Post-Election Litigation in Pennsylvania

The Article focuses on the causes and consequences of post-election litigation in Pennsylvania. The Authors conclude that the Pennsylvania Election Code has been strictly construed by Pennsylvania courts out of a reluctance to interfere with, and to promote, the finality of election returns

Velocity field distributions due to ideal line vortices

We evaluate numerically the velocity field distributions produced by a bounded, two-dimensional fluid model consisting of a collection of parallel ideal line vortices. We sample at many spatial points inside a rigid circular boundary. We focus on ``nearest neighbor'' contributions that result from vortices that fall (randomly) very close to the spatial points where the velocity is being sampled. We confirm that these events lead to a non-Gaussian high-velocity ``tail'' on an otherwise Gaussian distribution function for the Eulerian velocity field. We also investigate the behavior of distributions that do not have equilibrium mean-field probability distributions that are uniform inside the circle, but instead correspond to both higher and lower mean-field energies than those associated with the uniform vorticity distribution. We find substantial differences between these and the uniform case.Comment: 21 pages, 9 figures. To be published in Physical Review E (http://pre.aps.org/) in May 200

Synthesis of Cyclic Py-Im Polyamide Libraries

Cyclic Py-Im polyamides containing two GABA turn units exhibit enhanced DNA binding affinity, but extensive studies of their biological properties have been hindered due to synthetic inaccessibility. A facile modular approach toward cyclic polyamides has been developed via microwave-assisted solid-phase synthesis of hairpin amino acid oligomer intermediates followed by macrocyclization. A focused library of cyclic polyamides 1–7 targeted to the androgen response element (ARE) and the estrogen response element (ERE) were synthesized in 12–17% overall yield. The Fmoc protection strategy also allows for selective modifications on the GABA turn units that have been shown to improve cellular uptake properties. The DNA binding affinities of a library of cyclic polyamides were measured by DNA thermal denaturation assays and compared to the corresponding hairpin polyamides. Fluorescein-labeled cyclic polyamides have been synthesized and imaged via confocal microscopy in A549 and T47D cell lines. The IC_50 values of compounds 1–7 and 9–11 were determined, revealing remarkably varying levels of cytotoxicity

Magnetohydrodynamic activity inside a sphere

We present a computational method to solve the magnetohydrodynamic equations in spherical geometry. The technique is fully nonlinear and wholly spectral, and uses an expansion basis that is adapted to the geometry: Chandrasekhar-Kendall vector eigenfunctions of the curl. The resulting lower spatial resolution is somewhat offset by being able to build all the boundary conditions into each of the orthogonal expansion functions and by the disappearance of any difficulties caused by singularities at the center of the sphere. The results reported here are for mechanically and magnetically isolated spheres, although different boundary conditions could be studied by adapting the same method. The intent is to be able to study the nonlinear dynamical evolution of those aspects that are peculiar to the spherical geometry at only moderate Reynolds numbers. The code is parallelized, and will preserve to high accuracy the ideal magnetohydrodynamic (MHD) invariants of the system (global energy, magnetic helicity, cross helicity). Examples of results for selective decay and mechanically-driven dynamo simulations are discussed. In the dynamo cases, spontaneous flips of the dipole orientation are observed.Comment: 15 pages, 19 figures. Improved figures, in press in Physics of Fluid

Discovery of molecular subtypes in leiomyosarcoma through integrative molecular profiling.

Leiomyosarcoma (LMS) is a soft tissue tumor with a significant degree of morphologic and molecular heterogeneity. We used integrative molecular profiling to discover and characterize molecular subtypes of LMS. Gene expression profiling was performed on 51 LMS samples. Unsupervised clustering showed three reproducible LMS clusters. Array comparative genomic hybridization (aCGH) was performed on 20 LMS samples and showed that the molecular subtypes defined by gene expression showed distinct genomic changes. Tumors from the muscle-enriched cluster showed significantly increased copy number changes (P=0.04). A majority of the muscle-enriched cases showed loss at 16q24, which contains Fanconi anemia, complementation group A, known to have an important role in DNA repair, and loss at 1p36, which contains PRDM16, of which loss promotes muscle differentiation. Immunohistochemistry (IHC) was performed on LMS tissue microarrays (n=377) for five markers with high levels of messenger RNA in the muscle-enriched cluster (ACTG2, CASQ2, SLMAP, CFL2 and MYLK) and showed significantly correlated expression of the five proteins (all pairwise P<0.005). Expression of the five markers was associated with improved disease-specific survival in a multivariate Cox regression analysis (P<0.04). In this analysis that combined gene expression profiling, aCGH and IHC, we characterized distinct molecular LMS subtypes, provided insight into their pathogenesis, and identified prognostic biomarkers