. A recent study (Upton et al., 2015) reported high rates of somatic LINE-1 element (L1) retrotransposition in the hippocampus and(More)
DNA copy number variations (CNVs) play an important role in the pathogenesis and progression of cancer and confer susceptibility to a variety of human disorders. Array comparative genomic hybridization has been used widely to identify CNVs genome wide, but the next-generation sequencing technology provides an opportunity to characterize CNVs genome wide(More)
β-Lapachone (β-LAP) is a natural naphthoquinone compound isolated from the lapacho tree (Tabebuia sp.), and it has been used for treatment of rheumatoid arthritis, infection, and cancer. In the present study, we investigated whether β-LAP has anti-inflammatory effects under in vitro and in vivo neuroinflammatory conditions. The effects of β-LAP on the(More)
The focus of this paper is on incompressible flows in three dimensions modeled by least-squares finite element methods (LSFEM) and using a novel reformulation of the Navier-Stokes equations. LSFEM are attractive because the resulting discrete equations yield symmetric, positive definite systems of algebraic equations and the functional provides both a local(More)
Least-squares variational methods have several practical and theoretical advantages for solving elliptic partial differential equations, including symmetric positive definite discrete operators and a sharp error measure. One of the potential drawbacks, especially in three dimensions, is that mass conservation is achieved only in a least-squares sense, and(More)
A weighted-norm least-squares method is considered for the numerical approximation of solutions that have singularities at the boundary. While many methods suffer from a global loss of accuracy due to boundary singularities, the least-squares method can be particularly sensitive to a loss of regularity. The method we describe here requires only a rough(More)