uMELT: prediction of high-resolution melting curves and dynamic melting profiles of PCR products in a rich web application

ManuscriptuMeltSM is a flexible web-based tool for predicting DNA melting curves and denaturation profiles of PCR products. The user defines an amplicon sequence and chooses a set of thermodynamic and experimental parameters that include nearest-neighbor stacking energies, loop entropy effects, cation (monovalent and Mg++) concentrations and a temperature range. Using an accelerated partition function algorithm along with chosen parameter values, uMelt interactively calculates and visualizes the mean helicity and the dissociation probability at each sequence position at temperatures within the temperature range. Predicted curves display the mean helicity as a function of temperature or as derivative plots. Predicted profiles display stability as a function of sequence position either as 50% helicity temperatures or as the helicity probability at specific temperatures. The loss of helicity associated with increasing temperature may be viewed dynamically to visualize domain formation within the molecule. Results from fluorescent high-resolution melting experiments match the number of predicted melting domains and their relative temperatures. However, the absolute melting temperatures vary with the selected thermodynamic parameters and current libraries do not account for the rapid melting rates and helix stabilizing dyes used in fluorescent melting experiments. uMelt provides a convenient platform for simulation and design of high-resolution melting assays

Heterozygote PCR product melting curve prediction

pre-printMelting curve prediction of PCR products is limited to perfectly complementary strands. Multiple domains are calculated by recursive nearest-neighbor thermodynamics. However, the melting curve of an amplicon containing a heterozygous single nucleotide variant (SNV) after PCR is the composite of four duplexes: two matched homoduplexes and two mismatched heteroduplexes. To better predict the shape of composite heterozygote melting curves, 52 experimental curves were compared to brute force in silico predictions varying two parameters simultaneously: the relative contribution of heteroduplex products and an ionic scaling factor for mismatched tetrads. Heteroduplex products contributed 25.7 +/- 6.7% to the composite melting curve, varying from 23-28% for different SNV classes. The effect of ions on mismatch tetrads scaled to 76-96% of normal (depending on SNV class) and averaged 88 +/-16.4%. Based on uMelt (www.dna.utah.edu/umelt/umelt.html) with an expanded nearest neighbor thermodynamic set that UU IR Author Manuscript UU IR Author Manuscript University of Utah Institutional Repository Author Manuscript HETEROZYGOTE PCR PRODUCT MELTING CURVE PREDICTION 2 includes mismatched base pairs, uMelt HETS calculates helicity as a function of temperature for homoduplex and heteroduplex products, as well as the composite curve expected from heterozygotes. It is an interactive web tool for efficient genotyping design, heterozygote melting curve prediction, and quality control of melting curve experiments. The application was developed in Actionscript and can be found online at http://www.dna.utah.edu/hets/

Correction: Statistical modeling for selecting housekeeper genes

A correction to Statistical modeling for selecting housekeeper genes by Aniko Szabo, Charles M Perou, Mehmet Karaca, Laurent Perreard, John F Quackenbush, and Philip S Bernard. Genome Biology 2004, 5:R5

Jet-induced cratering of a granular surface with application to lunar spaceports

The erosion of lunar soil by rocket exhaust plumes is investigated experimentally. This has identified the diffusion-driven flow in the bulk of the sand as an important but previously unrecognized mechanism for erosion dynamics. It has also shown that slow regime cratering is governed by the recirculation of sand in the widening geometry of the crater. Scaling relationships and erosion mechanisms have been characterized in detail for the slow regime. The diffusion-driven flow occurs in both slow and fast regime cratering. Because diffusion-driven flow had been omitted from the lunar erosion theory and from the pressure cratering theory of the Apollo and Viking era, those theories cannot be entirely correct.Comment: 13 pages, link to published version: http://cedb.asce.org/cgi/WWWdisplay.cgi?090000

Factors controlling nitrate in ice cores: Evidence from the Dome C deep ice core

In order to estimate past changes in atmospheric NOx concentration, nitrate, an oxidation product of NOx, has often been measured in polar ice cores. In the frame of the European Project for Ice Coring in Antarctica (EPICA), a high-resolution nitrate record was obtained by continuous flow analysis (CFA) of a new deep ice core drilled at Dome C. This record allows a detailed comparison of nitrate with other chemical trace substances in polar snow under different climatic regimes. Previous studies showed that it would be difficult to make firm conclusions about atmospheric NOx concentrations based on ice core nitrate without a better understanding of the factors controlling NO3− deposition and preservation. At Dome C, initially high nitrate concentrations (over 500 ppb) decrease within the top meter to steady low values around 15 ppb that are maintained throughout the Holocene ice. Much higher concentrations (averaging 53 ppb) are found in ice from the Last Glacial Maximum (LGM). Combining this information with data from previous sampling elsewhere in Antarctica, it seems that under climatic conditions of the Holocene, temperature and accumulation rate are the key factors determining the NO3− concentration in the ice. Furthermore, ice layers with high acidity show a depletion of NO3−, but higher concentrations are found before and after the acidity layer, indicating that NO3− has been redistributed after deposition. Under glacial conditions, where NO3− shows a higher concentration level and also a larger variability, non-sea-salt calcium seems to act as a stabilizer, preventing volatilization of NO3− from the surface snow layers

Social Gerontology- Integrative and Territorial Aspects: A Citation Analysis of Subject Scatter and Database Coverage

To determine the mix of resources used in social gerontology research, a citation analysis was conducted. A representative sample of citations was selected from three prominent gerontology journals and information was added to determine subject scatter and database coverage for the cited materials. Results indicate that a significant portion of gerontology research, even from a social science perspective, relies roughly equally on medical resources as it does social science resources. Furthermore, there is a small but defined core of literature constituting scholarly “territory” unique to gerontology. Analysis of database indexing indicated that broad, interdisciplinary databases provide more comprehensive coverage of the cited materials than do subject-specific databases

Differential Equations, Mechanics, and Computation

This book provides a conceptual introduction to the theory of ordinary differential equations, concentrating on the initial value problem for equations of evolution and with applications to the calculus of variations and classical mechanics, along with a discussion of chaos theory and ecological models. It has a unified and visual introduction to the theory of numerical methods and a novel approach to the analysis of errors and stability of various numerical solution algorithms based on carefully chosen model problems. While the book would be suitable as a textbook for an undergraduate or elementary graduate course in ordinary differential equations, the authors have designed the text also to be useful for motivated students wishing to learn the material on their own or desiring to supplement an ODE textbook being used in a course they are taking with a text offering a more conceptual approach to the subject